Optimized model architectures for deep learning on genomic data.

The success of deep learning in various applications depends on task-specific architecture design choices, including the types, hyperparameters, and number of layers. In computational biology, there is no consensus on the optimal architecture design, and decisions are often made using insights from more well-established fields such as computer vision. These may not consider the domain-specific characteristics of genome sequences, potentially limiting performance. Here, we present GenomeNet-Architect, a neural architecture design framework that automatically optimizes deep learning models for genome sequence data. It optimizes the overall layout of the architecture, with a search space specifically designed for genomics. Additionally, it optimizes hyperparameters of individual layers and the model training procedure. On a viral classification task, GenomeNet-Architect reduced the read-level misclassification rate by 19%, with 67% faster inference and 83% fewer parameters, and achieved similar contig-level accuracy with ~100 times fewer parameters compared to the best-performing deep learning baselines.

Analysis of risk factors associated with pre-myopia among primary school students in the Mianyang Science City.

Objectives To find out the prevalence rate of pre-myopia among primary school students in the Mianyang Science City Area, analyze its related risk factors, and thus provide a reference for local authorities to formulate policies on the prevention and control of myopia for primary school students. Methods From September to October 2021, Cluster sampling was adopted by our research group to obtain the vision levels of primary school students employing a diopter test in the Science City Area. In addition, questionnaires were distributed to help us find the risk factors associated with pre-myopia. Through the statistical analysis, we identify the main risk factors for pre-myopia and propose appropriate interventions. Results The prevalence rate of pre-myopia among primary school students in the Science City Area was 45.27% (1020/2253), of which 43.82% were boys and 46.92% were girls, with no statistically significant difference in the prevalence rate of myopia between boys and girls (2 =2.171, P=0.141). The results of the linear trend test showed that the prevalence rate of pre-myopia tends to decrease with increasing age (Z=296.521, P=0.000). Logistic regression analysis demonstrated that the main risk factors for pre-myopia were having at least one parent with myopia, spending less than 2 hours a day outdoors, using the eyes continuously for more than 1 hour, looking at electronic screens for more than 2 hours, and having an improper reading and writing posture. Conclusion The Science City Area has a high prevalence rate of pre-myopia among primary school students. It is proposed that students, schools, families, and local authorities work together to increase the time spent outdoors, reduce digital screens and develop scientific use of eye habits.

Decorin in the spatial control of collagen mineralization.

Understanding the molecular mechanism by which the periodontal ligament (PDL) is maintained uncalcified between two mineralized tissues (cementum and bone) may facilitate the functional repair and regeneration of the periodontium complex, disrupted in the context of periodontal diseases. However, research that explores the control of type I collagen (COL I) mineralization fails to clarify the detailed mechanism of regulating spatial collagen mineralization, especially in the periodontium complex. In the present study, decorin (DCN), which is characterized as abundant in the PDL region and rare in mineralized tissues, was hypothesized to be a key regulator in the spatial control of collagen mineralization. The circular dichroism results confirmed that DCN regulated the secondary structure of COL I, and the surface plasmon resonance results indicated that COL I possessed a higher affinity for DCN than for other mineralization promoters, such as DMP-1, OPN, BSP and DSPP. These features of DCN may contribute to blocking intrafibrillar mineralization in COL I fibrils during the polymer-induced liquid-precursor mineralization process when the fibrils are cross-linked with DCN. This effect was more remarkable when the fibrils were phosphorylated by sodium trimetaphosphate, as shown by the observation of a tube-like morphology via TEM and mineral sheath via SEM. This study enhances the understanding of the role of DCN in mineralization regulation among periodontal tissues. This provides insights for the development of biomaterials for the regeneration of interfaces between soft and hard tissues.

Constructing Interfacial Charge Transfer Channels and Electric Field in Violet Phosphorus-Based van der Waals Heterojunction for Phototherapy of Periodontitis.

Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti3C2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport "bridge" (P-Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti3C2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O2 and H2O on the surfaces of Ti3C2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti3C2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli, respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti3C2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.

