Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching.

In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.

Molecular mechanisms of proteoglycan-mediated semaphorin signaling in axon guidance.

The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based on the degree of sulfation. Structural analysis of Sema2b unveiled multiple GAG-binding sites positioned outside canonical plexin-binding site, with the highest affinity binding site located at the C-terminal tail, characterized by a lysine-rich helical arrangement that appears to be conserved across secreted semaphorins. In vivo studies revealed a crucial role of the Sema2b C-terminal tail in specifying the trajectory of olfactory receptor neurons. We propose that secreted semaphorins tether to the cell surface through interactions with GAG chains of proteoglycans, facilitating their presentation to cognate receptors on passing axons.

A multiple Kirkendall strategy for converting nanosized zero-valent iron to highly active Fenton-like catalyst for organics degradation.

Nanosized zero-valent iron (nZVI) is a promising persulfate (PS) activator, however, its structurally dense oxide shell seriously inhibited electrons transfer for O-O bond cleavage of PS. Herein, we introduced sulfidation and phosphorus-doped biochar for breaking the pristine oxide shell with formation of FeS and FePO4-containing mixed shell. In this case, the faster diffusion rate of iron atoms compared to shell components triggered multiple Kirkendall effects, causing inward fluxion of vacancies with further coalescing into radial nanocracks. Exemplified by trichloroethylene (TCE) removal, such a unique "lemon-slice-like" nanocrack structure favored fast outward transfer of electrons and ferrous ions across the mixed shell to PS activation for high-efficient generation and utilization of reactive species, as evidenced by effective dechlorination (90.6%) and mineralization (85.4%) of TCE. [Formula: see text] contributed most to TCE decomposition, moreover, the SnZVI@PBC gradually became electron-deficient and thus extracted electrons from TCE with achieving nonradical-based degradation. Compared to nZVI/PS process, the SnZVI@PBC/PS system could significantly reduce catalyst dosage (87.5%) and PS amount (68.8%) to achieve nearly complete TCE degradation, and was anti-interference, stable, and pH-universal. This study advanced mechanistic understandings of multiple Kirkendall effects-triggered nanocrack formation on nZVI with corresponding rational design of Fenton-like catalysts for organics degradation.

Zebrafish and idiopathic scoliosis: the 'unknown knowns'.

The etiology and heterogeneity of idiopathic scoliosis (IS) are poorly understood. Studies using scoliotic zebrafish models have indicated a potential link between ciliary defects and scoliosis. They may further explain the onset of IS partially. However, it is necessary to further interpret the link between this progress and clinical medicine.

Highly stable fiber-based photonic delay line with large and tunable delay.

A stable photonic delay line with large and tunable delay is essential for large-distance simulation, beamforming, and diverse photonic signal processing applications. Here, we demonstrate a fiber-based tunable photonic delay line (TPDL) with a maximum delay of 905 µs. Its environmental-related delay jitter is compensated for by a homodyne phase-locked loop (PLL). Precise delay tuning is realized by changing the phase of the reference with a minimum tuning step of 0.5 ps without breaking its locking state. The demonstrated delay line shows exceptional stability, as indicated by an overlapping Allan deviation (ADEV) of 2.06 × 10-17 at the averaging time of 1000 s and the delay jitter below 20 fs. Its high stability, wide delay range, wideband characteristics, and precise tunability make the TPDL an ideal photonic delay line for the above-mentioned applications.

Hippocampal avoidance whole-brain radiotherapy with simultaneous integrated boost in lung cancer brain metastases and utility of the Hopkins verbal learning test for testing cognitive impairment in Chinese patients: a prospective phase II study.

BACKGROUND: This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. METHODS: Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. RESULTS: Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. CONCLUSIONS: HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

Identification and Characterization of Illegal Sales of Cannabis and Nicotine Delivery Products on Telegram Messaging Platform.

