The emerging role of extracellular vesicles in the diagnosis and treatment of autism spectrum disorders.

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by restricted, repetitive behavioral patterns and deficits in social interactions. The prevalence of ASD has continued to rise in recent years. However, the etiology and pathophysiology of ASD remain largely unknown. Currently, the diagnosis of ASD relies on behavior measures, and there is a lack of reliable and objective biomarkers. In addition, there are still no effective pharmacologic therapies for the core symptoms of ASD. Extracellular vesicles (EVs) are lipid bilayer nanovesicles secreted by almost all types of cells. EVs play a vital role in cell-cell communications and are known to bear various biological functions. Emerging evidence demonstrated that EVs are involved in many physiological and pathological processes throughout the body and the content in EVs can reflect the status of the originating cells. EVs have demonstrated the potential of broad applications for the diagnosis and treatment of various brain diseases, suggesting that EVs may have also played a role in the pathological process of ASD. Besides, EVs can be utilized as therapeutic agents for their endogenous substances and biological functions. Additionally, EVs can serve as drug delivery tools as nano-sized vesicles with inherent targeting ability. Here, we discuss the potential of EVs to be considered as promising diagnostic biomarkers and their potential therapeutic applications for ASD.

Prelimbic cortex-nucleus accumbens core projection positively regulates itch and itch-related aversion.

Itch is one of the most common clinical symptoms in patients with diseases of the skin, liver, or kidney, and it strongly triggers aversive emotion and scratching behavior. Previous studies have confirmed the role of the prelimbic cortex (Prl) and the nucleus accumbens core (NAcC), which are reward and motivation regulatory centers, in the regulation of itch. However, it is currently unclear whether the Prl-NAcC projection, an important pathway connecting these two brain regions, is involved in the regulation of itch and its associated negative emotions. In this study, rat models of acute neck and cheek itch were established by subcutaneous injection of 5-HT, compound 48/80, or chloroquine. Immunofluorescence experiments determined that the number of c-Fos-immunopositive neurons in the Prl increased during acute itch. Chemogenetic inhibition of Prl glutamatergic neurons or Prl-NAcC glutamatergic projections can inhibit both histaminergic and nonhistaminergic itch-scratching behaviors and rectify the itch-related conditioned place aversion (CPA) behavior associated with nonhistaminergic itch. The Prl-NAcC projection may play an important role in the positive regulation of itch-scratching behavior by mediating the negative emotions related to itch.

Three-Dimensional Polyoxometalate Organic Frameworks with One-Dimensional Channels Constructed by Multiple Helical Chains Based on 22-Core Ln/Mn/Mo Clusters for Proton Conduction.

Two unique 22-core sandwich {[Mn6Mo6O37]Ln3[MnMo6O24]} (Ln = La or Pr) units have been assembled, featuring an undisclosed {Mn6Mo6} cluster. This assembly is subsequently integrated into two three-dimensional polyoxometalate organic frameworks, which exhibit one-dimensional hydrophilic hexagonal channels formed by six intertwined 63 helical chains, leading to effective proton conduction primarily facilitated by an abundance of water molecules within the channels.

Oxidative cascade cyclization of N-arylacrylamides with TMSN3.

An azido-radical-triggered cyclization of N-(o-cyanobiaryl)acrylamides with TMSN3via a C(sp3)-N/C(sp2)-C(sp3)/C(sp2)-N bond formation cascade is described. This reaction features mild conditions and high bond-forming efficiency, making it an efficient method for the construction of azide-substituted pyridophenanthridines.

Translation and validation of the Chinese version of the comprehensive breastfeeding knowledge scale (CBKS).

