Deciphering single-cell protein secretion and gene expressions by constructing cell-antibody conjugates.

Secreted proteins play critical roles in regulating immune responses, exerting cytotoxic effects on tumor cells, promoting inflammatory processes, and influencing cellular metabolism. Deciphering the intricate relationship between the heterogeneity of secreted proteins and their transcriptional states is pivotal in the study of cellular heterogeneity. Here we proposed a cell-antibody conjugate-based sequencing methodology (Cellab-seq) for joint characterization of secreted proteins and transcriptome. Cellab-seq utilizes a chemoenzymatic strategy to construct cell-antibody conjugates, which enables the capture of secreted proteins and their signal transduction with the incorporation of barcode detection antibodies. We applied Cellab-seq to investigate how gene expression influences the activity of secreted proteins in NK cells. Altogether, this strategy facilitates a nuanced understanding of cellular dynamics under diverse physiological conditions, ultimately contributing to the prevention, diagnosis and treatment of diseases.

Chemoenzymatic Measurement of LacNAc in Single-Cell Multiomics Reveals It as a Cell-Surface Indicator of Glycolytic Activity of CD8+ T Cells.

Despite the rich information about the physiological state of a cell encoded in the dynamic changes of cell-surface glycans, chemical methods to capture specific glycan epitopes at the single-cell level are quite limited. Here, we report a chemoenzymatic method for the single-cell detection of N-acetyllactosamine (LacNAc) by labeling LacNAc with a specific DNA barcode. The chemoenzymatic labeling does not alter the transcriptional status of immune cells and is compatible with multiple scRNA-seq platforms. Integrated analysis of LacNAc and the transcriptome of T cells at the single-cell level reveals that the amount of cell-surface LacNAc is significantly upregulated in activated CD8+ T cells but maintained at basal levels in resting CD8+ T cells (i.e., naive and central memory T cells). Further analysis confirms that LacNAc levels are positively correlated with the glycolytic activity of CD8+ T cells during differentiation. Taken together, our study demonstrates the feasibility of the chemoenzymatic detection of cell-surface glycan in single-cell RNA sequencing-based multiomics with TCR sequence and cell-surface epitope information (i.e., scTCR and CITE-seq), and provides a new way to characterize the biological role of glycan in diverse physiological states.

Bio-Responsive Macromolecular Drug and Small-Molecular Drug Conjugates: Nanoparticulate Prodrugs for Tumor Microenvironment Heterogeneity Management and Therapeutic Response Enhancement.

How to break through the poor response of current drug therapy, which often resulted from tumor microenvironment heterogeneity (TMH), remains an enormous challenge in the treatment of critical diseases. In this work, a practical solution on bio-responsive dual-drug conjugates for overcoming TMH and improving antitumor treatment, which integrates the advantages of macromolecular drugs and small-molecular drugs, is proposed. Nanoparticulate prodrugs based on small-molecular drug and macromolecular drug conjugates are designed as a robust weapon for programmable multidrug delivery at tumor-specific sites: the tumor microenvironment acid condition triggers delivery of macromolecular aptamer drugs (AX102) to manage TMH (including tumor stroma matrix, interstitial fluid pressure, vasculature network, blood perfusion, and oxygen distribution), and intracellular lysosomal acid condition activates rapid release of small-molecular drugs (doxorubicin and dactolisib) to enhance curative effects. As compared with doxorubicin chemotherapy, the tumor growth inhibition rate is enhanced by 47.94% after multiple tumor heterogeneity management. This work verifies that the nanoparticulate prodrugs facilitate TMH management and therapeutic response enhancements, as well as elucidates synergetic mechanisms for drug resistance reversal and metastasis inhibition. It is hoped that the nanoparticulate prodrugs will be an excellent demonstration of the co-delivery of small-molecular drugs and macromolecular drugs.

Effects of leptin treatment immediately after neonatal seizures on serum clusterin and VEGF levels and brain oxidative stress-related proteins and neurobehavioral phenotypes.

