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2.
Front Cell Infect Microbiol ; 14: 1367975, 2024.
Article En | MEDLINE | ID: mdl-38736750

The endemic outbreak of SADS-CoV has resulted in economic losses and potentially threatened the safety of China's pig industry. The molecular epidemiology of SADS-CoV in pig herds has been investigated in many provinces in China. However, there are no data over a long-time span, and there is a lack of extensive serological surveys to assess the prevalence of SADS-CoV in Chinese swine herds since the discovery of SADS-CoV. In this study, an indirect anti-SADS-CoV IgG enzyme-linked immunosorbent assay (ELISA) based on the SADS-CoV S1 protein was established to investigate the seroprevalence of SADS-CoV in Chinese swine herds. Cross-reactivity assays, indirect immunofluorescence, and western blotting assays showed that the developed ELISA had excellent SADS-CoV specificity. In total, 12,978 pig serum samples from 29 provinces/municipalities/autonomous regions in China were tested from 2022 to 2023. The results showed that the general seroprevalence of SADS-CoV in China was 59.97%, with seroprevalence ranging from 16.7% to 77.12% in different provinces and from 42.61% to 68.45% in different months. SADS-CoV is widely prevalent in China, and its seroprevalence was higher in Northeast China, North China, and Central China than in other regions. Among the four seasons, the prevalence of SADS-CoV was the highest in spring and the lowest in autumn. The results of this study provide the general seroprevalence profile of SADS-CoV in China, facilitating the understanding of the prevalence of SADS-CoV in pigs. More importantly, this study is beneficial in formulating preventive and control measures for SADS-CoV and may provide directions for vaccine development.


Antibodies, Viral , Coronavirus Infections , Enzyme-Linked Immunosorbent Assay , Swine Diseases , Animals , China/epidemiology , Seroepidemiologic Studies , Swine , Enzyme-Linked Immunosorbent Assay/methods , Antibodies, Viral/blood , Swine Diseases/epidemiology , Swine Diseases/virology , Coronavirus Infections/veterinary , Coronavirus Infections/epidemiology , Coronavirus Infections/diagnosis , Immunoglobulin G/blood , Alphacoronavirus/immunology , Alphacoronavirus/genetics , Cross Reactions , Sensitivity and Specificity
3.
Adv Sci (Weinh) ; : e2403507, 2024 May 10.
Article En | MEDLINE | ID: mdl-38733084

The defects in perovskite film can cause charge carrier trapping which shortens carrier lifetime and diffusion length. So defects passivation has become promising for the perovskite studies. However, how defects disturb the carrier transport and how the passivating affects the carrier transport in CsPbBr3 are still unclear. Here the carrier dynamics and diffusion processes of CsPbBr3 and LiBr passivated CsPbBr3 films are investigated by using transient absorption spectroscopy and transient absorption microscopy. It's found that there is a fast hot carrier trapping process with the above bandgap excitation, and the hot carrier trapping would decrease the population of cold carriers which are diffusible, then lower the carrier diffusion constant. It's proved that LiBr can passivate the defect and lower the trapping probability of hot carriers, thus improve the carrier diffusion rate. The finding demonstrates the influence of hot carrier trapping to the carrier diffusion in CsPbBr3 film.

4.
Cell Mol Immunol ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38740925

The NLRP3 inflammasome functions as an inflammatory driver, but its relationship with lipid metabolic changes in early sepsis remains unclear. Here, we found that GITR expression in monocytes/macrophages was induced by lysophosphatidylcholine (LPC) and was positively correlated with the severity of sepsis. GITR is a costimulatory molecule that is mainly expressed on T cells, but its function in macrophages is largely unknown. Our in vitro data showed that GITR enhanced LPC uptake by macrophages and specifically enhanced NLRP3 inflammasome-mediated macrophage pyroptosis. Furthermore, in vivo studies using either cecal ligation and puncture (CLP) or LPS-induced sepsis models demonstrated that LPC exacerbated sepsis severity/lethality, while conditional knockout of GITR in myeloid cells or NLRP3/caspase-1/IL-1ß deficiency attenuated sepsis severity/lethality. Mechanistically, GITR specifically enhanced inflammasome activation by regulating the posttranslational modification (PTM) of NLRP3. GITR competes with NLRP3 for binding to the E3 ligase MARCH7 and recruits MARCH7 to induce deacetylase SIRT2 degradation, leading to decreasing ubiquitination but increasing acetylation of NLRP3. Overall, these findings revealed a novel role of macrophage-derived GITR in regulating the PTM of NLRP3 and systemic inflammatory injury, suggesting that GITR may be a potential therapeutic target for sepsis and other inflammatory diseases. GITR exacerbates LPC-induced macrophage pyroptosis in sepsis via posttranslational regulation of NLRP3. According to the model, LPC levels increase during the early stage of sepsis, inducing GITR expression on macrophages. GITR not only competes with NLRP3 for binding to the E3 ligase MARCH7 but also recruits MARCH7 to induce the degradation of the deacetylase SIRT2, leading to decreasing ubiquitination but increasing acetylation of NLRP3 and therefore exacerbating LPC-induced NLRP3 inflammasome activation, macrophage pyroptosis and systemic inflammatory injury.

