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1.
J Colloid Interface Sci ; 666: 540-546, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38613976

RESUMO

Na3V2(PO4)3 is considered as one of the most promising cathodes for sodium ion batteries owing to its fast Na+ diffusion, good structural stability and high working potential. However, its practical application is limited by its low intrinsic electronic conductivity. Herein, a carbon coated Cu2+-doped Na3V2(PO4)3 cathode was prepared. The carbon coating not only improve its apparent conductivity, but also inhibit crystal growth and prevent agglomeration of particles. Moreover, Cu2+ doping contributes to an enhanced intrinsic conductivity and decreased Na+ diffusion energy barrier, remarkably boosting its charge transfer kinetics. Based on the structure characterizations, electrochemical performances tests, charge transfer kinetics analyses and theoretical calculations, it's proved that such an elaborate design ensures the excellent rate performances (116.9 mA h g-1 at 0.1C; 92.6 mA h g-1 at 10C) and distinguished cycling lifespan (95.8 % retention after 300 cycles at 1C; 84.8 % retention after 3300 cycles at 10C). Besides, a two-phase reaction mechanism is also confirmed via in-situ XRD. This research is expected to promote the development of Na3V2(PO4)3-based sodium ion batteries with high energy/power density and excellent cycling lifespan.

2.
Int J Biol Macromol ; 267(Pt 2): 131477, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604430

RESUMO

Salt stress severely limits the growth and yield of wheat in saline-alkali soil. While nanozymes have shown promise in mitigating abiotic stress by scavenging reactive oxygen species (ROS) in plants, their application in alleviating salt stress for wheat is still limited. This study synthesized a highly active nanozyme catalyst known as ZnPB (Zn-modified Prussian blue) to improve the yield and quality of wheat in saline soil. According to the Michaelis-Menten equation, ZnPB demonstrates exceptional peroxidase-like enzymatic activity, thereby mitigating oxidative damage caused by salt stress. Additionally, studies have shown that the ZnPB nanozyme is capable of regulating intracellular Na+ efflux and K+ retention in wheat, resulting in a decrease in proline and soluble protein levels while maintaining the integrity of macromolecules within the cell. Consequently, field experiments demonstrated that the ZnPB nanozyme increased winter wheat yield by 12.15 %, while also significantly enhancing its nutritional quality. This research offers a promising approach to improving the salinity tolerance of wheat, while also providing insights into its practical application.

3.
Poult Sci ; 103(5): 103659, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38537401

RESUMO

Micro-organisms on the eggshell surface of affect the quality of the egg. Sometimes, these microbes even pose a serious threat to the health of the egg's consumer. Bacterial 16S rDNA and fungal internal transcribed spacer region were sequenced to analyze the microbial diversity on the shell surface of the eggs collected from 4 distinct regions of China: Guyuan (GY; 1.5 million hens), Langfang (LF; 0.1 million hens), Beihai (BH; 1.2 million hens), and Dongguan (DG; 0.2 million hens). The results showed a higher bacterial and fungal abundance on the eggs collected from the northern and southern China farms, respectively. The dominant bacterial phylum detected across all egg samples was Firmicutes. In addition, the shell surfaces of the DG and LF samples harbored abundant levels of Proteobacteria. The dominant fungal phyla detected across all egg samples were Ascomycota and Basidiomycota. The bacterial compositions on eggshell surfaces differed significantly across all geographic regions, and the fungal composition differed significantly between samples collected from the southern and northern farms (P < 0.05). The abundance and composition of microbial colonies on the eggshell surface varied based on their geographical location (climate and environment) and farming scale (management). Our findings provide an important reference for optimizing the cleaning and disinfection methods for fresh eggs collected from different sources.

4.
Aging Dis ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38502586

RESUMO

Various signaling pathways are regulated by reactive oxygen species (ROS), which are radical oxygen intermediates under normal physiological conditions. However, when the buffering capacity of antioxidant enzymes is exceeded by the accumulation of ROS, oxidative stress, and endothelial cell dysfunction occur, which have been recognized as key contributors to the development of atherosclerosis. In this review, an overview is provided on mechanisms underlying ROS generation in endothelial cells and the involved regulatory pathways. Further, we discuss the ROS induced endothelial cell dysfunction and its relationship with atherosclerosis. Current knowledge on ROS-induced endothelial impairment is presented, characterized by decreased NO bioavailability, intracellular dysfunction and ox-LDL accumulation. Furthermore, biomarkers such as oxidative products of lipid, protein, and nucleotide are discussed as measurements for ROS levels. Novel interventions targeting oxidative stress are listed as potential pharmacotherapies in clinical practice. In conclusion, this review presents a systematic analysis of the mechanisms underlying ROS generation and elucidates how manipulation of these mechanisms can safeguard endothelial cell function.