INTRODUCTION: Unregulated and potentially illegal sales of tobacco, nicotine, and cannabis products have been detected on various social media platforms, e-commerce sites, online retailers, and the dark web. New end-to-end encrypted messaging services are popular among online users and present opportunities for marketing, trading, and selling of these products. The purpose of this study was to identify and characterize tobacco, nicotine, and cannabis selling activity on the messaging platform Telegram. METHODS: The study was conducted in three phases: (1) identifying keywords related to tobacco, nicotine, and cannabis products for purposes of detecting Telegram groups and channel messages; (2) automated data collection from public Telegram groups; and (3) manual annotation and classification of messages engaged in marketing and selling products to consumers. RESULTS: Four keywords were identified ("Nicotine," "Vape," "Cannabis," and "Smoke") that yielded 20 Telegram groups with 262 506 active subscribers. Total volume of channel messages was 43 963 unique messages that included 3094 (7.04%) marketing/selling messages. The most commonly sold products in these groups were cannabis-derived products (83.25%, n = 2576), followed by tobacco/nicotine-derived products (6.46%, n = 200), and other illicit drugs (0.77%, n = 24). A variety of marketing tactics and a mix of seller accounts were observed, though most appeared to be individual suppliers. CONCLUSIONS: Telegram is an online messaging application that allows for custom group creation and global connectivity, but also includes unregulated activities associated with the sale of cannabis and nicotine delivery products. Greater attention is needed to conduct monitoring and enforcement on these emerging platforms for unregulated and potentially illegal cannabis and nicotine product sales direct-to-consumer. IMPLICATIONS: Based on study results, Telegram represents an emerging platform that enables a robust cannabis and nicotine-selling marketplace. As local, state, and national tobacco control regulations continue to advance sales restrictions and bans at the retail level, easily accessible and unregulated Internet-based channels must be further assessed to ensure that they do not act as conduits for exposure and access to unregulated or illegal cannabis and nicotine products.

Altered cortical microstructure in preterm infants at term-equivalent age relative to term-born neonates.

Preterm (PT) birth is a potential factor for abnormal brain development. Although various alterations of cortical structure and functional connectivity in preterm infants have been reported, the underlying microstructural foundation is still undetected thoroughly in PT infants relative to full-term (FT) neonates. To detect the very early cortical microstructural alteration noninvasively with advanced neurite orientation dispersion and density imaging (NODDI) on a whole-brain basis, we used multi-shell diffusion MRI of healthy newborns selected from the Developing Human Connectome Project. 73 PT infants and 69 FT neonates scanned at term-equivalent age were included in this study. By extracting the core voxels of gray matter (GM) using GM-based spatial statistics (GBSS), we found that comparing to FT neonates, infants born preterm showed extensive lower neurite density in both primary and higher-order association cortices (FWE corrected, P < 0.025). Higher orientation dispersion was only found in very preterm subgroup in the orbitofrontal cortex, fronto-insular cortex, entorhinal cortex, a portion of posterior cingular gyrus, and medial parieto-occipital cortex. This study provided new insights into exploring structural MR for functional and behavioral variations in preterm population, and these findings may have marked clinical importance, particularly in the guidance of ameliorating the development of premature brain.

Speaker-listener neural coupling reveals a right-lateralized mechanism for non-native speech-in-noise comprehension.

While the increasingly globalized world has brought more and more demands for non-native language communication, the prevalence of background noise in everyday life poses a great challenge to non-native speech comprehension. The present study employed an interbrain approach based on functional near-infrared spectroscopy (fNIRS) to explore how people adapt to comprehend non-native speech information in noise. A group of Korean participants who acquired Chinese as their non-native language was invited to listen to Chinese narratives at 4 noise levels (no noise, 2 dB, -6 dB, and - 9 dB). These narratives were real-life stories spoken by native Chinese speakers. Processing of the non-native speech was associated with significant fNIRS-based listener-speaker neural couplings mainly over the right hemisphere at both the listener's and the speaker's sides. More importantly, the neural couplings from the listener's right superior temporal gyrus, the right middle temporal gyrus, as well as the right postcentral gyrus were found to be positively correlated with their individual comprehension performance at the strongest noise level (-9 dB). These results provide interbrain evidence in support of the right-lateralized mechanism for non-native speech processing and suggest that both an auditory-based and a sensorimotor-based mechanism contributed to the non-native speech-in-noise comprehension.

