In situ heating characterization of structural evolution and size-dependent melting point depression in gold nanoclusters: a comprehensive thermodynamic investigation.

The investigation of nanocluster behaviors at elevated temperatures is important because it encompasses temperature-dependent structural evolution and size-dependent melting points. Size-selected Au2057±52, Au923±24, Au1846±48, and Au2769±72 clusters were generated using a gas-phase condensation cluster beam source equipped with a lateral time-of-flight mass selector. Comprehensive in situ heating characterization was conducted, revealing the structural evolution and size-dependent melting point depression of AuN clusters at atomic resolution via aberration-corrected scanning transmission electron microscopy (AC-STEM). Using quantitative (Q)STEM simulations, a comprehensive statistical analysis was conducted to investigate the structural characteristics of the Au clusters. These clusters tended to be kinetically trapped in metastable structures during nucleation, which subsequently served as "growth templates" for the formation of many metastable Au clusters. In situ heating experiments performed on Au2057±52 revealed a structural evolution trend from icosahedron (Ih) to decahedron (Dh) and finally to face-centered cubic (FCC) structures, with noticeable competition being observed between the Dh and FCC structures. AC-STEM imaging revealed that the melting of the Au clusters began with the formation of molten liquid shells on the surface. The liquid shells thickened at higher temperatures, and the solid core suddenly melted when its diameter decreased to a critical size. Furthermore, the melting points of the Au clusters were linearly dependent on the reciprocal diameter. Compared with the theoretical models, it was found that the liquid nucleation and growth model is in good agreement with the experimental results, indicating its suitability for describing the surface core melting processes of Au clusters at the studied scales.

Alternation of gene expression in brain-derived exosomes after cerebral ischemic preconditioning in mice.

Aims: Cerebral ischemic preconditioning is a neuroprotective therapy against cerebral ischemia and ischemia-reperfusion injury. This study aims to demonstrate the alternation of gene expression in exosomes from brain tissue of mice after ischemic preconditioning and their potential functions. Methods: Ten mice were divided into the sham and the cerebral ischemic preconditioning groups. Their brain tissues were harvested, from which the exosomes were extracted. The characteristics and protective effects of exosomes were evaluated. Whole transcriptome sequencing was used to demonstrate the gene expression discrepancy between the exosomes from the two groups of mice brains. Volcano graphs and heatmaps were used to picture the difference in expression quantity of mRNA, lncRNA, and circRNA. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to demonstrate the functions of differentially expressed RNAs. Results: Exosomes were successfully extracted, and those from the cerebral ischemic preconditioning group had better protective effects on cells that received oxygen-glucose deprivation and restoration injury. A total of 306 mRNAs and 374 lncRNAs were significantly upregulated, and 320 mRNAs and 405 lncRNAs were significantly downregulated in the preconditioning group. No circRNAs were differentially expressed between the two groups. GO and KEGG pathway analysis indicated that the functions of differentially expressed RNAs were related to both neural protective and injurious effects. Conclusion: The brain-derived exosomes may participate in the neuroprotective effect of cerebral ischemic preconditioning. Thorough research is necessary to investigate exosome functions derived from the ischemic preconditioned brain.

Coalescence behavior of size-selected gold and tantalum nanoclusters under electron beam irradiation: insights into nano-welding mechanisms.

The emerging technique of nano-welding (NW) via precisely regulating the fusion of nanoclusters (NCs) in nanotechnology has attracted significant attention for its innovative approach. Employing the gas-phase condensation cluster source with a lateral time-of-flight (TOF) mass-selector, size-selected gold (Au), and tantalum (Ta) NCs were prepared. This study explores the coalescence behavior of size-selected Au and Ta NCs under electron beam irradiation, aiming to investigate the related mechanism governing the welding process. Intrinsically driven by the reduction of excess surface energy, electron beam induces atomic thermal migration, fostering sintering neck growth at cluster interfaces. During this process, atomic diffusion and recrystallization enable NCs to alter shape while retaining stable facet planes. Aberration-corrected scanning transmission electron microscopy (AC-STEM) showcases the formation of single or polycrystalline sintered clusters, during which some lattice distortions can be eliminated. Interestingly, oxidized Ta clusters experience knock-on damage caused by elastic scattering of electron beams, partially deoxidizing them. Additionally, electron-phonon inelastic scattering transforms oxidized Ta clusters from amorphous to crystalline structures. Moreover, the quantum size effect and surface effect of NCs facilitate the surpassing of miscibility limits during Au-Ta heterogeneous welding processes. This investigation bridges the gap between fundamental research on cluster materials and their practical applications.

