The mechanism and therapeutic strategies in doxorubicin-induced cardiotoxicity: Role of programmed cell death.

Doxorubicin (DOX) is the most commonly used anthracycline anticancer agent, while its clinical utility is limited by harmful side effects like cardiotoxicity. Numerous studies have elucidated that programmed cell death plays a significant role in DOX-induced cardiotoxicity (DIC). This review summarizes several kinds of programmed cell death, including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis. Furthermore, oxidative stress, inflammation, and mitochondrial dysfunction are also important factors in the molecular mechanisms of DIC. Besides, a comprehensive understanding of specific signal pathways of DIC can be helpful to its treatment. Therefore, the related signal pathways are elucidated in this review, including sirtuin deacetylase (silent information regulator 2 [Sir2]) 1 (SIRT1)/nuclear factor erythroid 2-related factor 2, SIRT1/Klotho, SIRT1/Recombinant Sestrin 2, adenosine monophosphate-activated protein kinase, AKT, and peroxisome proliferator-activated receptor. Heat shock proteins function as chaperones, which play an important role in various stressful situations, especially in the heart. Thus, some of heat shock proteins involved in DIC are also included. Hence, the last part of this review focuses on the therapeutic research based on the mechanisms above.

Characteristics of methane and carbon dioxide in ice caves at a high-mountain glacier of China.

The exploration of the spatiotemporal distribution of greenhouse gas (GHG) exchange in the cryosphere (including ice sheet, glaciers, and permafrost) is important for understanding its future feedback to the atmosphere. Mountain glaciers and ice sheets may be potential sources of GHG emissions, but the magnitude and distribution of GHG emissions from glaciers and ice sheets remain unclear because observation data are lacking. In this study, in situ CH4 and CO2 and the mixing ratios of their carbon isotope signatures in the air inside an ice cave were measured, and CH4 and CO2 exchange in the meltwater of Laohugou glacier No. 12, a high-mountain glacier in an arid region of western China, was also analyzed and compared with the exchange in downstream rivers and a reservoir. The results indicated elevated CH4 mixing ratios (up to 5.7 ppm) and depleted CO2 (down to 168 ppm) in the ice cave, compared to ambient levels during field observations. The CH4 and CO2 fluxes in surface meltwater of the glacier were extremely low compared with their fluxes in rivers from the Tibetan Plateau (TP). CH4 and CO2 mixing ratios in the air inside the ice cave were mainly controlled by local meteorological conditions (air temperature, wind speed and direction) and meltwater runoff. The carbon isotopic compositions of CH4 and CO2 in the ice cave and terminus meltwater indicated δ13C-CH4 depletion compared to ambient air, suggesting an acetate fermentation pathway. The abundances of key genes for methanogenic archaea/genes encoding methyl coenzyme M reductase further indicated the production of CH4 by methanogenic archaea from the subglacial meltwater of high-mountain glaciers. The discovery of CH4 emissions from even small high-mountain glaciers indicates a more prevalent characteristic of glaciers to produce and release CH4 from the subglacial environment than previously believed. Nevertheless, further research is required to understand the relationship between this phenomenon and glacial dynamics in the third pole.

Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis.

Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein-protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP.

A highly integrated digital PCR system with on-chip heating for accurate DNA quantitative analysis.

Digital polymerase chain reaction (dPCR) is extensively used for highly sensitive disease diagnosis due to its single-molecule detection ability. However, current dPCR systems require intricate DNA sample distribution, rely on cumbersome external heaters, and exhibit sluggish thermal cycling, hampering efficiency and speed of the dPCR process. Herein, we presented the development of a microwell array based dPCR system featuring an integrated self-heating dPCR chip. By utilizing hydrodynamic and electrothermal simulations, the chip's structure is optimized, resulting in improved partitioning within microwells and uniform thermal distribution. Through strategic hydrophilic/hydrophobic modifications on the chip's surface, we effectively secured the compartmentalization of sample within the microwells by employing an overlaying oil phase, which renders homogeneity and independence of samples in the microwells. To achieve precise, stable, uniform, and rapid self-heating of the chip, the ITO heating layer and the temperature control algorithm are deliberately designed. With a capacity of 22,500 microwells that can be easily expanded, the system successfully quantified EGFR plasmid solutions, exhibiting a dynamic linear range of 105 and a detection limit of 10 copies per reaction. To further validate its performance, we employed the dPCR platform for quantitative detection of BCR-ABL1 mutation gene fragments, where its performance was compared against the QuantStudio 3D, and the self-heating dPCR system demonstrated similar analytical accuracy to the commercial dPCR system. Notably, the individual chip is produced on a semiconductor manufacturing line, benefiting from mass production capabilities, so the chips are cost-effective and conducive to widespread adoption and accessibility.