5.
Heliyon ; 10(5): e26904, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434290

RESUMO

Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2α-dependent manner. Furthermore, the effects of eIF2α on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. Conclusion: Our results indicate that morphological and functional changes in VSMC organelles, especially in ER whorls, can be used as reliable biomarkers for atherosclerotic progression. Moreover, eIF2α plays an important role in integrating multiple stress-signaling pathways to determine the behavior and fate of VSMCs.

6.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473740

RESUMO

The mottled leaf is one of the agronomic traits of zucchini and can be applied as a marker trait in aggregation breeding. However, the genetic mechanism responsible for mottled leaf has yet to be elucidated. In the present study, we used two inbred lines (line '19': silver mottled leaf; line '113': normal leaf) as parents for the physiological and genetic analysis of mottled leaf. The synthesis and net photosynthetic rate of chlorophyll were not significantly affected in the mottled areas of leaves. However, we detected a large space between the palisade parenchyma in the leaf mottle area of line '19', which may have caused the mottled leaf phenotype. Light also plays an important role in the formation of mottled leaf, and receiving light during the early stages of leaf development is a necessary factor. Genetic analysis has previously demonstrated that mottled leaf is a quantitative trait that is controlled by multiple genes. Based on the strategy of quantitative trait locus sequencing (QTL-seq), two QTLs were identified on chromosomes 1 and 17, named CpML1.1 and CpML17.1, respectively. Two major loci were identified using R/qtl software version 1.66 under greenhouse conditions in April 2019 (2019A) and April 2020 (2020A) and under open cultivation conditions in May 2020 (2020M). The major QTL, CpML1.1, was located in a 925.2-kb interval on chromosome 1 and explained 10.51%-24.15% of the phenotypic variation. The CpML17.1 was located in a 719.7-kb interval on chromosome 17 and explained 16.25%-38.68% of the phenotypic variation. Based on gene annotation, gene sequence alignment, and qRT-PCR analysis, the Cp4.1LG01g23790 at the CpML1.1 locus encoding a protein of the TPX2 family (target protein of Xklp2) may be a candidate gene for mottled leaf in zucchini. Our findings may provide a theoretical basis for the formation of mottled leaf and provide a foundation for the fine mapping of genes associated with mottled leaf. Molecular markers closely linked to mottled leaf can be used in molecular-assisted selection for the zucchini mottled leaf breeding.


Assuntos
Cucurbita , Cucurbita/genética , Melhoramento Vegetal , Mapeamento Cromossômico , Locos de Características Quantitativas , Folhas de Planta/genética
7.
J Nat Prod ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38417168

RESUMO

PD-1/PD-L1 monoclonal antibodies exhibit promising therapeutic effectiveness in multiple cancers. However, developing a simple and efficient non-antibody treatment strategy using the PD-1/PD-L1 signaling pathway still remains challenging. In this study, we developed a flow cytometry assay to screen bioactive compounds with PD-L1 inhibitory activity. A total of 409 marine natural products were screened, and sokotrasterol sulfate (SKS) was found to efficiently suppress the IFN-γ-induced PD-L1 expression. SKS sensitizes the tumor cells to antigen-specific T-cell killing in the T cell-tumor cell coculture system. Mechanistically, SKS directly targeted Janus kinase (JAK) to inhibit the downstream activation of signal transducer and activator of transcription (STAT) and the subsequent transcription of PDL1. Our findings highlight the immunological role of SKS that may act as a basis for a potential immunotherapeutic agent.

8.
Toxicol Pathol ; : 1926233241229808, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385340

RESUMO

Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neurons, and nerve fiber degeneration of sensory tracts in the spinal cord and of multiple nerves. AAV-associated clinical signs and incidence/severity of histologic findings indicated that rabbits were equally or more sensitive than NHPs to sensory neuron damage. Another study using human and rabbit transgene constructs of the same protein demonstrated comparable changes suggesting that the effects are not an immune response to the non-self protein transgene. Rabbit has not been characterized as a species for general toxicity testing of AAV gene therapies, but these studies suggest that it may be an alternative model to investigate mechanisms of AAV-mediated neurotoxicity and test novel AAV designs mitigating these adverse effects.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38206780

