Background: Virus-induced asthma exacerbation is a major cause of hospitalization and mortality in patients with asthma, yet the underlying immunopathology remains incompletely understood owing to the lack of human-relevant in vivo models. Humanized mice are powerful tools for biomedical investigation, but their application in studying asthma exacerbation has not yet been explored. Methods: We established a cytokine-optimized Thy/HSC humanized mouse model by combining transplantation of human fetal thymic tissue and CD34⁺ fetal liver cells with adeno-associated virus (AAV)-mediated delivery of human GM-CSF, IL-3, and IL-5. Asthmatic airway inflammation was induced by intranasal IL-33 administration, followed by H1N1 influenza infection to model viral-induced asthma exacerbation. Immunological, histopathological, and transcriptomic analyses were performed to characterize disease progression and therapeutic responses. Findings: AAV-mediated cytokine complementation markedly enhanced human myeloid reconstitution in vivo and enabled robust IL-33-driven airway inflammation characterized by peribronchial inflammatory cell infiltration, goblet cell hyperplasia, mucus hypersecretion, and elevated human type 2 cytokines. Subsequent influenza infection triggered severe asthma exacerbation accompanied by weight loss, mortality, neutrophilic inflammatory conversion, cytokine hyperproduction, and extensive lung injury, closely recapitulating clinical features observed in uncontrolled asthma exacerbation patients. Transcriptomic analyses identified IL-6 signaling as a central driver of inflammatory amplification and pathological remodeling. Therapeutic blockade of the IL-6 receptor with tocilizumab suppressed inflammatory cytokine production, reduced immune cell infiltration, alleviated lung pathology, promoted macrophage transition toward an anti-inflammatory phenotype, and significantly improved animal survival. Interpretation: We establish a humanized mouse model that recapitulates viral-induced asthma exacerbation through functional reconstruction of the human myeloid compartment. This platform provides a clinically relevant system for mechanistic investigation and preclinical therapeutic evaluation, while identifying IL-6 signaling as a potential therapeutic target in severe asthma exacerbation.

Asthma exhibits pronounced sex differences across the human lifespan, shifting from a predominance in males during childhood toward an increased prevalence, severity, and heterogeneity in females following puberty. These epidemiological patterns are not paralleled by uniform changes in disease phenotype, with adult females exhibiting a higher prevalence of non-type 2 inflammation. Mechanistically, estrogen has emerged as a key regulator of this heterogeneity through its pleiotropic effects on immune and structural cells. However, the immunological actions of estrogen are highly context-dependent, varying with receptor subtype (ERα versus ERβ), hormone concentration, and prevailing inflammatory milieu. Rather than uniformly amplifying immunity, estrogen’s principal nuclear receptors exert opposing effects. ERα predominantly promotes immune activation, whereas ERβ exerts counterbalancing anti-inflammatory and bronchoprotective functions. Estrogen promotes immune amplification rather than polarization by simultaneously disrupting regulatory pathways and enhancing T helper 2 (Th2)-, T helper 17 (Th17)-, and innate immune system-mediated responses. Sex chromosome-linked and epigenetic mechanisms, including X-chromosome inactivation escape, further contribute to immune activation in females, although direct evidence in the asthma-specific context remains limited. Importantly, asthma phenotypes are shaped across the female lifespan by interactions between hormonal signaling and other contributing factors such as obesity and other comorbidities, viral infection, and environmental pollutant exposure, as well as emerging non-type 2 pathways including NLRP3 inflammasome activation and neutrophil extracellular trap formation, leading to context-dependent inflammatory patterns. This review summarizes the role of estrogen receptors and various cell types in mediating asthma heterogeneity, providing a mechanistic basis for sex-specific disease variation and highlighting the need for precision strategies that account for hormonal and life-stage differences.

The genus Neisseria, a gram-negative diplococcus, includes commensal and pathogenic species that infect mucosal tissues, causing diseases such as gonorrhea and meningitis. The type VI secretion system (T6SS), a multifunctional molecular machine that facilitates the ability of gram-negative bacteria to deliver effectors for bacterial competition, virulence, and interaction with host cells, has been widely studied across various bacterial taxa. However, research on the T6SS in the genus Neisseria remains limited. In this study, we employed comparative genomics and pangenomics, among other bioinformatics approaches, to characterize the distribution of the T6SS and its related proteins, including effectors, immunity proteins and regulators, across different species within the genus. Through an analysis of 5,067 Neisseria genomes, we identified two complete T6SS loci. We found that more than half of the Neisseria species possess at least one complete T6SS locus. Further investigation revealed multiple T6SS-related loci. We also applied a statistics-based method for identifying T6SS-associated orthologous groups and revealed 64 new T6SS-associated proteins within the genus. Our research provides a comprehensive analysis of the T6SS in Neisseria, advancing the understanding of T6SS-related mechanisms.