Two way workable microchanneled hydrogel suture to diagnose, treat and monitor the infarcted heart.

During myocardial infarction, microcirculation disturbance in the ischemic area can cause necrosis and formation of fibrotic tissue, potentially leading to malignant arrhythmia and myocardial remodeling. Here, we report a microchanneled hydrogel suture for two-way signal communication, pumping drugs on demand, and cardiac repair. After myocardial infarction, our hydrogel suture monitors abnormal electrocardiogram through the mobile device and triggers nitric oxide on demand via the hydrogel sutures' microchannels, thereby inhibiting inflammation, promoting microvascular remodeling, and improving the left ventricular ejection fraction in rats and minipigs by more than 60% and 50%, respectively. This work proposes a suture for bidirectional communication that acts as a cardio-patch to repair myocardial infarction, that remotely monitors the heart, and can deliver drugs on demand.

High-Performance Plasma Biomarker Panel for Alzheimer's Disease Screening Using a Femtomolar-Level Label-Free Biosensing System.

Alzheimer's disease (AD) is the most common cause of dementia in older people. However, diagnosing AD through noncognitive methods, such as invasive cerebrospinal fluid sampling or radioactive positron emission tomography, has limited applications. Herein, the femtomolar levels of AD biomarkers amyloid ß 40 (Aß40), amyloid ß 42 (Aß42), phosphorylated tau 181 (P-tau181), phosphorylated tau 217 (P-tau217), and neurofilament light chain (NfL) were determined in human plasma in multicenter clinical cohorts using an ultrasensitive graphene field-effect transistor sensor. A machine-learning algorithm was also used to assemble these plasma biomarkers and optimize their performance in discriminating individual stages of Alzheimer's dementia progression. The "composite-info" biomarker panel, which combines these biomarkers and clinical information, considerably improved the staging performance in AD progression. It achieved an area under the curve of >0.94 in the receiver operator characteristic (ROC) curve. In addition, the panel demonstrated an advantage in the individual-based stage assessment compared with that of the Mini-Mental State Examination/Montreal Cognitive Assessment and nuclear magnetic resonance imaging. This study provides a composite biomarker panel for the screening and early diagnosis of AD using a rapid detection system.

Intracranial mesenchymal tumor with multiple extracranial metastases: A case report and literature review.

This study presents a rare case of an older woman with an intracranial mesenchymal tumor in the right frontal and parietal lobes. Despite prompt surgical intervention, her condition rapidly deteriorated because of tumor dissemination, leading to her demise. We highlight the tumor's marked invasiveness and heterogeneity, coupled with a propensity for distant systemic metastasis, which negatively impacted the patient's prognosis. This particular clinical behavior had not been previously reported, making this a novel observation. Thus, through a comprehensive review of relevant literature, we aim to provide valuable insights for further understanding, diagnosing, and treating such tumors.

Optimal systolic and diastolic blood pressure threshold that associated with lower risk of white matter hyperintensity progression.

Background: The optimal control thresholds for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with white matter hyperintensity (WMH) are still unclear. Method: A longitudinal retrospective study of patients with brain magnetic resonance imaging (MRI) scans with intervals of more than 3 years was conducted. Blood pressure records during hospitalization and from outpatient visits between baseline and the last MRI scan were collected. The outcome was the change in total WMH from baseline to the final visit. Results: Among the 965 patients with MRI scans, 457 patients with detailed longitudinal blood pressure records were ultimately included and classified into the WMH absent group (n = 121), mild WMH group (n = 126), and moderate to severe WMH group (n = 210). Both baseline and longitudinal mean SBP, DBP, and SBP SD were significantly associated with WMH severity (p < 0.05). An average SBP of 130-140 mmHg [vs. <130 mmHg, aOR, 1.80, (95% CI, 1.05-3.07), p = 0.03] was associated with a higher risk of WMH progression. DBP ≥ 90 mmHg [vs. <80 mmHg, OR, 1.81, (95% CI, 0.88-3.74), p = 0.02, aOR, 1.54, (95% CI, 0.66-3.53), p = 0.32] was associated with a higher risk of WMH progression, but was not after adjusted for other covariates. Longitudinal BP variability was not significantly associated with WMH progression. Conclusion: Both SBP and DBP had a stronger relationship with the severity of WMH. A target mean SBP of <130 mmHg and mean DBP of <80 mmHg was associated with a lower risk of WMH progression.

