Inflammasome Activation Triggers Caspase-1-Mediated Cleavage of cGAS to Regulate Responses to DNA Virus Infection.

Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc-/- and Casp1-/- macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge. Investigation of the underlying mechanism revealed that upon canonical and non-canonical inflammasome activation, caspase-1 interacted with cyclic GMP-AMP (cGAMP) synthase (cGAS), cleaving it and dampening cGAS-STING-mediated IFN production. Deficiency in inflammasome signaling enhanced host resistance to DNA virus in vitro and in vivo, and this regulatory role extended to other inflammatory caspases. Thus, inflammasome activation dampens cGAS-dependent signaling, suggesting cross-regulation between intracellular DNA-sensing pathways.

Efficacy Analysis of Extended Uvulopalatopharyngoplasty Combined With the Simultaneous Multiplane Operation to Treat Obstructive Sleep Apnea.

PURPOSE: The purpose of this study was to discuss the safety and long-term efficacy of extended uvulopalatopharyngoplasty combined with the simultaneous multiplane operation to treat obstructive sleep apnea (OSA). MATERIALS AND METHODS: Sixty-two patients confirmed with OSA by polysomnography received physical examinations, determination of nasal resistance, Muller's maneuver under electronic laryngoscope, and upper airway computed tomography scan to locate the obstruction planes. Then the patients received extended uvulopalatopharyngoplasty combined with the simultaneous multiplane operation of the nasal cavity and/or tongue root under general anesthesia. Body mass index, Epworth Sleepiness Scale (ESS) score, apnea-hypopnea index (AHI), and lowest arterial oxygen saturation (LSaO 2 ) were compared before and after surgery. Postoperative complications were recorded. All patients were followed up for 12 to 24 months after surgery. The above-mentioned indicators were determined. RESULTS: Fourteen patients (22.58%) achieved a cure, 20 patients (32.26%) marked effectiveness, 20 patients (32.26%) moderate effectiveness, and 8 patients (12.90%) ineffectiveness. The overall response rate was 87.10%. AHI and ESS score decreased, and LSaO 2 increased after surgery than before, all in a significant manner ( P <0.05). There was no significant difference in body mass index before and after surgery. No severe complications occurred in any patients. CONCLUSIONS: Extended uvulopalatopharyngoplasty combined with the simultaneous multiplane operation had a good safety for OSA, improving ESS, AHI, and LSaO 2 significantly. The patients enjoyed an improved life quality after surgery.

Association between schizoid tendencies and aggressive behaviors: mediating and moderating influences in childhood trauma and life events among Chinese adolescents.

BACKGROUND: This study investigated an association between schizoid tendencies and aggressive behaviors in Chinese adolescents, and explored the underlying mechanism. METHODS: The data of 3094 adolescents aged 12 to 16 years were collected from an epidemiological survey in China. All the subjects or their parents completed the Achenbach's Child Behavior Checklist, the Childhood Trauma Questionnaire-Short Form, and the Adolescent Self-rating Life Event Checklist (ASLEC). RESULTS: Relative to the non-schizoid group, adolescents with schizoid tendencies (male or female) showed significantly higher scores for aggressive behaviors, emotional abuse, and ASLEC. Regarding females only, those with schizoid tendencies had significantly higher (lower) scores for physical abuse and emotional neglect (physical neglect). The aggressive behaviors score was predicted by scores for schizoid tendencies (ßmale = 0.620, ßfemale = 0.638, both P < 0.001) and ASLEC (ßmale = 0.125, ßfemale = 0.061, both P < 0.01), and by childhood trauma score (males: emotional neglect [ß = 0.045, P = 0.021]; females: emotional abuse and sexual abuse [ß = 0.118 and - 0.062, both P < 0.01]). The ASLEC and childhood trauma scores mediated the association between scores for schizoid tendencies and aggressive behaviors, specifically, emotional neglect (emotional abuse and sexual abuse) in males (females). In females, the interaction between scores for childhood trauma and ASLEC affected the aggressive behaviors score (P = 0.023). CONCLUSIONS: Schizoid tendencies are associated with aggressive behaviors among Chinese adolescents. Recent life events and childhood trauma mediated an association between schizoid tendencies and aggressive behaviors. The interaction between childhood trauma and recent life events affected aggressive behaviors in females. Aggressive behaviors in adolescents may be ameliorated by reducing childhood trauma and life events.

