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Currently approved targeted treatment for ROS1-rearranged non-small-cell lung cancer (NSCLC) has either inadequate intracranial activity or CNS-related toxicities. We evaluated the efficacy and safety of foritinib, a novel ALK and ROS1 inhibitor, in patients with advanced ROS1-rearranged NSCLC.

IMPORTANCE: Uninterrupted targeted therapy until disease progression or intolerable toxic effects is currently the routine therapy for advanced non−small cell lung cancer (NSCLC) involving driver gene variations. However, drug resistance is inevitable. OBJECTIVE: To assess the clinical feasibility of adaptive de-escalation tyrosine kinase inhibitor (TKI) treatment guided by circulating tumor DNA (ctDNA) for achieving complete remission after local consolidative therapy (LCT) in patients with advanced NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This prospective nonrandomized controlled trial was conducted at a single center from June 3, 2020, to July 19, 2022, and included 60 patients with advanced NSCLC with driver variations without radiologically detectable disease after TKI and LCT. The median (range) follow-up time was 19.2 (3.8-29.7) months. Data analysis was conducted from December 15, 2022, to May 10, 2023. INTERVENTION: Cessation of TKI treatment and follow-up every 3 months. Treatment was restarted in patients with progressive disease (defined by the Response Evaluation Criteria in Solid Tumors 1.1 criteria), detectable ctDNA, or elevated carcinoembryonic antigen (CEA) levels, whichever manifested first, and treatment ceased if all indicators were negative during follow-up surveillance. MAIN OUTCOMES AND MEASURES: Progression-free survival (PFS). Secondary end points were objective response rate, time to next treatment, and overall survival. RESULTS: Among the total study sample of 60 participants (median [range] age, 55 [21-75] years; 33 [55%] were female), the median PFS was 18.4 (95% CI, 12.6-24.2) months and the median (range) total treatment break duration was 9.1 (1.5-28.1) months. Fourteen patients (group A) remained in TKI cessation with a median (range) treatment break duration of 20.3 (6.8-28.1) months; 31 patients (group B) received retreatment owing to detectable ctDNA and/or CEA and had a median PFS of 20.2 (95% CI, 12.9-27.4) months with a median (range) total treatment break duration of 8.8 (1.5-20.6) months; and 15 patients (group C) who underwent retreatment with TKIs due to progressive disease had a median PFS of 5.5 (95% CI, 1.5-7.2) months. For all participants, the TKI retreatment response rate was 96%, the median time to next treatment was 29.3 (95% CI, 25.3-35.2) months, and the data for overall survival were immature. CONCLUSIONS AND RELEVANCE: The findings of this nonrandomized controlled trial suggest that this adaptive de-escalation TKI strategy for patients with NSCLC is feasible in those with no lesions after LCT and a negative ctDNA test result. This might provide a de-escalation treatment strategy guided by ctDNA for the subset of patients with advanced NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03046316

A promising approach to prevent heat- and cold-related illnesses is the integration of zero-energy input control technology into personal thermal management (PTM) systems while reducing energy consumption. However, achieving optimal wearing comfort while maintaining subambient metabolic temperatures using thermally regulating materials without an energy supply remains challenging. In this study, we provide a simple and reliable methodology to produce a phase-changeable metafabric made of thermoplastic polyurethane and phase change capsule (PCC) particles with high moisture permeability and thermal comfort. This approach skillfully incorporates spray-formed PCC particles into a three-dimensional nanofibrous aggregate, forming a stable self-entangled network structure in a single step through simultaneous humidity-assisted electrospraying and electrospinning processes. Additionally, the metafabric demonstrates prominent water resistance and superhydrophobicity, which are attributed to the integration of PCC particles and nanofibers, resulting in the formation of a microporous/nanoporous structure resembling the surface of a lotus leaf. As a result, the phase-changeable metafabric shows an active and passive thermal control performance, with a water vapor transmittance rate of 13.1 kg m–2d–1and a phase change enthalpy of 115.05 J g–1even after 100 thermal cycles. Furthermore, it displays excellent waterproofing capability, characterized by a water contact angle of 158.7° and the ability to withstand a high hydrostatic pressure of 87 kPa. In addition, the metafabric exhibits a good mechanical performance, boasting a tensile strength of 10.5 MPa. Overall, the proposed economical metafabric is an exemplary candidate material for next-generation PTM systems.

The developments of modern surveillance technology pose great challenges to combat concealment for warfighters. Traditional camouflage suits cannot accommodate the need for camouflage stealth in complex warfare scenarios. Herein, a bidirectional diffusion-controlled in situ synthesis methodology is reported to achieve electrochromic nanofibrous membranes with mimetic chameleon skin structures (CSENs) by assembling electrochromic covalent organic frameworks on nanofibers. CSENs exhibit reversible color changes in the visible and near-infrared ranges under an applied potential with fast response times (25.8 s/26.2 s). The macro- and mesoporous structures in CSENs favored the transportation of electrolyte ions, achieving excellent color difference and coloration efficiency of 35.58 and 1053.26 cm2/C, respectively. Importantly, CSENs feature unique properties of self-standing, breathability, and flexibility, which are attributed to the micrometer pores constructed by entangled nanofibers. As a proof-of-concept study, the CSEN-based flexible electrochromic suit exhibits a dynamic camouflage function in real environments, showing promising properties as smart textiles for dynamic camouflage stealth.

Extracellular vesicles (EVs) have garnered significant attention in biomedical applications. However, the rapid, efficient, and unbiased separation of EVs from complex biological fluids remains a challenge due to their heterogeneity and low abundance in biofluids. Herein, we report a novel approach to reconfigure and modify an artificial insertion peptide for the unbiased and rapid isolation of EVs in 20 min with ∼80% recovery in neutral conditions. Moreover, the approach demonstrates exceptional anti-interference capability and achieves a high purity of EVs comparable to standard ultracentrifugation and other methods. Importantly, the isolated EVs could be directly applied for downstream protein and nucleic acid analyses, including proteomics analysis, exome sequencing analysis, as well as the detection of both epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) gene mutation in clinical plasma samples. Our approach offers great possibilities for utilizing EVs in liquid biopsy, as well as in various other biomedical applications.

