Effects of intestine-specific deletion of FGF15 on the development of fatty liver disease with vertical sleeve gastrectomy.

BACKGROUND: Vertical sleeve gastrectomy (SGx) is a type of bariatric surgery to treat morbid obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The molecular mechanisms of SGx to improve MASLD are unclear, but increased bile acids (BAs) and FGF19 (mouse FGF15) were observed. FGF15/19 is expressed in the ileum in response to BAs and is critical in not only suppressing BA synthesis in the liver but also promoting energy expenditure. We hypothesized the reduction of obesity and resolution of MASLD by SGx may be mediated by FGF15/19. METHODS: First, we conducted hepatic gene expression analysis in obese patients undergoing SGx, with the results showing increased expression of FGF19 in obese patients' livers. Next, we used wild-type and intestine-specific Fgf15 knockout mice (Fgf15ile-/-) to determine the effects of FGF15 deficiency on improving the metabolic effects. RESULTS: SGx improved metabolic endpoints in both genotypes, evidenced by decreased obesity, improved glucose tolerance, and reduced MASLD progression. However, Fgf15ile-/- mice showed better improvement compared to wild-type mice after SGx, suggesting that other mediators than FGF15 are also responsible for the beneficial effects of FGF15 deficiency. Further gene expression analysis in brown adipose tissue suggests increased thermogenesis. CONCLUSIONS: FGF15 deficiency, the larger BA pool and higher levels of secondary BAs may increase energy expenditure in extrahepatic tissues, which may be responsible for improved metabolic functions following SGx.

Lanthanum-modified pyroaurite as a geoengineering tool to simultaneously sink Microcystis cyanobacteria and immobilize phosphorus in eutrophic water.

Excessive phosphorus (P) in eutrophic water induces cyanobacterial blooms that aggravate the burden of in-situ remediation measures. In order to ensure better ecological recovery, Flock & Lock technique has been developed to simultaneously sink cyanobacteria and immobilize P but requires a combination of flocculent and P inactivation agent. Here we synthesized a novel lanthanum-modified pyroaurite (LMP), as an alternative for Flock & Lock of cyanobacteria and phosphorus at the background of rich humic acid and suspended solids. LMP shows a P adsorption capacity of 36.0 mg/g and nearly 100 % removal of chlorophyll-a (Chl-a), turbidity, UV254 and P at a dosage (0.3 g/L) much lower than the commercial analogue (0.5 g/L). The resultant sediment (98.2 % as immobile P) exhibits sound stability without observable release of P or re-growth of cyanobacteria over a 50-day incubation period. The use of LMP also constrains the release of toxic microcystins to 1.4 µg/L from the sunk cyanobacterial cells, outperforming the commonly used polyaluminum chloride (PAC). Similar Flock & Lock efficiency could also be achieved in real eutrophic water. The outstanding Flock & Lock performance of LMP is attributable to the designed La modification. During LMP treatment, La acts as not only a P binder by formation of LaPO4, but also a coagulant to create a synergistic effect with pyroaurite. The controlled hydrolysis of surface La(III) over pyroaurite aided the possible formation of La(III)-pyroaurite networking structure, which significantly enhanced the Flock & Lock process through adsorption, charge neutralization, sweep flocculation and entrapment. In the end, the preliminary economic analysis is performed. The results demonstrate that LMP is a versatile and cost-effective agent for in-situ remediation of eutrophic waters.

Mental stress-induced myocardial ischemia detected by global longitudinal strain and quantitative myocardial contrast echocardiography in women with nonobstructive coronary artery disease.

BACKGROUND: The utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network (DNN) model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow (MBF) and MSIMI. METHODS: 72 female patients aged 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA), and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. MSIMI was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain (LVGLS), ß and A×ß were obtained, and their trends during mental stress testing were observed. ΔGLS, ß reserve and A×ß reserve were respectively calculated. RESULTS: 32 ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P<0.01). For ANOCA patients with MSIMI, LVGLS, ß and A×ß declined to varied extent during mental stress testing compared to those without MSIMI and the controls (P<0.05). Bland-Altman plots demonstrated good consistency between ß reserve and A×ß reserve output by the DNN model and iMCE software. Receiver operating characteristic (ROC) curve analyses showed that ΔGLS, ß reserve and A×ß reserve demonstrated favorable ability to predict MSIMI, especially the combination of A×ß reserve using iMCE analysis and ΔGLS (area under the curve [AUC] 0.94, sensitivity 83%, specificity 97%). CONCLUSIONS: Novel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated MBF response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.

