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BACKGROUND: Cholestatic liver diseases induce local and systemic hypercoagulation, with neutrophil extracellular traps (NETs) serving as major drivers. These NETs have been linked to decreased liver function in patients with obstructive jaundice. However, the impact of NETs on liver hypercoagulation in cholestatic liver disease remains unknown. METHODS: We utilized bile duct ligation to create experimental mice and analyzed NETs formation in the liver. Fibrin deposition, tissue factor expression, and inflammation in the liver were visualized through western blot and immunohistochemical techniques. LSECs were incubated with isolated NETs, and we detected endothelial procoagulant activity using coagulation protein production assays and measuring endothelial permeability. In both in vivo and in vitro settings, DNase I was applied to clarify the effect of NETs on intrahepatic hypercoagulability, hepatotoxicity, LSEC, and macrophage activation or injury. RESULTS: Bile duct ligation mice exhibited significantly increased levels of NETs in liver tissue, accompanied by neutrophil infiltration, tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. Notably, NETs resulted in phosphatidylserine and tissue factor exposure on LSEC, enhancing coagulation Factor Xa and thrombin production. The enhanced procoagulant activity could be reversed by degrading NETs with DNase I. Additionally, NETs-induced permeability changes in LSECs, characterized by increased VE-cadherin expression and F-actin retraction, which could be rescued by DNase I. Meanwhile, NET formation is associated with KC activation and the formation of inflammatory factors. CONCLUSIONS: NETs promote intrahepatic activation of coagulation and inflammation, leading to liver tissue injury. Strategies targeting NET formation may offer a potential therapeutic approach for treating cholestatic liver disease.
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Armadilhas Extracelulares , Fígado , Trombose , Armadilhas Extracelulares/metabolismo , Animais , Camundongos , Fígado/patologia , Fígado/metabolismo , Trombose/etiologia , Trombose/patologia , Colestase/patologia , Colestase/complicações , Modelos Animais de Doenças , Masculino , Tromboplastina/metabolismo , Trombofilia/etiologia , Trombofilia/sangue , Fibrina/metabolismo , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Humanos , Infiltração de Neutrófilos , Fator Xa/metabolismo , Trombina/metabolismoRESUMO
Background: The sensitivity and specificity of current breath biomarkers are often inadequate for effective cancer screening, particularly in colorectal cancer (CRC). While a few exhaled biomarkers in CRC exhibit high specificity, they lack the requisite sensitivity for early-stage detection, thereby limiting improvements in patient survival rates. Methods: In this study, we developed an advanced Mass Spectrometry-based volatilomics platform, complemented by an enhanced breath sampler. The platform integrates artificial intelligence (AI)-assisted algorithms to detect multiple volatile organic compounds (VOCs) biomarkers in human breath. Subsequently, we applied this platform to analyze 364 clinical CRC and normal exhaled samples. Results: The diagnostic signatures, including 2-methyl, octane, and butyric acid, generated by the platform effectively discriminated CRC patients from normal controls with high sensitivity (89.7%), specificity (86.8%), and accuracy (AUC = 0.91). Furthermore, the metastatic signature correctly identified over 50% of metastatic patients who tested negative for carcinoembryonic antigen (CEA). Fecal validation indicated that elevated breath biomarkers correlated with an inflammatory response guided by Bacteroides fragilis in CRC. Conclusion: This study introduces a sophisticated AI-aided Mass Spectrometry-based platform capable of identifying novel and feasible breath biomarkers for early-stage CRC detection. The promising results position the platform as an efficient noninvasive screening test for clinical applications, offering potential advancements in early detection and improved survival rates for CRC patients.
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Inteligência Artificial , Biomarcadores Tumorais , Testes Respiratórios , Neoplasias Colorretais , Detecção Precoce de Câncer , Compostos Orgânicos Voláteis , Humanos , Neoplasias Colorretais/diagnóstico , Testes Respiratórios/métodos , Compostos Orgânicos Voláteis/análise , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer/métodos , Sensibilidade e Especificidade , Espectrometria de Massas/métodos , AdultoRESUMO
The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders.
