Trends in Intention to Take the Second Booster COVID-19 Vaccination and Associated Factors in China: Serial Cross-Sectional Surveys.

BACKGROUND: The escalating complexity of the COVID-19 epidemic underscores the need for heightened attention to booster vaccinations. This study aims to examine the changing trend in the public's intention to receive the second COVID-19 booster vaccination over time and the associated factors following the COVID-19 policy optimization in China. METHOD: Eight cross-sectional surveys utilizing SMS questionnaire links were conducted in Guangzhou, China, from December 2022 to April 2023. The Mann-Kendall test was employed to analyze the trend in intentions to receive the second booster vaccination across the survey time. Adjusted and multivariate logistic analyses were used to analyze the factors associated with vaccination intention. Parallel analyses were performed for two subgroups with different COVID-19 infection statuses. RESULTS: A total of 9860 respondents were surveyed in the eight rounds, of which 8048 completed the first booster vaccination and were included in the analysis. The overall COVID-19 infection rate was 60.0% (4832/8048), while the overall vaccination intention was 72.2% (5810/8048) among respondents. The vaccination intention exhibited a significant declining trend over time, decreasing from 81.5% in December 2022 to 52.2% in April 2023. An adjusted logistic regression analysis revealed that anxiety and depression were negatively associated with an intention to receive the second booster vaccination, while COVID-19-related preventive behaviors and a high engagement in COVID-19-related information were positively associated with an intention to receive the second booster vaccination. A subgroup analysis revealed that the association between psychological and behavioral characteristics and vaccination intention remained relatively stable among individuals with different histories of COVID-19 infections. CONCLUSION: There was a significant decline in the intention to receive the second booster vaccination following the optimization of the COVID policy in China. Our findings emphasize the urgency of the second booster vaccination and provide a foundation for the development of tailored interventions to enhance and sustain vaccination intention among the public.

Genetic Screening of Patients with Sporadic Alzheimer's Disease and Frontotemporal Lobar Degeneration in the Chinese Population.

Background: Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) account for the vast majority of neurodegenerative dementias. AD and FTLD have different clinical phenotypes with a genetic overlap between them and other dementias. Objective: This study aimed to identify the genetic spectrum of sporadic AD and FTLD in the Chinese population. Methods: A total of 74 sporadic AD and 29 sporadic FTLD participants were recruited. All participants underwent whole-exome sequencing (WES) and testing for a hexanucleotide expansion in C9orf72 was additionally performed for participants with negative WES results. Results: Four known pathogenic or likely pathogenic variants, including PSEN1 (p.G206D), MAPT (p.R5H), LRRK2 (p.W1434*), and CFAP43 (p.C934*), were identified in AD participants, and 1 novel pathogenic variant of ANXA11 (p.D40G) and two known likely pathogenic variants of MAPT (p.D177V) and TARDBP (p.I383V) were identified in FTLD participants. Twenty-four variants of uncertain significance as well as rare variants in risk genes for dementia, such as ABCA7, SORL1, TRPM7, NOS3, MPO, and DCTN1, were also found. Interestingly, several variants in participants with semantic variant primary progressive aphasia were detected. However, no participants with C9orf72 gene variants were found in the FTLD cohort. Conclusions: There was a high frequency of genetic variants in Chinese participants with sporadic AD and FTLD and a complex genetic overlap between these two types of dementia and other neurodegenerative diseases.

Protective Effects of Isoliquiritigenin and Licochalcone B on the Immunotoxicity of BDE-47: Antioxidant Effects Based on the Activation of the Nrf2 Pathway and Inhibition of the NF-κB Pathway.

