Comparison of the Effects of Multiple Frailty and Nutritional Indexes on Postoperative Outcomes in Critically Ill Patients Undergoing Lung Transplantation.

Background and Objective: Lung transplantation is the only life-extending therapy for end-stage pulmonary disease patients, but its risks necessitate an understanding of outcome predictors, with the frailty index and nutritional status being key assessment tools. This study aims to evaluate the relationship between preoperative frailty and nutritional indexes and the postoperative mortality rate in patients receiving lung transplants, and to determine which measure is a more potent predictor of outcomes. Materials and Methods: This study reviewed 185 adults who received lung transplants at a single medical center between January 2013 and May 2023. We primarily focused on postoperative 7-year overall survival. Other outcomes measured were short-term mortalities, acute rejection, kidney complications, infections, and re-transplantation. We compared the predictive abilities of preoperative nutritional and frailty indicators for survival using receiver operating characteristic curve analysis and identified factors affecting survival through regression analyses. Results: There were no significant differences in preoperative nutritional indicators between survivors and non-survivors. However, preoperative frailty indicators did differ significantly between these groups. Multivariate analysis revealed that the American Society of Anesthesiologists Class V, clinical frailty scale, and Charlson Comorbidity Index (CCI) were key predictors of 7-year overall survival. Of these, the CCI had the strongest predictive ability with an area under the curve of 0.755, followed by the modified frailty index at 0.731. Conclusions: Our study indicates that for critically ill patients undergoing lung transplantation, frailty indexes derived from preoperative patient history and functional autonomy are more effective in forecasting postoperative outcomes, including survival, than indexes related to preoperative nutritional status.

Effects of Qigong Therapy on the Psychological Well-Being, Physical Health State, Sleep State, and Life Satisfaction of Older Adults Living in Community.

Older adults living in a community are looking for alternative and complementary methods to improve their healthy longevity and quality of life. This study aimed to examine the effects of the Qigong therapy on psychological well-being, physical health state, sleep state, and life satisfaction of older adults living in community. This study used a quasi-experimental pretest-posttest control group design. The study samples were 69 older adults (intervention, n = 34; control, n = 35) over 65 years old in community in South Korea. Qigong therapy was performed 50 minutes per session, twice a week for a total of 20 times over a 10-week period in a comfortable and quiet environment without external noise. Measures were the study participant's general characteristics survey, psychological well-being scale, Cornell Medical Index-Korean version, sleep scale, and life satisfaction scale standardized for the elderly. Effects of Qigong therapy according to interaction effect over time and the group showed statistically significant differences in psychological well-being, physical health state, sleep state, and life satisfaction. This study suggests that Qigong therapy was an effective nursing intervention for improving the psychological well-being, physical health state, sleep state, and life satisfaction of older adults living in community.

Internal and External Validation of Machine Learning Models for Predicting Acute Kidney Injury Following Non-Cardiac Surgery Using Open Datasets.

This study developed and validated a machine learning model to accurately predict acute kidney injury (AKI) after non-cardiac surgery, aiming to improve patient outcomes by assessing its clinical feasibility and generalizability. We conducted a retrospective cohort study using data from 76,032 adults who underwent non-cardiac surgery at a single tertiary medical center between March 2019 and February 2021, and used data from 5512 patients from the VitalDB open dataset for external model validation. The predictive variables for model training consisted of demographic, preoperative laboratory, and intraoperative data, including calculated statistical values such as the minimum, maximum, and mean intraoperative blood pressure. When predicting postoperative AKI, our gradient boosting machine model incorporating all the variables achieved the best results, with AUROC values of 0.868 and 0.757 for the internal and external validations using the VitalDB dataset, respectively. The model using intraoperative data performed best in internal validation, while the model with preoperative data excelled in external validation. In this study, we developed a predictive model for postoperative AKI in adult patients undergoing non-cardiac surgery using preoperative and intraoperative data, and external validation demonstrated the efficacy of open datasets for generalization in medical artificial modeling research.

Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion.

Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors. SIGNIFICANCE: We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression.

Apolipoprotein D3 and LOX product play a role in immune-priming of a lepidopteran insect, Spodoptera exigua.

Immune-priming occurs in insects after a prior pathogen exposure. However, its underlying mechanism in insects remains elusive. In the present work, immune-priming was detected in a lepidopteran insect, Spodoptera exigua. Specifically, a prior infection with a heat-killed pathogenic bacterium, Escherichia coli, led to increased survival upon the second infection of different pathogens. Plasma collected from larvae with the prior infection possessed the immune-priming factor(s) that significantly up-regulated cellular and humoral immune responses of naïve larvae. Our study also finds that variations in the timing of plasma collection for priming larvae resulted in distinct impacts on both cellular and humoral responses. However, when the active plasma exhibiting the immune-priming was heat-treated, it lost this priming activity, therefore suggesting that protein factor(s) play a role in this immune-priming. An immunofluorescence assay showed that the hemocytes collected from the immune-primed larvae highly reacted to a polyclonal antibody specific to a vertebrate lipocalin, apolipoprotein D (ApoD). Among 27 ApoD genes (Se-ApoD1 âˆ¼ Se-ApoD27) of S. exigua, Se-ApoD3 was found to be highly induced during the immune-priming, in which it was shown to be expressed in hemocytes and fat body from a fluorescence in situ hybridization analysis. RNA interference of Se-ApoD3 expression significantly impaired the immune-priming of S. exigua larvae. Moreover, the inhibition of eicosanoid biosynthesis suppressed the immune-priming, in which treatment with a lipoxygenase (LOX) inhibitor-and not treatment with a cyclooxygenase inhibitor-suppressed immune-priming. Further, an addition of LOX product such as lipoxin A4 or lipoxin B4 significantly rescued the lost immune-priming activity. Taken together, these results suggest that a complex of ApoD3 and LOX product mediates the immune-priming activity of S. exigua.

Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration.

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three dimensional (3D) multiphasic scaffolds using a 'solids-of-revolution' inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates the number of cells migrated and proliferated onto the scaffolds are mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and high-throughput screening for optimized tissue regeneration.

Back-trajectory analyses for evaluating the transboundary transport effect to the aerosol pollution in South Korea.

This study performed a back-trajectory analysis to determine the influence of transboundary transport on the extent of aerosol pollution in South Korea, based on 5-year PM2.5 measurements (2015-2019) in five cities covering South Korea. A transboundary transport case was selected if a back trajectory passed over a dedicated region (BOX 1 and BOX 2) in the Yellow Sea. First, we found that the frequency of transboundary transport largely increases in the high pollution case, and this pattern is almost consistent for all months and all five cities, indicating the importance of investigating the horizontal direction of air mass movement associated with PM2.5, which has been discussed extensively in previous studies. In this study, we also examined the altitude change and straight moving distance (defined as travel distance) of back trajectories regarding the extent of local PM2.5. Consequently, we found that back trajectories in high aerosol pollution showed much lower altitudes and shorter travel differences, implying a significant contribution of surface emissions and stagnant air conditions to severe aerosol pollution. As a result, the local PM2.5 level was not significantly enhanced when the air mass passed over the Yellow Sea if transboundary transport occurred at high altitudes with rapid movement (i.e., high altitude and long travel distance back-trajectory). Based on these results, we suggest utilizing the combined information of the horizontal direction, altitude variation, and length of back trajectories to better evaluate transboundary transport.

Does source matter? Examining the effects of health experts, friends, and social media influencers on young adult perceptions of Instagram e-cigarette education messages.