Acinetobacter baumannii, a gram-negative bacterium, is notorious for causing severe infections with high mortality rates. Rapid and accurate detection of A. baumannii is crucial for prompt treatment, effective infection control, and curbing antibiotic resistance. However, there is no suitable method for rapid and easy on-site detection of A. baumannii. The DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) system offers a rapid, precise, and sensitive approach to A. baumannii detection by integrating the target-specific recognition capabilities of Cas12a with the isothermal amplification efficiency of Recombinase Polymerase Amplification (RPA). This protocol details the detection of A. baumannii using RPA combined with LbaCas12a endonuclease. The following steps are described in this article: extraction of DNA, selection of a specific DNA sequence, design of primer and CRISPR RNA (crRNA), construction of positive recombinant plasmid, setup of Cas12a-RPA assay, optimization of the RPA amplification system, visualization of the RPA-CRISPR/Cas12a assay using a fluorescence detection tool such as a real-time PCR instrument, and evaluation of sensitivity and specificity evaluation.

IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Emerging evidence suggests that gut microbiota dysbiosis contributes to pulmonary disorders, underscoring the therapeutic potential of probiotics.MethodsThree Lactobacillus strains—Lactiplantibacillus sp. LP03 (LP03), Levilactobacillus brevis LB06, and Loigolactobacillus coryniformis LC0—were isolated from Chinese sauerkraut juice and evaluated in a bleomycin (BLM)-induced mouse model of pulmonary fibrosis. Gut microbiota composition was analyzed, and serum metabolomics profiling was performed to explore underlying mechanisms. Further, the therapeutic role of palmitoylethanolamide (PEA) was assessed both in vivo and in vitro.ResultsAmong the three strains, LP03 exhibited the most pronounced antifibrotic effects, including reduced mortality, systemic inflammation, lung coefficient, interstitial thickening, and collagen deposition, as well as inhibition of BLM-induced epithelial-to-mesenchymal transition (EMT). LP03 treatment restored gut microbial balance, notably increasing beneficial genera such as Ligilactobacillus and Akkermansia. Metabolomic analysis revealed enhanced lipid metabolism, especially in glycerophospholipid and fatty acid pathways, and elevated serum PEA levels. Oral PEA supplementation independently alleviated fibrosis, while mechanistic studies demonstrated that PEA mitigated fibrosis by inhibiting EMT through suppression of the TGF-β1/Smad2/3 signaling pathway.DiscussionThese findings highlight LP03 as a promising probiotic candidate for pulmonary fibrosis therapy. Its therapeutic effects are mediated by remodeling of the gut microbiota and elevation of systemic PEA, which in turn regulates fibrotic signaling pathways.

Synergistic photodynamic therapy (PDT) with other therapeutic modalities can enhance the therapeutic efficacy of tumor treatment and reduce the adverse effects associated with drug leakage and off-target accumulation.

Lung adenocarcinoma (LUAD) has a poor prognosis. Circadian genes such as TIMELESS have been associated with several pathologies, including cancer. The expression of TIMELESS and the relationship between TIMELESS, infiltration of tumors and prognosis in LUAD requires further investigation. In this study, we investigated the expression of TIMELESS and its association with survival across several types of human cancer using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Program. Noncoding RNAs (ncRNAs) regulating overexpression of TIMELESS in lung adenocarcinoma (LUAD) were explored with expression, correlation, and survival analyses. Immune cell infiltration and biomarkers were analyzed between different TIMELESS expression levels. The relationship between TIMELESS expression and immunophenoscores, which were used to predict response to immunotherapy, was evaluated. TIMELESS was identified as a potential oncogene in LUAD. NcRNA analysis showed MIR4435-2HG/hsa-miR-1-3p may interact with TIMELESS in a competitive endogenous RNA network in LUAD tumor tissues. Most immune cells were significantly decreased in TCGA LUAD tumor tissues with high TIMELESS expression except for CD4+T cells and Th2 cells. TIMELESS expression in LUAD tumor tissues was significantly negatively correlated with neutrophil biomarkers, dendritic cell biomarkers (HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DPA1, CD1C) and an immunophenoscore that predicted outcomes associated with the use of immune checkpoint inhibitors. These findings imply that ncRNAs-mediated TIMELESS overexpression in LUAD tumor tissues correlated with poor prognosis, reduced immune cell infiltration in the tumor microenvironment, and poor response to immune checkpoint inhibitors.