RNA is an essential biomolecule that determines and regulates numerous biological process in cells. The sensitive and specific imaging of the expression level, localization and dynamic change of RNAs in living cells possesses great significance in biological and medicine. The fluorescence functional nucleic acid probes with well-designed sequences are increasingly reported to be applied for living cell imaging, ascribing to their exceptional sensitivity and designability. In this review, the importance and examples of the living cell imaging of different types of RNAs are discussed. The fluorescence imaging methods based on functional nucleic acid probes, including non-amplification and amplification methods, are detailedly introduced. Especially, the combination of different amplification methods to achieve superior imaging performance is an advanced strategy to overcome the disadvantages of single amplification methods, so these methods are also introduced in detail. Finally, the downstream applications including subcellular imaging, in-depth disease mechanism investigation and disease diagnosis are demonstrated. In general, functional nucleic acid probe is a promising tool for imaging of RNAs in living cells, and this technique is rapidly improving ascribing to the emerging advances in functional nucleic acid and microscopy technology.

Due to the substantial heterogeneity among extracellular vesicle (EV) subpopulations, single-EV analysis has the potential to elucidate the mechanisms behind EV biogenesis and shed light on the myriad functions, leading to the development of novel diagnostics and therapeutics. While many studies have been devoted to reveal between-EV variations in surface proteins and RNAs, DNA cargos (EV-DNA) have received little attention. Here, we report a hydrogel-based droplet digital multiple displacement amplification approach for the comprehensive analysis of EV-DNA at the single-EV level. Single EVs are dispersed in thousands of hydrogel droplets and lysed for DNA amplification and identification. The droplet microfluidics strategy empowers the assay with single-molecule sensitivity and capability for absolute quantification of DNA-containing EVs. In particular, our findings indicate that 5–40% EVs are associated with DNA, depending on the cell of origin. Large EVs exhibit a higher proportion of DNA-containing EVs and a more substantial presence of intraluminal DNA, compared to small EVs. These DNA-containing EVs carry multiple DNA fragments on average. Furthermore, both double-stranded DNA and single-stranded DNA were able to be detected at the single-EV level. Utilizing this method, the abundance, distribution, and biophysical properties of EV-DNA in various EV populations are evaluated. The DNA level within EVs provides insight into the status of the originating cells and offers valuable information on the outcomes of anticancer treatments. The utilization of single-EV analysis for EV-DNA holds significant promise for early cancer detection and treatment response monitoring.

The digitization of health records and growing availability of tumour DNA sequencing provide an opportunity to study the determinants of cancer outcomes with unprecedented richness. Patient data are often stored in unstructured text and siloed datasets. Here we combine natural language processing annotations1,2with structured medication, patient-reported demographic, tumour registry and tumour genomic data from 24,950 patients at Memorial Sloan Kettering Cancer Center to generate a clinicogenomic, harmonized oncologic real-world dataset (MSK-CHORD). MSK-CHORD includes data for non-small-cell lung (n= 7,809), breast (n= 5,368), colorectal (n= 5,543), prostate (n= 3,211) and pancreatic (n= 3,109) cancers and enables discovery of clinicogenomic relationships not apparent in smaller datasets. Leveraging MSK-CHORD to train machine learning models to predict overall survival, we find that models including features derived from natural language processing, such as sites of disease, outperform those based on genomic data or stage alone as tested by cross-validation and an external, multi-institution dataset. By annotating 705,241 radiology reports, MSK-CHORD also uncovers predictors of metastasis to specific organ sites, including a relationship between SETD2mutation and lower metastatic potential in immunotherapy-treated lung adenocarcinoma corroborated in independent datasets. We demonstrate the feasibility of automated annotation from unstructured notes and its utility in predicting patient outcomes. The resulting data are provided as a public resource for real-world oncologic research.

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In this work, static immersion and gravimetric methods were used to study the corrosion behavior of three common stainless steels and four Ni-based alloys in a NaCl–MgCl2–KCl mixed molten salt under vacuum atmosphere. The corrosion test was conducted at 700 °C, with a maximum exposure time of 100 h. Corrosion behavior was determined by measuring the mass loss of the sample at different time intervals and the corrosion rates at 100 h. The microstructure of the alloy was analyzed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), atomic force microscope (AFM), and X-ray diffraction (XRD). The results showed that stainless steels were generally more severely corroded than Ni-based alloys. 304 stainless steel and In800H exhibited the worst corrosion resistance, whereas Ni-based alloy In625 had the best corrosion resistance. Fe and Cr were dissolved in the molten chloride salts and reacted with the molten chloride salts. Mo played a positive role in suppressing the corrosion of the alloys in molten chloride salts by inhibiting the outward diffusion of the elements.

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The increasing utilization of X-rays has generated a growing need for efficient shielding materials. However, the existing Pb-based materials suffer from a narrow X-ray absorbing range, high weight, and rigidity. Inspired by the natural leaf, which can efficiently absorb light through chlorophyll and carotenoids in confined cells, we engineer ultralight and superelastic nanofibrous Bi2O3/Gd2O3meta-aerogels (BGAs) with X-ray nanotrap arrays by manipulating the 3D confined assembly of 1D Bi2O3and Gd2O3nanofibers. The BGAs can synergistically absorb X-ray photons from complementary energy ranges into the nanotraps and induce cyclic collisions with Bi2O3and Gd2O3nanofibers, maximizing the effective X-ray attenuation. The meta-aerogel exhibits the integrated performance of efficient X-ray shielding efficiency (60–83%, 16–90 keV), ultralow density (10 mg cm–3), and superelasticity. The production of these meta-aerogels presents an avenue for the development of next-generation X-ray protective materials and the resolution of X-ray imaging systems.

