E-cigarette use and associated factors among adults aged 18-44 years in China: Findings from an online survey.

INTRODUCTION: There needs to be more up-to-date evidence on the prevalence of e-cigarette use among Chinese adults. This study aims to investigate the prevalence and associated factors of e-cigarette use among adults aged 18-44 years in China. METHODS: Cross-sectional design and convenience sampling were used. The data for this study were obtained from an online survey conducted in mainland China from April to May 2023. The target population was adults aged 18-44 years. Descriptive analysis was employed to report the prevalence of e-cigarette use, while adjusted multivariable logistic regression was performed to examine the association between e-cigarette use and related factors. RESULTS: A total of 4256 participants were included in this study; 12.9% were current e-cigarette users, 5.9% were frequent users, and 7.0% were occasional users. The descriptive analysis results indicated that males and cigarette users had a higher prevalence of e-cigarette use. Multivariable analysis showed that e-cigarette use was significantly associated with female gender (AOR=0.76, 95% CI: 0.60-0.96), those aged 25-34 years with monthly income 6000-8999 CNY (AOR=2.01; 95% CI: 1.18-3.41), those aged 25-34 years with monthly income ≥9000 CNY (AOR=2.20; 95% CI: 1.26-3.82), college or undergraduate degree (AOR=1.91; 95% CI: 1.22-3.00), urban residence (AOR=1.72; 95% CI: 1.34-2.20), being a current smoker (AOR=3.32; 95% CI: 2.64-4.16), perception of harm (AOR=0.66; 95% CI: 0.60-0.73), and perception of benefit (AOR=2.31; 95% CI: 2.04-2.61). CONCLUSIONS: The prevalence of current e-cigarette use among adults in China was 12.9% within our sample. In addition to sociodemographic factors, individuals with a higher perception of the harm associated with e-cigarettes were less likely to engage in e-cigarette consumption. Conversely, individuals who perceive the 'benefits' of e-cigarettes more favorably use them. Targeted interventions, such as health education, are recommended to help adults develop a correct understanding of e-cigarettes and lower the prevalence of e-cigarette use.

Occurrence, potential sources, and ecological risk assessment of microplastics in the inland river basins in Northern China.

Microplastics (MPs) are the pollutants, found widely across various environmental media. However, studies on the MP pollution in urban rivers and the necessary risk assessments remain limited. In this study, the abundance and characteristics of microplastics in a typical urban river were examined to evaluate their distribution, sources, and ecological risks. It was observed that the abundance of MPs in sediments (220-2840 items·kg-1 dry weight (DW)) was much higher than that in surface water (2.9-10.3 items·L-1), indicating that the sediment is the "sink" of river MPs. Surface water and sediment were dominated by small particle size MPs (< 0.5 mm). Fiber and debris were common shapes of MPs in rivers and sediments. The microplastics in river water and sediments were primarily white and transparent, respectively. Polypropylene (PP) and polyethylene (PE) were the major polymers found.

Time-dependent proteomics and drug response in expanding cancer cells.

Cancer cell line is commonly used for discovery and development of anti-cancer drugs. It is generally considered that drug response remains constant for a certain cell line due to the identity of genetics thus protein patterns. Here, we demonstrated that cancer cells continued dividing even after reaching confluence, in that the proteomics was changed continuously and dramatically with strong relevance to cell division, cell adhesion and cell metabolism, indicating time-dependent intrinsically reprogramming of cells during expansion. Of note, the inhibition effect of most anti-cancer drugs was strikingly attenuated in culture cells along with cell expansion, with the strongest change at the third day when cells were still expanding. Profiling of an FDA-approved drug library revealed that attenuation of response with cell expansion is common for most drugs, an exception was TAK165 that was a selective inhibitor of mitochondrial respiratory chain complex I. Finally, we screened a panel of natural products and identified four pentacyclic triterpenes as selective inhibitors of cancer cells under prolonged growth. Taken together, our findings underscore that caution should be taken in evaluation of anti-cancer drugs using culture cells, and provide agents selectively targeting overgrowth cancer cells.

Development and psychometric assessment of Health Action Process Approach (HAPA) in terms of smoking cessation among Chinese smokers.