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The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.
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The restriction of the field of view (FOV) enlargement and spatial resolution increase during optical monitoring was investigated. Traditional optical instruments usually have a fixed FOV in one test; thus, they have low accuracy for small samples under large motions/deformations. To improve the spatial resolution in a relatively large FOV of an optical instrument, a multiple-view 3D digital image correlation (3D-DIC) method based on pseudo-overlapped imaging is proposed. Using a set of optical components, pseudo-overlapped imaging can image two FOVs with the same camera, which converts one pair of cameras to four virtual cameras. Each virtual camera has the same whole pixels. Therefore, compared with the conventional 3D-DIC system, the proposed method simultaneously enlarges FOVs and increases spatial resolutions by two times. The efficiency, accuracy, and feasibility of the technique were validated through experiments.
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African swine fever (ASF) is a fatal disease that threatens the health status of the swine population and thus can impact the economic outcome of the global pig industry. Monitoring the ASF virus (ASFV) is of utmost concern to prevent and control its distribution. This study aims to identify a suitable sampling strategy for ASFV detection in living and deceased pigs under field conditions. A range of samples, comprising tissues obtained from deceased pigs, as well as serum and tonsil swab samples from live pigs, were gathered and subjected to detection using the qPCR method. The findings revealed that the mandibular lymph nodes demonstrated the highest viral loads among superficial tissues, thereby indicating their potential suitability for detecting ASFV in deceased pigs. Additionally, the correlations between virus loads in various tissues have demonstrated that tonsil swab samples are a viable specimen for monitoring live pigs, given the strong associations observed with other tissues. These findings indicated two dependable sample types for the detection of ASFV: mandibular lymph nodes for deceased pigs and tonsil swabs for live pigs, which supply some references for the development of efficacious preventive measures against ASFV.
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Structural-colored fabrics have been attracting much attention due to their eco-friendliness, dyelessness, and anti-fading properties. Monodisperse microspheres of metal, metal oxide, and semiconductors are promising materials for creating photonic crystals and structural colors owing to their high refractive indices. Herein, Cu2O microspheres were prepared by a two-step reduction method at room temperature; the size of Cu2O microspheres was controlled by changing the molar ratio of citrate to Cu2+; and the size of Cu2O microspheres was tuned from 275 nm to 190 nm. The Cu2O microsphere dispersions were prepared with the monodispersity of Cu2O microspheres. Furthermore, the effect of the concentration of Cu2O microsphere and poly(butyl acrylate) on the structural color was also evaluated. Finally, the stability of the structural color against friction and bending was also tested. The results demonstrated that the different structural colors of fabrics were achieved by adjusting the size of the Cu2O microsphere, and the color fastness of the structural color was improved by using poly(butyl acrylate) as the adhesive.
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Chiral spin textures, as exotic phases in magnetic materials, hold immense promise for revolutionizing logic, and memory applications. Recently, chiral spin textures have been observed in centrosymmetric magnetic insulators (FMI), due to an interfacial Dzyaloshinskii-Moriya interaction (iDMI). However, the source and origin of this iDMI remain enigmatic in magnetic insulator systems. Here, the source and origin of the iDMI in Pt/Y3Fe5O12 (YIG)/substrate structures are deeply delved by examining the spin-Hall topological Hall effect (SH-THE), an indication of chiral spin textures formed due to an iDMI. Through carefully modifying the interfacial chemical composition of Pt/YIG/substrate with a nonmagnetic Al3+ doping, the obvious dependence of SH-THE on the interfacial chemical composition for both the heavy metal (HM)/FMI and FMI/substrate interfaces is observed. The results reveal that both interfaces contribute to the strength of the iDMI, and the iDMI arises due to strong spin-orbit coupling and inversion symmetry breaking at both interfaces in HM/FMI/substrate. Importantly, it is shown that nonmagnetic substitution and interface engineering can significantly tune the SH-THE and iDMI in ferrimagnetic iron garnets. The approach offers a viable route to tailor the iDMI and associated chiral spin textures in low-damping insulating magnetic oxides, thus advancing the field of spintronics.
