Rh(III)-Catalyzed [3 + 3]-Coupling Cyclization of 3-Hydroxyisoindolinones with Carbenoids: Rapid Access to Spirolactam Skeletons.

A Rh(III)-catalyzed [3 + 3]-coupling cyclization of 3-hydroxy-3-phenylisoindolinone with carbenoids has been developed. The method provides an efficient approach to access polyfunctionalized-spiro[isochromene-1,1'-isoindolin]-3'-ones with good to excellent reaction conversions.

Impaired IL-27 signaling aggravates macrophage senescence and sensitizes premature ovarian insufficiency induction by high-fat diet.

Premature ovarian insufficiency (POI) critically affects female reproductive health, with obesity being a significant and recognized risk factor. Interleukin-27 (IL-27), known for its role in immune modulation and inflammation, has garnered attention in metabolic syndrome research. Nonetheless, the role of these immunometabolic factors on the initiation of POI remains to be unraveled. Our investigation delves into the influence of impaired IL-27 signaling on POI induction, particularly under the challenge of a high-fat diet (HFD). We analyzed patients' serum profiles and established a correlation of increased serum triglycerides with decreased IL-27 levels in POI cases. Experiments on C57BL/6 mice lacking the IL-27 receptor alpha (Il27ra-/-) revealed that when subjected to HFD, these mice developed hallmark POI symptoms. This includes escalated lipid deposition in both liver and ovarian tissues, increased ovarian macrophages cellular aging, and diminished follicle count, all pointing to compromised ovarian function. These findings unveil a novel pathway wherein impaired IL-27 signaling potentiates the onset of POI in the presence of HFD. Understanding the intricate interplay between IL-27, metabolic alterations, and immune dysregulation sheds light on potential therapeutic avenues for managing POI, offering hope for improved reproductive health outcomes.

Enhancing Flexural Behavior of Reinforced Concrete Beams Strengthened with Basalt Fiber-Reinforced Polymer Sheets Using Carbon Nanotube-Modified Epoxy.

The external bonding (EB) of fiber-reinforced polymer (FRP) is a usual flexural reinforcement method. When using the technique, premature debonding failure still remains a factor of concern. The effect of incorporating multi-wall carbon nanotubes (MWCNTs) in epoxy resin on the flexural behavior of reinforced concrete (RC) beams strengthened with basalt fiber-reinforced polymer (BFRP) sheets was investigated through four-point bending beam tests. Experimental results indicated that the flexural behavior was significantly improved by the MWCNT-modified epoxy. The BFRP sheets bonded by the MWCNT-modified epoxy more effectively mitigated the debonding failure of BFRP sheets and constrained crack development as well as enhanced the ductility and flexural stiffness of strengthened beams. When the beam was reinforced with two-layer BFRP sheets, the yielding load, ultimate load, ultimate deflection, post-yielded flexural stiffness, energy absorption capacity and deflection ductility of beams strengthened using MWCNT-modified epoxy increased by 7.4%, 8.3%, 18.2%, 22.6%, 29.1% and 14.3%, respectively, in comparison to the beam strengthened using pure epoxy. It could be seen in scanning electron microscopy (SEM) images that the MWCNTs could penetrate into concrete and their pull-out and crack bridging consumed more energy, which remarkably enhanced the flexural behavior of the strengthened beams. Finally, an analytical model was proposed for calculating characteristic loads and characteristic deflections of RC beams strengthened with FRP sheets, which indicated a reasonably good correlation with the experimental results.

Vertical InGaN Light-Emitting Diode with Hybrid Distributed Bragg Reflectors.