IFNα-induced BST2+ tumor-associated macrophages facilitate immunosuppression and tumor growth in pancreatic cancer by ERK-CXCL7 signaling.

Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.

The direct Z-scheme character and roles of S vacancy in BiOCl/Bi2S3-(001) heterostructures for superior photocatalytic activity: a hybrid density functional investigation.

Given some current speculations and controversies regarding the type of BiOCl/Bi2S3-(001) heterostructure in experiments, it is of great importance to clarify these controversies and further explain the relevant experimental results. In this work, based on first-principles hybrid density functional calculations, it is verified that the BiOCl/Bi2S3-(001) heterostructure is a direct Z-scheme photocatalyst with high photo-generated carrier separation efficiency and strong redox ability that can react with O2 and OH- to produce photocatalytic active species of superoxide ions (˙O2-) and hydroxyl radicals (˙OH), respectively. This is consistent with the experimental findings and explains the excellent photocatalytic performance of the BiOCl/Bi2S3-(001) heterostructure in experiments. Besides, excitingly, it is found that the optical absorption, built-in electric field intensity, interlayer recombination probability, hydrogen evolution reaction ability, and the difference in electron-hole mobility are further enhanced via S vacancy introduction in BiOCl/Bi2S3-(001). Therefore, the significant roles of S vacancy in further improving the photocatalytic properties of the BiOCl/Bi2S3-(001) heterostructure are profoundly revealed. This work can provide valuable theoretical insights for designing the superior direct Z-scheme BiOCl/VS-Bi2S3-(001) heterostructure with promising photocatalytic properties.

Characterization of individual bile acids in vivo utilizing a novel low bile acid mouse model.

Bile acids (BAs) are signaling molecules synthesized in the liver initially by CYP7A1 and CYP27A1 in the classical and alternative pathways, respectively. BAs are essential for cholesterol clearance, intestinal absorption of lipids, and endogenous modulators of farnesoid x receptor (FXR). FXR is critical in maintaining BA homeostasis and gut-liver crosstalk. Complex reactions in vivo and the lack of suitable animal models impede our understanding of the functions of individual BAs. In this study, we characterized the in vivo effects of three-day feeding of cholic acid (CA), deoxycholic acid (DCA), or ursodeoxycholic acid (UDCA) at physiological/non-hepatotoxic concentrations in a novel low-BA mouse model (Cyp7a1-/-/Cyp27a1-/-, DKO). Liver injury, BA levels and composition and BA signaling by the FXR-fibroblast growth factor 15 (FGF15) axis were determined. Overall, higher basal inflammation and altered lipid metabolism in DKO mice might be associated with low BAs. CA, DCA, and UDCA feeding activated FXR signals with tissue specificity. Dietary CA and DCA similarly altered tissue BA profiles to be less hydrophobic, while UDCA promoted a more hydrophobic tissue BA pool with the profiles shifted toward non-12α-OH BAs and secondary BAs. However, UDCA did not offer any overt protective effects as expected. These findings allow us to determine the precise effects of individual BAs in vivo on BA-FXR signaling and overall BA homeostasis in liver physiology and pathologies.

Surface termination modulation for superior S-Scheme Bi2WO6/BiOI heterojunction photocatalyst: a hybrid density functional study.

The prevailing theoretical frameworks indicate that depending on the growth conditions, the Bi2WO6(001) surface can manifest in three distinct terminations-DL-O-Bi (DL: double layers), O-Bi, and O-W. In this study, we conduct a comprehensive examination of the interplay between these terminations on Bi2WO6(001) and the 1I-terminated BiOI(001) facet, especially focusing on their impact on the photocatalytic activity of Bi2WO6/BiOI heterostructure, applying hybrid functional calculations. The models formulated for this research are designated as Bi2WO6(O-Bi)/BiOI(1I), Bi2WO6(DL-O-Bi)/BiOI(1I), and Bi2WO6(O-W)/BiOI(1I). Our findings reveal that Bi2WO6(O-Bi)/BiOI(1I) shows a type II band alignment, which facilitates the spatial separation of photo-generated electrons and holes. Notably, the Bi2WO6(DL-O-Bi)/BiOI(1I) configuration has the lowest binding energy and results in an S-scheme (or Step-scheme) heterostructure. In contrast to the type II heterostructure, this particular configuration demonstrates enhanced photocatalytic efficiency due to improved photo-generated carrier separation, augmented oxidation capability, and better visible-light absorption. Conversely, Bi2WO6(O-W)/BiOI(1I) presents a type I projected band structure, which is less conducive for the separation of photo-generated electron-hole pairs. In summation, this investigation points out that one could significantly refine the photocatalytic efficacy of not only Bi2WO6/BiOI but also other heterostructure photocatalysts by modulating the coupling of different terminations via precise crystal synthesis or growth conditions.