The tremendous menace of the COVID-19 pandemic has underscored the urgency for antipathogen masks to stop the transmission of airborne infectious diseases. Most prevailing antipathogen masks manifest a slower sterilization rate that lags behind the pathogen momentum traversing the masks, thereby engendering an elevated susceptibility to infection. Here we tailor nanofibrous meta-aerogel electric traps, 3D-assembled from self-knotted carbon nanotube networks in an all rigid nanofibrous skeleton. This superior configuration revolves around the creation of numerous “dielectrophoretic–aerodynamic grippers”, which are capable of directional manipulation of microbes toward the region of the lethal intensive electric field. Based on this, we present a disinfection unit comprising a pair of aerogel electrodes that demonstrate a rapid killing rate (>99.99% biocidal efficacy within 0.016 s) and long-term durability (12 h of continuous operation). Additionally, a microbutton lithium cell is employed as a power supply to fabricate an antipathogen face mask with this disinfection unit, which exhibits superior pathogen inactivation efficacy compared to commercial masks. This scalable biocidal protective equipment holds great potential for use in emergency medical services.

Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, to cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.

Objective: To investigate comorbidities among hospitalized patients with dementia. Method: Data were extracted from the discharge records in our hospital. Comorbidities based on ICD-10 were selected from the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). The distributions of these comorbidities were described in dementia inpatients and age- and sex-matched nondementia controls, as well as in inpatients with Alzheimer’s disease and vascular dementia. A logistic regression model was applied to identify dementia-specific morbid conditions. Results: A total of 3355 patients with dementia were included, with a majority of 1503 (44.8%) having Alzheimer's disease, 395 (11.8%) with vascular dementia, and 441 (13.1%) with mixed dementia. The mean number of comorbidities was 3.8 in dementia patients (vs. 2.9 in controls). The most prevalent comorbidities in inpatients with dementia compared with those without dementia were cerebral vascular disease (73.0% vs. 35.9%), hypertension (62.8% vs. 56.2%), and peripheral vascular disease (53.7% vs. 31.2%). Comorbidities associated with dementia included epilepsy (OR 4.8, 95% CI 3.5–6.8), cerebral vascular disease (OR 4.1, 95% CI 3.7–4.5), depression (OR 4.0, 95% CI 3.2–5.0), uncomplicated diabetes (OR 1.5, 95% CI 1.4–1.7), peripheral vascular disease (OR 1.8, 95% CI 1.6–2.0), rheumatoid arthritis collagen vascular disease (OR 1.7, 95% CI 1.3–2.3), and anemia (OR 1.2, 95% CI 1.04–1.3). Some comorbidities suggested a protective effect against dementia. They were hypertension (OR 0.8, 95% CI 0.7–0.9), COPD (OR 0.6, 95% CI 0.5–0.6), and solid tumor without metastasis (OR 0.4, 95% CI 0.3–0.4). Vascular dementia has more cardiovascular and cerebrovascular comorbidities than Alzheimer's disease. Conclusion: Patients with dementia coexisted with more comorbidities than those without dementia. Comorbidities (esp. cardio-cerebral vascular risks) in patients with vascular dementia were more than those in patients with AD. Specifically, vascular and circulatory diseases, epilepsy, diabetes and depression increased the risk of dementia.

To explore targeted treatment options in patients with non-small-cell lung cancer (NSCLC) with rare genetic mutations in the context of a patient-centric clinical trial, we initiated, in parallel, a phase 2 adaptive umbrella trial consisting of a criteria-fulfilled (CF) cohort and a compassionate use (CU) cohort under expanded eligibility criteria, and a prospective real-world study (RWS). Here, we present efficacy and safety data from 48 patients with treatment-naive, advanced HER2-mutant NSCLC treated with the pan-HER receptor tyrosine kinase inhibitor pyrotinib (CF and CU cohorts) or physician’s therapy of choice (RWS cohort). In the phase 2 trial CF cohort (n= 28), the primary endpoint was reached with an objective response rate of 35.7% after pyrotinib treatment. Secondary endpoints included disease control rate (89.3%), median progression-free survival (PFS) (7.3 months), median overall survival (OS) (14.3 months) and toxicity, which was acceptable, with grade 3 or 4 treatment-related adverse events occurring in three patients (10.7%). The phase 2 trial CU cohort (n= 12) showed an objective response rate of 16.7%, disease control rate of 83.4%, median PFS of 4.7 months and median OS of 14.2 months after pyrotinib treatment. The RWS cohort (n= 8) had no responses to physician’s therapy of choice, while median PFS and OS were 3.0 and 12.2 months, respectively. Phase 2 umbrella trial, clinicaltrials.gov identifier: NCT03574402. RWS, clinicaltrials.gov identifier: NCT03605602.

In this work, four new cyclodepsipeptides, fusarihexins C–E (1–3) and enniatin Q (4), four new cyclopentane derivatives, fusarilins A–D (5–8), together with eight known compounds (9–16), were isolated from cultures of the endophytic fungus Fusariumsp. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR spectroscopic data. The absolute configurations were determined using Marfey’s method, a modified Mosher’s method, single-crystal X-ray diffraction analysis, and ECD analysis. The antitumor activities of the isolated compounds in vitro were evaluated. Cyclodepsipeptides displayed cytotoxicities against the Huh-7, MRMT-1, and HepG-2 cell lines. Compounds 4, 9, 10, and 12with IC50values of 1.0–9.1 μM exhibited the most potent cytotoxicities against the three cell lines as compared to the positive control-5-fluorouracil. Compounds 1–3and 11exhibited moderate cytotoxic activities (IC50values of 10.7–20.1 μM).

The widespread use of X-rays has prompted a surge in demand for effective and wearable shielding materials. However, the Pb-containing materials currently used to shield X-rays are commonly bulky, hard, and biotoxic, severely limiting their applications in wearable scenarios. Inspired by the nacre, we report on ultralight, superelastic, and nontoxic X-ray shielding nanofibrous aerogels with microarch-engineered brick/mortar structure by combining polyurethane/Bi2O3nanofibers (brick) and Gd2O3nanosheets (mortar). The synergistic attenuation effect toward X-rays from the reflection of microarches and absorption of Bi/Gd elements significantly enhances the shielding efficiency of aerogels, and microarches/robust nanofibrous networks endow the materials with superelasticity. The resultant materials exhibit integrated properties of superior X-ray shielding efficiency (91–100%), ultralow density (52 mg cm–3), large stretchability of 800% reversible elongation, and high water vapor permeability (8.8 kg m–2day–1). The fabrication of such novel aerogels paves the way for developing next-generation effective and wearable X-ray shielding materials.

