Dual-channel deep graph convolutional neural networks.

The dual-channel graph convolutional neural networks based on hybrid features jointly model the different features of networks, so that the features can learn each other and improve the performance of various subsequent machine learning tasks. However, current dual-channel graph convolutional neural networks are limited by the number of convolution layers, which hinders the performance improvement of the models. Graph convolutional neural networks superimpose multi-layer graph convolution operations, which would occur in smoothing phenomena, resulting in performance decreasing as the increasing number of graph convolutional layers. Inspired by the success of residual connections on convolutional neural networks, this paper applies residual connections to dual-channel graph convolutional neural networks, and increases the depth of dual-channel graph convolutional neural networks. Thus, a dual-channel deep graph convolutional neural network (D2GCN) is proposed, which can effectively avoid over-smoothing and improve model performance. D2GCN is verified on CiteSeer, DBLP, and SDBLP datasets, the results show that D2GCN performs better than the comparison algorithms used in node classification tasks.

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.

Bimetallic Fe/Ni metal organic framework-based hypoxanthine biosensor for early monitoring of freshness changes of aquatic products.

The timely detection of freshness changes of aquatic products is crucial. In this study, we have developed a reliable, cost-effective, and user-friendly method for rapidly detecting hypoxanthine using a xanthine oxidase (XOD)/nanozyme enzymatic cascade system. The nanozyme, derived from the Fe7/Ni3 metal-organic framework (Fe7Ni3MOF), exhibited good peroxidase-mimetic activity and stability. Our proposed XOD/Fe7Ni3MOF enzymatic cascade system demonstrated a linear response to hypoxanthine in the range of 3-70 µM, with a low detection limit of 1.39 µM. We also analyzed hypoxanthine in actual aquatic products, achieving spiked recoveries ranging from 90.04 % to 107.37 %. The correlation coefficient between our developed colorimetric method and the HPLC method was 0.98. Importantly, our proposed method holds several advantages over alternative techniques, particularly in terms of cost-effectiveness, precision, and speed. Consequently, this methodology shows great promise for the early detection of freshness changes in aquatic samples.

Network pharmacology and untargeted metabolomic-based investigation of anti-osteoporotic effects of viscozyme-assisted polysaccharide from Portulaca oleracea L.

Osteoporosis is a metabolic bone disease closely associated with oxidative stress. We had previously confirmed that the Viscozyme-assisted polysaccharide from Portulaca oleracea L (VPOP1) protects against antioxidant stress and evaluated the structure of VPOP1. In this study, we aimed to explore the anti-osteoporotic effects of VPOP1 on H2O2-induced osteoblast apoptosis. In addition, untargeted zebrafish metabolomics based on UPLC-Q-Orbitrap-HRMS was used to investigate the potential anti-osteoporotic mechanisms of VPOP1. The levels of Bcl-2 decreased significantly and those of caspase-3, Bax, and cytochrome C increased after treatment with H2O2. VPOP1 inhibited apoptosis in H2O2-induced MC3T3 cells. Metabolomic analyses showed that 28 potential biomarkers were gradually restored to normal levels after treatment with VPOP1 compared with that in the model group. Among them, leukotrienes D4 and A4, L-dopa, and L-tyrosine are important biomarkers and therapeutic targets. Pathway analysis revealed that arachidonic acid, tyrosine, phenylalanine, and sphingolipid metabolism were the major intervening pathways. Collectively, these results help us understand the protective activity of large molecular weight compounds, such as VPOP1, against osteoporosis.

Interplay between acetylation and ubiquitination of imitation switch chromatin remodeler Isw1 confers multidrug resistance in Cryptococcus neoformans.

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites revealed that the acetylation status of Isw1K97 coordinates with its ubiquitination processes at Isw1K113 and Isw1K441 through modulating the interaction between Isw1 and Cdc4, an E3 ligase. Additionally, clinical isolates of C. neoformans overexpressing the degradation-resistant ISW1K97Q allele showed impaired drug-resistant phenotypes. Collectively, our studies revealed a sophisticated acetylation-Isw1-ubiquitination regulation axis that controls multidrug resistance in C. neoformans.