The size distribution of the agitated saline microbubbles for contrast transcranial Doppler generated using standard manual methods.

Agitated saline microbubbles (MBs) are a common contrast agent for determining right-to-left shunt (RLS) by the contrast transcranial Doppler (c-TCD). The size of the generated bubbles is not standardized in clinical practice. MBs were generated using the recommended manual method by reciprocating motion through two syringes. The bubble size distributions (BSD) were measured using the microscopic shadow imaging technique. The results show that the diameter of MBs is mainly distributed between 10 and 100 µm, the mean bubble size is between 21 and 34 µm, the Sauter mean diameter (D32) is primarily between 50 and 300 µm, and the standard deviation (SD) is between 6 and 17 µm in 80 experiments. It provides a more accurate basis for the recommended manual method instability. The high variance values of the BSD indicate that the manual method has low stability and repeatability. The results of this study can be useful for further improvement of the reliability of c-TCD in detecting RLS. RESEARCH HIGHLIGHTS: This study provided the first detailed descriptions of the MBs size distribution in a flowing contrast agent by the microscopic shadow imaging technique. It reveals significant differences in the bubble size of manual foaming during repeated manipulations for each individual and between individuals.

Recent advances in targeted protein degraders as potential therapeutic agents.

Targeted protein degradation (TPD) technology has gradually become widespread in the past 20 years, which greatly boosts the development of disease treatment. Contrary to small inhibitors that act on protein kinases, transcription factors, ion channels, and other targets they can bind to, targeted protein degraders could target "undruggable targets" and overcome drug resistance through ubiquitin-proteasome pathway (UPP) and lysosome pathway. Nowadays, some bivalent degraders such as proteolysis-targeting chimeras (PROTACs) have aroused great interest in drug discovery, and some of them have successfully advanced into clinical trials. In this review, to better understand the mechanism of degraders, we elucidate the targeted protein degraders according to their action process, relying on the ubiquitin-proteasome system or lysosome pathway. Then, we briefly summarize the study of PROTACs employing different E3 ligases. Subsequently, the effect of protein of interest (POI) ligands, linker, and E3 ligands on PROTAC degradation activity is also discussed in detail. Other novel technologies based on UPP and lysosome pathway have been discussed in this paper such as in-cell click-formed proteolysis-targeting chimeras (CLIPTACs), molecular glues, Antibody-PROTACs (Ab-PROTACs), autophagy-targeting chimeras, and lysosome-targeting chimeras. Based on the introduction of these degradation technologies, we can clearly understand the action process and degradation mechanism of these approaches. From this perspective, it will be convenient to obtain the development status of these drugs, choose appropriate degradation methods to achieve better disease treatment and provide basis for future research and simultaneously distinguish the direction of future research efforts.

Evaluation of Fourier deconvolution ion mobility spectrometer as high-performance gas chromatography detector for the analysis of plant extract flavors.

The Fourier deconvolution ion mobility spectrometer (FDIMS) offers multiplexing and improves the resolving power and signal-to-noise ratio. To evaluate the FDIMS as a detector for gas chromatography for the analysis of complex samples, we connected a drift tube ion mobility spectrometer to a commercial gas chromatograph and compared the performance including resolving power, sensitivity, and linear range using 2,6-di­tert-butylpyridine. Mixed standards were also injected into the tandem system to evaluate the performance under optimized conditions. A complex plant extract sample used as natural flavoring was investigated using the resulting system. The results show that the instrument implemented with the Fourier deconvolution multiplexing method demonstrated higher performance over the traditional signal averaging method including higher resolving power, better limit of detection, and wider linear range for a variety of compounds and natural plant extract flavorings.

Erratum: Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma.

[This corrects the article on p. 546 in vol. 9, PMID: 30949409.].

In vitro induction of tetraploidy and its effects on phenotypic variations in Populus hopeiensis.

