An open‐cage 60fullerene was prepared through a multiple‐step sequence based on peroxide‐mediated cage‐opening reactions. Key steps include repeated C60‐sensitized singlet‐oxygen oxidation of ...electron‐rich amino enol double bonds to form two lactone and two lactam moieties on the rim of the orifice. Single‐crystal X‐ray analysis shows that the 22‐membered orifice has an ellipsoid shape with the major axis at 6.7 Å and the minor axis at 3.5 Å. Encapsulation of H2O2 was observed under atmospheric pressure at room temperature. Oxygen is also effectively trapped during the process.
Genie in a bottle: An open‐cage 60fullerene was prepared through a multiple‐step sequence based on peroxide‐mediated cage‐opening reactions. There are two lactone and two lactam moieties on the rim of the 22‐membered orifice, which has an ellipse shape with the major axis at 6.7 Å and the minor axis at 3.5 Å. Efficient encapsulation of H2O2 and O2 was achieved under atmospheric pressure at room temperature.
•Lp and CPP-Lp can enhance the permeability across BBB in vitro.•IN administration improve drug distribution in CNS regions most affected by AD.•The lagging-intense inhibition of AChE and BuChE was ...related to distribution.•Very mild nasal toxicity of rivastigmine formulations was found.•Cp and CPP-Lp afford BBB penetration and nasal olfactory pathway into brain by IN administration.
Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder associated with cholinergic neurons degeneration. The blood–brain barrier (BBB) not only provides protection for the brain but also hinders the treatment and diagnosis of this neurological disease, because the drugs must cross BBB to reach the lesions. The present work was aimed at formulating rivastigmine liposomes (Lp) and cell-penetrating peptide (CPP) modified liposomes (CPP-Lp) to improve rivastigmine distribution in brain and proceed to enhance pharmacodynamics by intranasal (IN) administration and minimize side effects. The results revealed that Lp especially the CPP-Lp can enhance the permeability across the BBB by murine brain microvascular endothelial cells model in vitro. IN administration of rivastigmine solution and rivastigmine liposomes demonstrated the capacity to improve rivastigmine distribution and adequate retention in CNS regions especially in hippocampus and cortex, which were the regions most affected by AD, than that of IV administration. Importantly, the lagging but intense inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were relative to the extended release, absorption and retention. In addition, there was very mild nasal toxicity of liposomal formulations. The data suggest that rivastigmine liposomes especially CPP-Lp improve the brain delivery and enhance pharmacodynamics which respect to BBB penetration and nasal olfactory pathway into brain after IN administration, and simultaneously decrease the hepatic first pass metabolism and gastrointestinal adverse effects.
The interfacial zone between aggregate particles and asphalt mortar presents a significant effect on the strength of an asphalt mixture. In this paper, basalt, limestone, and diabase were selected, ...and the influence of these aggregates on the mechanical characteristics and microstructures of the interfacial zone was investigated. Nanoindentation was employed to measure the change law of mechanical behavior in the region of the interfacial zone, and corresponding viscoelastic parameters were deduced; microstructural morphology was observed by scanning electron microscopy, and the effect of the mineralogical components on the interfacial zone was analyzed as well. Results show that the mechanical behavior of the interfacial transition zone is complicated. The modulus and hardness of asphalt mortar decrease with the increases in the aggregate surface distance, and then keep stable after the distance is greater than 40 μm. Both the relaxation time and dissipated energy ratio of the interfacial zone affected by the different aggregate types show a similar change law. These states indicate that aggregate types have little influence on the stress dissipation of asphalt mortar. However, creep compliances that quantify the ability of the deformation resistance show a significant difference; microstructure morphologies of the interfacial zone are affected by aggregates obviously, and micro pores present a different distribution and state in the interfacial zone.
The identification of early plasma biomarkers for clinical outcomes and drug resistance has key importance for risk stratification in anaplastic lymphoma kinase (ALK)-positive advanced non-small cell ...lung cancer (NSCLC) patients. Moreover, it remains unclear whether the anti-angiogenic drug anlotinib can reverse the resistance of ALK-tyrosine kinase inhibitor (ALK-TKI) crizotinib, and no research has explored the effect of anlotinib combined with crizotinib on ALK-positive patients.
In this study, 76 baseline and longitudinal plasma samples from 61 ALK-positive NSCLC patients receiving crizotinib treatment were analyzed by Luminex liquid suspension chip for 40 chemokines. RNA sequence (RNA-seq) was used to identify differentially expressed genes (DEGs) between H3122 and H3122-crizotinib resistant (H3122CR) cells. Tube formation assay was performed to investigate the effect of chemokines on angiogenesis. And H3122CR-derived xenograft model was constructed to validate the efficacy and safety of anlotinib combined with crizotinib in vivo.
Baseline and progression plasma samples detection suggested that CCL20 played a crucial role in monitoring and predicting the clinical response of crizotinib (hazard ratio for progression-free survival: 2.27 (1.13-4.58); for overall survival: 2.7 (1.23-5.8)). RNA-seq results for H3122 and H3122CR cells showed that high expression of chemokines and angiogenesis pathways were involved in crizotinib resistance. Subsequently, in vitro experiments indicated that CCL20 may induce crizotinib resistance by activation of angiogenesis via JAK2/STAT3-CCL20-VEGFA/IL6 axis. We further found that anti-angiogenic TKI anlotinib could reverse crizotinib resistance by inhibiting chemokines-induced angiogenesis, and anlotinib combined with crizotinib has a better antitumor effect than monotherapy in vitro & in vivo.
Overall, CCL20-mediated angiogenesis is involved in crizotinib resistance and could be overcome by using anlotinib in EML4-ALK positive NSCLC. The combination of anlotinib and crizotinib is a promising strategy for patients resistant to ALK-TKIs.
Background/Aims: We previously performed microRNA (miRNA) microarray to identify effective indicators of clear cell renal cell carcinoma (ccRCC) tissue samples and preoperative/postoperative plasma ...in which we identified miR-144-3p as an oncomiRNA. However, the molecular mechanism of miR-144-3p remains unclear. This study aims to explore the roles of miR-144-3p in the invasion, migration and Sunitinib-resistance in ccRCC and to elucidate the underlying mechanisms. Methods: Gain and loss of function approaches were used to investigate the cell proliferation, cycle distribution, clonogenicity, migration, invasion, chemosensitivity of miR-144-3p in vitro. The xenograft model was used to assess the effects of miR-144-3p overexpression on tumorigenesis. Bioinformatics analysis and dual-luciferase reporter assay were used to indentify AT-rich interactive domain 1A (ARID1A) as a direct target gene of miR-144-3p. Quantitative RT-PCR, Western blotting, and immunohistochemical (IHC) staining were used to explore ARID1A expression level of the mRNA and protein. Results: We found that miR-144-3p overexpression enhanced cell proliferation, clonogenicity, migration, invasion, and chemoresistance in ccRCC cells. Notably, the oncotumor activities of miR-144-3p were mediated by repressing the expression of ARID1A. The downregulation of ARIDIA could promote the function of miR-144-3p in cell proliferation, metastasis and chemoresistance. Consistently, ARID1A mRNA and protein levels were decreased in ccRCC and in nude mice, and they negatively correlated with miR-144-3p. Conclusion: Higher miR-144-3p may enhance malignancy and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may uncover novel strategies of ccRCC treatment.
The long noncoding RNA
, located in the human chromosome 9p21 region, has been reported to be involved in tumor progression.
regulates gene expression via recruiting PRC2 or titrating miRNA; it also ...participates in signaling pathways. Evidence has indicated that
is overexpressed in many cancer types and is capable of enhancing cell proliferation and cell cycle progression and inhibiting apoptosis and senescence.
has the potential to serve as a biomarker for diagnosis and prognosis in cancer. In this article we focus on recent advances in studies of the oncogenic role of
and its potential role in cancer medicine.
Chemotherapy for brain glioma has been of limited value due to the inability of transport of drug across the blood-brain barrier (BBB) and poor penetration of drug into the tumor. For overcoming ...these hurdles, the dual-targeting daunorubicin liposomes were developed by conjugating with p-aminophenyl-α-D-manno-pyranoside (MAN) and transferrin (TF) for transporting drug across the BBB and then targeting brain glioma. The dual-targeting effects were evaluated on the BBB model in vitro, C6 glioma cells in vitro, avascular C6 glioma tumor spheroids in vitro, and C6 glioma-bearing rats in vivo, respectively. After applying dual-targeting daunorubicin liposomes, the transport ratio across the BBB model was significantly increased up to 24.9%. The most significant uptake by C6 glioma was evidenced by flow cytometry and confocal microscope. The C6 glioma spheroid volume ratio was significantly lowered to 54.7%. The inhibitory rate to C6 glioma cells after crossing the BBB was significantly enhanced up to 64.0%. The median survival time of tumor bearing rats after administering dual-targeting daunorubicin liposomes (22
days) was significantly longer than that after giving free daunorubicin (17
days,
P
=
0.001) or other controls. In conclusion, the dual-targeting daunorubicin liposomes are able to improve the therapeutic efficacy of brain glioma in vitro and in animals.
Fig. 1. Overall schematic representation for the preparation of daunorubicin liposomes modified with p-aminophenyl-α-D-manno-pyranoside (MAN) and transferrin (TF).
