CircNUP54 promotes hepatocellular carcinoma progression via facilitating HuR cytoplasmic export and stabilizing BIRC3 mRNA.

Circular RNAs (circRNAs) have been implicated in tumorigenesis and progression of various cancers. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) have not been fully elucidated. Herein, a new oncogenic circRNA, hsa_circ_0070039 (circNUP54), was identified to be significantly upregulated in HCC through circRNA sequencing. As verified in 68 HCC samples, circNUP54 overexpression was correlated with aggressive cancerous behaviors and poor outcomes. Moreover, the function experiments showed that knockdown of circNUP54 inhibited the malignant progression of HCC in vitro and in vivo, whereas overexpression of circNUP54 had the opposite role. Mechanistic investigations carried out by RNA pull-down, RNA immunoprecipitation, and immunofluorescence revealed that circNUP54 interacted with the RNA-binding protein Hu-antigen R (HuR) and promoted its cytoplasmic export. The cytoplasmic accumulation of HuR stabilized the downstream BIRC3 mRNA through its binding to the 3' UTR region. Consequently, the encoded protein of BIRC3, cellular inhibitor of apoptosis 2 (cIAP2), proceeded to activate the NF-κB signal pathway and ultimately contributed to HCC progression. In addition, depletion of BIRC3 rescued the pro-tumorigenic effect of circNUP54 on HCC cells. Overall, this study demonstrated that circNUP54 facilitates HCC progression via regulating the HuR/BIRC3/NF-κB axis, which may serve as a promising therapeutic target for HCC treatment.

A novel risk score system based on immune subtypes for identifying optimal mRNA vaccination population in hepatocellular carcinoma.

PURPOSE: Although mRNA vaccines have shown certain clinical benefits in multiple malignancies, their therapeutic efficacies against hepatocellular carcinoma (HCC) remains uncertain. This study focused on establishing a novel risk score system based on immune subtypes so as to identify optimal HCC mRNA vaccination population. METHODS: GEPIA, cBioPortal and TIMER databases were utilized to identify candidate genes for mRNA vaccination in HCC. Subsequently, immune subtypes were constructed based on the candidate genes. According to the differential expressed genes among various immune subtypes, a risk score system was established using machine learning algorithm. Besides, multi-color immunofluorescence of tumor tissues from 72 HCC patients were applied to validate the feasibility and efficiency of the risk score system. RESULTS: Twelve overexpressed and mutated genes associated with poor survival and APCs infiltration were identified as potential candidate targets for mRNA vaccination. Three immune subtypes (e.g. IS1, IS2 and IS3) with distinct clinicopathological and molecular profiles were constructed according to the 12 candidate genes. Based on the immune subtype, a risk score system was developed, and according to the risk score from low to high, HCC patients were classified into four subgroups on average (e.g. RS1, RS2, RS3 and RS4). RS4 mainly overlapped with IS3, RS1 with IS2, and RS2+RS3 with IS1. ROC analysis also suggested the significant capacity of the risk score to distinguish between the three immune subtypes. Higher risk score exhibited robustly predictive ability for worse survival, which was further independently proved by multi-color immunofluorescence of HCC samples. Notably, RS4 tumors exhibited an increased immunosuppressive phenotype, higher expression of the twelve potential candidate targets and increased genome altered fraction, and therefore might benefit more from vaccination. CONCLUSIONS: This novel risk score system based on immune subtypes enabled the identification of RS4 tumor that, due to its highly immunosuppressive microenvironment, may benefit from HCC mRNA vaccination.

Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma.

BACKGROUND: Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. METHODS: Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells. RESULTS: FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan-Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role. CONCLUSION: Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment.

Gaze Point Tracking Based on a Robotic Body-Head-Eye Coordination Method.