Hyperactivation of the NLRP3 inflammasome protects mice against influenza A virus infection via IL-1ß mediated neutrophil recruitment.

Host innate immune system is critical for combating invading microbes including Influenza A virus (IAV). As an important arm of the innate immunity, the NLRP3 inflammasome has been found essential for protecting host against IAV challenge, while the mechanism remained elusive. Here we found that mice carrying a gain-of-function mutation in the Nlrp3 gene (Nlrp3R258W) are strongly resistant to IAV infection. Upon H1N1 IAV infection, the Nlrp3R258W mice exhibited decreased weight loss, increased survival rate and attenuated lung damage compared with WT littermate controls. Mechanistically, the resistance of Nlrp3R258W mice to IAV infection was dependent on IL-1ß-mediated neutrophil recruitment. Upon IAV infection, mice carrying the Nlrp3R258W mutation produced more IL-1ß than WT mice in the lung, which enhanced neutrophil recruitment locally. The recruited neutrophils facilitated IAV clearance, so that the viral load in Nlrp3R258W mice was lower than that in control mice. Conversely, neutrophil depletion in Nlrp3R258W mice compromised IAV clearance. Taken together, our results demonstrate a previously undescribed mechanism by which hyperactivation of the NLRP3 Inflammasome protects mice from IAV infection through IL-1ß mediated neutrophil recruitment, thus suggest that positively fine tuning the physiological function of NLRP3 inflammasome can be beneficial for a mammalian host against IAV challenge.

Hyperactivation of the NLRP3 Inflammasome in Myeloid Cells Leads to Severe Organ Damage in Experimental Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model. It was discovered that more severe lupus-like syndrome developed in Nlrp3-R258W mice carrying the gain-of-function mutation. Nlrp3-R258W mutant mice exhibited significantly higher mortality upon pristane challenge. Moreover, prominent hypercellularity and interstitial nephritis were evident in the glomeruli of Nlrp3-R258W mice. In addition, hyperactivation of the NLRP3 inflammasome in this mouse line resulted in proteinuria and mesangial destruction. Importantly, all of these phenotypes were largely attributed to the Nlrp3-R258W mutation expressed in myeloid cells, because Cre recombinase-mediated depletion of this mutant from such cells rescued mice from experimental lupus. Taken together, our study demonstrates a critical role for NLRP3 in the development of SLE and suggests that modulating the inflammasome signal may help to control the inflammatory damage in autoimmune diseases, including lupus.

Methylation status and expression patterns of myomaker gene play important roles in postnatal development in the Japanese flounder (Paralichthys olivaceus).

Myomaker is a membrane protein that plays a crucial role in the fusion of myoblasts during muscle growth. DNA methylation, a significant factor, regulates gene expression. The aim of this study was to examine the methylation and mRNA expression patterns of the myomaker gene during 8 different postnatal developmental stages in the Japanese flounder (L: 7 days post hatch (dph); M1: 21 dph; M2: 28 dph; M3: 35 dph; J1: 90 dph; J2: 180 dph; A1: 24 months; A2: 36 months). Muscle tissue samples were taken from Japanese flounder at different postnatal development stages to measure the extent of DNA methylation and gene expression. Methylation level in the promoter and exon 1 of myomaker was measured using bisulfite sequencing, and the relative expression of myomaker during each developmental stage was measured by quantitative PCR. The relative expression levels of myomaker were up-regulated from stages L to M2, M3 to J2, and methylation of myomaker was negatively correlated with mRNA expression. Furthermore, the CpG site located at -26 bp in the promoter was the lowest methylated region in all developmental stages. These results offer a basis for understanding the mechanism by which myomaker regulates muscle formation during postnatal development.

Semipermeable Functional DNA-Encapsulated Nanocapsules as Protective Bioreactors for Biosensing in Living Cells.