Imaging of tumor-associated microRNAs (miRNAs) can provide abundant information for cancer diagnosis, whereas the occurrence of trace amounts of miRNAs in normal cells inevitably causes an undesired false-positive signal in the discrimination of cancer cells during miRNA imaging. In this study, we propose a dual-locked (D-locked) platform consisting of the enzyme/miRNA-D-locked DNAzyme sensor and the honeycomb MnO2nanosponge (hMNS) nanocarrier for highly specific cancer cell imaging. For a proof-of-concept demonstration, apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 were chosen as key models. The hMNS nanocarrier can efficiently release the D-locked DNAzyme sensor in living cells due to the decomposition of hMNS by glutathione, which can also supply Mn2+for DNAzyme cleavage. Ascribing to the smart design of the D-locked DNAzyme sensor, the fluorescence signal can only be generated by the synergistic response of APE1 and miR-21 that are overexpressed in cancer cells. Compared with the miRNA single-locked DNAzyme sensor and the small-molecule (ATP)/miRNA D-locked DNAzyme sensor, the proposed enzyme (APE1)/miRNA D-locked DNAzyme sensor exhibited 2.6-fold and 2.4-fold higher discrimination ratio (Fcancer/Fnormal) for cancer cell discrimination, respectively. Owing to the superior performance, the D-locked strategy can selectively generate a fluorescence signal in cancer cells, facilitating accurate discrimination of cancer both in vitroand in vivo. Furthermore, this D-locked platform is easily adaptable toward other target molecules by redesigning the DNA sequences. The outstanding performance and expansibility of this D-locked platform holds promising prospects for cancer diagnosis and related biomedical applications.

Small extracellular vesicles (sEVs) play important roles in mediating intercellular communication and regulating biological processes. Facile sEV isolation is the essential and preliminary issue for their function investigation and downstream biomedical applications, while the traditional methods are challenged by tedious procedures, low purity, low yield, and potential damage. In this work, we developed an sEV isolation paper-based device (sEV-IsoPD) based on a three-dimensional (3D) paper chip, which is composed of a porous membrane for size exclusion and a metal–organic framework (MOF)/antibody-modified paper for immunoaffinity capture. In combination with a peristaltic pump-driven flow system, the sEV-IsoPD can efficiently isolate EV from cell culture medium and serum. Compared with the ultracentrifugation method, sEV-IsoPD exhibited a 5.1 times higher yield (1.7 × 109mL–1), 1.6 times higher purity (1.6 × 1011mg–1), and 7.5 times higher recovery (77.3%) with only 8.3% of the time (30 min) and 1.0% of the instrument cost ($710). Moreover, sEV concentration can be visually detected in a quantitative manner with this paper-based device with a linear range from 3.0 × 106to 3.0 × 1010mL–1and a detection limit of 2.2 × 106mL–1. The sEV-IsoPD provides an efficient and practical approach for the rapid isolation and visible detection of sEVs, which are promising for the preparation of sEVs and diagnosis of disease.

Soybean is one of the most important food crops worldwide. Like other legumes, soybean can form symbiotic relationships with Rhizobiumspecies. Nitrogen fixation of soybean viaits symbiosis with Rhizobiumis pivotal for sustainable agriculture. Type III effectors (T3Es) are essential regulators of the establishment of the symbiosis, and nodule number is a feature of nitrogen-affected nodulation. However, genes encoding T3Es at quantitative trait loci (QTLs) related to nodulation have rarely been identified. Chromosome segment substitution lines (CSSLs) have a common genetic background but only a few loci with heterogeneous genetic information; thus, they are suitable materials for identifying candidate genes at a target locus. In this study, a CSSL population was used to identify the QTLs related to nodule number in soybean. Single nucleotide polymorphism (SNP) markers and candidate genes within the QTLs interval were detected, and it was determined which genes showed differential expression between isolines. Four candidate genes (GmCDPK28, GmNAC1, GmbHLH, and GmERF5) linked to the SNPs were identified as being related to nodule traits and pivotal processes and pathways involved in symbiosis establishment. A candidate gene (GmERF5) encoding a transcription factor that may interact directly with the T3E NopAA was identified. The confirmed CSSLs with important segments and candidate genes identified in this study are valuable resources for further studies on the genetic network and T3Es involved in the signaling pathway that is essential for symbiosis establishment.

Dynamic observation of the behaviors of nanomaterials in the cellular environment is of great significance in mechanistic investigations on nanomaterial-based diagnostics and therapeutics. Realizing label-free observations with nanometer resolution is necessary but still has major challenges. Herein, we propose a NanoSuit-assisted liquid-cell scanning electron microscopy (NanoSuit-LCSEM) method that enables imaging of the behaviors of nanoparticles in living cells. Taking A549 cells and gold nanoparticles (AuNPs) as a cell–nanoparticle interaction model, the NanoSuit-LCSEM method showed a significantly improved resolution to 10 nm, which is high enough to distinguish single and two adjacent 30 nm AuNPs in cells. The continuous observation time for living cells is extended to 30 min, and the trajectories and velocities for the transmembrane movement of AuNP aggregates are obtained. This study provides a new approach for dynamic observation of nanomaterials in intact living cells and will greatly benefit the interdisciplinary research of nanomaterials, nanomedicine, and nanotechnology.

The influence of MgO content in slag on wetting and corrosion behavior between slag and MgO–C refractory was investigated. It can be known from the high-temperature wetting experiment that as the MgO content in the slag increases, the final contact angle between the slag and the MgO–C refractory gradually increases and the penetration depth of the slag into the refractory gradually decreases from 60.54 μm (when the MgO content is 8%) to 28.11 μm (when the MgO content is 12%). The CaO and SiO2in the slag penetrate into the MgO–C refractory along the pores or surface cracks formed by carbon oxidation and react with MgO to generate a large amount of low-melting compound CaO–MgO–SiO2, which accelerates the corrosion of the refractory. As the MgO content in slag increases, the viscosity of the slag increases and the fluidity becomes worse, so that the mass transfer and diffusion of molecules or ions in the slag are weakened. In addition, the increase in MgO reduces the activity of FeO in the slag, which inhibits the interfacial chemical reaction, thereby weakening the wetting effect caused by the reaction.