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.

Identification of characteristics and construction of nomogram to predict the survival probability of mesonephric carcinoma patients: A population-based analysis and a case report.

BACKGROUND: Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of published guidelines. OBJECTIVE: To summarize the characteristics and construct an external-validated nomogram to predict the survival of MC patients. METHOD: Sixty-four qualified patients derived from the Surveillance, Epidemiology, and End Results Plus database, and one patient from the Guangzhou Red Cross Hospital were enrolled. The entire cohort was randomly divided into a development (70%) and a validation cohort (30%). The Kaplan-Meier method and univariate and multivariate Cox regression analyses were applied. Two nomograms were established to predict the 3-to-8-year survival probability of MC patients, which were evaluated by C-index, ROC curves, DCA curves, and calibration plots. RESULTS: The average survival time of MC patients was 84.22 ± 50.66 months. No significant difference was shown among different groups of race, primary site, tumor differentiated grade, and FIGO stages, while different SEER stages did distinguish patients' survival time, which indicated that the SEER stage standards might be a better staging system in the MC patients than FIGO stage (p = .0835). Additional survival analyses showed that MC patients benefited from shorter waiting times to begin treatment, accepting surgery, regional lymph node examination, radiotherapy, and chemotherapy. Two nomograms were established, both of which got satisfied scores in C-index, ROC curves, DCA curves, and calibration plots. CONCLUSION: Sufficient regional lymph nodes examined, and applying radiotherapy in high-risk patients are recommended in MC patients. Nomograms established in the present study had good predicting and discriminating capabilities, which would be helpful in patients' individual risk estimation, management, counseling, and follow-up.

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.

Resveratrol-derived inhibitors of the E3 ubiquitin ligase PELI1 inhibit the metastasis of triple-negative breast cancer.

Triple-negative breast cancer (TNBC), as the most challenging subtype of breast cancer, exerts highly invasive ability and metastatic nature to the lymph nodes, which is correlated with poor survival rates among patients. Pellino-1 (PELI1) is an E3 ubiquitin ligase involved in tumor invasion and metastasis, and has the potential to be developed as a novel therapeutic target for TNBC. In this study, we identified a potent inhibitor of PELI1, namely compound 3d, on the basis of natural stilbene framework through medicinal chemistry approaches. This novel PELI1 inhibitor 3d showed potent binding affinity to PELI1 (Kd 8.2 µM) in fluorescence quenching assay, and markedly interrupted the interaction of PELI1 and SNAIL/SLUG confirmed by co-immunoprecipitation. Moreover, 3d exhibited potent antitumor activity in inhibiting tumor cell migration in scratch wound healing assay without affecting cell proliferation in vitro, and down-regulated the downstream EMT-effectors of PELI1 as assessed by western blotting. In the experimental lung metastasis model, 3d showed anti-TNBC metastasis efficacy without observable toxicity in vivo.

Detection and Characterization of Web-Based Pediatric COVID-19 Vaccine Discussions and Racial and Ethnic Minority Topics: Retrospective Analysis of Twitter Data.