Lung adenocarcinoma discovered during the follow-up of lung-dominant connective tissue disease: a case report and literature review.

Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Dual-ligand quasi-2D perovskites with chiral-induced spin selectivity for room temperature spin-LEDs.

Spin-LEDs have been a central topic in semiconductor spintronics research and represent a promising avenue for advanced optoelectronic devices and applications. The future advancements of spin-LEDs will undoubtedly hinge on the generation and manipulation of spin-polarized population at room temperature. In this research, we elucidate the development of room-temperature spin-LEDs using quasi-2D perovskites, based on the chiral-induced spin selectivity (CISS) effect. During the carrier transfer from the chiral n2 phase to the randomly oriented high-n phase caused by the bandgap gradient distribution, CISS works to generate non-equilibrium spin population, leading to room-temperature spin-polarized fluorescence. A spin-polarization of ∼93% is observed for the films. Finally, we realize spin-LEDs at room temperature, exhibiting a |gCP-EL| value of 0.05 and an EQE of 3.8%. This work highlights the potential of integrating dual ligands to optimize the phase distribution and crystalline orientation in quasi-2D films to achieve efficient CISS for spin-LED applications.

Structural mechanism underlying variations in DNA binding by the androgen receptor.

The androgen receptor (AR) is a steroid activated transcription factor which recognizes DNA motifs resembling inverted repeats of a conserved 5'-AGAACA-3'-like hexanucleotides separated by a three-nucleotide spacer from a similar, but less conserved hexanucleotide. Here, we report the structures of the human AR DNA binding domain (DBD) bound to two natural AREs (C3 and MTV) in head-to-head dimer conformations, diffracting at 2.05 Šand 2.25 Å, respectively. These structures help to explain the impact of androgen insensitivity mutations on the structure integrity, DNA binding and DBD dimerization. The binding affinity of the AR DBD to different DNA motifs were measured by the BioLayer Interferometry (BLI) and further validated by Molecular Dynamics (MD) simulations. This shows that the high binding affinity of the first DBD to the upstream 5'-AGAACA-3' motif induces the cooperative binding of the second DBD to the second hexanucleotide. Our data indicate identical interaction of the DBDs to the upstream hexanucleotides, while forming an induced closer contact of the second DBD on the non-canonical hexanucleotides. The variation in binding between the DBD monomers are the result of differences in DNA occupancy, protein-protein interactions, DNA binding affinity, and DNA binding energy profiles. We propose this has functional consequences.

Prevalence and molecular characterization of Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis in dairy cattle in Ningxia, northwestern China.

Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis are common intestinal pathogens that infect humans and animals. To date, research regarding these three protozoa in the Ningxia Hui Autonomous Region (Ningxia) has mostly been limited to a single pathogen, and comprehensive data on mixed infections are unavailable. This study aimed to evaluate the zoonotic potential of these three protozoa. In this study, small subunit ribosomal RNA (SSU rRNA) and 60 kDa glycoprotein (gp60) genes of Cryptosporidium; internal transcribed spacer (ITS) gene of E. bieneusi; and SSU rRNA, glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis were examined. DNA extraction, polymerase chain reaction, and sequence analysis were performed on fecal samples collected from 320 dairy cattle at three intensive dairy farms in Ningxia in 2021 to determine the prevalence and genetic characteristics of these three protozoa. The findings revealed that 61.56% (197/320) of the samples were infected with at least one protozoan. The overall prevalence of Cryptosporidium was 19.38% (62/320), E. bieneusi was 41.56% (133/320), and G. duodenalis was 29.38% (94/320). This study identified four Cryptosporidium species (C. bovis, C. andersoni, C. ryanae, and C. parvum) and the presence of mixed infections with two or three Cryptosporidium species. C. bovis was the dominant species in this study, while the dominant C. parvum subtypes were IIdA15G1 and IIdA20G1. The genotypes of E. bieneusis were J, BEB4, and I alongside the novel genotypes NX1-NX8, all belonging to group 2, with genotype J being dominant. G. duodenalis assemblages were identified as assemblages E, A, and B, and a mixed infection involving assemblages A + E was identified, with assemblage E being the dominant one. Concurrently, 11 isolates formed 10 different assemblage E multilocus genotypes (MLGs) and 1 assemblage A MLG and assemblage E MLGs formed 5 subgroups. To the best of our knowledge, this is the first report on mixed infection with two or three Cryptosporidium species in cattle in Ningxia and on the presence of the C. parvum subtype IIdA20G1 in this part of China. This study also discovered nine genotypes of E. bieneusis and novel features of G. duodenalis assemblages in Ningxia. This study indicates that dairy cattle in this region may play a significant role in the zoonotic transmission of Cryptosporidium spp., E. bieneusi, and G. duodenalis.

