Effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine: a cross-sectional study in Shanghai, China.

BACKGROUND: The association of anxiety and depression with adverse reactions after receipt of coronavirus disease 2019 (COVID-19) vaccine is not clear among the general population. This study aims to evaluate the effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine. METHODS: The cross-sectional study was conducted during April-July 2021. Participants completing the two doses of vaccine were included in this study. Sociodemographic information, anxiety and depression levels and adverse reactions after the first dose of vaccine for all participants were collected. The anxiety and depression levels were assessed by the Seven-item Generalized Anxiety Disorder Scale and the Nine-item Patient Health Questionnaire Scale, respectively. The multivariate logistic regression analysis was used to examine the association between anxiety and depression and adverse reactions. RESULTS: A total of 2161 participants were enrolled in this study. The prevalence of anxiety and depression was 13% (95% confidence interval (CI), 11.3-14.2%) and 15% (95%CI, 13.6-16.7%), respectively. Of the 2161 participants, 1607 (74%; 95% CI, 73-76%) reported at least one adverse reaction after the first dose of the vaccine. Pain at the injection site (55%) and fatigue and headache (53% and 18%, respectively) were the most commonly reported local and systemic adverse reactions, respectively. Participants with anxiety or depression or both were more likely to report local and systemic adverse reactions (P < 0.05). CONCLUSION: The results suggest that anxiety and depression increase the risk of self-reported adverse reactions to COVID-19 vaccine. Consequently, appropriate psychological interventions before vaccination will help to reduce or alleviate symptoms of vaccination.

Single-cell RNA sequencing of mouse left ventricle reveals cellular diversity and intercommunication.

Previous studies have revealed the diversity of the whole cardiac cellulome but not refined the left ventricle, which was essential for finding therapeutic targets. Here, we characterized single-cell transcriptional profiles of the mouse left ventricular cellular landscape using single-cell RNA sequencing (10× Genomics). Detailed t-distributed stochastic neighbor embedding (tSNE) analysis revealed the cell types of left ventricle with gene markers. Left ventricular cellulome contained cardiomyocytes highly expressed Trdn, endothelial cells highly expressed Pcdh17, fibroblast highly expressed Lama2, and macrophages highly expressed Hpgds, also proved by in situ hybridization. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis (ListHits > 2, P < 0.05) were employed with the DAVID database to investigate subtypes of each cell type with the underlying functions of differentially expressed genes (DEGs). Endothelial cells included 5 subtypes, fibroblasts comprising 7 subtypes, and macrophages contained 11 subtypes. The key representative DEGs (P < 0.001) were Gja4 and Gja5 in cluster 3 of endothelial cells, Aqp2 and Thbs4 in cluster 2 of fibroblasts, and Clec4e and Trem-1 in cluster 3 of macrophages perhaps involved in the occurrence of atherosclerosis, heart failure, and acute myocardial infarction proved by literature review. We also revealed extensive networks of intercellular communication in left ventricle. We suggested possible therapeutic targets for cardiovascular disease and autocrine and paracrine signaling underpins left ventricular homeostasis. This study provided new insights into the structure and function of the mammalian left ventricular cellulome and offers an important resource that will stimulate studies in cardiovascular research.

miR-3677-3p promotes hepatocellular carcinoma progression via inhibiting GSK3ß.

MicroRNAs play important roles in regulating hepatocellular carcinoma (HCC) formation, progression and metastasis. However, their functions and the underlying molecular mechanisms are still unclear. Here, we found that miR-3677-3p was highly expressed in primary tumor tissues of HCC patients. And its inhibition by using sponge in HCC cells could suppress cell proliferation significantly, but it has no effect on cell apoptosis. Through directly targeting to the 3' untranslated region of glycogen synthase kinase 3-ß (GSK3ß), miR-3677-3p could inhibit GSK3ß expression. Our study revealed that the miR-3677-3p/GSK3ß axis may play a crucial role in HCC and miR-3677-3p may serve as a potential diagnostic biomarker or a therapeutic target for HCC.