A vertical-type InGaN light-emitting diode with a resonant cavity was demonstrated with a 9 µm aperture size and a short cavity formed by hybrid distributed Bragg reflectors (DBRs). The approach involved designing epitaxial structures and utilizing an electrochemical etching process to convert heavily doped n-type gallium nitride (n+-GaN) layers into porous GaN layers as a porous-GaN DBR structure. Thirteen pairs of the conductive porous-GaN:Si/GaN:Si DBR structure provided a vertical current path in a vertical-type light-emitting diodes (LED) structure. The LED epitaxial layers were separated from sapphire for membrane-type LED structures through a laser lift-off process. During the free-standing membrane fabrication process, the dielectric DBR deposited on ITO/p-GaN:Mg layers was inverted from top to bottom, thereby establishing the concept of higher reflectivity for the bottom DBR compared to the porous-GaN DBR. The physical cavity length was reduced from about 2.3 µm for the LED membrane to 0.74 µm for the membrane-type LED with the embedded porous-GaN DBR structure. The divergent angles and line width of EL emission light were reduced from 124°/31.7 nm to 44°/3.3 nm due to the resonant cavity effect. The membrane-type LED structures with hybrid DBRs consisted of small divergent angles, narrow line width, and vertical current injection properties that have potential for directional emission light sources and vertical-cavity surface-emitting diode laser applications.

Reference Twice: A Simple and Unified Baseline for Few-Shot Instance Segmentation.

Few-Shot Instance Segmentation (FSIS) requires detecting and segmenting novel classes with limited support examples. Existing methods based on Region Proposal Networks (RPNs) face two issues: 1) Overfitting suppresses novel class objects; 2) Dual-branch models require complex spatial correlation strategies to prevent spatial information loss when generating class prototypes. We introduce a unified framework, Reference Twice (RefT), to exploit the relationship between support and query features for FSIS and related tasks. Our three main contributions are: 1) A novel transformer-based baseline that avoids overfitting, offering a new direction for FSIS; 2) Demonstrating that support object queries encode key factors after base training, allowing query features to be enhanced twice at both feature and query levels using simple cross-attention, thus avoiding complex spatial correlation interaction; 3) Introducing a class-enhanced base knowledge distillation loss to address the issue of DETR-like models struggling with incremental settings due to the input projection layer, enabling easy extension to incremental FSIS. Extensive experimental evaluations on the COCO dataset under three FSIS settings demonstrate that our method performs favorably against existing approaches across different shots, e.g., +8.2/ + 9.4 performance gain over state-of-the-art methods with 10/30-shots. Source code and models will be available at this github site.

Optical and Electrical Properties of AlGaN-Based High Electron Mobility Transistors and Photodetectors with AlGaN/AlN/GaN Channel-Stacking Structure.

High channel current of the high electron mobility transistors (HEMTs) and high relative responsivity of the photodetectors (PDs) were demonstrated in the AlGaN/AlN/GaN channel-stacking epitaxial structures. The interference properties of the X-ray curves indicated high-quality interfaces of the conductive channels. The AlGaN/AlN/GaN interfaces were observed clearly in the transmission electron microscope micrograph. The saturation I ds currents of the HEMT structures were increased by adding a number of channels. The conductive properties of the channel-stacking structures corresponded to the peaks of the transconductance (g m) spectra in the HEMT structures. The depletion-mode one- and two-channel HEMT structures can be operated at the cutoff region by increasing the reverse V gs bias voltages. Higher I ds current in the active state and lower current in the cutoff state were observed in the two-channel HEMT structure compared with one- and three-channel HEMT structures. For the channel-stacking metal-semiconductor-metal photodetector structures, the peak responsivity was observed at almost 300 nm incident monochromic light, which was increased by adding a number of channel layers. The channel current of the HEMT devices and the photocurrent in the PD devices were increased by adding a number of two-dimensional electron gas (2DEG) channels. By using a flat gate metal layer, the two-channel AlGaN/AlN/GaN HEMT structures exhibited a high I ds current, a low cutoff current, and a high peak g m value and have the potential for GaN-based power devices, fast portable chargers, and ultraviolet PD applications.

ENO1 promotes trophoblast invasion regulated by E2F8 in recurrent miscarriage.

