Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway.

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.

The reactivation kinetic analysis, molecular docking, and dynamics of oximes against three V-type nerve agents inhibited four human cholinesterases.

Nerve agents pose significant threats to civilian and military populations. The reactivation of acetylcholinesterase (AChE) is critical in treating acute poisoning, but there is still lacking broad-spectrum reactivators, which presents a big challenge. Therefore, insights gained from the reactivation kinetic analysis and molecular docking are essential for understanding the behavior of reactivators towards intoxicated AChE. In this research, we present a systematic determination of the reactivation kinetics of three V agents-inhibited four human ChEs [(AChE and butyrylcholinesterase (BChE)) from either native or recombinant resources, namely, red blood cell (RBC) AChE, rhAChE, hBChE, rhBChE) reactivated by five standard oximes. We unveiled the effect of native and recombinant ChEs on the reactivation kinetics of V agents ex vitro, where the reactivation kinetics characteristic of Vs-inhibited BChE was reported for the first time. In terms of the inhibition type, all of the five oxime reactivators exhibited noncompetitive inhibition. The inhibition potency of these reactivators would not lead to the difference in the reactivation kinetics between native and recombinant ChE. Despite the significant differences between the native and recombinant ChEs observed in the inhibition, aging, and spontaneous reactivation kinetics, the reactivation kinetics of V agent-inhibited ChEs by oximes were less differentiated, which were supported by the ligand docking results. We also found differences in the reactivation efficiency between five reactivators and the phosphorylated enzyme, and molecular dynamic simulations can further explain from the perspectives of conformational stability, hydrogen bonding, binding free energies, and amino acid contributions. By Poisson-Boltzmann surface area (MM-PBSA) calculations, the total binding free energy trends aligned well with the experimental kr2 values.

The cGAS/STING signaling pathway is involved in sevoflurane induced neuronal necroptosis via regulating microglia M1 polarization.

OBJECTIVE: The specific mechanisms of sevoflurane-induced neurotoxicity are still undetermined. The aim of the current study was to investigate the role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in sevoflurane-induced neuronal necroptosis. METHODS: BV2 microglial cells were divided into a control group and a 4% sevoflurane exposure group. Western blotting was used to detect expression of the M1 polarization marker inducible nitric oxide synthase (iNOS). RNA was collected for RNA sequencing analysis. After STING knockdown in microglia, western blotting was performed to examine expression of the pro-inflammatory markers CD16 and CD32. The tumor necrosis factor-α (TNF-α) level in media was detected using an enzyme-linked immunosorbent assay. BV2 microglia conditioned media was collected to incubate HT22 neuronal cells, and their cell activity was measured using a CCK8 assay. Calcium was observed by fluorescence. Western blotting was performed to evaluate receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) expression. Neuronal necroptosis rate were detected using flow cytometry. RESULTS: Sevoflurane exposure promoted microglial M1 polarization. The cGAS/STING pathway was screened and identified by RNA sequencing analysis of sevoflurane-exposed microglia and the control group. Compared with the control group, STING knockdown in microglia rescued the amoeboid morphology, inhibited TNF-α release, and significantly decreased iNOS, CD16, and CD32 expression. Moreover, calcium ions and necroptosis within neurons were decreased, and RIPK1, RIPK3, and p-MLKL expression was markedly decreased in microglia media culture with STING knockdown. CONCLUSION: These results suggest that sevoflurane can regulate microglial M1 polarization by activating the cGAS/STING signaling pathway and increasing immune factor release, thus accelerating the neuronal necroptosis induced by calcium overload.

Genetically engineered membrane-based nanoengagers for immunotherapy of pancreatic cancer.