To date, the reckless use of deadly chemical warfare agents (CWAs) has posed serious risks to humanity, property, and ecological environment. Therefore, necessary materials able to rapidly adsorb and securely decompose these hazardous toxics are in urgent demand. Herein, three-dimensional (3D) reduced graphene oxide/Zr-doped TiO2nanofibrous aerogels (RGO/ZT NAs) are synthesized by feasibly combining sol–gel electrospinning technology and a unidirectional freeze-drying approach. Benefiting from the synergetic coassembly of flexible ZT nanofibers and pliable RGO nanosheets, the hierarchically entangled fibrous frameworks feature ultralow density, superior elasticity, and robust fatigue resistance over 106compressive cycles. In particular, the RGO incorporation is attributed to the achieved increased surface area, stronger light absorption, and decreased recombination of charge-carriers for photocatalysis. The highly porous 3D RGO/ZT NAs deliver enhanced photothermal catalytic activity for CWA degradation as well as excellent recyclability and good photostability. This work opens fresh horizons for developing advanced 3D aerogel-based photocatalysts in a controlled fashion.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

The development of targeted drugs in the Eastern Asia region is going through a flourishing stage. With the continuous advancement of technology and medical research, biotechnology companies and research institutions in the region have made significant progress in cancer field. The Eastern Asian region not only actively participates in clinical trials, but is also committed to developing personalized medical plans to meet the diverse genotypes and phenotypes of patients. The governments and enterprises are increasingly valuing innovation, strengthening international cooperation, and promoting drug development. This paper summarizes the development of genetic testing technology, targeted drugs approval, ongoing promising clinical trials in the field of lung cancer and the important progress made by governments in the Eastern Asian region, and proposed key factors that will contribute to the promising future prospects in the region. The targeted drug market in the Eastern Asian region is expected to drive the medical field forward.

Waterborne pathogenic diseases serve as a driving force for the development of effective water disinfection technologies to ensure safe drinking water. However, current water disinfection methods fail to simultaneously achieve instant biocide action, low energy consumption, and high throughput. Here, we design a meta-membrane electric nanotrap, assembled from Ag nanowires self-assembled within a SiO2nanofibrous framework. By capitalizing on the synergistic effects of trapping and electroporation, this innovative nanotrap configuration enables instant and efficient sterilization. To demonstrate it, we present a disinfection unit equipped with the above membranes that exhibits a swift killing rate (over 6-log antibacterial efficacy within 0.053 s), operating at a high flux (11,200 L m−2 h−1) and an ultra-low driving voltage (1 V). This scalable and highly effective water disinfection technology possesses significant potential for application in daily life and emergency response situations.

High-performance thermally insulating ceramic materials with robust mechanical properties, high-temperature resistance, and excellent thermal insulation characteristics are highly desirable for thermal management systems under extreme conditions. However, the large-scale application of traditional ceramic granular aerogels is still limited by their brittleness and stiff nature, while ceramic fibrous aerogels often display high thermal conductivity. To meet the above requirements, in this study, ceramic nanofibrous-granular composite aerogels with lamellar multiarch cellular structure and leaf-like fibrous-granular binary networks are designed and fabricated. The resulting composite aerogels possess ultralow weight, superelasticity with recoverable compression strain up to 80%, and large mechanical strength. Furthermore, excellent fatigue resistance with 1.2% plastic deformation after 1000 cyclic compressions, temperature-invariant dynamic mechanical stability from −100 to 500 °C, and an operational temperature range from −196 to 1100 °C are successfully achieved in the proposed composites. The nanosized silica granular aerogels are assembled into a leaf-like shape and wrapped around the fibrous cell walls, endowing low thermal conductivity (0.024 W m–1K–1) as well as favorable high-temperature thermal superinsulation properties. Benefiting from the favorable compatibility, the present strategy for nanofiber-granular composite ceramic aerogels provides a dominant route to produce thermally insulated and mechanically robust composite cellular materials for use in harsh environments.

A continuous selective catalysis of 4-(Trifluoromethoxy)aniline, a key intermediate in the preparation of riluzole, was studied using a micropacked-bed reactor (µPBR) packed with Pt/BAC catalysts. The effects of technological parameters such as solvent types, gas flow rates and liquid flow rates were investigated. It was indicated that the continuous hydrogenation process exhibited higher efficiency, selectivity and safety with less energy consumption compared to the traditional batch reduction process. The newly developed reactor system demonstrated a sustained and stable catalytic performance after 20 h running.A continuous selective catalysis of 4-(trifluoromethoxy)aniline, a key intermediate in the preparation of the riluzole, was studied using a micropacked-bed reactor (µPBR) packed with Pt/BAC catalysts. It was indicated that the continuous hydrogenation process exhibited higher efficiency, selectivity and safety with less energy consumption compared to the traditional batch reduction process.

Traffic noise has been regarded as one of the most annoying pollutions that induce severe hazards to human health, both physiological and psychological. The commonly used fibrous noise absorption materials are limited by their large density, poor sound absorption ability at low frequencies, and unsatisfactory fire-resistant ability. Here, we develop hierarchically structured elastic ceramic electrospun nanofibrous aerogels, which possess lightweight properties (density of 13.29 mg cm–3) and superior low-frequency sound absorption ability (NRC value of 0.59). Specifically, the obtained ceramic electrospun nanofibrous aerogel is nonflammable on exposure to fire and can be compressed and quickly recover to its original height without any visible damage. Moreover, the resultant aerogels could be facilely and efficiently manufactured into designed shapes on a large scale, demonstrating their potential for industrialization. The successful design of such ceramic-based bulk materials may provide new insights for the further development of the next-generation high-efficiency sound-absorbing products.