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Selective addition to the C70 cage divides its π‐conjugated system into various smaller π‐conjugated systems with enhanced fluorescent properties. Key reactions include chlorination, methoxylation, ...ozonation, and Bingel or Bingel–Hirsch reactions. The maximum emission wavelength of the C70 multiadducts ranges from 450 to 655 nm. Among the C70 multiadducts, C70(OMe)8(C(COOEt)2)3 showed the highest quantum yield (ΦF=0.18) and the largest Δλmax(emission)− λmax(absorption) (402 nm), with maximum emission at 655 nm.
Amazing Technicolor Dream‐cage: Selective addition to the C70 cage divides its π‐conjugated system into various smaller π‐conjugated systems with enhanced fluorescence properties. Key reactions include chlorination, methoxylation, ozonation, and Bingel or Bingel–Hirsch reactions. C70(OMe)8(C(COOEt)2)3 (10) showed a quantum yield of ΦF=0.18 and a Δλmax(emission)−λmax(absorption) of 402 nm, with maximum emission at 655 nm.
Background
R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL). However, 20%–40% of ...patients survive less than 5 years. Novel prognostic biomarkers remain in demand.
Methods
Baseline plasma autoantibodies (AAbs) were assessed in 336 DLBCLs. In the discovery phase (n = 20), a high‐density antigen microarray (∼21,000 proteins) was used to expound AAb profiles. In the verification phase (n = 181), with a DLBCL‐focused microarray, comparative results based on event‐free survival at 24 months (EFS24) and lasso Cox regression models of progression‐free survival (PFS) and overall survival (OS) were integrated to identify potential biomarkers. They were further validated by enzyme‐linked immunosorbent assay in validation phase 1 (n = 135) and a dynamic cohort (n = 12). In validation phase 2, a two‐AAb‐based risk score was established. They were further validated in an immunohistochemistry cohort (n = 55) and four independent Gene Expression Omnibus datasets (n = 1598).
Results
Four AAbs (CREB1, N4BP1, UBAP2, and DEAF1) were identified that showed associations with EFS24 status (p < .05) and superior PFS and OS (p < .05). A novel risk score model based on CREB1 and N4BP1 AAbs was developed to predict PFS with areas under the curve of 0.72, 0.71, 0.76, and 0.82 at 1, 3, 5, and 7 years, respectively, in DLBCL treated with R‐CHOP independent of the International Prognostic Index (IPI) and provided significant additional recurrence risk discrimination (p < .05) for the IPI. CREB1 and N4BP1 proteins and messenger RNAs were also associated with better PFS and OS (p < .05).
Conclusions
This study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL.
Autoantibodies (AAbs) have the potential for personalized monitoring of tumor recurrence. Serological AAbs against N4BP1, CREB1, DEAF1, and UBAP2 were independent of International Prognostic Index traditional risk factors for diffuse large B‐cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Notably, two of these biomarkers, CREB1 and N4BP1, exhibited prognostic significance at multiple levels, including messenger RNA, protein, and AAb. These findings suggest that monitoring AAb levels during treatment may be a useful tool for predicting prognosis and guiding personalized treatment strategies for patients with DLBCL.
The global hospitality industry is fast-turning sustainable and environmentally friendly. Behaviour-driven energy conservation is an emerging green hotel operation strategy to support this change. ...The long-stay accommodation services have gained momentum in the hospitality sector since the COVID-19 pandemic. However, the characteristics of long-stay hotel guests are often overlooked in sustainable interventions. Based on an empirical survey in China, this study aims to explore the factors driving energy-saving behaviours of long-stay hotel guests and to compare their effects on guests for different visiting purposes (leisure, business, and extended-stay resident). The analysis indicates that attitude, personal norm and place attachment present a direct contribution to energy-saving behaviour. Besides, the results support that attitude and personal norm connect environmental values and energy-saving behaviour. Both altruistic and biospheric values have positive effects, while egoistic values seem to play a negative role. Biospheric values have stronger impact on attitude and personal norm of business guests. Place attachment has a stronger influence on extended-stay residents while its contribution to energy-saving behaviours of business guests is smaller than other guests. Besides, leisure guests are more sensitive to moral obligations. This research sheds novel lights on the psychological perspectives of the observed heterogeneity of energy-saving behaviours of hotel guests with different visiting purposes. The findings provide hotel operators with a novel theoretical reference for targeted energy-saving interventions to promote energy-saving actions of long-term hotel guests. The study, therefore, can contribute to sustainable tourism policymaking and behaviour-driven hotel energy management.
•Altruistic and biospheric values play positive roles in hotel energy-saving behaviours.•Place attachment significantly contributes to attitude, personal norms and behaviours.•Attitude and personal norms bridge environmental values and energy-saving behaviours.•Psychological factors present different effects on guests with different visiting purposes.•Leisure guests are more sensitive to moral obligations.
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