Refinement of sensitive azides via in situ generated azole-based metal-organic frameworks towards stable energetic materials.

Energetic materials (EMs) have been widely employed in both military and civilian areas for nearly two centuries. The introduction of high-energy azide anions to assemble energetic metal-organic frameworks (EMOFs) is an efficient strategy to enhance energetic properties. However, azido-based EMOFs always suffer low stabilities to external mechanical stimulation. Herein, we employed an in situ hydrothermal reaction as a technique to refine azide anions with a neutral triazole-cyano-based ligand TrzAt (TrzAt = 2-(1H-1,2,4-triazol-1-yl)acetonitrile) to yield two tetrazole-based EMOFs, namely, [ZnBr(trmetz)]n1 and [Cd(trmetz)2]n2 (Htrmetz = 5-(1,2,4-triazol-1-ylmethyl)-1H-tetrazole). Compound 1 features a closely packed 2D layered network, while compound 2 exhibits a 3D architecture. With azide anions inlaid into a nitrogen-rich and chelating ligand in the EMOFs, compounds 1 and 2 present remarkable decomposition temperatures (Tdec ≥ 300 °C), low impact sensitivities (IS ≥ 32 J) and low friction sensitivities (FS ≥ 324 N). The calculated heat of detonation (ΔHdet) values of 1 and 2 are 3.496 and 4.112 kJ g-1, respectively. In particular, the ΔHdet value of 2 is higher than that of traditional secondary explosives such as 2,4,6-trinitrotoluene (TNT, ΔHdet = 3.720 kJ g-1). These results indicate that EMOFs 1 and 2 may serve as potential replacements for traditional secondary explosives. This work provides a simple and effective strategy to obtain two EMOFs with satisfactory energy densities and reliable stabilities through an in situ hydrothermal technique for desensitization of azide anions.

Fast and visual detection of nucleic acids using a one-step RPA-CRISPR detection (ORCD) system unrestricted by the PAM.

CRISPR-Cas12a (Cpf1) is widely used for pathogen detection. However, most Cas12a nucleic acid detection methods are limited by a PAM sequence requirement. Moreover, preamplification and Cas12a cleavage are separate. Here, we developed a one-step RPA-CRISPR detection (ORCD) system unrestricted by the PAM sequence with high sensitivity and specificity that offers one-tube, rapid, and visually observable detection of nucleic acids. In this system, Cas12a detection and RPA amplification are performed simultaneously, without separate preamplification and product transfer steps, and 0.2 copies/µL of DNA and 0.4 copies/µL of RNA can be detected. In the ORCD system, the activity of Cas12a is the key to the nucleic acid detection; specifically, reducing Cas12a activity increases the sensitivity of ORCD assay detection of the PAM target. Furthermore, by combining this detection technique with a nucleic acid extraction-free method, our ORCD system can be used to extract, amplify and detect samples within 30 min, as verified with tests of 82 Bordetella pertussis clinical samples with a sensitivity and specificity of 97.30% and 100% compared with PCR. We also tested 13 SARS-CoV-2 samples with RT-ORCD, and the results were consistent with RT-PCR.

Coordination polymerization of nitrogen-rich linkers and dicyanamide anions toward energetic coordination polymers with low sensitivities.

The design and synthesis of energetic materials (EMs) with high energy and reliable stabilities has attracted much attention in the field of EMs. In this work, we employed a strategy of the coordination polymerization of mild dicyanamide ions (DCA-), two isomeric ligands 1-methyl-5-aminotetrazole (1-MAT) and 2-methyl-5-aminotetrazole (2-MAT) to construct energetic coordination polymers (ECPs). Four new ECPs {[Co(DCA)2(1-MAT)2]·H2O}n1, [Cu(DCA)2(1-MAT)]n2, [Cd(DCA)2(1-MAT)2]n3 and [Cd(DCA)2(2-MAT)2]n4 were successfully synthesized through solvent evaporation routes. Compounds 1 and 4 display 1D chains, while 2 and 3 exhibit 2D-layered structures. Compounds 1-3 with the 1-MAT ligand all exhibit reliable thermal stabilities (> 200 °C). The calculated heats of detonation (ΔHdet) of 1-3 are all higher than 1.4 kJ g-1, which are higher than traditional explosive TNT (1.22 kJ g-1) and the reported ECP AgMtta (HMtta = 5-methyl-1H-tetrazole, ΔHdet = 1.32 kJ g-1). Furthermore, sensitivity testing demonstrates that 1-4 features low mechanical sensitivity to external mechanical action in contrast with the extremely sensitive azide-based ECPs [Cu3(2-MAT)2(N3)6]n. In addition, compound 2 shows hypergolic properties via an 'oxidizer-fuel' drop experiment, demonstrating its application prospects in the field of propellants. This work details an approach of synthesizing multipurpose ECPs with reliable stabilities by introducing mild dicyanamide anions into nitrogen-rich skeletons.