The development of functional DNA-based nanosensors in living cells has experienced some design challenges, including, for example, poor cellular uptake, rapid nuclease degradation, and high false positives. Herein, we designed selectively permeable poly(methacrylic acid) (PMA) nanocapsules to encapsulate functional DNAs for metal ions and small-molecules sensing in living cells. Since functional DNAs are concentrated in the nanocapsules, an increasing reaction rate is obtained in vitro. During endocytosis, polymeric capsules simultaneously improve cellular uptake of functional DNAs and preserve their structural integrity inside the confined capsule space. More importantly, selective shell permeability allows for the free diffusion of small molecular targets through capsule shells but limits the diffusion of large biomolecules, such as nuclease and nonspecific protein. Compared to the free DNAzyme, PMA nanocapsules could reduce false positives and enhance detection accuracy. Furthermore, PMA nanocapsules are biocompatible and biodegradable. Through the controllability of wall thickness, permeability, and size distribution, these nanocapsules could be expanded easily to other targets, such as microRNAs, small peptides, and metabolites. These nanocapsules will pave the way for in situ monitoring of various biological processes in living cells and in vivo.

Facile Phase Transfer and Surface Biofunctionalization of Hydrophobic Nanoparticles Using Janus DNA Tetrahedron Nanostructures.

Hydrophobic nanoparticles have shown substantial potential for bioanalysis and biomedical applications. However, their use is hindered by complex phase transfer and inefficient surface modification. This paper reports a facile and universal strategy for phase transfer and surface biofunctionalization of hydrophobic nanomaterials using aptamer-pendant DNA tetrahedron nanostructures (Apt-tet). The Janus DNA tetrahedron nanostructures are constructed by three carboxyl group modified DNA strands and one aptamer sequence. The pendant linear sequence is an aptamer, in this case AS1411, known to specifically bind nucleolin, typically overexpressed on the plasma membranes of tumor cells. The incorporation of the aptamers adds targeting ability and also enhances intracellular uptake. Phase-transfer efficiency using Apt-tet is much higher than that achieved using single-stranded DNA. In addition, the DNA tetrahedron nanostructures can be programmed to permit the incorporation of other functional nucleic acids, such as DNAzymes, siRNA, or antisense DNA, allowing, in turn, the construction of promising theranostic nanoagents for bioanalysis and biomedical applications. Given these unique features, we believe that our strategy of surface modification and functionalization may become a new paradigm in phase-transfer-agent design and further expand biomedical applications of hydrophobic nanomaterials.

Pathogenic fungus Microsporum canis activates the NLRP3 inflammasome.

Microsporum canis is a pathogenic fungus with worldwide distribution that causes tinea capitis in animals and humans. M. canis also causes invasive infection in immunocompromised patients. To defy pathogenic fungal infection, the host innate immune system is the first line of defense. As an important arm of innate immunity, the inflammasomes are intracellular multiprotein complexes that control the activation of caspase-1, which cleaves proinflammatory cytokine pro-interleukin-1ß (IL-1ß) into its mature form. To determine whether the inflammasome is involved in the host defense against M. canis infection, we challenged human monocytic THP-1 cells and mouse dendritic cells with a clinical strain of M. canis isolated from patients with tinea capitis. We found that M. canis infection triggered rapid secretion of IL-1ß from both THP-1 cells and mouse dendritic cells. Moreover, by using gene-specific shRNA and competitive inhibitors, we determined that M. canis-induced IL-1ß secretion was dependent on NLRP3. The pathways proposed for NLRP3 inflammasome activation, namely, cathepsin B activity, K(+) efflux, and reactive oxygen species production, were all required for the inflammasome activation triggered by M. canis. Meanwhile, Syk, Dectin-1, and Card9 were found to be involved in M. canis-induced IL-1ß secretion via regulation of pro-IL-1ß transcription. More importantly, our data revealed that M. canis-induced production of IL-1ß was dependent on the NLRP3 inflammasome in vivo. Together, this study unveils that the NLRP3 inflammasome exerts a critical role in host innate immune responses against M. canis infection, and our data suggest that diseases that result from M. canis infection might be controlled by regulating the activation of inflammasomes.

The Optimal Cut-Off Point of Physical Activity for the Prevention of Childhood Overweight and Obesity.