Modulating macrophages presents a promising avenue in tumor immunotherapy. However, tumor cells have evolved mechanisms to evade macrophage activation and phagocytosis. Herein, we introduced a bispecific antibody-based nanoengager to facilitate the recognition and phagocytosis of tumor cells by macrophages. Specifically, we genetically engineered two single chain variable fragments (scFv) onto cell membrane: anti-CD40 scFv for engaging with macrophages and anti-Claudin18.2 (CLDN18.2) scFv for interacting with tumor cells. These nanoengagers were further constructed by coating scFv-anchored membrane into PLGA nanoparticle core. Our developed nanoengagers significantly boosted immune responses, including increased recognition and phagocytosis of tumor cells by macrophages, enhanced activation and antigen presentation, and elevated cytotoxic T lymphocyte activity. These combined benefits resulted in enhancing antitumor efficacy against highly aggressive "cold" pancreatic cancer. Overall, this study offers a versatile nanoengager design for immunotherapy, achieved through genetically engineering to incorporate antibody-anchored membrane.

The Norepinephrine-QseC Axis Aggravates F. nucleatum-associated Colitis Through Interkingdom Signaling.

AIMS: Inflammatory bowel disease (IBD) is associated with F. nucleatum, and chronic stress can increase the risk of aggravation. However, whether norepinephrine (NE) can enhance the pathogenicity of F. nucleatum to aggravate dextran sulfate sodium salt (DSS)-induced colitis is unclear. METHODS: Transcriptome sequencing was used to identify differentially expressed genes in bacteria treated with NE. Affinity testing and molecular docking were applied to calculate and predict the binding of NE and Quorum sensing  regulators C (QseC). The pathogenicity of Fusobacterium nucleatum treated with NE and QseC inhibitors was examined in vitro and further verified using the IBD mouse model induced by DSS. RESULTS: Norepinephrine could bind to QseC directly to upregulate the quorum sensing pathway of F. nucleatum and enhance its virulence gene expression (FadA, FomA, Fap2) and invasiveness in vitro. Meanwhile, it promoted the invasion of F. nucleatum into the intestine and increased the expression of host inflammatory cytokines (IL-6, IL-1ß) to aggravate colonic inflammation in IBD mice. The QseC inhibitor LED209 inhibited the effect of NE on F. nucleatum and partially restored short-chain fatty acid (SCFA)-producing bacteria (Prevotellaceae, Lactobacillaceae) to attenuate colonic inflammation in IBD mice. CONCLUSIONS: Generally, the NE-QseC axis enhanced the pathogenicity of F. nucleatum through interkingdom signaling to aggravate colonic inflammation in IBD mice. We see that QseC may be a potential target for microbiota management of IBD under chronic pressure.

Norepinephrine could bind to QseC directly to enhance the pathogenicity of F. nucleatum to aggravate colonic inflammation. The QseC inhibitor inhibited the effect of NE on F. nucleatum and partially restored short-chain fatty acid­producing bacteria to attenuate colonic inflammation.

Newly discovered variants in unexplained neonatal encephalopathy.

BACKGROUND: The genetic background of neonatal encephalopathy (NE) is complicated and early diagnosis is beneficial to optimizing therapeutic strategy for patients. METHODS: NE Patients with unclear etiology received regular clinical tests including ammonia test, metabolic screening test, amplitude-integrated electroencephalographic (aEEG) monitoring, brain Magnetic Resonance Imaging (MRI) scanning, and genetic test. The protein structure change was predicted using Dynamut2 and RoseTTAFold. RESULTS: 15 out of a total of 113 NE Patients were detected with newly reported pathogenic variants. In this sub-cohort, (1) seizure was the primary initial symptoms; (2) four patients had abnormal metabolic screening results, and two of them were also diagnosed with excessive blood ammonia concentration; (3) the brain MRI results were irregular in three infants and the brain waves were of moderate-severe abnormality in about a half of the patients. The novel pathogenic variants discovered in this study belonged to 12 genes, and seven of them were predicted to introduce a premature translation termination. In-silicon predictions showed that four variants were destructive to the protein structure of KCNQ2. CONCLUSION: Our study expands the mutation spectrum of genes associated with NE and introduces new evidence for molecular diagnosis in this newborn illness.

Reprogramming macrophage by targeting VEGF and CD40 potentiates OX40 immunotherapy.