Medicine for chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis.

PURPOSE: The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs). METHODS: A predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials (RCTs) were included for meta-analysis to provide clinical evidence of the intervention effects. A network meta-analysis using Bayesian networks was conducted to observe the relative effects of different intervention measures and possible ranking of effects. The composition of the TCM formulation in the experimental group was analysed, and association rule mining was performed to identify hub herbal medicines. Target genes for CAG were searched in GeneCards, Online Mendelian Inheritance in Man, PharmGKB, Therapeutic Target Database and DrugBank. A regulatory network was constructed to connect the target genes with active ingredients of the hub herbal medicines. Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the central targets from a comprehensive viewpoint. Protein-protein interaction networks (PPINs) were constructed to identify hub genes and conduct molecular docking with differentially expressed genes (DEGs) and corresponding active molecules. RESULTS: A total of 1140 participants from 12 RCTs were included in the statistical analysis, confirming that the experimental group receiving the addition of TCM intervention had better clinical efficacy. Seven hub TCMs (Paeonia lactiflora, Atractylodes macrocephala, Pinellia ternata, Citrus reticulata, Codonopsis pilosula, Salvia miltiorrhiza and Coptis chinensis) were identified through association rule analysis of all included TCMs. Thirteen hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14 and AKT1) were obtained from 90 gene PPINs. Differential gene expression analysis between the disease and normal gastric tissue identified MAPK1 and MAPK3 as the significant genes. Molecular docking analysis revealed that naringenin, luteolin and quercetin were the main active compounds with good binding activities to the two hub targets. GO analysis demonstrated the function of the targets in protein binding, while KEGG analysis indicated their involvement in important pathways related to cancer. CONCLUSIONS: The results of a meta-analysis of 12 RCTs indicate that TCM intervention can improve the clinical treatment efficacy of CAG. NPAs identified seven hub TCM and 13 target genes associated with their actions, while bioinformatics analysis identified two DEGs between normal and CAG gastric tissues. Finally, molecular docking was employed to reveal the mechanism of action of the active molecules in TCM on the DEGs. These findings not only reveal the mechanisms of action of the active components of the TCMs, but also provide support for the development of new drugs, ultimately blocking the progression from chronic gastritis to gastric cancer.

Predictors of Change in Play-Based Communication and Behavior Intervention for High-Risk ASD: The Role of Mother-Child Dyadic Synchrony.

Background: Interindividual variability is important in the evolution of adaptative profiles of children with ASD having benefited from an early intervention make up for deficits in communication, language and social interactions. Therefore, this paper aimed to determine the nature of factors influencing the efficacy variability of a particular intervention technique i.e., "Play-based communication and behavior intervention" (PCBI). Methods: The participants comprised 70 13-30-month-old toddlers with ASD enrolled in PCBI for 12 weeks. The Autism Treatment Evaluation Checklist (ATEC) was used to evaluate the efficacy of PCBI. Video recordings of 5 min of free-play before and after PCBI were used to examine behaviors of mothers and children and parent-child dyadic synchrony. Hierarchical multiple regression analyses and machine learning algorithms were performed to explore the effect of these potential predictors (mothers' factors, children's factors and videotaped mother-child interaction) of intervention efficacy. Results: The hierarchical regression analysis and the machine learning algorithms indicated that parenting stress, level of completion of training at home and mother-child dyadic synchrony were crucial factors in predicting and monitoring the efficacy of PCBI. Conclusions: In summary, the findings suggest that PCBI could be particularly beneficial to children with ASD who show a good performance in the mother-child dyadic synchrony evaluation. A better dyadic mother-child synchrony could enhance the PCBI efficacy through adapted emotional and behavioral responses of the mother and the child and has a beneficial influence on the child's psychological development.

Study on Aberrant Eating Behaviors, Food Intolerance, and Stereotyped Behaviors in Autism Spectrum Disorder.