BACKGROUND: The level of breastfeeding knowledge of nursing students may influence their ability to support breastfeeding families. However, to date, it has not been possible to measure this accurately due to the lack of existence of a validated tool in Chinese. OBJECTIVES: To translate the Comprehensive Breastfeeding Knowledge Scale (CBKS) into Chinese, and then evaluate its psychometric properties among Chinese undergraduate nursing students in order to inform and evaluate a nursing breastfeeding education programme. METHODS: The Brislin translation model was followed, and a three-phase process (translation, back-translation and cultural adaptation) was used to sinicize the CBKS and evaluate its content validity. Construct validity was evaluated with exploratory factor analysis (EFA), and the reliability of internal consistency of the Chinese version of the CBKS was tested by calculating Cronbach's alpha coefficient and the half reliability coefficient. SETTINGS: Two nursing schools in Beijing and Nanjing, China. PARTICIPANTS: Four hundred and thirty-nine undergraduate nursing students (257 from Beijing and 182 from Nanjing). RESULTS: Five experts rated the content validity of the Chinese version of the CBKS as excellent. EFA showed that the Chinese version of the CBKS had three subscales and 23 items. Cronbach's alpha coefficient of the Chinese version of the CBKS and the half reliability coefficient were 0.70 and 0.73, respectively. Students who had completed an obstetrics or paediatric nursing course had significantly higher total scores and mean scores for most items compared with those who had not taken a course. Most of the indictors of EFA met the standards of construct validity, and some were very close to the cut-off. CONCLUSION: Overall, the 23-item Chinese version of the CBKS is an acceptable tool to measure the level of breastfeeding knowledge among undergraduate nursing students. This scale can be used to inform the design and evaluation of breastfeeding education materials for nursing students or other health profession students.

[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Visible-Light-Promoted Cascade Cyclization of 3-Ethynyl-[1,1'-biphenyl]-2-Carbonitriles with Unsaturated α-Bromocarbonyls.

A visible-light-promoted cascade cyclization of 3-ethynyl-[1,1'-biphenyl]-2-carbonitriles with unsaturated α-bromocarbonyls for the synthesis of tetrahydrobenzo[mn]cyclopenta[b]acridines is described. Three C(sp3)-C(sp2) bonds, one C(sp2)-N bond, and three cycles can be formed in a single reaction through the addition of a C-centered radical to the carbon-carbon triple bond and three radical cyclizations. This reaction features mild conditions, wide substrate scope, and high bond-forming efficiency.

N-N-Bridged Polynuclear POM-Based Coordination Polymers Based on a V-Type Ligand: Proton Conduction and Magnetism.

The construction of polyoxometalate (POM)-based coordination polymers, in the presence of a nitrogen heterocyclic ligand, is intriguing due to the potential for obtaining diverse structures. These structures exhibit extensive application possibilities in the fields of proton conductivity and magnetism. Herein, four new POM-based polynuclear coordination polymers with the formulas of {[Fe2(btb)3(H2O)2(SiW12O40)]·3H2O}n (1), {[Cd2(btb)2(H2O)6(HPMoVI10MoV2O40)]·2H2O}n (2), {[Co3(OH)2(btb)2(H2O)5(HPMoVI10MoV2O40)]·7H2O}n (3), and {[Cu3(OH)(btb)2(H2O)(HP2Mo5O23)]·6H2O}n (4) have been prepared using the V-type 1,3-bis(4H-1,2,4-triazole-4-yl)benzene (btb) ligand. Compounds 1 and 2 feature similar two-dimensional (2D) structures, derived from the binuclear Fe2N6 and Cd2N4 subunits connected by tridentate btb ligands. Meanwhile, in compound 3, hexanuclear Co6(OH)4 units are bound by quadridentate btb ligands forming a 2D layer with the same 4-c sql topology simplification as compounds 1 and 2. In compound 1, Keggin-type polyoxoanions are monodentate-coordinated to metal ions and suspended on the 2D structure, while, in compounds 2 and 3, they act as discrete counterions residing in the interstitial spaces between two adjacent layers, thereby extending the 2D structures into 3D structures through hydrogen bonding interactions. In compound 4, trinuclear Cu3(OH) subunits are further constructed into a 3D framework through cooperation with four tridentate and quadridentate btb ligands as well as Strandberg-type anions. Furthermore, the proton conduction of the four compounds has been investigated. They display high proton conductivities at 358 K and 98% RH with powdered samples, which are 1.26 × 10-3, 1.24 × 10-3, 3.24 × 10-4, and 2.57 × 10-4 S cm-1, respectively. Interestingly, by mixing with Nafion, the composite membranes of compounds 2 and 4 exhibit enhanced proton conductivities, measuring at 4.87 × 10-2 and 1.28 × 10-2 S cm-1, respectively, at 358 K and 98% RH, which suggests excellent potential for applications. In addition, compounds 1, 3, and 4 display antiferromagnetic behaviors due to similar magnetic interactions. This work can provide research insights into the assembly of 2D POM-based coordination polymers with nitrogen heterocyclic ligands and Keggin-type POMs and further promote their research progress in proton conduction.