RESUMO

Real-time electrocardiogram (ECG) monitoring and diagnosis through Internet of Things (IoT) are crucial for addressing the severity and timely treatment of cardiovascular diseases, enabling timely intervention and preventing life-threatening complications. However, current ECG monitoring research predominantly focuses on individual aspects such as signal compression, diagnostic analysis, or secure transmission, lacking joint optimization of various modules in IoT scenarios. To address this gap, this work proposes a novel framework based on superimposed semantic communication for real-time ECG monitoring in IoT. The framework comprises three hierarchical levels: the edge level for data collection and processing, the relay level for signal compression and coding, and the cloud level for data analysis and reconstruction. The proposed framework offers several unique advantages. By employing semantic encoding guided by ECG classification tasks, it selectively extracts crucial features within and between signals, improving compression ratio and adaptability to channel noise. The superimposed semantic encoding achieves content encryption without requiring any additional operations. Moreover, the framework utilizes lightweight anomaly detection neural networks, reducing edge device power consumption and conserving communication resources. Simulation and real experimental results demonstrate that the proposed method achieves real-time encoding and transmission of ECG signals with a compression ratio of 0.019 on the MIT-BIH dataset. Furthermore, it attains a heartbeat classification accuracy of 0.988 and a reconstruction error of 0.061.

11.
Adv Sci (Weinh) ; 11(3): e2306715, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37997289

RESUMO

Targeting the niche components surrounding glioblastoma stem cells (GSCs) helps to develop more effective glioblastoma treatments. However, the mechanisms underlying the crosstalk between GSCs and microenvironment remain largely unknown. Clarifying the extracellular molecules binding to GSCs marker CD133 helps to elucidate the mechanism of the communication between GSCs and the microenvironment. Here, it is found that the extracellular domain of high mannose type CD133 physically interacts with Collagen 1 (COL1) in GSCs. COL1, mainly secreted by cancer-associated fibroblasts, is a niche component for GSCs. COL1 enhances the interaction between CD133 and p85 and activates Akt phosphorylation. Activation of Akt pathway increases transcription factor ATF4 protein level, subsequently enhances SLC1A5-dependent glutamine uptake and glutathione synthesis. The inhibition of CD133-COL1 interaction or down-regulation of SLC1A5 reduces COL1-accelerated GSCs self-renewal and tumorigenesis. Analysis of glioma samples reveals that the level of COL1 is correlated with histopathological grade of glioma and the expression of SLC1A5. Collectively, COL1, a niche component for GSCs, enhances the tumorigenesis of GSCs partially through CD133-Akt-SLC1A5 signaling axis, providing a new mechanism underlying the cross-talk between GSCs and extracellular matrix (ECM) microenvironment.


Assuntos
Glioblastoma , Glioma , Humanos , Glioblastoma/metabolismo , Glutamina/metabolismo , Manose/metabolismo , Manose/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células-Tronco Neoplásicas/metabolismo , Carcinogênese/metabolismo , Transformação Celular Neoplásica , Glioma/metabolismo , Colágeno/metabolismo , Microambiente Tumoral , Antígenos de Histocompatibilidade Menor/metabolismo , Antígenos de Histocompatibilidade Menor/farmacologia , Sistema ASC de Transporte de Aminoácidos/metabolismo
12.
World Neurosurg ; 181: 90-92, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36627020

RESUMO

Both spinal dural arteriovenous fistula (SDAVF) and spinal cavernous malformation (SCM) are uncommon vascular malformations. To our knowledge, such a case of SDAVF concomitant with SCM has not been reported. We encountered a case of a 55-year-old man who had weakness and numbness in both lower extremities. Magnetic resonance imaging showed a round-shape lesion identified as a cavernous malformation in the middle segment of the thoracic spine, with spinal edema and obvious flow voids. Diagnostic angiography revealed an SDAVF fed by the right T7 radicular artery with venous drainage. The intramedullary venous hypertension due to fistula was suspected of inducing the formation of SCM. This case may provide new insight into the pathogenesis of SCM.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Anormalidades Musculoesqueléticas , Masculino , Humanos , Pessoa de Meia-Idade , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Medula Espinal/irrigação sanguínea , Coluna Vertebral , Angiografia , Imageamento por Ressonância Magnética/métodos , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia
13.
Heart Fail Rev ; 29(1): 113-123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37823952

RESUMO

The progression of heart failure is reported to be strongly associated with homeostatic imbalance, such as mitochondrial dysfunction and abnormal autophagy, in the cardiomyocytes. Mitochondrial dysfunction triggers autophagic and cardiac dysfunction. In turn, abnormal autophagy impairs mitochondrial function and leads to apoptosis or autophagic cell death under certain circumstances. These events often occur concomitantly, forming a vicious cycle that exacerbates heart failure. However, the role of the crosstalk between mitochondrial dysfunction and abnormal autophagy in the development of heart failure remains obscure and the underlying mechanisms are mainly elusive. The potential role of the link between mitochondrial dysfunction and abnormal autophagy in heart failure progression has recently garnered attention. This review summarized recent advances of the interactions between mitochondria and autophagy during the development of heart failure.