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Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.
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Ansiedade , Vias Neurais , Córtex Pré-Frontal , Estresse Psicológico , Animais , Ansiedade/psicologia , Ansiedade/fisiopatologia , Masculino , Estresse Psicológico/psicologia , Estresse Psicológico/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/fisiologia , Camundongos , Medo/fisiologia , Medo/psicologia , Camundongos Endogâmicos C57BL , Área Tegmentar Ventral/fisiopatologia , Tálamo/fisiopatologia , Núcleo Mediodorsal do Tálamo/fisiologia , Núcleo Mediodorsal do Tálamo/fisiopatologiaRESUMO
The objective of this study is to delve into the underlying mechanisms between mindfulness and burnout among preschool teachers. Employing a cross-sectional research design, this study surveyed 1,980 Chinese preschool teachers using the Mindful Attention Awareness Scale (MAAS), Preschool Teacher Dispositional Equanimity Questionnaire (PTDEQ), Empathy Scale (ME), and Maslach Burnout Inventory for Educators (MBI-ES). The results revealed a significant negative correlation between preschool teachers' mindfulness and burnout. A mediation analysis demonstrated that dispositional equanimity served as a mediator between mindfulness and preschool teacher burnout. Furthermore, a moderation analysis indicated that empathy moderated the influence of dispositional equanimity on preschool teacher burnout. These findings suggest that mindfulness can enable preschool teachers to better cope with workplace challenges with a more peaceful mindset.
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African swine fever (ASF) is a severe, hemorrhagic, and highly contagious disease caused by the African swine fever virus (ASFV) in both domestic pigs and wild boars. In China, ASFV has been present for over six years, with three genotypes of strains prevalent in field conditions: genotype I, genotype II, and genotype I/II recombinant strains. In order to differentiate among these three ASFV genotypes, a duplex fluorescent quantitative PCR method was established using specific probes and primers designed based on viral genes MGF_110-1L and O61R from ASFV strains reported in the GenBank database. Following optimization of reaction conditions, a duplex fluorescent quantitative PCR method was successfully developed. This method demonstrated no cross-reactivity with porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine reproductive and respiratory syndrome virus (PRRSV), classic swine fever virus (CSFV), porcine pseudorabies virus (PRV), porcine circovirus 2 (PCV2), porcine circovirus 3 (PCV3), highlighting its specificity. Sensitivity analysis revealed that the limits of detection (LODs) of this method were 2.95 × 10-1 copies/µL for the MGF_110-1L gene and 2.95 × 100 copies/µL for the O61R gene. The inter- and intra-group coefficients of variation were both <1%, indicating high reproducibility. In summary, the establishment of this duplex fluorescent quantitative PCR method not only addresses the identification of the ASFV recombinant strains but also allows for simultaneous identification of the three epidemic genotype strains.
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Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disease (IBD) characterized by colorectal inflammation. The N6-methyladenosine (m6A) modification of RNA regulates gene expression through the modulation of RNA metabolism, thus influencing various physiological and pathological processes. The aim of this study was to investigate the biological function of m6A methyltransferase METTL14 in colorectal epithelial cell inflammation. Bioinformatics analysis indicated that METTL14 expression was decreased in UC and was associated with disease severity and immune infiltration. We also noted a downregulation of METTL14 expression and a decrease in the total m6A RNA levels in TNF-α-stimulated Caco-2 cells. Moreover, METTL14 knockdown promoted inflammation and inhibited autophagy in TNF-α-stimulated Caco-2 cells, as indicated by the upregulation of NF-κB signaling and pro-inflammatory cytokine expression as well as LC3B protein downregulation. Treatment with the autophagy activator Torin-1 ameliorated the pro-inflammatory effects of METTL14 silencing. Furthermore, METTL14 knockdown significantly reduced the expression of ATG5. ATG5 overexpression could nullify the pro-inflammatory effect of METTL14 knockdown in TNF-α-stimulated Caco-2 cells. Mechanistically, METTL14 knockdown promoted ATG5 mRNA degradation, and luciferase analysis identified ATG5 as a target of m6A modification by METTL14. Taken together, silencing METTL14 promoted inflammation in Caco-2 cells via the downregulation of ATG5. Our findings revealed the importance of the m6A modification in colonic inflammation and autophagy, indicating that targeting METTL14 might be a potential therapeutic strategy for anti-inflammatory treatment in UC.
