Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor substance. In this study, we investigated the effect of
PP‐22, a monomer purified from
P. polyphylla var. yunnanensis, ...on the nasopharyngeal carcinoma cell line CNE‐2 in vitro. The results showed that
PP‐22 could inhibit the proliferation of CNE‐2 cells via the induction of apoptosis, with evidence of the characteristic morphological changes in the apoptosis in the nucleus and an increase in Annexin V‐positive cells. In addition, we found that
PP‐22 could activate the p38 mitogen‐activated protein kinase (MAPK) pathway and that this activation was reversed by SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast,
PP‐22 promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum stress pathway, in a caspase‐dependent manner. A further study showed that
PP‐22 also induced apoptosis by downregulating the signal transducers and activators of transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by STAT3 small interfering RNA. In addition,
PP‐22 could promote autophagy by inhibiting the extracellular regulated protein kinases (ERK) pathway. And autophagy plays a protective role against apoptosis. Together, these data show that
PP‐22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE‐2 cell line.
PP‐22 activates p‐p38 and endoplasmic reticulum (ER) stress and inhibits the signal transducers and activators of transcription 3 (STAT3) pathway to activate the caspase‐9/3 signaling pathway to trigger apoptosis. In addition, PP‐22 inhibits the mitogen‐activated protein kinase (MAPK)/ERK pathway to induce autophagy in CNE‐2 cells. Furthermore, autophagy is a protective mechanism for CNE‐2 cells in the context of PP‐22‐induced apoptotic cell death.
This study aimed to assess the effects of restricting mobile phone use before bedtime on sleep, pre-sleep arousal, mood, and working memory.
Thirty-eight participants were randomized to either an ...intervention group (n = 19), where members were instructed to avoid using their mobile phone 30 minutes before bedtime, or a control group (n = 19), where the participants were given no such instructions. Sleep habit, sleep quality, pre-sleep arousal and mood were measured using the sleep diary, the Pittsburgh sleep quality index, the Pre-sleep Arousal Scale and the Positive and Negative Affect Schedule respectively. Working memory was tested by using the 0-,1-,2-back task (n-back task).
Restricting mobile phone use before bedtime for four weeks was effective in reducing sleep latency, increasing sleep duration, improving sleep quality, reducing pre-sleep arousal, and improving positive affect and working memory.
Restricting mobile phone use close to bedtime reduced sleep latency and pre-sleep arousal and increased sleep duration and working memory. This simple change to moderate usage was recommended to individuals with sleep disturbances.
Drug-target interaction (DTI) is the basis of drug discovery. However, it is time-consuming and costly to determine DTIs experimentally. Over the past decade, various computational methods were ...proposed to predict potential DTIs with high efficiency and low costs. These methods can be roughly divided into several categories, such as molecular docking-based, pharmacophore-based, similarity-based, machine learning-based, and network-based methods. Among them, network-based methods, which do not rely on three-dimensional structures of targets and negative samples, have shown great advantages over the others. In this article, we focused on network-based methods for DTI prediction, in particular our network-based inference (NBI) methods that were derived from recommendation algorithms. We first introduced the methodologies and evaluation of network-based methods, and then the emphasis was put on their applications in a wide range of fields, including target prediction and elucidation of molecular mechanisms of therapeutic effects or safety problems. Finally, limitations and perspectives of network-based methods were discussed. In a word, network-based methods provide alternative tools for studies in drug repurposing, new drug discovery, systems pharmacology and systems toxicology.
Metal nanoparticles (NPs) with size comparable to their electron mean free path possess unusual properties and functionalities, serving as model systems to explore quantum and classical coupling ...interactions as well as building blocks of practical applications. Although advances in strategies for synthesizing metal NPs have enabled control of size, composition and shape, the requirement that defects are simultaneously controlled, to ensure essential perfect nanocrystallinity for physics modelling as well as device optimization, is a potentially more significant issue, but has posed substantial technological challenges. Here we report that crystallinity of monodisperse silver NPs can be well controlled by judicious choice of functional groups of molecular precursors, thus facilitating investigation of their scope for versatile applications. We demonstrate how nanoscale chemical transformation, electron-phonon interactions and nanomechanical properties are modified by nanocrystallinity. Lastly, we find that performance of NP-based molecular sensing devices can be optimized with significant improvement of figure of merit if perfect single-crystalline NPs are applied. Our approach represents a versatile synthetic route for other metal nanomaterials with unprecedented control of their structure, creating a rational pathway for understanding and manipulating nanoscale chemical and physical processes as well as technological applications of metal NPs.