2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is a polybrominated diphenyl ether (PBDE) homologue that is ubiquitous in biological samples and highly toxic to humans and other organisms. Prior research has confirmed that BDE-47 can induce oxidative damage in RAW264.7 cells, resulting in apoptosis and impaired immune function. The current study mainly focused on how Isoliquiritigenin (ISL) and Licochalcone B (LCB) might protect against BDE-47's immunotoxic effects on RAW264.7 cells. The results show that ISL and LCB could increase phagocytosis, increase the production of MHC-II, and decrease the production of inflammatory factors (TNF-α, IL-6, and IL-1ß) and co-stimulatory factors (CD40, CD80, and CD86), alleviating the immune function impairment caused by BDE-47. Secondly, both ISL and LCB could reduce the expressions of the proteins Bax and Caspase-3, promote the expression of the protein Bcl-2, and reduce the apoptotic rate, alleviating the apoptosis initiated by BDE-47. Additionally, ISL and LCB could increase the levels of antioxidant substances (SOD, CAT, and GSH) and decrease the production of reactive oxygen species (ROS), thereby counteracting the oxidative stress induced by BDE-47. Ultimately, ISL and LCB suppress the NF-κB pathway by down-regulating IKBKB and up-regulating IκB-Alpha in addition to activating the Nrf2 pathway and promoting the production of HO-1 and NQO1. To summarize, BDE-47 causes oxidative damage that can be mitigated by ISL and LCB through the activation of the Nrf2 pathway and inhibition of the NF-κB pathway, which in turn prevents immune function impairment and apoptosis. These findings enrich the current understanding of the toxicological molecular mechanism of BDE-47 and the detoxification mechanism of licorice.

Mental Imagery in the Relationship between Alexithymia and Parental Psychological Control.

This study aims to explore the mediating role of mental imagery in the relationship between alexithymia and parental psychological control among Chinese university students. Conducted between March and April 2023, this descriptive study involved 282 volunteer participants from a university in southern China. Data collection included the Toronto Alexithymia Scale (TAS), the Parental Psychological Control Scale (PPC), and the Vividness of Visual Mental Imagery questionnaire (VVIQ). The results revealed that: (1) based on established cut-off, 81 students were identified as highly alexithymic; (2) the alexithymia group scored higher on both the TAS and PPC and lower on the VVIQ compared to the non-alexithymia and possible-alexithymia groups; and (3) mediating analysis demonstrated a strong and positive correlation between parental psychological control and alexithymia for all participants, with visual mental imagery mediating this relationship. This study underscores the interconnectedness of parental psychological control, visual mental imagery, and alexithymia among college students. The theoretical and clinical implications of these findings are also discussed.

Precision cardiac targeting: empowering curcumin therapy through smart exosome-mediated drug delivery in myocardial infarction.

Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.

An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage-dependent mechanism.

Mesenchymal stromal/stem cells (MSCs) have emerged as a promising approach against myocardial infarction. Due to hostile hyperinflammation, however, poor retention of transplanted cells seriously impedes their clinical applications. Proinflammatory M1 macrophages, which rely on glycolysis as their main energy source, aggravate hyperinflammatory response and cardiac injury in ischemic region. Here, we showed that the administration of an inhibitor of glycolysis, 2-deoxy-d-glucose (2-DG), blocked the hyperinflammatory response within the ischemic myocardium and subsequently extended effective retention of transplanted MSCs. Mechanistically, 2-DG blocked the proinflammatory polarization of macrophages and suppressed the production of inflammatory cytokines. Selective macrophage depletion abrogated this curative effect. Finally, to avoid potential organ toxicity caused by systemic inhibition of glycolysis, we developed a novel chitosan/gelatin-based 2-DG patch that directly adhered to the infarcted region and facilitated MSC-mediated cardiac healing with undetectable side effects. This study pioneered the application of an immunometabolic patch in MSC-based therapy and provided insights into the therapeutic mechanism and advantages of this innovative biomaterial.

Case report: Compound heterozygous nonsense PCDH15 variant and a novel deep-intronic variant in a Chinese child with profound hearing loss.