PURPOSE: Young adults' e-cigarette use is a leading public health concern. Using messages from credible sources can help improve message acceptance, yet little research has examined the role of source credibility on young adults' responses to e-cigarette education messages. METHODS: We examined the impact of source on young adults' perceptions of e-cigarette education messages and e-cigarettes. In July 2022, we conducted an experimental study using an online sample of young adults (N=459, Mage=24.6) who were randomized to one of three source conditions: expert, friend, or influencer, and viewed e-cigarette education messages. We used one-way ANOVA to estimate the association between the conditions and outcomes (perceived source credibility, message trust, curiosity, use interests, perceived message effectiveness, beliefs, harm perceptions, and intentions to refrain). RESULTS: The expert condition was associated with significantly higher perceived source credibility (vs. friend, influencer; p<0.001), message trust (vs. friend, influencer; p<0.001), and curiosity (vs. influencer; p's<0.05). CONCLUSIONS: Public health campaigns may leverage health experts to deliver e-cigarette education messages targeting young adults to improve effectiveness of the messages.

Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity.

Upon immune challenge, recognition signals trigger insect immunity to remove the pathogens through cellular and humoral responses. Various immune mediators propagate the immune signals to nearby tissues, in which polyunsaturated fatty acid (PUFA) derivatives play crucial roles. However, little was known on how the insects terminate the activated immune responses after pathogen neutralization. Interestingly, C20 PUFA was detected at the early infection stage and later C18 PUFAs were induced in a lepidopteran insect, Spodoptera exigua. This study showed the role of epoxyoctadecamonoenoic acids (EpOMEs) in the immune resolution at the late infection stage to quench the excessive and unnecessary immune responses. In contrast, dihydroxy-octadecamonoenoates (DiHOMEs) were the hydrolyzed and inactive forms of EpOMEs. The hydrolysis is catalyzed by soluble epoxide hydrolase (sEH). Inhibitors specific to sEH mimicked the immunosuppression induced by EpOMEs. Furthermore, the inhibitor treatments significantly enhanced the bacterial virulence of Bacillus thuringiensis against S. exigua. This study proposes a negative control of the immune responses using EpOME/DiHOME in insects.

Evaluation of the reliability and validity of the upright head roll test for lateral semicircular canal benign paroxysmal positional vertigo.

BACKGROUND: The upright head roll test (UHRT) is a recently introduced diagnostic maneuver for lateral semicircular canal benign paroxysmal positional vertigo (LSC-BPPV). OBJECTIVE: This study aimed to evaluate the reliability and validity of the UHRT. METHODS: Two separate studies were conducted. Study 1 analyzed 827 results of videonystagmography (VNG) to assess UHRT reliability, and Study 2 analyzed 130 LSC-BPPV cases to evaluate UHRT validity. RESULTS: The inter-test reliability between UHRT and the supine head roll test (SHRT) showed substantial agreement (Cohen's kappa = 0.753) in direction-changing positional nystagmus (DCPN) and almost perfect agreement (Cohen's kappa = 0.836) in distinguishing the direction of DCPN. The validity assessment of UHRT showed high accuracy in diagnosing LSC-BPPV (80.0%) and in differentiating the variant types (74.6%). UHRT was highly accurate in diagnosing the canalolithiasis type in LSC-BPPV patients (Cohen's kappa = 0.835); however, it showed only moderate accuracy in diagnosing the cupulolithiasis type (Cohen's kappa = 0.415). The intensity of nystagmus in UHRT was relatively weaker than that in SHRT (P < 0.05). CONCLUSION: UHRT is a reliable test for diagnosing LSC-BPPV and distinguishing subtypes. However, UHRT has a limitation in discriminating the affected side owing to a weaker intensity of nystagmus than SHRT.

Impact of Financial Disclosures and Health Warnings on Youth and Young Adult Perceptions of Pro-E-cigarette Instagram Posts.