Childhood obesity might threaten children's current and adulthood health outcomes. Previous studies have illustrated the positive effects of physical activity on weight control; however, there is a lack of evidence on the optimal dose of physical activity. Therefore, we aimed to explore the relationship between physical activity and overweight and obesity, as well as the optimal threshold for physical activity. The median (interquartile range) and number (proportion) were used to describe the statistics. The Mann-Whitney U test and chi-square test were used for an univariable analysis. The generalized additive model with a smooth function was used to depict the preliminary relationship between physical activity and overweight and obesity. The cut-off level of physical activity was identified using AddFor algorithms, and a logistic regression model was applied to explore the multivariable relationship between physical activity and overweight and obesity after adjusting for control variables. According to the statistical analyses, 24.3% of 842 children and adolescents had overweight and obesity. The average number of days that the participants engaged in more than one hour of physical activity was three days a week. The optimal cut-off level of physical activity for the prevention of childhood overweight and obesity was 4 times a week. The participants who exercised more than four times a week (AOR(95% CI) = 0.56(0.38, 0.83), p = 0.004) were less likely to be overweight and obese. In the context of the general lack of physical activity among children and adolescents, we recommend that children and adolescents engage in 60 min of physical activity more than four times a week for a healthy weight.

The Effectiveness of Improving Infectious Disease-Specific Health Literacy Among Residents: WeChat-Based Health Education Intervention Program.

BACKGROUND: Infectious disease-specific health literacy (IDSHL) has become an important determinant of infectious disease incidence. It can not only reduce the incidence of re-emerging infectious diseases, but also effectively prevent the emergence of new infectious diseases such as COVID-19. WeChat, as a new media, has been proven to greatly reduce the chance of infectious diseases spreading from person to person, especially in case of respiratory infections. However, there is currently no concrete health education invention program to improve IDSHL using a WeChat public account. OBJECTIVE: The aims of this study were as follows: (1) to determine the IDSHL of the population in Zhejiang, China; (2) to develop a health education program for the improvement of IDSHL using a WeChat public account; and (3) to evaluate the effectiveness of the health education program that was implemented in the prevention of infectious disease outbreaks. METHODS: We used a standardized questionnaire, which consisted of 28 closed-ended questions, to measure the level and score of IDSHL before and after intervention. A multiple-stage stratified random sampling technique was used to select study participants from Zhejiang province in China, who were further divided randomly into 2 groups: the intervention and control groups. From July 2014 to January 2015, a WeChat-based health education intervention program was carried out on the intervention group. Standard descriptive statistics and chi-square and t tests were conducted to analyze the data. RESULTS: A total of 3001 residents participated in the baseline survey of this study. At baseline, participant IDSHL rates were 73.29% and 72.12% for the intervention and control groups, respectively (Χ21=0.5; P=.50). After 7 months of intervention, 9.90% (297/3001) of participants dropped out of the study. Of the lost participants, 119 were from the intervention group and 178 were from the control group. There were significant differences between follow-up and lost participants with respect to age (P=.04), marital status (P=.02) and occupations (P=.002). After intervention, the intervention group scores in the different domains were higher than those in the control group (infectious disease-related knowledge, prevention, management, or treatment, identification of pathogens and infection sources, and cognitive ability). There were significant improvements in the IDSHL of participants in both the intervention and control groups (Χ21=135.9; P<.001 vs Χ21=9.1; P=.003), and there was a greater change in the IDSHL among the intervention group participants than among the control group participants (1230/1359, 90.51% vs 1038/1359, 77.17%). CONCLUSIONS: The health education intervention program using a WeChat public account proved to be an effective, feasible, and well-accepted means to improve the IDSHL of the general population. In the future, this health education intervention program can be used as a reference for prevention and treatment of infectious diseases.

Atypical frontotemporal cortical activity in first-episode adolescent-onset schizophrenia during verbal fluency task: A functional near-infrared spectroscopy study.

