Exploring the effects of cannabis health warnings on protective health intentions among US adults in legal recreational states.

BACKGROUND: As cannabis policy trends toward liberalization, assessing cannabis health warning effects becomes increasingly important. This study investigated underlying mechanisms accounting for the effectiveness of cannabis health warnings on protective health intentions. METHOD: A sample of 1,095 adults (21+) living in legal recreational US states who reported using cannabis in the past 12 months participated in an online experiment. Participants were randomly assigned to view cannabis health warnings that described risks of impaired driving, mental health, and smoke exposure and varied pictures and text (vs. text-only) attributes in warnings. Outcomes were message reactions (cognitive elaboration, fear, and hope), attitudes and beliefs (perceived severity of cannabis harms and perceived susceptibility to cannabis harms, and perceived response and self-efficacy to prevent cannabis harms), and protective health intentions (information-seeking about cannabis health effects and having interpersonal discussions about cannabis harms with family, friends, and medical professionals). RESULTS: MANCOVA results showed no significant differences between text-only vs. pictorial attributes on protective health intentions; thus, warning conditions were controlled and analyzed using structural equation modeling (SEM). SEM results showed that attention to cannabis health warnings (text-only or pictorial) elicited higher cognitive elaboration, fear, and hope-an emotion associated with coping actions that motivate positive expectations of future events. These outcomes, in turn, were associated with greater perceived severity and susceptibility and greater perceived response efficacy, respectively. Hope, perceived severity, and perceived response and self-efficacy were independently associated with greater intentions to seek information about cannabis health effects and to discuss cannabis health harms. CONCLUSION: Attention to warnings impacted emotions, attitudes, and protective health intentions. Fear is commonly associated with health warning effects, and our results suggest that hope is also an important factor. This research contributes to understanding the effects of cannabis health warnings and can inform regulatory agencies that mandate warnings on cannabis products.

Impact of baseline and longitudinal allostatic load changes on incident cardiovascular disease and all-cause mortality: A 7-year population-based cohort study in China.

BACKGROUND: We aimed to prospectively examine the association of baseline allostatic load (AL) and longitudinal AL changes with incident cardiovascular disease (CVD) and all-cause mortality among middle-aged and elderly Chinese populations and evaluate the relative contributions of each physiological system of AL. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) among adults aged 45 years or older were analyzed. Cox regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for the associations between baseline AL/longitudinal AL changes with incident CVD and all-cause mortality. RESULTS: Compared with adults with AL 0-1, HRs of those with baseline AL 2-3 and AL ≥ 4 were 1.24 (95 % CI: 1.06, 1.45) and 1.51 (95 % CI: 1.27, 1.80) for incident CVD, and 1.39 (95 % CI: 1.11, 1.75) and 2.02 (95 % CI: 1.60, 2.54) for all-cause mortality. Similar results were found when we treated baseline AL as a continuous variable. We also found per AL score increase during 4 years of follow-up was related to a 11 % (HR, 1.11; 95 % CI: 1.03, 1.20) and 21 % (HR, 1.21; 95 % CI: 1.10, 1.34) increase in incident CVD and all-cause mortality, respectively. LIMITATIONS: Self-reported physician-diagnosed CVD was used to assess the incident CVD. CONCLUSIONS: Both baseline AL and longitudinal increases in AL were positively associated with incident CVD and all-cause mortality in middle-aged and elderly adults. Individuals with high AL need to be dynamically monitored for CVD and pre-mature mortality prevention.

Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer.

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes (STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates (I and II) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immune-activating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate I upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer (NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy.

INTransformer: Data augmentation-based contrastive learning by injecting noise into transformer for molecular property prediction.

