Influences of Pre-Existing Fissure Angles and Bridge Angles on Concrete Tensile Failure Characteristics: Insights from Meshless Numerical Simulations.

The existence of cracks is a key factor affecting the strength of concrete. However, traditional numerical methods still have some limitations in the simulation of crack growth in fissured concrete structures. Based on this background, the numerical treatment method of particle failure in smoothed particle hydrodynamics (SPH) is proposed, and the generation method for concrete meso-structures under the smoothed particle hydrodynamics (SPH) framework is developed. The concrete meso-models under different pre-existing micro-fissure inclinations and bridge angles (the inner tip line of the double pre-existing micro-fissure is defined as a bridge, and the angle between the bridge and the horizontal direction is defined as the bridge angle) were established, and numerical simulations of the crack propagation processes of concrete structures under tensile stress were carried out. The main findings were as follows: The concrete meso-structures and the pre-existing micro-fissures all have great impacts on the final failure modes of concrete. The stress-strain curve of the concrete model presents four typical stages. Finally, the crack initiation and propagation mechanisms of fissured concrete are discussed, and the application of smoothed particle hydrodynamics (SPH) in crack simulations of fissured concrete is prospected.

Inhibition of RAN attenuates influenza a virus replication and nucleoprotein nuclear export.

Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.

Prevalence and clinical correlates of benzodiazepine use in the patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population. METHODS: A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use. RESULTS: The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001). LIMITATIONS: The cross-sectional design of this study precludes establishing causal relationships. CONCLUSION: Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD.

Experimental and Meshless Numerical Simulations on the Crack Propagation of Semi-Circular Bending Specimens Containing X-Shaped Fissures Under Three-Point Bending.

Cracks in rock and concrete have a great adverse effect on the stability of engineering structures; however, there are few studies on X-shaped fissures which widely exist in rock and concrete structures. Based on this background, three-point bending fracture tests of SCB specimens containing X-shaped fissures are carried out. The momentum equations in the SPH method are improved, and the crack propagations of SCB specimens under three-point bending are simulated. The results show that cracks grow simply along the vertical direction in the sample with no X-shaped fissures, and the existence of an X-shaped fissure changes the crack growth path and final failure modes of the SCB samples. The crack propagation simulation results are consistent with the experimental results, which verifies the rationality of the improved SPH method. The load-displacement curves mainly present three typical stages: the initial compaction stage, linear elastic deformation stage, and failure stage. The peak load decreases first then increases with an increase in eccentricity. With an increase in X-shaped fissure length and decrease in X-shaped fissure angle, the peak load decreases. The damage counts remain at 0 at the initial loading stage, corresponding to the initial compaction stage and the linear elastic deformation stage, and increase sharply at the later loading stage, corresponding to the failure stage, which is consistent with the experimental results. The influence mechanisms of X-shaped fissures on the crack propagation paths are discussed; the existence of different X-shaped fissure morphologies aggravate the tensile stress concentration at specific positions, leading to different crack propagation modes in the experiments. The research results can provide a certain reference for understanding the failure mechanisms of engineering structures containing X-shaped fissures and promote the applications of the SPH method into the simulations of cross-fissure crack propagations.

Trusting young children to help causes them to cheat less.

Trust and honesty are essential for human interactions. Philosophers since antiquity have long posited that they are causally linked. Evidence shows that honesty elicits trust from others, but little is known about the reverse: does trust lead to honesty? Here we experimentally investigated whether trusting young children to help can cause them to become more honest (total N = 328 across five studies; 168 boys; mean age, 5.94 years; s.d., 0.28 years). We observed kindergarten children's cheating behaviour after they had been entrusted by an adult to help her with a task. Children who were trusted cheated less than children who were not trusted. Our study provides clear evidence for the causal effect of trust on honesty and contributes to understanding how social factors influence morality. This finding also points to the potential of using adult trust as an effective method to promote honesty in children.

The RNA-Splicing Ligase RTCB Promotes Influenza A Virus Replication by Suppressing Innate Immunity via Interaction with RNA Helicase DDX1.