Background: Despite pediatric populations representing a smaller proportion of COVID-19 cases and having a less severe prognosis, those belonging to racial and ethnic minority groups are at an increased risk of developing more severe COVID-19-related outcomes. Vaccine coverage is crucial to pandemic mitigation efforts, yet since the start of the COVID-19 pandemic, vaccine hesitancy has increased and routine pediatric immunizations have decreased. Limited research exists on how vaccine hesitancy may contribute to low pediatric COVID-19 vaccine uptake among racial and ethnic minority populations. Objective: This study aimed to characterize COVID-19 vaccine-related discussion and sentiment among Twitter users, particularly among racial and ethnic minority users. Methods: We used the Twitter application programming interface to collect tweets and replies. Tweets were selected by filtering for keywords associated with COVID-19 vaccines and pediatric-related terms. From this corpus of tweets, we used the Biterm Topic Model to output topics and examined the top 200 retweeted tweets that were coded for pediatric COVID-19 vaccine relevance. Relevant tweets were analyzed using an inductive coding approach to characterize pediatric COVID-19 vaccine-related themes. Replies to relevant tweets were collected and coded. User metadata were assessed for self-reporting of race or ethnic group affiliation and verified account status. Results: A total of 863,007 tweets were collected from October 2020 to October 2021. After outputting Biterm Topic Model topics and reviewing the 200 most retweeted tweets, 208,666 tweets and 3905 replies were identified as being pediatric COVID-19 vaccine related. The majority (150,262/208,666, 72.01%) of tweets expressed vaccine-related concerns. Among tweets discussing vaccine confidence, user replies expressing agreement were significantly outweighed by those expressing disagreement (1016/3106, 32.71% vs 2090/3106, 67.29%; P<.001). The main themes identified in the Twitter interactions were conversations regarding vaccine-related concerns including adverse side effects, concerns that the vaccine is experimental or needs more testing and should not be tested on pediatric populations, the perception that the vaccine is unnecessary given the perceived low risk of pediatric infection, and conversations associated with vaccine-related confidence (ie, the vaccine is protective). Among signal tweets and replies, we identified 418 users who self-identified as a racial minority individual and 40 who self-identified as an ethnic minority individual. Among the subcodes identified in this study, the vaccine being protective was the most discussed topic by racial and ethnic minority groups (305/444, 68.7%). Conclusions: Vaccine-related concerns can have negative consequences on vaccine uptake and participation in vaccine-related clinical trials. This can impact the uptake and development of safe and effective vaccines, especially among racial and ethnic minority populations.

Synergism between IL-33 and MRGPRX2/FcεRI Is Primarily Due to the Complementation of Signaling Modules, and Only Modestly Supplemented by Prolonged Activation of Selected Kinases.

Skin mast cells (MCs) express high levels of MRGPRX2, FcεRI, and ST2, and vigorously respond to their ligands when triggered individually. IL-33/ST2 also potently synergizes with other receptors, but the molecular underpinnings are poorly understood. Human skin-derived MCs were stimulated via different receptors individually or jointly in the presence/absence of selective inhibitors. TNF was quantified by ELISA. Signaling cascades were studied by immunoblot. TNF was stimulated by FcεRI ≈ ST2 > MRGPRX2. Surprisingly, neither FcεRI nor MRGPRX2 stimulation elicited NF-κB activation (IκB degradation, p65 phosphorylation) in stark contrast to IL-33. Accordingly, TNF production did not depend on NF-κB in FcεRI- or MRGPRX2-stimulated MCs, but did well so downstream of ST2. Conversely, ERK1/2 and PI3K were the crucial modules upon FcεRI/MRGPRX2 stimulation, while p38 was key to the IL-33-elicited route. The different signaling prerequisites were mirrored by their activation patterns with potent pERK/pAKT after FcεRI/MRGPRX2, but preferential induction of pp38/NF-κB downstream of ST2. FcεRI/MRGPRX2 strongly synergized with IL-33, and some synergy was still observed upon inhibition of each module (ERK1/2, JNK, p38, PI3K, NF-κB). IL-33's contribution to synergism was owed to p38 > JNK > NF-κB, while the partner receptor contributed through ERK > PI3K ≈ JNK. Concurrent IL-33 led to slightly prolonged pERK (downstream of MRGPRX2) or pAKT (activated by FcεRI), while the IL-33-elicited modules (pp38/NF-κB) remained unaffected by co-stimulation of FcεRI/MRGPRX2. Collectively, the strong synergistic activity of IL-33 primarily results from the complementation of highly distinct modules following co-activation of the partner receptor rather than by altered signal strength of the same modules.

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 twenty Telegram groups with 262,506 active subscribers. Total volume of channel messages were 43,963 unique messages that included 3,094 (7.04%) marketing/selling messages. The most commonly sold products in these groups were cannabis-derived products (83.25%, n=2,576), 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.

Efficient Treatment of Pulpitis via Transplantation of Human Pluripotent Stem Cell-Derived Pericytes Partially through LTBP1-Mediated T Cell Suppression.

Dental pulp pericytes are reported to have the capacity to generate odontoblasts and express multiple cytokines and chemokines that regulate the local immune microenvironment, thus participating in the repair of dental pulp injury in vivo. However, it has not yet been reported whether the transplantation of exogenous pericytes can effectively treat pulpitis, and the underlying molecular mechanism remains unknown. In this study, using a lineage-tracing mouse model, we showed that most dental pulp pericytes are derived from cranial neural crest. Then, we demonstrated that the ablation of pericytes could induce a pulpitis-like phenotype in uninfected dental pulp in mice, and we showed that the significant loss of pericytes occurs during pupal inflammation, implying that the transplantation of pericytes may help to restore dental pulp homeostasis during pulpitis. Subsequently, we successfully generated pericytes with immunomodulatory activity from human pluripotent stem cells through the intermediate stage of the cranial neural crest with a high level of efficiency. Most strikingly, for the first time we showed that, compared with the untreated pulpitis group, the transplantation of hPSC-derived pericytes could substantially inhibit vascular permeability (the extravascular deposition of fibrinogen, ** p < 0.01), alleviate pulpal inflammation (TCR+ cell infiltration, * p < 0.05), and promote the regeneration of dentin (** p < 0.01) in the mouse model of pulpitis. In addition, we discovered that the knockdown of latent transforming growth factor beta binding protein 1 (LTBP1) remarkably suppressed the immunoregulation ability of pericytes in vitro and compromised their in vivo regenerative potential in pulpitis. These results indicate that the transplantation of pericytes could efficiently rescue the aberrant phenotype of pulpal inflammation, which may be partially due to LTBP1-mediated T cell suppression.

Treatment Outcome of Response-Based Radiation Therapy in Children and Adolescents With Central Nervous System Nongerminomatous Germ Cell Tumors: Results of a Prospective Study.

PURPOSE: The optimal dose and range of radiation therapy for central nervous system nongerminomatous germ cell tumors (NGGCTs) have not been uniformly established. Therefore, this study aimed to investigate the effect of individualized radiation therapy, based on the response to induction chemotherapy combined with surgery, on the prognosis of patients with NGGCTs. METHODS AND MATERIALS: Based on the imaging examination and tumor markers after induction chemotherapy and pathologic results of second-look surgery, patients with NGGCT received different radiation therapy strategies, including 30.6 Gy whole ventricular irradiation + tumor-bed boost to 54 Gy, 30.6 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, 36 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, and 36 Gy craniospinal irradiation + 54 Gy tumor-bed boost with 45 Gy to metastatic spinal lesions. RESULTS: A total of 51 patients were enrolled between January 2015 and March 2021, with a median age of 10.3 years. The 3-year event-free survival and overall survival (OS) of the entire cohort were 70.2% ± 6.9% and 77.5% ± 6.0%, respectively. The 3-year OS of patients achieving partial response after induction chemotherapy was higher than that of patients with stable disease (P = .03) or progressive disease (P = .002). The 3-year event-free survival and OS of the 18 patients receiving 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed boost were 88.9% ± 7.4% and 94.4% ± 5.4%, respectively. CONCLUSIONS: The results suggest that an individualized radiation therapy strategy based on response to induction chemotherapy and surgery is a feasible and promising means of achieving reduction in dose and extent of radiation in patients while still providing good response.

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.

Optimum Fermentation Conditions for Bovine Lactoferricin-Lactoferrampin-Encoding LimosiLactobacillus reuteri and Regulation of Intestinal Inflammation.

The multifunctional antibacterial peptide lactoferricin-lactoferrampin (LFCA) is derived from bovine lactoferrin. Optimization of the fermentation process should be studied since different microorganisms have their own favorable conditions and processes for growth and the production of metabolites. In this study, the culture conditions of a recombinant strain, pPG-LFCA-E/LR-CO21 (LR-LFCA), expressing LFCA was optimized, utilizing the high-density fermentation process to augment the biomass of LimosiLactobacillus reuteri and the expression of LFCA. Furthermore, an assessment of the protective effect of LR-LFCA on intestinal inflammation induced by lipopolysaccharide (LPS) was conducted to evaluate the impact of LR-LFCA on the disease resistance of piglets. The findings of this study indicate that LR-LFCA fermentation conditions optimally include 2% inoculation volume, 36.5 °C fermentation temperature, 9% dissolved oxygen concentration, 200 revolutions/minute stirring speed, pH 6, 10 mL/h glucose flow, and 50% glucose concentration. The inclusion of fermented LR-LFCA in the diet resulted in an elevation of immunoglobulin levels, significant upregulation of tight junction proteins ZO-1 and occludin, reinforcement of the intestinal barrier function, and significant amelioration of the aberrant alterations in blood physiological parameters induced by LPS. These results offer a theoretical framework for the implementation of this micro-ecological preparation in the field of piglet production to enhance intestinal well-being.

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.

Molecular Characteristics and Polymorphisms of Buffalo (Bubalus bubalis) ABCG2 Gene and Its Role in Milk Fat Synthesis.

The ATP-binding cassette subfamily G member 2 (ABCG2) serves crucial roles in secreting riboflavin and biotin vitamins into the milk of cattle, mice, and humans, as well as in the transportation of xenotoxic and cytostatic drugs across the plasma membrane. However, the specific role of the ABCG2 gene in water buffaloes (Bubalus bubalis), especially its effect on milk fat synthesis in buffalo mammary epithelial cells (BuMECs), remains inadequately understood. In this study, the full-length CDS of the buffalo ABCG2 gene was isolated and identified from the mammary gland in buffaloes. A bioinformatics analysis showed a high degree of similarity in the transcriptional region, motifs, and conservative domains of the buffalo ABCG2 with those observed in other Bovidae species. The functional role of buffalo ABCG2 was associated with the transportation of solutes across lipid bilayers within cell membranes. Among the 11 buffalo tissues detected, the expression levels of ABCG2 were the highest in the liver and brain, followed by the mammary gland, adipose tissue, heart, and kidney. Notably, its expression in the mammary gland was significantly higher during peak lactation than during non-lactation. The ABCG2 gene was identified with five SNPs in river buffaloes, while it was monomorphic in swamp buffaloes. Functional experiments revealed that ABCG2 increased the triglyceride (TAG) content by affecting the expression of liposynthesis-related genes in BuMECs. The results of this study underscore the pivotal role of the ABCG2 gene in influencing the milk fat synthesis in BuMECs.

Built-In Electric Field-Driven Ultrahigh-Rate K-Ion Storage via Heterostructure Engineering of Dual Tellurides Integrated with Ti3C2Tx MXene.

Exploiting high-rate anode materials with fast K+ diffusion is intriguing for the development of advanced potassium-ion batteries (KIBs) but remains unrealized. Here, heterostructure engineering is proposed to construct the dual transition metal tellurides (CoTe2/ZnTe), which are anchored onto two-dimensional (2D) Ti3C2Tx MXene nanosheets. Various theoretical modeling and experimental findings reveal that heterostructure engineering can regulate the electronic structures of CoTe2/ZnTe interfaces, improving K+ diffusion and adsorption. In addition, the different work functions between CoTe2/ZnTe induce a robust built-in electric field at the CoTe2/ZnTe interface, providing a strong driving force to facilitate charge transport. Moreover, the conductive and elastic Ti3C2Tx can effectively promote electrode conductivity and alleviate the volume change of CoTe2/ZnTe heterostructures upon cycling. Owing to these merits, the resulting CoTe2/ZnTe/Ti3C2Tx (CZT) exhibit excellent rate capability (137.0 mAh g-1 at 10 A g-1) and cycling stability (175.3 mAh g-1 after 4000 cycles at 3.0 A g-1, with a high capacity retention of 89.4%). More impressively, the CZT-based full cells demonstrate high energy density (220.2 Wh kg-1) and power density (837.2 W kg-1). This work provides a general and effective strategy by integrating heterostructure engineering and 2D material nanocompositing for designing advanced high-rate anode materials for next-generation KIBs.

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.