Correlation Between Intracoronary Vascular Ultrasound Indexes in Patients with Coronary Heart Disease.

Background: Coronary atherosclerosis is a serious and progressive condition characterized by the accumulation of plaques, consisting of fat, cholesterol, and other substances, within the arteries that supply blood to the heart. These plaques can harden and narrow the arteries, leading to reduced blood flow to the heart muscle. Objective: The primary objective of this study is to investigate the correlation between specific cardiovascular parameters and intracoronary vascular ultrasound indexes in patients diagnosed with coronary heart disease. This investigation aims to explore the relationships between intracoronary vascular ultrasound measurements and three key cardiovascular parameters: epicardial fat pad thickness, mono-platelet polymer levels, and small dense low-density lipoprotein cholesterol (sdLDL-C) levels. Methods: In this investigation, we applied a comprehensive method to evaluate atherosclerotic plaque characteristics in patients with diverse stages of coronary heart disease (CHD), contrasting these profiles with those of healthy individuals. Our study included 80 acute myocardial infarction (AMI) patients, 145 with unstable angina pectoris (UAP), 175 with stable angina pectoris (SAP), and 100 controls. We utilized intravascular ultrasound (IVUS), an advanced imaging technique that surpasses traditional angiography by providing detailed, high-resolution images of both the coronary artery lumen and wall, including plaque composition. This approach is pivotal for assessing plaque stability, a key factor in the risk of rupture and subsequent cardiovascular events, indicated by features like lipid-rich cores and thin fibrous caps. During IVUS, we quantified parameters such as plaque area, load, and the remodeling index, the latter offering insights into vascular adaptation to plaque buildup. Additionally, we conducted a correlation analysis between IVUS indices and three cardiovascular markers: epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels. The goal was to ascertain the predictive value of these markers in tandem with IVUS for determining the stability of coronary artery atherosclerotic plaques. This integrative approach enhances understanding of plaque formation and destabilization, potentially informing more effective CHD prevention and management strategies. Results: Our study revealed distinct variations in key parameters across patient groups with different forms of CHD and healthy controls. Notably, we observed significant differences in gender distribution, hypertension, and diabetes mellitus prevalence among these groups. In terms of IVUS indexes and cardiovascular parameters, the SAP group exhibited markedly different results compared to the AMI and UAP groups. Specifically, the SAP patients showed the lowest values for EMMA, plaque area, plaque burden, reconstruction index, and positive remodeling. Additionally, they exhibited the thickest fibrous caps. In contrast, the AMI and UAP groups presented similar outcomes in these aspects. Regarding the epicardial fat pad thickness, the positive rate of monocyte-platelet aggregates, and the levels of sdLDL-C, there were no significant differences between the AMI and UAP groups. However, these parameters were notably higher in the AMI and UAP groups compared to the SAP group. Crucially, we established a significant correlation between the thickness of the epicardial fat pad, the positive rate of monocyte-platelet aggregates, and the sdLDL-C levels with plaque loading rate and remodeling index. These correlations underscore the potential utility of these parameters as indicators of plaque stability and cardiovascular risk in patients with CHD. This highlights the complexity of atherosclerotic disease progression and underscores the importance of a multifaceted approach to assessing and managing CHD. Conclusion: Our research delineates the critical role of the remodeling index, epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels as key prognostic tools for assessing coronary plaque stability in coronary artery disease (CAD). These biomarkers collectively provide an enhanced perspective on plaque vulnerability, an essential aspect in the genesis of acute coronary events. Clinically, these findings are pivotal. They offer a refined approach to CAD management and risk evaluation, allowing for the precise identification of patients at increased risk of plaque rupture, a precursor to acute coronary syndromes. This precision facilitates the adoption of more individualized treatment strategies, focusing on aggressive interventions for high-risk patients and more conservative management for those with stable plaques.