The developing infant brain has a different response mechanism and repair potential for injury than the adult brain. There is an urgent need for new anticonvulsants to effectively control neonatal seizures while minimizing the drug's toxic damage to the developing brain. Leptin protects neuronal plasma membrane integrity, while it has clinical advantages in terms of anticonvulsant properties as well. This study aimed to evaluate the effect of immediate leptin treatment on the serum concentration of clusterin and vascular endothelial growth factor (VEGF), neuronal plasma membrane integrity-related proteins, and the neurobehavioral phenotypes following neonatal seizures. Leptin was injected i.p at a dose of 4 mg/kg 1 hour after daily 30 minutes prolonged seizures for consecutive 10 days. The serum biomarkers (clusterin and VEGF), and brain protein expression of ATF-4/GRP78/autophagy axis were measured by enzyme-linked immunosorbent assay and western blot in the acute phase (24 hours after the last seizures), respectively. Behavioral and histopathological phenotypes and seizure threshold were conducted from P23 to P34, respectively. There were rapid elevation of serum VEGF and clusterin as well as upregulated protein expression of ATF-4, GRP78, Beclin-1, and LC3 in the cerebral cortex and hippocampus following a neonatal seizure, which was restored by immediate treatment with leptin after seizures. In addition, leptin improved seizure-induced impaired neuropsychological, and cognitive functioning. Furthermore, leptin succeeded in ameliorating markers of neuronal excitability, including seizure threshold and hippocampal mossy fiber sprouting. In conclusion, this study verified that immediate treatment with leptin after neonatal seizures restored both rapid elevation of serum clusterin as well as upregulated protein expression of ATF-4/GRP78/autophagy axis in the cerebral cortex and hippocampus, which contributes to the recovery of neurological function.

Effectiveness of dual antiplatelet de-escalation therapy on the prognosis of patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention.

AIM: To investigate the effectiveness of de-escalation of ticagrelor (from ticagrelor 90 mg to clopidogrel 75 mg or ticagrelor 60 mg) on the prognosis of patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) after 3 months of oral dual antiplatelet therapy (DAPT). METHODS: From March 2017 to August 2021, 1056 patients with STEMI in a single centre, through retrospective investigation and analysis, were divided into intensive (ticagrelor 90 mg), standard (clopidogrel 75 mg after PCI) and de-escalation groups (clopidogrel 75 mg or ticagrelor 60 mg after 3 months of treatment with 90 mg ticagrelor) based on the type and dose of P2Y12 inhibitor 3 months after PCI, and the patients had a ≥ 12-month history of oral DAPT. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during the 12-month follow-up period, including composite end points of cardiac death, myocardial infarction, ischaemia-driven revascularization and stroke. The major safety endpoint was bleeding events. RESULTS: The results showed that during the follow-up period, there was no statistically significant difference in the incidence of MACCEs between the intensive and de-escalation groups (P > 0.05). The incidence of MACCEs in the standard treatment group was higher than that in the intensive treatment group (P = 0.014), but the incidence of bleeding events in the de-escalation group was significantly lower than that in the standard group (9.3% vs. 18.4%, χ²=7.191, P = 0.027). The Cox regression analysis showed that increases in haemoglobin (HGB) (HR = 0.986) and estimated glomerular filtration rate (eGFR) (HR = 0.983) could reduce the incidence of MACCEs, while old myocardial infarction (OMI) (P = 0.023) and hypertension (P = 0.013) were independent predictors of MACCEs. CONCLUSION: For STEMI patients undergoing PCI, the de-escalation scheme of ticagrelor to clopidogrel 75 mg or ticagrelor 60 mg at 3 months after PCI was related to the reduction of bleeding events, especially minor bleeding events, without an increase in ischaemic events.

Analyzing U.S. State Governments' COVID-19 Homepages during the Initial Lockdown in March and April 2020: Information Content and Interactivity.

During times of a pandemic, government emergency response webpages are an important communication channel and if properly managed, will mitigate pandemic impacts. Guided by the Crisis and Emergency Risk Communication (CERC) framework and web interactivity literature, this study examined the information content and interactivity of U.S. state governments' COVID-19 homepages when many states declared stay-at-home orders in March or April of 2020. Using a web archive service, we retrieved 48 state governments' COVID-19 homepages. Three coders coded these pages for the presence or absence of information content on five dimensions (timely updates, sensemaking information, efficacy information, targeted guidance, and anti-stigma communication) and interactivity on four dimensions (accessibility, navigability, media richness, and engagement). Results revealed that a large proportion of state governments' COVID-19 homepages provided timely information facilitating people's understanding of the pandemic. Yet, there were some information gaps regarding how to cope with the pandemic or its related problems, such as mental stress and social discrimination. While many COVID-19 homepages allowed easy navigation, page engagement and accessibility seemed inadequate. U.S. state governments' COVID-19 homepages could be a good source for sensemaking. Practitioners and researchers should explore how to better harness interactive Internet technologies and present information that fosters people's efficacy to manage through the pandemic.