Acute ischemic stroke with or without asymptomatic intracranial hemorrhage after endovascular treatment: a propensity-score matching study.

BACKGROUND: The long-term follow-up of asymptomatic intracranial hemorrhage (aICH) in patients with acute ischemic stroke after endovascular treatment (EVT) remains controversial.ObjectiveTo evaluate the potential effect of aICH in a real-world practice setting using a matched prospective database. METHODS: This observational cohort study enrolled patients between January 2015 and December 2022 in a prospective database. Eligible patients with occlusions in the anterior circulation were given endovascular treatment and achieved successful reperfusion. The primary outcome was functional independence (modified Rankin Scale (mRS) score 0-2). Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: 732 patients, 516 without any ICH and 216 with aICH, were included. 418 and 348 patients were identified after matching in the aICH substudy and hemorrhagic infarction type aICH substudy, respectively. In the postmatched population, patients with aICH had worse functional outcomes (mRS score 0-2) at 90 days than patients without any ICH (37.8% vs 55.5%: P<0.001). Worse functional outcomes were seen in patients with aICH who were older (OR=5.59 (95% CI 2.91 to 10.74)), had higher baseline National Institutes of Health Stroke Scale score (OR=6.80 (95% CI 3.72 to 12.43)), lower baseline Alberta Stroke Program Early CT Score (OR=2.08 (95% CI 1.23 to 3.51)), and who received general anesthesia (OR=3.37 (95% CI 1.92 to 5.90)). CONCLUSIONS: This matched-control study largely confirmed that asymptomatic ICH after EVT is associated with worse functional outcomes, and the harmful effect is more significant in older patients and those with severe baseline clinical and radiological features.

The Driving Mechanism of Phytoplankton Resource Utilization Efficiency Variation on the Occurrence Risk of Cyanobacterial Blooms.

Algae are highly sensitive to environmental factors, especially nutrient fluctuations; excessive nutrients can lead to the proliferation of specific algae species, resulting in dominance. In this study, we aimed to reevaluate changes in algal dominance from the perspective of resource utilization efficiency (RUE). We established 80 monitoring sites across different water systems, collecting water and phytoplankton samples. Using canonical correspondence analysis (CCA) and a generalized additive model (GAM), we analyzed the correlation between phytoplankton RUE and nutrient concentrations, quantifying the corresponding relationship between algal dominance and RUE. Our results indicate a significant negative correlation between the RUE of total phosphorus (TP) and total nitrogen (TN) concentration, but a positive correlation with N:P. The RUE of TN was negatively correlated with TN concentration and N:P. We constructed GAMs with interaction terms and confirmed a nonlinear relationship between algal dominance and RUE. When the RUE of TN was low, a positive correlation was observed, while a negative correlation was observed otherwise. These findings reveal the ecological adaptability of algal communities and provide valuable insights for predicting the risk of algal bloom outbreaks.

Regulation and mechanistic insights into tensile strain in mesenchymal stem cell osteogenic differentiation.

Bone marrow mesenchymal stem cells (BMSCs) are integral to bone remodeling and homeostasis, as they are capable of differentiating into osteogenic and adipogenic lineages. This differentiation is substantially influenced by mechanosensitivity, particularly to tensile strain, which is a prevalent mechanical stimulus known to enhance osteogenic differentiation. This review specifically examines the effects of various cyclic tensile stress (CTS) conditions on BMSC osteogenesis. It delves into the effects of different loading devices, magnitudes, frequencies, elongation levels, dimensionalities, and coculture conditions, providing a comparative analysis that aids identification of the most conducive parameters for the osteogenic differentiation of BMSCs. Subsequently, this review delineates the signaling pathways activated by CTS, such as Wnt/ß-catenin, BMP, Notch, MAPK, PI3K/Akt, and Hedgehog, which are instrumental in mediating the osteogenic differentiation of BMSCs. Through a detailed examination of these pathways, this study elucidates the intricate mechanisms whereby tensile strain promotes osteogenic differentiation, offering valuable guidance for optimizing therapeutic strategies aimed at enhancing bone regeneration.

Recent Advances of Neoadjuvant Immunotherapy for Urothelial Bladder Cancer.

Urothelial bladder cancer is one of the most common malignant tumors of the urinary system, which accounts for 90~95% of urothelial carcinoma. Despite the current standard neoadjuvant management for localized urothelial MIBC (T2-4cN0M0) is cisplatin-based chemotherapy before radical cystectomy, there still had poor performances and less overall survival benefits in patients with localized urothelial MIBC. Moreover, nearly half of MIBC patients were ineligible for receiving cisplatin because of chronic kidney disease and performance status. Although immunotherapy, immune checkpoint inhibitors (ICIs) has been identified as first or second-line treatments for localized and metastasis bladder cancer based on less adverse reactions and favorable outcomes, neoadjuvant immunotherapy had rarely used for the treatment of these patients because of less large-scale clinical randomized studies and limited outcomes. Therefore, we reviewed the advances of efficacy and safety with neoadjuvant immunotherapy for urothelial bladder cancer depended on published articles and clinical studies, which could provide more theoretical evidences and promising strategy for clinical therapeutic development.

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Energy-transfer Enabled Divergent Synthesis of Polycyclic γ-Sultines.

A visible-light-initiated energy-transfer enabled radical cyclization for the divergent synthesis of polycyclic γ-sultine derivatives has been developed. The reaction provides an alternative and expeditious access to benzofused γ-sultine frameworks, the analogues of γ-lactones and γ-sultones, and features good functional group compatibility, mild reaction conditions and excellent diastereoselectivity. The robustness and application potential of this method have also been successfully displayed by two gram-scale reactions and the synthesis of polycyclic sultones. Mechanistic studies indicated the transformations through a possible energy-transfer enabled intramolecular radical homolytic substitution or hydrogen atom transfer process mainly.

Interferon-induced MXB protein restricts vimentin-dependent viral infection.

Type I interferon (IFN) inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins. As an IFN-induced protein, myxovirus resistance B (MXB) protein was reported to inhibit multiple highly pathogenic human viruses. It remains to be determined whether MXB employs a common mechanism to restrict different viruses. Here, we find that IFN alters the subcellular localization of hundreds of host proteins, and this IFN effect is partially lost upon MXB depletion. The results of our mechanistic study reveal that MXB recognizes vimentin (VIM) and recruits protein kinase B (AKT) to phosphorylate VIM at amino acid S38, which leads to reorganization of the VIM network and impairment of intracellular trafficking of virus protein complexes, hence causing a restriction of virus infection. These results highlight a new function of MXB in modulating VIM-mediated trafficking, which may lead towards a novel broad-spectrum antiviral strategy to control a large group of viruses that depend on VIM for successful replication.

Evaluation of the flavor profiles of Yanbian-style sauced beef from differently treated raw beef samples.

In this study, we investigated the volatile flavor compounds and sensory perceptions of Yanbian-style sauced beef prepared from raw meats subjected to different treatments (hot fresh, chilled, and frozen beef). The results indicated that the treatment of raw beef significantly impacted the quality and flavor of sauced beef. Sauced chilled beef (CRSB) exhibited the highest content of fatty acids and total amino acids. A total of 48 volatile compounds were identified. Moreover, a relative odor activity value analysis identified hexanal, nonanal, heptanal, 1-octen-3-ol, and 2,3-octanedione as the characteristic flavor compounds in Yanbian-style sauced beef. The sensory evaluation demonstrated that CRSB was the most palatable and flavorful. Additionally, correlation loading plot analysis indicated strong correlations between sensory evaluation, fatty acids, amino acids, and volatile flavor compounds. These results suggest that chilled beef meat is the best raw material for the production of Yanbian-style sauced beef.

Development of an mRNA-based therapeutic vaccine mHTV-03E2 for high-risk HPV-related malignancies.

Human papillomavirus (HPV) 16 and 18 infections are related to many human cancers. Despite several preventive vaccines for high-risk (hr) HPVs, there is still an urgent need to develop therapeutic HPV vaccines for targeting pre-existing hrHPV infections and lesions. In this study, we developed a lipid nanoparticle (LNP)-formulated mRNA-based HPV therapeutic vaccine (mHTV)-03E2, simultaneously targeting the E2/E6/E7 of both HPV16 and HPV18. mHTV-03E2 dramatically induced antigen-specific cellular immune responses, leading to significant CD8+ T cell infiltration and cytotoxicity in TC-1 tumors derived from primary lung epithelial cells of C57BL/6 mice expressing HPV E6/E7 antigens, mediated significant tumor regression, and prolonged animal survival, in a dose-dependent manner. We further demonstrated significant T cell immunity against HPV16/18 E6/E7 antigens for up to 4 months post-vaccination in immunological and distant tumor rechallenging experiments, suggesting robust memory T cell immunity against relapse. Finally, mHTV-03E2 synergized with immune checkpoint blockade to inhibit tumor growth and extend animal survival, indicating the potential in combination therapy. We conclude that mHTV-03E2 is an excellent candidate therapeutic mRNA vaccine for treating malignancies caused by HPV16 or HPV18 infections.

ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling.

TGFBR2, a key regulator of the TGFß signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin ß5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFß signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFß signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies.

16S rRNA sequencing in chronic dacryocystitis.

CLINICAL RELEVANCE: The pathogenesis of chronic dacryocystitis (CDC) is associated with a variety of bacteria. Investigating microflora has the potential to provide a theoretical basis for preventing and treating CDC. BACKGROUND: 16S rRNA sequencing is a sequence-based bacterial analysis. The application of 16S rRNA sequencing in CDC is rarely reported. METHODS: A case-control study of infected and healthy eyes diagnosed as CDC patients was conducted. Seventy-eight patients were divided into A (conjunctival sac secretions from healthy eyes), B (conjunctival sac secretions from affected eyes), and C (lacrimal sac secretions from affected eyes) groups. The flora of samples was analysed with 16S rRNA sequencing, and the data was analysed using QIIME, R, LefSE and other software. The potential functions were analysed by PICRUSt. RESULTS: A total of 1440 operational taxonomic units (OTUs) were obtained, 139 specific to group A, 220 specific to group B, and 239 specific to group C. There was no significant difference in α index between the three groups. The beta diversity and grouping analysis data indicated that the three groups of flora were similar in species richness and diversity, but there were some differences in composition. In group A, the abundance of Pseudomonadaceae, Chlorobacteria, Moraceae, Staphylococcaceae, Bacillariophyceae, Immunobacterium spp. and Bacillus spp. was higher; in group B, the abundance of Burkholderiaceae, Sphingomonas, Rhizobia, Stalked Bacteria, Sphingomonadaceae, Enterobacteriaceae, Shortwaveomonas spp. was higher; in group C, the abundance of Streptococcus digestiveis, Propionibacterium, Enterobacteriaceae, Anaerobacteriaceae, Propionibacteriaceae, Bacillus spp. Neisseria spp. and Shortactomonas spp. was higher. Six pathways were identified to assess the potential microbial functions. CONCLUSION: Alterations in the microbiota of the conjunctiva and lacrimal sac are associated with the pathogenesis of CDC, which may provide certain guidance for antibiotic treatment of CDC.

SARS-CoV-2 Omicron Variants Show Attenuated Neurovirulence Compared with the Wild-Type Strain in Elderly Human Brain Spheroids.

Infection with severe acute respiratory syndrome coronavirus 2 Omicron variants still causes neurological complications in elderly individuals. However, whether and how aging brains are affected by Omicron variants in terms of neuroinvasiveness and neurovirulence are unknown. Here, we utilize resected paracarcinoma brain tissue from elderly individuals to generate primary brain spheroids (BSs) for investigating the replication capability of live wild-type (WT) strain and Omicron (BA.1/BA.2), as well as the mechanisms underlying their neurobiological effects. We find that both WT and Omicron BA.1/BA.2 are able to enter BSs but weakly replicate. There is no difference between Omicron BA.1/BA.2 and WT strains in neurotropism in aging BSs. However, Omicron BA.1/BA.2 exhibits ameliorating neurological damage. Transcriptional profiling indicates that Omicron BA.1/BA.2 induces a lower neuroinflammatory response than WT strain in elderly BSs, suggesting a mechanistic explanation for their attenuated neuropathogenicity. Moreover, we find that both Omicron BA.1/BA.2 and WT strain infections disrupt neural network activity associated with neurodegenerative disorders by causing neuron degeneration and amyloid-ß deposition in elderly BSs. These results uncover Omicron-specific mechanisms and cellular immune responses associated with severe acute respiratory syndrome coronavirus 2-induced neurological complications.

Arbuscular Mycorrhizal Fungi Improve Lycium barbarum Potassium Uptake by Activating the Expression of LbHAK.

Arbuscular mycorrhizal (AM) fungi can establish a mutualistic relationship with the roots of most terrestrial plants to increase plant nutrient uptake. The effects of potassium uptake and transport by AM symbiosis are much less reported compared to other nutrients. In this research, a heterologous yeast system was used to verify that the LbHAK has capacity for potassium uptake. The split-roots system implemented using seedlings of Lycium barbarum confirmed that R. irregularis locally induced LbHAK expression, which means that LbHAK is only expressed in mycorrhizal roots. Furthermore, the impacts of overexpression of LbHAK on the growth, nutrients and water uptake, and transport of mycorrhizal tobacco (inoculation with Rhizophagus irregularis) at 0.2 mM and 2 mM K conditions were assessed. The mycorrhizal tobacco growth and potassium accumulation were significantly enhanced through LbHAK overexpression in tobacco. In addition, overexpression of LbHAK substantially enhanced phosphorus content, while stimulating the expression of NtPT4, Rir-AQP1, and Rir-AQP2 in mycorrhizal tobacco. Moreover, LbHAK overexpression greatly promoted AM colonization. LbHAK has a potential role in facilitating potassium absorption through the mycorrhizal pathway, and overexpression of LbHAK in tobacco may promote the transport of potassium, phosphorus, and water from AM fungi to tobacco. These data imply the important roles played by the LbHAK in AM-fungi-induced potassium uptake in L. barbarum and in improving plant nutrients and AM colonization.

A universal strategy to enhance photothermal conversion efficiency by regulating the molecular aggregation states for safe photothermal therapy of bacterial infections.

Photothermal therapy (PTT) has emerged as a promising approach for treating bacterial infections. However, achieving a high photothermal conversion efficiency (PCE) of photothermal agents (PTAs) remains a challenge. Such a problem is usually compensated by the use of a high-intensity laser, which inevitably causes tissue damage. Here, we present a universal strategy to enhance PCE by regulating the molecular aggregation states of PTAs within thermoresponsive nanogels. We demonstrate the effectiveness of this approach using aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) PTAs, showing significant enhancements in PCE without the need for intricate molecular modifications. Notably, the highest PCEs reach up to 80.9% and 64.4% for AIE-NG and ACQ-NG, respectively, which are nearly 2-fold of their self-aggregate counterparts. Moreover, we elucidate the mechanism underlying PCE enhancement, highlighting the role of strong intermolecular π-π interactions facilitated by nanogel-induced volume contraction. Furthermore, we validate the safety and efficacy of this strategy in in vitro and in vivo models of bacterial infections at safe laser power densities, demonstrating its potential for clinical translation. Our findings offer a straightforward, universal, and versatile method to improve PTT outcomes while minimizing cytotoxicity, paving the way for enhanced treatment of bacterial infections with safe PTT protocols.

Oxidation behavior and atomic structural transition of size-selected coalescence-resistant tantalum nanoclusters.

Herein a series of size-selected TaN(N = 147, 309, 561, 923, 1415, 2057, 6525, 10 000, 20 000) clusters are generated using a gas-phase condensation cluster beam source equipped with a lateral time-of-flight mass-selector. Aberration-corrected scanning transmission electron microscopy (AC-STEM) imaging reveals good thermal stability of TaNclusters in this study. The oxidation-induced amorphization is observed from AC-STEM imaging and further demonstrated through x-ray photoelectron spectroscopy and energy-dispersive spectroscopy. The oxidized Ta predominantly exists in the +5 oxidation state and the maximum spontaneous oxidation depth of the Ta cluster is observed to be 5 nm under prolonged atmosphere exposure. Furthermore, the size-dependent sintering and crystallization processes of oxidized TaNclusters are observed with anin situheating technique, and eventually, ordered structures are restored. As the temperature reaches 1300 °C, a fraction of oxidized Ta309clusters exhibit decahedral and icosahedral structures. However, the five-fold symmetry structures are absent in larger clusters, instead, these clusters exhibit ordered structures resembling those of the crystalline Ta2O5films. Notably, the sintering and crystallization process occurs at temperatures significantly lower than the melting point of Ta and Ta2O5, and the ordered structures resulting from annealing remain well-preserved after six months of exposure to ambient conditions.

Harnessing Nanochaperone-Mediated Autophagy for Selective Clearance of Pathogenic Tau Protein in Alzheimer's Disease.

Accumulation of pathological tau is a hallmark of Alzheimer's disease (AD), which correlates more closely with cognitive impairment than does the amyloid-ß (Aß) burden. Autophagy is a powerful process for the clearance of toxic proteins including aberrant tau. However, compromised autophagy is demonstrated in neurodegeneration including AD, and current autophagy inducers remain enormously challenging due to inability of restoring autophagy pathway and lack of targeting specificity. Here, pathogenic tau-specific autophagy based on customized nanochaperone is developed for AD treatment. In this strategy, the nanochaperone can selectively bind to pathogenic tau and maintain tau homeostasis, thereby ensuring microtubule stability which is important for autophagy pathway. Meanwhile, the bound pathogenic tau can be sequestered in autophagosomes by in situ autophagy activation of nanochaperone. Consequently, autophagosomes wrapping with pathogenic tau are able to be trafficked along the stabilized microtubule to achieve successful fusion with lysosomes, resulting in the enhancement of autophagic flux and pathologic tau clearance. After treatment with this nanochaperone-mediated autophagy strategy, the tau burden, neuron damages, and cognitive deficits of AD mice are significantly alleviated in the brain. Therefore, this work represents a promising candidate for AD-targeted therapy and provides new insights into future design of anti-neurodegeneration drugs.