Azido-difluoromethylthiolation of Alkenes with TMSN3 and PhSO2SCF2H.

An oxidative azido-difluoromethylthiolation of alkenes by employing TMSN3 as the azide source and PhSO2SCF2H as the difluoromethylthiolation reagent is reported. The present method is characterized by good functional group tolerance, broad substrate scope, and short reaction time, thereby providing an efficient access to synthetically useful ß-difluoromethylthiolated azides. Mechanistic studies indicate a radical pathway involved in the reaction.

Copper-Catalyzed Cascade Multicomponent Reaction of Azides, Alkynes, and Selenium: Synthesis of Ditriazolyl Diselenides.

A copper-catalyzed cascade multicomponent reaction for synthesizing ditriazolyl diselenides from azides, terminal alkynes, and elemental selenium has been developed. The present reaction features utilizing readily available and stable reagents, high atom-economy, and mild reaction conditions. A possible mechanism is proposed.

Cost-effectiveness of immune checkpoint inhibition and targeted treatment in combination as adjuvant treatment of patient with BRAF-mutant advanced melanoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) and targeted treatments have improved the health outcomes of patients with advanced melanoma. However, due to the high cost of novel therapies, it is crucial to evaluate their value by considering both effectiveness and cost. To compare the cost-effectiveness of these novel agents (atezolizumab-vemurafenib-cobimetinib, vemurafenib-plus-cobimetinib, dabrafenib-plus-trametinib, and encorafenib-plus-binimetinib) for first-line treatment of metastatic melanoma with the BRAFV600 mutation. METHODS: A patient-level model was developed to project the health outcomes of 4 strategies for patients with advanced melanoma. We estimated transition probabilities from the IMspire150 (ClinicalTrials.gov, NCT02908672), COMBI-AD (NCT01682083), and COLUMBUS (NCT01909453) trials using a parametric survival model. All health outcomes, including direct cost, quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER), were estimated from the US payer perspective. Lifetime cost, QALYs, life-years (LYs), and ICERs were calculated. Univariable and probabilistic sensitivity analyses were performed to test model robustness, along with multiple scenario analyses. RESULTS: Of the 4 competing strategies, atezolizumab-vemurafenib-cobimetinib produced the best health outcomes, and the vemurafenib-cobimetinib strategy was the least expensive option. Atezolizumab-vemurafenib-cobimetinib, dabrafenib-plus-trametinib, and vemurafenib-cobimetinib formed the cost-effective frontier, indicating that the ordered ICERs were $325,113/QALYs for dabrafenib-plus-trametinib vs. vemurafenib-cobimetinib strategies and $2,247,500/QALYs for atezolizumab-vemurafenib-cobimetinib vs. dabrafenib-plus-trametinib strategies. Encorafenib-plus-binimetinib was dominated by the other 3 competing strategies. The drug price and first-line utility significantly influenced the model utcomes. CONCLUSIONS: For BRAF-mutant advanced melanoma, the vemurafenib-cobimetinib strategy could be considered the most cost-effective treatment at the willingness-to-pay threshold of $150,000.

Oxidative Dehydrogenative Coupling of Thiols with Alkanes for the Synthesis of Sulfoxides.

An oxidative dehydrogenative coupling of thiols with alkanes via direct C(sp3)-H bond functionalization to form a new C-S bond and S═O double bond was developed. The present reaction features the use of readily available reagents and high step- and atom-efficiency, thus providing an efficient access to sulfoxides. A possible mechanism is proposed.

Downregulation of DDIT4 ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway.

