Regulations of m6A and other RNA modifications and their roles in cancer.

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N6,2'-O-dimethyladenosine (m6Am), N4-acetylcytidine (ac4C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m6A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

The influencing factors of college students' legal emotion and the mechanism of its effect on aggressive behavior.

Current research has increasingly focused on the preventive role of individual legal socialization in crime. The socialization of legal emotions is an important part of legal socialization. Building upon existing literature, this study, conducted through two sub-studies, investigated the influencing factors of legal emotions in N mainland Chinese university students and the mechanisms through which legal emotions impact aggressive behavior. In study 1, the results indicated that mother-child attachment, innovation spirit, and positive emotional expression positively predicted positive legal emotion, while mother-child attachment, dependency dimension in adult attachment, and positive emotional expression negatively predicted negative legal emotions. The anxiety dimension in adult attachment and negative emotional expression positively predicted negative legal emotions. In study 2, Positive legal emotion among university students could directly negatively predict aggressive behavior or exert influence through social alienation. Negative legal emotions could not only directly positively predict aggressive behavior but also partly affect it through social alienation. In summary, our study not only identified factors that influence legal emotions, but also found that legal emotions have an impact on aggressive behavior directly or indirectly through social alienation. Our research findings have significant implications for cultivating positive legal emotion in university students and curbing aggressive behavior. This can be achieved by promoting the legal socialization of university students and ultimately contributing to crime prevention.

[Pathogenesis and Therapeutic Prospects of Chronic Graft-Versus-Host Disease --Review].

Chronic graft-versus-host disease (cGVHD) is one of a major complication that affecting the long-term survival and living quality of patients after allogeneic hematopoietic stem cell transplantation, with the incidence of 30%-70%. Unlike acute GVHD, cGVHD involves a large number of immune cells and cytokines in addition to T cell, which is activated abnormally by the donor, and cytokine storms, which characterized by infiltration of donor lymphocytes and damage to host target organ. Recent studies have further made progress in targeting related immune cells and cytokines. In this review, the pathogenesis and therapeutic prospects of cGVHD were summarized from the perspectives of classical innate and adaptive immunity.

Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Nomogram for Predicting the Risk of Complications in Hospitalized Children With Peripheral Intravenous Catheters.

OBJECTIVE: The aim of the study is to identify the hospitalized children at risk of peripheral intravenous catheter (PIVC) complications by severity prediction. METHODS: The study included the data of 301 hospitalized children with PIVC complications in 2 tertiary teaching hospitals. A researcher-designed tool was used to collect risk factors associated with PIVC complications. Predictors of PIVC complications at univariate analysis and multivariable logistic regression analysis by backward stepwise. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing complications. RESULTS: A total of 182 participants (60.5%) had a moderate injury from PIVC complications. Multivariable logistic regression analysis indicated that the vascular condition, limb immobilization, needle adjustment in venipuncture, infusion length, infusion speed, and insertion site were independent predictors. The nomogram for assessing the severity of PIVC complications indicated good predictive accuracy (area under the curve = 0.79) and good discrimination (concordance index = 0.779). Decision curve analysis demonstrated that the nomogram was a good clinical value with a wide range of threshold probabilities (4%-100%). CONCLUSIONS: The risk prediction model has good predictive performance, and the nomogram provides an easy-to-use visualization to identify the severity of PIVC complications and guide timely nursing care management.

Incongruent gestures slow the processing of facial expressions in university students with social anxiety.

In recent years, an increasing number of studies have examined the mechanisms underlying nonverbal emotional information processing in people with high social anxiety (HSA). However, most of these studies have focused on the processing of facial expressions, and there has been scarce research on gesture or even face-gesture combined processing in HSA individuals. The present study explored the processing characteristics and mechanism of the interaction between gestures and facial expressions in people with HSA and low social anxiety (LSA). The present study recruited university students as participants and used the Liebowitz Social Anxiety Scale scores to distinguish the HSA and LSA groups. We used a 2 (group: HSA and LSA) × 2 (emotion valence: positive, negative) × 2 (task: face, gesture) multifactor mixed design, and videos of a single face or gesture and combined face-gesture cues were used as stimuli. We found that (1) there is a distinction in the processing of faces and gestures, with individuals recognizing gestures faster than faces; (2) there is an attentional enhancement in the processing of gestures, particularly for negative gestures; and (3) when the emotional valence of faces and gestures align, it facilitates the recognition of both. However, incongruent gestures have a stronger impact on the processing of facial expressions compared to facial expressions themselves, suggesting that the processing of facial emotions is more influenced by environmental cues provided by gestures. These findings indicated that gestures played an important role in emotional processing, and facial emotional processing was more dependent on the environmental cues derived from gestures, which helps to clarify the reasons for biases in the interpretation of emotional information in people with HSA.