5.
Appl Spectrosc ; : 37028241254391, 2024 May 21.
Article En | MEDLINE | ID: mdl-38772555

An infrared squaraine dye was utilized to detect Cu2+ in solvents based on H-aggregates of squaraine dye. H-aggregates are a type of aggregation with enhanced photophysical properties compared to monomers. In the presence of a Ca2+ solution, F-Cl offers exceptional H-aggregators that can be transformed into monomers by adding Cu2+. Furthermore, this mode successfully demonstrated fluorescence changes in HeLa cells cultured in vitro after the addition of Ca2+ or Cu2+. A highly specific detection of Cu2+ was achieved using this transformation mode.

6.
Cell Death Dis ; 15(5): 343, 2024 May 17.
Article En | MEDLINE | ID: mdl-38760361

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.


Mice, Knockout , Netrin-1 , Pyramidal Tracts , Animals , Netrin-1/metabolism , Netrin-1/genetics , Mice , Pyramidal Tracts/metabolism , Pyramidal Tracts/pathology , Axons/metabolism , Axons/pathology
8.
Sci Rep ; 14(1): 10405, 2024 05 06.
Article En | MEDLINE | ID: mdl-38710809

As the most popular sport among middle-aged and elderly women in China, square dancing has both physical and psychological benefits for menopausal women. Previous studies have shown that square dance exercises can promote the physical health of older women, but there is a lack of research on the influence of middle-aged and elderly women on mental health and mediating variables. Therefore, this study starts with one of the important indicators of mental health-positive affects, aiming to explore the impact of square dance on the positive emotions of elderly women and further explore the mediating mechanisms involved. We send out The Physical Activity Rating Scale, the Positive and Negative Affect Scale, the Connor-Davidson Resilience Scale, and the Satisfaction With Life Scale to a total of 2311 middle-aged and elderly women. SPSS 23 software and PROCESS were used to perform regression analysis and establish mediation models. Modeling results show square dance exercises could positively predict positive affect through the chain mediating effect of psychological resilience and life satisfaction. The results of this study are of great significance for promoting the extensive participation of middle-aged and elderly women in sports and protecting their mental health.


Dancing , Mental Health , Personal Satisfaction , Humans , Female , Dancing/psychology , Middle Aged , Aged , Aging/psychology , Exercise/psychology , China , Resilience, Psychological , Quality of Life , Psychological Well-Being
9.
J Multidiscip Healthc ; 17: 2031-2038, 2024.
Article En | MEDLINE | ID: mdl-38706503

Background: Patients on maintenance hemodialysis have an increased risk of fracture. However, the relationship between fracture and poor prognosis is not clear. Methods: A total of 182 maintenance hemodialysis patients were enrolled in the study. The relationship between fracture and poor prognosis (cardiovascular events, stroke, malignancy and 5-year all-cause mortality) were analyzed. Results: 21 of 182 patients had a history of fracture at the time of enrollment. 26 patients had a new fracture after enrollment. A total of 57 fractures occurred in 47 patients, the most common fracture site was the rib. Patients with fracture group had a higher proportion of elderly and female, higher serum phosphorus and B-type natriuretic peptide and lower hemoglobin, albumin, and potassium compared with those without fracture. Age (OR=3.809, 95% CI: 1.064-8.966, p=0.038), hemoglobin (OR=0.961, 95% CI: 0.925-0.997, p=0.035), and serum phosphorus (OR=3.325, 95% CI:1.104-10.019, p=0.033) were the independent risk factors of new fractures in MHD patients. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture (p<0.05). But there was no significant difference in the incidence of acute myocardial infarction or stroke. Conclusion: 25.8% of maintenance hemodialysis patients had at least one fracture, with rib fractures accounting for the highest proportion. Age, hemoglobin and serum phosphorus were the independent risk factors of new fractures. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture, but there was no significant difference in the incidence of acute myocardial infarction and stroke.