COVID-19 Message Fatigue: How Does It Predict Preventive Behavioral Intentions and What Types of Information are People Tired of Hearing About?

This study examines the impact of message fatigue and what makes people fatigued in the context of the COVID-19 pandemic. Data collected with a Qualtrics panel (N = 744) showed that both active (i.e., reactance) and passive (i.e., inattention) resistance in message processing mediated the relationships between message fatigue and intentions to follow three types of preventive behaviors against COVID-19 (i.e., wearing masks, social distancing, and washing hands). The indirect effect of message fatigue on intention to seek COVID-19 information was explained by inattention but not reactance. Analyses of open-ended responses identified 18 types of COVID-related information that individuals were tired of hearing about. About 73.38% of participants (n = 546) reported that they were tired of hearing about at least one type of information about COVID-19, with mask-wearing being the most frequently mentioned (21.91%). The results extend existing research on message fatigue-evoked resistance to persuasion and provide practical implications for public health message design.

COVID-19 Vaccines #ForYou: Analyzing COVID-19 Vaccine Videos on TikTok During the Early Phase of the Vaccine Rollout in the U.S.

This study examined COVID-19 vaccine videos on TikTok (n = 216 collected in March 2021) during the early days of the vaccine rollout in the U.S., including video source, overall stance toward COVID-19 vaccines, Health Belief Model (HBM)-related content, message features (i.e. humor, video type, message sensation value, on-screen text, and unoriginal sound), and user engagement indices (number of views, shares, comments, and likes). Regarding source, health professionals and general users were two of the main sources, which varied depending on video stance. Pro-vaccine videos occurred the most often from health professionals whereas anti-vaccine videos occurred the most often from general users. Health professionals (vs. general users) generated more views, shares, comments, and likes. Regarding stance, we found more pro- than anti-vaccine videos (57.9% vs. 37.5%). Stance was not related with any user engagement index. Though many videos were pro-vaccine, the content corresponding to HBM-specified factors, which likely facilitate a positive behavioral change, was largely lacking, such as mentions of COVID-19 severity (5.6%), susceptibility (2.8%) and information boosting vaccination self-efficacy (3.7%). Mentions of side effects (34%) emerged as the major vaccination barrier. HBM-related mentions were not related with any user engagement index. COVID-19 vaccine videos used several features, which varied across stance. Pro-vaccine videos featured more musical performance, while anti-vaccine videos used more humor, playacting, sound effects, and unoriginal sound. Several message features (e.g. humor and on-screen text) were positively associated with users' engagement with a video. Practical and theoretical implications of the findings are discussed.

Electron Density Changes and Ultrafast Carrier Dynamics of the Antiferromagnetic Semiconductor MnPS3 through Magnetic Phase Transition.

Studying ultrafast dynamics provides us with a way to modify materials from the timescale of particle interaction, and the related research on antiferromagnetic semiconductors is still inadequate. Based on the electron density reconstruction, we achieve the visualization of magnetic interactions of bulk antiferromagnetic MnPS3 in the ground state, reveal the role of two atomic site occupations of S atoms in different magnetic phase transitions, and provide the theoretical and experimental support for modifying magnetic properties by selectively replacing the S atom. The ultrafast carrier dynamics can provide information from the excited state to the ground state. Based on time-resolved transmittance measurements, ultrafast carrier dynamics of MnPS3 are reported. The phonon-assisted gap transition driven by the electronic structure is characterized. The coupling relationship among electrons, spin, and phonons is established. Furthermore, the spin orientations within different phases are confirmed.

A Content Analysis of U.S. Adults' Open-Ended Responses to E-Cigarette Risk Messages.