BACKGROUND: Usher syndrome is a condition characterized by partial or total hearing loss and progressive pigmentary retinopathy. Usher syndrome type 1F is caused by biallelic loss-of-function variants in Protocadherin 15 (PCDH15), which encodes the PCDH15 protein that plays an important role in the morphogenesis and cohesion of stereocilium bundles and retinal photoreceptor cell maintenance and function. METHODS: We report a child with bilateral nonsyndromic sensorineural hearing loss who received an inconclusive diagnosis based on clinical gene panel testing, which identified a paternal heterozygous nonsense variant (NM_033056.4: c.733C>T, p.R245*) in PCDH15. This variant has been described as a founder variant in the Ashkenazi Jewish population. RESULTS: A novel deep-intronic variant (NM_033056.4: c.705+3767_705+3768del) inherited from the patient's mother was identified by trio-based whole-genome sequencing (WGS). A minigene splicing assay revealed that c.705+3767_705+3768del results in aberrant retention of 50 or 68 bp of intron 7. CONCLUSION: Our genetic test results provided precise genetic counseling and prenatal diagnosis for this family, and our findings highlight the power of WGS for detecting deep-intronic variants in patients with undiagnosed rare diseases. Additionally, this case expands the variant spectrum of the PCDH15 gene and our results support the extremely low carrier frequency of c.733C>T in the Chinese population.

Test development, optimization and validation of a WGS pipeline for genetic disorders.

BACKGROUND: With advances in massive parallel sequencing (MPS) technology, whole-genome sequencing (WGS) has gradually evolved into the first-tier diagnostic test for genetic disorders. However, deployment practice and pipeline testing for clinical WGS are lacking. METHODS: In this study, we introduced a whole WGS pipeline for genetic disorders, which included the entire process from obtaining a sample to clinical reporting. All samples that underwent WGS were constructed using polymerase chain reaction (PCR)-free library preparation protocols and sequenced on the MGISEQ-2000 platform. Bioinformatics pipelines were developed for the simultaneous detection of various types of variants, including single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs) and balanced rearrangements, mitochondrial (MT) variants, and other complex variants such as repeat expansion, pseudogenes and absence of heterozygosity (AOH). A semiautomatic pipeline was developed for the interpretation of potential SNVs and CNVs. Forty-five samples (including 14 positive commercially available samples, 23 laboratory-held positive cell lines and 8 clinical cases) with known variants were used to validate the whole pipeline. RESULTS: In this study, a whole WGS pipeline for genetic disorders was developed and optimized. Forty-five samples with known variants (6 with SNVs and Indels, 3 with MT variants, 5 with aneuploidies, 1 with triploidy, 23 with CNVs, 5 with balanced rearrangements, 2 with repeat expansions, 1 with AOHs, and 1 with exon 7-8 deletion of SMN1 gene) validated the effectiveness of our pipeline. CONCLUSIONS: This study has been piloted in test development, optimization, and validation of the WGS pipeline for genetic disorders. A set of best practices were recommended using our pipeline, along with a dataset of positive samples for benchmarking.

Structure, stability, antioxidant activity, and controlled-release of selenium nanoparticles decorated with lichenan from Usnea longissima.

Selenium nanoparticles (SeNPs) have attracted widespread attention, but the poor water dispersibility restricted their applications seriously. Herein, Usnea longissima lichenan decorated selenium nanoparticles (L-SeNPs) were constructed. The formation, morphology, particle size, stability, physicochemical characteristics, and stabilization mechanism of L-SeNPs were investigated via TEM, SEM, AFM, EDX, DLS, UV-Vis, FT-IR, XPS, and XRD. The results indicated that the L-SeNPs displayed orange-red, amorphous, zero-valent, and uniform spherical nanoparticles with an average diameter of 96 nm. Due to the formation of CO⋯Se bonds or the hydrogen bonding interaction (OH⋯Se) between SeNPs and lichenan, L-SeNPs exhibited better heating and storage stability, which kept stable for more than one month at 25 °C in an aqueous solution. The decoration of the SeNPs surface with lichenan endowed the L-SeNPs with superior antioxidant capability, and their free radicals scavenging ability exhibited in a dose-dependent manner. Furthermore, L-SeNPs showed excellent selenium controlled-release performance. In simulated gastric liquids, selenium release kinetics from L-SeNPs followed the Linear superimposition model, which was governed by the polymeric network retardation of macromolecular, while in simulated intestinal liquids, it was well fitted to the Korsmeyer-Peppas model and followed a Fickian mechanism controlled by diffusion.