As the last line of protection for humans, chemical protective suits provided safe and effective protection where chemical warfare agents (CWAs) or chemical reagents leaked; however, the existing chemical protective clothing had poor wearing pressure comfort due to the limitation of inherent materials. Herein, we reported a scalable strategy to fabricate chemical protective fabric (CPF) with a biomimetic extracellular matrix (ECM) barrier layer composed of an elastic fiber framework based on the cross-linked nanofiber membrane and the styrene–butadiene–styrene block copolymer (SBS)/acticarbon matrix. The construction of the reliable and strategical biomimetic ECM structure succeeded in fulfilling hazardous chemical barrier properties, recoverable deformation, and thermal comfort improvement. The resulting CPF exhibited waterproofness with exceeding 200 kPa hydrostatic pressure and exceptional WVT of 550.96 g m–2d–1, rapid elastic recovery from a strain of 80%, high-cycle fatigue resistance, superior barrier performance against toxic chemicals, and keeping CEES resistance after 100 tensile loading cycles. The successful preparation of the fascinating biomimetic nanofibrous membrane may provide a particular research foundation for developing chemical protective clothing in the future.

A reliable and sensitive strategy which can assess nucleic acid levels in living cells would be essential for fundamental research of biomedical applications. Some nanomaterial-based fluorescence biosensors recently developed for detecting nucleic acids, however, are often with expensive, complicated and time-consuming preparation process. Here, by using a facile bottom-up synthesis method, a two-dimensional (2D) coordination polymer (CP) nanosheet, [Cu(tz)] (Htz = 1,2,4-triazole), was successfully prepared after optimizing reaction conditions. These ultrathin CP nanosheets with thickness of 4.7 ± 1.1 nm could readily form nanosensors by assembly with DNA probes, which exhibited a low limit of detection (LOD) for p53 DNA fragment as 144 pmol/L. Furthermore, by integrating [Cu(tz)] nanosheets with hybridization chain reaction (HCR) probes, miR-21, one kind of microRNA upregulated in many cancer cells, can be sensitively detected with a LOD of 100 pmol/L and monitored in living cells, giving consistent results with those obtained by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Thus [Cu(tz)] nanosheets, which not only possess much better nucleic acids sensing performance than bulk cystals, but also exhibit nucleic acid delivery functions, could be used as a novel nanoplatform in biomedical imaging and sensing applications.

Recycling of deactivated palladium (Pd)-based catalysts can not only lower the economic cost of their industrial use but also save the cost for waste disposal. Considering that the sulfur-poisoned Pd (PdxSy) with a strong Pd–S bond is difficult to regenerate, here, we propose a direct reuse of such waste materials as an efficient catalyst for decontamination via Fenton-like processes. Among the PdxSymaterials with different poisoning degrees, Pd4S stood out as the most active catalyst for peroxymonosulfate activation, exhibiting pollutant-degradation performance rivaling the Pd and Co2+benchmarks. Moreover, the incorporated S atom was found to tune the surface electrostatic potentials and charge densities of the Pd active site, triggering a shift in catalytic pathway from surface-bound radicals to predominantly direct electron transfer pathway that favors a highly selective oxidation of phenols. The catalyst stability was also improved due to the formation of strong Pd–S bond that reduces corrosion. Our work paves a new way for upcycling of Pd-based industrial wastes and for guiding the development of advanced oxidation technologies toward higher sustainability.

EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation.

Due to its high strength, excellent electrical conductivity and high resistance to stress corrosion, Cu-Ni-Sn alloy has been selected as a kind of advanced metal material which can be used as the manufacture of springs, connectors, bearings and so on. In addition, the addition of Nb can efficiently improve the comprehensive properties of the alloy. In the present work, the effect of heat treatment conditions on microstructure and mechanical properties were studied in a Cu-9Ni-6Sn-0.22Nb alloy by means of optical microscopy (OM), transmission electron microscopy (TEM), tensile test and microhardness tests. The results show that before ageing, a large number of fine γ precipitates with DO22 type structure are distributed on the matrix. With the prolongation of ageing time, the ultimate tensile strength (UTS), yield strength (YS) and Vickers hardness increased firstly, and then decline. The reason can be attributed to the occurrence of spinodal decomposition and the formation of discontinuous precipitation (DP). At first, spinodal decomposition induced the enhanced interaction between dislocations and internal stress field, resulting in an increase of mechanical properties. Then the increased DP at grain boundaries leads to the decline of strength in the material. Finally, the relationship between the microstructure and the electrical conductivity was also analyzed, and the results show that the electrical conductivity increased with ageing time/ageing temperature increasing for the present alloy. Through the analysis of Matthiessen’ s rule, the variation of electrical resistivity depends on precipitates, solute atoms, dislocations, vacancies and grain boundaries, and the precipitates play an important role among them. Besides, more precipitates improve electrical conductivity. Therefore, the increase of ageing time/ageing temperature induced the increase of DP, resulting in an increase of electrical conductivity.

The uncertainty of distributed energy generation and the uncertainty risk of system components failure are important means to ameliorate the economy and reliability of Active Distribution Network (ADN). In this paper, a two-stage optimal scheduling method for ADN considering uncertainty risk is proposed. Considering the uncertainty risk of renewable resources, load and electricity price, and the uncertainty risk of system component failure, the two-stage optimal dispatching process of ADN with energy storage system is investigated. Firstly, the first stage model is established to minimize the cost of operation of ADN under normal operation conditions, and then the second stage model is established to minimize the load reduction under emergency operation. Particle Swarm Optimization (PSO) algorithm is proposed for model optimization. The simulation outcomes on IEEE-33 bus system simulation demonstrated high effectiveness of the proposed method.

