The transmembrane P-glycoprotein (P-gp) pumps that efflux drugs are a major mechanism of cancer drug resistance. They are also important in protecting normal tissue cells from poisonous xenobiotics ...and endogenous metabolites. Here, we report a fucoidan-decorated silica-carbon nano-onion (FSCNO) hybrid nanoparticle that targets tumor vasculature to specifically release P-gp inhibitor and anticancer drug into tumor cells. The tumor vasculature targeting capability of the nanoparticle is demonstrated using multiple models. Moreover, we reveal the superior light absorption property of nano-onion in the near infrared region (NIR), which enables triggered drug release from the nanoparticle at a low NIR power. The released inhibitor selectively binds to P-gp pumps and disables their function, which improves the bioavailability of anticancer drug inside the cells. Furthermore, free P-gp inhibitor significantly increases the systemic toxicity of a chemotherapy drug, which can be resolved by delivering them with FSCNO nanoparticles in combination with a short low-power NIR laser irradiation.
The aim of this study is to explore the potential of technology for detecting mind wandering, particularly during video-based distance learning, with the ultimate benefit of improving learning ...outcomes. To overcome the challenges of previous mind wandering research in ecological validity, sample balance, and dataset size, this study utilized practical electroencephalography (EEG) recording hardware and designed a paradigm consisting of viewing short-duration video lectures under a focused learning condition and a future planning condition. Participants estimated statistics of their attentional state at the end of each video, and we combined this rating scale feedback with self-caught key press responses during video watching to obtain binary labels for classifier training. EEG was recorded using an 8-channel system, and spatial covariance features processed by Riemannian geometry were employed. The results demonstrate that a radial basis function kernel support vector machine classifier, using Riemannian-processed covariance features from delta, theta, alpha, and beta bands, can detect mind wandering with a mean area under the receiver operating characteristic curve (AUC) of 0.876 for within-participant classification and AUC of 0.703 for cross-lecture classification. Furthermore, our results suggest that a short duration of training data is sufficient to train a classifier for online decoding, as cross-lecture classification remained at an average AUC of 0.689 when using 70% of the training set (about 9 min). The findings highlight the potential for practical EEG hardware in detecting mind wandering with high accuracy, which has potential application to improving learning outcomes during video-based distance learning.
Nitrous acid (HONO) can powerfully influence atmospheric photochemistry by producing hydroxyl radical (OH), which is a crucial oxidant that controls the fate of atmospheric trace species. To deduce ...HONO formation mechanisms in polluted regions, two field observations were conducted in urban Beijing during the early summer of 2017 and the winter of 2018. These two seasons bore distinguishing pollution characteristics with a higher degree of ageing and heavier aerosol loading in the early summer and more abundant NOx (NOx = NO + NO2) in the winter. Elevated concentrations of HONO were observed during these two seasons, with the mean ± standard deviation (maximum) concentrations of 1.25 ± 0.94 (6.69) ppbv and 1.04 ± 1.27 (9.55) ppbv in early summer and winter, respectively. The observed daytime (08:00–17:00 h, local time) HONO production rate was several times higher in early summer than in winter (4.44 ± 1.93 ppbv h−1 vs. 0.88 ± 0.49 ppbv h−1). Budget analysis revealed distinct daytime HONO formation mechanisms during these two seasons. Photo-induced heterogeneous conversion of NO2 on the ground surface dominated in early summer, and homogeneous reaction of NO + OH was dominant in winter. Photolysis of HONO was the major source of primary OH in both seasons, and thus, played a key role in the regulation of atmospheric oxidising capacity. This study demonstrates the significant seasonal variations in HONO budget and underlines the predominant role of HONO in primary OH production in Beijing. Our findings will be helpful to gain an understanding of the chemical mechanisms underlying the formation of secondary pollution in metropolitan areas.
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•The HONO/NOx ratio in early summer is twice that in winter in urban Beijing.•Heterogeneous reaction of NO2 on the ground governs HONO formation in early summer.•Homogeneous reaction of NO + OH is the dominant source of HONO in winter.•HONO is the major precursor of primary OH in both early summer and winter.
Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb’s quality. AS-IV is a tetracyclic ...triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS—IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects.
Aims
Clinical trials for calcitonin gene-related peptide (CGRP) inhibitors excluded the concomitant use of onabotulinumtoxinA; thus, there is a lack of efficacy and safety data of the combined ...therapies. Our study aims to examine the effectiveness of CGRP inhibitors with onabotulinumtoxinA by evaluating migraine reductions in headache days and severity.