INTRODUCTION: We examined the impact of financial disclosures and warning labels on pro-e-cigarette Instagram posts and their association with attitudes toward the ad and product among youth and young adults. METHODS: During March to May 2021, we conducted a factorial experiment using an online convenience sample of youth and young adults (N = 1687, Mage = 21.54). Participants were randomized to one of four conditions: pro-e-cigarette Instagram posts with only a financial disclosure, only a warning label, both a financial disclosure + warning label, or no financial disclosure or warning label. After viewing the posts, participants answered questions regarding their attitude toward the ad and the product. We used one-way ANOVA to estimate the association of condition on outcomes controlling for demographics. RESULTS: Young adults who viewed Instagram posts with only a financial disclosure reported more positive attitudes toward the ad than those who viewed posts with both a financial disclosure + warning label (p < .05). Young adults who viewed posts with only a financial disclosure reported more positive attitudes toward the product than those who viewed posts with only a warning label, both a financial disclosure + warning label, and without either (ps < .05). Differences were not statistically significant for youth. E-cigarette use status was associated with increased positive attitudes toward the ad (p < .001) and product (p < .001) for all participants. CONCLUSIONS: Our results can inform policy interventions to mitigate the effects of e-cigarette social media marketing among youth and young adults. Including financial disclosures may not decrease appeal of e-cigarettes compared to posts without either. IMPLICATIONS: Findings from the study suggest that a warning label may be more effective in reducing the effects of pro-e-cigarette social media posts than a financial disclosure among young adults. Public health officials should examine additional strategies beyond financial disclosures and warning labels (eg, social media peer mentoring program) to offset the persuasive effects of pro-e-cigarette social media marketing posts on young people. Additional policy interventional efforts are needed to limit the impact of e-cigarette social media marketing.

N-cadherin and ß1 integrin coordinately regulate growth plate cartilage architecture.

Spatial and temporal regulation of chondrocyte maturation in the growth plate drives growth of many bones. One essential event to generate the ordered cell array characterizing growth plate cartilage is the formation of chondrocyte columns in the proliferative zone via 90-degree rotation of daughter cells to align with the long axis of the bone. Previous studies have suggested crucial roles for cadherins and integrin ß1 in column formation. The purpose of this study was to determine the relative contributions of cadherin- and integrin-mediated cell adhesion in column formation. Here we present new mechanistic insights generated by application of live time-lapse confocal microscopy of cranial base explant cultures, robust genetic mouse models, and new quantitative methods to analyze cell behavior. We show that conditional deletion of either the cell-cell adhesion molecule Cdh2 or the cell-matrix adhesion molecule Itgb1 disrupts column formation. Compound mutants were used to determine a potential reciprocal regulatory interaction between the two adhesion surfaces and identified that defective chondrocyte rotation in a N-cadherin mutant was restored by a heterozygous loss of integrin ß1. Our results support a model for which integrin ß1, and not N-cadherin, drives chondrocyte rotation and for which N-cadherin is a potential negative regulator of integrin ß1 function.

The Combined Effects on Human Dental Pulp Stem Cells of Fast-Set or Premixed Hydraulic Calcium Silicate Cements and Secretome Regarding Biocompatibility and Osteogenic Differentiation.

An important part of regenerative endodontic procedures involving immature permanent teeth is the regeneration of the pulp-dentin complex with continuous root development. Hydraulic calcium silicate cements (HCSCs) are introduced for the pulpal treatment of immature permanent teeth. The stem-cell-derived secretome recently has been applied for the treatment of various damaged tissues. Here, we evaluated the biocompatibility and osteogenic differentiation of HCSCs combined with secretome on human dental pulp stem cells. In the Cell Counting Kit-8 test and wound healing assays, significantly higher cell viability was observed with secretome application. In alkaline phosphatase analysis, the activity was significantly higher with secretome application in all groups, except for RetroMTA on day 2 and Endocem MTA Premixed on day 4. In an Alizarin Red S staining analysis, all groups with secretome application had significantly higher staining values. Quantitative real-time polymerase chain reaction results showed that the day 7 expression of OSX significantly increased with secretome application in all groups. SMAD1 and DSPP expression also increased significantly with secretome addition in all groups except for Biodentine. In conclusion, HCSCs showed favorable biocompatibility and osteogenic ability and are predicted to demonstrate greater synergy with the addition of secretome during regenerative endodontic procedures involving immature permanent teeth.