Fall risk perception in older adults: A concept analysis.

BACKGROUND: Fall prevention is crucial for older adults. Enhanced fall risk perception can encourage older adults to participate in fall prevention programs. However, there is still no unified definition of the concept of fall risk perception. OBJECTIVE: To explore the concept of fall risk perception in older adults. DESIGN: A concept analysis. DATA SOURCES: The literature was searched using online databases including PubMed, Cochrane Library, Embase, CINAHL Complete, PsycINFO, Web of Science, China National Knowledge Infrastructure, WangFang and SinoMed. Searches were also conducted in Chinese and English dictionaries. The literature dates from the establishment of the database to April 2023. METHODS: The methods of Walker and Avant were used to identify antecedents, attributes and consequences of the concept of "fall risk perception" in older adults. RESULTS: Eighteen publications were included eventually. The attributes were identified as: (1) dynamic change, with features of continuum and stage; (2) whether falls are taken seriously; (3) a self-assessment of the fall probability, which is driven by individual independence; and (4) involves multiple complex emotional responses. The antecedents were identified as: (1) demographic and disease factors; (2) psychological factors and (3) environmental factors. The consequences were identified as: (1) risk-taking behaviour; (2) risk compensation behaviour; (3) risk transfer behaviour; and (4) emotions. CONCLUSION: A theoretical definition of fall risk perception was identified. A conceptual model was developed to demonstrate the theoretical relationships between antecedents, attributes and consequences. This is helpful for the development of relevant theories and the formulation of fall prevention measures based on fall risk perception as the intervention target.

The cognitive appraisal path of stroke knowledge, coping traits, family functioning and stigma among stroke patients: A moderated parallel mediation model.

AIMS: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. BACKGROUND: Stroke-related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. DESIGN: A cross-sectional design. METHODS: The cross-sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. RESULTS: All 144 samples reported stigma symptoms with a moderate-to-high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co-mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. CONCLUSION: Among the cognitive appraisal factors affecting stroke-related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. RELEVANCE TO CLINICAL PRACTICE: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. PATIENT OR PUBLIC CONTRIBUTION: None.

[miR-342-3p Promotes the Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma Cells by Targeted Inhibition of PPM1E]. / miR-342-3p通过靶向抑制PPM1E促进肾透明细胞癌细胞的增殖、迁移和侵袭.

Objective: To explore the effects of microRNA-342-3p/Mg2+Mn2+-dependent protein phosphatase 1E (miR-342-3p/PPM1E) on the proliferation, migration, and invasion of clear cell renal cell carcinoma (ccRCC) cells. Methods: The gene chips GSE12105, GSE23085, GSE66271, and GSE66270 were searched, and the relationship between miR-342-3p, PPM1E, and the clinical malignant phenotypes of ccRCC was analyzed. ACHN and 769-P cells were transfected with miR-342-3p inhibitor. The effects of miR-342-3p on cell proliferation, migration, and invasion were examined. ACHN cell line with stable and high expression of miR-342-3p was constructed, and the tumorigenicity of the cell line in BALB/c nude mice was observed. The targeted relationship between miR-342-3p and PPM1E was verified by dual-luciferase reporter gene assay. The cells were transfected with miR-342-3p mimic and pcDNA-PPM1E plasmids to observe whether PPM1E could reverse the effects of miR-342-3p overexpression on the proliferation, migration, and invasion of the cells. Results: The expression of miR-342-3p was upregulated in ccRCC, and there were significant differences among patients with tumors of different T stages and G stages and those with different prognoses (P<0.05). The overall survival in the miR-342-3p high-expression group was significantly shorter than that in the low-expression group (P<0.05). Compared with those in the miR-NC group, the miR-342-3p level was significantly downregulated in the inhibitor group, and the cell proliferation ability and the numbers of migrating and invading cells were also significantly decreased (P<0.05). Compared with the miR-NC group, miR-342-3p group had significantly increased volume and mass of tumor tissues and miR-342-3p level, but significantly decreased level of PPM1E mRNA (P<0.05). The expression of PPM1E was downregulated in ccRCC, and there were significant differences among patients with tumors of different M stages, N stages, and G stages, and different recurrence statuses (P<0.05). The miR-342-3p could inhibit the expression of PPM1E in a targeted way. Compared with the miR-NC group, the miR-342-3p group had significantly increased cell proliferation ability and increased numbers of migrating and invading cells (P<0.05). However, PPM1E could reverse the promotion effect of miR-342-3p mimic on ccRCC cells (P<0.05). Conclusion: The miR-342-3p can inhibit PPM1E expression in a targeted way, and thus promotes the proliferation, migration, and invasion of ccRCC cells.

Predictors of Time to Coronavirus Disease 2019 Infection in the National Basketball Association: A Retrospective Case-Control Study.

A case-control study was conducted between 1 December 2021 and 31 January 2022 to identify factors, which increase risk for coronavirus disease 2019 (COVID-19) among athletes in the National Basketball Association (NBA). Behavioral factors and stadium attendance significantly decreased time to COVID-19 infection, but local COVID-19 rates were not associated in a multivariable model.

Leading and following: Noise differently affects semantic and acoustic processing during naturalistic speech comprehension.

Despite the distortion of speech signals caused by unavoidable noise in daily life, our ability to comprehend speech in noisy environments is relatively stable. However, the neural mechanisms underlying reliable speech-in-noise comprehension remain to be elucidated. The present study investigated the neural tracking of acoustic and semantic speech information during noisy naturalistic speech comprehension. Participants listened to narrative audio recordings mixed with spectrally matched stationary noise at three signal-to-ratio (SNR) levels (no noise, 3 dB, -3 dB), and 60-channel electroencephalography (EEG) signals were recorded. A temporal response function (TRF) method was employed to derive event-related-like responses to the continuous speech stream at both the acoustic and the semantic levels. Whereas the amplitude envelope of the naturalistic speech was taken as the acoustic feature, word entropy and word surprisal were extracted via the natural language processing method as two semantic features. Theta-band frontocentral TRF responses to the acoustic feature were observed at around 400 ms following speech fluctuation onset over all three SNR levels, and the response latencies were more delayed with increasing noise. Delta-band frontal TRF responses to the semantic feature of word entropy were observed at around 200 to 600 ms leading to speech fluctuation onset over all three SNR levels. The response latencies became more leading with increasing noise and decreasing speech comprehension and intelligibility. While the following responses to speech acoustics were consistent with previous studies, our study revealed the robustness of leading responses to speech semantics, which suggests a possible predictive mechanism at the semantic level for maintaining reliable speech comprehension in noisy environments.

Treatment outcomes for response-based radiotherapy in children and adolescents with central nervous system germinoma: a prospective study.

PURPOSE: The optimal dose and range of radiotherapy for central nervous system (CNS) germinoma have not yet been established. This study aimed to investigate the effects of individualized radiotherapy on the prognosis of patients with germinoma. METHODS: Based on imaging examination, tumor markers, and pathologic results, patients with germinoma received different radiotherapy strategies, including R1 (24 Gy whole ventricular irradiation + tumor-bed boost to 40 Gy), R2 (24-30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy), R3 (24 Gy craniospinal irradiation + tumor-bed boost to 40 Gy), and R4 (30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy with 45 Gy to spinal metastasis). RESULTS: A total of 77 patients were enrolled in this study between January 2015 and March 2021. The 3-year event-free survival (EFS) and overall survival (OS) of the whole cohort were 94.7% ± 2.6% and 96.0% ± 2.3%, respectively. The 3-year EFS for patients with localized and metastatic disease were 96.6% ± 2.4% and 89.2% ± 7.2%, respectively. The 3-year EFS of patients receiving R1, R2, R3, and R4 radiotherapy were 100%, 94.1% ± 5.7%, 100%, and 86.2% ± 9.1%, respectively. CONCLUSION: Good prognosis was still achieved after reducing dose and extent of radiation for the patients who achieved complete response (CR) after induction chemotherapy or pathological CR after second-look surgery.

Identification and Characterization of Synthetic Nicotine Product Promotion and Sales on Instagram Using Natural Language Processing.

INTRODUCTION: There has been a rapid proliferation of synthetic nicotine products in recent years, despite newly established regulatory authority and limited research into its health risks. Previous research has implicated social media platforms as an avenue for nicotine product unregulated sales. Yet, little is known about synthetic nicotine product content on social media. We utilized natural language processing to characterize the sales of synthetic nicotine products on Instagram. METHODS: We collected Instagram posts by querying Instagram hashtags (e.g., "#tobaccofreenicotine) related to synthetic nicotine. Using BERT, collected posts were categorized into thematically related topic clusters. Posts within topic clusters relevant to study aims were then manually annotated for variables related to promotion and selling (e.g., cost discussion, contact information for offline sales). RESULTS: A total of 7,425 unique posts were collected with 2,219 posts identified as related to promotion and selling of synthetic nicotine products. Nicotine pouches (52.9%, n=1174), ENDS (30.6%, n=679), and flavored e-liquids (14.1%, n=313) were most commonly promoted. 16.1% (n=345) of posts contained embedded hyperlinks and 5.8% (n=129) provided contact information for purported offline transactions. Only 17.6% (n=391) of posts contained synthetic nicotine specific health warnings. CONCLUSIONS: In the United States, synthetic nicotine products can only be legally marketed if they have received premarket authorization from the FDA. Despite these prohibitions, Instagram appears to be a hub for potentially unregulated sales of synthetic and "tobacco-free" products. Efforts are needed by platforms and regulators to enhance content moderation and prevent unregulated online sales of existing and emerging synthetic nicotine products. IMPLICATIONS: There is limited clinical understanding of synthetic nicotine's unique health risks and how these novel products are changing over time due to regulatory oversight. Despite synthetic nicotine specific regulatory measures, such as the requirement for premarket authorization and FDA warning letters issued to unauthorized sellers, access to and promotion of synthetic nicotine is widely occurring on Instagram, a platform with over 2 billion users and one that is popular among youth and young adults. Activities include direct-to-consumer sales from questionable sources, inadequate health warning disclosure, and exposure with limited age restrictions, all conditions necessary for the sale of various tobacco products. Notably, the number of these Instagram posts increased in response to the announcement of new FDA regulations. In response, more robust online monitoring, content moderation, and proactive enforcement is needed from platforms who should work collaboratively with regulators to identify, report, and remove content in clear violation of platform policies and federal laws. Regulatory implementation and enforcement should prioritize digital platforms as conduits for unregulated access to synthetic nicotine products and other future novel and emerging tobacco products.

CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells.