Rational evolution for altering the ligand preference of estrogen receptor alpha.

Estrogen receptor α is commonly used in synthetic biology to control the activity of genome editing tools. The activating ligands, estrogens, however, interfere with various cellular processes, thereby limiting the applicability of this receptor. Altering its ligand preference to chemicals of choice solves this hurdle but requires adaptation of unspecified ligand-interacting residues. Here, we provide a solution by combining rational protein design with multi-site-directed mutagenesis and directed evolution of stably integrated variants in Saccharomyces cerevisiae. This method yielded an estrogen receptor variant, named TERRA, that lost its estrogen responsiveness and became activated by tamoxifen, an anti-estrogenic drug used for breast cancer treatment. This tamoxifen preference of TERRA was maintained in mammalian cells and mice, even when fused to Cre recombinase, expanding the mammalian synthetic biology toolbox. Not only is our platform transferable to engineer ligand preference of any steroid receptor, it can also profile drug-resistance landscapes for steroid receptor-targeted therapies.

International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Engineering Compositionally Uniform Yeast Whole-Cell Biocatalysts with Maximized Surface Enzyme Density for Cellulosic Biofuel Production.

In recent decades, whole-cell biocatalysis has played an increasingly important role in the food, pharmaceutical, and energy sector. One promising application is the use of ethanologenic yeast displaying minicellulosomes on the cell surface to combine cellulose hydrolysis and fermentation into a single step for consolidated bioprocessing. However, cellulosic ethanol production using existing yeast whole-cell biocatalysts (yWCBs) has not reached industrial feasibility due to their inefficient cellulose hydrolysis. As prior studies have demonstrated enzyme density on the yWCB surface to be one of the most important parameters for enhancing cellulose hydrolysis, we sought to maximize this parameter at both the population and single-cell levels in yWCBs displaying tetrafunctional minicellulosomes. At the population level, enzyme density is limited by the presence of a nondisplay population constituting 25-50% of all cells. In this study, we identified the cause to be plasmid loss and successfully eliminated the nondisplay population to generate compositionally uniform yWCBs. At the single-cell level, we demonstrate that enzyme density is limited by molecular crowding, which hinders minicellulosome assembly. By adjusting the integrated gene copy number, we obtained yWCBs of tunable enzyme display levels. This tunability allowed us to avoid the crowding-limited regime and achieve a maximum enzyme density per cell. As a result, the best strain showed a cellulose-to-ethanol yield of 4.92 g/g, corresponding to 96% of the theoretical maximum and near-complete conversion (∼96%) of the starting cellulose (1% PASC). Our holistic engineering strategy that combines a population and single-cell level approach is broadly applicable to enhance the WCB performance in other biocatalytic cascade schemes.

Glutamine suppresses senescence and promotes autophagy through glycolysis inhibition-mediated AMPKα lactylation in intervertebral disc degeneration.

Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5'-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.

Micro Trojan horses: Engineering extracellular vesicles crossing biological barriers for drug delivery.

The biological barriers of the body, such as the blood-brain, placental, intestinal, skin, and air-blood, protect against invading viruses and bacteria while providing necessary physical support. However, these barriers also hinder the delivery of drugs to target tissues, reducing their therapeutic efficacy. Extracellular vesicles (EVs), nanostructures with a diameter ranging from 30 nm to 10 µm secreted by cells, offer a potential solution to this challenge. These natural vesicles can effectively pass through various biological barriers, facilitating intercellular communication. As a result, artificially engineered EVs that mimic or are superior to the natural ones have emerged as a promising drug delivery vehicle, capable of delivering drugs to almost any body part to treat various diseases. This review first provides an overview of the formation and cross-species uptake of natural EVs from different organisms, including animals, plants, and bacteria. Later, it explores the current clinical applications, perspectives, and challenges associated with using engineered EVs as a drug delivery platform. Finally, it aims to inspire further research to help bioengineered EVs effectively cross biological barriers to treat diseases.

High-resolution self-corrected single-pixel imaging through dynamic and complex scattering media: erratum.

We correct typographical errors in our paper [Opt. Express31, 23027 (2023)10.1364/OE.489808]. The corrections have no influence on the results and conclusions of the original paper.

Synthetic enhancers including TFREs improve transgene expression in CHO cells.

The human cytomegalovirus major immediate early gene (CMV) promoter is currently the most preferred promoter for recombinant therapeutic proteins (RTPs) production in CHO cells. To enhance the production of RTPs, five synthetic enhancers including multiple transcription factor regulatory elements (TFREs) were evaluated to enhance recombinant protein level in transient and stably transfected CHO cells. Compared with the control, four elements can enhance the report genes expression under both two transfected states. Further, the function of these four enhancers on human serum albumin (HSA) were investigated. We found that the transient expression can increase by up to 1.5 times, and the stably expression can maximum increase by up to 2.14 times. The enhancement of transgene expression was caused by the boost of their corresponding mRNA levels. Transcriptomics analysis was performed and found that transcriptional activation and cell cycle regulation genes were involved. In conclusion, optimization of enhancers in the CMV promoter could increase the production yield of transgene in transfected CHO cells, which has significance for developing high-yield CHO cell expression system.

[Research progress on the mechanism of the impact of maternal childhood trauma on intergenerational transmission]. / æ¯äº²ç«¥å¹´æœŸåˆ›ä¼¤å¯¹ä»£é™ ä¼ é€’å½±å“æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

Childhood trauma refers to trauma experiences encountered during childhood and adolescence. Maternal childhood trauma experiences have a lasting impact on the next generation, affecting their physical and mental well-being. The mechanisms involved include the hypothalamic-pituitary-adrenal axis, inflammatory factors, brain structure and function, gene interactions, and parenting styles. This paper systematically reviews the mechanisms of the impact of maternal childhood trauma on intergenerational transmission, providing insights for the prevention of intergenerational transmission of childhood trauma.

Discriminatory fluorescence and FRET in the chiral-perovskite/RhB system.

Förster resonance energy transfer (FRET) holds a significant position in various natural and artificial systems, especially within donor-acceptor systems encompassing chiral components. Despite extensive investigations, a clear understanding of the effects of chirality and FRET on discriminatory fluorescence remains elusive. Here, chiral perovskite nanowires (CPNWs) and achiral rhodamine B (RhB) are employed to examine the FRET and discriminatory fluorescence behavior in a donor-acceptor system involving a chiral nanostructure. A notable FRET from the CPNWs to RhB is observed, along with circular dichroism (CD) and circularly polarized luminescence (CPL) activities in RhB. Although the FRET interaction remains consistent over time, a notable inversion in the polarity preference of the CD and CPL of RhB is observed. This reveals that the discriminatory fluorescence of the acceptor arises from the electromagnetic influence of the chiral donor. These findings elucidate that "chirality", as a property related to spatial orientation, cannot accompany the transfer of energy (which is a scalar) from chiral nanostructures to achiral molecules, which helps advance the understanding of the discriminatory fluorescence in the donor-acceptor system with a chiral nanostructure.

Remodeling of the Intra-Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein-Based Conduit.

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing.

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.