Evaluation of cholesterol transformation abilities and probiotic properties of Bacteroides dorei YGMCC0564.

Hypercholesterolemia, a risk factor for cardiovascular disease (CVD), often requires therapeutic agents with varying degrees of side effects. This has created a need for safe and natural alternatives such as medications or functional foods that can improve lipid metabolism and reduce cholesterol levels. In recent years, Next-generation probiotics (NGPs) have recently emerged as a potential solution, offering distinct mechanisms compared to traditional probiotics. Among the NGPs, Bacteroides, a dominant bacterial genus in the human gut, has gained significant attention due to its prevalence, ability to break down plant polysaccharides, and production of short-chain fatty acids (SCFAs). Recent evidence has demonstrated that Bacteroides effectively reduces cholesterol levels, prevents obesity, and lowers the risk of CVD. However, research on Bacteroides is currently limited to a few species, leaving rooms for exploration of the beneficial functions of different species in this genus. In this study, we isolated 66 Bacteroides strains, including 9 distinct species, from healthy adults' fecal samples. By comparing their ability to assimilate cholesterol, we found that the transformation ability was not specific to any particular species. Notably, Bacteroides dorei YGMCC0564 revealed superior cholesterol-lowering capabilities and bile salt hydrolase (BSH) activity in vitro, surpassing that of Lactobacillus GG (LGG). YGMCC0564 exhibited favorable probiotic characteristics, including high survival rate in vitro simulation of gastrointestinal digestion, excellent adhesion ability, susceptibility to antibiotics, absence of hemolysis or virulence genes, and substantial production of SCFAs. The strain also demonstrated remarkable bile salt deconjugation activities and upregulation of the BT_416 gene associated with cholesterol, providing insights into a possible molecular mechanism underlying its cholesterol-reducing activity. These findings establish YGMCC0564 as a promising NPG candidate for improving cardiovascular health.

A genome-wide transposon mutagenesis screening identifies LppB as a key factor associated with Mycoplasma bovis colonization and invasion into host cells.

Mycoplasma spp., the smallest self-replicating and genome-reduced organisms, have raised a great concern in both the medical and veterinary fields due to their pathogenicity. The molecular determinants of these wall-less bacterium efficiently use their limited genes to ensure successful infection of the host remain unclear. In the present study, we used the ruminant pathogen Mycoplasma bovis as a model to identify the key factors for colonization and invasion into host cells. We constructed a nonredundant fluorescent transposon mutant library of M. bovis using a modified transposon plasmid, and identified 34 novel adhesion-related genes based on a high-throughput screening approach. Among them, the ΔLppB mutant exhibited the most apparent decrease in adhesion to embryonic bovine lung (EBL) cells. The surface-localized lipoprotein LppB, which is highly conserved in Mycoplasma species, was then confirmed as a key factor for M. bovis adhesion with great immunogenicity. LppB interacted with various components (fibronectin, vitronectin, collagen IV, and laminin) of host extracellular matrix (ECM) and promoted plasminogen activation through tPA to degrade ECM. The 439-502 amino acid region of LppB is a critical domain, and F465 and Y493 are important residues for the plasminogen activation activity. We further revealed LppB as a key factor facilitating internalization through clathrin- and lipid raft-mediated endocytosis, which helps the Mycoplasma invade the host cells. Our study indicates that LppB plays a key role in Mycoplasma infection and is a potential new therapeutic and vaccine target for Mycoplasma species.

Engineered exosomes reprogram Gli1+ cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels.

Calcification of autologous pathological vessels and tissue engineering blood vessels (TEBVs) is a thorny problem in clinic. However, there is no effective and noninvasive treatment that is available against the calcification of TEBVs and autologous pathological vessels. Gli1+ cells are progenitors of smooth muscle cells (SMCs) and can differentiate into osteoblast-like cells, leading to vascular calcification. Our results showed that the spatiotemporal distribution of Gli1+ cells in TEBVs was positively correlated with the degree of TEBV calcification. An anticalcification approach was designed consisting of exosomes derived from mesenchymal stem cells delivering lncRNA-ANCR to construct the engineered exosome-Ancr/E7-EXO. The results showed that Ancr/E7-EXO effectively targeted Gli1+ cells, promoting rapid SMC reconstruction and markedly inhibiting Gli1+ cell differentiation into osteoblast-like cells. Moreover, Ancr/E7-EXO significantly inhibited vascular calcification caused by chronic kidney disease. Therefore, Ancr/E7-EXO reprogrammed Gli1+ cells to prevent calcification of vascular graft and autologous pathological vessel, providing unique insights for an effective anticalcification.