To better understand the processing of e-cigarette prevention messages, we conducted a content analysis of 1,968 participants' open-ended responses to one of four messages, which focused on industry manipulation (Big tobacco), financial and psychological cost of vaping (Can't afford), harmful chemicals in e-cigarettes (Formaldehyde), or uncertainty about the ingredients of e-liquids (Top secret). Health Belief Model (HBM) and perceived message effectiveness (PME) constructs were coded and the frequency of each variable was compared across message conditions. Among the HBM constructs, perceived health threat had the most mentions overall (38.8%). Self-efficacy of staying away from vaping had the fewest mentions across all messages (0.56%). For PME, participants more frequently mentioned message perceptions (15.75% positive message perceptions, 8.38% negative) than effect perceptions (3.46% positive effect perceptions, 1.37% negative). Big tobacco received the highest number of mentions for positive message perceptions and Formaldehyde received the highest number of mentions for positive effect perceptions. Future anti-vaping messages are recommended to address the efficacy element and to combine different themes to communicate harms of e-cigarettes.

Low-Cost Metamaterial Antennas: Forward-Looking Imaging Experiment and Analysis.

A phase error correction method is proposed to compensate for the phase error in super-resolution correlated imaging based on metamaterial antennas. The varying carrier frequencies of a metamaterial antenna can generate the random radiation field for super-resolution correlation imaging, but the variation of the signal carrier frequency leads to large phase errors in the imaging results. In this proposed method, the sampling matrix in the super-resolution correlated imaging algorithm is used to compensate for the phase errors. Each element of the matrix is multiplied by a compensation phase corresponding to the phase error, and the error is subtly removed from the algorithm. In the experiment, the antenna pattern at each frequency of the metamaterial antenna is measured and recorded. In addition, an external field experiment is also carried out, and the collected data are imaged with the improved algorithm. Experimental results show that this technology can effectively solve the effect of phase errors on imaging results caused by signal carrier frequency changes.

The impact of COVID-19-related anti-Asian discrimination on sexual communication and relationships among Asian individuals in the United States.

Asian individuals in the United States have experienced heightened racial discrimination during the COVID-19 pandemic, which may reduce positive relationship processes and damage intimate relationships, including their sexual behaviors and quality. Guided by the chilling effect and Interpersonal Exchange Model of Sexual Satisfaction, this study explores how COVID-19-related anti-Asian discrimination moderates the relationships between sexual relationship power, sexual self-disclosure, and sexual satisfaction. Results (N = 294 partnered Asian adults) showed that as racial discrimination increased, the positive relationship between sexual relationship power and sexual self-disclosure decreased. As people experienced more racial discrimination, the positive effects of sexual self-disclosure on sexual satisfaction also decreased. Sexual power positively predicted sexual satisfaction via sexual communication, only when COVID-19-related discrimination was low or moderate. This study demonstrates how racial discrimination interacts with relational factors to predict Asian individuals' sexual communication and, in turn, sexual satisfaction. More public attention and efforts should be devoted to combating anti-Asian discrimination during the pandemic and beyond.

Polarization induced reconfigurable multiple OAM vortex waves through a composite meta-surface beam former.

We demonstrate a composite meta-surface beam former to generate reconfigurable multiple orbital angular momentum (OAM) vortex waves by integrating a polarization conversion meta-mirror with a multi-functional anisotropic meta-lens. More specifically, electromagnetic fields from the feed would be firstly reflected by the meta-mirror, and then transmit through the meta-lens to form the well converged OAM vortex waves with tailored beam numbers, radiation directions and topological charges. Especially, we show that the anisotropic characteristics of the meta-lens would create different multiple OAM vortex waves when the meta-mirror is rotated or equipped with active circuits to have different polarized illuminations on the meta-lens. Our design should pave the way for the reconfigurable design of generating multiple OAM vortex waves to further expand the communication capacity.

Compact cascaded meta-surface system for controlling the spin and orbital angular momentum of electromagnetic fields simultaneously.

We propose a compact cascaded meta-surface system (CCMS) to produce well converged orbital angular momentum (OAM) vortex waves with tailored spin angular momentum (SAM) by integrating a meta-surface lens (ML) with an assistant meta-mirror (AM). Specifically, the co-linearly polarized (LP) waves from the feed would be reflected by the ML firstly and then twisted into the cross-LP counterparts by the AM to penetrate the ML for the perfect synthesis of the OAM vortex beams while performing the linear-to-circular polarization conversion. Especially, the CCMS can pack the ML and the AM closely together with a quarter of the ML focal length when we apply proper phase distributions on the AM. In addition, the proposed CCMS can readily be extended to the generation of multiple circularly polarized OAM vortex waves with different modes. Our design should thus pave the way for building up more efficient wireless communication systems with expanded channel capacity.