Objective: To investigate the aberrant eating behaviors (EBs), gastrointestinal (GI) symptoms, and food intolerance in children with autism spectrum disorder (ASD) and their association with clinical core symptoms of ASD. Method: A total of 94 preschool children with ASD treated at the Child Mental Health Research Center of Nanjing Brain Hospital between October 2016 and April 2018 were enrolled. In addition, 90 children with typical development (TD) in the community during the same period were recruited. The conditions of aberrant EBs and GI symptoms in children were investigated using questionnaire surveys. Serum specific IgG antibodies against 14 kinds of food were detected using enzyme-linked immunosorbent assays (ELISAs). Results: The detection rate of aberrant EBs in the ASD group was significantly higher than that in the TD group (67.39 vs. 34.94%), and the rate of GI symptoms was also higher in the ASD group than that in the TD group (80.22 vs. 42.11%). Detection of food intolerance in children with ASD showed that the positive rate was 89.89% and that the majority of children had multiple food intolerances. The correlation analysis results showed that the severity of aberrant EBs positively correlated with stereotyped behavior of children with ASD (r = 0.21, P = 0.04) and that food-specific IgG antibodies concentrations positively correlated with high-level stereotyped behavior in children with ASD (r = 0.23, P = 0.03). Conclusion: ASD with aberrant EBs or high food-specific IgG antibodies concentrations had more severe stereotyped behavior, which may have implications for exploring the immune mechanism of ASD. Clinical Trial Registration: ChiCTR-RPC-16008139.

Application of the Still-Face Paradigm in Early Screening for High-Risk Autism Spectrum Disorder in Infants and Toddlers.

Background: Although autism spectrum disorder (ASD) can currently be diagnosed at the age of 2 years, age at ASD diagnosis is still 40 months or even later. In order to early screening for ASD with more objective method, behavioral videos were used in a number of studies in recent years. Method: The still-face paradigm (SFP) was adopted to measure the frequency and duration of non-social smiling, protest behavior, eye contact, social smiling, and active social engagement in high-risk ASD group (HR) and typical development group (TD) (HR: n = 45; TD: n = 43). The HR group was follow-up until they were 2 years old to confirm final diagnosis. Machine learning methods were used to establish models for early screening of ASD. Results: During the face-to-face interaction (FF) episode of the SFP, there were statistically significant differences in the duration and frequency of eye contact, social smiling, and active social engagement between the two groups. During the still-face (SF) episode, there were statistically significant differences in the duration and frequency of eye contact and active social engagement between the two groups. The 45 children in the HR group were reclassified into two groups after follow-up: five children in the N-ASD group who were not meet the criterion of ASD and 40 children in the ASD group. The results showed that the accuracy of Support Vector Machine (SVM) classification was 83.35% for the SF episode. Conclusion: The use of the social behavior indicator of the SFP for a child with HR before 2 years old can effectively predict the clinical diagnosis of the child at the age of 2 years. The screening model constructed using SVM based on the SF episode of the SFP was the best. This also proves that the SFP has certain value in high-risk autism spectrum disorder screening. In addition, because of its convenient, it can provide a self-screening mode for use at home. Trial registration: Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.

[Characteristics of vocalization in children with autism spectrum disorder during the still-face paradigm].

OBJECTIVE: To study the characteristics of vocalization during the still-face paradigm (SFP) before the age of 2 years and their correlation with the severity of autism spectrum disorder (ASD) symptoms at diagnosis in children with ASD. METHODS: A total of 43 children aged 7-23 months, who were suspected of ASD, were enrolled as the suspected ASD group, and 37 typical development (TD) children, aged 7-23 months, were enrolled as the TD group. The frequency and durations of vocalization in the SFP were measured. The children in the suspected ASD group were followed up to the age of 2 years, and 34 children were diagnosed with ASD. Autism Diagnostic Observation Schedule (ADOS) was used to assess the severity of symptoms. The correlation of the characteristics of vocalization before the age of 2 years with the severity of ASD symptoms was analyzed. RESULTS: Compared with the TD group, the ASD group had significant reductions in the frequency and durations of meaningful vocalization and vocalization towards people and a significant increase in the duration of vocalization toward objects (P<0.05). The Spearman correlation analysis showed that in the ASD group, the frequency and durations of total vocalization, non-speech vocalization, babbling, vocalization towards people, and vocalization towards objects were negatively correlated with the score of communication in ADOS (P<0.05). The frequency and durations of total vocalization, babbling, and vocalization towards people and the duration of vocalization towards objects were negatively correlated with the score of reciprocal social interaction in ADOS (P<0.05). The frequency of total vocalization, the duration of babbling, and the frequency and duration of vocalization towards people were negatively correlated with the score of play in ADOS (P<0.05). The frequency of total vocalization and non-speech vocalization and the frequency and durations of vocalization towards people were negatively correlated with the score of stereotyped behaviors and restricted interests in ADOS (P<0.05). The multiple linear regression analysis showed that the frequency of total vocalization was a negative predictive factor for the score of communication in ADOS (P<0.001), and the duration of vocalization towards people was a negative predictive factor for the score of reciprocal social interaction in ADOS (P<0.05). CONCLUSIONS: SFP can better highlight the abnormal vocalization of ASD children before the age of 2 years, and such abnormalities can predict the severity of ASD symptoms early.

The fair decision-making of children and adolescents with high-functioning autism spectrum disorder from the perspective of dual-process theories.

BACKGROUND: Fairness has received much attention in our society. At present, the findings regarding fair decision-making in high-functioning autism spectrum disorder (HF-ASD) are inconsistent. Previous studies have shown that the fair decision-making of typically developing children is influenced by theory of mind (ToM) and executive functioning (EF). As those with HF-ASD have defects in both domains, this study aims to explore the differences in fair decision-making between children and adolescents with HF-ASD and those with typical development (TD). METHODS: We used a simple ultimatum game (UG) to explore 31 children and adolescents with HF-ASD and 38 children and adolescents with TD. T tests and chi-square tests were used to compare group differences, and Pearson correlation analysis and stepwise regression analysis were used to analyse the mechanisms influencing the two groups' unfair acceptance rates. RESULTS: The results show that children with HF-ASD are more likely to accept unfair offers, but for adolescents, the difference is not significant. Regression analysis showed that the interaction between the behavior regulation index (BRI) and age could negatively predict the unfair acceptance rate of children and adolescents with HF-ASD. Working memory and ToM can negatively predict the unfair acceptance rate of those with TD. CONCLUSION: This study concluded that the development of fair decision-making by children and adolescents with HF-ASD falls far behind that of those with TD. Intuition processes play a dominant role in the fair decision-making processes of children and adolescents with HF-ASD, and we believe that comorbidity, age, experience and emotional management are important factors influencing the fair decision-making of individuals with HF-ASD.

Exploring the relationship between fairness and 'brain types' in children with high-functioning autism spectrum disorder.

BACKGROUND: Existing research typically focuses on only one domain of cognition with regard to fairness-theory of mind or executive function. However, children with High-functioning autism spectrum disorder (HF-ASD) are cognitively impaired in both domains. Moreover, little is known about fairness characteristics in children with HF-ASD in relation to both domains of cognition. METHODS: Thirty children with HF-ASD as well as 39 children with typical development (TD) were evaluated in this study. We investigated the development of children's fairness characteristics as a responder in a mini ultimatum game (UG). The different 'brain types,' i.e., with or without HF-ASD, were evaluated using the Empathy Questionnaire-Systemizing Questionnaire (E/SC-Q). Furthermore, we explored the relationship between fairness and brain types using Pearson correlation analyses. RESULTS: Children in the HF-ASD group were more likely to accept unfair offers than were children in the TD group (χ2 = 17.513, p = .025). In the HF-ASD group, the acceptance rate of unfair offers was correlated with the discrepancy score (r = 0.363, p = .048), while there were no significant correlations in the TD group. In HF-ASD group, compared with Type S, acceptance rate of unfair offer was significant higher in Extreme Type S 'brain type' (F = 28.584, p < .001). While dividing TD participants by 'brain type', there was no significant difference in acceptance rate of unfair offer among five difference 'brain types' (F = 1.131, p = .358). Stepwise regression revealed that Extreme Type S positively predicted acceptance of unfair offers (F [1, 68] = 8.695, p < .001). DISCUSSION: Our findings show that children with HF-ASD were more likely to accept an unfair offer; in particular, the more unbalanced the development of empathy and systemizing was, the more significant the unfairness preference observed. Extreme Type S positively predicted the acceptance of unfair offers by children with HF-ASD. REGISTRATION OF CLINICAL TRIALS: World Health Organization class I registered international clinical trial platform, ChiCTR-ROC-17012877.