Clinical Outcomes by Consolidation of Bone Marrow Stem Cell Therapy and Coronary Artery Bypass Graft in Patients With Heart Failure With Reduced Ejection Fraction: A Meta-analysis.

Bone marrow stem cell (BMSC) transplantation during coronary artery bypass graft (CABG) is an innovative treatment for ischemic heart disease (IHD). We conduct a meta-analysis to examine whether patients with IHD presenting heart failure with reduced ejection fraction (HFrEF) can be beneficent from CABG with additional BMSC transplantation. Electronic searches were performed on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov from their inception to July 2021. The efficacy was based on left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), and 6-min walk test (6MWT) change after treatment. Eight randomized-controlled trials (RCTs) were included in this meta-analysis, with a total of 350 patients. Results showed BMSC transplantation significantly improved the LVEF [mean difference (MD) = 6.23%, 95% confidence interval (CI): 3.22%-9.24%, P < 0.0001], LVEDVi (MD = -20.15 ml/m2, 95% CI: -30.49 to -9.82 ml/m2, P < 0.00001), and LVESVi (MD = -17.69 ml/m2, 95% CI: -25.24 to -10.14 ml/m2, P < 0.00001). There was no statistically significant difference in the improvement of LVEDD, LVEDV, and 6MWT between the cell transplantation group and control groups. Subgroup analysis revealed that the intervention for control group could affect the efficacy of BMSC transplantation. Sensitivity analysis found the conclusion of LVEDD, LVEDV, and 6MWT changes was not stable. Therefore, among patients with IHD presenting HFrEF, BMSC transplantation during CABG is promising to be beneficial for postoperative left ventricular (LV) function improvement. However, according to the unstable results of the sensitivity analysis, it cannot be concluded whether the extra step has a positive effect on left ventricular remodeling and exercise capacity. RCTs with larger cohorts and more strict protocols are needed to validate these conclusions.

Rapid and massive fractionation of hemicelluloses for purifying cellulose at room temperature by tetramethylammonium hydroxide.

The fractionation of hemicelluloses is a promising method to improve the comprehensive utilization of lignocellulosic biomass. However, the effective fractionation of hemicelluloses is always limited by the structural complexity and easy degradability. In this study, tetramethylammonium hydroxide (TMAH) was developed to fractionate hemicelluloses from poplar holocellulose with high molecular weights and high yields at room temperature. Approximately 90% of hemicelluloses could be dissolved at room temperature in 1 h, and the yield was up to 81.9%. Compared with the fractionation using NaOH solution, the hemicelluloses isolated by TMAH solvent showed a more complete structure and higher purity. Meanwhile, the retention rate of cellulose after treatment with TMAH was up to 90.2%, and the crystal structure of cellulose in the residues was practically unchanged. Moreover, the TMAH solvent could be recycled to fractionate hemicelluloses. The work provides an elegant and significantly efficient method towards hemicelluloses fractionation and cellulose purification.

The Characteristic of Resident Macrophages and their Therapeutic Potential for Myocardial Infarction.

Resident macrophages (R-mac) are a subset of macrophages with self-renewal functions, which play a pivotal role in the homeostasis, inflammation, injury, and repair of the heart. In this paper, we summarize the knowledge related to cardiac R-mac and describe their dominating functions in myocardial infarction, such as inhibiting fibrosis and adverse remodeling, promoting revascularization and improving arrhythmia, etc. In the last, we sketch out the extended application of R-mac in tissue engineering, providing a novel direction of research and application for the therapy in the future.

Prevalence of syphilis and risk factors among HIV-positive men who have sex with men in Guangdong province.