Interlukin-4 weakens resistance to stress injury and megakaryocytic differentiation of hematopoietic stem cells by inhibiting Psmd13 expression.

Thrombocytopenia is a major and fatal complication in patients with acute myeloid leukemia (AML), which results from disrupted megakaryopoiesis by leukemic niche and blasts. Our previous research revealed that elevated interleukin-4 (IL-4) in AML bone marrow had adverse impact on multiple stages throughout megakaryopoiesis including hematopoietic stem cells (HSCs), but the specific mechanism remains unknown. In the present study, we performed single-cell transcriptome analysis and discovered activated oxidative stress pathway and apoptosis pathway in IL-4Rαhigh versus IL-4Rαlow HSCs. IL-4 stimulation in vitro led to apoptosis of HSCs and down-regulation of megakaryocyte-associated transcription factors. Functional assays displayed higher susceptibility of IL-4Rαhigh HSCs to tunicamycin and irradiation-induced apoptosis, demonstrating their vulnerability to endoplasmic reticulum (ER) stress injury. To clarify the downstream signaling of IL-4, we analyzed the transcriptomes of HSCs from AML bone marrow and found a remarkable down-regulation of the proteasome component Psmd13, whose expression was required for megakaryocytic-erythroid development but could be inhibited by IL-4 in vitro. We knocked down Psmd13 by shRNA in HSCs, and found their repopulating capacity and megakaryocytic differentiation were severely compromised, with increased apoptosis in vivo. In summary, our study uncovered a previous unrecognized regulatory role of IL-4-Psmd13 signaling in anti-stress and megakaryocytic differentiation capability of HSCs.

Prognostic value of cranial radiotherapy and optimal timing stratified by lung-molGPA for NSCLC patients with brain metastases.

PURPOSE: The updated Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (lung-molGPA) index provide more accurate survival prediction for patients diagnose with advanced non-small cell lung cancer (NSCLC) with brain metastases (BM). Given that the value of cranial radiotherapy (CRT) is still controversial for NSCLC patients with BM, this retrospective study aimed to evaluate the value of CRT and optimal timing in NSCLC patients with initial BM after stratified with lung-molGPA index. METHODS: This study screened NSCLC patients with initial BM in our cancer center from February 2012 to July 2018. The prognosis value of CRT and optimal timing was evaluated with Kaplan-Meier survival analysis and the patients were classified into lung-molGPA0-2 and lung-molGPA2.5-4 group. Upfront CRT was defined as received CRT within 3 months after initial diagnosis and without BM progression, other CRT was classified into deferred CRT. RESULTS: Overall, 288 patients were enrolled in our study, 156 patients received CRT. The median follow-up time was 47 months. In the entire cohort, the median PFS and OS were 9.2 and 17.0 months, respectively. In the lung-molGPA2.5-4 group, CRT can bring significantly overall survival benefit for NSCLC patients with initial BM (HR: 0.48, 95% CI: 0.34-0.68, P < 0.0001), and the upfront CRT can further expand this survival benefits compared with deferred CRT (HR: 0.49, 95% CI: 0.27-0.89, P = 0.0026). But this phenomenon was not observed in lung-molGPA0-2 group patients. CONCLUSION: Upfront CRT could bring significantly overall survival benefit for these patients with lung-molGPA2.5-4 but not for patients with lung-molGPA0-2.

Deciphering a global source of non-genetic heterogeneity in cancer cells.