cAMP response element binding protein (CREB) functions as a prototypical stimulus-inducible transcription factor (TF) that initiates multiple cellular changes in response to activation. Despite pronounced expression in mast cells (MCs), CREB function is surprisingly ill-defined in the lineage. Skin MCs (skMCs) are critical effector cells in acute allergic and pseudo-allergic settings, and they contribute to various chronic dermatoses such as urticaria, atopic dermatitis, allergic contact dermatitis, psoriasis, prurigo, rosacea and others. Using MCs of skin origin, we demonstrate herein that CREB is rapidly phosphorylated on serine-133 upon SCF-mediated KIT dimerization. Phosphorylation initiated by the SCF/KIT axis required intrinsic KIT kinase activity and partially depended on ERK1/2, but not on other kinases such as p38, JNK, PI3K or PKA. CREB was constitutively nuclear, where phosphorylation occurred. Interestingly, ERK did not translocate to the nucleus upon SCF activation of skMCs, but a fraction was present in the nucleus at baseline, and phosphorylation was prompted in the cytoplasm and nucleus in situ. CREB was required for SCF-facilitated survival, as demonstrated with the CREB-selective inhibitor 666-15. Knock-down of CREB by RNA interference duplicated CREB's anti-apoptotic function. On comparison with other modules (PI3K, p38 and MEK/ERK), CREB was equal or more potent at survival promotion. SCF efficiently induces immediate early genes (IEGs) in skMCs (FOS, JUNB and NR4A2). We now demonstrate that CREB is an essential partaker in this induction. Collectively, the ancient TF CREB is a crucial component of skMCs, where it operates as an effector of the SCF/KIT axis, orchestrating IEG induction and lifespan.

Engineered nanomaterials-based sensing systems for assessing the freshness of meat and aquatic products: A state-of-the-art review.

Meat and aquatic products are susceptible to spoilage during distribution, transportation, and storage, increasing the urgency of freshness evaluation. Engineered nanomaterials (ENMs) typically with the diameter in the range of 1-100 nm exhibit fascinating physicochemical properties. ENMs-based sensing systems have received extensive attention for food freshness assessment due to the advantages of being fast, simple, and sensitive. This review focuses on summarizing the recent application of ENMs-based sensing systems for food freshness detection. First, chemical indicators related to the freshness of meat and aquatic products are described. Then, how to apply the ENMs including noble metal nanomaterials, metal oxide nanomaterials, carbon nanomaterials, and metal-organic frameworks for the construction of different sensing systems were described. Besides, the recent advance in ENMs-based colorimetric, fluorescent, electrochemical, and surface-enhanced Raman spectroscopy sensing systems for assessing the freshness of meat and aquatic products were outlined. Finally, the challenges and future research perspectives for the application of ENMs-based sensing systems were discussed. The ENMs-based sensing systems have been demonstrated as effective tools for freshness evaluation. The sensing performance of ENMs employed in different sensing systems depends on their composition, size, shape, and stability of nanoparticles. For the real application of ENMs in food industries, the risks and regulatory issues associated with nanomaterials need to be further considered. With the continuous development of nanomaterials and sensing devices, the ENMs-based sensors are expected to be applied in-field for rapid detection of the freshness of meat and aquatic products in the future.

Speaker-Listener Neural Coupling Reveals an Adaptive Mechanism for Speech Comprehension in a Noisy Environment.

Comprehending speech in noise is an essential cognitive skill for verbal communication. However, it remains unclear how our brain adapts to the noisy environment to achieve comprehension. The present study investigated the neural mechanisms of speech comprehension in noise using an functional near-infrared spectroscopy-based inter-brain approach. A group of speakers was invited to tell real-life stories. The recorded speech audios were added with meaningless white noise at four signal-to-noise levels and then played to listeners. Results showed that speaker-listener neural couplings of listener's left inferior frontal gyri (IFG), that is, sensorimotor system, and right middle temporal gyri (MTG), angular gyri (AG), that is, auditory system, were significantly higher in listening conditions than in the baseline. More importantly, the correlation between neural coupling of listener's left IFG and the comprehension performance gradually became more positive with increasing noise level, indicating an adaptive role of sensorimotor system in noisy speech comprehension; however, the top behavioral correlations for the coupling of listener's right MTG and AG were only obtained in mild noise conditions, indicating a different and less robust mechanism. To sum up, speaker-listener coupling analysis provides added value and new sight to understand the neural mechanism of speech-in-noise comprehension.