Background: HIV-positive men who have sex with men (MSM) tend to have high syphilis incidence. Our objective is to evaluate the prevalence of syphilis and determine the risk factors of syphilis among HIV-positive MSM. Methods: A cross-sectional study with convenience sampling was performed among HIV-positive MSM in six cities of Guangdong Province from June 2020 to August 2021. Participants completed a survey including social-demographic characteristics, sexual behaviors and self-reported syphilis, chlamydia, gonorrhea, herpes, human papillomavirus statuses after HIV diagnosis. Multivariate logistic regression was used to determine the factors associated with syphilis and sexually transmitted diseases (STD). Results: Among 944 HIV-positive MSM, 141 (14.9, 95% CI: 12.7-17.2%) men had syphilis and 220 (23.3, 95% CI: 20.6-26.0%) men had STD. Multivariate analysis indicated that MSM who met male sexual partners mainly through traditional meeting places (spa or bath house, sauna, foot or body massage parlor) in the last 6 months [adjusted Odds Ratio (aOR) = 2.91, 95% CI: 1.09-7.79], and who were diagnosed with herps after the HIV diagnosis (aOR = 3.79, 95% CI: 1.16-12.39) were more likely to have syphilis. In addition, MSM who met male sexual partners mainly through traditional meeting places in the last 6 month (aOR = 2.55, 95% CI: 1.01-6.42), and who had more than one male sexual partner in the last 6 months (aOR = 1.88, 95% CI: 1.17-3.02) were more likely to have STD. Conclusions: The prevalence of syphilis and other STDs is relatively high among HIV-positive MSM in southern China. Routine syphilis screening as a part of HIV monitoring among HIV-positive MSM will have important epidemiological significance for the management of infected patients, and can help reduce the spread of syphilis.

Robust association tests for quantitative traits on the X chromosome.

The genome-wide association study is an elementary tool to assess the genetic contribution to complex human traits. However, such association tests are mainly proposed for autosomes, and less attention has been given to methods for identifying loci on the X chromosome due to their distinct biological features. In addition, the existing association tests for quantitative traits on the X chromosome either fail to incorporate the information of males or only detect variance heterogeneity. Therefore, we propose four novel methods, which are denoted as QXcat, QZmax, QMVXcat and QMVZmax. When using these methods, it is assumed that the risk alleles for females and males are the same and that the locus being studied satisfies the generalized genetic model for females. The first two methods are based on comparing the means of the trait value across different genotypes, while the latter two methods test for the difference of both means and variances. All four methods effectively incorporate the information of X chromosome inactivation. Simulation studies demonstrate that the proposed methods control the type I error rates well. Under the simulated scenarios, the proposed methods are generally more powerful than the existing methods. We also apply our proposed methods to data from the Minnesota Center for Twin and Family Research and find 10 single nucleotide polymorphisms that are statistically significantly associated with at least two traits at the significance level of 1 × 10-3.

Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Attenuate Myocardial Infarction Injury via miR-24-3p-Promoted M2 Macrophage Polarization.

Exosomes derived from human umbilical cord mesenchymal stem cells (UMSC-Exos) have shown encouraging effects in regulating inflammation and attenuating myocardial injury. Macrophages are regulated dynamically in response to environmental cues. However, the underlying mechanisms by which UMSC-Exos regulate macrophage polarization are still not well understood. Herein, it is aimed to explore the effects of UMSC-Exos on macrophage polarization and their roles in cardiac repair after myocardial infarction (MI). These results show that UMSC-Exos improve cardiac function by increasing M2 macrophage polarization and reducing excessive inflammation. RNA-sequencing results identify Plcb3 as a key gene involved in UMSC-Exo-facilitated M2 macrophage polarization. Further bioinformatic analysis identifies exosomal miR-24-3p as a potential effector mediating Plcb3 downregulation in macrophages. Increasing miR-24-3p expression in macrophages effectively enhances M2 macrophage polarization by suppressing Plcb3 expression and NF-κB pathway activation in the inflammatory environment. Furthermore, reducing miR-24-3p expression in UMSC-Exos attenuates the effects of UMSC-Exos on M2 macrophage polarization. This study demonstrates that the cardiac therapeutic effects of UMSC-Exos are at least partially through promoting M2 macrophage polarization in an inflammatory microenvironment. Mechanistically, exosomal miR-24-3p is found to inhibit Plcb3 expression and NF-κB pathway activation to promote M2 macrophage polarization.

