Background Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been ...confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. Methods The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. Results We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Conclusions Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression. Keywords: LncRNAs, Exosome, Multivesicular body, Invadopodia, Hepatocellular carcinoma
Wound healing, known as a fundamental healthcare issue worldwide, has been attracting great attention from researchers. Here, novel bioactive gellan gum microfibers loaded with antibacterial peptides ...(ABPs) and vascular endothelial growth factor (VEGF) are proposed for wound healing by using microfluidic spinning. Benefitting from the high controllability of microfluidics, bioactive microfibers with uniform morphologies are obtained. The loaded ABPs are demonstrated to effectively act on bacteria at the wound site, reducing the risk of bacterial infection. Besides, sustained release of VEGF from microfibers helps to accelerate angiogenesis and further promote wound healing. The practical value of woven bioactive microfibers is demonstrated via animal experiments, where the wound healing process is greatly facilitated because of the excellent circulation of air and nutritious substances. Featured with the above properties, it is believed that the novel bioactive gellan gum microfibers would have a remarkable effect in the field of biomedical application, especially in promoting wound healing.
Ethnopharmacological relevance: Dried and mature seeds of Vaccaria segetalis (Neck.) Garcke ex Asch. (VS) are known for their therapeutic effects, as they stimulate blood circulation, promote ...menstruation and diuresis and eliminate gonorrhoea. However, due to its hard shell, the dissolution of its active ingredients is often improved by steaming and frying in clinical applications. Among the processed products, wine-steamed Vaccaria segetalis (WVS) is one of the commonly used ones. Numerous historical records have shown that wine steaming can enhance the efficacy of drugs to promote blood circulation and remove blood stasis. However, the differences in the efficacy of VS and WVS in promoting blood circulation and removing blood stasis have not been thoroughly studied, and the possible reasons for these differences have not been reported.
The objective of this study was to identify quality markers (Q-markers) that could differentiate the efficacy of promoting blood circulation and removing blood stasis of VS and WVS, which could serve as a basis for the rational application of VS and WVS in clinical settings.
A pharmacodynamic comparison between the water extracts of VS and WVS was carried out based on a mouse acute blood stasis model (ABS) and thrombus zebrafish model. The potential bioactive substances of WVS were screened by investigating the correlation between common peaks identified for 10 batches of WVS by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and their rate of thrombosis inhibition in zebrafish. Furthermore, multivariate statistical analysis of chemical components between VS and WVS was conducted to speculate the Q-markers combined with the results of the bioactive components. Based on the efficacy verification of Q-markers, the content of Q-markers in 10 batches of WVS was evaluated.
The results of efficacy comparison assays demonstrated that the efficacy of WVS was more prominent than VS at the same dose. 5 components were screened as effective components of WVS for promoting blood circulation and removing blood stasis by correlation analysis. Furthermore, a total of 24 common ingredients were identified in VS and WVS extracts, and 9 of them showed increased dissolution rate after wine steaming, including 4 active ingredients, Hypaphorine, Vaccarin, Saponarin, and Isovitexin-2″-O-arabinoside, which were screened out by correlation analysis. The monomer test suggested that these 4 components could activate blood circulation and remove blood stasis in a dose-dependent manner. Consequently, Hypaphorine, Vaccarin, Saponarin, and Isovitexin-2″-O-arabinoside were selected as Q-markers to distinguish between VS and WVS. The content determination showed that the total contents of 4 Q-markers of WVS from 10 batches with different origins ranged from 0.478% to 0.716%.
This study compared the efficacy of VS and WVS in promoting blood circulation and resolving stasis and revealed Q-markers that reflected the difference in efficacy between them for the first time, which laid the foundation for establishing quality standards for WVS.
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It is now widely accepted that radiotherapy (RT) can provoke a systemic immune response, which gives a strong rationale for the combination of RT and immune checkpoint inhibitors (ICIs). However, RT ...is a double-edged sword that not only enhances systemic antitumor immune response, but also promotes immunosuppression to some extent. Nevertheless, many aspects regarding the efficacy and safety of this combination therapy remain unknown. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/chemoradiotherapy (CRT) and ICI combination therapy for non-small cell lung cancer (NSCLC) patients.
PubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 28
of February 2022.
3,652 articles were identified for screening and 25 trials containing 1,645 NSCLC patients were identified. For stage II-III NSCLC, the one- and two-year overall survival (OS) was 83.25% (95% confidence interval (CI): 79.42%-86.75%) and 66.16% (95% CI: 62.3%-69.92%), respectively. For stage IV NSCLC, the one- and two-year OS was 50% and 25%. In our study, the pooled rate of grade 3-5 adverse events (AEs) and grade 5 AEs was 30.18% (95% CI: 10.04%-50.33%, I
: 96.7%) and 2.03% (95% CI: 0.03%-4.04%, I
: 36.8%), respectively. Fatigue (50.97%), dyspnea (46.06%), dysphagia (10%-82.5%), leucopenia (47.6%), anaemia (5%-47.6%), cough (40.09%), esophagitis (38.51%), fever (32.5%-38.1%), neutropenia (12.5%-38.1%), alopecia (35%), nausea (30.51%) and pneumonitis (28.53%) were the most common adverse events for the combined treatment. The incidence of cardiotoxicity (0%-5.00%) was low, but it was associated with a high mortality rate (0%-2.56%). Furthermore, the incidence of pneumonitis was 28.53% (95% CI: 19.22%-38.88%, I
: 92.00%), grade ≥ 3 pneumonitis was 5.82% (95% CI: 3.75%-8.32%, I
: 57.90%) and grade 5 was 0%-4.76%.
This study suggests that the addition of ICIs to RT/CRT for NSCLC patients may be both safe and feasible. We also summarize details of different RT combinations with ICIs to treat NSCLC. These findings may help guide the design of future trials, the testing of concurrent or sequential combinations for ICIs and RT/CRT could be particularly useful to guide the treatment of NSCLC patients.
A discount strategy in word-of-mouth marketing Zhang, Tianrui; Li, Pengdeng; Yang, Lu-Xing ...
Communications in nonlinear science & numerical simulation,
07/2019, Letnik:
74
Journal Article
Recenzirano
•We propose a novel discount strategy for WOM marketing (the IBD strategy).•We model the WOM spreading process as a dynamic model (the DPA model).•We investigate the dynamics of the DPA model.•We ...examine the effect of different factors on the expected net profit of the IBD strategy.•Based on the above study, we suggest some promotional strategies.
This paper addresses the issue of discount pricing in word-of-mouth (WOM) marketing. First, we propose a novel discount strategy we refer to as the Influence-Based Discount (IBD) strategy, in which each buyer would enjoy a discount that is linearly proportional to his/her influence in the WOM network. For the purpose of evaluating the performance of an IBD strategy, we model the associated WOM spreading process as a higher-dimensional nonlinear differential dynamical system we refer to as the Dormant-Potential-Adopting (DPA) model. Next, we examine the dynamics of a DPA model through computer experiments. Thereby, we estimate the expected net profit of an IBD strategy and inspect how different factors influence this profit through numerical experiments. On this basis, we suggest some feasible promotional measures.
Incorporating plasticizers is an effective way to facilitate conduction of ions in solid polymer electrolytes (SPEs). However, this conductivity enhancement often comes at the cost of reduced ...mechanical properties, which can make the electrolyte membrane more difficult to process and increase safety hazards. Here, a novel crosslinking strategy, wherein metal‐alkoxy‐terminated polymers can be crosslinked by precisely controlling the content of H2O as an initiator, is proposed. As a proof‐of‐concept, trimethylaluminum (TMA)‐functionalized poly(ethylene oxide) (PEO) is used to demonstrate that ultrafine Al–O nanoclusters can serve as nodes to crosslink PEO chains with a wide range of molecular weights from 10 000 to 8 000 000 g mol−1. The crosslinked polymer network can incorporate a high concentration of plasticizers, with a total weight percentage over 75%, while still maintaining excellent stretchability (4640%) and toughness (3.87 × 104 kJ m−3). The resulting electrolyte demonstrates high ionic conductivity (1.41 mS cm−1), low interfacial resistance toward Li metal (48.1 Ω cm2), and a wide electrochemical window (>4.8 V vs Li+/Li) at 30 °C. Furthermore, the LiFePO4/Li battery shows stable cycle performance with a capacity retention of 98.6% (146.3 mAh g−1) over 1000 cycles at 1C (1C = 170 mAh g−1) at 30 °C.
A novel crosslinking strategy where metal‐alkoxy‐terminated polymers can be crosslinked by precisely controlling the content of H2O as an initiator is proposed. After incorporating a high concentration of plasticizers, the polymer‐in‐plasticizer solid electrolyte still maintains outstanding mechanical properties, thus demonstrating fast lithium‐conduction kinetics and effective inhibition of lithium dendrites simultaneously.
Background and Objective
Renal impairment is common in patients with cancer and can alter the PK and thus the safety and efficacy of drugs. We assessed the impact of renal impairment during treatment ...with ribociclib, a cyclin-dependent kinase 4/6 inhibitor, and determined dose recommendations for patients with advanced breast cancer with renal impairment.
Methods
A comprehensive assessment integrating pharmacokinetic, safety, and efficacy data from a phase I dedicated renal impairment study in non-cancer subjects and six phase I–III trials in patients with cancer was performed.
Results
Ribociclib showed higher pharmacokinetic exposure in subjects with renal impairment than those with normal renal function following a single 400-mg dose in the dedicated renal impairment study. However, in patient trials, both single-dose and steady‑state ribociclib exposure was comparable between patients with cancer with mild/moderate renal impairment and those with normal renal function following the recommended starting dose of 600 mg. Model-predicted steady‑state exposure in patients with advanced breast cancer was also similar across the renal function groups. Progression-free survival was similar and safety profiles were generally consistent across the renal cohorts (normal/mild/moderate) in patients with advanced breast cancer, with low-grade and manageable adverse events, demonstrating a positive benefit-risk profile.
Conclusions
From the collective evidence and considering a real-world clinical setting, no dose adjustment is recommended for patients with mild/moderate renal impairment, whereas a reduced dose is recommended for patients with severe renal impairment. This report presented a holistic and innovative strategy to determine dose in patients with renal impairment and demonstrated the effectiveness of integrating the data of both a clinical pharmacology study and patient trials to justify doses in patients with renal impairment.
Clinical Trial Registration
Clinicaltrials.gov identifiers: NCT02431481, NCT01958021, NCT02422615, NCT02278120, NCT01237236, NCT01898845, NCT01872260.
The aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer.
We ...retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors.
A total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio aOR 1.99, 95% confidence interval CI 1.25-3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39-0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups.
The presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.
To explore the risk factors and develop a nomogram to predict Double J stent encrustation incidence. The general demographic characteristics and underlying risk factors of 248 patients with upper ...urinary tract calculus who underwent endoscopic lithotripsy and Double J stenting at the Fifth Affiliated Hospital of Sun Yat-Sen University between January 1st, 2018 and January 1st, 2023 were retrospectively analyzed. Among them,173 patients were randomly selected to form the development cohort. A multivariate logistic regression model was employed to identify the independent risk factors associated with Double J stent encrustation, and a nomogram was developed for predicting its occurrence. Additionally, 75 patients were randomly selected to form the validation cohort to validate the nomogram. Multivariate logistic regression analysis revealed that several factors were significantly associated with Double J stent encrustation: indwelling time (odds ratio OR1.051; 95% confidence interval CI 1.030-1.073, P < .001), urine PH (OR 2.198; 95% CI 1.061-4.539, P = .033), fasting blood glucose (OR 1.590; 95% CI 1.300-1.943, P < .001), and total cholesterol (OR 2.676; 95% CI 1.551-4618, P < .001).Based on these findings, A nomogram was developed to predict the occurrence of Double J stent encrustation. The nomogram demonstrated good performance with an area under the curve of 0.870 and 0.862 in the development and validation cohorts, respectively. Furthermore, the calibration curve indicated a well-fitted model. We constructed and validated an accessible nomogram to assist urologists in evaluating the risk factors associated with Double J stent encrustation and predicting its likelihood.
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