Background: Frontotemporal cortex dysfunction has been found to be associated with cognitive impairment in patients with schizophrenia (SCZ). In patients with adolescent-onset SCZ, a more serious type of SCZ with poorer functional outcome, cognitive impairment appeared to occur at an early stage of the disease. However, the characteristics of frontotemporal cortex involvement in adolescent patients with cognitive impairment are still unclear. In the present study, we aimed to illustrate the frontotemporal hemodynamic response during a cognitive task in adolescents with first-episode SCZ. Methods: Adolescents with first-episode SCZ who were aged 12-17 and demographically matched healthy controls (HCs) were recruited. We used a 48-channel functional near-infrared spectroscopy (fNIRS) system to record the concentration of oxygenated hemoglobin (oxy-Hb) in the participants' frontotemporal area during a verbal fluency task (VFT) and analyzed its correlation with clinical characteristics. Results: Data from 36 adolescents with SCZ and 38 HCs were included in the analyses. Significant differences were found between patients with SCZ and HCs in 24 channels, mainly covering the dorsolateral prefrontal cortex, superior and middle temporal gyrus and frontopolar area. Adolescents with SCZ showed no increase of oxy-Hb concentration in most channels, while the VFT performance was comparable between the two groups. In SCZ, the intensity of activation was not associated with the severity of symptoms. Finally, receiver operating characteristic analysis indicated that the changes in oxy-Hb concentration could help distinguish the two groups. Conclusion: Adolescents with first-episode SCZ showed atypical cortical activity in the frontotemporal area during the VFT, and fNIRS features might be more sensitive indicators in cognitive assessment, indicating that the characteristic hemodynamic response pattern might be potential imaging biomarkers for this population.

IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells.

Both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to synergistically induce c-MYC and phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular helper (TFH)-derived cytokine, affects GCBCs is unclear. Like BCR and CD40 signals, IL-21 receptor (IL-21R) plus CD40 signals also synergize to induce c-MYC and p-S6 in GCBCs. However, IL-21R plus CD40 stimulation differentially affects GCBC fate compared with BCR plus CD40 ligation-engaging unique molecular mechanisms-as revealed by bulk RNA sequencing (RNA-seq), single-cell RNA-seq, and flow cytometry of GCBCs in vitro and in vivo. Whereas both signal pairs induced BLIMP1 in some GCBCs, only the IL-21R/CD40 combination induced IRF4hi/CD138+ cells, indicative of plasma cell differentiation, along with CCR6+/CD38+ memory B cell precursors. These findings reveal a second positive selection pathway in GCBCs, document rewired IL-21R signaling in GCBCs, and link specific TFH- and Ag-derived signals to GCBC differentiation.

Association between childhood trauma and affective lability among adolescents: A moderated mediation model.

BACKGROUND: Affective lability is an important feature of psychopathology. However, there is limited relevant research involving adolescents. To fill this research gap, the present study assessed the relationship between childhood trauma and affective lability among adolescents using a moderated mediation model. METHODS: A total of 3738 students were recruited from four high schools in Shenzhen, China, between September and December 2019. The participants completed self-reported questionnaires measuring childhood trauma, affective lability, body image dissatisfaction, and the experience of being bullied. Linear regression and moderated mediation analyses were used in this study. RESULTS: Linear regression analysis showed that emotional abuse and body image dissatisfaction positively predicted affective lability in boys and girls (all p < 0.001). Body image dissatisfaction mediated the relationship between emotional abuse and affective lability. In the moderated mediation model, being bullied moderated the direct path from emotional abuse to affective lability (p = 0.0236, p = 0.0188), and gender did not have a significant moderating effect on any direct or indirect path (all p > 0.05). LIMITATIONS: A causal relationship could not be ascertained due to the cross-sectional design, and the results cannot be generalized to other populations. CONCLUSIONS: The findings support that childhood trauma has an impact on affective lability in adolescents. Specifically, body image dissatisfaction and being bullied affect the relationship between emotional abuse and affective lability.

Machine learning-based early diagnosis of autism according to eye movements of real and artificial faces scanning.