Molecular property prediction plays an essential role in drug discovery for identifying the candidate molecules with target properties. Deep learning models usually require sufficient labeled data to train good prediction models. However, the size of labeled data is usually small for molecular property prediction, which brings great challenges to deep learning-based molecular property prediction methods. Furthermore, the global information of molecules is critical for predicting molecular properties. Therefore, we propose INTransformer for molecular property prediction, which is a data augmentation method via contrastive learning to alleviate the limitations of the labeled molecular data while enhancing the ability to capture global information. Specifically, INTransformer consists of two identical Transformer sub-encoders to extract the molecular representation from the original SMILES and noisy SMILES respectively, while achieving the goal of data augmentation. To reduce the influence of noise, we use contrastive learning to ensure the molecular encoding of noisy SMILES is consistent with that of the original input so that the molecular representation information can be better extracted by INTransformer. Experiments on various benchmark datasets show that INTransformer achieved competitive performance for molecular property prediction tasks compared with the baselines and state-of-the-art methods.

Anisotropic carrier dynamics and laser-fabricated luminescent patterns on oriented single-crystal perovskite wafers.

Perovskite materials and their applications in optoelectronics have attracted intensive attentions in recent years. However, in-depth understanding about their anisotropic behavior in ultrafast carrier dynamics is still lacking. Here we explore the ultrafast dynamical evolution of photo-excited carriers and photoluminescence based on differently-oriented MAPbBr3 wafers. The distinct in-plane polarization of carrier relaxation dynamics of the (100), (110) and (111) wafers and their out-of-plane anisotropy in a picosecond time scale were found by femtosecond time- and polarization-resolved transient transmission measurements, indicating the relaxation process dominated by optical/acoustic phonon interaction is related to photoinduced transient structure rearrangements. Femtosecond laser two-photon fabricated patterns exhibit three orders of magnitude enhancement of emission due to the formation of tentacle-like microstructures. Such a ultrafast dynamic study carried on differently-oriented crystal wafers is believed to provide a deep insight about the photophysical process of perovskites and to be helpful for developing polarization-sensitive and ultrafast-response optoelectronic devices.

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

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.

Systemic Administration with Bacteria-Inspired Nanosystems for Targeted Oncolytic Therapy and Antitumor Immunomodulation.

Malignant tumors represent a formidable global health challenge, compelling the pursuit of innovative treatment modalities. Oncolytic therapy has emerged as a promising frontier in antitumor strategies. However, both natural agents (such as oncolytic bacteria or viruses) and synthetic oncolytic peptides confront formidable obstacles in clinical trials, which include the delicate equilibrium between safety and efficacy, the imperative for systemic administration with targeted therapy, and the need to counteract oncolysis-induced immunosuppression. To overcome these dilemmas, we have developed biomimetic nanoengineering to create oncolytic bacteria-inspired nanosystems (OBNs), spanning from hierarchical structural biomimicry to advanced bioactive biomimicry. Our OBNs harbor inherent oncolytic potential, including functionalized oligosaccharides mimicking bacterial cell walls for optimal blood circulation and tumor targeting, tumor acidity-switchable decoration for tumor-specific oncolysis, stereospecific tryptophan-rich peptides for robust oncolytic activity, encapsulated tumor immunomodulators for enhanced immunotherapy, and innate multimodal imaging potential for biological tracing. This work elucidates the efficacy and mechanisms of OBNs, encompassing primary tumor suppression, metastasis prevention, and recurrence inhibition. Systemic administration of d-chiral OBNs has demonstrated superior oncolytic efficacy, surpassing intratumoral injections of clinical-grade oncolytic peptides. This work heralds an era in biomimetic engineering on oncolytic agents, promising the revolutionization of contemporary oncolytic therapy paradigms for clinical translation.

Effect of pretreatment with a P2Y12 inhibitor in patients with non-ST-elevation acute coronary syndrome: a systematic review and network meta-analysis.