Recurrent miscarriage (RM) is related to the dysfunction of extravillous trophoblast cells (EVTs), but the comprehensive mechanisms remain largely unexplored. We analyzed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing and microarray datasets obtained from Gene Expression Omnibus (GEO) database to explore the hub genes in the mechanisms of RM. We identified 1724 differentially expressed genes (DEGs) in EVTs from the RM, and they were all expressed along the trajectory of EVTs. These DEGs were associated with hypoxia and glucose metabolism. Single-cell Regulatory Network Inference and Clustering (SCENIC) analysis revealed that E2F transcription factor (E2F) 8 (E2F8) was a key transcription factor for these DEGs. And the expression of ENO1 can be positively regulated by E2F8 via RNA sequencing analysis. Subsequently, we performed immunofluorescence assay (IF), plasmid transfection, western blotting, chromatin immunoprecipitation (ChIP), real-time quantitative polymerase chain reaction (qRT-PCR), and transwell assays for validation experiments. We found that the expression of alpha-Enolase 1 (ENO1) was lower in the placentas of RM. Importantly, E2F8 can transcriptionally regulate the expression of ENO1 to promote the invasion of trophoblast cells by inhibiting secreted frizzled-related protein 1/4 (SFRP1/4) to activate Wnt signaling pathway. Our results suggest that ENO1 can promote trophoblast invasion via an E2F8-dependent manner, highlighting a potential novel target for the physiological mechanisms of RM.

IM-IAD: Industrial Image Anomaly Detection Benchmark in Manufacturing.

Image anomaly detection (IAD) is an emerging and vital computer vision task in industrial manufacturing (IM). Recently, many advanced algorithms have been reported, but their performance deviates considerably with various IM settings. We realize that the lack of a uniform IM benchmark is hindering the development and usage of IAD methods in real-world applications. In addition, it is difficult for researchers to analyze IAD algorithms without a uniform benchmark. To solve this problem, we propose a uniform IM benchmark, for the first time, to assess how well these algorithms perform, which includes various levels of supervision (unsupervised versus fully supervised), learning paradigms (few-shot, continual and noisy label), and efficiency (memory usage and inference speed). Then, we construct a comprehensive IAD benchmark (IM-IAD), which includes 19 algorithms on seven major datasets with a uniform setting. Extensive experiments (17 017 total) on IM-IAD provide in-depth insights into IAD algorithm redesign or selection. Moreover, the proposed IM-IAD benchmark challenges existing algorithms and suggests future research directions. For reproducibility and accessibility, the source code is uploaded to the website: https://github.com/M-3LAB/open-iad.

Acupoint herbal patching for postherpetic neuralgia: A systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically evaluate the clinical effectiveness and safety of acupoint herbal patching in the treatment of postherpetic neuralgia. METHODS: Eight databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan-Fang Database, China Biomedical Literature Service System, and Chongqing VIP Chinese Science were searched. The search time was set to October 2023. Two researchers independently screened the literature according to the inclusion and exclusion criteria; extracted the basic information, acupoints, Chinese herbal medicine, pain score, sleep score, depression score, and other information of the subjects, and independently assessed the risk of bias by 2 researchers. Meta-analysis of the included studies was performed using the StataMP 16 software. RESULTS: Fifteen studies with 1362 participants were included in this meta-analysis. Ashi is the acupoint frequency at the forefront, and Borneol is the Chinese herbal medicine frequency at the forefront. The acupoint herbal patching group showed significant improvements in visual analog score (SMD: -2.09; 95% Cl: -2.77, -1.42; P < .001), sleep score (SMD: -1.58; 95% Cl: -2.11, -1.05; P < .001), depression score (SMD: -1.61; 95% Cl: -2.22, -0.99; P < .001), Chinese medicine syndrome score (SMD: -2.32; 95% Cl: -2.84, -1.80; P = .06), dermatology life quality index (weighted mean differences: -4.11; 95% Cl: -4.58, -3.63; P = .98), and related laboratory indicators compared to the control group, and the total effective rate was significantly higher (relative risk: 1.20; 95% confidence interval: 1.15, 1.26; P = .99) than the control group. Two studies reported adverse reactions, but the 2 groups were not statistically significant. CONCLUSIONS: Acupoint herbal patching intervention in postherpetic neuralgia is effective in improving the pain, sleep, anxiety, depression, quality of life of patients, and related laboratory indicators.