To determine the incidence of fractures in hemodialysis patients, we conducted this single center, prospective observational study. 182 patients were enrolled. We also recorded the 5-year incidence of acute myocardial infarction(AMI), stroke, malignancy, and mortality. Our results showed that the incidence of fracture in hemodialysis patients was 25.8%. The most common fracture site was the rib. There were significant statistical differences in age, gender, hemoglobin, serum albumin, B-type natriuretic peptide, potassium and phosphorus between patients with and without fractures. Logistic regression analysis suggested that advanced age, anaemia and hyperphosphatemia were independent risk factors for new fractures in hemodialysis patients. We followed 182 patients for 5 years and recorded the incidence of stroke, AMI and malignancy. The rates of AMI and stroke did not differ significantly between the two groups. However, the incidence of malignancy in patients with fractures is significantly higher than that in patients without fractures. In our study, a total of 74 patients died, including 24 deaths in the fracture group and 50 deaths in the non-fracture group. The main causes of death in 74 cases were cardiovascular events. Our study provides some insight into the association between fractures and poor outcomes in hemodialysis patients.

10.
Redox Biol ; 73: 103183, 2024 May 13.
Article En | MEDLINE | ID: mdl-38759418

AIMS: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. METHODS AND RESULTS: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. CONCLUSIONS: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

11.
J Biol Chem ; : 107379, 2024 May 16.
Article En | MEDLINE | ID: mdl-38762184

Bacterial RecJ exhibits 5'→3' exonuclease activity that is specific to single-stranded DNA (ssDNA); however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.

13.
PLoS One ; 19(5): e0302498, 2024.
Article En | MEDLINE | ID: mdl-38758804

BACKGROUND: Medical Waste (MW), conceptualized as waste generated in the diagnosis, treatment, or immunization of human beings or animals, posing massive threat to public health. Environment-friendly public attitudes promotes the shaping of pro-environmental behavior. However, the public attitudes of MW and the potential determinants remained scarce. The present study aims to reveal globally public attitudes towards MW and captured the determinants. METHODS: We integrated the crawler technology with sentiment analysis to captured the public attitudes toward MW across 141 specific countries from 3,789,764 related tweets. Multiple cross-national databases were integrated to assess characteristics including risk, resistance, environment, and development. The spatial regression model was taken to counterbalence the potential statistical bias. RESULTS: Overall, the global public attitudes towards MW were positive, and varied significantly across countries. Resilience (ß = 0.78, SD = 0.14, P < 0.01) and development (ß = 1.66, SD = 0.13, P < 0.01) posed positive influence on public attitudes towards MW, meanwhile, risk (ß = -0.1, SD = 0.12, P > 0.05) and environment (ß = 0.09, SD = 0.09, P > 0.05) were irrelated to the shaping of positive MW public attitudes. Several positive moderating influences was also captured. Additionally, the cross-national disparities of the determiants were also captured, more specific, public attitudes towards MW in extremely poor areas were more likely to be negatively affected by risks, resilience and development. CONCLUSIONS: This study focused mainly on the public attitudes as well as captured the potential determinants. Public attitudes towards MW were generally positive, but there were large cross-national disparities. Stakeholders would need to designate targeted strategies to enhance public satisfaction with MW management.


Medical Waste , Public Opinion , Humans , Attitude , Medical Waste Disposal/methods
14.
Mol Plant ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38720462

N6-methyladenosine (m6A) is one of the most abundant modifications in eukaryotic mRNA, but the comprehensive biological functionality continues to be a subject for exploration. In this study, we identified and characterized a new flowering-promoting gene EARLY HEADING DATE6 (EHD6) in rice. EHD6 encodes an RNA recognition motif (RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein (RNP) granules and can bind both m6A-modified RNA and unmodified RNA indiscriminately. We found that EHD6 can physically interact with YTH07, a YTH (YT521-B homology) domain containing m6A reader, and their interaction enhances the binding of m6A-modified RNA and triggers relocation of a part of YTH07 from the cytoplasm into RNP granules through phase-separated condensation. Within these condensates, the mRNA of a rice flowering repressor, CONSTANS-like 4 (OsCOL4), becomes sequestered, leading to a reduction in its protein abundance and thus affect flowering through the Early heading date 1 pathway. Our results not only shed new light on the molecular mechanism of efficient m6A recognition by the collaboration between the RNA binding protein and YTH family m6A reader, but also uncovers a potential m6A mediated translation regulation through phase-separated ribonucleoprotein condensation in rice.