The RNA-splicing ligase RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB) is a catalytic subunit of the tRNA-splicing ligase complex, which plays an essential role in catalyzing tRNA splicing and modulating the unfolded protein response. However, the function of RTCB in influenza A virus (IAV) replication has not yet been described. In this study, RTCB was revealed to be an IAV-suppressed host factor that was significantly downregulated during influenza virus infection in several transformed cell lines, as well as in primary human type II alveolar epithelial cells, and its knockout impaired the propagation of the IAV. Mechanistically, RTCB depletion led to a robust elevation in the levels of type I and type III IFNs and proinflammatory cytokines in response to IAV infection, which was confirmed by RTCB overexpression studies. Lastly, RTCB was found to compete with DDX21 for RNA helicase DDX1 binding, attenuating the DDX21-DDX1 association and thus suppressing the expression of IFN and downstream IFN-stimulated genes. Our study indicates that RTCB plays a critical role in facilitating IAV replication and reveals that the RTCB-DDX1 binding interaction is an important innate immunomodulator for the host to counteract viral infection.

Default settings affect children's decisions about whether to be honest.

Behavioral economics research has revealed that our decision-making can be biased by default settings. That is, all other things being equal, adults tend to choose default options even when the effort involved in choosing other options is minimal. Extensive evidence shows that default settings can systematically influence adult decisions in a wide variety of domains (e.g., pension choices, organ donation), but little is known about their developmental origin. Of interest in the present research is whether default settings can influence young children's decisions about whether to be honest. We investigated this question in two studies of 5- and 6-year-old Chinese children (total N = 120; 60 girls; Mage = 5.81, SDage = 0.14). Each study used a specially designed device that allowed children to play a guessing game in either a Cheating Default condition in which they would cheat by doing nothing or in an Honesty Default condition in which they would be honest by doing nothing. In each condition, they had the option of taking a trivially easy action to override the default (pushing a button in Study 1 or moving a screen in Study 2). In both studies, children decided to cheat significantly more often in the Cheating Default condition than in the Honesty Default condition. Additionally, overall cheating rates were significantly higher in Study 2 than in Study 1 (55% vs. 25%), which suggests that even though the default setting effect generalized across different actions, the specific action in question can also affect the cheating rate. Taken together, these results indicate that default setting effects that have been observed in adults have origins in childhood, and they point toward new ways to use nudges to promote positive social development and moral decision-making.

Glycyrrhizic Acid-Based Carbonized Dots Boost Antiviral Activity against Influenza A Virus via Multisite Inhibition Mechanisms.

Influenza A virus (IVA) has been continuously causing pandemics in several animal hosts and has become a worldwide public health threat. Currently, antiviral drugs have become associated with a lot of side effects and limited activity against emerging drug-resistant influenza viruses. Therefore, the development of novel antiviral drugs is of great importance. In this study, we synthesized a kind of carbon dots (CDs) with high dispersibility from glycyrrhizic acid (GA) using a simple dry heating method. Compared with glycyrrhizic acid alone, GA-CDs exhibit superior solubility and significantly improve the antiviral property against IVA. Investigation of the mechanism revealed that GA-CDs act against IVA mainly by inhibiting viral internalization, replication of the viral genome, neuraminidase activity, and host inflammatory responses. More importantly, in a mouse model, GA-CDs can significantly alleviate the clinical symptoms and decrease mortality and lung viral titers. In vitro and in vivo experiments demonstrate that GA-CDs possess extraordinary therapeutic effects; therefore, we propose that GA-CDs may be a promising alternative therapy for IVA infection.

Academic cheating interferes with learning among middle school children.

There has been extensive research on the causes of academic cheating, but little is known about its consequences. The current research sought to fill this gap in the literature by examining how cheating by middle school children (total N = 198) affects their learning outcomes. In a naturalistic paradigm, children scored a math test they had taken previously, which gave them an opportunity to cheat by falsely scoring incorrect answers to be correct. Results from this phase showed that 54 % of the children cheated on at least one question. One week later, the children took the same test again, but this time without being given an opportunity to cheat. Among children who cheated, items they had answered incorrectly on the first round showed significantly less improvement on the second round if they had dishonestly scored them as correct rather than honestly scoring them as incorrect. This finding provides the first experimental evidence that academic cheating can interfere with children's learning.

YWHAG inhibits influenza a virus replication by suppressing the release of viral M2 protein.

Influenza A virus (IAV) poses a serious threat to human life and property. The IAV matrix protein 2 (M2) is significant in viral budding. Increasing studies have proven the important roles of host factors in IAV replication. In this study, immunoprecipitation combined with mass spectrometry revealed that the host protein tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG), which belongs to the 14-3-3 protein scaffold family, interacts with M2. Their interactions were further confirmed by co-immunoprecipitation (Co-IP), immunofluorescence, and confocal microscopy of virus-infected HeLa cells. Moreover, we constructed YWHAG-KO and YWHAG-overexpressing cells and found that YWHAG knockout significantly increased viral production, whereas its overexpression reduced the titer of virus progeny. Therefore, YWHAG is a negative regulatory factor during IAV infection. Further, YWHAG knockout or overexpression had no effect on the binding, entry, or viral RNA replication in the early stages of the virus life cycle. On the contrary, it impaired the release of virions at the plasma membrane as determined using transmission electron microscopy and suppressed the M2-mediated budding of the influenza virus. Importantly, the H158F mutation of YWHAG was found to affect interaction with M2 and its budding. Collectively, our work demonstrates that YWHAG is a novel cellular regulator that targets and mediates the interaction and release of M2.

Dataset of the effect of difficulty messaging on academic cheating in middle school Chinese children.

The present dataset was reported in a paper entitled "Effects of test difficulty messaging on academic cheating among middle school children" [1]. It reports the findings of an experimental study that used a naturalistic math test-taking paradigm to assess children's academic cheating behavior under different test difficulty messaging conditions. The participants were Grade 8 middle school children (N = 201). The primary dependent measures were whether each participant spontaneously decided to cheat (presence of cheating), and among participants who cheated, the specific number of test items on which they cheated (extent of cheating). We used logistic regression, ANOVA, and Pearson correlation to assess whether various predictor variables (e.g., conditions) predicted the presence of cheating or the extent of cheating. This dataset should be of interest to researchers who are interested in the development of moral behavior in children generally, and academic dishonesty in particular.

PSMD12-Mediated M1 Ubiquitination of Influenza A Virus at K102 Regulates Viral Replication.

The M1 of influenza A virus (IAV) is important for the virus life cycle, especially for the assembly and budding of viruses, which is a multistep process that requires host factors. Identifying novel host proteins that interact with M1 and understanding their functions in IAV replication are of great interest in antiviral drug development. In this study, we identified 19 host proteins in DF1 cells suspected to interact with the M1 protein of an H5N6 virus through immunoprecipitation (IP)/mass spectrometry. Among them, PSMD12, a 26S proteasome regulatory subunit, was shown to interact with influenza M1, acting as a positive host factor in IAV replication in avian and human cells. The data showed that PSMD12 promoted K63-linked ubiquitination of M1 at the K102 site. H5N6 and PR8 with an M1-K102 site mutant displayed a significantly weaker replication ability than the wild-type viruses. Mechanistically, PSMD12 promoted M1-M2 virus-like particle (VLP) release, and an M1-K102 mutation disrupted the formation of supernatant M1-M2 VLPs. An H5N6 M1-K102 site mutation or knockdown PSMD12 disrupted the budding release of the virus in chicken embryo fibroblast (CEF) cells, which was confirmed by transmission electron microscopy. Further study confirmed that M1-K102 site mutation significantly affected the virulence of H5N6 and PR8 viruses in mice. In conclusion, we report the novel host factor PSMD12 which affects the replication of influenza virus by mediating K63-linked ubiquitination of M1 at K102. These findings provide novel insight into the interactions between IAV and host cells, while suggesting an important target for anti-influenza virus drug research. IMPORTANCE M1 is proposed to play multiple biologically important roles in the life cycle of IAV, which relies largely on host factors. This study is the first one to identify that PSMD12 interacts with M1, mediates K63-linked ubiquitination of M1 at the K102 site, and thus positively regulates influenza virus proliferation. PSMD12 promoted M1-M2 VLP egress, and an M1-K102 mutation affected the M1-M2 VLP formation. Furthermore, we demonstrate the importance of this site to the morphology and budding of influenza viruses by obtaining mutant viruses, and the M1 ubiquitination regulator PSMD12 has a similar function to the M1 K102 mutation in regulating virus release and virus morphology. Additionally, we confirm the reduced virulence of H5N6 and PR8 (H1N1) viruses carrying the M1-K102 site mutation in mice. These findings provide novel insights into IAV interactions with host cells and suggest a valid and highly conserved candidate target for antiviral drug development.

Effects of test difficulty messaging on academic cheating among middle school children.

Academic cheating is a serious worldwide problem that begins during childhood. However, to date there has been little research on academic cheating with children before high school age. The current study used a naturalistic experimental paradigm to evaluate the possibility that systematically manipulating messages about the difficulty of a test can affect whether middle school children (N = 201) would cheat by reporting a falsely inflated test score. We found that test difficulty messaging significantly affected children's cheating behavior. Specifically, telling children that a test was either easy or hard produced higher rates of cheating than telling them that the difficulty level was on par with their current skills. In addition, among the children who chose to cheat, telling them that the test was easy led to a greater degree of cheating. These findings are consistent with theories of academic cheating that point to the importance of approach and avoidance motives in achievement motivation. The findings also suggest that simple messaging can have a significant impact on children's moral behavior and that seemingly innocuous messages such as describing the difficulty of a test can influence children's decisions about whether and how much to cheat.

Effects of Trust and Threat Messaging on Academic Cheating: A Field Study.

Morality-based interventions designed to promote academic integrity are being used by educational institutions around the world. Although many such approaches have a strong theoretical foundation and are supported by laboratory-based evidence, they often have not been subjected to rigorous empirical evaluation in real-world contexts. In a naturalistic field study (N = 296), we evaluated a recent research-inspired classroom innovation in which students are told, just prior to taking an unproctored exam, that they are trusted to act with integrity. Four university classes were assigned to a proctored exam or one of three types of unproctored exam. Students who took unproctored exams cheated significantly more, which suggests that it may be premature to implement this approach in college classrooms. These findings point to the importance of conducting ecologically valid and well-controlled field studies that translate psychological theory into practice when introducing large-scale educational reforms.

Using environmental nudges to reduce academic cheating in young children.

Previous research on nudges conducted with adults suggests that the accessibility of behavioral options can influence people's decisions. The present study examined whether accessibility can be used to reduce academic cheating among young children. We gave children a challenging math test in the presence of an answer key they were instructed not to peek at, and manipulated the accessibility of the answer key by placing various familiar objects on top of it. In Study 1, we used an opaque sheet of paper as a two-dimensional occluder, and found that it significantly reduced cheating compared to a transparent plastic sheet. In Study 2, we used a three-dimensional occluder in the form of a tissue box to make the answer key appear even less accessible, and found it was significantly more effective in reducing cheating than the opaque paper. In Study 3, we used two symbolic representations of the tissue box: a realistic color photo and a line drawing. Both representations were effective in reducing cheating, but the realistic photo was more effective than the drawing. These findings demonstrate that manipulating accessibility can be an effective strategy to nudge children away from cheating in an academic context. They further suggest that different types of everyday objects and their symbolic representations can differentially impact children's moral behavior.

139D in NS1 Contributes to the Virulence of H5N6 Influenza Virus in Mice.

H5N6, the highly pathogenic avian influenza A virus (IAV) of clade 2.3.4.4, causes global outbreaks in poultry. H5N6 has become the dominant IAV subtype in waterfowls and causes human infections with high mortality rates. Here, we isolated two strains of H5N6, XGD and JX, from chickens and ducks, respectively. Growth kinetics were evaluated in duck embryo fibroblasts, chicken embryo fibroblasts, Madin-Darby canine kidney cells, and A549 lung carcinoma cells. Receptor binding specificity was analyzed via sialic acid-binding activity assay. The virulence of each strain was tested in BALB/c mice, and recombinant viruses were constructed via reverse genetics to further analyze the pathogenicity. The two strains showed no significant differences in growth kinetics in vitro; however, JX was more virulent in mice than XGD. We also identified 13 mutations in six viral proteins of the two strains through genetic analysis. Our study showed that the NS1 protein played a crucial role in enhancing the virulence of JX. Specifically, the amino acid 139D in NS1 contributed to the high pathogenicity. Therefore, 139D in NS1 might provide insight into the underlying mechanism of IAV adaptation in mammals.

Overheard conversations can influence children's generosity.

Understanding the factors that promote the development of generosity has both theoretical and practical importance. This study examines one potential influence: overheard conversations that contain evaluative statements about the behavior of others that were described as widely shared opinions. In Study 1 (N = 120), younger (mean age 4.1 years old) and older (mean age 5.9 years old) participants overheard two adults discuss a target child's act of generosity, and in a between-subjects manipulation, the conversation included either praise for the target child, or criticism. Participants in the older group were more likely to behave generously on a distribution task if the overheard conversation involved praise rather than criticism, but the participants in the younger group showed no such effect. Study 2 (N = 150) and Study 3 (N = 60) were preregistered follow-up studies that included older children only (a 5-year-old group). Study 2 showed that children were again more likely to share after overhearing a conversation in which an individual who behaved generously was described in favorable terms, and the same effect was seen when the overheard conversation involved criticism of an individual who did not share. The procedure of Study 3 matched that of Study 1, except the distributions were made in private, and the overheard conversation effect was seen once again. These findings suggest that by age 5, children can use information they hear about individuals who are not present to guide their own behavior, and that overheard evaluative comments can promote generosity.

hnRNPH2 as an Inhibitor of Chicken MDA5-Mediated Type I Interferon Response: Analysis Using Chicken MDA5-Host Interactome.

RIG-I and MDA5 are two key pattern recognition receptors that sense the invasion of RNA viruses and initiate type I interferon (IFN) response. Although these receptors are generally conserved in vertebrates, RIG-I is absent in chickens, whereas MDA5 is present. Chicken MDA5 (chMDA5) plays a pivotal role in sensing the invasion of RNA viruses into cells. However, unlike mammalian MDA5, where there are in-depth and extensive studies, regulation of the chMDA5-mediated signaling pathway remains unexplored. In this study, we performed a pulldown assay and mass spectrometry analysis to identify chicken proteins that could interact with the N terminal of chMDA5 (chMDA5-N) that contained two CARDs responsible for binding of the well-known downstream adaptor MAVS. We found that 337 host proteins could potentially interact with chMDA5-N, which were integrated to build a chMDA5-N-host association network and analyzed by KEGG pathway and Gene Ontology annotation. Results of our analysis revealed that diverse cellular processes, such as RNA binding and transport and protein translation, ribosome, chaperones, and proteasomes are critical cellular factors regulating the chMDA5-mediated signaling pathway. We cloned 64 chicken genes to investigate their effects on chMDA5-mediated chicken IFN-ß production and confirmed the association of chicken DDX5, HSPA8, HSP79, IFIT5, PRDX1, and hnRNPH2 with chMDA5-N. In particular, we found that chicken hnRNPH2 impairs the association between chMDA5-N and MAVS and thus acts as a check on the chMDA5-mediated signaling pathway. To our knowledge, this study is the first to analyze the chicken MDA5-host interactome, which provides fundamental but significant insights to further explore the mechanism of chicken MDA5 signaling regulation in detail.

Transcriptomic Analysis of the Chicken MDA5 Response Genes.

RIG-I and MDA5 are two key pattern recognition receptors that sense RNA virus invasion, but RIG-I is absent in chickens. Although chickens have intact MDA5, the genes downstream of chicken MDA5 (chMDA5) that may mediate antiviral response are not well studied. We compared the transcriptional profile of chicken embryonic fibroblasts (DF1) transfected with chMDA5, and poly(I:C), using RNA-seq. Transfected chMDA5 and poly(I:C) in DF1 cells were associated with the marked induction of many antiviral innate immune genes compared with control. Interestingly, nine interferon-stimulated genes (ISGs) were listed in the top 15 upregulated genes by chMDA5 and poly(I:C) transfection. We used real-time PCR to confirm the upregulation of the nine ISGs, namely, MX1, IFI6, IFIT5, RSAD2, OASL, CMPK2, HELZ2, EPSTI1, and OLFML1, by chMDA5 and poly(I:C) transfection in DF1 cells. However, avian influenza virus H5N6 infection only increased MX1, IFI6, IFIT5, RSAD2, and OASL expression levels. Further study showed that the overexpression of these five genes could significantly inhibit H5N6 virus replication. These results provide some insights into the gene expression pattern induced by chMDA5, which would be beneficial for understanding and identifying innate immune genes of chicken that may lead to new antiviral therapies.

Transcriptome Profiles of Highly Pathogenic Pure Avian H7N9 Virus-Infected Lungs of BALB/c Mice.

Avian influenza A (H7N9) viruses emerged in China in 2013 and caused a zoonotic disease associated with a high case-fatality ratio of more than 30%. Transcriptional profiles obtained using animal models reveal host responses to the disease, thereby providing insights into disease pathogenesis. Therefore, we aimed to characterize the host responses of the H7N9 virus infected-mouse lungs in this study. First, we isolated an avian-originated H7N9 strain, which was shown to be highly pathogenic to both chickens and mice. Genomic analysis results suggested that a 12-nucleotide-insertion was present at the hemagglutinin cleavage site, and both the hemagglutinin and neuraminidase genes belonged to the Yangtze River Delta lineage. RNA sequencing results revealed 566 differentially expressed genes in the H7N9-infected lungs. Moreover, transcriptome analysis revealed that over-activated antiviral signals and intense interferon-stimulated gene products possibly contributed to the high virulence of the virus in mice. Importantly, lung concentrations of inflammatory cytokines, including interleukin-1ß and interleukin-6, interferon-ß, and tumor necrosis factor-α, were upregulated in response to H7N9 virus infection. Overall, the present study provided a comprehensive understanding of H7N9 virus pathogenicity and correlated host immune responses.