Exogenous Indole-3-Acetic Acid Suppresses Rice Infection of Magnaporthe oryzae by Affecting Plant Resistance and Fungal Growth.

Auxin is an important phytohormone that regulates diverse biologic processes, including plant growth and immunity. Indole-3-acetic acid (IAA), known as one of the main forms of auxin, is able to activate plant immunity. However, it is unknown whether IAA enhances plant resistance and/or suppresses the growth of the fungal pathogen Magnaporthe oryzae. Here, we found that IAA could induce expression levels of pathogenesis-related genes to enhance disease resistance and could control the development of blast disease through inhibiting M. oryzae infection. Exogenous IAA suppressed mycelial growth and delayed spore germination by inhibiting fungal endogenous IAA biosynthesis and impairing redox homeostasis, respectively. When applied to a field test, two IAA analogues, 1-naphthaleneacetic acid and 2,4-dichlorophenoxy acetic acid, can effectively control rice blast disease. Our study advances the understanding of IAA in controlling rice blast disease through suppressing pathogen growth and enhancing plant resistance.

Characterization of a broad-spectrum antifungal strain, Streptomyces graminearus STR-1, against Magnaporthe oryzae.

Fungal diseases such as the devastating rice blast pose severe threats to crop production worldwide. Biological control of crop diseases caused by fungal pathogens is an environment-friendly approach for safeguarding crop production. But the insufficient availability of microbial agents effective against various fungal diseases has hampered the development of green production in crops. In this study, we identified a broad-spectrum antifungal bacterium, Streptomyces graminearus STR-1, showing antagonistic activity to diverse fungal pathogens including Magnaporthe oryzae, Rhizoctonia solani, Fusarium graminearum, Ustilaginoidea virens, and Bipolaris maydis. Its antifungal activity was relatively stable and less affected by temperature and pH. Evaluation of the biocontrol activity of STR-1 revealed that STR-1 prevented and controlled rice blast disease via eliciting plant immunity and suppressing fungal infection-structure development. STR-1 broth extract inhibited spore germination, likely through inhibiting protein synthesis. Combining LC-MS and chromatography analysis of the antimicrobial compounds purified from STR-1 broth extract, together with decoding STR-1 genomic sequence, we identified 4-oxo-4-[(1-phenylethyl)amino]but-2-enoic acid, 1,3,5-Trimethylpyrazole and SMA-1 as the potential main STR-1 secondary metabolites associated with its antifungal effects. This study suggests that bacterial strain STR-1 could be used for identifying highly effective and broad-spectrum secondary metabolites for containing rice blast and other crop diseases. The application of the active compounds offers a promising measure to tackle fungal disease.

Excess homocysteine inhibits pancreatic ß-cell secretory function by repressing Zbtb20 expression.

Homocysteine (Hcy) is a sulfur-containing amino acid. An elevated level of Hcy is a risk factor for diabetes development. However, the mechanism of its effect on pancreatic ß-cell function is unclear. In this study, we constructed a hyperhomocysteinemia (HHcy) mouse model by feeding mice a high methionine diet (HMD). The mice suffered impaired glucose tolerance and reduced insulin secretion. Furthermore, at the cellular level, INS1 cells exhibited impaired insulin secretory function after the Hcy intervention. Transcriptomics revealed that Zbtb20 expression was downregulated and the downstream gene Fbp1 was upregulated in HHcy-induced mice compared with mice fed with normal diet. Insulin secretion could be restored by Zbtb20 overexpression or fructose 1,6-bisphosphatase (FBPase) activity inhibition in INS1 cells. In conclusion, our study suggested that Hcy inhibited the insulin secretory function of pancreatic ß-cells by suppressing Zbtb20 expression, leading to the development of diabetes. Zbtb20 may be a key target in the development of diabetes associated with elevated Hcy levels.

Variability of large timescale functional networks in patients with disorders of consciousness.