Effects of Sport Stacking on Neuropsychological, Neurobiological, and Brain Function Performances in Patients With Mild Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Controlled Trial.

Objective: To investigate the effects of sport stacking on the overall cognition and brain function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A single-blind randomized controlled design was performed using sport stacking for 30 min, 5 days/week for 12 weeks. Forty-eight subjects with mild AD or MCI were randomly divided into the sport stacking group (T-mAD = 12, T-MCI = 12) and the active control group (C-mAD = 11, C-MCI = 13). Auditory Verbal Learning Test (AVLT), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), Geriatric Depression Scale (GDS-30), and Pittsburgh Sleep Quality Index (PSQI) were performed, the level of amyloid ß-protein-40 (Aß-40), Aß-42, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1(IGF-1), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and soluble trigger receptor expressed on myeloid cells 2 (sTREM2) in plasma were tested, and brain functional connectivity in resting state and activation under finger movement task were analyzed by functional near-infrared spectroscopy (fNIRS). Results: Thirty-nine patients completed the trial. After 4 weeks, we found a significant increase in AVLT score in T-MCI (6.36 ± 5.08 vs. -1.11 ± 4.23, p = 0.004), and T-mAD group (4.60 ± 4.77 vs. -0.11 ± 2.89, p = 0.039). After 12 weeks, there was a significantly improved in AVLT (9.64 ± 4.90 vs. -0.33 ± 6.10, p = 0.002) and ADCS-ADL (3.36 ± 3.59 vs. -1.89 ± 2.71, p = 0.003) in T-MCI. There was a significant improvement in AVLT (5.30 ± 5.42 vs. 0.44 ± 2.40) in T-mAD (p < 0.05). Plasma levels of BDNF were upregulated in both T-MCI and T-mAD, and IGF-1 increased in T-MCI (P < 0.05) compared to the control groups. The functional connectivity in MCI patients between DLPFC.R and SCA.R, SMA.L, and SCA.R was decreased. In contrast, in mAD patients, the brain regional function connection was increased between DLPFC.R and Broca's.L. The activation of channel 36 located in the left primary somatosensory cortex was significantly increased after 12-week training, which was correlated with the improved AVLT and the increase of BDNF. Conclusion: Our findings suggested that sport stacking is effective for patients with MCI and mild AD, possibly through increasing the expression of neuroprotective growth factors and enhancing neural plasticity to improve neurocognitive performance. Clinical Trial Registration: https://www.ClinicalTrials.gov, ChiCTR.org.cn, identifier: ChiCTR-2100045980.

BEXCIS: Bayesian methods for estimating the degree of the skewness of X chromosome inactivation.

BACKGROUND: X chromosome inactivation (XCI) is an epigenetic phenomenon that one of two X chromosomes in females is transcriptionally silenced during early embryonic development. Skewed XCI has been reported to be associated with some X-linked diseases. There have been several methods measuring the degree of the skewness of XCI. However, these methods may still have several limitations. RESULTS: We propose a Bayesian method to obtain the point estimate and the credible interval of the degree of XCI skewing by incorporating its prior information of being between 0 and 2. We consider a normal prior and a uniform prior for it (respectively denoted by BN and BU). We also propose a penalized point estimate based on the penalized Fieller's method and derive the corresponding confidence interval. Simulation results demonstrate that the BN and BU methods can solve the problems of extreme point estimates, noninformative intervals, empty sets and discontinuous intervals. The BN method generally outperforms other methods with the lowest mean squared error in the point estimation, and well controls the coverage probability with the smallest median and the least variation of the interval width in the interval estimation. We apply all the methods to the Graves' disease data and the Minnesota Center for Twin and Family Research data, and find that SNP rs3827440 in the Graves' disease data may undergo skewed XCI towards the allele C. CONCLUSIONS: We recommend the BN method for measuring the degree of the skewness of XCI in practice. The R package BEXCIS is publicly available at https://github.com/Wen-YiYu/BEXCIS .