Biomimetic Antithrombotic Tissue-Engineered Vascular Grafts for Converting Cholesterol and Free Radicals into Nitric Oxide.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Herein, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen-gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming "harmful" substances into "beneficial" factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.

Future Projection of Extreme Precipitation Indices over the Qilian Mountains under Global Warming.

The Qilian Mountains are a climate-sensitive area in northwest China, and extreme precipitation events have an important impact on its ecological environment. Therefore, considering the global warming scenario, it is highly important to project the extreme precipitation indices over the Qilian Mountains in the future. This study is based on three CMIP6 models (CESM2, EC-Earth3, and KACE-1-0-G). A bias correction algorithm (QDM) was used to correct the precipitation outputs of the models. The eight extreme precipitation indices over the Qilian Mountains during the historical period and in the future were calculated using meteorological software (ClimPACT2), and the performance of the CMIP6 models to simulate the extreme precipitation indices of the Qilian Mountains in the historical period was evaluated. Results revealed that: (1) The corrected CMIP6 models could simulate the changes in extreme precipitation indices over the Qilian Mountains in the historical period relatively well, and the corrected CESM2 displayed better simulation as compared to the other two CMIP6 models. The CMIP6 models performed well while simulating R10mm (CC is higher than 0.71) and PRCPTOT (CC is higher than 0.84). (2) The changes in the eight extreme precipitation indices were greater with the enhancement of the SSP scenario. The growth rate of precipitation in the Qilian Mountains during the 21st century under SSP585 is significantly higher than the other two SSP scenarios. The increment of precipitation in the Qilian Mountains mainly comes from the increase in heavy precipitation. (3) The Qilian Mountains will become wetter in the 21st century, especially in the central and eastern regions. The largest increase in precipitation intensity will be observed in the western Qilian Mountains. Additionally, total precipitation will also increase in the middle and end of the 21st century under SSP585. Furthermore, the precipitation increment of the Qilian Mountains will increase with the altitude in the middle and end of the 21st century. This study aims to provide a reference for the changes in extreme precipitation events, glacier mass balance, and water resources in the Qilian Mountains during the 21st century.

Top-Emission ZnSeTe/ZnSe/ZnS-Based Blue Quantum Dot Light-Emitting Diodes with Enhanced Chroma Efficiency.

A high-performance quantum dot light-emitting diode (QLED) with heavy metal free (HMF) quantum dots (QDs) is urgently needed for its application in next-generation eco-friendly displays. However, the preparation of high-performance HMF QD materials and the corresponding electroluminescent devices remain challenges at present, especially for blue-emitting devices. In this work, by adjusting the Te/Se ratio of the ZnSeTe core, ZnSeTe/ZnSe/ZnS blue QDs with adjustable energy levels and emission peaks are demonstrated. These QDs are utilized to fabricate top-emitting QLEDs, yielding a peak current efficiency (CE) of 11.8 cd A-1. To make it one step further to meet the requirement of the wide color gamut in displays, the devices' color coordinates and current efficiency are simultaneously optimized by adjusting their microcavity structure and electrical properties. Finally, the chroma efficiency (current efficiency/CIEy) of the blue devices is optimized to 72, which is 2.2 times that of the control device.

High-efficiency and high-resolution patterned quantum dot light emitting diodes by electrohydrodynamic printing.

The development of quantum dot light-emitting diode (QLED) fabrication technologies for high-definition and low-cost displays is an important research topic. However, commercially available piezoelectric inkjet printing has reached its limit in reducing pixel sizes, which restricts its potential use in high-resolution displays. Here, we exhibit an electrohydrodynamic (EHD) printing method for manufacturing QLEDs with a high resolution of 500 ppi that remarkably surpasses the resolution of conventional inkjet printing displays. By optimizing the EHD printing process, a high-resolution pixelated bottom-emitting passive matrix QLED with a maximal current efficiency of 14.4 cd A-1 in a pixel size of 5 µm × 39 µm was achieved, indicating the capability of the EHD method in superfine printing and high efficiency QLED. Moreover, a top-emitting device is designed using a capping layer; the maximal current efficiency of top-emission passive matrix QLED devices can reach up to 16.5 cd A-1. Finally, a two-color (red and green) bottom-emission QLED device with 500 ppi was fabricated. The successful fabrication of these high-efficiency QLEDs with 500 ppi demonstrated that the EHD printing strategy has numerous potential applications in high-resolution and high-performance QLEDs for a range of applications, such as mobile or wearable devices.