Nanowire-Enhanced Fully Transparent and Flexible Indium Gallium Zinc Oxide Transistors with Chitosan Hydrogel Gate Dielectric: A Pathway to Improved Synaptic Properties.

In this study, a transparent and flexible synaptic transistor was fabricated based on a random-network nanowire (NW) channel made of indium gallium zinc oxide. This device employs a biocompatible chitosan-based hydrogel as an electrolytic gate dielectric. The NW structure, with its high surface-to-volume ratio, facilitated a more effective modulation of the channel conductance induced by protonic-ion polarization. A comparative analysis of the synaptic properties of NW- and film-type devices revealed the distinctive features of the NW-type configuration. In particular, the NW-type synaptic transistors exhibited a significantly larger hysteresis window under identical gate-bias conditions. Notably, these transistors demonstrated enhanced paired-pulse facilitation properties, synaptic weight modulation, and transition from short- to long-term memory. The NW-type devices displayed gradual potentiation and depression of the channel conductance and thus achieved a broader dynamic range, improved linearity, and reduced power consumption compared with their film-type counterparts. Remarkably, the NW-type synaptic transistors exhibited impressive recognition accuracy outcomes in Modified National Institute of Standards and Technology pattern-recognition simulations. This characteristic enhances the efficiency of practical artificial intelligence (AI) processes. Consequently, the proposed NW-type synaptic transistor is expected to emerge as a superior candidate for use in high-efficiency artificial neural network systems, thus making it a promising technology for next-generation AI semiconductor applications.

A Facile Strategy for the Fabrication of Cell-laden Porous Alginate Hydrogels Based on Two-phase Aqueous Emulsions.

Porous alginate hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden alginate hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of alginate and caseinate, are crosslinked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the caseinate phase from the ion-crosslinked alginate hydrogel. Those porous alginate hydrogels possess heterogeneous pores around 100 µm and interconnected paths. Human white adipose progenitors (WAPs) encapsulated in these hydrogels self-organize into spheroids and show enhanced viability, proliferation, and adipogenic differentiation, compared to non-porous constructs. As a proof of concept, this porous alginate hydrogel platform is employed to prepare core-shell spheres for coculture of WAPs and colon cancer cells, with WAP clusters distributed around cancer cell aggregates, to investigate cellular crosstalk. This efficacious approach is believed to provide a robust and versatile platform for engineering porous-structured alginate hydrogels for applications as cell carriers and in disease modeling.

Developing Mood-Based Computer-Tailored Health Communication for Smoking Cessation: Feasibility Randomized Controlled Trial.

BACKGROUND: Computer-tailored health communication (CTHC), a widely used strategy to increase the effectiveness of smoking cessation interventions, is focused on selecting the best messages for an individual. More recently, CTHC interventions have been tested using contextual information such as participants' current stress or location to adapt message selection. However, mood has not yet been used in CTCH interventions and may increase their effectiveness. OBJECTIVE: This study aims to examine the association of mood and smoking cessation message effectiveness among adults who currently smoke cigarettes. METHODS: In January 2022, we recruited a web-based convenience sample of adults who smoke cigarettes (N=615; mean age 41.13 y). Participants were randomized to 1 of 3 mood conditions (positive, negative, or neutral) and viewed pictures selected from the International Affective Picture System to induce an emotional state within the assigned condition. Participants then viewed smoking cessation messages with topics covering five themes: (1) financial costs or rewards, (2) health, (3) quality of life, (4) challenges of quitting, and (5) motivation or reasons to quit. Following each message, participants completed questions on 3 constructs: message receptivity, perceived relevance, and their motivation to quit. The process was repeated 30 times. We used 1-way ANOVA to estimate the association of the mood condition on these constructs, controlling for demographics, cigarettes per day, and motivation to quit measured during the pretest. We also estimated the association between mood and outcomes for each of the 5 smoking message theme categories. RESULTS: There was an overall statistically significant effect of the mood condition on the motivation to quit outcome (P=.02) but not on the message receptivity (P=.16) and perceived relevance (P=.86) outcomes. Participants in the positive mood condition reported significantly greater motivation to quit compared with those in the negative mood condition (P=.005). Participants in the positive mood condition reported higher motivation to quit after viewing smoking cessation messages in the financial (P=.03), health (P=.01), quality of life (P=.04), and challenges of quitting (P=.03) theme categories. We also compared each mood condition and found that participants in the positive mood condition reported significantly greater motivation to quit after seeing messages in the financial (P=.01), health (P=.003), quality of life (P=.01), and challenges of quitting (P=.01) theme categories than those in the negative mood condition. CONCLUSIONS: Our findings suggest that considering mood may be important for future CTHC interventions. Because those in the positive mood state at the time of message exposure were more likely to have greater quitting motivations, smoking cessation CTHC interventions may consider strategies to help improve participants' mood when delivering these messages. For those in neutral and negative mood states, focusing on certain message themes (health and motivation to quit) may be more effective than other message themes.