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Spontaneous splenic rupture is an extremely rare occurrence, often attributed to tumorous pathologies. Among these, primary splenic angiosarcoma stands as a malignancy arising from the endothelial cells within the spleen. While sporadic cases have been reported globally, there remains a lack of comprehensive consensus on standardized approaches for diagnosis and treatment. We report a case of an 83-year-old male who underwent emergency enhanced CT due to sudden shock, revealing significant intra-abdominal fluid accumulation. Emergency surgery revealed splenic rupture necessitating splenectomy. Histopathological examination confirmed the diagnosis of splenic angiosarcoma. Despite successful surgery, the patient succumbed to severe complications two weeks postoperatively.
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Introduction: Porcine viral diarrhea is a common clinical disease, which results in high mortality and economic losses in the pig industry. Porcine epidemic diarrhea virus (PEDV), porcine rotavirus (PoRV), and porcine deltacoronavirus (PDCoV) are important diarrhea viruses in pig herds. The similarities of their clinical symptoms and pathological changes make it difficult to distinguish these three viruses clinically. Therefore, there is a need for a highly sensitive and specific method to simultaneously detect and differentiate these viruses. Methods: A multiplex real-time PCR assay using TaqMan probes was developed to simultaneously detect PEDV, PoRV, and PDCoV. To assess the efficacy of the established assay, 30 clinical samples with diarrhea symptoms were used to compare the results obtained from the multiplex real-time PCR assay with those obtained from commercial singleplex real-time PCR kit. Importantly, a total of 4,800 diarrhea samples were tested and analyzed to validate the utility of the assay. Results: This multiplex real-time PCR assay showed high sensitivity, specificity, and excellent repeatability with a detection limit of 1 × 102 copies/µL. Comparing the results of the commercial singleplex real-time PCR kit and the multiplex real-time PCR method for detecting PEDV, PoRV, and PDCoV, there was complete agreement between the two approaches. Clinical data revealed single infection rates of 6.56% for PEDV, 21.69% for PoRV, and 6.65% for PDCoV. The co-infection rates were 11.83% for PEDV + PoRV, 0.29% for PEDV + PDCoV, 5.71% for PoRV + PDCoV, and 1.29% for PEDV + PDCoV + PoRV, respectively. Discussion: The multiplex real-time PCR method established in this study is a valuable diagnostic tool for simultaneously differentiating PEDV, PoRV, and PDCoV. This method is expected to significantly contribute to prevent and control the spread of infectious diseases, as well as aid in conducting epidemiological investigations.