Methods
Seventeen patients with chronic migraines were identified who had a partial or poor response to onabotulinumtoxinA, and were placed on dual therapy with a CGRP inhibitor. Patients’ initial headache days and severity ratings were compared to final values taken 1–6 months after adding the CGRP inhibitor to their treatment regime. Comparisons between headache days and severity ratings prior to and during dual treatment were performed utilizing the Kruskal–Wallis test. The significance was set at
p
< 0.05.
Results
Of 17 patients (16F/1 M),
n
= 9 were taking fremanezumab,
n
= 4 were taking erenumab, and
n
= 4 were taking galcanezumab. Patients’ average headache days per month was reduced from 27.6 ± 4.8 initially to 18.6 ± 9.4 post-treatment (
p
= 0.00651), and their average pain level was reduced from 8.4 ± 1.4 out of 10 to 5.4 ± 2.5 (
p
= 0.00074). No serious adverse side effects were reported from patients on dual therapy.
Conclusion
Patients with suboptimal response to onabotulinumtoxinA may benefit from CGRP inhibitors’ addition to their migraine regimens. Placebo-controlled randomized studies are advised to corroborate this finding.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a local or systemic inflammatory response. At present, the increasing research results show that the pathogenesis of the ...disease is complex, and the methods of clinical treatment also show diversity. This review analyzes and summarizes the existing mechanism research and drug treatment methods in order to provide a reference value for further drug research and development.
We carried out a thorough literature search using databases. According to the main purpose of the article, irrelevant articles were excluded after further examination and directly relevant articles were included. Finally, the information related to the article was summarized.
In this article, seventy-four articles are included. According to related articles, there are mainly four kinds of drugs, namely antimalarial drugs, glucocorticoids, immunosuppressive agents and biological agents. About fifty-five articles summarized the drugs for the treatment of systemic lupus erythematosus. The rest of the articles were related to the research progress of the mechanism of systemic lupus erythematosus.
This article describes the pathogenesis of systemic lupus erythematosus, and summarizes the traditional and new therapeutic drugs, which is not only beneficial to the treatment of lupus erythematosus patients, but also plays a vital reference significance for the future development of new systemic lupus erythematosus drugs.
Following the coronavirus disease-2019 outbreak caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an ongoing need to seek drugs that target COVID-19. First off, ...novel drugs have a long development cycle, high investment cost, and are high risk. Second, novel drugs must be evaluated for activity, efficacy, safety, and metabolic performance, contributing to the development cycle, investment cost, and risk. We searched the Cochrane COVID-19 Study Register (including PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and WHO COVID-19 Coronaviral Disease Global Literature to identify completed and ongoing studies as of February 20, 2024. We evaluated the pharmacological effects, in vivo and in vitro data of the 16 candidates in the paper. The difficulty of studying these candidates in clinical trials involving COVID-19 patients, dosage of repurposed drugs, etc. is discussed in detail. Ultimately, Metformin is more suitable for prophylactic administration or mildly ill patients; the combination of Oseltamivir, Tamoxifen, and Dexamethasone is suitable for moderately and severely ill patients; and more clinical trials are needed for Azvudine, Ribavirin, Colchicine, and Cepharanthine to demonstrate efficacy.
Cancer stem cells (CSCs) are rare cancer cells that are postulated to be responsible for cancer relapse and metastasis. However, CSCs are difficult to isolate and poorly understood. Here, a ...bioinspired approach for label‐free isolation and culture of CSCs, by microencapsulating one cancer cell in the nanoliter‐scale hydrogel core of each prehatching embryo‐like core–shell microcapsule, is reported. Only a small percentage of the individually microencapsulated cancer cells can proliferate into a cell colony. Gene and protein expression analyses indicate high stemness of the cells in the colonies. Importantly, the colony cells are capable of cross‐tissue multilineage (e.g., endothelial, cardiac, neural, and osteogenic) differentiation, which is not observed for “CSCs” isolated using other contemporary approaches. Further studies demonstrate the colony cells are highly tumorigenic, metastatic, and drug resistant. These data show the colony cells obtained with the bioinspired one‐cell‐culture approach are truly CSCs. Significantly, multiple pathways are identified to upregulate in the CSCs and enrichment of genes related to the pathways is correlated with significantly decreased survival of breast cancer patients. Collectively, this study may provide a valuable method for isolating and culturing CSCs, to facilitate the understanding of cancer biology and etiology and the development of effective CSC‐targeted cancer therapies.
A bioinspired technology is developed to isolate cancer stem cells (CSCs) by culturing one cell in the nanoliter‐scale hydrogel core of the prehatching embryo‐like core–shell microcapsules. The CSCs are capable of cardiac, neural, osteogenic, and endothelial differentiation, and are highly tumorigenic, metastatic, and drug resistant. The technology may be valuable for understanding cancer biology/etiology and developing CSC‐targeted effective cancer therapies.
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