MCD-Net: Toward RGB-D Video Inpainting in Real-World Scenes.

Video inpainting gains an increasing amount of attention ascribed to its wide applications in intelligent video editing. However, despite tremendous progress made in RGB video inpainting, the existing RGB-D video inpainting models are still incompetent to inpaint real-world RGB-D videos, as they simply fuse color and depth via explicit feature concatenation, neglecting the natural modality gap. Moreover, current RGB-D video inpainting datasets are synthesized with homogeneous and delusive RGB-D data, which is far from real-world application and cannot provide comprehensive evaluation. To alleviate these problems and achieve real-world RGB-D video inpainting, on one hand, we propose a Mutually-guided Color and Depth Inpainting Network (MCD-Net), where color and depth are reciprocally leveraged to inpaint each other implicitly, mitigating the modality gap and fully exploiting cross-modal association for inpainting. On the other hand, we build a Video Inpainting with Depth (VID) dataset to supply diverse and authentic RGB-D video data with various object annotation masks to enable comprehensive evaluation for RGB-D video inpainting under real-world scenes. Experimental results on the DynaFill benchmark and our collected VID dataset demonstrate our MCD-Net not only yields the state-of-the-art quantitative performance but successfully achieves high-quality RGB-D video inpainting under real-world scenes. All resources are available at https://github.com/JCATCV/MCD-Net.

Potential Causal Association between Plasma Metabolites, Immunophenotypes, and Female Reproductive Disorders: A Two-Sample Mendelian Randomization Analysis.

BACKGROUND: While extensive research highlighted the involvement of metabolism and immune cells in female reproductive diseases, causality remains unestablished. METHODS: Instrumental variables for 486 circulating metabolites (N = 7824) and 731 immunophenotypes (N = 3757) were derived from a genome-wide association study (GWAS) meta-analysis. FinnGen contributed data on 14 female reproductive disorders. A bidirectional two-sample Mendelian randomization study was performed to determine the relationships between exposures and outcomes. The robustness of results, potential heterogeneity, and horizontal pleiotropy were examined through sensitivity analysis. RESULTS: High levels of mannose were found to be causally associated with increased risks of gestational diabetes (GDM) (OR [95% CI], 6.02 [2.85-12.73], p = 2.55 × 10-6). A genetically predicted elevation in the relative count of circulating CD28-CD25++CD8+ T cells was causally related to increased female infertility risk (OR [95% CI], 1.26 [1.14-1.40], p = 1.07 × 10-5), whereas a high absolute count of NKT cells reduced the risk of ectopic pregnancy (OR [95% CI], 0.87 [0.82-0.93], p = 5.94 × 10-6). These results remained consistent in sensitivity analyses. CONCLUSIONS: Our study supports mannose as a promising GDM biomarker and intervention target by integrating metabolomics and genomics.

Recent progress in SEI engineering for boosting Li metal anodes.

Lithium metal anodes (LMAs) are ideal anode candidates for achieving next-generation high-energy-density battery systems due to their high theoretical capacity (3680 mA h g-1) and low working potential (-3.04 V versus the standard hydrogen electrode). However, the non-ideal solid electrolyte interface (SEI) derived from electrolyte/electrode interfacial reactions plays a vital role in the lithium deposition/stripping process and battery cycling performance. The composition and morphology of a SEI, which is sensitive to the outside environment, make it difficult to characterize and understand. With the development of characterization techniques, the mechanism, composition, and structure of a SEI can be better understood. In this review, the mechanism formation, the structure model evolution, and the composition of a SEI are briefly presented. Moreover, the development of in situ characterization techniques in recent years is introduced to better understand a SEI followed by the properties of the SEI, which are beneficial to the battery performance. Furthermore, recent optimization strategies of the SEI including the improvement of intrinsic SEIs and construction of artificial SEIs are summarized. Finally, the current challenges and future perspectives of SEI research are summarized.