Novel Flexible Ag/AgCl Quasi-Reference Electrode with Fishbone Nanowire Structure for Remarkable Potential Stability, Long-Term Reliability, and Noninvasive Electrocardiography.

The roadblocks for the planar silver/silver chloride (Ag/AgCl) quasi-reference electrode (qRE) development are the potential stability and long-term reliability as potentiometric sensors. Although there is a significant amount of work on potentiometric screen-printed and inkjet-printed sensors, none of the REs has comparable performance to that of the conventional glass RE and knowledge on reliable planar Ag/AgCl qREs is still limited. Here, a novel fishbone-structured flexible Ag/AgCl qRE (Fishbone-Ag/AgCl qRE) was developed and its stability and long-term reliability were significantly improved. The stability of the Fishbone-Ag/AgCl qRE was comparable to that of a commercial glass Ag/AgCl RE. In a long-term stability test, the Fishbone-Ag/AgCl qRE could continuously and stably operate for more than 4 h. Shelf-life testing revealed a 6 month life span. The conductivity and diameter of the nanowires in the fishbone structure of the Ag/AgCl qRE had important influences on electrochemical properties. The conductivity of the qRE influenced the charge-transfer rate in the electrode so that it affected the potential stability. Thicker diameter and slight chlorination on the surface of the AgNWs resulted in enhanced long-term reliability of the qRE. The capabilities of this new nanostructured material were applied in vivo for noninvasive monitoring of electrocardiogram. The discovery is elementary and substantially informs improved nanostructure RE design for testing and commercial medical device applications.

Application of stem cells in engineered vascular graft and vascularized organs.

Recent studies report that stem cell therapies have been applied successfully to patients, This has increased anticipations that this regeneration strategy could be a potential method to treat a wide range of intractable diseases some day. Stem cells offer new prospects for the treatment of incurable diseases and for tissue regeneration and repairation because of their unique biological properties. Angiogenesis a key process in tissue regeneration and repairation. Vascularization of organs is one of the main challenges hindering the clinical application of engineered tissues. Efficient production of engineered vascular grafts and vascularized organs is of critical importance for regenerative medicine. In this review, we focus on the types of stem cells that are widely used in tissue engineering and regeneration, as well as their application of these stem cells in the construction of tissue-engineered vascular grafts and vascularization of tissue-engineered organs.

Temporary Survival Increasing the Diversity of Culturable Heterotrophic Bacteria in the Newly Exposed Moraine at a Glacier Snout.

Laohugou Glacier No. 12 is located on the northern slope of the western Qilian Mountains with a temperate continental wet climate and an extremely cold winter. Bacteria in a newly exposed moraine have to cope with various pressures owing to deglaciation at the glacier snout. However, limited information is available regarding the high diversity and temporary survival of culturable heterotrophic bacteria under various environmental stresses. To examine the tolerance of extremophiles against varying environmental conditions in a newly exposed moraine, we simulated environmental stress in bacterial cultures. The results showed that the isolated strains belonged to actinobacteria, Proteobacteria, Bacteroidetes, Deinococcus-Thermus, and Firmicutes. Actinobacteria was the most abundant phylum, followed by Proteobacteria, at both high and low temperatures. Pseudarthrobacter was the most abundant genus, accounting for 14.2% of the total isolates. Although several microorganisms grew at 10 °C, the proportion of microorganisms that grew at 25 °C was substantially higher. In particular, 50% of all bacterial isolates grew only at a high temperature (HT), whereas 21.4% of the isolates grew at a low temperature (LT), and 38.6% of the isolates grew at both HT and LT. In addition, many radiation-resistant extremophiles were identified, which adapted to both cold and oxidative conditions. The nearest neighbors of approximately >90% of bacteria belonged to a nonglacial environment, such as oil-contaminated soil, rocks, and black sand, instead of glacial niches. This study provides insights into the ecological traits, stress responses, and temporary survival of culturable heterotrophic bacteria in a newly exposed moraine with variable environmental conditions and the relationship of these communities with the non-glacial environment. This study may help to understand the evolution, competition, and selective growth of bacteria in the transition regions between glaciers and retreats in the context of glacier melting and retreat owing to global warming.

Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts.

Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.