BACKGROUND: Artificial induction of polyploidy is the most common and effective way to improve the biological properties of Populus and develop new varieties of this tree. In this study, in order to confirm and expand earlier findings, we established a protocol using colchicine and based on an efficient shoot regeneration system of leaf blades to induce tetraploidy in vitro in three genotypes from diploid Populus hopeiensis. The stomatal characteristics, leaf blade size, and growth were evaluated for diploids and tetraploids of three genotypes. RESULTS: We found that genotype, preculture duration, colchicine concentration, and colchicine exposure time had highly significant effects on the tetraploid induction rate. The optimal protocol for inducing tetraploidy in P. hopeiensis was to preculture leaf blades for 7 days and then treat them for 4 days with 40 mg/L colchicine. The tetraploid induction rates of genotypes BT1, BT3, and BT8 were 21.2, 11.4 and 16.7%, respectively. A total of 136 tetraploids were identified by flow cytometry analysis and somatic chromosome counting. The stomatal length, width, and density of leaf blades significantly differed between diploid and tetraploid plants. Compared with their diploid counterparts, the tetraploids produced larger leaf blades and had a slower growth rate. Our findings further document the modified morphological characteristics of P. hopeiensis following whole-genome duplication (e.g., induced tetraploidy). CONCLUSIONS: We established a protocol for in vitro induction of tetraploidy from diploid leaf blades treated with colchicine, which can be applied to different genotypes of P. hopeiensis.

Deep-Learning-Based Mixture Identification for Nuclear Magnetic Resonance Spectroscopy Applied to Plant Flavors.

Nuclear magnetic resonance (NMR) is a crucial technique for analyzing mixtures consisting of small molecules, providing non-destructive, fast, reproducible, and unbiased benefits. However, it is challenging to perform mixture identification because of the offset of chemical shifts and peak overlaps that often exist in mixtures such as plant flavors. Here, we propose a deep-learning-based mixture identification method (DeepMID) that can be used to identify plant flavors (mixtures) in a formulated flavor (mixture consisting of several plant flavors) without the need to know the specific components in the plant flavors. A pseudo-Siamese convolutional neural network (pSCNN) and a spatial pyramid pooling (SPP) layer were used to solve the problems due to their high accuracy and robustness. The DeepMID model is trained, validated, and tested on an augmented data set containing 50,000 pairs of formulated and plant flavors. We demonstrate that DeepMID can achieve excellent prediction results in the augmented test set: ACC = 99.58%, TPR = 99.48%, FPR = 0.32%; and two experimentally obtained data sets: one shows ACC = 97.60%, TPR = 92.81%, FPR = 0.78% and the other shows ACC = 92.31%, TPR = 80.00%, FPR = 0.00%. In conclusion, DeepMID is a reliable method for identifying plant flavors in formulated flavors based on NMR spectroscopy, which can assist researchers in accelerating the design of flavor formulations.

Exploring the effects of different crystal facet combinations and I-doping in the BiOCl/BiOI heterostructure on photocatalytic properties: a hybrid density functional investigation.

This study uses hybrid functional calculations to investigate the effects of various crystal facet combinations in BiOCl and BiOI on the photocatalytic activity of the BiOCl/BiOI heterostructure. The results show that the separation efficiencies of photo-generated electron-hole pairs in BiOCl(010)/BiOI(001) and BiOCl(010)/BiOI(010) are constrained by type I band alignments in principle. In contrast, BiOCl(001)/BiOI(001) and BiOCl(001)/BiOI(010) heterostructures, which operate under the direct Z-scheme type, exhibit an enhanced photo-generated charge separation efficiency, superior redox capacity, and enhanced visible light absorption. Specifically, BiOCl(001)/BiOI(010) exhibits a more remarkable reduction ability that can reduce O2 to ˙O2-. Furthermore, our investigations demonstrate that targeted I element doping in BiOCl(001)/BiOI(010) can reduce the band gap of the BiOCl(001) sheet, enhance visible light absorption, and maintain the direct Z-scheme characteristics, thereby further improving the photocatalytic performance. Additionally, we discovered that I doping can transform the BiOCl(010)/BiOI(001) heterostructure from type I into a direct Z-scheme heterostructure, resulting in a substantial enhancement in the separation efficiency and reduction ability of photo-generated carriers as well as visible light absorption with increasing I doping concentration. Considering the excellent charge injection efficiency observed in experiments with the BiOCl(010)/BiOI(001) heterostructure, I-BiOCl(010)/BiOI(001) may represent a superior photocatalyst. Thus, this study highlights the crucial and substantial roles of engineering specific crystal facet combinations and I doping in enhancing the photocatalytic performance of the BiOCl/BiOI heterostructure. This theoretical study contributes to the comprehension of related experimental findings and offers valuable insights for the development of novel BiOCl/BiOI heterostructures with superior photocatalytic activity.

Defect physics of intrinsic point defects in BiPO4 photocatalysts: a hybrid functional study.