Abemaciclib induces apoptosis in cardiomyocytes by activating the Hippo signaling pathway.

Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor that has received approval from the US Food and Drug Administration for using in patients with advanced breast cancer. However, its potential adverse effects on cardiomyocytes remain unknown. In this study, we used the cell counting kit-8 assay, western blot analysis, flow cytometry, immunostaining, and quantitative polymerase chain reaction to investigate the role of abemaciclib in inducing apoptosis and in inhibiting the viability and proliferation of AC16 human cardiomyocyte cells. The results revealed that abemaciclib induced apoptosis and inhibited cell proliferation by activating the Hippo signaling pathway. This work demonstrates the molecular basis by which abemaciclib induces cardiac side effects, providing a theoretical basis and effective targets for the treatment of cardiac diseases.

Pwp1 is required for the differentiation potential of mouse embryonic stem cells through regulating Stat3 signaling.

Leukemia inhibitory factor/Stat3 signaling is critical for maintaining the self-renewal and differentiation potential of mouse embryonic stem cells (mESCs). However, the upstream effectors of this pathway have not been clearly defined. Here, we show that periodic tryptophan protein 1 (Pwp1), a WD-40 repeat-containing protein associated with histone H4 modification, is required for the exit of mESCs from the pluripotent state into all lineages. Knockdown (KD) of Pwp1 does not affect mESC proliferation, self-renewal, or apoptosis. However, KD of Pwp1 impairs the differentiation potential of mESCs both in vitro and in vivo. PWP1 chromatin immunoprecipitation-seq results revealed that the PWP1-occupied regions were marked with significant levels of H4K20me3. Moreover, Pwp1 binds to sites in the upstream region of Stat3. KD of Pwp1 decreases the level of H4K20me3 in the upstream region of Stat3 gene and upregulates the expression of Stat3. Furthermore, Pwp1 KD mESCs recover their differentiation potential through suppressing the expression of Stat3 or inhibiting the tyrosine phosphorylation of STAT3. Together, our results suggest that Pwp1 plays important roles in the differentiation potential of mESCs.

[Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

Prediction on Air-Nasal Mucus Partition Coefficients of Odor Compounds.

The air-nasal mucus partition coefficient is a crucial property among all of the interaction mechanisms between odor molecules and olfactory receptors, since this property contributes to our sense of smell. Due to the complexity of the mucus composition, in vivo determination of the air-mucus partition coefficient is a technical challenge. A predictable model of the air-mucus partition coefficient can provide valuable insights into the chemical properties that govern olfactory perception and can help design desired odorants. In this study, we propose a novel model based on the deep-layer neural network (DNN) algorithm to predict the air-mucus partition coefficients for a range of odor compounds. The molecular surface charge density (σ-profile) calculated from the COnductor like Screening MOdel for Real Solvents (COSMO-RS) thermodynamic package was adapted as descriptors of structural features of odor molecules. The results revealed that the air-mucus partition coefficients are highly correlated to the σ-profile of the studied compounds. The information obtained from the study provided interpretable results, which not only help in identifying the molecular features that contribute to the air-mucus partition coefficient of odorants but also aid in the design of compounds with the desired odor properties.

Regression Study of Odorant Chemical Space, Molecular Structural Diversity, and Natural Language Description.

Odor is analyzed on the human olfactometry systems in various steps. The mapping from chemical structures to olfactory perceptions of smell is an extremely challenging task. Scientists have been unable to find a measure to distinguish the perceptual similarity between odorants. In this study, we report regression analysis and visualization based on the odorant chemical space. We discuss the relation between the odor descriptors and their structural diversity for odorants groups associated with each odor descriptor. We studied the influence of structural diversity on the odor descriptor predictability. The results suggest that the diversity of molecular structures, which is associated with the same odor descriptor, is related to the resolutional confusion with the odor descriptor.

Understanding the differential impact of PFOS and F-53B pollution on reed-mediated soil organic matter decomposition: Insights from rhizosphere priming effect.

Plants affect soil microorganisms through the release of root exudates under pollution stress. This process may affect rhizosphere priming effect (RPE) and alter the rate of soil organic matter decomposition. However, the influence of plants on the decomposition of organic matter in soil subjected to pollution stress remains unclear. We studied the effects of exposure to perfluorooctanesulfonic (PFOS) and its alternative, chlorinated polyfluoroalkyl ether sulfonic (F-53B), at concentrations of 0.1 mg/kg and 50 mg/kg on the RPE of reed. We conducted our experiments in an artificial climate chamber and used the natural 13C tracer method to determine RPE. In the PFOS-exposed groups, the RPE was negative, with values of -11.45 mg C kg-1 soil d-1 in the low PFOS group and -8.04 mg C kg-1 soil d-1 in the high PFOS group. In contrast, in the F-53B-exposed groups, the RPE was positive, with values of 8.26 mg C kg-1 soil d-1 in the low F-53B group and 12.18 mg C kg-1 soil d-1 in the high F-53B group. Exposure of reeds to PFOS/F-53B stress resulted in differential effects on extracellular enzyme activities. The observed positive and negative RPE phenomena could be attributed to variations in extracellular enzyme activities. In conclusion, RPE responded differently under PFOS/F-53B exposure.

Adsorption and uptake of functionalized nanoplastics (NPs) by wetland plant (Sphagnum): A unique pathway for polystyrene-NPs reduction in non-vascular plants.

Wetlands are sources and sinks for nanoplastics (NPs), where adsorption and uptake by plants constitute a crucial pathway for NPs accumulation. This study found that Sphagnum exhibited a high potential (~89.75 %) to intercept NPs despite the lack of root systems and stomata. Two pathways for 100nm polystyrene NPs accumulation in Sphagnum were located: (i) Spiral interception and foliar adsorption. Efficient adsorption is credited to the micro/nano-interlocked leaf structure, which is porous, hydrophilic and rough. (ii) Intracellular enrichment through pores. Fluorescence tracking indicates pseudo-leaves (lateral > cephalic branches) as primary organs for internalization. Accumulation of differently functionalized NPs was characterized: PS-Naked-NPs (PS), PS-COOH-NPs (PC) and PS-NH2-NPs (PN) were all largely retained by pathway (i), while pathway (ii) mainly uptake PN and PC. Unlike PS aggregation in transparent cells, PC enrichment in chloroplast cells and PN in intercellular spaces reduced pigment content and fluorescence intensity. Further, the effects of the accumulated NPs on the ecological functions of Sphagnum were evaluated. NPs reduce carbon flux (assimilation rate by 57.78 %, and respiration rate by 33.50%), significantly decreasing biomass (PS = 13.12 %, PC = 26.48 %, PN = 35.23 %). However, toxicity threshold was around 10 µg/mL, environmental levels (≤1 µg/mL) barely affected Sphagnum. This study advances understanding of the behavior and fate of NPs in non-vascular plants, and provides new perspectives for developing Sphagnum substrates for NPs interception.

Molybdenum disulphide nanoparticles accelerate the transformation of levofloxacin in planting soil upon exposure.

The use of nanocatalytic particles for the removal of refractory organics from wastewater is a rapidly growing area of environmental purification. However, little has been done to investigate the effects of nanoparticles on soil-plant systems with antibiotic contamination. This work assessed the effect of molybdenum disulfide (MoS2) on the soil-Phragmites communis system containing levofloxacin (LVX). The results showed that the addition of MoS2 had restoration potential for stressed plant. The MoS2 with catalytic activity promoted the transformation of LVX in rhizosphere soils. The transformation pathways of LVX in the different exposure groups were proposed. The continuous output of radicals in the high MoS2 dosage group facilitated the transformation of LVX to small molecule compounds, which were eventually mineralized. Moreover, the electron-density-difference analysis revealed the easier flow of electrons from the MoS2 surface towards the LVX molecules. This finding provides theoretical support for the application of nanocatalytic particles in ecological environments.