Cell-to-cell variability within a clonal population, also known as non-genetic heterogeneity, has created significant challenges for intervening with diseases such as cancer. While non-genetic heterogeneity can arise from the variability in the expression of specific genes, it remains largely unclear whether and how clonal cells could be heterogeneous in the expression of the entire transcriptome. Here, we showed that gene transcriptional activity is globally modulated in individual cancer cells, leading to non-genetic heterogeneity in the global transcription rate. Such heterogeneity contributes to cell-to-cell variability in transcriptome size and displays both dynamic and static characteristics, with the global transcription rate temporally modulated in a cell-cycle-coupled manner and the time-averaged rate being distinct between cells and heritable across generations. Additional evidence indicated the role of ATP metabolism in this heterogeneity, and suggested its implication in intrinsic cancer drug tolerance. Collectively, our work shed light on the mode, mechanism, and implication of a global but often hidden source of non-genetic heterogeneity.

Remote cardiac rehabilitation program during the COVID-19 pandemic for patients with stable coronary artery disease after percutaneous coronary intervention: a prospective cohort study.

OBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic restricts rapid implementation of in-person delivery of cardiac rehabilitation (CR) at the center for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI), thus enabling a cohort comparison of in-person vs. remote CR program. This study aims to investigate outcomes of exercise capacity, health-related quality of life (HRQL), mental health, and family burden of stable CAD patients undergoing PCI in low-to-moderate risk after different delivery models of CR program. METHODS: The study included a cohort of stable CAD patients undergoing PCI who had experienced two naturally occurring modes of CR program after hospital discharge at two time periods, January 2019 to December 2019 (in-person CR program) and May 2020 to May 2021 (remote CR program). The exercise capacity was assessed by means of 6-min walk test (6MWT), maximal oxygen uptake (VO2max) and the respiratory anaerobic threshold (VO2AT) before discharge, at the end of the 8-week and 12-week in-person or remote CR program after discharge. RESULTS: No adverse events occurred during the CR period. CAD patients had a longer distance walked in 6 min with a higher VO2max after 8-week and 12-week CR program whether in-person or remote model (p < 0.05). The distance walked in 6 min was longer and the maximal oxygen uptake (VO2max) was higher at the end of the 12-week in-person or remote CR program than 8-week in-person or remote CR program (p < 0.05). The respiratory anaerobic threshold (VO2AT) of CAD patients was decreased after 8-week CR program whether in-person or remote model (p < 0.05). CAD patients receiving remote CR program exhibited higher HRQL scores in domains of vitality (p = 0.048), role emotional (p = 0.039), mental health (p = 0.014), and the summary score of the mental composite (p = 0.048) compared to in-person CR program after 8 weeks. The anxiety and depression scores of CAD patients undergoing PCI were decreased after 8-week CR program whether in-person or remote model (p < 0.05). The CAD patients receiving remote delivery showed lower anxiety and depression scores compared to those receiving in-person delivery at the end of the 8-week CR program (p < 0.05). It was found that the family burden scores of CAD patients undergoing PCI were reduced after 8-week and 12-week CR program whether in-person or remote model (p < 0.05). The CAD patients receiving remote CR program showed lower family burden scores than those receiving in-person CR program after whether 8 weeks or 12 weeks (p < 0.05). CONCLUSION: These data indicate that a properly designed and monitored remote delivery represents a feasible and safe model for low-to-moderate-risk, stable CAD patients undergoing PCI inaccessible to in-person CR during the COVID-19 pandemic.

Effect of mindfulness-based stress reduction in patients with acute myocardial infarction after successful primary percutaneous coronary intervention: a retrospective study.

OBJECTIVE: This study aimed to examine the effects of mindfulness-based stress reduction (MBSR) in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PPCI). METHODS: A retrospective study was conducted with data collected from AMI patients who underwent successful PPCI. The study included 61 cases that received 8-week MBSR intervention (MBSR group) and 61 cases that received weekly health education (control group) over the same period. Outcome measures, including hemodynamic parameters, psychosocial characteristics [Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Perceived Social Support Scale (PSSS)], health-related quality of life [HRQoL, 7-item Seattle Angina Questionnaire (SAQ-7)], and major adverse cardiovascular events (MACE), were assessed at baseline (T1), post-intervention (T2), 1 month after the post-intervention (T3) and 3 months after the post-intervention (T4). RESULTS: Compared to the control group, the MBSR group showed improvements in blood pressure, specifically in systolic blood pressure (SBP) at T4, and diastolic blood pressure (DBP) at T3 and T4, and mean arterial blood pressure (MABP) at T3 and T4. Additionally, the MBSR group had lower scores of anxiety and perceived stress (HADS, PSS) and higher scores of perceived social support (PSSS) after the intervention. Furthermore, the MBSR group had higher scores on the SAQ-7 at all measurement points. The control group had a significantly higher total MACE rate compared to the MBSR group (26.23% vs. 9.84%). CONCLUSIONS: This study provides support for the potential benefits of MBSR as an adjunctive treatment for AMI patients undergoing PPCI.