APOA1 Is a Novel Marker for Preeclampsia.

Preeclampsia (PE) is one of the pregnancy complications, leading to major maternal and fetal morbidity and mortality; however, the underlying mechanisms of PE still remain unclear. We aimed to explore the role of apolipoprotein A1 (APOA1) in the pathophysiology of PE. The expression of APOA1 was elevated in both plasma and placental tissues, as detected by Western blotting, immunohistochemistry, and a qRT-PCR assay. Importantly, we detected the concentration of APOA1 using the ELISA assay in normal control women (n = 30) and women with preeclampsia (n = 29) from a prospective cohort study. The concentration of APOA1 was not significantly altered in plasma during early and mid-term gestation of the PE patients compared to the NP patients; however, it was elevated during late gestation. Additionally, the concentration of APOA1 was positively associated with systolic blood pressure during late gestation. The proliferation and invasion of trophoblast were all increased in HTR8/SVneo cells transfected with APOA1 siRNA and decreased in HTR8/SVneo cells treated with the recombinant human APOA1 protein (rhAPOA1). Additionally, we used public datasets to investigate the downstream genes of APOA1 and qRT-PCR for validation. Furthermore, we explored the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARγ) in APOA1 by using a luciferase assay, which showed that the APOA1 promoter was activated by PPARγ. Additionally, the inhibitory effect of rhAPOA1 on the ability of trophoblast invasion and proliferation can be rescued by the PPARγ inhibitor. Our findings suggest the crucial role of APOA1 in PE, which might provide a new strategy for the prevention and treatment of PE.

CD74 deficiency reduces trophoblast invasion and proliferation mediated by SIRT1 in preeclampsia.

In brief: Preeclampsia (PE) is a severe complication that leads to major maternal and fetal mortality and morbidity, and one of its causes is extravillous trophoblast (EVT) dysfunction. This study revealed the role of CD74 in the invasion and proliferation of EVTs. Abstract: PE is a severe hypertensive disorder during pregnancy, and one of its causes is the dysfunction of EVTs. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of placentas from PE patients and the sirtuin 1 (SIRT1) heterozygous knockout mouse model, which exhibited typical PE-like symptoms. We identified 134 differentially expressed genes (DEGs) with similar trends in EVTs of PE patients and in parietal trophoblast giant cells (P-TGCs) of Sirt1-/- (HO) placentas from Sirt1+/- (HE) pregnant mice. Interestingly, Kyoto Encyclopedia of Genes and Genomes analysis showed that 134 overlapping genes were related to the MAPK signaling pathway. We validated several DEGs using immunofluorescence at the protein level. Finally, we selected CD74 for further experiments, which showed a decrease in EVTs of PE patients and in P-TGCs of Sirt1-/- placentas from Sirt1+/- pregnant mice. Additionally, cell proliferation assays and transwell assays showed that the proliferation and invasion abilities were decreased in CD74 knockdown HTR8/SVneo cells using lentivirus transfection, which can be improved by adding the SIRT1 agonist SRT1720 or metformin, an agonist of the MAPK signaling pathway. Importantly, the expression of CD74 can be positively regulated by SIRT1. These data suggest that CD74 plays an important protective role in the pathogenesis of preeclampsia by regulating the MAPK signaling pathway, which can be regulated by SIRT1.

Dynamic Frame Interpolation in Wavelet Domain.

Video frame interpolation is an important low-level vision task, which can increase frame rate for more fluent visual experience. Existing methods have achieved great success by employing advanced motion models and synthesis networks. However, the spatial redundancy when synthesizing the target frame has not been fully explored, that can result in lots of inefficient computation. On the other hand, the computation compression degree in frame interpolation is highly dependent on both texture distribution and scene motion, which demands to understand the spatial-temporal information of each input frame pair for a better compression degree selection. In this work, we propose a novel two-stage frame interpolation framework termed WaveletVFI to address above problems. It first estimates intermediate optical flow with a lightweight motion perception network, and then a wavelet synthesis network uses flow aligned context features to predict multi-scale wavelet coefficients with sparse convolution for efficient target frame reconstruction, where the sparse valid masks that control computation in each scale are determined by a crucial threshold ratio. Instead of setting a fixed value like previous methods, we find that embedding a classifier in the motion perception network to learn a dynamic threshold for each sample can achieve more computation reduction with almost no loss of accuracy. On the common high resolution and animation frame interpolation benchmarks, proposed WaveletVFI can reduce computation up to 40% while maintaining similar accuracy, making it perform more efficiently against other state-of-the-arts.

Amine-Directed Regioselective Pyridyl Csp2-H Aminovinylation.

A Rh-catalyzed amine-directed cross-coupling of 2-aminopyridines with 1-sulfonyl-triazoles has been developed. The method provides an efficient approach to access 5-aminovinylpyridines with wide functional group tolerance.

Soil Moisture Content Dominates the Photosynthesis of C3 and C4 Plants in a Desert Steppe after Long-Term Warming and Increasing Precipitation.

Plant photosynthesis has a non-negligible influence on forage quality and ecosystem carbon sequestration. However, the influence of long-term warming, increasing precipitation, and their interactions on the photosynthesis of dominant species in desert steppe remains unclear, and the main factors regulating plant photosynthesis in desert steppes have remained unrevealed. Therefore, we measured the photosynthetic parameters and specific leaf area of the dominant species and calculated the water and nitrogen content of leaves and soil in a desert steppe after long-term warming and increasing precipitation (air temperature, W0, air temperature increases of 2 °C and 4 °C, W1 and W2; natural precipitation, P0, natural precipitation increases of 25% and 50%, P1 and P2). Results showed that warming and increasing precipitation significantly enhanced photosynthesis in C3 and C4 species (p < 0.05). Compared to W0P0, the net photosynthetic rate of C3 and C4 species in W2P2 increased by 159.46% and 178.88%, respectively. Redundancy analysis showed that soil water content significantly explained the photosynthesis of C3 and C4 plants (the degree of explanation was 48% and 67.7%), followed by soil-available nitrogen content (the degree of explanation was 19.6% and 5.3%). Therefore, our study found that climate change enhanced photosynthesis in C3 and C4 plants, and soil water content plays a critical role in regulating photosynthesis in desert steppes.

Crosstalk between Placental Trophoblast and Decidual Immune Cells in Recurrent Miscarriage.

Recurrent miscarriage (RM) is a pregnancy complication associated with dysregulation of the maternal-fetal interface. We aimed to identify dysfunctional interactions between trophoblast cells and decidual immune cells in RM. We downloaded single-cell RNA sequencing (scRNA-seq) datasets (GSE214607) from the Gene Expression Omnibus (GEO) datasets for further analysis using the R software. The data comprised of paired placental and decidual tissues, including those from patients diagnosed with RM and matched healthy controls. A total of 22976 cells were identified in 11 cell types, including trophoblasts, immune cells, and other cells. We divided trophoblast cells into three types and analyzed their interactions with decidual immune cells. Additionally, we re-clustered NK&T cells and macrophages, identified differentially expressed genes (DEGs), enriched their functions, and compared the cell interactions with trophoblast cells in each cell type. Our single-cell atlas of the maternal-fetal interface revealed alterations in the cellular organization of the decidua and placenta, cell type-specific transcriptome, and cell communication between immune and non-immune cells in RM, which are critical for illuminating the pathophysiology of RM.

The stability of perennial grasses mediates the negative impacts of long-term warming and increasing precipitation on community stability in a desert steppe.

Background: Desert steppe, as an ecotone between desert and grassland, has few species and is sensitive to climate change. Climate change alters species diversity and the stability of functional groups, which may positively or negatively affect community stability. However, the response of plant community stability in the desert steppe to experimental warming and increasing precipitation remains largely unexplored. Methods: In a factorial experiment of warming and increasing precipitation for five to seven years (ambient precipitation (P0), ambient precipitation increased by 25% and 50% (P1 and P2), ambient temperature (W0), ambient temperature increased by 2°C and 4°C (W1 and W2)), we estimated the importance value (IV) of four functional groups (perennial grasses, semi-shrubs, perennial forbs and annual herbs), species diversity and community stability. Results: Compared to W0P0, the IV of perennial grasses was reduced by 37.66% in W2P2, whereas the IV of perennial forbs increased by 48.96%. Although increasing precipitation and experimental warming significantly altered species composition, the effect on species diversity was insignificant (P > 0.05). In addition, increasing precipitation and experimental warming had a significant negative impact on community stability. The stability of perennial grasses significantly explained community stability. Conclusion: Our results suggest that the small number of species in desert steppe limits the contribution of species diversity to regulating community stability. By contrast, maintaining high stability of perennial grasses can improve community stability in the desert steppe.

Effects of a Nonwearable Digital Therapeutic Intervention on Preschoolers With Autism Spectrum Disorder in China: Open-Label Randomized Controlled Trial.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause difficulty with communication and social interactions as well as complicated family dynamics. Digital health interventions can reduce treatment costs and promote healthy lifestyle changes. These therapies can be adjunctive or replace traditional treatments. However, issues with cooperation and compliance prevent preschool patients with ASD from applying these tools. In this open-label, randomized controlled trial, we developed a nonwearable digital therapy called virtual reality-incorporated cognitive behavioral therapy (VR-CBT). OBJECTIVE: The aim of this study was to assess the adjunctive function of VR-CBT by comparing the effects of VR-CBT plus learning style profile (LSP) intervention with those of LSP-only intervention in preschool children with ASD. METHODS: This trial was performed in China on 78 preschool children (age 3-6 years, IQ>70) diagnosed with ASD who were randomized to receive a 20-week VR-CBT plus LSP intervention (intervention group, 39/78, 50%) or LSP intervention only (control group, 39/78, 50%). The primary outcome was the change of scores from baseline to week 20, assessed by using the parent-rated Autism Behavior Checklist (ABC). Secondary outcomes included the Childhood Autism Rating Scale (CARS), Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV), and behavioral performance data (accuracy and reaction time) in go/no-go tasks. All primary and secondary outcomes were analyzed in the intention-to-treat population. RESULTS: After the intervention, there was an intervention effect on total ABC (ß=-5.528; P<.001) and CARS scores (ß=-1.365; P=.02). A similar trend was observed in the ABC subscales: sensory (ß=-1.133; P=.047), relating (ß=-1.512; P=.03), body and object use (ß=-1.211; P=.03), and social and self-help (ß=-1.593; P=.03). The intervention also showed statistically significant effects in improving behavioral performance (go/no-go task, accuracy, ß=2.923; P=.04). Moreover, a significant improvement of ADHD hyperactivity-impulsivity symptoms was observed in 53 children with comorbid ADHD based on ADHD-RS-IV (ß=-1.269; P=.02). No statistically significant intervention effect was detected in the language subscale of ABC (ß=-.080; P=.83). Intervention group girls had larger improvements in ABC subscales, that is, sensory and body and object use and in the CARS score and accuracy of go/no-go task (all P<.05) than the control group girls. Statistically significant intervention effects could be observed in hyperactivity-impulsivity symptoms in the intervention group boys with comorbid ADHD compared with those in the control group boys (ß=-1.333; P=.03). CONCLUSIONS: We found potentially positive effects of nonwearable digital therapy plus LSP on core symptoms associated with ASD, leading to a modest improvement in the function of sensory, motor, and response inhibition, while reducing impulsivity and hyperactivity in preschoolers with both ASD and ADHD. VR-CBT was found to be an effective and feasible adjunctive digital tool. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100053165; http://www.chictr.org.cn/showproj.aspx?proj=137016.