When the magnitude of a gaze is too large, human beings change the orientation of their head or body to assist their eyes in tracking targets because saccade alone is insufficient to keep a target at the center region of the retina. To make a robot gaze at targets rapidly and stably (as a human does), it is necessary to design a body-head-eye coordinated motion control strategy. A robot system equipped with eyes and a head is designed in this paper. Gaze point tracking problems are divided into two sub-problems: in situ gaze point tracking and approaching gaze point tracking. In the in situ gaze tracking state, the desired positions of the eye, head and body are calculated on the basis of minimizing resource consumption and maximizing stability. In the approaching gaze point tracking state, the robot is expected to approach the object at a zero angle. In the process of tracking, the three-dimensional (3D) coordinates of the object are obtained by the bionic eye and then converted to the head coordinate system and the mobile robot coordinate system. The desired positions of the head, eyes and body are obtained according to the object's 3D coordinates. Then, using sophisticated motor control methods, the head, eyes and body are controlled to the desired position. This method avoids the complex process of adjusting control parameters and does not require the design of complex control algorithms. Based on this strategy, in situ gaze point tracking and approaching gaze point tracking experiments are performed by the robot. The experimental results show that body-head-eye coordination gaze point tracking based on the 3D coordinates of an object is feasible. This paper provides a new method that differs from the traditional two-dimensional image-based method for robotic body-head-eye gaze point tracking.

Effect of non-permeable cryoprotectant sucrose on the development of spotted knifejaw (Oplegnathus punctatus) embryos.

In this study, the toxicity of sucrose to Oplegnathus punctatus embryos was evaluated. Embryos at the 4-6 somite, tail-bud, heart formation, and heart-beating stages were exposed to 0, 0.5, 1,1.5, 2, 2.5, or 3 M sucrose for 1 h. Survival rates of embryos at the tail-bud, heart formation, and heart-beating stages after rehydration for 1 h were not affected by treatment with 2 M sucrose (the maximum concentration). Embryos at the tail-bud, heart formation, and heart-beating stages were exposed to 2 M sucrose for 0, 30, 60, 90, 120, 150, or 180 min. Long-term developmental indicators, including rates of survival, hatching, swimming, and malformation, were evaluated for 4 days after rehydration. Based on the survival rates 10 min after rehydration, the longest tolerance time for embryos at the three stages was 120 min. Based on long-term developmental indicators, the longest tolerance times were 60 min at the tail-bud, 60 min at the heart formation stage and 30 min at the heart beating stage. The malformation rates increased as the treatment time increased. The malformation rates were 100% when embryos were exposed to sucrose for ≥120 min. Malformation was divided into larval and embryonic abnormality. As the exposure time increased for tail-bud stage embryos, the rate of larval malformation increased. Treatment at heart formation and heart-beating stages resulted in higher rates of failure to hatch at exposure time. Based on these results, toxicity tests of non-permeable cryoprotectant in embryos requires the observation of development for at least 2 days after rehydration. Based on long-term observation, it was concluded that dehydration before freezing was not the direct cause of larvae deformity that hatched from frozen-thawing embryo. These results provide a reference for the singly use of representative non-permeable cryoprotectant sucrose.

Cross-Attention Based Multi-Resolution Feature Fusion Model for Self-Supervised Cervical OCT Image Classification.

Cervical cancer seriously endangers the health of the female reproductive system and even risks women's life in severe cases. Optical coherence tomography (OCT) is a non-invasive, real-time, high-resolution imaging technology for cervical tissues. However, since the interpretation of cervical OCT images is a knowledge-intensive, time-consuming task, it is tough to acquire a large number of high-quality labeled images quickly, which is a big challenge for supervised learning. In this study, we introduce the vision Transformer (ViT) architecture, which has recently achieved impressive results in natural image analysis, into the classification task of cervical OCT images. Our work aims to develop a computer-aided diagnosis (CADx) approach based on a self-supervised ViT-based model to classify cervical OCT images effectively. We leverage masked autoencoders (MAE) to perform self-supervised pre-training on cervical OCT images, so the proposed classification model has a better transfer learning ability. In the fine-tuning process, the ViT-based classification model extracts multi-scale features from OCT images of different resolutions and fuses them with the cross-attention module. The ten-fold cross-validation results on an OCT image dataset from a multi-center clinical study of 733 patients in China indicate that our model achieved an AUC value of 0.9963 ± 0.0069 with a 95.89 ± 3.30% sensitivity and 98.23 ± 1.36 % specificity, outperforming some state-of-the-art classification models based on Transformers and convolutional neural networks (CNNs) in the binary classification task of detecting high-risk cervical diseases, including high-grade squamous intraepithelial lesion (HSIL) and cervical cancer. Furthermore, our model with the cross-shaped voting strategy achieved a sensitivity of 92.06% and specificity of 95.56% on an external validation dataset containing 288 three-dimensional (3D) OCT volumes from 118 Chinese patients in a different new hospital. This result met or exceeded the average of four medical experts who have used OCT for over one year. In addition to promising classification performance, our model has a remarkable ability to detect and visualize local lesions using the attention map of the standard ViT model, providing good interpretability for gynecologists to locate and diagnose possible cervical diseases.

Trends in prevalence and all-cause mortality of metabolic dysfunction-associated fatty liver disease among adults in the past three decades: Results from the NHANES study.

BACKGROUND: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades. METHODS: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype). RESULTS: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality. CONCLUSIONS: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality.

Identification of a Novel Ferroptosis-Related Gene Signature for Predicting Prognosis and Responsiveness to Immunotherapy in Hepatocellular Carcinoma.

Purpose: Ferroptosis has been reported to regulate multiple biological behaviors. However, the prognostic and oncologic values of ferroptosis-related genes (FRGs) have not been comprehensively elucidated in hepatocellular carcinoma (HCC). Here, we aimed to construct FRGs-associated signature for stratification of the prognosis of HCC patients. Methods: A list of FRGs was generated from FerrDb. Public databases were used to extract expression matrices and clinical information. TCGA cohort was randomly divided into a training set and a validation set. Prognostic signature for Overall Survival (OS) was established in training set and validated in internal cohorts (TCGA validation set and entire set) and external cohort (ICGC cohort). Additionally, the role of signature in HCC was well investigated by analysis of mutations, gene set enrichment analysis (GSEA), analysis of immune infiltrates, and analysis of response to immune checkpoint blockade (ICB) treatment. The oncogenic effects of ZFP69B on HCC were also investigated in vitro. Results: We identified 12 FRGs-based signature for OS with LASSO regression. Patients were partitioned into different risk groups based on the signature. Overall, patients in different groups had different prognosis. The signature independently predicted OS in multivariate Cox regression analyses. Anti-tumor immune cells including activated CD8 T cells, cytolytic activity, and Th1 cells were negatively correlated with risk score in both TCGC and ICGC cohorts. Furthermore, low-risk patients responded better to ICB than high-risk patients. In addition, knockdown of ZFP69B reduced proliferation, migration, and invasion, and promoted erastin-induced ferroptosis of HCC cells. Conclusion: We developed a prognostic signature based on FRGs to predict OS of HCC patients. And the signature may facilitate clinicians in identifying those who are likely to benefit from ICIs. The results also indicated that ZFP69B might regulate the process of ferroptosis and could be used as a novel potential target for HCC.

Glutathione and neodiosmin feedback sustain plant immunity.

Plants have evolved a two-layer immune system comprising pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) that is activated in response to pathogen invasion. Microbial patterns and pathogen effectors can be recognized by surface-localized pattern-recognition receptors (PRRs) and intracellularly localized nucleotide-binding leucine-rich repeat receptors (NLRs) to trigger PTI and ETI responses, respectively. At present, the metabolites activated by PTI and ETI and their roles and signalling pathways in plant immunity are not well understood. In this study, metabolomic analysis showed that ETI and PTI induced various flavonoids and amino acids and their derivatives in plants. Interestingly, both glutathione and neodiosmin content were specifically up-regulated by ETI and PTI, respectively, which significantly enhanced plant immunity. Further studies showed that glutathione and neodiosmin failed to induce a plant immune response in which PRRs/co-receptors were mutated. In addition, glutathione-reduced mutant gsh1 analysis showed that GSH1 is also required for PTI and ETI. Finally, we propose a model in which glutathione and neodiosmin are considered signature metabolites induced in the process of ETI and PTI activation in plants and further continuous enhancement of plant immunity in which PRRs/co-receptors are needed. This model is beneficial for an in-depth understanding of the closed-loop mode of the positive feedback regulation of PTI and ETI signals at the metabolic level.

Discovery of a novel nucleoside immune signaling molecule 2'-deoxyguanosine in microbes and plants.

INTRODUCTION: Beneficial microorganisms play essential roles in plant growth and induced systemic resistance (ISR) by releasing signaling molecules. Our previous study obtained the crude extract from beneficial endophyte Paecilomyces variotii, termed ZNC (ZhiNengCong), which significantly enhanced plant resistance to pathogen even at 100 ng/ml. However, the immunoreactive components of ZNC remain unclear. Here, we further identified one of the immunoreactive components of ZNC is a nucleoside 2'-deoxyguanosine (2-dG). OBJECTIVES: This paper intends to reveal the molecular mechanism of microbial-derived 2'-deoxyguanosine (2-dG) in activating plant immunity, and the role of plant-derived 2-dG in plant immunity. METHODS: The components of ZNC were separated using a high-performance liquid chromatography (HPLC), and 2-dG is identified using a HPLC-mass spectrometry system (LC-MS). Transcriptome analysis and genetic experiments were used to reveal the immune signaling pathway dependent on 2-dG activation of plant immunity. RESULTS: This study identified 2'-deoxyguanosine (2-dG) as one of the immunoreactive components from ZNC. And 2-dG significantly enhanced plant pathogen resistance even at 10 ng/ml (37.42 nM). Furthermore, 2-dG-induced resistance depends on NPR1, pattern-recognition receptors/coreceptors, ATP receptor P2K1 (DORN1), ethylene signaling but not salicylic acid accumulation. In addition, we identified Arabidopsis VENOSA4 (VEN4) was involved in 2-dG biosynthesis and could convert dGTP to 2-dG, and vne4 mutant plants were more susceptible to pathogens. CONCLUSION: In summary, microbial-derived 2-dG may act as a novel immune signaling molecule involved in plant-microorganism interactions, and VEN4 is 2-dG biosynthesis gene and plays a key role in plant immunity.

Convivial cooking: Impacts of an educational intervention on college students' food agency.

Objective: This research examines the effects of educational materials, delivered with "take-home and cook-with-friends" meal kits, on college students' food agency. Participants: In the spring of 2021, 186 students were recruited at a US public university and randomly allocated into either an intervention group that received meal kits and educational materials or a control group that received only meal kits. Methods: Meal kits containing local ingredients were distributed weekly to the participants and surveys were conducted to measure participants' food agency, using the Cooking and Food Provisioning Action Scale (CAFPAS). Hypothesis tests and regression analysis were then conducted to examine the educational intervention's effects on the CAFPAS scores. Results: The educational intervention had a positive and statistically significant effect on students' CAFPAS scores. Conclusions: Educational interventions hold promise in enhancing college students' food agency, at least in the short term.

A chromosome-level genome assembly of the potato grouper (Epinephelus tukula).

The potato grouper, Epinephelus tukula, is one of the largest coral reef teleost, and it is an important germplasm resource for selection and cross breeding. Here we report a potato grouper genome assembly generated using PacBio long-read sequencing, Illumina sequencing and high-throughput chromatin conformation capture (Hi-C) technology. The genome size was 1.13 Gb, with a total of 508 contigs anchored into 24 chromosomes. The scaffold N50 was 42.65 Mb. For the genome models, our assembled genome contained 98.11% complete BUSCO with the vertebrata_odb9 database. One more copies of Gh and Hsp90b1 were identified in the E. tukula genome, which might contribute to its fast growth and high resistance to stress. In addition, 435 putative antimicrobial peptide (AMP) genes were identified in the potato grouper. This study provides a good reference for whole genome selective breeding of the potato grouper and for future development of novel marine drugs.

Endophytic extract Zhinengcong alleviates heat stress-induced reproductive defect in Solanum lycopersicum.

High temperature negatively affects reproductive process significantly, leading to tremendous losses in crop quality and yield. Zhinengcong (ZNC), a crude extract from the endophytic fungus Paecilomyces variotii, has been shown to improve plant growth and resistance to biotic and abiotic stresses. We show here that ZNC can also alleviate heat stress-induced reproductive defects in Solanum lycopersicum, such as short-term heat-induced inhibition on pollen viability, germination and tube growth, and long-term heat stress-induced pollen developmental defects. We further demonstrated that ZNC alleviates heat stress by downregulating the expressions of ROS production-related genes, RBOHs, and upregulating antioxidant related genes and the activities of the corresponding enzymes, thus preventing the over accumulation of heat-induced reactive oxygen species (ROS) in anther, pollen grain and pollen tube. Furthermore, spraying application of ZNC onto tomato plants under long-term heat stress promotes fruit and seed bearing in the field. In summary, plant endophytic fungus extract ZNC promotes the reproductive process and yield of tomato plants under heat stress and presents excellent potential in agricultural applications.

Identification of LSM Family Members as Novel Unfavorable Biomarkers in Hepatocellular Carcinoma.

Background: Smith-like (LSM) family members play critical roles in multiple oncologic processes in several types of malignancies. The study on LSM family members of HCC might provide new insights into the tumorigenesis and therapeutic strategies of HCC. Methods: The clinical significance and oncologic biological functions of LSM family members were assessed through multiple bioinformatics methods and in vitro studies. The potential correlation between LSM family members and tumor immunity was also investigated using single sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. Results: LSM family member overexpression in HCC was significantly correlated with poor clinical outcomes such as higher TNM stage, advanced histologic grade, and worse prognosis. A risk score system based on LSM5, LSM10, LSM12, and LSM14B showed a reliable predictive ability for OS of HCC patients. Functional enrichment analysis demonstrated that LSM family members overexpressed were all involved in cell cycle related biological processes. Besides, LSM12, LSM14A, and LSM14B were found to be significantly associated with PI3K-Akt-mTOR and T cell receptor signaling pathways. Tumors with LSM12, LSM14A, and LSM14B overexpression exhibited lower infiltration of activated CD8+ T cells with declined cytolytic activity and immune score, but increased infiltration of Th2 cells and Th2/Th1. LSM12, LSM14A, and LSM14B overexpression is also associated with higher tumor-related immune checkpoints (e.g., PD-L1, B7-H3, and PVR) expression and increased therapeutic insensitivity to immune checkpoint blockade (ICB). Moreover, the knockdown of LSM12, LSM14A, and LSM14B significantly inhibited the proliferation and invasion of HCC cells. Conclusion: This study systematically investigated the expression pattern and biological values of LSM family members in HCC and identified LSM family members as novel therapeutic targets in HCC.

CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3ß/ß-catenin signaling pathway.

Circular RNAs have been reported to play essential roles in the tumorigenesis and progression of various cancers. However, the biological processes and mechanisms involved in hepatocellular carcinoma (HCC) remain unclear. Initial RNA-sequencing data and qRT-PCR results in our cohort showed that hsa_circ_0072309 (also called circLIFR) was markedly downregulated in HCC tissues. Kaplan-Meier analysis indicated that higher levels of circLIFR in HCC patients correlated with favorable overall survival and recurrence-free survival rates. Both in vitro and in vivo experiments indicated that circLIFR inhibited the proliferation and invasion abilities of HCC cells. We therefore conducted related experiments to explore the mechanism of circLIFR in HCC. Fluorescence in situ hybridization results revealed that circLIFR was mainly located in the cytoplasm, and RNA immunoprecipitation assays indicated that circLIFR was significantly enriched by Ago2 protein. These results suggested that circLIFR may function as a sponge of miRNAs to regulate HCC progression. We further conducted bioinformatics prediction as well as dual-luciferase reporter assays, and the results of which showed that circLIFR could sponge miR-624-5p to stabilize glycogen synthase kinase 3ß (GSK-3ß) expression. Loss and gain of function experiments demonstrated that regulation of the expression of miR-624-5p or GSK-3ß markedly affected HCC progression induced by circLIFR. Importantly, we also proved that circLIFR could facilitate the degradation of ß-catenin and prevent its translocation to the nucleus in HCC cells. Overall, our study demonstrated that circLIFR acts as a tumor suppressor in HCC by regulating miR-624-5p and inactivating the GSK-3ß/ß-catenin signaling pathway.

NeuRec: Incorporating Interpatient prior to Sparse-View Image Reconstruction for Neurorehabilitation.

Medical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) imaging are indispensable for contemporary neurorehabilitation diagnostics, intervention, and monitoring. It would be desirable to reconstruct images from sparse measurements to reduce the ionizing radiation and motion artifacts. Although recent coordinate-based representation methods have shown promise advances for sparse-view reconstruction, they overfit a single MLP on a single patient. In this work, we generalize it across many patients by incorporating an interpatient prior into the ill-posed inverse/reconstruction problem, which is the missing ingredient in the previous works. The experiment demonstrates that our method significantly improves image quality over the state-of-the-art both qualitatively and quantitatively. Thus, our method provides a powerful and principled means to deal with the measurement-scarce problem.

Out of the shadows: Impact of SARS experience on Chinese netizens' willingness to donate for COVID-19 pandemic prevention and control.

While charitable donations help to raise funds and contribute to pandemic prevention and control, there are many unanswered questions about how people make such donation decisions, especially in countries like China where charitable donations have played an increasing role in recent years. This study contributes to the literature by assessing the potential impacts of Chinese netizens' experience with the 2002 severe acute respiratory syndrome (SARS) epidemic on their willingness to donate for COVID-19 pandemic prevention and control. Specifically, this study applies a difference-in-differences (DID) model to a dataset collected from a nationwide survey to examine how individuals' exposure to the SARS epidemic affects their willingness to donate to alleviate the COVID-19 pandemic. The results suggest that individuals' SARS epidemic experiences in their early lives, especially during the "childhood-adolescence" period, had a lasting and far-reaching impact on their willingness to donate toward COVID-19 pandemic prevention and control. Also, the impacts were likely heterogeneous by such sociodemographic factors as educational background, health status, and income level. The empirical findings highlight the importance of considering early-life experiences in developing and implementing epidemic prevention and control policies. While the SARS experience likely affected Chinese netizens' willingness to donate toward COVID-19 pandemic prevention and control, lessons learned from both the SARS epidemic and COVID-19 pandemic could be used to develop more effective public health education and prevention programs as well as to increase public donations for future pandemic prevention and control.

A Novel Guanine Elicitor Stimulates Immunity in Arabidopsis and Rice by Ethylene and Jasmonic Acid Signaling Pathways.

Rice sheath blight (ShB) caused by Rhizoctonia solani is one of the most destructive diseases in rice. Fungicides are widely used to control ShB in agriculture. However, decades of excessive traditional fungicide use have led to environmental pollution and increased pathogen resistance. Generally, plant elicitors are regarded as environmentally friendly biological pesticides that enhance plant disease resistance by triggering plant immunity. Previously, we identified that the plant immune inducer ZhiNengCong (ZNC), a crude extract of the endophyte, has high activity and a strong ability to protect plants against pathogens. Here, we further found that guanine, which had a significant effect on inducing plant resistance to pathogens, might be an active component of ZNC. In our study, guanine activated bursts of reactive oxygen species, callose deposition and mitogen-activated protein kinase phosphorylation. Moreover, guanine-induced plant resistance to pathogens depends on ethylene and jasmonic acid but is independent of the salicylic acid signaling pathway. Most importantly, guanine functions as a new plant elicitor with broad-spectrum resistance to activate plant immunity, providing an efficient and environmentally friendly biological elicitor for bacterial and fungal disease biocontrol.

Cervical optical coherence tomography image classification based on contrastive self-supervised texture learning.

BACKGROUND: Cervical cancer (CC) seriously affects the health of the female reproductive system. Optical coherence tomography (OCT) emerged as a noninvasive, high-resolution imaging technology for cervical disease detection. However, OCT image annotation is knowledge-intensive and time-consuming, which impedes the training process of deep-learning-based classification models. PURPOSE: This study aims to develop a computer-aided diagnosis (CADx) approach to classifying in-vivo cervical OCT images based on self-supervised learning. METHODS: In addition to high-level semantic features extracted by a convolutional neural network (CNN), the proposed CADx approach designs a contrastive texture learning strategy to leverage unlabeled cervical OCT images' texture features. We conducted 10-fold cross-validation on the OCT image dataset from a multicenter clinical study on 733 patients from China. RESULTS: In a binary classification task for detecting high-risk diseases, including high-grade squamous intraepithelial lesion and CC, our method achieved an area-under-the-curve value of 0.9798 ± 0.0157 with a sensitivity of 91.17% ± 4.99% and a specificity of 93.96% ± 4.72% for OCT image patches; also, it outperformed two out of four medical experts on the test set. Furthermore, our method achieved 91.53% sensitivity and 97.37% specificity on an external validation dataset containing 287 three-dimensional OCT volumes from 118 Chinese patients in a new hospital using a cross-shaped threshold voting strategy. CONCLUSIONS: The proposed contrastive-learning-based CADx method outperformed the end-to-end CNN models and provided better interpretability based on texture features, which holds great potential to be used in the clinical protocol of "see-and-treat."

SLC39A1 Overexpression is Associated with Immune Infiltration in Hepatocellular Carcinoma and Promotes Its Malignant Progression.

BACKGROUND: Solute carrier family 39 member 1 (SLC39A1) has been identified as a zinc ion transport protein that possesses oncogenic properties in various types of cancers. However, its potential function in hepatocellular carcinoma (HCC) remains unknown. This study aimed to investigate the expression profile and potential mechanisms of SLC39A1 in HCC. METHODS: SLC39A1 expression was analyzed using multiple databases. The clinical significance and associated biological pathways of SLC39A1 were investigated using bioinformatics analysis. Potential correlations between SLC39A1 expression and tumor immunity in HCC were also evaluated using single-sample gene set enrichment analysis (GSEA). Sixty paired HCC samples were used to verify the expression pattern of SLC39A1. In vitro studies were performed to investigate the oncogenic effects of SLC39A1 in HCC. Western blot analysis was conducted to further investigate the possible involved signaling pathways. RESULTS: The overexpression of SLC39A1 in HCC was determined by bioinformatics analysis and was confirmed in tissues from our center. SLC39A1 overexpression was also significantly correlated with worse prognosis, advanced TNM stage, and histological grade. GSEA analysis demonstrated that SLC39A1 overexpression was involved in various tumor-related pathways, such as the cell cycle and Wnt signaling pathway. SLC39A1 knockdown repressed the proliferation, invasion, and migration abilities of HCC cells. Furthermore, SLC39A1 knockdown decreased the expression of the tumor progression-related proteins (eg, cyclin D1 and MMP2) and Wnt signaling pathway-related proteins (eg, Wnt3A and ß-catenin). In addition, SLC39A1 overexpression may be associated with impaired tumor immunity in HCC, as evidenced by the increased infiltration of Th2 cells and reduced infiltration of cytotoxic cells. CONCLUSION: These findings preliminarily suggested the crucial effect of SLC39A1 overexpression on HCC tumor progression and immunosuppression, suggesting its potential as a novel prognostic and therapeutic target in HCC.