In this work, the intrinsic point defect properties of bulk BiPO4 under different growth conditions are intensively investigated and explored using first-principles hybrid functional calculations. It is found that Bi vacancies and O vacancies are the primary native defects in BiPO4. Under O-poor conditions, BiPO4 acts as an intrinsic insulator because the O vacancy defects (donor) and the Bi vacancy defects (acceptor) compensate for each other. Under Bi-poor conditions, good p-type conductivity is observed in BiPO4, which affirms the observed p-type conductivity behavior in experiments. Bi vacancies in BiPO4 are very shallow, which make it an excellent acceptor and are mostly responsible for the p-type character. In addition, it is found that the primary Bi vacancy defects of BiPO4 hardly affect its electronic structure and optical absorption spectrum regardless of the charge states. In contrast, the neutral O vacancy defects in BiPO4 introduce an impurity energy level near the VBM and induce a new optical absorption peak at around 370 nm. Furthermore, the O vacancies should be favorable for enhancing the production and separation efficiencies of the photo-generated electrons and holes in BiPO4. While Bi vacancies easily provide p-type carriers, simultaneously, they could become the active sites for the photocatalytic reactions because of their dominant -3 charge state. Therefore, understanding the defect physics in BiPO4 photocatalysts is believed to be beneficial for more research in developing BiPO4 or BiPO4-based photocatalysts.

Predicting minty compounds binary mixtures' pleasantness by odor intensity in aqueous solutions.

The aroma of mint is well-liked by the public, and key flavor odorants in mint aroma had been found, but how these molecules interact and form a satisfying odor remains a challenge. Quality, intensity, and pleasantness are our most basic perceptions of aromas; both intensity and pleasantness can be quantified. However, compared to intensity, research on pleasantness was lacking. Pleasantness was one of the most important indicators for formulating a satisfying mint flavor, and the study of binary mixtures was fundamental to our understanding of more complex mixtures. Therefore, the purpose of this study was to explore the characteristics of pleasantness as a function of concentration and, at the same time, to investigate the relationship between intensity and pleasantness in binary mixtures. Thirty sensory evaluation volunteers participated in the evaluation of the intensity and pleasantness of six key flavor odorants of mint and five binary mixtures. The results showed that the pleasantness increased first and then decreased or stabilized with the rising of concentration; even though the interactions in binary mixtures were not the same, their pleasantness could be predicted using the intensities of the components by Response Surface Design of Experiments, and the goodness of fit was greater than 0.92, indicating that the models had the great predictive ability. PRACTICAL APPLICATION: Whether blending flavors or evaluating them, a great deal of experience is required, yet the acquisition of this experience is a long process. Performing these tasks is difficult for the novice, and it helps to quantify the feeling for the flavor and build some mathematical models.

Prognosis value of EAS index in patients with obstructive coronary artery disease.

Background: EAS index is reported to be an adjunctive tool for risk stratification in addition to left ventricular ejection fraction (LVEF). This study aimed to verify the predictive value of EAS index among coronary artery disease (CAD) patients with different cardiac systolic function levels. Methods: A total of 477 patients with obstructive CAD were included in the exploratory analysis of a prospective cohort between October 2017 and January 2018 at Guangdong Provincial People's Hospital. EAS index, e'/(a' × s'), is a novel parameter assessed by tissue Doppler imaging (TDI) indicating combined diastolic and systolic performance. Any occurrence of major adverse cardiovascular event (MACE) was recorded, including first onset of myocardial infarction, stroke, readmission for heart failure, coronary revascularization, or cardiovascular death that occurred within 6 months of the first admission. Kaplan-Meier survival and Cox regression analyses were applied to testify the predictive value of EAS index for cardiovascular outcome. Results: A total of 415 patients (87.2%) completed the follow-up (median, 25.9 months) and experienced 101 (24.3%) MACEs, 17 (4.0%) deaths, and 139 (33.4%) composite events. Elevated EAS index was significantly associated with a higher incidence of MACE, even after adjustment for age, sex, body mass index, N-terminal pro brain natriuretic peptide, high-sensitivity troponin T, high-density lipoprotein, stenosis degree, and other TDI parameters [Model 3, hazard ratio: 1.81, 95% confidence interval (CI): 1.15-2.85]. For different levels of cardiac function, Kaplan-Meier survival analysis revealed that elevated EAS index was associated with higher MACE incidence only in patients with LVEF ≥50% (P<0.05). Conclusions: EAS index is an independent predictor of MACE in patients with obstructive CAD, which could be utilized as a tool for risk stratification in CAD patients or incorporated into a prediction model to improve efficacy.

Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles.

Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine.