Collaborative augmented reconstruction of 3D neuron morphology in mouse and human brains.

Digital reconstruction of the intricate 3D morphology of individual neurons from microscopic images is a crucial challenge in both individual laboratories and large-scale projects focusing on cell types and brain anatomy. This task often fails in both conventional manual reconstruction and state-of-the-art artificial intelligence (AI)-based automatic reconstruction algorithms. It is also challenging to organize multiple neuroanatomists to generate and cross-validate biologically relevant and mutually agreed upon reconstructions in large-scale data production. Based on collaborative group intelligence augmented by AI, we developed a collaborative augmented reconstruction (CAR) platform for neuron reconstruction at scale. This platform allows for immersive interaction and efficient collaborative editing of neuron anatomy using a variety of devices, such as desktop workstations, virtual reality headsets and mobile phones, enabling users to contribute anytime and anywhere and to take advantage of several AI-based automation tools. We tested CAR's applicability for challenging mouse and human neurons toward scaled and faithful data production.

Trophic Stoichiometry of Macroelements and Metals in a Terrestrial Food Web.

In order to understand the transfer of macroelements and toxic metals in the terrestrial food web, barn swallows, terrestrial frogs, and insects were collected from farmlands in the Leizhou Peninsula, and analyzed for macroelements carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) and trace metals nickel (Ni), zinc (Zn), selenium (Se), copper (Cu), chromium (Cr), cadmium (Cd), lead (Pb), and mercury (Hg). The multi-element ecological stoichiometry was discussed to trace the food web flow of nutrients and toxicants. The percentage contents of C, N, P, and S were 35.43-59.91%, 6.89-12.11%, 0.49-4.66%, and 0.44-2.19%, respectively. The concentrations of Ni, Zn, Se, Cu, Cr, Cd, Pb, and Hg were 0.163-116 mg/kg, 38.7-227 mg/kg, 0.0453-3.82 mg/kg, 3.11-141 mg/kg, not detected-79.6 mg/kg, 0.0203-0.358 mg/kg, 0.148-4.57 mg/kg, and 0.00159-1.46 mg/kg, respectively. Organisms at high trophic levels had higher contents of N, P, and S, and lower contents of C. Significant correlations were observed between δ15N and ratios of C: N, C: P, C: S, N: P, N: S, and S: P, indicating selective transfer of biogenic elements for predators in the terrestrial food web. Most metals including Ni, Zn, Se, Cu, Cr, Pb, and Hg had biomagnification factors and trophic magnification factors higher than 1, because the whole body of organisms rather than tissues were used. The negative correlations between the detoxification ratios of Se: X (each toxic metal) and metal concentrations suggest potential adverse effect of metals on terrestrial organisms.

Self-Assembled Peptide with Morphological Structure for Bioapplication.

Peptide materials, such as self-assembled peptide materials, are very important biomaterials. Driven by multiple interaction forces, peptide molecules can self-assemble into a variety of different macroscopic forms with different properties and functions. In recent years, the research on self-assembled peptides has made great progress from laboratory design to clinical application. This review focuses on the different morphologies, including nanoparticles, nanovesicles, nanotubes, nanofibers, and others, formed by self-assembled peptide. The mechanisms and applications of the morphology transformation are also discussed in this paper, and the future direction of self-assembled nanomaterials is envisioned.

mhealth-based interventions to improving liver cancer screening among high-risk populations: a study protocol for a randomized controlled trial.

BACKGROUND: Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people's main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg's Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. METHODS: We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. DISCUSSION: The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

Human and bats genome robustness under COSMIC mutational signatures.

Carcinogenesis is an evolutionary process, and mutations can fix the selected phenotypes in selective microenvironments. Both normal and neoplastic cells are robust to the mutational stressors in the microenvironment to the extent that secure their fitness. To test the robustness of genes under a range of mutagens, we developed a sequential mutation simulator, Sinabro, to simulate single base substitution under a given mutational process. Then, we developed a pipeline to measure the robustness of genes and cells under those mutagenesis processes. We discovered significant human genome robustness to the APOBEC mutational signature SBS2, which is associated with viral defense mechanisms and is implicated in cancer. Robustness evaluations across over 70,000 sequences against 41 signatures showed higher resilience under signatures predominantly causing C-to-T (G-to-A) mutations. Principal component analysis indicates the GC content at the codon's wobble position significantly influences robustness, with increased resilience noted under transition mutations compared to transversions. Then, we tested our results in bats at extremes of the lifespan-to-mass relationship and found the long-lived bat is more robust to APOBEC than the short-lived one. By revealing APOBEC as the prime driver of robustness in the human (and other mammalian) genome, this work bolsters the key potential role of APOBECs in carcinogenesis, as well as evolved countermeasures to this innate mutagenic process. It also provides the baseline of the human and bat genome robustness under mutational processes associated with cancer.

Dual-Mechanism Design Strategy for High-Efficiency and Long-Lived Organic Afterglow Materials.

Organic room-temperature phosphorescence (RTP) and afterglow materials hold great potential for various applications, but there remain inherent trade-offs between the afterglow efficiency and the lifetime. Here, we propose a dual-mechanism design strategy, leveraging the RTP or thermally activated delayed fluorescence (TADF) mechanism for a high afterglow efficiency and the organic long-persistent luminescence (OLPL) mechanism for a prolonged afterglow duration. The intramolecular charge transfer (ICT)-type difluoroboron ß-diketonate molecules with a large S1 dipole moment are doped as the luminescent component into the organic matrix with a large dipole moment, and a series of TADF-type afterglow materials can be achieved with an afterglow efficiency of up to 88.7% and an afterglow lifetime of 200 ms. To prolong the afterglow duration, an electron donor is introduced as the third component to generate traps and facilitate charge separation. The obtained materials exhibit a dual afterglow mechanism, first exhibiting a TADF/RTP afterglow with an afterglow efficiency of up to 50.9%, followed by an hours-long OLPL afterglow emission with an afterglow efficiency of up to 13.1%. Further investigations reveal that an appropriate heavy-atom effect can facilitate the intersystem crossing process, which can promote the charge separation process and thus improve the OLPL afterglow performance. Additionally, rare-earth upconversion materials are introduced into OLPL materials to enable their near-infrared excitation properties, showcasing their potential applications in bioimaging.

Progress towards understanding the effects of artificial light on the transmission of vector-borne diseases.

Artificial light at night (ALAN) is a common form of light pollution worldwide, and the intensity, timing, duration, and wavelength of light exposure can affect biological rhythms, which can lead to metabolic, reproductive, and immune dysfunctions and consequently, host-pathogen interactions. Insect vector-borne diseases are a global problem that needs to be addressed, and ALAN plays an important role in disease transmission by affecting the habits and physiological functions of vector organisms. In this work, we describe the mechanisms by which ALAN affects host physiology and biochemistry, host-parasite interactions, and vector-borne viruses and propose preventive measures for related infectious diseases to minimize the effects of artificial light on vector-borne diseases.

Polymer-Based Room-Temperature Phosphorescence Materials Exhibiting Emission Lifetimes up to 4.6 s under Ambient Conditions.

The long-emission-lifetime nature of room-temperature phosphorescence (RTP) materials lays the foundation of their applications in diverse areas. Despite the advantage of mechanical property, processability and solvent dispersity, the emission lifetimes of polymer-based room-temperature phosphorescence materials remain not particularly long because of the labile nature of organic triplet excited states under ambient conditions. Specifically, ambient phosphorescence lifetime (τP) longer than 2 s and even 4 s have rarely been reported in polymer systems. Here, luminescent compounds with small phosphorescence rate on the order of approximately 10-1 s-1 are designed, ethylene-vinyl alcohol copolymer (EVOH) as polymer matrix and antioxidant 1010 to protect organic triplets are employed, and ultralong phosphorescence lifetime up to 4.6 s under ambient conditions by short-term and low-power excitation are achieved. The resultant materials exhibit high afterglow brightness, long afterglow duration, excellent processability into large area thin films, high transparency and thermal stability, which display promising anticounterfeiting and data encryption functions.

Native T1 mapping-based radiomics diagnosis of kidney function and renal fibrosis in chronic kidney disease.

Chronic kidney disease (CKD) raises major concerns for global public health as it is characterized by high prevalence, low awareness, high healthcare costs, and poor prognosis. Therefore, our study prospectively established and validated native T1 mapping-based radiomics models for the prediction of renal fibrosis and renal function in patients with CKD. Moreover, the area under the receiver operating characteristic curve (AUC) and diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate its performance. Thus, our results show that radiomics based on native T1 mapping images can better identify renal function and renal fibrosis in patients with CKD and outperform conventional T1 mapping parameters of ΔT1 and T1%, thus providing more information for CKD management and clinical decision-making.

Habitat Imaging With Tumoral and Peritumoral Radiomics for Prediction of Lung Adenocarcinoma Invasiveness on Preoperative Chest CT: A Multicenter Study.

Background: Tumors' growth processes result in spatial heterogeneity, with the development of tumor subregions (i.e., habitats) having unique biologic characteristics. Objective: To develop and validate a habitat model combining tumor and peritumoral radiomics features on chest CT for predicting invasiveness of lung adenocarcinoma. Methods: This retrospective study included 1156 patients (mean age, 57.5 years; 464 male, 692 female) from three centers and a public dataset, who underwent chest CT before lung adenocarcinoma resection (variable date ranges across datasets). Patients from one center formed training (n=500) and validation (n=215) sets; patients from the other sources formed three external test sets (n=249, 113, 79). For each patient, a single nodule was manually segmented on chest CT. The nodule segmentation was combined with an automatically generated 4-mm peritumoral region into a whole-volume volume-of-interest (VOI). A Gaussian mixture model (GMM) identified voxel clusters with similar first-order energy across patients. GMM results were used to divide each patient's whole-volume VOI into multiple habitats, defined consistently across patients. Radiomic features were extracted from each habitat. After feature selection, a habitat model was developed for predicting invasiveness, using pathologic assessment as a reference. An integrated model was constructed, combining features extracted from habitats and whole-volume VOIs. Model performance was evaluated, including in subgroups based on nodule density (pure ground-glass, part-solid, solid). Results: Invasive cancer was diagnosed in 625/1156 patients. GMM identified four as the optimal number of voxel clusters and thus of per-patient tumor habitats. The habitat model had AUC of 0.932 in the validation set, and 0.881, 0.880, and 0.764 in the three external test sets. The integrated model had AUC of 0.947 in the validation set and 0.936, 0.908, and 0.800 in the three external test sets. In the three external test sets combined, across nodule densities, AUCs for the habitat model were 0.836-0.969 and for the integrated model were 0.846-0.917. Conclusions: Habitat imaging combining tumoral and peritumoral radiomic features could help predict lung adenocarcinoma invasiveness. Prediction is improved when combining information on tumor subregions and the tumor overall. Clinical Impact: The findings may aid personalized preoperative assessments to guide clinical decision-making in lung adenocarcinoma.

Proton pump inhibitors may increase the risk of cisplatin-induced acute kidney injury in patients with nasopharyngeal carcinoma: a prospective cohort study.

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

Predictive Modeling of Early Neurological Deterioration in Patients with Acute Ischemic Stroke.

BACKGROUND: Ischaemic stroke is the leading cause of death worldwide, and early neurological deterioration(END) occurs in 20%-40% of patients, which is the main cause of severe neurological deficits and disability, and even increased mortality. The occurrence of END is closely related to the poor prognosis of the patients, so it is important to identify the risk factors for the occurrence of END in patients with AIS and target intervention at an early stage factors and targeted intervention is of great significance. METHODS: Up to December 20, 2023, a comprehensive search was conducted across PubMed, Embase, Web of Science, MedLine, and The Cochrane Library for studies focusing on predictive models for END in acute stroke patients. Included studies either developed or validated predictive models. The Prediction Model Risk of Bias Assessment tool was utilized to assess bias in these prediction models. Pooled area under the curve values were calculated using DerSimonian and Laird random-effects model. RESULTS: Nineteen studies, each presenting an original model, were identified. Predominantly constructed through logistic multiple regression, these models demonstrated robust predictive performance (area under the curve ≥0.80). Key predictors of END in acute ischemic stroke patients included blood glucose levels, baseline National Institute of Health Stroke Scale scores, extent of cerebral infarction, and stenosis in the carotid and middle cerebral arteries. DISCUSSION: Clinical practitioners should closely monitor high-frequency predictors of END in patients. However, the varying quality of current models necessitates the selection of models that balance performance with operational simplicity in clinical practice.

Multi-Axial Self-Driven X-Ray Detection by a Two-Dimensional Biaxial Hybrid Organic-Inorganic Perovskite Ferroelectric.

Metal halide perovskite ferroelectrics combining spontaneous polarization and excellent semiconducting properties is an ideal platform for enabling self-driven X-ray detection. However, achievements to date have been only based on uniaxiality, which increases the complexity of device fabrication. Multi-axial ferroelectric materials have multiple equivalent polarization directions, making them potentially amenable to multi-axial self-driven X-ray detection, but the report on these types of materials is still a huge blank. Herein, a high-quality (BA)2(EA)2Pb3I10 (1) biaxial ferroelectric single crystal was successfully grown, which exhibited significant spontaneous polarization along the c-axis and b-axis. Under X-ray irradiation, bulk photovoltaic effect (BPVE) was exhibited along both the c-axis and b-axis, with open circuit voltages (Voc) of 0.23 V and 0.22 V, respectively. Then, the BPVE revealed along the inversion of polarized direction with the polarized electric fields. Intriguingly, due to the BPVE of 1, 1 achieved multi-axial self-driven X-ray detection for the first time (c-axis and b-axis) with relatively high sensitivities and ultralow detection limits (17.2 nGyair s-1 and 19.4 nGyair s-1, respectively). This work provides a reference for the subsequent use of multi-axial ferroelectricity for multi-axial self-driven optoelectronic detection.

Case report: Xeroderma pigmentosum Group A with erythropoietic protoporphyria in a young Chinese patient.

Xeroderma pigmentosum is a rare autosomal recessive genodermatoses characterized by a deficiency in nucleotide excision repair. Erythropoietic protoporphyria is a rare inherited metabolic disease caused by the perturbation of heme. Xeroderma pigmentosum-erythropoietic protoporphyria is exceedingly rare. Hereby, we firstly report a young Chinese patient of xeroderma pigmentosum Group A with erythropoietic protoporphyria carrying an XPA Met214AsnfsTer7 frameshift mutation and a homozygous splicing mutation, c.315-48T>C, in the proband's intron3 of FECH.

Peritumoral radiomics increases the efficiency of classification of pure ground-glass lung nodules: a multicenter study.

PURPOSE: We aimed to evaluate the efficiency of computed tomography (CT) radiomic features extracted from gross tumor volume (GTV) and peritumoral volumes (PTV) of 5, 10, and 15 mm to identify the tumor grades corresponding to the new histological grading system proposed in 2020 by the Pathology Committee of the International Association for the Study of Lung Cancer (IASLC). METHODS: A total of 151 lung adenocarcinomas manifesting as pure ground-glass lung nodules (pGGNs) were included in this randomized multicenter retrospective study. Four radiomic models were constructed from GTV and GTV + 5/10/15-mm PTV, respectively, and compared. The diagnostic performance of the different models was evaluated using receiver operating characteristic curve analysis RESULTS: The pGGNs were classified into grade 1 (117), 2 (34), and 3 (0), according to the IASLC grading system. In all four radiomic models, pGGNs of grade 2 had significantly higher radiomic scores than those of grade 1 (P < 0.05). The AUC of the GTV and GTV + 5/10/15-mm PTV were 0.869, 0.910, 0.951, and 0.872 in the training cohort and 0.700, 0.715, 0.745, and 0.724 in the validation cohort, respectively. CONCLUSIONS: The radiomic features we extracted from the GTV and PTV of pGGNs could effectively be used to differentiate grade-1 and grade-2 tumors. In particular, the radiomic features from the PTV increased the efficiency of the diagnostic model, with GTV + 10 mm PTV exhibiting the highest efficacy.

Discovery of a Potent and Orally Bioavailable Xanthine Oxidase/Urate Transporter 1 Dual Inhibitor as a Potential Treatment for Hyperuricemia and Gout.

The main uric acid-lowering agents in clinical use for hyperuricemia and gout are xanthine oxidase (XO) inhibitors or urate transporter 1 (URAT1) inhibitors. While these therapies can partially control the disease, they have various limitations. The development of XO/URAT1 dual inhibitors offers the potential to enhance therapeutic potency and reduce toxicity compared with single-target inhibitors. Through scaffold hopping from the XO inhibitor febuxostat (2) and the URAT1 inhibitor probenecid (3), followed by structure-activity relationship (SAR) studies, we identified compound 27 as a potent dual inhibitor of XO and URAT1. Compound 27 demonstrated significant dual inhibition in vitro (XO IC50 = 35 nM; URAT1 IC50 = 31 nM) and exhibited favorable pharmacology and pharmacokinetic (PK) profiles in multiple species including monkeys. Furthermore, toxicity studies in rats and monkeys revealed general safety profiles, supporting that compound 27 emerges as a promising novel drug candidate with potent XO/URAT1 dual inhibition for the treatment of gout.

The Effect of Rifapentine and Rifampicin on Serum Voriconazole Levels Persist for 5 Days and 7 Days or More After Discontinuation in Tuberculosis Patients with Chronic Pulmonary Aspergillosis.

Purpose: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine. Patients and Methods: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses. Results: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (>70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine. Conclusion: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.

Bottlenose dolphins (Tursiops truncatus) display gaze alternation and referential communication in an impossible task.

Gaze cues play a vital role in conveying critical information about objects and locations necessary for survival, such as food sources, predators, and the attentional states of conspecific and heterospecific individuals. During referential intentional communication, the continuous alternation of gaze between a communicative partner and a specific object or point of interest attracts the partner's attention towards the target. This behaviour is considered by many as essential for understanding intentions and is thought to involve mental planning. Here, we investigated the behavioural responses of seven bottlenose dolphins (Tursiops truncatus) that were given an impossible task in the presence of two experimenters (a 'commanding experimenter' and a 'non-commanding experimenter'), whose attentional state towards the dolphins varied. We found that the dolphins spontaneously displayed gaze alternation, specifically triadic referential pointing, only when the human commanding experimenter was facing them. However, they ceased to alternate their gaze between the impossible object and the commanding experimenter when the experimenter had their back turned. Notably, the dolphins' behaviour differed from general pointing and gaze, as their triadic sequence occurred within a narrow time window. These findings suggest that the dolphins were sensitive to human attentional cues and utilized their own gaze cue (pointing) as a salient signal to attract the attention of the commanding experimenter towards a specific location.

Machine learning-derived prognostic signature for progression-free survival in non-metastatic nasopharyngeal carcinoma.

BACKGROUND: Early detection of high-risk nasopharyngeal carcinoma (NPC) recurrence is essential. We created a machine learning-derived prognostic signature (MLDPS) by combining three machine learning (ML) models to predict progression-free survival (PFS) in patients with non-metastatic NPC. METHODS: A cohort of 653 patients with non-metastatic NPC was divided into a training (n = 457) and validation (n = 196) dataset (7:3 ratio). The study included clinicopathological characteristics, hematologic markers, and MRI findings in three machine learning models-random forest (RF), extreme gradient boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO)-to predict progression-free survival (PFS). A Venn diagram identified the overlapping signatures from the three ML algorithms. Cox proportional hazard analysis determined the MLDPS for PFS. RESULTS: The RF, XGBoost, and LASSO algorithms identified six consensus factors from the 33 signatures. Cox proportional hazards analysis showed that the MLDPS includes age, lymphocyte count, number of positive lymph nodes, and regional lymph node density. Additionally, MLDPS effectively stratified prognosis, with low-risk individuals showing better PFS than high-risk individuals (p < 0.001). CONCLUSION: MLDPS, based on clinicopathological characteristics, hematologic markers, and MRI findings, is crucial for guiding clinical management and personalizing treatments for patients with non-metastatic NPC.

A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.

The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.