The low clinical response rate of checkpoint blockades, such as PD-1 and CTLA-4, highlighted the requirements of agonistic antibodies to boost optimal T cell responses. OX40, a co-stimulatory receptor on the T cells, plays a crucial role in promoting T cell survival and differentiation. However, the clinical efficacy of anti-OX40 agonistic antibodies was unimpressive. To explore the mechanism underlying the action of anti-OX40 agonists to improve the anti-tumor efficacy, we analyzed the dynamic changes of tumor-infiltrating immune cells at different days post-treatments using single-cell RNA-sequencing (scRNA-seq). In this study, we found that tumor-infiltrating regulatory T (Treg) cells were reduced after two rounds of anti-OX40 treatment, but the increase of infiltration and activation of CD8+ effector T cells, as well as M1 polarization in the tumor were only observed after three rounds of treatments. Moreover, our group first analyzed the antitumor effect of anti-OX40 treatments on regulating the macrophages and discovered the dynamic changes of vascular endothelial growth factor (VEGF) and CD40 signaling pathways on macrophages, indicating their possibility to being potential combination targets to improve the anti-OX40 agonists efficacy. The combination of VEGFR inhibitors or anti-CD40 agonist antibody with anti-OX40 agonists exhibited more remarkable inhibition of tumor growth. Therefore, the mechanism-driven combination of anti-OX40 agonists with VEGFR inhibitors or anti-CD40 agonists represented promising strategies.

The application and effect of predictive nursing in the prevention of accidental events during operations for SMI patients.

OBJECTIVE: To explore the status and influencing factors of job burnout among psychiatric nurses and provide a reference for hospital managers to carry out occupational and psychological interventions. METHODS: Between September 2021 and September 2022, the psychiatric nurses in Wuhan Wudong Hospital (Wuhan Second Psychiatric Hospital) were selected as research participants using convenience sampling. The Chinese version of the nursing burnout scale was used to investigate the psychiatric nurses in the hospital, and a multiple linear regression analysis was performed on the factors affecting job burnout. RESULTS: Among the 121 psychiatric nurses, 57.85 % had no or only mild job burnout, 36.36 % had mild to moderate job burnout and 5.79 % had severe job burnout. The one-way analysis of variance indicated that there were statistical differences in the scores in terms of marital status, educational background, working years, income, work departments and shifts (p < 0.05). The multiple linear regression analysis indicated that the main influencing factors of job burnout were working years and work department (p < 0.05). CONCLUSION: The detection rate of nurses' job burnout in the featured psychiatric hospital was 42.10 %. The main influencing factors of job burnout were working years and work department, and targeted intervention can be carried out according to these two factors.

Gut microbiota-derived autoinducer-2 regulates lung inflammation through the gut-lung axis.

OBJECTIVE: This study aimed to determine whether autoinducer-2 (AI-2), a crucial bacterial metabolite and quorum sensing molecule, is involved in lung immunity through the gut-lung axis. METHODS: The level of AI-2 and the gut microbiome composition were analysed in the stools from pneumonic patients and the mouse model of acute lung injury. The effect of AI-2 on lung inflammation was further investigated in the mouse model. RESULTS: The diversity of the faecal microbiota was reduced in pneumonic patients treated with antibiotics compared with healthy volunteers. The AI-2 level in the stool was positively correlated with inflammatory molecules in the serum of pneumonic patients. Intraperitoneal injection of AI-2 reinforced lung inflammation in the acute lung injury mouse model, characterized by increased secretion of inflammatory molecules, including IL-6, IL-1ß, C-C chemokines, and CXCL chemokines, which were alleviated by the AI-2 inhibitor D-ribose. CONCLUSIONS: Our results suggested that gut microbiota-derived AI-2 could modulate lung inflammation through the gut-lung axis.

Prognostic prediction of idiopathic membranous nephropathy using interpretable machine learning.

BACKGROUND: Established prognostic models of idiopathic membranous nephropathy (IMN) were limited to traditional modeling methods and did not comprehensively consider clinical and pathological patient data. Based on the electronic medical record (EMR) system, machine learning (ML) was used to construct a risk prediction model for the prognosis of IMN. METHODS: Data from 418 patients with IMN were diagnosed by renal biopsy at the Fifth Clinical Medical College of Shanxi Medical University. Fifty-nine medical features of the patients could be obtained from EMR, and prediction models were established based on five ML algorithms. The area under the curve, recall rate, accuracy, and F1 were used to evaluate and compare the performances of the models. Shapley additive explanation (SHAP) was used to explain the results of the best-performing model. RESULTS: One hundred and seventeen patients (28.0%) with IMN experienced adverse events, 28 of them had compound outcomes (ESRD or double serum creatinine (SCr)), and 89 had relapsed. The gradient boosting machine (LightGBM) model had the best performance, with the highest AUC (0.892 ± 0.052, 95% CI 0.840-0.945), accuracy (0.909 ± 0.016), recall (0.741 ± 0.092), precision (0.906 ± 0.027), and F1 (0.905 ± 0.020). Recursive feature elimination with random forest and SHAP plots based on LightGBM showed that anti-phospholipase A2 receptor (anti-PLA2R), immunohistochemical immunoglobulin G4 (IHC IgG4), D-dimer (D-DIMER), triglyceride (TG), serum albumin (ALB), aspartate transaminase (AST), ß2-microglobulin (BMG), SCr, and fasting plasma glucose (FPG) were important risk factors for the prognosis of IMN. Increased risk of adverse events in IMN patients was correlated with high anti-PLA2R and low IHC IgG4. CONCLUSIONS: This study established a risk prediction model for the prognosis of IMN using ML based on clinical and pathological patient data. The LightGBM model may become a tool for personalized management of IMN patients.

Epidemiological characteristics of common respiratory infectious diseases in children before and during the COVID-19 epidemic.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), public's awareness of infection prevention and control has increased overall, and various prevention and control measures have been adopted. These measures may also have a certain impact on the occurrence of other infectious diseases. Therefore, we collected information on children with several respiratory infectious diseases in Jinan Children's Hospital in China from 2016 to 2022 and analyzed their changes. Method: We collected data on age, sex and number of cases of pertussis, measles, scarlet fever, pulmonary tuberculosis, mumps and influenza, which were diagnosed by clinical and laboratory criteria, from 1 January 2016 to 31 December 2022 in Jinan Children's Hospital in Jinan, Shandong Province, China. Data on the number of people affected by these diseases in China from the Chinese Center for Disease Control and Prevention were compared. Then, we processed the data by using WPS Excel 2019 and SPSS. Results: A total of 12,225 cases were included in this study in Jinan Children's Hospital, which consisted of 3,688 cases of pertussis (2,200 cases before COVID-19 and 1,488 during COVID-19), 680 cases of measles (650 cases before COVID-19 and 30 during COVID-19), 4,688 cases of scarlet fever (4,001 cases before COVID-19 and 687 during COVID-19), 114 cases of tuberculosis (86 cases before COVID-19 and 28 during COVID-19), 449 cases of mumps (340 cases before COVID-19 and 109 during COVID-19) and 2,606 cases of influenza (1,051 cases before COVID-19 and 1,555 during COVID-19). The numbers of children in the hospital with pertussis, measles, scarlet fever, mumps and influenza decreased substantially during COVID-19 in 2020-2022 compared with numbers in 2016-2019, while numbers of patients in China with all six respiratory infectious diseases, including pulmonary tuberculosis, declined during the pandemic. A rebound of pertussis, scarlet fever and influenza was observed in 2021 and 2022. Conclusions: The study found that viral pathogens such as those causing measles, mumps and influenza all decreased during the pandemic, after which influenza rebounded. Infection diseases caused by bacteria such as scarlet fever and pertussis also decreased during COVID-19, and then a rebound occurred. However, tuberculosis stayed relatively constant.

OX40L-Armed Oncolytic Virus Boosts T-cell Response and Remodels Tumor Microenvironment for Pancreatic Cancer Treatment.

Rationale: The resistance of pancreatic ductal adenocarcinoma (PDAC) to immunotherapies is caused by the immunosuppressive tumor microenvironment (TME) and dense extracellular matrix. Currently, the efficacy of an isolated strategy targeting stromal desmoplasia or immune cells has been met with limited success in the treatment of pancreatic cancer. Oncolytic virus (OV) therapy can remodel the TME and damage tumor cells either by directly killing them or by enhancing the anti-tumor immune response, which holds promise for the treatment of PDAC. This study aimed to investigate the therapeutic effect of OX40L-armed OV on PDAC and to elucidate the underlying mechanisms. Methods: Murine OX40L was inserted into herpes simplex virus-1 (HSV-1) to construct OV-mOX40L. Its expression and function were assessed using reporter cells, cytopathic effect, and immunogenic cell death assays. The efficacy of OV-mOX40L was then evaluated in a KPC syngeneic mouse model. Tumor-infiltrating immune and stromal cells were analyzed using flow cytometry and single-cell RNA sequencing to gain insight into the mechanisms of oncolytic virotherapy. Results: OV-mOX40L treatment delayed tumor growth in KPC tumor-bearing C57BL/6 mice. It also boosted the tumor-infiltrating CD4+ T cell response, mitigated cytotoxic T lymphocyte (CTL) exhaustion, and reduced the number of regulatory T cells. The treatment of OV-mOX40L reprogrammed macrophages and neutrophils to a more pro-inflammatory anti-tumor state. In addition, the number of myofibroblastic cancer-associated fibroblasts (CAF) was reduced after treatment. Based on single-cell sequencing analysis, OV-mOX40L, in combination with anti-IL6 and anti-PD-1, significantly extended the lifespan of PDAC mice. Conclusion: OV-mOX40L converted the immunosuppressive tumor immune microenvironment to a more activated state, remodeled the stromal matrix, and enhanced T cell response. OV-mOX40L significantly prolonged the survival of PDAC mice, either as a monotherapy or in combination with synergistic antibodies. Thus, this study provides a multimodal therapeutic strategy for pancreatic cancer treatment.

Clinical effect of modified electroconvulsive therapy on schizophrenia.

OBJECTIVE: To investigate the clinical efficacy of modified electroconvulsive therapy (MECT) in patients with schizophrenia and provide a reference for the selection of safe and effective treatment options in clinical practice. METHODS: A total of 200 patients with schizophrenia, who were admitted to Wuhan Wudong Hospital Psychiatric Hospital from January 2019 to December 2020, were selected as the study subjects. They were divided into an observation group and a control group (100 cases in each group) according to a random number table. The control group was treated with conventional antipsychotics (risperidone and aripiprazole), and the observation group was given conventional antipsychotics (risperidone and aripiprazole) with MECT. After 8 weeks, the clinical efficacy, cognitive and memory functions and the occurrence of adverse reactions between the two groups were compared. RESULTS: The total clinical effective rate of the observation group was 90%, which was higher than that of the control group (74%), and the difference was statistically significant (p<0.05). The Wisconsin Card Sorting Test results of the observation group were better than those of the control group, and the cognitive function of the observation group was better than that of the control group (p<0.05). The Wechsler Adult Intelligence Scale-Fourth Edition index of the observation group was higher than that of the control group, and the memory function of the observation group was better than that of the control group (p<0.05). The overall incidence of adverse reactions in the observation group was lower than that in the control group, and the difference was statistically significant (p=0.001). CONCLUSION: The application of MECT in patients with schizophrenia can produce a good clinical curative effect, which is beneficial to the improvement and promotion of memory and cognitive functions in patients. Since the occurrence of adverse reactions is controllable, and safety is ideal, MECT has value in clinical application.

Expression of circulating angiotensin-converting enzyme 2 in children with asthma and the effects of inhaled corticosteroids.

BACKGROUND: The global spread of coronavirus disease 2019 (COVID-19) has resulted in a significant disease burden, yet asthma patients do not have the expected high morbidity and mortality rates in the pandemics of COVID-19. OBJECTIVE: To find the difference of angiotensin-converting enzyme 2 (ACE2) in asthma and nonasthma children and evaluate the effect of inhaled corticosteroids (ICS) on its expression. METHODS: The ACE2, immunoglobulin E (IgE), and eosinophils were tested in different children. RESULTS: A total of 157 children aged 3-16 years were enrolled. The expression of ACE2 in asthma children were lower than nonasthma children (T = -2.512, p = .013). Allergic nonasthma children had a significant higher ACE2 expression than children with allergic asthma (p = .013) and nonallergic asthma (p = .029). The expression of ACE2 had no significant difference between first-diagnosed asthma children and that had been treated with ICS for ≥6 months (F = 0.028, p = .598). The allergic asthma children showed a significantly higher eosinophils cells (EC) count than the allergic nonasthma (W = 200, p < .001) and nonallergic nonasthma children (W = 1089, p < .001). Nonallergic asthma children also had a significant higher EC count than the allergic non-asthma (W = 182.5, p < .001) and nonallergic non-asthma (W = 200.5, p < .001) children. There was no significant difference in IgE levels between asthmatic children and non-asthmatic children (W = 2792.5, p = .18). CONCLUSION: Circulating ACE2 levels in asthmatic children were lower than those in non-asthmatic children and ICS treatment for ≥6 months did not affect the expression of ACE2 in peripheral blood in the asthma children.

A Multifactorial Risk Score System for the Prediction of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Purpose: In-depth investigations of risk factors for the identification of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) are rare. We aimed to investigate the risk factors for developing DKD from multiple types of clinical data and conduct a comprehensive risk assessment for individuals with diabetes. Methods: We carried out a case-control study, enrolling 958 patients to identify the risk factors for developing DKD in T2DM patients from a database established from inpatient electronic medical records. Multivariable logistic regression was applied to develop a prediction model and the performance of the model was evaluated using the area under the curve (AUC) and calibration curve. A multifactorial risk score system was established according to the Framingham Study risk score. Results: DKD accounted for 34.03% of eligible patients in total. Twelve risk factors were selected in the final prediction model, including age, duration of diabetes, duration of hypertension, fasting blood glucose, fasting C-peptide, insulin use, systolic blood pressure, low-density lipoprotein, γ-glutamyl transpeptidase, platelet, uric acid, and thyroid stimulating hormone; and one protective factor, serum albumin. The prediction model showed an AUC of 0.862 (95% Confidence Interval (CI) 0.834-0.890) with an accuracy of 81.5% in the derivation dataset and an AUC of 0.876 (95% CI 0.825-0.928) in the validation dataset. The calibration curves were excellent and the estimated probability of DKD was more than 80% when the cumulative score for risk factors reached 17 points. Conclusion: Newly recognized risk factors were applied to assess the development of DKD in T2DM patients and the established risk score system was a reliable and feasible tool for assisting clinicians to identify patients at high risk of DKD.

The kinetic and molecular docking analysis of interactions between three V-type nerve agents and four human cholinesterases.

G and V-type nerve agents represent the most toxic chemical warfare agents. Their primary toxicity was the consequence of the covalent inhibition of the pivotal acetylcholinesterase (AChE), which induces overstimulation of cholinergic receptors and overaccumulation of cholines, eventually leading to death by respiratory arrest. The inhibitory and reactivation kinetics of cholinesterase (ChE) are essential for the toxicology and countermeasures of nerve agents. Medical defensive research on V-type nerve agents (V agents) has been mainly reported on VX and VR. Here we demonstrated the first systematical kinetic analysis between the type of ChE [native or recombinant human AChE and butyrylcholinesterase (BChE)] and three V agents, including VX, VR, and Vs, another isomer of VX, and highlighted the effects of native and recombinant ChE differences. The spontaneous reactivation and aging kinetics data of Vs-inhibited BChEs were firstly reported here. The results showed that AChE was more easily inhibited by three V agent compared to BChE, regardless of whether it is native or recombinant. The increased inhibitory potency order on AChE was VX, Vs, then VR, and on BChE was VX, then Vs and VR. The difference between native and recombinant ChE could influence the inhibition, aging, and spontaneous reactivation kinetics of three V agents, whether AChE or BChE, which was systematically revealed for the first time. For inhibition kinetics, the ki of three V agents for recombinant AChE was significantly higher than native AChE, and the stronger the inhibitory potency of V agents, the more pronounced difference in ki. In terms of aging and spontaneous reactivation kinetics, recombinant ChE was found to be more prone to spontaneous reactivation, but more resistant to aging compared to native ChE, particularly for AChE. The performed covalent molecular docking results partially explained the effects of differences between native and recombinant ChE on enzyme kinetics from the perspective of binding energy and conformation.

A Randomized Controlled Trial of A Theory-Based Concussion Education Video for NCAA Division I Athletes.

A large body of research demonstrates that concussions are exceedingly common and extremely difficult to detect. Despite medical efforts to develop sophisticated tools to detect concussions, research continues to demonstrate that proper detection relies on prompt and thorough symptom reporting from the injured athlete. In the context of sports, such reporting requirements are complicated by systems that reward athletic performance. This study seeks to provide student athletes who play NCAA Division I high-contact sports with a theoretically driven intervention to improve their attitudes and behavior toward concussion reporting. Division I student athletes (N = 345) viewed one of three conditions: an NCAA handout consistent with current practices, the experimental video, or a non-treatment control video, then responded to questions regarding attitudes and behaviors toward concussion reporting. Overall, results support the video's effectiveness in changing perceptions of concussion injuries. Nuances of the findings lead to a discussion for practical implications to transform concussion-reporting attitudes and behaviors among athletes.

College students' influenza vaccine hesitation: a reasoned action investigation with quantitative and qualitative data.

This two-wave longitudinal study (performed pre-COVID), using both quantitative and qualitative data, investigated college students' influenza vaccine hesitancy and confidence using the theory of planned behavior (TPB). At Time 1, college students (n = 277) completed TPB measures and reported past influenza vaccine behavior. At Time 2 (30 days later), participants indicated whether they received the influenza vaccine since Time 1. At Time 2, participants who indicated that they had not received the influenza vaccine since Time 1 also described their most important reasons for not doing so. The TPB model fit the quantitative data well; direct paths from attitude and norms to intention, and from intention to future behavior, were strong and significant. The TPB model explained 71% of the variance in intention and 28% of the variance in future behavior. Neither perceived behavioral control nor past behavior improved the model's ability to predict intentions or future behavior. From the qualitative data, participants' reasons for not getting vaccinated focused on perceived behavioral control (e.g., time cost) and attitudes (e.g., unimportance and low susceptibility). Theoretical implications for message development are discussed.

An empirical study on the development of metaphorical comprehension of Chinese children.

Metaphor affects how people focus, remember, and process information and significantly influences children's language development. The study explored metaphorical comprehension by Chinese children of different ages (5-8 years). We collected response times and accuracy rates when they processed metaphorical and literal sentences with the graded salience. Linear mixed-effects modeling showed that Chinese children's metaphorical ability improved with age. Subsequent analysis found that the perception period of metaphorical knowledge was at age 5, the development stage of metaphorical knowledge was at age 6 and 7, and the rational decision period of metaphorical ability was at age 8. After 8-year-old, children can invoke the knowledge of the intention schema while activating the source domain, and this knowledge can be automatically and quickly mapped to the target domain. Meanwhile, language development and cognitive processing influenced the metaphorical comprehension of Chinese children, especially children of 8 years of age who had the highest correct rate and the shortest reaction time to process low-saliency metaphorical sentences, while 5-year-old children had the highest accuracy in high-saliency metaphorical sentence and 6-year-old children got the longest reaction time to process sentence in high-saliency metaphor. This study may provide evidence for improving and training metaphor comprehension in children with special needs such as those with an autism spectrum disorder.