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The adult brain retains a high repopulation capacity of astrocytes after deletion, and both mature astrocytes in the neocortex and neural stem cells in neurogenic regions possess the potential to generate astrocytes. However, the origin and the repopulation dynamics of the repopulating astrocytes after deletion remain largely unclear. The number of astrocytes is reduced in the medial prefrontal cortex (mPFC) of patients with depression, and selective elimination of mPFC astrocytes is sufficient to induce depression-like behaviors in rodents. However, whether astrocyte repopulation capacity is impaired in depression is unknown. In this study, we used different transgenic mouse lines to genetically label different cell types and demonstrated that in the mPFC of normal adult mice of both sexes, mature astrocytes were a major source of the repopulating astrocytes after acute deletion induced by an astrocyte-specific toxin, L-alpha-aminoadipic acid (L-AAA), and astrocyte regeneration was accomplished within two weeks accompanied by reversal of depression-like behaviors. Furthermore, re-ablation of mPFC astrocytes post repopulation led to reappearance of depression-like behaviors. In adult male mice subjected to 14-day chronic restraint stress, a well-validated mouse model of depression, the number of mPFC astrocytes was reduced; however, the ability of mPFC astrocytes to repopulate after L-AAA-induced deletion was largely unaltered. Our study highlights a potentially beneficial role for repopulating astrocytes in depression and provides novel therapeutic insights into enhancing local mature astrocyte generation in depression.
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Astrócitos , Depressão , Camundongos Transgênicos , Córtex Pré-Frontal , Animais , Astrócitos/metabolismo , Córtex Pré-Frontal/metabolismo , Masculino , Depressão/genética , Depressão/patologia , Feminino , Camundongos Endogâmicos C57BL , Camundongos , Modelos Animais de Doenças , Restrição Física , Ácido 2-Aminoadípico , Estresse Psicológico/patologia , Estresse Psicológico/metabolismoRESUMO
Tryptophan metabolism plays a crucial role in facilitating various cellular processes essential for maintaining normal cellular function. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), thereby initiating the degradation of Trp. The resulting Kyn metabolites have been implicated in the modulation of immune responses. Currently, the role of IDO1-mediated tryptophan metabolism in the process of viral infection remains relatively unknown. In this study, we discovered that classical swine fever virus (CSFV) infection of PK-15 cells can induce the expression of IDO1, thereby promoting tryptophan metabolism. IDO1 can negatively regulate the NF-κB signaling by mediating tryptophan metabolism, thereby facilitating CSFV replication. We found that silencing the IDO1 gene enhances the expression of IFN-α, IFN-ß, and IL-6 by activating the NF-κB signaling pathway. Furthermore, our observations indicate that both silencing the IDO1 gene and administering exogenous tryptophan can inhibit CSFV replication by counteracting the cellular autophagy induced by Rapamycin. This study reveals a novel mechanism of IDO1-mediated tryptophan metabolism in CSFV infection, providing new insights and a theoretical basis for the treatment and control of CSFV.IMPORTANCEIt is well known that due to the widespread use of vaccines, the prevalence of classical swine fever (CSF) is shifting towards atypical and invisible infections. CSF can disrupt host metabolism, leading to persistent immune suppression in the host and causing significant harm when co-infected with other diseases. Changes in the host's metabolic profiles, such as increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, can also influence virus replication. Mammals utilize various pathways to modulate immune responses through amino acid utilization, including increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, thereby limiting viral replication. Therefore, this study proposes that targeting the modulation of tryptophan metabolism may represent an effective approach to control the progression of CSF.
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Vírus da Febre Suína Clássica , Indolamina-Pirrol 2,3,-Dioxigenase , NF-kappa B , Transdução de Sinais , Triptofano , Replicação Viral , Triptofano/metabolismo , Animais , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , NF-kappa B/metabolismo , Suínos , Vírus da Febre Suína Clássica/fisiologia , Linhagem Celular , Cinurenina/metabolismo , Peste Suína Clássica/virologia , Peste Suína Clássica/metabolismo , AutofagiaRESUMO
Influenza A virus (IAV) is a highly contagious pathogen causing dreadful losses to humans and animals around the globe. As is known, immune escape is a strategy that benefits the proliferation of IAVs by antagonizing, blocking, and suppressing immune surveillance. The HA protein binds to the sialic acid (SA) receptor to enter the cytoplasm and initiate viral infection. The conserved components of the viral genome produced during replication, known as the pathogen-associated molecular patterns (PAMPs), are thought to be critical factors for the activation of effective innate immunity by triggering dependent signaling pathways after recognition by pattern recognition receptors (PRRs), followed by a cascade of adaptive immunity. Viral infection-induced immune responses establish an antiviral state in the host to effectively inhibit virus replication and enhance viral clearance. However, IAV has evolved multiple mechanisms that allow it to synthesize and transport viral components by "playing games" with the host. At its heart, this review will describe how host and viral factors interact to facilitate the viral evasion of host immune responses.
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Aplasia cutis congenita (ACC) is a congenital disorder that can be classified into nine types, with Type I ACC being the most common. Type V ACC associated with fetus papyraceus is a rare subtype of ACC. We report the case of a Type V ACC in a male newborn with extensive abdominal skin defects. The patient received conservative treatment using hydrogel foam and silicone foam dressings. Approximately five weeks later, the patient was discharged when more than 60% of the skin had completed epithelialization. After discharge from West China Second University Hospital, Chengdu , the patient continued to be followed up regularly at the Burns and Plastic Surgery Clinic at local hospital in Gansu. We followed up the child by telephone. After 4 months of follow-up, scar tissue formation was observed in the trunk area. The infant is 2 years and 5 months old now, physical examination did not reveal any organ problems.
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Tratamento Conservador , Displasia Ectodérmica , Humanos , Masculino , Displasia Ectodérmica/terapia , Recém-Nascido , BandagensRESUMO
The oncogenic protein E7 of the Human Papillomavirus (HPV) is constitutionally expressed in HPV-associated tumors and has the potential to be targeted in T cell receptor (TCR)-based immunotherapy. Adoptive transfer of TCR-engineered T (TCR-T) cells has shown promise as a therapeutic approach for HPV-induced tumors. This study aimed to identify HPV-E7 specific TCRs from HLA-A11:01 transgenic mice through single-cell sorting and sequencing facilitated by E789-97/HLA-A11:01 tetramer. Two dominant TCRs were identified, which exhibited specific binding to E789-97 presented in the context of HLA-A*11:01. TCR-T cells were prepared by infecting primary T cells with lentiviruses containing the TCR genes, and the two TCRs demonstrated substantial responsiveness and showed CD8+ dependent cytokine secretion characteristics. Further analyses of the cytokine profiles revealed that the two TCRs were capable of exerting polyfunctional responses upon specific stimulation. These findings suggest that the two TCRs represent promising candidates for the development of future therapeutic drugs targeting HPV-E7 in the context of HLA-A*11:01 for tumor immunotherapy.
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Camundongos Transgênicos , Proteínas E7 de Papillomavirus , Receptores de Antígenos de Linfócitos T , Animais , Camundongos , Proteínas E7 de Papillomavirus/imunologia , Humanos , Receptores de Antígenos de Linfócitos T/imunologia , Imunoterapia/métodos , Linfócitos T CD8-Positivos/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/terapia , Camundongos Endogâmicos C57BL , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Neoplasias/imunologia , FemininoRESUMO
The storage and transmission of videos at high spatial resolution remain a great challenge in image-based optical techniques. The uncertainty of digital image correlation (DIC) was assessed following speckle video compression under High Efficiency Video Coding (HEVC/H.265). First, the evaluation criterion for the DIC accuracy affected by compression was provided. The stability of H.265 video compression in DIC was studied considering different compressed frames under different target quantization parameters (QPs) and compression ratios (CRs). The deformation uncertainty of the DIC itself as affected by H.265 video compression was further investigated through uniform translation and non-uniform sinusoidal deformation performance. Moreover, the optimized digital speckle pattern (DSP) was re-evaluated considering video compression-induced uncertainty. DSPs with parameters of different diameters and randomness were compressed using various QPs and CRs. In addition, DSP evaluation was performed under both translation and non-homogeneous deformation conditions. The feasibility of the re-optimized DSP under H.265 video compression was validated using a defective bending beam, and DSP videos with a speckle size of 8 pixels reached a high CR within an acceptable margin of error.