Advancements in Complementary Metal-Oxide Semiconductor-Compatible Tunnel Barrier Engineered Charge-Trapping Synaptic Transistors for Bio-Inspired Neural Networks in Harsh Environments.

This study aimed to propose a silicon-on-insulator (SOI)-based charge-trapping synaptic transistor with engineered tunnel barriers using high-k dielectrics for artificial synapse electronics capable of operating at high temperatures. The transistor employed sequential electron trapping and de-trapping in the charge storage medium, facilitating gradual modulation of the silicon channel conductance. The engineered tunnel barrier structure (SiO2/Si3N4/SiO2), coupled with the high-k charge-trapping layer of HfO2 and high-k blocking layer of Al2O3, enabled reliable long-term potentiation/depression behaviors within a short gate stimulus time (100 µs), even under elevated temperatures (75 and 125 °C). Conductance variability was determined by the number of gate stimuli reflected in the maximum excitatory postsynaptic current (EPSC) and the residual EPSC ratio. Moreover, we analyzed the Arrhenius relationship between the EPSC as a function of the gate pulse number (N = 1-100) and the measured temperatures (25, 75, and 125 °C), allowing us to deduce the charge trap activation energy. A learning simulation was performed to assess the pattern recognition capabilities of the neuromorphic computing system using the modified National Institute of Standards and Technology datasheets. This study demonstrates high-reliability silicon channel conductance modulation and proposes in-memory computing capabilities for artificial neural networks using SOI-based charge-trapping synaptic transistors.

A CRISPR activation screen identifies MUC-21 as critical for resistance to NK and T cell-mediated cytotoxicity.

BACKGROUND: Immunotherapy has significantly advanced cancer treatments, but many patients do not respond to it, partly due to immunosuppressive mechanisms used by tumor cells. These cells employ immunosuppressive ligands to evade detection and elimination by the immune system. Therefore, the discovery and characterization of novel immunosuppressive ligands that facilitate immune evasion are crucial for developing more potent anti-cancer therapies. METHODS: We conducted gain-of-function screens using a CRISPRa (CRISPR activation) library that covered the entire human transmembrane sub-genome to identify surface molecules capable of hindering NK-mediated cytotoxicity. The immunosuppressive role and mechanism of MUC21 were validated using NK and T cell mediated cytotoxicity assays. Bioinformatics tools were employed to assess the clinical implications of mucin-21 (MUC21) in cancer cell immunity. RESULTS: Our genetic screens revealed that MUC21 expression on cancer cell surfaces inhibits both the cytotoxic activity of NK cells and antibody-dependent cellular cytotoxicity, but not affecting complement-dependent cytotoxicity. Additionally, MUC21 expression hinders T cell activation by impeding antigen recognition, thereby diminishing the effectiveness of the immune checkpoint inhibitor, anti-PD-L1. Moreover, MUC21 expression suppress the antitumor function of both CAR-T cells and CAR-NK cells. Mechanistically, MUC21 facilitates immune evasion by creating steric hindrance, preventing interactions between cancer and immune cells. Bioinformatics analysis revealed elevated MUC21 expression in lung cancer, which correlated with reduced infiltration and activation of cytotoxic immune cells. Intriguingly, MUC21 expression was higher in non-small cell lung cancer (NSCLC) tumors that were non-responsive to anti-PD-(L)1 treatment compared to responsive tumors. CONCLUSIONS: These findings indicate that surface MUC21 serves as a potent immunosuppressive ligand, shielding cancer cells from NK and CD8+T cell attacks. This suggests that inhibiting MUC21 could be a promising strategy to improve cancer immunotherapy.