Formation mechanism and prediction model of juvenile delinquency.

Exploring the formation mechanism of juvenile delinquency is of great significance to prevent juvenile delinquency. The present study examined relations and interactions among juvenile delinquents' self-consciousness, family factors, social relationships, belief in a just world, and legal consciousness, and then developed a predictive model to distinguish between juvenile delinquents and non-delinquents. The results showed that family factors have a significant influence on the formation of juvenile delinquents' self-consciousness and there are notable differences in family environment and self-consciousness between delinquent and non-delinquent adolescents. Due to the complex interactions among juvenile delinquency's self-consciousness, family factors, social relationships, belief in a just world and legal consciousness, adolescents' self- consciousness and social relationships can be utilized to predict and classify the groups of delinquent and non-delinquent adolescents effectively. Therefore, the key to preventing juvenile delinquency is to improve their self-consciousness and develop their prosocial relationships.

Brain injury after cranial radiotherapy combined with immunotherapy for brain metastases in lung cancer: a retrospective study.

Aim: To explore whether immune checkpoint inhibitors (ICIs) increase the incidence of radiation-induced brain injury in lung cancer patients with brain metastases. Methods: According to whether they received ICIs within 6 months before and after cranial radiotherapy (CRT), all patients were divided into two groups: ICIs + CRT group and CRT + non-ICIs group. Results: The incidence of radiation necrosis (RN) in the CRT + ICIs group was 14.3%, while that in the CRT + non-ICIs group was 5.8% (p = 0.090). If ICIs were used within 3 months of CRT, there was statistical significance. A maximum diameter of brain metastasis >3.3 cm and cumulative radiation dose of metastatic lesions >75.7 Gy were risk factors for RN. Conclusion: ICIs could increase the risk of RN, especially when used within 3 months of CRT.

Pre-immunotherapy radiotherapy enhanced the efficacy of multi-line sintilimab in unresectable advanced esophageal squamous cell carcinoma.

Background: The use of immunotherapy for the treatment of esophageal squamous cell carcinoma (ESCC) is gradually increasing. In this retrospective study, we evaluated the efficacy and explored potential factors of prognosis in multi-line sintilimab for unresectable advanced ESCC. Methods: All pathological specimens were available from our Department of Pathology. We performed PD-L1 immunohistochemical staining of surgical or puncture specimens from 133 patients. We evaluated the efficacy of multi-line sintilimab and found potential factors according to multivariate analysis. We assessed the relationship between radiotherapy and immunotherapy, and according to whether patients had received radiotherapy within 3 months prior to immunotherapy, we attempted to analyze differences in progression-free survival (PFS) and overall survival (OS). Results: A total of 133 patients were enrolled in this retrospective study between January 2019 and December 2021. The median follow-up was 16.1 months. All patients were treated with at least two cycles of sintilimab. Of all patients, a total of 74 experienced disease progression, with a median progression-free survival of 9.0 months (95% CI 7.701-10.299). We found that pre-immunotherapy radiotherapy was a possible predictor that affected the prognosis of multi-line sintilimab and that 3 months was a significant cutoff. A total of 128 patients (96.2%) had received radiotherapy prior to immunotherapy. Of those patients, 89 (66.9%) had received radiation therapy within 3 months prior to immunotherapy. PFS was considerably longer in patients who were treated within 3 months of radiotherapy than in patients who did not receive radiation therapy within 3 months of radiation therapy prior to immunotherapy (median progression-free survival 10.0 months [95% CI 8.030-11.970] vs. 5.0 months [95% CI 2.755-7.245]). Among all patients, the median overall survival was 14.9 months (95% CI 12.558-17.242). Overall survival was significantly longer in patients who had previously received radiotherapy within 3 months prior to immunotherapy than in those who had not (median overall survival 15.3 months [95% CI 13.724-16.876] vs. 12.2 months [10.001-14.399]. Conclusion: Based on this retrospective study, sintilimab is a significant option for patients with unresectable advanced ESCC who have been previously treated, and pre-immunotherapy radiotherapy within 3 months enhanced the efficacy.