Communicating COVID-19 information on TikTok: a content analysis of TikTok videos from official accounts featured in the COVID-19 information hub.

Amid the COVID-19 pandemic, TikTok, an emerging social media platform, has created an information hub to provide users with engaging and authoritative COVID-19 information. This study investigates the video format, type and content of the COVID-19 TikTok videos, and how those video attributes are related to quantitative indicators of user engagement, including numbers of views, likes, comments and shares. A content analysis examined 331 videos from official accounts featured in the COVID-19 information hub. As of 5 May 2020, the videos received 907 930 000 views, 29 640 000 likes, 168 880 comments and 781 862 shares. About one in three videos had subtitles, which were positively related to the number of shares. Almost every video included a hashtag, and a higher number of hashtags was related to more likes. Video types included acting, animated infographic, documentary, news, oral speech, pictorial slideshow and TikTok dance. Dance videos had the most shares. Video themes included anti-stigma/anti-rumor, disease knowledge, encouragement, personal precautions, recognition, societal crisis management and work report. Videos conveying alarm/concern emotions, COVID-19 susceptibility and severity, precaution response efficacy had higher user engagement. Public health agencies should be aware of the opportunity of TikTok in health communication and create audience-centered risk communication to engage and inform community members.

A study of the phosphorylation proteomic skin characteristics of Tan sheep during the newborn and er-mao stages.

In this experiment, in order to study the formation mechanism of the lamb fur of Tan sheep, skin samples were collected from Tan sheep at the newborn and er-mao stages. Then, the phosphorylated proteomes of the skin samples of Tan sheep at the two different stages were compared and analyzed using a TMT labeled quantitative phosphorylation proteomic technique. A total of 2806 phosphorylated proteins were identified, including 8184 phosphorylation sites. The results of this study's quantitative analysis showed that when compared with the skin samples at the er-mao stage, the phosphorylation levels of 171 sites had been upregulated in the skin samples at newborn stage. Meanwhile, 125 sites had been downregulated at the same stage. As shown by the results of the functional enrichment analysis of the differentially phosphorylated proteins, they had been mainly enriched in the cysteine and methionine metabolism. In addition, the phosphorylation levels of KAP4.7 and KAP13.1 had also varied during the different skin stages. These results indicated that the cysteine metabolism pathways, as well as the phosphorylation modifications of the keratin associated proteins in the skin, played important roles in the formation of the er-mao stage fur of the Tan sheep. Therefore, the findings of this study provided a new angle for interpreting the formation mechanism of er-mao stage fur properties.

Inhibition of Immunosuppressive Tumors by Polymer-Assisted Inductions of Immunogenic Cell Death and Multivalent PD-L1 Crosslinking.

Checkpoint blockade immunotherapies harness the host's own immune system to fight cancer, but only work against tumors infiltrated by swarms of pre-existing T cells. Unfortunately, most cancers to date are immune-deserted. Here, we report a polymer-assisted combination of immunogenic chemotherapy and PD-L1 degradation for efficacious treatment in originally non-immunogenic cancer. "Priming" tumors with backbone-degradable polymer-epirubicin conjugates elicits immunogenic cell death and fosters tumor-specific CD8+ T cell response. Sequential treatment with a multivalent polymer-peptide antagonist to PD-L1 overcomes adaptive PD-L1 enrichment following chemotherapy, biases the recycling of PD-L1 to lysosome degradation via surface receptor crosslinking, and produces prolonged elimination of PD-L1 rather than the transient blocking afforded by standard anti-PD-L1 antibodies. Together, these findings established the polymer-facilitated tumor targeting of immunogenic drugs and surface crosslinking of PD-L1 as a potential new therapeutic strategy to propagate a long-term antitumor immunity, which might broaden the application of immunotherapy to immunosuppressive cancers.

High-purity polarized multi-beams from polarization-twisting meta-surface Cassegrain systems.

Bi-functional meta-surfaces capable of simultaneously controlling polarization states and wave-fronts of electromagnetic fields are introduced into the design of Cassegrain system for the synthesis of multi-beams. More specifically, electromagnetic fields reflected by the secondary meta-surface with tailored diverged wave-fronts would be collimated by the primary meta-surface into multi-beams with transformed polarization states that can directly go through the secondary meta-surface without any blockage. Especially, we show that such a polarization-twisting meta-surface Cassegrain system can possess much more compact configuration by properly devising the phase distribution over the secondary meta-surface, and can also achieve high-purity polarized multiple radiations when we enlarge the secondary meta-surface as a radome. The present approach of integrating two bi-functional meta-surfaces into the design of Cassegrain system for the generation of multi-beams should pave the way for building up more advanced meta-surface based architectures with specific characteristics.

Higher negative emotions in response to cigarette pictorial warning labels predict higher quit intentions among smokers.

BACKGROUND: Cigarette pictorial warning labels (PWLs) could produce stronger quit intentions than text-only warning labels (TWLs) due to greater emotional arousal. Yet, it remains unclear whether PWLs that elicit different levels of emotions produce different outcomes. To better understand the role of negative emotions in the effects of PWLs, this study developed two sets of PWLs arousing different emotional levels (high vs low) but equally high on informativeness and compared them to each other and to the current TWLs. METHODS: Adult US smokers (n=1503) were randomised to view nine high-emotion-arousing or low-emotion-arousing PWLs or TWLs. After each label, participants reported the negative emotions they felt while looking at the label. After seeing all the labels, participants reported their intentions to quit smoking. Mediation analyses tested whether message condition influenced quit intentions indirectly through negative emotions. RESULTS: Compared with TWLs, PWLs produced higher levels of negative emotions (b=0.27, SE=0.04, p<0.001). Compared with low-emotion arousing PWLs, high-emotion-arousing PWLs produced higher levels of negative emotions (b=0.24, SE=0.07, p<0.001). Higher negative emotions predicted stronger quit intentions (b=0.20, SE=0.03, p<0.001). Negative emotions mediated the effects of PWLs versus TWLs and high-emotion-arousing versus low- emotion-arousing PWLs on quit intentions. CONCLUSIONS: The results provide additional evidence for negative emotions as the mechanism through which PWLs motivate smokers to consider quitting. The findings call on the Food and Drug Administration to design and implement high-emotion-arousing cigarette warning labels.

Modifications to Electronic Nicotine Delivery Systems: Content Analysis of YouTube Videos.

BACKGROUND: As user modification can alter the addictiveness and toxicity of electronic nicotine delivery systems (ENDS), more research is needed to understand the types, motivations, risks, and information sources that lead to these product alterations. YouTube has been identified as a major platform where ENDS users obtain and share information about ENDS products and modifications. However, a comprehensive study of ENDS modification videos on YouTube is lacking. OBJECTIVE: This study aimed to analyze the content of YouTube videos depicting modifications of ENDS. METHODS: YouTube was searched in March 2019 to identify videos depicting ENDS modifications. Search terms were derived from interviews with ENDS users and current literature. We used 28 search phrases that combined the words vape and vaping with modification-related key terms (eg, custom build, modification, and dripping). The final sample included 168 videos. RESULTS: Videos were 1 to 108 min long (median 9.55). Presenters were largely male (117/168, 69.6%), white (94/168, 56.0%), and older than 25 years (94/168, 56.0%). Most videos gave how to instructions (148/168, 88.1%), but few offered warnings (30/168, 17.9%) or mentioned commercial alternatives to modifications they presented (16/168, 9.5%). The ENDS devices most often featured were drippers (63/168, 37.5%) and refillable tanks (37/168, 22.0%). The most often modified ENDS components were coils (82/168, 48.8%) and e-liquids (34/168, 20.2%), which included adding other substances, such as cannabis, to the e-liquids (6/168, 3.6%). Most videos portrayed ENDS modifications positively (106/168, 63.1% positive; 60/168, 35.7% neutral; and 2/168, 1.2% negative) and were either neutral or positive in their overall portrayal of ENDS devices (78/168, 46.4% positive; 89/168, 53.0% neutral; and 1/168, 0.6% negative). CONCLUSIONS: This study identified several concerning trends in popular YouTube videos on ENDS modifications, including lack of warnings, the addition of marijuana derivatives to e-liquids, and the positive portrayal of ENDS devices and modifications. By identifying the types of modifications (coil and e-liquid being the most prevalent), this study sets an agenda for research on the effects of modifications.