Assuntos
Insuficiência Cardíaca , Doenças Mitocondriais , Humanos , Insuficiência Cardíaca/metabolismo , Autofagia/fisiologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Doenças Mitocondriais/metabolismo
14.
Sci Rep ; 13(1): 22065, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087014

RESUMO

Traditionally, the clinical evaluation of respiratory diseases was pulmonary function testing, which can be used for the detection of severity and prognosis through pulmonary function parameters. However, this method is limited by the complex process, which is impossible for patients to monitor daily. In order to evaluate pulmonary function parameters conveniently with less time and location restrictions, cough sound is the substitute parameter. In this paper, 371 cough sounds segments from 150 individuals were separated into 309 and 62 as the training and test samples. Short-time Fourier transform (STFT) was applied to transform cough sound into spectrogram, and ResNet50 model was used to extract 2048-dimensional features. Through support vector regression (SVR) model with biological attributes, the data were regressed with pulmonary function parameters, FEV1, FEV1%, FEV1/FVC, FVC, FVC%, and the performance of this models was evaluated with fivefold cross-validation. Combines with deep learning and machine learning technologies, the better results in the case of small samples were achieved. Using the coefficient of determination (R2), the ResNet50 + SVR model shows best performance in five basic pulmonary function parameters evaluation as FEV1(0.94), FEV1%(0.84), FEV1/FVC(0.68), FVC(0.92), and FVC%(0.72). This ResNet50 + SVR hybrid model shows excellent evaluation of pulmonary function parameters during coughing, making it possible to realize a simple and rapid evaluation for pneumonia patients. The technology implemented in this paper is beneficial in judge the patient's condition, realize early screening of respiratory diseases, evaluate postoperative disease changes and detect respiratory infectious diseases without time and location restrictions.


Assuntos
Transtornos Respiratórios , Doenças Respiratórias , Humanos , Espirometria , Pulmão , Tosse/diagnóstico , Volume Expiratório Forçado , Capacidade Vital
15.
Artigo em Inglês | MEDLINE | ID: mdl-38083402

RESUMO

Recurrence plot (RP) has been widely used to transform 1D ECG waveforms into 2D images and explore the recurrence patterns of the electrical signals generated by the cardiac system. However, selecting the critical parameter time-delay τ for creating an RP has not been well-reported. In this work, we investigated the influence of different τ values on the RP-based AF prediction. And the results illustrated that the best classification performance could be achieved at τ=1 with full characters of the dynamic system.Clinical Relevance-This work established the AF classification system based on recurrence features and found the optimal parameters of the recurrence plot improving the ECG-based classification performance.


Assuntos
Fibrilação Atrial , Humanos , Coração , Eletricidade
16.
Opt Lett ; 48(21): 5471-5474, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910680

RESUMO

We have innovatively introduced the pulsated orifice ejection method into the preparation of glass fibers, successfully preparing high-purity Ge28Sb12Se60 glass fibers. These fibers have a smooth surface, uniform elemental distribution, and excellent bending properties, with a minimal bending radius of 2 mm. In the infrared spectrum from 2.5 to 13.5 µm, the fibers achieve 65% transmission. Additionally, the fibers possess a density of 4.586 g/cm3, a diameter of 35 µm, a glass transition temperature (Tg) of 369°C, and an onset crystallization temperature (Tx) of 557°C. We have also measured the surface tension of the glass fibers, finding values from 0.288 N/m to 0.124 N/m as temperatures rose from 450°C to 500°C. The POEM holds the potential to achieve fiber cores of lengths up to hundreds of meters in theory. Our work provides a distinctive perspective for the preparation of glass fibers.