The Health Action Process Approach (HAPA) is a two-stage (pre-intentional and post-intentional) behavioral change model that distinguishes between motivation and volition in behavior change process. This study aims to develop HAPA-based assessments for smoking cessation among current smokers. The HAPA-based measures were developed and the draft measures included nine constructs, namely, risk perception in smoking-induced cancer, risk perception in smoking-induced systemic disease, positive outcome expectancy, negative outcome expectancy, self-efficacy in quitting smoking, self-efficacy in maintaining, self-efficacy in re-initiating, quitting planning and coping planning in smoking cessation, with a total of 26 items. A cross-sectional survey was conducted in China in 2022. Principal Component Analysis was used for Exploratory Factor Analysis (EFA). Cronbach's α coefficient was calculated to evaluate the internal consistency. Variables such as severity of smoking addiction were selected to evaluate the correlation between the HAPA scale and these variables. Of the 928 participants, 76.4% (709/928) were male and the median age was 35 years. Five factors were extracted by EFA. The factor loadings of each item were all greater than 0.60, and the cumulative variance contribution rate was 90.15%. The Cronbach's α coefficient of each HAPA-based subscales was 0.929-0.986. The HAPA-based measurements are comprehensive, reliable and valid in the assessment of smokers' smoking cessation cognition, which can be used to guide the design and implementation of intervention and the development of theory.

Long-acting inhaled medicines: Present and future.

Inhaled medicines continue to be an essential part of treatment for respiratory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. In addition, inhalation technology, which is an active area of research and innovation to deliver medications via the lung to the bloodstream, offers potential advantages such as rapid onset of action, enhanced bioavailability, and reduced side effects for local treatments. Certain inhaled macromolecules and particles can also end up in different organs via lymphatic transport from the respiratory epithelium. While the majority of research on inhaled medicines is focused on the delivery technology, particle engineering, combination therapies, innovations in inhaler devices, and digital health technologies, researchers are also exploring new pharmaceutical technologies and strategies to prolong the duration of action of inhaled drugs. This is because, in contrast to most inhaled medicines that exert a rapid onset and short duration of action, long-acting inhaled medicines (LAIM) improve not only the patient compliance by reducing the dosing frequency, but also the effectiveness and convenience of inhaled therapies to better manage patients' conditions. This paper reviews the advances in LAIM, the pharmaceutical technologies and strategies for developing LAIM, and emerging new inhaled modalities that possess a long-acting nature and potential in the treatment and prevention of various diseases. The challenges in the development of the future LAIM are also discussed where active research and innovations are taking place.

Ravidomycin Analogs from Streptomyces sp. Exhibit Altered Antimicrobial and Cytotoxic Selectivity.

Six new ravidomycin analogs (1-4, 6, and 7) were isolated from Streptomyces sp. Am59 using UV- and LCMS-guided separation based on Global Natural Products Social (GNPS) molecular networking analysis. Furthermore, we isolated fucomycin V (9), which possesses the same chromophore as ravidomycin but features a d-fucopyranose instead of d-ravidosamine. This is the first report of 9 as a natural product. Four new analogs (10-13) of 9 were also isolated. The structures were elucidated by combined spectroscopic and computational methods. We also found an inconsistency with the published [α]D25 of deacetylravidomycin, which is reported to have a (-) sign. Instead, we observed a (+) specific rotation for the reported absolute configuration of deacetylravidomycin (containing d-ravidosamine). We confirmed the positive sign by reisolating deacetylravidomycin from S. ravidus and by deacetylating ravidomycin. Finally, antibacterial, antifungal, and cytotoxicity activities were determined for the compounds. Compared to deacetylravidomycin, the compounds 4-6, 9, 11, and 12 exhibited greater antibacterial selectivity.

A Personalized Mobile Cessation Intervention to Promote Smokers From the Preparation Stage to the Action Stage: Double-blind Randomized Controlled Trial.

BACKGROUND: Most mobile cessation studies have found that such interventions have a higher quitting rate than interventions providing minimal smoking cessation support. However, why such interventions are effective has been almost unstudied by researchers. OBJECTIVE: This paper describes the principles of the personalized mobile cessation intervention-based WeChat app and used generalized estimated equations to assess why a personalized mobile cessation intervention was more likely to promote smokers from the preparation stage to the action stage than a nonpersonalized intervention. METHODS: This is a 2-arm, double-blind, randomized controlled trial in five cities in China. The intervention group received a personalized mobile cessation intervention. The control group received a nonpersonalized SMS text message smoking cessation intervention. All information was sent by the WeChat app. The outcomes were the change in protection motivation theory construct scores and the change in transtheoretical model stages. RESULTS: A total of 722 participants were randomly assigned to the intervention or control group. Compared with those who received the nonpersonalized SMS text message intervention, smokers who received the personalized intervention presented lower intrinsic rewards, extrinsic rewards, and response costs. Intrinsic rewards were determinants of stage change, thus explaining why the intervention group was more likely to promote smokers from the preparation stage to the action stage (odds ratio 2.65, 95% CI 1.41-4.98). CONCLUSIONS: This study identified the psychological determinants at different stages to facilitate smokers moving forward to the next stage of quitting behavior and provides a framework to explore why a smoking cessation intervention is effective. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100041942; https://tinyurl.com/2hhx4m7f.

[Microplastic Pollution Status and Ecological Risk Evaluation in Weihe River].

This study aimed to explore the occurrence state, morphological characteristics, polymer types, as well as potential ecology of microplastics in the Weihe River in Northwest China. Thus, we identified the abundance distribution, shape, particle size, color, and polymer type of microplastics in the surface water of the Weihe River by conducting field sampling, microscope observation, Fourier infrared spectroscopy, Micro-Raman spectroscopy, etc., during the normal water period (May) of 2021. Subsequently, we analyzed the potential ecological and environmental risks of microplastics using the pollution load index method and species sensitivity distribution method. The results showed that microplastics were detected to exist in all sampling points and the abundance ranged from (2.9±0.8) to (10.3±2.8) n·L-1. The concentration of microplastics in the main stream of the Weihe River was higher than that in the tributaries. Fiber (15.04%-77.03%), small size (<0.5 mm) (27.27%-89.38%), and colored (15.85%-49.53%) were the predominant microplastic types. Polyethylene (32.98%), polypropylene (29.79%), polystyrene (21.21%), and polyethylene (10.61%) terephthalate were the main types of polymers detected. In general, the microplastic pollution in Weihe River was at a medium level and had not affected aquatic organisms, but its high concentration and the characteristic of the plastics to adsorb other pollutants are still of concern.

Eltrombopag binds SDC4 directly and enhances MAPK signaling and macropinocytosis in cancer cells.

Syndecan-4 (SDC4) is a single-pass transmembrane glycoprotein implicated in a variety of oncogenic signaling pathways. It is also an intrinsically disordered protein and considered "undruggable". In the present study, we confirmed that knocking out SDC4 in pancreatic cancer cells markedly impaired macropinocytosis, colony formation, as well as xenograft tumor initiation and growth. Quantitative proteomic profiling of Sdc4 knockout (KO) cells revealed significant changes in cell metabolic pathways. In a cellular protein-based ligand interaction screening, we identified that Eltrombopag (ETBP), an FDA-approved agonist of the thrombopoietin receptor (TPOR) for immune thrombocytopenia, could directly bind to SDC4 with a Kd value of ~2 µM. We showed that the transmembrane motif was essential for SDC4 binding to ETBP. Unexpectedly, ETBP not only increased SDC4 abundance, but also enhanced SDC4-associated MAPK signaling pathway and macropinocytosis in cancer cells. Our results indicate that ETBP is a potential agonist of SDC4 in a fashion similar to its original target TPOR, and that caution should be taken when using ETBP for chemotherapy-induced thrombocytopenia in cancer patients.

Neddylation is essential for ß-catenin degradation in Wnt signaling pathway.

ß-Catenin is a central component in the Wnt signaling pathway; its degradation has been tightly connected to ubiquitylation, but it is rarely examined by loss-of-function assays. Here we observe that endogenous ß-catenin is not stabilized upon ubiquitylation depletion by a ubiquitylation inhibitor, TAK-243. We demonstrate that N-terminal phosphorylated ß-catenin is quickly and strongly stabilized by a specific neddylation inhibitor, MLN4924, in all examined cell types, and that ß-catenin and TCF4 interaction is strongly enhanced by inhibition of neddylation but not ubiquitylation. We also confirm that the E3 ligase ß-TrCP2, but not ß-TrCP1, is associated with neddylation and destruction of ß-catenin. GSK3ß and adenomatous polyposis coli (APC) are not required for ß-catenin neddylation but essential for its subsequent degradation. Our findings not only clarify the process of ß-catenin modification and degradation in the Wnt signaling pathway but also highlight the importance of reassessing previously identified ubiquitylation substrates.

Liquidambaric acid inhibits Wnt/ß-catenin signaling and colon cancer via targeting TNF receptor-associated factor 2.

Wnt/ß-catenin signaling is a well-established driver of colon cancer; however, a targeted therapeutic agent has not reached clinics yet. In the present study, we report that the natural compound liquidambaric acid (LDA) inhibits oncogenic Wnt/ß-catenin signaling in vitro and in vivo through its direct target tumor necrosis factor receptor-associated factor 2 (TRAF2). Mechanistically, TRAF2 positively regulates Wnt signaling by interacting with the N-terminal of ß-catenin via its TRAF-C domain; this interaction is disrupted in presence of LDA. Particularly, a TRAF2/ß-catenin/TCF4/TNIK complex is present in colon cancer cells, where TRAF2 is indispensable for the complex formation, and TRAF2/ß-catenin and ß-catenin/TCF4 interactions are disrupted upon LDA treatment. Our findings not only highlight that TRAF2 is an oncogenic regulator of Wnt/ß-catenin signaling and colon cancer but also provide a lead compound targeting TRAF2 for cancer therapy.

Precisely Regulated Luminescent Gold Nanoparticles for Identification of Cancer Metastases.

The nanoprobes for identification of cancer metastases in the mononuclear phagocyte system (MPS) organs are of significant importance but are limited due to the long-standing challenge of low tumor-targeting specificity with inadequate targeting efficiency and high nonspecific accumulation. Here, we report a surface regulation strategy that integrates the tumor-acidity-activated charge-reversal behavior and precise control in both hydrodynamic diameter (HD) and surface charge on ultrasmall luminescent gold nanoparticles (AuNPs) to achieve significantly high tumor-targeting specificity. The precise regulation of AuNPs to a rational HD and surface charge could rapidly and selectively recognize small metastatic tumors (∼1 mm) in liver and lung with high signal-to-noise ratios of 4.6 and 4.5, respectively. These results help further understand the in vivo transport of nanoprobes and provide guidance for design of translatable nanosized nanomedicines in cancer metastasis theranostics.

Quality by design thinking in the development of long-acting injectable PLGA/PLA-based microspheres for peptide and protein drug delivery.

Adopting the Quality by Design (QbD) approach in the drug development process has transformed from "nice-to-do" into a crucial and required part of the development, ensuring the quality of pharmaceutical products throughout their whole life cycles. This review is discussing the implementation of the QbD thinking into the production of long-acting injectable (LAI) PLGA/PLA-based microspheres for the therapeutic peptide and protein drug delivery. Various key elements of the QbD approaches are initially elaborated using Bydureon®, a commercial product of LAI PLGA/PLA-based microspheres, as a classical example. Subsequently, the factors influencing the release patterns and the stability of the peptide and protein drugs are discussed. This is followed by a summary of the state-of-the-art of manufacturing LAI PLGA/PLA-based microspheres and the related critical process parameters (CPPs). Finally, a landscape of generic product development of LAI PLGA/PLA-based microspheres is reviewed including some major challenges in the field.

Minimalist linkers suitable for irreversible inhibitors in simultaneous proteome profiling, live-cell imaging and drug screening.

Activity-based protein profiling (ABPP) and bioimaging have been powerful approaches for in situ drug screening and target identification. However, these approaches are still hindered by the preparation of high-quality probes. To address this challenge, we developed a series of novel minimalist linkers for irreversible inhibitors by incorporation of various bioorthogonal handles into an α,ß-unsaturated amide, a common moiety of many irreversible inhibitors. The linker-containing probes have been demonstrated to be suitable for simultaneous protein labelling, live cell imaging and drug screening.

A microfluidic device for studying chemotaxis mechanism of bacterial cancer targeting.

Bacterial cancer targeting may become an efficacious cancer therapy, but the mechanisms underlying bacterial specificity for cancer cells need to be explored prior to adopting it as a new clinical application. To characterize the mechanism of bacterial chemotactic preference towards cancer cells, we developed a microfluidic device for in vitro study. The device consists of a cell culture chamber on both sides of a central bacteria channel, with micro-channels used as barriers between them. The device, when used as model for lung cancer, was able to provide simultaneous three-dimensional co-culture of multiple cell lines in separate culture chambers, and when used as model for bacterial chemotaxis, established constant concentration gradients of biochemical compounds in a central channel by diffusion through micro-channels. Fluorescence intensity of green fluorescence protein (GFP)-encoding bacteria was used to measure bacterial taxis behavior due to established chemotactic gradients. Using this platform, we found that Escherichia coli (E. coli) clearly illustrated the preference for lung cancer cells (NCI-H460) which was attributed to biochemical factors secreted by carcinoma cells. Furthermore, by secretome analysis and validation experiments, clusterin (CLU) was found as a key regulator for the chemotaxis of E. coli in targeting lung cancer.

Integrated proteomic and N-glycoproteomic analyses of doxorubicin sensitive and resistant ovarian cancer cells reveal glycoprotein alteration in protein abundance and glycosylation.

Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics. A total of 1525 unique N-glycosite-containing peptides from 740 N-glycoproteins were identified and quantified, of which 253 N-glycosite-containing peptides showed significant change in the NCI/ADR-RES cells. Meanwhile, stable isotope labeling by amino acids in cell culture (SILAC) based comparative proteomic analysis of the two ovarian cancer cells led to the quantification of 5509 proteins. As about 50% of the identified N-glycoproteins are low-abundance membrane proteins, only 44% of quantified unique N-glycosite-containing peptides had corresponding protein expression ratios. The comparison and calibration of the N-glycoproteome versus the proteome classified 14 change patterns of N-glycosite-containing peptides, including 8 up-regulated N-glycosite-containing peptides with the increased glycosylation sites occupancy, 35 up-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy, 2 down-regulated N-glycosite-containing peptides with the decreased glycosylation sites occupancy, 46 down-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy. Integrated proteomic and N-glycoproteomic analyses provide new insights, which can help to unravel the relationship of N-glycosylation and multidrug resistance (MDR), understand the mechanism of MDR, and discover the new diagnostic and therapeutic targets.