16.
Article En | MEDLINE | ID: mdl-38595104

OBJECTIVE: The purpose of this study is to identify the presence of occult peritoneal metastasis (OPM) in patients with advanced gastric cancer (AGC) by using clinical characteristics and abdominopelvic computed tomography (CT) features. METHODS: This retrospective study included 66 patients with OPM and 111 patients without peritoneal metastasis (non-PM [NPM]) who underwent preoperative contrast-enhanced CT between January 2020 and December 2021. Occult PMs means PMs that are missed by CT but later diagnosed by laparoscopy or laparotomy. Patients with NPM means patients have neither PM nor other distant metastases, indicating there is no evidence of distant metastases in patients with AGC. Patients' clinical characteristics and CT features such as tumor marker, Borrmann IV, enhancement patterns, and pelvic ascites were observed by 2 experienced radiologists. Computed tomography features and clinical characteristics were combined to construct an indicator for identifying the presence of OPM in patients with AGC based on a logistic regression model. Receiver operating characteristic curves and the area under the receiver operating characteristic curve (AUC) were generated to assess the diagnostic performance of the combined indicator. RESULTS: Four independent predictors (Borrmann IV, pelvic ascites, carbohydrate antigen 125, and normalized arterial CT value) differed significantly between OPM and NPM and performed outstandingly in distinguishing patients with OPM from those without PM (AUC = 0.643-0.696). The combined indicator showed a higher AUC value than the independent risk factors (0.820 vs 0.643-0.696). CONCLUSIONS: The combined indicator based on abdominopelvic CT features and carbohydrate antigen 125 may assist clinicians in identifying the presence of CT OPMs in patients with AGC.

17.
Abdom Radiol (NY) ; 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38634880

PURPOSE: To explore whether dual-energy CT (DECT) quantitative parameters could provide analytic value for the diagnosis of patients with occult peritoneal metastasis (OPM) in advanced gastric cancer preoperatively. MATERIALS AND METHODS: This retrospective study included 219 patients with advanced gastric cancer and DECT scans. The patient's clinical data and DECT related iodine concentration (IC) parameters and effective atomic number (Zeff) were collated and analyzed among noun-peritoneal metastasis (NPM), OPM and radiologically peritoneal metastasis (RPM) groups. The predictive performance of the DECT parameters was compared with that of the conventional CT features and clinical characteristics through evaluating area under curve of the precision-recall (AUC-PR), F1 score, balanced accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Borrmann IV type diagnosed on CT and serum tumor indicator CA125 index were statistically different between the NPM and OPM groups. DECT parameters included IC, normalized IC (NIC), and Zeff of PM group were lower than the NPM group. The DECT predictive nomogram combined three independent DECT parameters produced a better diagnostic performance than the conventional CT feature Borrmann IV type and serum CA125 index in AUC-PR with 0.884 vs 0.368 vs 0.189, but similar to the combined indicator which was based on the DECT parameters, the conventional CT feature, and serum CA125 index in AUC-PR with 0.884 vs 0.918. CONCLUSION: The lower quantitative NIC, IC ratio, and Zeff on DECT was associated with peritoneal metastasis in advanced gastric cancer and was promising to identify patients with OPM noninvasively.

18.
J Hazard Mater ; 470: 134188, 2024 May 15.
Article En | MEDLINE | ID: mdl-38579587

Microplastic contamination presents a significant global environmental threat, yet scientific understanding of its morphological distribution within ecosystems remains limited. This study introduces a pioneering method for comprehensive microplastic assessment and environmental monitoring, integrating photoacoustic imaging and advanced deep learning techniques. Rigorous curation of diverse microplastic datasets enhances model training, yielding a high-resolution imaging dataset focused on shape-based discrimination. The introduction of the Vector-Quantized Variational Auto Encoder (VQVAE2) deep learning model signifies a substantial advancement, demonstrating exceptional proficiency in image dimensionality reduction and clustering. Furthermore, the utilization of Vector Quantization Microplastic Photoacoustic imaging (VQMPA) with a proxy task before decoding enhances feature extraction, enabling simultaneous microplastic analysis and discrimination. Despite inherent limitations, this study lays a robust foundation for future research, suggesting avenues for enhancing microplastic identification precision through expanded sample sizes and complementary methodologies like spectroscopy. In conclusion, this innovative approach not only advances microplastic monitoring but also provides valuable insights for future environmental investigations, highlighting the potential of photoacoustic imaging and deep learning in bolstering sustainable environmental monitoring efforts.