Quantitative analysis of 5-hydroxymethylcytosine (5hmC) has remarkable clinical significance to early cancer diagnosis; however, it is limited by the requirement in current assays for large amounts of starting material and expensive instruments requring expertise. Herein, we present a highly sensitive fluorescence method, termed hmC-TACN, for global 5hmC quantification from several nanogram inputs based on terminal deoxynucleotide transferase (TdT)-assisted formation of fluorescent copper (Cu) nanotags. In this method, 5hmC is labeled with click tags by T4 phage β-glucosyltransferase (β-GT) and cross-linked with a random DNA primer via click chemistry. TdT initiates the template-free extension along the primer at the modified 5hmC site and then generates a long polythymine (T) tail, which can template the production of strongly emitting Cu nanoparticles (CuNPs). Consequently, an intensely fluorescent tag containing numerous CuNPs can be labeled onto the 5hmC site, providing the sensitive quantification of 5hmC with a limit of detection (LOD) as low as 0.021% of total nucleotides (S/N= 3). With only a 5 ng input (∼1000 cells) of genomic DNA, global 5hmC levels were accurately determined in mouse tissues, human cell lines (including normal and cancer cells of breast, lung, and liver), and urines of a bladder cancer patient and healthy control. Moreover, as few as 100 cells can also be distinguished between normal and cancer cells. The hmC-TACN method has great promise of being cost effective and easily mastered, with low-input clinical utility, and even for the microzone analysis of tumor models.

Poisons and poisonous weapons in armed conflict, especially chemical warfare agents (CWAs), pose serious threats to global security. Porous materials have recently been regarded as promising candidates to defend personnel in a CWA-contaminated environment, but challenges remain for integrating these materials into protective garments without sacrificing the intrinsic flexibility of fibers. Here, we report a rigid–flexible coupling hypercross-linking methodology to create flexible sponge-like nanofibers featuring hierarchical radial gradient porous nanoarchitectures, in which the inner structure is a mesoporous multichambered network, and the outer structure is a dense domain with a microporous network structure. Experimental and computational evidence supports the contention that sponge nanofibers with distinctive pore topology and robust bendability can be designed by manipulating the flexibility of building blocks. The resulting heterogeneous nanofibers exhibit integrated properties of spatially selective superstructures, abundant micropores, interconnected mesopores, a high surface area (579 m2g–1), remarkable flexibility, and exceptional CWA affinity, which are extraordinarily effective for adsorptive performance (498 mg g–1). The successful synthesis of these materials might inspire the development of chemical protective materials in an efficient, self-standing, and structurally adaptive form.

Polymeric fiber molecular sieves (PFMs) with ultrahigh surface areas, well-defined Murray’s-law hierarchical nanoporous structures, and superior self-standing properties are of great interest for molecular-level separation applications. However, creating such PFMs has been proven extremely challenging. Herein, we report a cross-scale pore-forming strategy to create intriguing sponge fiber molecular sieves with hierarchical, tailorable, and molecularly defined nanoporosity by nanospace-confined chain-packing modulation at the molecular level. Robust secondary ultramicropores (<7 Å) and micropores (<2 nm) are in situconstructed in the macro/mesoporous skeletons of sponge fibers to realize a tunable pore size distribution. The resultant PFMs exhibit the integrated properties of ultrahigh surface area (860 m2g–1), large pore volume (0.6 cm3g–1), self-standing properties, and excellent molecular sieving performance and are widely applied in acetophenone/phenyl ethanol separation, hydrogen peroxide purification, ethyl acetate separation, and CO2adsorption fields. The fabrication of such PFMs provides a feasible way for the design and development of polymeric fibrous sieves for molecular separation in large-scale chemical, energy, and environmental operation processes.

Zeroing neural dynamics (ZND) model is a powerful tool for solving dynamic problems. This study presents an accelerated neural dynamics (AND) model by solving a dynamic nonlinear optimization (DNO) problem. Different from the classical activation function (AF), the AND model describes a novel accelerated convergence strategy that designs a nonlinear dynamic variable according to the error paradigm. Additionally, the AND model can be converted into a paradigm-based dynamical mode, which provides a quantification of the convergence time. Notably, the AND model shows outstanding robustness to various perturbations in the computational environment. The superiority of the AND model is further validated by comparing different models. Subsequently, the model's practicality is shown through the utilization of acoustic-based time difference of arrival (TDOA) localization. • On the basis of the original ZND model, the AND model is designed, which allows the convergence rate of the error to be scaled up with time. Namely, the AND model can obtain a theoretical solution to the DNO problem in a finite time. • Based on the adaptive acceleration design, the AND model is transformed into a dynamic mode based on scalar, and the quantization of the convergence time is achieved by this mode. • The AND model can maintain high robustness when there are perturbations in the computed environment. [ABSTRACT FROM AUTHOR]

People living in very cold climates urgently desire warmth retention equipment to remain healthy. However, creating materials that exhibit both effective warm retention and robust mechanical properties to maintain stable structures is extremely challenging. Herein, we report a facile and time-saving strategy for preparing ultralight, mechanically robust, and high-performance warmth retention materials via direct electrospinning and thermal crosslinking. Fluffy fibrous assemblies with stereoscopic fiber networks are fabricated with a humidity-induced electrospinning technique, followed by heating to create semi-interpenetrating polymer networks (semi-IPNs) within fibers to acquire fibrous sponges (FSs). The semi-IPN-based FSs (semi-IPN FSs) present integrated properties of high tensile stress (∼1 MPa), good fatigue resistance (∼0% plastic deformation after 1000 cyclic tensile or compressive tests), and nondestructive resilience in liquid nitrogen (−196 °C). Furthermore, the semi-IPN FSs exhibit a low volume density of ∼2.2 mg cm–3, effective heat preservation ability (low thermal conductivity ∼25.8 mW m–1K–1), and desired waterproofness and breathability. The successful synthesis of semi-IPN FSs provides a novel attempt to develop high-performance materials with robust mechanical properties for numerous applications.

Objective. The current study screened major depression in people with epilepsy (PWE) during the epidemic of the novel coronavirus‐related disease COVID‐19, in order to identify whether the outbreak generated negative psychological impact on PWE. Methods. A Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C‐NDDI‐E), a self‐reporting depression inventory, was applied for rapid detection of major depression. Assessment was carried out online during three different periods (prior to, during, and after the outbreak of COVID‐19), with the aim of identifying changes in prevalence of depression and associated risk factors. Results. A total of 158 PWE were recruited into the study (48.7% female). The questionnaire completion rates were 94.3% and 70.9% during and after the outbreak, respectively. The prevalence of depression prior to the epidemic, as the baseline, was 34.8% and increased to 42.3% during the period of the epidemic. Towards the end of the outbreak, the prevalence declined towards the baseline (36.6%). Factors such as living alone (OR = 4.022, 95% CI: 1.158‐13.971, P = 0.028) and active seizures before the epidemic (OR = 2.993, 95% CI: 1.197‐7.486, P = 0.019) were associated with depression during the epidemic. Monotherapy appeared to be protective against depression (OR = 0. 105, 95% CI: 0.047‐0.235, P <0.001). Significance. Our results suggest that the pandemic exerts negative influence on PWE's mental health. Depression is one of the common psychological disorders that needs greater attention during this extraordinary period.

Current treatment options for lung disease caused by Mycobacterium abscessuscomplex infections have limited effectiveness. To maximize the use of existing antibacterials and to help inform regimen design for treatment, we assessed the in vitrobactericidal activity of single drugs against actively multiplying and net nonreplicating M. abscessuspopulations in nutrient-rich and nutrient-starvation conditions, respectively. As single drugs, bedaquiline and rifabutin exerted bactericidal activity only against nutrient-starved and actively growing M. abscessus, respectively.

Waterproof and breathable membranes (WBMs) are highly demanded worldwide due to their promising applications in outdoor protective clothing, medical hygiene, and electronic devices. However, the design of such materials integrated with environmental friendliness and high functionality has been considered a long-standing challenge. Herein, we report the green-solvent-processed polyamide fibrous membranes with amphiphobicity and bonding structure via ethanol-based electrospinning and water-based impregnating techniques, endowing the fibrous membranes with outstanding water/oil/dust-resistant and good breathable properties. The developed green smart fibrous membranes exhibit integrated properties with robust water and oil intrusion pressures of 101.2 and 32.4 kPa, respectively, excellent dust removal efficiency of above 99.9%, good water vapor transmission rate of 11.2 kg m–2d–1, air permeability of 2.6 mm s–1, tensile strength of 15.6 MPa, and strong toughness of 22.8 MJ m–3, enabling the membranes to protect human beings and electronic devices effectively. This work may shed light on designing the next generation green smart fibrous WBMs for protective textiles.

This paper studies the impact of route choice set of networks on the day-to-day traffic dynamics through conducting a group of experiments, in which four traffic networks with different sets for choice are used. It is observed that a deterministic user equilibrium (DUE) state is difficult to sustain and the probability of reaching DUE is larger in a network with smaller route choice set. Three day-to-day models are calibrated by using the experimental data. Results reveal that (1) there are linear relationships between traffic volume/flow changes obtained from the experiments and models; (2) when the same model is applied to different networks, the calibrated adjustment parameters are statistically different; and (3) the same model reveals different performances for different networks. Besides, it is shown the participants are more likely to change route choices in a network with larger route choice set and tend to switch away after experiencing a longer travel time.

ABSTRACTIntroductionNon-small cell lung cancer (NSCLC) accounts for most lung cancers worldwide and has a poor prognosis at later stages; programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have provided promising new treatment approaches for these patients. Tislelizumab, an anti-PD-1 monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Tislelizumab has demonstrated clinical activity and is approved in China for treatment of previously treated classical Hodgkin lymphoma and previously treated metastatic PD-L1–high urothelial carcinoma.Areas coveredThis review summarizes the clinical efficacy, safety, and tolerability of tislelizumab in patients with NSCLC and examines the mechanism of action, pharmacokinetic, and pharmacodynamic profiles of tislelizumab.Expert opinionTislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab, potentially due to its differential PD‑1 binding orientation. Tislelizumab demonstrated encouraging efficacy results, long duration of response, and a manageable safety profile across multiple clinical trials in advanced NSCLC. Ongoing trials of drug combinations (e.g. tislelizumab plus angiogenesis inhibitors, immune checkpoint inhibitors, or immune agonists) and examining efficacy across the severity of disease will provide opportunities to understand and feature tislelizumab in clinical practice.

Advanced ceramic aerogel materials with a performance combining sufficient mechanical robustness and splendid high-temperature resistance are urgently needed as thermal insulators in harsh environments. However, the practical applications of ceramic aerogel materials are always limited by poor mechanical performance and degradation under thermal shock. Here, we report the facile creation of lamellar multiarch structured ceramic nanofibrous aerogels that are simultaneously ultrastrong, superelastic, and high temperature resistant by combining ZrO2–Al2O3nanofibers with Al(H2PO4)3matrices. The resulting ZrO2–Al2O3nanofibrous aerogels exhibit the integrated properties of rapid recovery from a strain of 90%, high compression strength of more than 1100 kPa (at a strain of 90%), high fatigue resistance, and temperature-invariant superelasticity. Moreover, the all-ceramic component feature also provides the ceramic nanofibrous aerogels with high-temperature resistance up to 1300 °C and thermal insulation performance with low thermal conductivity (0.0322 W m–1K–1). These superior performances make the ceramic aerogels ideal for high-temperature thermal insulation materials in extreme conditions.

Biofunctional proteins such as active enzymes and therapeutic proteins show tremendous promise in disease treatment. However, intracellular delivery of proteins is facing substantial challenges owing to their vulnerability to degradation and denaturation and the presence of various biological barriers such as their low membrane transport efficiency. Herein, we report a magnetically driven and redox-responsive nanotransporter (MRNT) for highly efficient intracellular delivery of biofunctional proteins. The MRNT has remarkably high cargo capacity, compared with that without nanoscale cargo compartments. We have demonstrated the directional and dynamic motion of the MRNT using both nanoparticle tracking analysis and magnetic driving evaluation. Moreover, the active MRNT can translocate into the cytosol and sense the reducing cytosolic environment to discharge protein cargoes autonomously. The internalization mechanism of the MRNT has been studied using endocytosis inhibitors. Under the magnetic drive, the MRNT can promote a protein transduction efficiency of over 95%, and the intracellular protein delivery by the active MRNT shows significantly higher (∼4 times) enzymatic activity and therapeutic efficiency than those achieved by the static ones. Our proof-of-concept study provides a valuable tool for intracellular protein transduction and contributes to biotechnology and protein therapeutics.