Metabolomic analysis reveals linkage between chemical composition and sensory quality of different floral honey samples.

Honey has a distinct flavor characterized by various volatiles and non-volatiles from diverse origins. In this study, metabolomics combined with sensory analysis was performed to identify relationships between chemical profile and sensory quality of honey. Targeted metabolomic analysis was conducted to determine volatile and non-volatile profiles of seven different honey. Volatile profile was analyzed using headspace solid-phase microextraction (HS-SPME) coupled to GC - MS. LC - MS/MS, HPLC - UV, and HPLC-RI were employed to analyze flavonoids, organic acids, and sugars, respectively. Authentic standards were utilized for confirmation of metabolites. Sensory evaluation included quantitative descriptive analysis and consumer acceptance test. The results showed that sucrose (sweetness) was responsible for a positive hedonic perception, while organic acids and flavonoids (sourness, astringency, bitterness) negatively affected consumer acceptance. Volatiles with floral notes (e.g. decyl formate) were preferred, but others with off-flavors (e.g. 2-methylbenzofuran) were not preferred by consumers. Flavor familiarity was strongly correlated with the consumer acceptance of honey, indicating that the balance between volatiles and non-volatiles is significant for honey flavor quality. This work demonstrates the role of key flavor compounds in honey quality, and may be applicable to the quality control of honey.

Sexual orientation and gender identity differences in perceptions and product appeal in response to e-cigarette advertising.

INTRODUCTION: E-cigarette use is disparately high among sexual minoritized populations. As e-cigarette advertising may influence product appeal, this study tested sexual orientation- and gender-based differences in response to e-cigarette advertisement exposure on advertisement perceptions and product appeal. METHODS: We recruited 497 adults (mean age=31.9 years, 45.1% women, 54.3% heterosexual, 71.2% Non-Hispanic White) living in the United States via the crowdsourcing platform Prolific. Participants viewed two randomly selected e-cigarette advertisements (from n=173 advertisements). Post-exposure, participants rated the perceived advertisement effectiveness, relevance, and product use intention. Associations between sexual orientation and outcomes were estimated using multivariable linear mixed-effects models. We tested interaction effects between sexual orientation, gender, and advertisement feature (e.g. presence of humans, flavors, and product packaging), and ran Tukey post hoc tests for pairwise comparisons. RESULTS: Post-exposure, heterosexual women, sexual minoritized men, and sexual minoritized women (reference group: heterosexual men) rated perceived advertisement effectiveness and relevance lower after viewing advertisements featuring flavors (vs no flavors; all p<0.001). Sexual minoritized men and sexual minoritized women rated perceived advertisement relevance lower after viewing advertisements featuring humans (all p<0.001) or fruit (all p<0.001). Heterosexual women, sexual minoritized men, and sexual minoritized women reported lower product use intention after viewing advertisements featuring an e-liquid bottle (vs no e-liquid bottle; all p<0.05). CONCLUSIONS: Sexual minoritized women and men reported lower e-cigarette advertisement appeal and product use intentions than heterosexual men. More evidence is needed to understand advertisement perceptions and product appeal in this group to inform e-cigarette advertising regulations and anti-tobacco messaging campaigns that aim to reduce tobacco-related health inequities.