19.
Environ Int ; 187: 108687, 2024 May.
Article En | MEDLINE | ID: mdl-38677088

The biotoxicity of perfluoroalkyl and polyfluoroalkyl substances (PFASs) to aquatic organisms has been widely concerned. However, studies on toxic effects of PFASs are usually evaluated directly by using laboratory exposure rather than laboratory validation based on data obtained in the field. In this study, wild catfish (Silurus meridinalis) was explored on the relationship between PFASs bioaccumulation and lipid disorders. Nine and thirteen lipid metabolites were significantly associated with perfluorooctane sulfonate (PFOS) and 6:2/8:2Cl-PFESA (trade name F-53B) exposures, respectively; and the correlated lipid metabolites were the fatty acid (FA) and conjugates, FA esters, steroids, and glycerophosphate subclasses. The effects of PFASs on lipid metabolism of fish and its mechanism were further analyzed through exposure experiments. Zebrafish (Danio rerio) of different sexes underwent PFOS and F-53B exposures for 21 days at 100 ng/L and 100 µg/L. By determining gene expression levels, hepatic lipid contents, and histopathological change, the adverse effects order on lipid metabolism in male or female was 100 µg/L F-53B > 100 µg/L PFOS > 100 ng/L F-53B > 100 ng/L PFOS; the stress response in male was more intensive than that in female. PFOS and F-53B activated the peroxisome proliferator-activated receptor pathway, promoting the processes of FA and total cholesterol (T-CHO) transport, FA ß-oxidation, FA synthesis, and finally induced FA and T-CHO transportation from blood into liver, then accelerated FA to FA ester transformation, and CHO into steroids. Laboratory experiments confirmed the field analysis. This study innovatively explored the adverse effects of PFOS and F-53B on lipid metabolism and their mechanisms at field and laboratory levels, highlighting concerns regarding PFASs health risks.


Fluorocarbons , Lipid Metabolism , Water Pollutants, Chemical , Zebrafish , Animals , Lipid Metabolism/drug effects , Fluorocarbons/toxicity , Water Pollutants, Chemical/toxicity , Male , Female , Catfishes/metabolism , Alkanesulfonic Acids/toxicity , Liver/drug effects , Liver/metabolism
20.
Biomater Sci ; 12(10): 2660-2671, 2024 May 14.
Article En | MEDLINE | ID: mdl-38592706

The endo-lysosomal pathway is a major barrier for the trans-epithelial transport of nanoparticles (NPs), but escape strategies could facilitate trans-epithelial delivery. Based on the polarization properties of the epithelium, different escape compartments may result in different exocytosis fates of NPs and further affect the delivery efficiency. Therefore, optimizing the escape sites is critical for trans-epithelial delivery. Here, commonly used PEG-coated-poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles were fabricated as model nanoparticles (MNPs) and the intestinal epithelium was chosen as the polarized epithelium. The MNPs were incubated with different endosomolytic agents for early endosomal escape, late endosomal escape and lysosomal escape, respectively. According to in vitro and in vivo studies, MNPs escaping from early endosomes and late endosomes exhibited stronger capacity for trans-epithelial transport than those escaping from lysosomes. By further probing into the mechanism, we surprisingly found that although MNPs escaping from early endosomes quickly egressed from the apical side of epithelia, they were subsequently followed by "reuptake" via caveolae and trafficked through the endoplasmic reticulum-Golgi apparatus (ER/GA) secretory pathway, achieving efficient trans-epithelial transport; MNPs escaping from late endosomes, which were located near the nucleus, were prone to enter the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes were detained within cells by autophagosomes. Collectively, our research suggested that early endosomes and late endosomes were ideal escape sites for trans-epithelial delivery.


Endosomes , Exocytosis , Lysosomes , Nanoparticles , Lysosomes/metabolism , Exocytosis/physiology , Animals , Nanoparticles/chemistry , Endosomes/metabolism , Polyethylene Glycols/chemistry , Humans , Mice , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Dogs , Intestinal Mucosa/metabolism
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