Comparative cytotoxicity, endocrine-disrupting effects, oxidative stress of halophenolic disinfection byproducts and the underlying molecular mechanisms revealed by transcriptome analysis.

Halophenolic disinfection byproducts (DBPs) are a class of emerging pollutants whose adverse effects on human cells and the underlying molecular mechanisms still need further exploration. In this study, we found that when halophenolic DBPs were substituted with the same halogen, the more substitution sites, the more cytotoxic, while when they were substituted at the same sites, the most toxic chemical was iodophenols, followed by bromophenols and chlorophenols. In addition, several of them exerted significant endocrine-disrupting effects at sublethal concentrations. 2,4,6-triiodophenol (TIP) and 2,4-dichlorophenol (2,4-DCP) showed the highest estradiol equivalent factor (EEF) of 4.41 × 10-8 and flutamide equivalent factor (FEF) of 0.4, respectively. Furthermore, all of the halophenolic DBPs except for 2-chlorophenol (2-CP) and 2-bromophenol (2-BP) significantly increased the levels of reactive oxygen species (ROS) or 8-hydroxydeoxyguanosine (8-OHdG) in HepG2 cells. The lowest cytotoxicity and unchanged ROS and 8-OHdG levels after 2-CP exposure may result from the activation of the transporters of the adenosine triphosphate (ATP) binding cassette in cells. Transcriptome analysis revealed distinct grouping patterns of 2-CP, 2,6-dibromophenol (2,6-DBP), and TIP at the concentrations of EC20, and the top differentially expressed genes (DEGs) were involved in the antioxidant-, immune-, and endocrine-associated systems. The weighted gene correlation network analysis well connected the phenotypes (EC50, EEF, FEF, ROS, 8-OHdG, and ABC transporters) with the DEGs and revealed that the MAPK signaling pathway played a vital role in regulating the biological response after exposure to halophenolic DBPs. This study provides deep insights into the underlying mechanisms of the toxic effects induced by halophenolic DBPs.

Immunotherapy combined with chemotherapy improved clinical outcomes over bevacizumab combined with chemotherapy as first-line therapy in adenocarcinoma patients.

PURPOSE: No definite conclusion has yet to be reached for the first-line treatment combined with chemotherapy for advanced adenocarcinoma NSCLC patients with negative driver genes. This study sought to compare the clinical outcomes of Beva+ChT and IO+ChT as first-line treatment for this population and investigated whether the statuses of BM, PD-L1 expression, and KRAS and TP53 mutations could influence the results. PATIENTS AND METHODS: The clinical data of patients with adenocarcinoma NSCLC who received first-line therapy were retrospectively collected and the patients were assigned to the IO+ChT and Beva+ChT groups. The disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated between the two groups. The survival effects of BM, PD-L1 expression, and KRAS and TP53 mutations were also evaluated. RESULTS: From April 2018 to October 2020, a total of 105 patients with first-line therapy were included in our analysis; 54 (51.4%) patients were included in the IO+ChT group and 51 (48.6%) patients were included in the Beva+ChT group. The results showed that OS (NR vs. 18.3 m, p = 0.011) and PFS (14.9 m vs. 6.3 m, p < 0.001) were superior in patients in the IO+ChT group than in patients in the Beva+ChT group. Further analysis revealed that the OS (median OS: NR vs. 14.7 months, p = 0.039) and PFS (median PFS: 18.5 vs. 5.5 months, p < 0.001) advantages of the IO+ChT group were also seen in the PD-L1 > 1% subgroup but were not seen in the PD-L1 < 1%, BM or KRAS mutation subgroups. CONCLUSIONS: ICIs combined with ChT improved clinical outcomes over Beva combined with ChT as first-line therapy for adenocarcinoma patients without driver gene alterations, especially in patients with PD-L1 ≥ 1%.

Comparative Transcriptome Analysis to Investigate the Immunotoxicity Mechanism Triggered by Dimethomorph on Human Jurkat T Cell Lines.

Dimethomorph (DMM) is a broad-spectrum fungicide used globally in agricultural production, but little is known regarding the immunotoxicity of DMM in humans. In this study, the immunotoxicity of DMM on human Jurkat T cells was evaluated in vitro. The results indicated that the half-effective concentration (EC50) of DMM for Jurkat cells was 126.01 mg/L (0.32 mM). To further elucidate the underlying mechanism, transcriptomics based on RNA sequencing for exposure doses of EC25 (M21) and EC10 (L4) was performed. The results indicated that compared to untreated samples (Ctr), 121 genes (81 upregulated, 40 downregulated) and 30 genes (17 upregulated, 13 downregulated) were significantly differentially regulated in the L4 and M21 samples, respectively. A gene ontology analysis indicated that the significantly differentially expressed genes (DEGs) were mostly enriched in the negative regulation of cell activities, and a KEGG pathway analysis indicated that the DEGs were mainly enriched in the immune regulation and signal transduction pathways. A quantitative real-time PCR for the selected genes showed that compared to the high-dose exposure (M21), the effect of the low-dose DMM exposure (L4) on gene expression was more significant. The results indicated that DMM has potential immunotoxicity for humans, and this toxicity cannot be ignored even at low concentrations.

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves.

OBJECTIVE: To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021. REVIEW METHODS: Two blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery. MAIN OUTCOME MEASURES: The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste. RESULTS: 18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I2=70%, τ2=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I2=67%, τ2=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I2=0.0-77.2%, τ2=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I2=0.0-72.1%, τ2=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I2=20%, τ2=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I2=78%, τ2=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I2=10%, τ2<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I2=0%, τ2<0.001) were less likely to recover their sense of smell. CONCLUSIONS: A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021283922.

Effect of Peer Attachment on Legal Emotion Among Junior Middle School Students: The Mediation Role of Self-Esteem.

Legal consciousness is the individual consciousness which reflects legal phenomena. Well-developed legal consciousness plays a crucial role in informing citizens of his legal right and ability to exercise these rights, therefore forms certain connections of individuals and society, and its development is a key part of individual's socialization process. Here, we investigated the emotion aspect of legal consciousness (henceforth legal emotion) and tried to identify several factors affecting the development of legal emotion and several factors affected by legal emotion. A large sample of Chinese junior middle school students (N = 967) completed a battery of self-reported questionnaires regarding legal emotion, peer attachment, self-esteem, prosocial tendencies, and interpersonal trust. The results indicated that for early adolescents, peer attachment predicts both positive and negative legal emotion. Importantly, peer attachment affects legal emotion partially through self-esteem. We also showed that negative legal emotion acted as a mediator on the relationship between interpersonal trust and prosocial tendencies. The results provided important insights into the role of legal emotion, the emotion aspect of legal consciousness, in the social interactions and its potential psychological mechanism.

Synergistic Effects in N,O-Comodified Carbon Nanotubes Boost Highly Selective Electrochemical Oxygen Reduction to H2 O2.

Electrochemical 2-electron oxygen reduction reaction (ORR) is a promising route for renewable and on-site H2 O2 production. Oxygen-rich carbon nanotubes have been demonstrated their high selectivity (≈80%), yet tailoring the composition and structure of carbon nanotubes to further enhance the selectivity and widen working voltage range remains a challenge. Herein, combining formamide condensation coating and mild temperature calcination, a nitrogen and oxygen comodified carbon nanotubes (N,O-CNTs) electrocatalyst is synthesized, which shows excellent selective (>95%) H2 O2 selectivity in a wide voltage range (from 0 to 0.65 V versus reversible hydrogen electrode). It is significantly superior to the corresponding selectivity values of CNTs (≈50% in 0-0.65 V vs RHE) and O-CNTs (≈80% in 0.3-0.65 V vs RHE). Density functional theory calculations revealed that the C neighbouring to N is the active site. Introducing O-related species can strengthen the adsorption of intermediates *OOH, while N-doping can weaken the adsorption of in situ generated *O and optimize the *OOH adsorption energy, thus improving the 2-electron pathway. With optimized N,O-CNTs catalysts, a Janus electrode is designed by adjusting the asymmetric wettability to achieve H2 O2 productivity of 264.8 mol kgcat -1 h-1 .