Background: Studies on eye movements found that children with autism spectrum disorder (ASD) had abnormal gaze behavior to social stimuli. The current study aimed to investigate whether their eye movement patterns in relation to cartoon characters or real people could be useful in identifying ASD children. Methods: Eye-tracking tests based on videos of cartoon characters and real people were performed for ASD and typically developing (TD) children aged between 12 and 60 months. A three-level hierarchical structure including participants, events, and areas of interest was used to arrange the data obtained from eye-tracking tests. Random forest was adopted as the feature selection tool and classifier, and the flattened vectors and diagnostic information were used as features and labels. A logistic regression was used to evaluate the impact of the most important features. Results: A total of 161 children (117 ASD and 44 TD) with a mean age of 39.70 ± 12.27 months were recruited. The overall accuracy, precision, and recall of the model were 0.73, 0.73, and 0.75, respectively. Attention to human-related elements was positively related to the diagnosis of ASD, while fixation time for cartoons was negatively related to the diagnosis. Conclusion: Using eye-tracking techniques with machine learning algorithms might be promising for identifying ASD. The value of artificial faces, such as cartoon characters, in the field of ASD diagnosis and intervention is worth further exploring.

Prevalence of co-occurring severe depression and psychotic symptoms in college students and its relationship with childhood maltreatment.

BACKGROUND: It has been demonstrated that childhood maltreatment (CM) is associated with an increased risk of depression and psychotic symptoms. However, there is still a lack of studies on the prevalence of co-occurring severe depression and psychotic symptoms (CSDPS) and the association between CM and CSDPS among college students. OBJECTIVE: We aim to investigate the prevalence and demographic distribution of CSDPS among Chinese college students and to examine its relationship with CM. PARTICIPANTS AND SETTING: A total of 7351 college students aged 18 and above completed the survey. Finally, 6854 valid questionnaires were included for further analysis. METHODS: The Childhood Trauma Questionnaire and the item for witnessing domestic violence were used to assess the CM. The Prodromal Questionnaire-16 and the depression subscale of the Depression Anxiety and Stress-21 scale were used to assess psychotic symptoms and depressive symptoms. RESULTS: The prevalence of CSDPS was 1.47 % among the college students. The multivariate logistic regression analysis showed that emotional abuse and emotional neglect were associated with an increased risk of CSDPS (all p < 0.05). The risk of CSDPS was dramatically increased for individuals who had experienced ≥3 types of CM (OR = 22.929, p < 0.001), as compared to those who had experienced 1-2 types of CM (OR = 4.452, p < 0.001) and those without the experience of CM. CONCLUSION: CM was found to be associated with an increased risk of CSDPS among the college students. Notably, experiencing more types of CM was also associated with a higher risk of CSDPS.

High-Q Resonator-Inductor Using LiNbO3 Plate for Frequency Tuning in 1-5 GHz.

In this article, a new high quality factor ( Q ) inductor with piezoacoustic plate acoustic wave (PAW) resonators is presented. As indicated by the investigation of the acoustic wave propagation characteristics and transducer materials, the coupling coefficient ( k2 ) of the shear-horizontal plate (SH0) mode that propagates in the LiNbO3 plate increases to 55.7%, which leads to a wide inductive bandwidth of 29%. The longitudinal and transversal spurious modes are inhibited through novel edge reflector design and transducer engineering. The peak inductor quality factor ( [Formula: see text]) of the acoustic resonator-inductor is obtained as 347, and a large range of inductance values are achieved to be up to 49 nH by regulating the interdigital transducer (IDT) number of fingers (NF). It is noteworthy that a larger inductance is realized in a more miniaturized device. Furthermore, the wavelength-scaling-induced physics is investigated for frequency tuning in 1-5 GHz, which reveals the multifrequency ability on a single chip of the SH0 acoustic resonator-inductor.

High-Frequency and Spectrum-Clean Shear-Horizontal Acoustic Wave Resonators with AlN Overlay.