Detection of Parent-of-Origin Effects for the Variants Associated With Behavioral Disinhibition in the MCTFR Data.

Behavioral disinhibition is one of the important characteristics of many mental diseases. It has been reported in literature that serious behavioral disinhibition will affect people's health and greatly reduce people's quality of life. Meanwhile, behavioral disinhibition can easily lead to illegal drug abuse and violent crimes, etc., which will bring great harm to the society. At present, large-scale genome-wide association analysis has identified many loci associated with behavioral disinhibition. However, these studies have not incorporated the parent-of-origin effects (POE) into analysis, which may ignore or underestimate the genetic effects of loci on behavioral disinhibition. Therefore, in this article, we analyzed the five phenotypes related to behavioral disinhibition in the Minnesota Center for Twin and Family Research data (nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance use related behavioral disinhibition), to further explore the POE of variants on behavioral disinhibition. We applied a linear mixed model to test for the POE at a genome-wide scale on five transformed phenotypes, and found nine SNPs with statistically significant POE at the significance level of 5 × 10-8. Among them, SNPs rs4141854, rs9394515, and rs4711553 have been reported to be associated with two neurological disorders (restless legs syndrome and Tourette's syndrome) which are related to behavioral disinhibition; SNPs rs12960235 and rs715351 have been found to be associated with head and neck squamous cell carcinoma, skin cancer and type I diabetes, while both SNPs have not been identified to be related to behavioral disinhibition in literature; SNPs rs704833, rs6837925, rs1863548, and rs11067062 are novel loci identified in this article, and their function annotations have not been reported in literature. Follow-up study in molecular genetics is needed to verify whether they are surely related to behavioral disinhibition.

Comparative Transcriptome Analysis of Spleen Reveals Potential Regulation of Genes and Immune Pathways Following Administration of Aeromonas salmonicida subsp. masoucida Vaccine in Atlantic Salmon (Salmo salar).

Aeromonas salmonicida is a global fish pathogen. Aeromonas salmonicida subsp. masoucida (ASM) is classified as atypical A. salmonicida and caused huge losses to salmonid industry in China. Hence, it is of great significance to develop ASM vaccine and explore its protection mechanism in salmonids. In this regard, we conducted RNA-seq analysis with spleen tissue of Atlantic salmon after ASM vaccination to reveal genes, their expression patterns, and pathways involved in immune protections. In our results, a total of 441.63 million clean reads were obtained, and 389.37 million reads were mapped onto the Atlantic salmon reference genome. In addition, 1125, 2126, 1098, 820, and 1351 genes were significantly up-regulated, and 747, 2626, 818, 254, and 908 genes were significantly down-regulated post-ASM vaccination at 12 h, 24 h, 1 month, 2 months, and 3 months, respectively. Subsequent pathway analysis revealed that many differentially expressed genes (DEGs) following ASM vaccination were involved in cytokine-cytokine receptor interaction (TNFRSF11b, IL-17RA, CCR9, and CXCL11), HTLV-I infection (MR1 and HTLV-1), MAPK signaling pathway (MAPK, IL8, and TNF-α-1), PI3K-Akt signaling pathway (PIK3R3, THBS4, and COL2A1), and TNF signaling pathway (PTGS2, TNFRSF21-l, and CXCL10). Finally, the results of qRT-PCR showed a significant correlation with RNA-seq results, suggesting the reliability of RNA-seq for gene expression analysis. This study provided insights into regulation of gene expression and their involved pathways in Atlantic salmon spleen in responses to vaccine, and set the foundation for further study on the vaccine protective mechanism in Atlantic salmon as well as other teleost species.

Correction: Incidence, clinical course and risk factor for recurrent PCR positivity in discharged COVID-19 patients in Guangzhou, China: A prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pntd.0008648.].