Autism spectrum disorder (ASD) is a complex disease with unclear etiology. Studies have shown that ferroptosis is also related to ASD progression, but the specific mechanism is still unclear. Valproic acid (VPA) induced neuronal ferroptosis in vitro. Mechanistic studies showed that both VPA and ferroptosis inducers promoted the expression of DDIT4 in neurons, thereby inhibiting the activation of the PI3K/Akt pathway. DDIT4 increased the accumulation of ROS, MDA and Fe2+, inhibited neuronal viability and downregulated GPX4 expression by inactivating the PI3K/Akt pathway. Ferroptosis inhibitors reversed the anti-survival effect of DDIT4, indicating that DDIT4 enhances ferroptosis through the PI3K/Akt pathway, thereby inhibiting neuronal viability. Further in vivo experiments found that autistic mice had high levels of ROS, MDA and Fe2+, increased DDIT4 expression, and downregulated expression levels of GPX4, p-PI3K and p-Akt; after downregulation of DDIT4 expression, the accumulation of ROS, MDA and Fe2+ was significantly reduced, while the expression levels of GPX4, p-PI3K and p-Akt were upregulated, indicating that DDIT4 knockdown reduces ferroptosis in autistic mice. In addition, DDIT4 downregulation, PI3K/Akt pathway activation, and ferroptosis inhibitors all improved social behavior deficits, repetitive stereotyped and compulsive behaviors, anxiety and exploratory behaviors in autistic mice, but PI3K/Akt pathway inhibitors significantly blocked the rescue of abnormal behaviors by DDIT4 downregulation in autistic mice. Therefore, downregulation of DDIT4 expression ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway, indicating that DDIT4, the PI3K/Akt pathway and ferroptosis have key roles in autism.

Association between type 1 diabetes and neurodevelopmental disorders in children and adolescents: A systematic review and meta-analysis.

Type 1 diabetes and neurodevelopmental disorders are common chronic conditions in childhood and adolescence, and having one may lead to an increased chance of developing the other. Type 1 diabetes mellitus is mainly manifested by elevated blood glucose, while neurodevelopmental diseases are composed of a variety of diseases, which are relatively complex. The purpose of this meta-analysis was to find out the prevalence of type 1 diabetes-related neurodevelopmental disorders in children and adolescents and to explore the potential association between neurodevelopmental disorders and type 1 diabetes. PubMed, Embase and Web of science databases were searched from the inception to May 22, 2022 to identify relevant studies, Finally, 24 original studies were included in the meta-analysis. Prevalence estimates for neurodevelopmental disorders in the type 1 diabetes adolescent and their 95% confidence intervals were pooled using random effects models. The pooled estimates for autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) in the type 1 diabetes population were 1.2 and 5.3%, respectively, both of which are higher than the 2019 global prevalence of ASD and ADHD in the general population. The results of the subgroup analysis showed that the prevalence of ASD and ADHD in the T1DM population tended to increase with age. In conclusion, there may be a potential link between the occurrence of type 1 diabetes mellitus and the development of neurodevelopmental disorders in children and adolescents, but more relevant studies are needed to understand the link between the underlying pathogenesis of type 1 diabetes and neurodevelopmental disorders. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CDR42022333443].

Ultrastable Polyoxometalate-Encapsulated Supramolecular Metal-Organic Nanotubes for Single-Crystal Proton Conduction.

Two unique polyoxometalate (POM)-encapsulated tubular materials with the formula K(H2O)6[M6(btp)6(H2O)22](P2W18O62)3(Hbtp)5(btp)3·52H2O [M = Mn (1) and Co (2); btp = 2,6-bis(1,2,4-triazol-1-yl)pyridine] were designed and synthesized based on the Dawson POM and V-type btp ligand, as confirmed by IR, X-ray diffraction (XRD), and element analysis. Single-crystal XRD analyses of compound 1 show that two kinds of remarkable metal-organic supramolecular nanotubes, including trigonal and hexagonal nanotubes, are constructed along the c-axis direction via π···π-packing interactions between {Mn3(btp)3} rings and the btp ligands, of which [α-P2W18O62]6- anions are confined in channels, making the entire structure extraordinarily stable. Meanwhile, the coordinated [α-P2W18O62]6- anion within the hexagonal channel makes the channel highly hydrophilic and attracts a number of guest water molecules to fill in the free space, conducive to proton transport. Therefore, the single-crystal sample of 1 exhibits a high proton conductivity of 6.39 × 10-3 S cm-1 along one-dimensional channels, 30 times higher than that of a pellet sample at 358 K and 98% relative humidity.

Genetic, environmental and other risk factors for progression of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect on the progression of RP, such as inheritance patterns, genotype, gender, age, smoking, physical activity, and other demographic and environmental factors. Baseline visual field conditions, changes of ellipsoid zone, photoreceptor layer thickness, and choroidal structure are reported to be the phenotype risk factors for RP progression. Moreover, aqueous flare and high-sensitivity C-reactive protein are probable inflammation biomarkers for assessing the progression of RP. Increased oxidative stress is considered to be one of the potential factors for the existence of RP. The risk factors can be combined to form a corresponding prediction model to predict disease progression. This review is to summarize the current literature that studies the genetic, environmental, phenotypic, demographic, inflammatory and other risk factors of RP progression and discuss the most reliable risk factors that could provide predictive models.

Free Radical Cascade Carbochloromethylations of Activated Alkenes.

Free radical carbochloromethylations of ortho-cyanoarylacrylamides and N-(arylsulfonyl)acrylamides have been developed by employing simple alkyl chlorides as the chloromethyl source. The transformations are characterized by wide functional group compatibility and utilizing readily available reagents, thus providing efficient methods for constructing polychloromethyl-substituted quinoline-2,4-diones and α-aryl-ß-polychloromethylated amides.

Effects of Disease-Related Knowledge on Illness Perception and Psychological Status of Patients With COVID-19 in Hunan, China.

OBJECTIVE: The aim of this study was to assess the current status of disease-related knowledge and to analyze the relationship among the general condition, illness perception, and psychological status of patients with coronavirus disease 2019 (COVID-19). METHODS: A hospital-based cross-sectional study was conducted on 118 patients using convenience sampling. The general questionnaire, disease-related knowledge questionnaire of COVID-19, Illness Perception Questionnaire (IPQ), and Profile of Mood States (POMS) were used to measure the current status of participants. RESULTS: The overall average score of the disease-related knowledge of patients with COVID-19 was (79.19 ± 14.25), the self-care situation was positively correlated with knowledge of prevention and control (r = 0.265; P = 0.004) and total score of disease-related knowledge (r = 0.206; P = 0.025); the degree of anxiety was negatively correlated with the knowledge of diagnosis and treatment (r = -0.182; P = 0.049). The score of disease-related knowledge was negatively correlated with negative cognition (volatility, consequences, emotional statements) and negative emotions (tension, fatigue, depression) (P < 0.05); positively correlated with positive cognition (disease coherence) and positive emotion (self-esteem) (P < 0.05). CONCLUSIONS: It was recommended that we should pay more attention to the elderly and low-income groups, and increase the knowledge about diagnosis and treatment of COVID-19 and self-care in the future health education for patients.

Preserving extracellular vesicles for biomedical applications: consideration of storage stability before and after isolation.

Extracellular vesicles (EVs) are nanovesicles released by various cell types. EVs are known for cell-to-cell communications and have potent biological activities. Despite great progress in recent years for studies exploring the potentials of EVs for early disease detection, therapeutic application and drug delivery, determination of the favorable storage conditions of EVs has been challenging. The understanding of the impact of storage conditions on EVs before and after isolation is still limited. Storage may change the size, number, contents, functions, and behaviors of EVs. Here, we summarized current studies about the stability of EVs in different conditions, focusing on temperatures, durations, and freezing and thawing cycles. -80 °C seems to remain the most favorable condition for storage of biofluids and isolated EVs, while isolated EVs may be stored at 4 °C shortly. Lyophilization is promising for storage of EV products. Challenges remain in the understanding of storage-mediated change in EVs and in the development of advanced preservation techniques of EVs.