By bonding the sub-wavelength-thick lithium niobate (LiNbO3) layer to high-phase-velocity (vp) substrates, such as Si, the shear-horizontal (SH) modes no longer couple with the bulk modes leaking into substrates. As the propagation loss is no longer the major concern for these types of nonleaky SH wave devices, the YX-LiNbO3 with a low rotation angle providing ultra-large coupling coefficient (keff2) can be used. In addition, by overlaying a high-velocity layer such as AlN on top of LiNbO3/Si, the vp of the SH wave can be significantly enhanced at a small cost of keff2. By a careful design of the stack, both the wide-band spurious (Lamb wave) and near-band spurious (Rayleigh wave) are suppressed successfully. This paper focuses on the design of layered substrate not only to optimize its resonance characteristics-series frequency (fs), quality factor (Q), keff2, and temperature coefficient of frequency (TCF)-but also for eliminating the out-of-band spurious responses. The optimized substrate design demonstrates the minimal propagation loss, high fs of 3 GHz, large keff2 of 14.4% and a spurious-free response at 0-6 GHz. These novel nonleaky SH wave devices can potentially enable the low loss and wideband processing functions, which is promising for the 5G/6G radio frequency (RF) communication systems.

Prevalence and associated factors of school bullying among Chinese college students in Changsha, China.

BACKGROUND: School bullying has attracted worldwide attention for its adverse outcomes; however, there is still a lack of research among college students. The aim of this study was to investigate the prevalence of school bullying victimization and the associated factors among Chinese college students. METHODS: 8098 Chinese college students from two universities in Hunan province were recruited in this cross-sectional study, and data on participants' demographic information, bullying history, suicidal behaviors, anxiety (Self-Rating Anxiety Scale) and depression (Self-reporting Depression Scale) were collected. Binary logistic regression was used to analyze the independent correlates of school bullying. RESULTS: The prevalence of school bullying was 8.03% in our study. Gender (OR,0.792;95%CI[0.660,0.950]; p = 0.012); depression (OR,1.979; 95%CI[1.359,2.883]; p < 0.001); anxiety (OR,1.996; 95%CI[1.388, 2.869]; p < 0.001); suicidal ideation (OR,1.353;95%CI[1.087,1.684]; p = 0.007); suicide attempts (OR,1.772;95%CI[1.306,2.403]; p < 0.001); family income between 30,000 and 70,000/year (yuan) (OR,0.763;95% CI[0.627,0.929]; p = 0.007) and family income more than 70,000/year (yuan) (OR,0.578;95%CI[0.461,0.725]; p < 0.001) were independent correlates of school bullying. The bullying score was positively correlated with physical or mental disorder history, family history of mental disorder, suicidal ideation, suicide plans, suicide attempts, anxiety, depression, smoking and drinking alcohol (all p < 0.05), and negatively correlated with right-handedness, good relationship with parents and family income (all p < 0.05). LIMITATIONS: No causal relationship could be drawn due to the cross-sectional design. CONCLUSION: School bullying is quite common among college students. In order to improve students' mental health and prevent suicide, we should pay attention to the negative effects of bullying victimization such as depression, anxiety, suicidal behaviors and so on, apart from putting in place anti-bullying interventions.

Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (Paralichthys olivaceus).

Japanese flounder (Paralichthys olivaceus) responsive mechanisms to hypoxia are still not fully understood. Therefore, we performed an acute hypoxic treatment (dissolved oxygen at 2.07 ± 0.08 mg/L) on Japanese flounder. It was confirmed that the hypoxic stress affected the physiological phenotype through changes in blood physiology (RBC, HGB, WBC), biochemistry (LDH, ALP, ALT, GLU, TC, TG, ALB), and hormone (cortisol) indicators. Hypoxia inducible factor-1 (HIF-1), an essential oxygen homeostasis mediator in organisms consisting of an inducible HIF-1α and a constitutive HIF-1ß, and its target gene LDH-A were deeply studied. Results showed that HIF-1α and LDH-A genes were co-expressed and significantly affected by hypoxic stress. The dual-luciferase reporter assay confirmed that transcription factor HIF-1 transcriptionally regulated the LDH-A gene, and its transcription binding sequence was GGACGTGA located at -2343~-2336. The DNA methylation status of HIF-1α and LDH-A genes were detected to understand the mechanism of environmental stress on genes. It was found that hypoxia affected the HIF-1α gene and LDH-A gene methylation levels. The study uncovered HIF-1/LDH-A signaling pathway responsive mechanisms of Japanese flounder to hypoxia in epigenetic modification and transcriptional regulation. Our study is significant to further the understanding of environmental responsive mechanisms as well as providing a reference for aquaculture.