Sorafenib is the most recommended first‐line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have ...demonstrated that a vascular pattern, named VETC (Vessels that Encapsulate Tumor Clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC‐mediated metastasis relies on vascular pattern, but not on migration and invasion of cancer cells. In this study, we aimed to explore whether vascular pattern could predict sorafenib benefit. Two cohorts of patients were recruited from four academic hospitals. The survival benefit of sorafenib treatment for patients with or without the VETC pattern (VETC+/VETC–) was investigated. Kaplan‐Meier analyses revealed that sorafenib treatment significantly reduced death risk and prolonged overall survival (OS; in cohort 1/2, P = 0.004/0.005; hazard ratio HR = 0.567/0.408) and postrecurrence survival (PRS; in cohort 1/2, P = 0.001/0.002; HR = 0.506/0.384) in VETC+ patients. However, sorafenib therapy was not beneficial for VETC‐ patients (OS in cohort 1/2, P = 0.204/0.549; HR = 0.761/1.221; PRS in cohort 1/2, P = 0.121/0.644; HR = 0.728/1.161). Univariate and multivariate analyses confirmed that sorafenib treatment significantly improved OS/PRS in VETC+, but not VETC–, patients. Further mechanistic investigations showed that VETC+ and VETC– HCCs displayed similar levels of light chain 3 (LC3) and phosphorylated extracellular signal‐regulated kinase (ERK) in tumor tissues (pERK) or endothelial cells (EC‐pERK), and greater sorafenib benefit was consistently observed in VETC+ HCC patients than VETC– irrespective of levels of pERK/EC‐pERK/LC3, suggesting that the different sorafenib benefit between VETC+ and VETC– HCCs may not result from activation of Raf/mitogen‐activated protein kinase kinase (MEK)/ERK and vascular endothelial growth factor (VEGF)A/VEGF receptor 2 (VEGFR2)/ERK signaling or induction of autophagy. Conclusion: Sorafenib is effective in prolonging the survival of VETC+, but not VETC–, patients. VETC pattern may act as a predictor of sorafenib benefit for HCC.
The ribosome is centrally situated to sense metabolic states, but whether its activity, in turn, coherently rewires transcriptional responses is unknown. Here, through integrated chemical-genetic ...analyses, we found that a dominant transcriptional effect of blocking protein translation in cancer cells was inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for anabolic metabolism, cellular proliferation, and tumorigenesis. These analyses linked translational flux to the regulation of HSF1 transcriptional activity and to the modulation of energy metabolism. Targeting this link with translation initiation inhibitors such as rocaglates deprived cancer cells of their energy and chaperone armamentarium and selectively impaired the proliferation of both malignant and premalignant cells with early-stage oncogenic lesions.
Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties play key roles in the discovery/development of drugs, pesticides, food additives, consumer products, and industrial ...chemicals. This information is especially useful when to conduct environmental and human hazard assessment. The most critical rate limiting step in the chemical safety assessment workflow is the availability of high quality data. This paper describes an ADMET structure–activity relationship database, abbreviated as admetSAR. It is an open source, text and structure searchable, and continually updated database that collects, curates, and manages available ADMET-associated properties data from the published literature. In admetSAR, over 210 000 ADMET annotated data points for more than 96 000 unique compounds with 45 kinds of ADMET-associated properties, proteins, species, or organisms have been carefully curated from a large number of diverse literatures. The database provides a user-friendly interface to query a specific chemical profile, using either CAS registry number, common name, or structure similarity. In addition, the database includes 22 qualitative classification and 5 quantitative regression models with highly predictive accuracy, allowing to estimate ecological/mammalian ADMET properties for novel chemicals. AdmetSAR is accessible free of charge at http://www.admetexp.org.
Happiness, defined as a state of well-being and contentment, is a central human goal. Despite advances in customer behavior research related to value co-creation, the link between customer happiness ...and these behaviors remains unclear. This study therefore examines customers' in-role participation behavior and extra-role citizenship behavior to determine their influence on customers' happiness. Customer participation and citizenship behaviors relate positively to customers' perceptions of both service performance and their contributions to others' welfare. In addition, collectivism moderates the relationship between perceived contributions to others' welfare and happiness; individualism instead moderates the relationship between perceived service performance and happiness. These findings provide both managerial implications and directions for business marketing ethics.
The interplay between light and matter is the basis of many fundamental processes and various applications. Harnessing light-matter interactions in principle allows operation of solid state devices ...under new physical principles: for example, the a.c. optical Stark effect (OSE) has enabled coherent quantum control schemes of spins in semiconductors, with the potential for realizing quantum devices based on spin qubits. However, as the dimension of semiconductors is reduced, light-matter coupling is typically weakened, thus limiting applications at the nanoscale. Recent experiments have demonstrated significant enhancement of nanoscale light-matter interactions, albeit with the need for a high-finesse cavity, ultimately preventing device down-scaling and integration. Here we report that a sizable OSE can be achieved at substantial energy detuning in a cavity-free colloidal metal-semiconductor core-shell hetero-nanostructure, in which the metal surface plasmon is tuned to resonate spectrally with a semiconductor exciton transition. We further demonstrate that this resonantly enhanced OSE exhibits polarization dependence and provides a viable mechanism for coherent ultrafast spin manipulation within colloidal nanostructures. The plasmon-exciton resonant nature further enables tailoring of both OSE and spin manipulation by tuning plasmon resonance intensity and frequency. These results open a pathway for tailoring light-matter-spin interactions through plasmon-exciton resonant coupling in a judiciously engineered nanostructure, and offer a basis for future applications in quantum information processing at the nanoscale. More generally, integrated nanostructures with resonantly enhanced light-matter interactions should serve as a test bed for other emerging fields, including nano-biophotonics and nano-energy.
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