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Interpersonal communication facilitates symptom measures of autistic sociability to enhance clinical decision-making in identifying children with autism spectrum disorder (ASD). Traditional methods are carried out by clinical practitioners with assessment scales, which are subjective to quantify. Recent studies employ engineering technologies to analyze children's behaviors with quantitative indicators, but these methods only generate specific rule-driven indicators that are not adaptable to diverse interaction scenarios. To tackle this issue, we propose a Computational Interpersonal Communication Model (CICM) based on psychological theory to represent dyadic interpersonal communication as a stochastic process, providing a scenario-independent theoretical framework for evaluating autistic sociability. We apply CICM to the response-to-name (RTN) with 48 subjects, including 30 toddlers with ASD and 18 typically developing (TD), and design a joint state transition matrix as quantitative indicators. Paired with machine learning, our proposed CICM-driven indicators achieve consistencies of 98.44% and 83.33% with RTN expert ratings and ASD diagnosis, respectively. Beyond outstanding screening results, we also reveal the interpretability between CICM-driven indicators and expert ratings based on statistical analysis.

Bioactive Cell‐free Conducting Hydrogel In article 2304207, Sanyuan Zhang, Sheng He, Ren‐Ke Li, Jun Xie, and co‐workers show new strategies for heart tissue engineering. PPY‐CHI is conductive biomaterial and can repair damaged conduction in heart. This biocompatible conductive hydrogel is a platform to carry biological hEMSCExo for long‐term releasing and become a multifunctional biomaterial. It not only enhances tissue regeneration but also reduces arrhythmia through resynchronization.

Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)‐derived exosomes (hEMSC‐Exo) into poly‐pyrrole‐chitosan (PPY‐CHI), to yield an injectable hydrogel that can effectively treat MI. In vitro, PPY‐CHI/hEMSC‐Exo, compared to untreated controls, PPY‐CHI, or hEMSC‐Exo alone, alleviates H2O2‐induced apoptosis and promotes tubule formation, while in vivo, PPY‐CHI/hEMSC‐Exo improves post‐MI cardiac functioning, along with counteracting against ventricular remodeling and fibrosis. All these activities are facilitated via increased epidermal growth factor (EGF)/phosphoinositide 3‐kinase (PI3K)/AKT signaling. Furthermore, the conductive properties of PPY‐CHI/hEMSC‐Exo are able to resynchronize cardiac electrical transmission to alleviate arrythmia. Overall, PPY‐CHI/hEMSC‐Exo synergistically combines the cardiac regenerative capabilities of hEMSC‐Exo with the conductive properties of PPY‐CHI to improve cardiac functioning, via promoting angiogenesis and inhibiting apoptosis, as well as resynchronizing electrical conduction, to ultimately enable more effective MI treatment. Therefore, incorporating exosomes into a conductive hydrogel provides dual benefits in terms of maintaining conductivity, along with facilitating long‐term exosome release and sustained application of their beneficial effects. Incorporating human endometrial mesenchymal stem cell‐derived exosomes (hEMSC‐Exo) into poly‐pyrrole‐chitosan (PPY‐CHI) yields an injectable hydrogel, possessing conductive and sustained exosome release properties. PPY‐CHI/hEMSC‐Exo counteracts against H2O2‐induced apoptosis among H9c2, and promotes angiogenesis among human umbilical cord vein endothelial cells. In vivo, it combines the cardiac regenerative capabilities of hEMSC‐Exo with PPY‐CHI conductive properties to alleviate myocardial infarction and arrhythmia.

Human pluripotent stem cell-derived kidney organoids offer unprecedented opportunities for studying polycystic kidney disease (PKD), which still has no effective cure. Here, we developed both in vitroand in vivoorganoid models of PKD that manifested tubular injury and aberrant upregulation of renin-angiotensin aldosterone system. Single-cell analysis revealed that a myriad of metabolic changes occurred during cystogenesis, including defective autophagy. Experimental activation of autophagy via ATG5 overexpression or primary cilia ablation significantly inhibited cystogenesis in PKD kidney organoids. Employing the organoid xenograft model of PKD, which spontaneously developed tubular cysts, we demonstrate that minoxidil, a potent autophagy activator and an FDA-approved drug, effectively attenuated cyst formation in vivo. This in vivoorganoid model of PKD will enhance our capability to discover novel disease mechanisms and validate candidate drugs for clinical translation.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity. In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novomutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P < 2.2 × 10−16) in exonic (1.37 × 10−8) and 3′-UTR regions (1.42 × 10−8) was revealed in comparison with that of whole genome (1.05 × 10−8). Using an integrated model, we identified 87 potentially risk genes (P < 0.01) from 4832 genes harboring various rare deleterious variants, including CHD8and NRXN2, implying that the disorders may be in favor to multiple-hit. In particular, frequent rare inherited mutations of several microcephaly-associated genes (ASPM, WDR62, and ZNF335) were found in ASD. In chromosomal structure analyses, we found four de novoCNVs and one de novochromosomal rearrangement event, including a de novoduplication of UBE3A-containing region at 15q11.2-q13.1, which causes Angelman syndrome and microcephaly, and a disrupted TNRdue to de novochromosomal translocation t(1; 5)(q25.1; q33.2). Taken together, our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD. Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders, such as ASD, could provide novel insights into pathogenesis, diagnosis and treatment.

Human pluripotent stem cell-derived kidney organoids recapitulate developmental processes and tissue architecture, but intrinsic limitations, such as lack of vasculature and functionality, have greatly hampered their application. Here we establish a versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, producing a correlative level of vascular endothelial growth factor A (VEGFA) to define a resident vascular network. Single-cell RNA sequencing identifies a subset of nephron progenitor cells as a potential source of renal vasculature. These kidney organoids undergo further structural and functional maturation upon implantation. Using this kidney organoid platform, we establish an in vitromodel of autosomal recessive polycystic kidney disease (ARPKD), the cystic phenotype of which can be effectively prevented by gene correction or drug treatment. Our studies provide new avenues for studying human kidney development, modeling disease pathogenesis, and performing patient-specific drug validation.