17.
Aquat Toxicol ; 265: 106763, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37980848

RESUMO

Microcystins (MCs) are biologically active cyclic heptapeptide compounds released by cyanobacteria in water bodies, and MC-LR is one of the most widespread and toxic isoforms. It frequently poses a serious threat to Penaeus vannamei aquaculture. Our previous study revealed that the supplementation of Lactobacillus plantarum Ep-M17 has a probiotic effect on P. vannamei health and whether Ep-M17 can alleviate the stressful effects of MC-LR on shrimp remains unclear. Therefore, in the present work, shrimp were fed MC-LR alone or combined with Ep-M17 for six weeks, and then evaluated the effects on histology, enzyme activity, gene expression, and intestinal flora. The results showed that MC-LR stress lead to slow growth and reduced survival rates in shrimp. However, feeding Ep-M17 significantly increased both the growth rate and survival rate. Meanwhile, MC-LR stress caused severe tissue damage in the hepatopancreas and intestines of shrimp, but Ep-M17 significantly reduced the toxic effects and protected the integrity of these tissues. Additionally, Ep-M17 significantly enhanced the activities of antioxidant enzymes and digestive enzymes, and induced higher expression of immune-related genes, thereby promoting the digestive and immune responses in shrimp. Furthermore, MC-LR stress disrupted the intestinal flora in shrimp intestines, while the use of Ep-M17 significantly increased the abundance of immune- and metabolism-related bacteria and inhibited the growth of pathogenic bacteria to maintain intestinal flora balance and intestinal health. In conclusion, our results indicate that Ep-M17 can reduce the toxic effect of MC-LR on shrimp and has a positive function in the prevention and control of shrimp diseases caused by MC-LR.


Assuntos
Cianobactérias , Microbioma Gastrointestinal , Lactobacillus plantarum , Penaeidae , Poluentes Químicos da Água , Animais , Lactobacillus plantarum/metabolismo , Microcistinas/toxicidade , Microcistinas/metabolismo , Penaeidae/fisiologia , Poluentes Químicos da Água/toxicidade , Cianobactérias/metabolismo
18.
Langmuir ; 39(47): 16750-16759, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37963300

RESUMO

Low-molecular-weight peptide hydrogels can be formed by self-assembly through weak interactions, but the application of the hydrogel is influenced by its weak mechanical properties. Therefore, it is important to construct low-molecular-weight peptide hydrogels with excellent mechanical properties. In this work, we designed the pentapeptide molecule Fmoc-FFCKK-OH (abbreviated as FFCKK) with a sulfhydryl group, and another low-molecular-weight cross-linker N,N'-methylenebis(acrylamide) (MBA) was introduced to construct a hydrogel with excellent mechanical properties. The secondary structure change process of FFCKK and the assembly mechanism of hydrogel were analyzed using theoretical calculations and experimental characterizations. The occurrence of thiol-ene click chemistry provides covalent interaction in the hydrogel, and the synergistic effect ofcovalent interaction and hydrogen bonding improves the mechanical properties of the hydrogel by nearly 10-fold. The hydrogel was observed to be able to withstand a stress of 368 Pa and to break in a layer-by-layer manner by compression testing. The micromechanics of the hydrogels were characterized, and the excellent mechanical properties of the hydrogels were confirmed. The synergistic approach provides a new idea for the preparation of low-molecular-weight peptide hydrogels and facilitates the expansion of their potential applications in biomedical fields.


Assuntos
Química Click , Hidrogéis , Hidrogéis/química , Compostos de Sulfidrila/química , Peptídeos/química
19.
Mol Cancer Ther ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37963566

RESUMO

Aberrant N-linked glycosylation is a prominent feature of cancers. Perturbance of oligosaccharide structure on cell surfaces directly affects key processes in tumor development and progression. In spite of the critical role played by N-linked glycans in tumor biology, the discovery of small molecules that specifically disturbs the N-linked glycans is still under investigation. To identify more saccharide-structure-perturbing compounds, a repurposed drug screen by using a library consisting of 1530 FDA-approved drugs was performed. Interestingly, an antipsychotic drug, penfluridol, was identified as being able to decrease cell surface Wheat germ agglutinin (WGA) staining. In the presence of penfluridol, cell membrane glycoproteins PD-L1 shifted to a lower molecular weight. Further studies demonstrated that penfluridol treatment caused an accumulation of high-mannose oligosaccharides, especially Man5-7GlcNAc2 glycan structures. Mechanistically, this effect is due to direct targeting of MAN1A1 mannosidase, a Golgi enzyme involved in N-glycan maturation. Moreover, we found that altered glycosylation of PD-L1 caused by penfluridol disrupted interactions between PD-1 and PD-L1, resulting in activation of T-cell tumor immunity. In a mouse xenograft and glioma model, penfluridol enhanced the anti-tumor effect of the anti-PD-L1 antibody in vivo. Overall, these findings revealed an important biological activity of the antipsychotic drug penfluridol as an inhibitor of glycan processing and proposed a repurposed use of penfluridol in anti-tumor therapy through activation of T-cell immunity.

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