Objective: Most brain function assessments for disorders of consciousness (DOC) utilized quantified characteristics, measured only once, ignoring the variation of patients' brain states. The study aims to investigate the brain activities of patients with DOC from a new perspective: variability of a large timescale functional network. Methods: Forty-nine patients were enrolled in this study and performed a 1-week behavioral assessment. Subsequently, each patient received electroencephalography (EEG) recordings five times daily at 2-h intervals. Functional connectivity and networks were measured by weighted phase lag index and complex network parameters (characteristic path length, cluster coefficient, and betweenness centrality). The relative coefficient of variation (CV) of network parameters was measured to evaluate functional network variability. Results: Functional networks of patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS) showed significantly higher segregation (characteristic path length) and lower centrality (betweenness centrality) than emerging from the minimal conscious state (EMCS) and minimal conscious state (MCS), as well as lower integration (cluster coefficient) than MCS. The functional networks of VS/UWS patients consistently presented the highest variability in segregation and integration (i.e., highest CV values of characteristic path length and cluster coefficient) on a larger time scale than MCS and EMCS. Moreover, the CV values of characteristic path length and cluster coefficient showed a significant inverse correlation with the Coma Recovery Scale-Revised scores (CRS-R). The CV values of network betweenness centrality, particularly of the cento-parietal region, showed a positive correlation with the CRS-R. Conclusion: The functional networks of VS/UWS patients present the most invariant segregation and integration but divergent centrality on the large time scale networks than MCS and EMCS. Significance: The variations observed within large timescale functional networks significantly correlate with the degree of consciousness impairment. This finding augments our understanding of the neurophysiological mechanisms underpinning disorders of consciousness.

Rice false smut virulence protein subverts host chitin perception and signaling at lemma and palea for floral infection.

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.

Being there and being with them: the effects of visibility affordance of online short fitness video on users' intention to cloud fitness.

Introduction: Cloud fitness is transforming indoor exercise for young people in China. Recent studies have explored the correlation between media use and health-promoting behavior by examining the motivation of individuals and the credibility of influencers. However, the role of media affordance has thus far been largely overlooked. Drawing on the theory of Stimulus-Organism-Response (SOR), the study investigated the indirect effect of visibility affordance on the intention to exercise with fitness influencers in the context of cloud fitness through psychological variables. Methods: This paper, based on the online survey data (N = 456), analyses the effect of visibility affordance on the intention to fitness following with influencers. A moderated parallel mediation model was constructed to examine the relationship among related variables. Results: The paper draws the following conclusions: (1) Visibility affordance is positively related to the intention to exercise with fitness influencers. (2) Both the sense of social presence and immersion positively mediate the relationship between visibility affordance and the intention to exercise with fitness influencers. (3) The perceived popularity of the influencer positively moderates the relationship between social presence and the intention to exercise with fitness influencers and moderates the mediating role of social presence. Discussion: Consequently, this study enhances the existing body of knowledge in exercise behavior and health communication literature, and provides practical implications for short video platform, influencers and individuals in promoting healthier behaviors.

Mental health associated with the cluster of childhood trauma and resilience among nursing students: A cross-sectional study.

OBJECTIVE: This study aimed to propose clusters of the association between childhood trauma and resilience in nursing students and to examine their mental health according to these clusters. METHOD: A cross-sectional study was carried out between September 2018 and May 2019. A total of 1,245 undergraduate nursing students (104 male, 1,141 female) were enrolled in a medical university in East China to complete the Childhood Trauma Questionnaire, Connor-Davidson Resilience Scale, Self-Rating Anxiety Scale, and Self-Rating Depression Scale. RESULTS: The cluster analysis identified three clusters as follows: the self-healing group (40.7%), the mildly traumatized with low resiliency group (22.2%), and the healthy group (37.1%). The logistic regression analysis revealed that the levels of anxiety and depression significantly differed between the three clusters, with the mildly traumatized with low resiliency group having the highest odds to have anxiety and depression. CONCLUSION: This study identified three clusters of the association between childhood trauma and resilience in undergraduate nursing students and indicated that each cluster was associated with a different level of anxiety and depression. The unique characteristics of the three clusters may help identify and develop appropriate interventions to promote the mental health of undergraduate nursing students. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Magnaporthe oryzae effector MoSPAB1 directly activates rice Bsr-d1 expression to facilitate pathogenesis.

Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

Identifying Mental Health Literacy as a Key Predictor of COVID-19 Vaccination Acceptance among American Indian/Alaska Native/Native American People.

BACKGROUND: This study examines how health literacy and mental health literacy associate with the willingness to receive a COVID-19 vaccination among American Indian/Alaska Native/Native American (AI/AN) people. METHODS: The data were collected with an online Qualtrics survey in February 2021 (n = 563). A purposive snowball sampling strategy was used by sending recruitment flyers to colleagues and organizations who work with AI/AN communities to share with appropriate potential respondents. We performed linear regression analyses examining the relationships between the willingness to receive a COVID-19 vaccination and socio-demographic characteristics such as age, gender, education, health literacy, mental health literacy, self-rated physical and mental health status, worry about getting COVID-19, perceived COVID-19 susceptibility, and perceived COVID-19 severity. RESULTS: Mental health literacy and health literacy predicted 30.90% and 4.65% of the variance (R2adjusted) in the willingness to receive a COVID-19 vaccine, respectively. After holding the self-rated physical/mental health status, worry about getting COVID-19, perceived susceptibility, perceived severity, health literacy, and socio-demographics constant, mental health literacy was still a strong predictor (b = 0.03, p < 0.001) for the willingness to receive a COVID-19 vaccine (model R2adjusted = 40.14%). CONCLUSIONS: We identified mental health literacy as a substantial factor associated with the willingness to receive a COVID-19 vaccination among AI/AN respondents.

Chinese Americans' Information Sources on, Preferred Types of, and Satisfaction with COVID-19 Vaccination.

According to the Centers for Disease Control and Prevention (CDC), about 87% of Asian Americans had received at least one dose of the COVID-19 vaccine as of July 2023. The purpose of this study is to identify the sources of information, preferred vaccine types, and levels of satisfaction related to COVID-19 vaccination among Chinese Americans, the largest subgroup of Asian immigrants living in the U.S. Our survey data were collected from 241 Chinese American early adopters of the COVID-19 vaccine, who completed at least one dose of the COVID-19 vaccine in June 2021. Our results indicated that their major information sources regarding COVID-19 vaccination included health officials and authorities, local news, family/friends/co-workers, social media platforms, and healthcare professionals. More than half of the participants expressed a preference for the Pfizer-BioNTech (New York, U.S.) vaccine based on the primary considerations of safety, efficacy, credibility of the developer, and availability. A majority of the participants felt satisfied with their experience of receiving the COVID-19 vaccination. Participants with higher levels of self-efficacy and subjective norms related to receiving the COVID-19 vaccine were more likely to express satisfaction with the vaccination. These findings provide valuable insights into Chinese Americans' information sources, vaccine preferences, and satisfaction levels regarding COVID-19 vaccination. This knowledge can help guide future vaccination interventions and campaigns.

Mental fatigue assessment by an arbitrary channel EEG based on morphological features and LSTM-CNN.

In order to achieve more sensitive mental fatigue assessment (MFA) based on an arbitrary channel EEG, this study proposed a series of feature extraction methods that combine mathematical morphology (MM), as well as an LSTM-CNN architecture. Firstly, 37 subjects had their resting-state EEGs collected at rested wakefulness (RW) and after 24 h of sleep deprivation (SD) using a 30-channel EEG acquisition device, the RW and SD groups were regarded as the negative and positive groups of mental fatigue, respectively, and the EEG collection were further categorized into two conditions: eye-opened state (EO) and eye-closed state (EC). Then, since MM can reflect the morphological characteristics of EEG rhythms and their potentials relatively independently of the time-frequency analysis and phase calculation, the MM methods were found to better reflect the mental fatigue after SD statistically, whether for single features (ANOVA: p<0.000001), multiple features (clustering by K-means, t-test: p<0.01), or time series feature spaces (calculating CD, t-test: p<0.01) of a single channel. Finally, the LSTM-CNN enhanced the generalization ability when dealing with different single-channel EEG by combining GRUs with convolutional layers: comparing the AUCs of different architectures for MFA based on an arbitrary channel, LSTM-CNN (0.992) > LSTM network (0.94) > CNN (0.831) > MLP (0.754). Moreover, the use of MM also improved the accuracy of analyzed architectures, and the true/false positive rate (TPR/FPR) of the LSTM-CNN architecture for MFA based on an arbitrary channel reached 97.024 %/3.497 %, which provided a feasible solution for the arbitrary channel EEG-based MFA.

Behind the Indolent Facade: Uncovering the Molecular Features and Malignancy Potential in Lung Minimally Invasive Adenocarcinoma by Single-Cell Transcriptomics.

The increased use of low-dose computed tomography screening has led to more frequent detection of early stage lung tumors, including minimally invasive adenocarcinoma (MIA). To unravel the intricacies of tumor cells and the immune microenvironment in MIA, this study performs a comprehensive single-cell transcriptomic analysis and profiles the transcriptomes of 156,447 cells from fresh paired MIA and invasive adenocarcinoma (IA) tumor samples, peripheral blood mononuclear cells, and adjacent normal tissue samples from three patients with synchronous multiple primary lung adenocarcinoma. This study highlights a connection and heterogeneity between the tumor ecosystem of MIA and IA. MIA tumor cells exhibited high expression of aquaporin-1 and angiotensin II receptor type 2 and a basal-like molecular character. Furthermore, it identifies that cathepsin B+ tumor-associated macrophages may over-activate CD8+ T cells in MIA, leading to an enrichment of granzyme K+ senescent CD8+ T cells, indicating the possibility of malignant progression behind the indolent appearance of MIA. These findings are further validated in 34 MIA and 35 IA samples by multiplexed immunofluorescence. These findings provide valuable insights into the mechanisms that maintain the indolent nature and prompt tumor progression of MIA and can be used to develop more effective therapeutic targets and strategies for MIA patients.

Sequential and Simultaneous Interactions of Plant Allelochemical Flavone, Bt Toxin Vip3A, and Insecticide Emamectin Benzoate in Spodoptera frugiperda.

Target pests of genetically engineered crops producing both defensive allelochemicals and Bacillus thuringiensis (Bt) toxins often sequentially or simultaneously uptake allelochemicals, Bt toxins, and/or insecticides. How the three types of toxins interact to kill pests remains underexplored. Here we investigated the interactions of Bt toxin Vip3A, plant allelochemical flavone, and insecticide emamectin benzoate in Spodoptera frugiperda. Simultaneous administration of flavone LC25 + Vip3A LC25, emamectin benzoate LC25 + Vip3A LC25, and flavone LC15 + emamectin benzoate LC15 + Vip3A LC15 but not flavone LC25 + emamectin LC25 yielded a mortality significantly higher than their expected additive mortality (EAM). One-day pre-exposure to one toxin at LC5 followed by six-day exposure to the same toxin at LC5 plus another toxin at LC50 showed that the mortality of flavone LC5 + Vip3A LC50, emamectin benzoate LC5 + Vip3A LC50, and Vip3A LC5 + emamectin benzoate LC50 were significantly higher than their EAM, while that of flavone LC5 + emamectin benzoate LC50 was significantly lower than their EAM. No significant difference existed among the mortalities of Vip3A LC5 + flavone LC50, emamectin benzoate LC5 + flavone LC50, and their EAMs. The results suggest that the interactions of the three toxins are largely synergistic (inductive) or additive, depending on their combinations and doses.

Selenoprotein K knockdown induces apoptosis in skeletal muscle satellite cells via calcium dyshomeostasis-mediated endoplasmic reticulum stress.

Skeletal muscle satellite cells (SMSCs), known as muscle stem cells, play an important role in muscle embryonic development, post-birth growth, and regeneration after injury. Selenoprotein K (SELENOK), an endoplasmic reticulum (ER) resident selenoprotein, is known to regulate calcium ion (Ca2+) flux and ER stress (ERS). SELENOK deficiency is involved in dietary selenium deficiency-induced muscle injury, but the regulatory mechanisms of SELENOK in SMSCs development remain poorly explored in chicken. Here, we established a SELENOK deficient model to explore the role of SELENOK in SMSCs. SELENOK knockdown inhibited SMSCs proliferation and differentiation by regulating the protein levels of paired box 7 (Pax7), myogenic factor 5 (Myf5), CyclinD1, myogenic differentiation (MyoD), and Myf6. Further analysis exhibited that SELENOK knockdown markedly activated the ERS signaling pathways, which ultimately induced apoptosis in SMSCs. SELENOK knockdown-induced ERS is related with ER Ca2+ ([Ca2+]ER) overload via decreasing the protein levels of STIM2, Orai1, palmitoylation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1), phospholamban (PLN), and plasma membrane Ca2+-ATPase (PMCA) while increasing the protein levels of sarco/endoplasmic Ca2+-ATPase 1 (SERCA1) and Na+/Ca2+ exchanger 1 (NCX1). Moreover, thimerosal, an activator of IP3R1, reversed the overload of [Ca2+]ER, ERS, and subsequent apoptosis caused by SELENOK knockdown. These findings indicated that SELENOK knockdown triggered ERS driven by intracellular Ca2+ dyshomeostasis and further induced apoptosis, which ultimately inhibited SMSCs proliferation and differentiation.

Disruption of the Novel Small Protein RBR7 Leads to Enhanced Plant Resistance to Blast Disease.

Plant disease is a threat to global food security. Breeding crops carrying broad-spectrum resistance loci is an effective way to control infectious disease. Disease-resistant mutants are valuable resources for deciphering the underlying mechanisms of plant immunity and could provide genetic loci to generate disease-resistant crops. Here, we identified a rice mutant, rbr7 (rice blast resistance 7), that confers resistance against different strains of Magnaporthe oryzae. Disease-mimicking necrotic lesions started to appear on the leaves of rbr7 four weeks after sowing. Histochemical analysis revealed reactive oxygen species accumulation and cell death accompanied by spontaneous lesion formation in rbr7. Map-based cloning and bulk segregation analysis showed a 2855 bp fragment deletion on chromosome 5, leading to the disruption of the LOC_Os05g28480-coding protein. Transgenic rbr7 complementation plants showed compromised resistance to rice blast, indicating that LOC_Os05g28480, or Rbr7, regulates the rice immune response. Rbr7 encodes a small protein of unknown function with 85 amino acids. Transcriptomic analysis revealed that disruption of RBR7 led to the upregulation of genes responding to salicylic acid, systemic acquired resistance and pathogenesis-related genes. Taken together, our findings reveal insights into a novel small protein involved in regulating plant resistance to rice blast and provide a potential target for crop breeding.

Adaptation and validation of the Abrams geriatric self-neglect assessment scale among older Chinese people admitted to the hospital.

OBJECTIVES: Elder self-neglect is a global public health problem, and older people admitted to the hospital may have a higher risk of self-neglect due to their deteriorating health conditions. This study aimed to translate, adapt and validate the Abrams geriatric self-neglect assessment scale (AGSS) among older Chinese people admitted to the hospital. METHODS: Data were derived from a cross-sectional survey of a convenience sample of 452 older people admitted to a general hospital. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the structural validity of the AGSS. Content validity, criterion validity, internal consistency reliability, and test-retest reliability were also conducted to assess the psychometric properties of the scale. RESULTS: EFA yielded a 6-item one-factor model, which was supported by CFA and explained 44.74% of the total variance. The internal consistency was acceptable (Cronbach α = 0.740), and the test-retest reliability with a 14-day interval was good (intraclass correlation coefficient, ICC = 0.966). Significantly positive correlations with the caregiver-rated elder self-neglect assessment scale (r = 0.648) supported the concurrent validity of the scale. Significant differences in scores between respondents with different ages, marital statuses, educational levels and numbers of chronic diseases demonstrated the discriminative validity. CONCLUSION: The Chinese version of the AGSS is an easy-to-use, reliable and valid measure with satisfactory psychometric properties. Future studies should recruit a more representative sample of older people in China to verify the applicability of the scale. IMPLICATIONS FOR PRACTICE: The Chinese version of the AGSS enables clinical staff to accurately screen for and assess elder self-neglect upon hospital admission, which can inform the development of specific interventions and assignment of additional guardianship to those at risk of elder self-neglect.

Identifying immune cell infiltration and diagnostic biomarkers in heart failure and osteoarthritis by bioinformatics analysis.

Heart failure (HF) and osteoarthritis (OA) are medical conditions that can significantly impact daily activities. Evidence has shown that HF and OA may share some pathogenic mechanisms. However, the underlying genomic mechanisms remain unclear. This study aimed to explore the underlying molecular mechanism and identify diagnostic biomarkers for HF and OA. With the cutoff criteria of fold change (FC) > 1.3 and P < .05, 920, 1500, 2195, and 2164 differentially expressed genes (DEGs) were identified in GSE57338, GSE116250, GSE114007, and GSE169077, respectively. After making the intersection of DEGs, we obtained 90 upregulated DEGs and 51 downregulated DEGs in HF datasets and 115 upregulated DEGs and 75 downregulated DEGs in OA datasets. Afterward, we conducted genome ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, protein-protein interaction (PPI) networks, and hub genes screening based on DEGs. Then, 4 common DEGs (fibroblast activation protein alpha [FAP], secreted frizzled-related protein 4 (SFRP4), Thy-1 cell surface antigen (THY1), matrix remodeling associated 5 [MXRA5]) between HF and OA were screened and validated in GSE5406 and GSE113825 datasets, based on which we established the support vector machine (SVM) models. The combined area under the receiver operating characteristic curve (AUC) of THY1, FAP, SFRP4, and MXRA5 in the HF training and test sets reached 0.949 and 0.928. While in the OA training set and test set, the combined AUC of THY1, FAP, SFRP4, and MXRA5 reached 1 and 1, respectively. The analysis of immune cells in HF revealed high levels of dendritic cell (DC), B cells, natural killer T cell (NKT), Type 1 regulatory T cell (Tr1), cytotoxic T cell (Tc), exhausted T cell (Tex), and mucosal-associated invariant T cell (MAIT), while displaying lower levels of monocytes, macrophages, NK, CD4 + T, gamma delta T (γδ T), T helper type 1 (Th1), T helper type 2 (Th2), and effector memory T cell (Tem). Moreover, the 4 common DEGs were positively correlated with DCs and B cells and negatively correlated with γδ T. In OA patients, the abundance of monocyte, macrophage, CD4 + naïve, and natural T regulatory cell (nTreg) was higher, while the infiltration of CD8 + T, γδ T, CD8 + naïve, and MAIT was lower. The expression of THY1 and FAP was significantly correlated with macrophage, CD8 + T, nTreg, and CD8 + naïve. SFRP4 was correlated with monocyte, CD8 + T, γδ T, CD4 + naïve, nTreg, CD8 + naïve and MAIT. MXRA5 was correlated with macrophage, CD8 + T, nTreg and CD8 + naïve. FAP, THY1, MXRA5, and SFRP4 may be diagnostic biomarkers for both HF and OA, and their correlation with immune cell infiltrations suggests shared immune pathogenesis.

Targeting inhibition of prognosis-related lipid metabolism genes including CYP19A1 enhances immunotherapeutic response in colon cancer.

BACKGROUND: Lipid metabolic reprogramming in colon cancer shows a potential impact on tumor immune microenvironment and is associated with response to immunotherapy. Therefore, this study aimed to develop a lipid metabolism-related prognostic risk score (LMrisk) to provide new biomarkers and combination therapy strategies for colon cancer immunotherapy. METHODS: Differentially expressed lipid metabolism-related genes (LMGs) including cytochrome P450 (CYP) 19A1 were screened to construct LMrisk in TCGA colon cancer cohort. The LMrisk was then validated in three GEO datasets. The differences of immune cell infiltration and immunotherapy response between LMrisk subgroups were investigated via bioinformatic analysis. These results were comfirmed by in vitro coculture of colon cancer cells with peripheral blood mononuclear cells, human colon cancer tissue microarray analysis, multiplex immunofluorescence staining and mouse xenograft models of colon cancer. RESULTS: Six LMGs including CYP19A1, ALOXE3, FABP4, LRP2, SLCO1A2 and PPARGC1A were selected to establish the LMrisk. The LMrisk was positively correlated with the abundance of macrophages, carcinoma-associated fibroblasts (CAFs), endothelial cells and the levels of biomarkers for immunotherapeutic response including programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden and microsatellite instability, but negatively correlated with CD8+ T cell infiltration levels. CYP19A1 protein expression was an independent prognostic factor, and positively correlated with PD-L1 expression in human colon cancer tissues. Multiplex immunofluorescence analyses revealed that CYP19A1 protein expression was negatively correlated with CD8+ T cell infiltration, but positively correlated with the levels of tumor-associated macrophages, CAFs and endothelial cells. Importantly, CYP19A1 inhibition downregulated PD-L1, IL-6 and TGF-ß levels through GPR30-AKT signaling, thereby enhancing CD8+ T cell-mediated antitumor immune response in vitro co-culture studies. CYP19A1 inhibition by letrozole or siRNA strengthened the anti-tumor immune response of CD8+ T cells, induced normalization of tumor blood vessels, and enhanced the efficacy of anti-PD-1 therapy in orthotopic and subcutaneous mouse colon cancer models. CONCLUSION: A risk model based on lipid metabolism-related genes may predict prognosis and immunotherapeutic response in colon cancer. CYP19A1-catalyzed estrogen biosynthesis promotes vascular abnormality and inhibits CD8+ T cell function through the upregulation of PD-L1, IL-6 and TGF-ß via GPR30-AKT signaling. CYP19A1 inhibition combined with PD-1 blockade represents a promising therapeutic strategy for colon cancer immunotherapy.

Trust in and Use of COVID-19 Information Sources Differs by Health Literacy among College Students.

People's health information-seeking behaviors differ by their health literacy levels. This study assessed the relationship between health literacy and college students' levels of trust in and use of a range of health information sources of COVID-19. We collected data from August to December 2020 among college students (n = 763) through an online survey. We used a health literacy measure containing three self-reported survey questions, developed by the CDC. We assessed the extent to which participants trusted and used any of the sixteen different sources of information about COVID-19. Respondents reported high levels of trusting and using COVID-19 information from the CDC, health care providers, the WHO, state/county/city health departments, and official government websites when compared to other sources. After controlling for demographic characteristics (i.e., gender, age, race, ethnicity, and income), those who reported having lower health literacy were significantly less likely to trust and use COVID-19 information from these health authorities when compared to participants who reported having higher health literacy. Students with lower self-reported health literacy indicated not trusting or using official health authority sources for COVID-19 information. Relying on low-quality information sources could create and reinforce people's misperceptions regarding the virus, leading to low compliance with COVID-19-related public health measures and poor health outcomes.