Background: This study aimed to systematically evaluate the effects of different types and doses of pretreatment with P2Y12 inhibitors in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). Methods: Electronic databases were searched for studies comparing pretreatment with different types and doses of P2Y12 inhibitors or comparison between P2Y12 inhibitor pretreatment and nonpretreatment. Electronic databases included the Cochrane Library, PubMed, EMBASE, and Web of Science. Literature was obtained from the establishment of each database until June 2022. The patients included in the study had pretreatment with P2Y12 inhibitors with long-term oral or loading doses, or conventional aspirin treatment (non-pretreatment). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) during follow-up within 30 days after PCI, which included determining the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The safety endpoint was a major bleeding event. Results: A total of 119,014 patients from 21 studies were enrolled, including 13 RCTs and eight observational studies. A total of six types of interventions were included-nonpretreatment (placebo), clopidogrel pretreatment, ticagrelor pretreatment, prasugrel pretreatment, double loading pretreatment (double loading dose of clopidogrel, ticagrelor, prasugrel) and P2Y12 inhibitors pretreatment (the included studies did not distinguish the types of P2Y12 inhibitors, including clopidogrel, ticagrelor, and prasugrel). The network meta-analysis results showed that compared to patients without pretreatment, patients receiving clopidogrel pretreatment (RR = 0.78, 95% CI:0.66, 0.91, P < 0.05) and double-loading pretreatment (RR = 0.62, 95% CI:0.41, 0.95, P < 0.05) had a lower incidence of MACCEs. There was no statistically significant difference in the incidence of major bleeding events among the six pretreatments (P > 0.05). Conclusions: In patients with NSTE-ACS, pretreatment with P2Y12 inhibitors before percutaneous intervention reduced the incidence of recurrent ischemic events without increasing the risk of major bleeding after PCI compared with nonpretreatment. Clopidogrel or double loading dose P2Y12 inhibitors can be considered for the selection of pretreatment drugs.

Enantiomeric Virus-Inspired Oncolytic Particles for Efficient Antitumor Immunotherapy.

Synthesizing biomimetic systems with stereospecific architectures and advanced bioactivity remains an enormous challenge in modern science. To fundamentally eliminate biosafety issues of natural oncolytic viruses, the development of synthetic virus-inspired particles with high oncolytic activity is urgently needed for clinical antitumor treatments. Here, we describe the design and synthesis of enantiomeric virus-inspired particles for efficient oncolytic therapy from homochiral building blocks to stereospecific supramolecular constructions. The L-virus-inspired oncolytic particles (L-VOPs) and D-VOPs possess similar biomimetic nanostructures but mirror-imaged enantiomeric forms. It is important that both L-VOPs and D-VOPs successfully mimic the pharmacological activity of oncolytic viruses, including direct tumor lysis and antitumor immune activation. D-VOPs provide quite better oncolytic efficacy than that of clinical-grade oncolytic agents (LTX-315, IC50 = 53.00 µg mL-1) with more than 5-fold decrease in IC50 value (10.93 µg mL-1) and close to 100% tumor suppression (98.79%) against 4T1 tumor-bearing mice, attributed to the chirality-dependent tumor recognition, interaction, antidegradation, and immunotherapy. This work provides a strategy for the synthesis of stereospecific biomimetic material systems as well as develops an advanced candidate for biomimetic oncolytic agents without biosafety risks.

A novel de-escalation antiplatelet therapy for patients with acute coronary syndrome undergoing percutaneous coronary intervention.

To investigate the effect of different DAPTs in patients with ACS undergoing PCI, and to identify the most efficient DAPT to reduce the risk of ischemia and bleeding after PCI. Between March 2017 and December 2021, 1598 patients with ACS who underwent PCI were included in the study. The DAPT protocol included the clopidogrel group (aspirin 100 mg + clopidogrel 75 mg), ticagrelor group (aspirin 100 mg + ticagrelor 90 mg), de-escalation Group 1 (reduced dose of ticagrelor [from 90 mg to 60 mg]) after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]), and de-escalation Group 2 (switched from ticagrelor to clopidogrel after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]). All patients received a 12-month follow-up. The primary endpoint was net adverse clinical events (NACEs) that included the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, stroke, and bleeding events. There were 2 secondary endpoints, major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding. No statistically significant difference was found in the incidence of NACEs between the 4 groups at the average 12-month follow-up (15.7% vs 19.2% vs 16.7% vs 20.4%). Cox regression analysis revealed that DAPT ticagrelor group regimen (hazard ratio [HR] 0.547; 95% confidence interval [CI]: 0.334-0.896; P  = .017) were associated with a lower risk of MACCEs. Age (HR 1.024; 95% CI: 1.003-1.046; P  = .022). DAPT de-escalation Group 2 regimen (HR 1.665; 95% CI: 1.001-2.767; P  = .049) were marginally associated with a higher risk of MACCEs. Ticagrelor group regimen (HR 1.856; 95% CI: 1.376-2.504; P  < .001) was associated with higher risk of bleeding events. Ticagrelor group regimen (HR 1.606; 95% CI: 1.179-2.187; P  = .003) were associated with a higher risk of minor bleeding events. For patients with ACS underwent PCI, there were no significant difference in the incidence of NACEs between 3 and 12 months after PCI between de-escalation and non-de-escalation therapies. Compared with ticagrelor-based 12-month DAPT, there was no significant difference in MACCEs and bleeding events in patients receiving de-escalation treatment (ticagrelor reduction from 90 to 60 mg, 3 months after PCI).

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.

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.

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.

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.

When Cigarette Smoking Meets COVID-19: How the Two Types of Threat and Efficacy Perceptions Interactively Predict Danger Control and Fear Control Processes.

Growing evidence indicates that communicating the combined risk of smoking and COVID-19 encourages smoking cessation. Guided by the Extended Parallel Process Model (EPPM), we examined how perceived threats of smoking and COVID-19 independently and interactively predicted danger control responses (i.e., quit intentions and COVID-19-protective behavioral intentions) and fear control responses (i.e., fear and fatalism). We also explored the direct and interactive impacts of perceived efficacy of quitting smoking and COVID-protective behaviors on message outcomes. Structural equation modeling results (N = 747 U.S. adults who smoke) indicated that the perceived efficacy of COVID-protective behaviors positively predicted quit intentions. Higher perceived threat of COVID-19 and greater quitting efficacy predicted higher quit intentions directly and indirectly via fear. As perceived COVID-protective efficacy increased, the positive association between perceived quitting efficacy and quit intentions also increased. Smoking-related threat and efficacy perceptions did not predict COVID-protective behavioral intentions. This study added to EPPM by considering how threat and efficacy perceptions deriving from two different yet closely related risks affect protective behaviors. Thus, combining multiple threats in a single message might be a promising strategy to motivate smoking cessation amid the pandemic.

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.

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.

Perceived Message Effectiveness: Do People Need to Think About Message Effectiveness to Report the Message as Effective?

How people make perceived message effectiveness (PME) judgments remains mostly unexplored. This study assessed whether people need to spontaneously think about message effectiveness to report the message as effective on rating scales and investigated emotions as precursors to PME. After viewing one of four e-cigarette prevention messages, 1,968 adult current and former smokers and nonsmokers freely expressed thoughts about the messages in an open-ended question and answered close-ended PME items. Four expressed PME variables (positive message perceptions, negative message perceptions, positive effect perceptions, and negative effect perceptions) were coded (1 = present, 0 = absent) in the open-ended responses, and all were significantly associated with measured PME. Positive and negative emotions predicted both expressed and measured PME. Negative message perceptions was the only expressed PME construct that mediated the relationships between emotions and measured PME and outcomes (perceived risk and behavioral intentions). This suggests that messages may not need to induce effectiveness thoughts to be reported as effective, but thoughts of message ineffectiveness are a useful indicator deserving further research.