Investigation on the effects of an elliptical wall on the dynamic behaviors of a bubble restricted by two parallel plates.

The present paper investigates the dynamic behaviors of a bubble restricted by two parallel plates near an elliptical wall. The typical experimental phenomena of the bubble are recorded employing the high-speed photography and a theoretical Kelvin impulse model is established. The impacts of the spatial position and the curvature of the wall on the bubble collapse behaviors are quantitatively investigated through the theoretical model and verified against the experimental results. The Kelvin impulse intensity and the direction during the bubble collapse process are compared and discussed for different elliptical-shaped walls. The main conclusions include: (1) During the bubble collapse process, the phenomenon of the bubble uneven splitting is discovered. (2) At different spatial positions and wall curvatures, the bubble collapse jet angle, movement distance, and velocity are in good agreement with the theoretical Kelvin impulse predictions. (3) As the short-to-long axis ratio increases, the differences in the distributions of the Kelvin impulse intensity and the direction near the elliptical wall gradually become larger, and the range of the influence of the impulse intensity expands.

Single-Cell Atlas of Neonatal Mouse Hearts Reveals an Unexpected Cardiomyocyte.

BACKGROUND: Single-cell RNA sequencing is widely used in cancer research and organ development because of its powerful ability to analyze cellular heterogeneity. However, its application in cardiomyocytes is dissatisfactory mainly because the cardiomyocytes are too large and fragile to withstand traditional single-cell approaches. METHODS AND RESULTS: Through designing the isolation procedure of neonatal mouse cardiac cells, we provide detailed cellular atlases of the heart at single-cell resolution across 4 different stages after birth. We have obtained 10 000 cardiomyocytes; to our knowledge, this is the most extensive reference framework to date. Moreover, we have discovered unexpected erythrocyte-like cardiomyocyte-terminal cardiomyocytes, comprising more than a third of all cardiomyocytes. Only a few genes are highly expressed in these cardiomyocytes. They are highly differentiated cardiomyocytes that function as contraction pumps. In addition, we have identified 2 cardiomyocyte-like conducting cells, lending support to the theory that the sinoatrial node pacemaker cells are specialized cardiomyocytes. Notably, we provide an initial blueprint for comprehensive interactions between cardiomyocytes and other cardiac cells. CONCLUSIONS: This mouse cardiac cell atlas improves our understanding of cardiomyocyte heterogeneity and provides a valuable reference in response to varying physiological conditions and diseases.

Plant rhizosphere defense system respond differently to emerging polyfluoroalkyl substances F-53B and PFOS stress.

Chlorinated polyfluoroalkyl ether sulfonate (F-53B) and perfluorooctanesulfonate (PFOS) are used and emitted as fog inhibitors in the chromium plating industry, and they are widely detected worldwide. To study the effects of F-53B and PFOS on the rhizosphere defense system, they were added at two levels (0.1 and 50 mg L-1) to the soil where different plants (Lythrum salicaria and Phragmites communis) were grown. In bulk soils, high concentrations of F-53B/PFOS resulted in significant increases in soil pH, NH4+-N, and NO3--N (the effect of PFOS on NO3--N was not significant). Moreover, the extent of the effects of PFOS and F-53B on the physicochemical properties of bulk soils were different (e.g., PFOS caused an increase of NH4+-N by 8.94%-45.97% compared to 1.63%-25.20% for F-53B). Root exudates and PFASs together influenced the physicochemical properties of rhizosphere soils (e.g., TOC increased significantly in contaminated rhizosphere soils but did not change in non-bulk soils). Under the influence of F-53B/PFOS, the root exudates regulated by plants were changed and weakened the effect of F-53B/PFOS on microbial community of rhizosphere soil. The rhizosphere defense systems of different plants have both similarities and differences in response to different substances and concentrations.

Clinical factors affecting the long-term survival of breast cancer patients.

OBJECTIVE: The average 5-year survival rate of breast cancer (BC) patients has been significantly prolonged with new therapeutic methods. However, their effects on BC patient long-term survival rates are unclear. Therefore, this study aimed to analyze the specific clinical factors that can affect BC long-term survival. METHODS: Here, we conducted a retrospective study and analyzed long-term survival using data of 3,240 BC patients from 1977 to 2005 from the Genotype-Tissue Expression (GTEx) database using the Kaplan-Meier method. RESULTS: Breast tumor size and stage were negatively correlated with long-term survival, but age showed no significant correlation. Estrogen receptor (ER) and progesterone receptor (PR) expression were each positively correlated with patient survival time, while ERBB2 receptor (HER2) expression was negatively correlated with survival time. Patients with high Nottingham prognostic index (NPI) values did not benefit from available therapies. Furthermore, breast-conserving surgery is more conducive to BC patient long-term survival than mastectomy. CONCLUSIONS: Early detection and breast-conserving surgery may support long-term survival for BC patients. Elevated expression of ER and PR were both associated with longer patient survival time, while positive expression of HER2 showed the opposite trend. The long-term survival rates of patients with high NPI values can potentially be increased.

Theoretical Study on the Kinetics of the Rubisco Carboxylase Reaction by a Model Based on Quantum Chemistry and Absolute Reaction Rate Theory.

The rate of the Rubisco carboxylase reaction is evaluated by statistical mechanics and hybrid density functional theory (DFT). The Rubisco molecular model given by Kannappan et al. was modified and used in the present calculation. The activation energies of CO2 addition reaction, H2O addition reaction, C2-C3 bond scission, and C2 protonation are estimated. We calculated the turnover number (TON) for each of the four reaction steps based on a revised absolute reaction rate theory, which became applicable to soft matter reactions. The molecular parameters used in TON calculations were obtained by DFT calculations. The TON of the total Rubisco reaction was finally evaluated using rate equations. The calculation in a vacuum gave the total TON to be around 5 × 10-5, which was much lower than the experimental value. The DFT calculation in water solvent gave the total TON to be around 0.1, which agreed reasonably well with experimentally reported values (∼2.71). The rate-limiting process was the scission reaction. The present calculation showed that both the phosphate groups in the substrate accelerate each reaction step. The present calculation showed that a more comprehensive molecular model including enolization and quantum chemical methods is necessary to make a more precise reaction model including the irreversibility of some reactions.

Integrative analysis of DNA methylation and gene expression reveals key molecular signatures in acute myocardial infarction.

BACKGROUNDS: Acute myocardial infarction (AMI) has been one of the most fatal diseases among all types of heart diseases due to its rapid onset and high rates of fatality. Understanding accurately how multi-omics molecular features change at the early stage of AMI is crucial for its treatment. Currently, the changes involved in DNA methylation modification and gene expression of multiple genes have remained unexplored. RESULTS: We used the RNA-seq and MeDIP-seq on heart tissues from AMI mouse models at series of time points (Sham, AMI 10-min, 1-h, 6-h, 24-h and 72-h), to comprehensively describe the transcriptome and genome-wide DNA methylation changes at above time points. We identified 18814, 18614, 23587, 26018 and 33788 differential methylation positions (DMPs) and 123, 135, 731, 1419 and 2779 differentially expressed genes (DEGs) at 10-min, 1-h, 6-h, 24-h and 72-h AMI, respectively, compared with the sham group. Remarkably, the 6-h AMI with the drastic changes of DEGs and a large number of enriched functional pathways in KEGG may be the most critical stage of AMI process. The 4, 9, 40, 26, and 183 genes were further identified at each time point, based on the negative correlation (P < 0.05) between the differential mRNA expression and the differential DNA methylation. The mRNA and the promoter methylation expressions of five genes (Ptpn6, Csf1r, Col6a1, Cyba, and Map3k14) were validated by qRT-PCR and BSP methods, and the mRNA expressions were further confirmed to be regulated by DNA methylation in cardiomyocytes in vitro. CONCLUSIONS: Our findings profiled the molecular variations from the perspective of DNA methylation in the early stage of AMI and provided promising epigenetic-based biomarkers for the early clinical diagnosis and therapeutic targets of AMI.

The Association between Socio-Demographics and Mental Distress Following COVID-19 Vaccination-Mediation of Vaccine Hesitancy.

The COVID-19 vaccine has been administered to over 200 countries and regions. With the unprecedented vaccination scale and speed, vaccination correlated mental health issues should be paid precise attention to. This study aims to assess the association between socio-demographic factors and mental health following vaccination and to analyze the mediation effect of vaccine hesitancy. This study recruited 2112 individuals who took two doses of the COVID-19 vaccine in Shanghai. Structural equation modeling was performed to assess factors associated with anxiety and depression of the vaccinated individuals and the underlying mechanism. The results yielded that vaccine hesitancy partially mediated/suppressed the effect from gender and employment status to anxiety/depression and fully mediated the effects from education to anxiety/depression. This study advanced the understanding of mental health disparity among different socio-demographic groups after vaccination and the impact of vaccine hesitancy on the vaccinated population's mental health. The finding offered insights into the possible mental vulnerability of people holding a hesitant attitude before vaccination and suggested that vaccine hesitancy played a crucial role in people's mental health after vaccination. Health promotion programs can target vaccine hesitancy to prevent unfavorable mental health consequences among specific populations.

Molecular characterization of long-term survivors of hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most fatal cancers, and the majority of patients die within three years. However, a small proportion of patients overcome this fatal disease and survive for more than five years. To determine the molecular characteristics of long-term survivors (survival ≥ 5 years), we analyzed the genomic and clinical data of hepatocellular carcinoma patients from The Cancer Genome Atlas and the International Cancer Genome Consortium databases, and identified molecular features that were strongly associated with the patients' prognosis. Genes involved in the cell cycle were expressed at lower levels in tumor tissues from long-term survivors than those from short-term survivors (survival ≤ 1 years). High levels of positive regulators of the G1/S cell cycle transition (cyclin-dependent kinase 2 [CDK2], CDK4, Cyclin E2 [CCNE2], E2F1, E2F2) were potential markers of poor prognosis. Hepatocellular carcinoma patients with TP53 mutations were mainly belonged to the short-term survivor group. Abemaciclib, an FDA-approved selective inhibitor of CDK4/6, inhibited the cell proliferation and tumor growth of hepatocellular carcinoma cells in vitro and in vivo. Thus, high G1/S transition-related gene levels and TP53 mutations are promising diagnostic biomarkers for short-term survivals, and abemaciclib may be a potential targeted drug for hepatocellular carcinoma.

Pyroptosis inhibition improves the symptom of acute myocardial infarction.

Acute myocardial infarction (AMI), the leading cause of mortality worldwide, is a rapidly developing and irreversible disease. Therefore, proper prompt intervention at the early stage of AMI is crucial for its treatment. However, the molecular features in the early stage have not been clarified. Here, we constructed mouse AMI model and profiled transcriptomes and proteomes at the early stages of AMI progress. Immune system was extensively activated at 6-h AMI. Then, pyroptosis was activated at 24-h AMI. VX-765 treatment, a pyroptosis inhibitor, significantly reduced the infarct size and improved the function of cardiomyocytes. Besides, we identified that WIPI1, specifically expressed in heart, was significantly upregulated at 1 h after AMI. Moreover, WIPI1 expression is significantly higher in the peripheral blood of patients with AMI than healthy control. WIPI1 can serve as a potential early diagnostic biomarker for AMI. It likely decelerates AMI progress by activating autophagy pathways. These findings shed new light on gene expression dynamics in AMI progress, and present a potential early diagnostic marker and a candidate drug for clinical pre-treatment to prolong the optimal cure time.