Understanding the pathogenesis of different phenotypes of asthma, including glucocorticoid-dependent and glucocorticoid-resistant asthma, is crucial for the development of effective treatments. Autophagy, a fundamental cellular process involved in cell homeostasis, has been implicated in asthma, although the exact mechanisms remain unclear. Recent studies have identified autophagy activation in eosinophilic, neutrophilic, and paucigranulocytic asthma, providing novel insights into the disease. This comprehensive review examines the role of autophagy in the pathogenesis and treatment of asthma, with a focus on various cell types. The goal is to uncover potential therapeutic targets and innovative treatment modalities to improve patient outcomes in clinical settings.

Asthma is a prevalent chronic respiratory disease, yet understanding its ecology and pathogenesis remains a challenge. Trim27, a ubiquitination ligase belonging to the TRIM (tripartite motif-containing) family, has been implicated in regulating multiple pathophysiological processes such as inflammation, oxidative stress, apoptosis, and cell proliferation. However, the role of Trim27 in asthma has not been investigated. Our study found that Trim27 expression significantly increases in the airway epithelium of asthmatic mice. Knockdown of Trim27 expression effectively relieved ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) and lung tissue histopathological changes. Moreover, Trim27 knockdown exhibited a significant reduction in airway inflammation and oxidative stress in asthmatic mice, and in vitro analysis confirmed the favorable effect of Trim27 deletion on inflammation and oxidative stress in mouse airway epithelial cells. Furthermore, our study revealed that deletion of Trim27 in MLE12 cells significantly decreased NLRP3 inflammasome activation, as evidenced by reduced expression of NLRP3, ASC, and pro-IL-1β mRNA. This downregulation was reversed when Trim27, but not its mutant lacking ubiquitination ligase activity, was replenished in these cells. Consistent with these findings, protein levels of NLRP3, pro-caspase-1, pro-IL-1β, cleaved-caspase-1, and cleaved-IL-1β were higher in Trim27-replenished cells compared to cells expressing Trim27C/A. Functionally, the downregulation of IL-1β and IL-18 levels induced by Trim27 deletion was rescued by replenishing Trim27. Overall, our findings provide evidence that Trim27 contributes to airway inflammation and oxidative stress in asthmatic mice via NLRP3 inflammasome activation, providing crucial insights into potential therapeutic interventions targeting Trim27 as a way to treat asthma.

Sepsis, a frequently fatal condition, emerges from an exaggerated inflammatory response to infection, resulting in multi-organ dysfunction and alarmingly high mortality rates. Despite the urgent need for effective treatments, current therapeutic options remain limited to antibiotics, with no other efficacious alternatives available. Echinatin (Ecn), a potent bioactive compound extracted from the roots and rhizomes of licorice, has gained significant attention for its broad pharmacological properties, particularly its ability to combat oxidative stress. Recent research highlights the crucial role that oxidative stress plays in the onset and progression of sepsis further emphasizing the potential therapeutic value of Ecn in this context. In this study, we explored the protective effects of Ecn in a murine model of sepsis induced by cecal ligation and puncture (CLP). Ecn demonstrated a significant reduction in the levels of inflammatory cytokines and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Network pharmacology analysis identified 41 targets and top 15 pathways involved in the Ecn-mediated signaling network, revealing that Ecn might exert its effects through key targets including the NF-κB and MAPK signaling pathways. Molecular docking studies suggested a strong affinity between Ecn and MEK, with kinetic simulations and binding energy calculations confirming a stable interaction. Mechanistically, Ecn treatment inhibited NF-κB and the MEK/ERK signaling pathway, as evidenced by decreased phosphorylation of IκBα and nuclear p65, along with reduced phosphorylation of MEK and ERK in both LPS-stimulated RAW 264.7 macrophages and septic mice. Furthermore, the administration of MEK signaling agonists reversed the anti-inflammatory effects of Ecn, indicating the involvement of this signaling pathway in Ecn's protective mechanism. Notably, our investigation revealed that Ecn did not affect bacterial proliferation either in vivo or in vitro, underscoring its specific immunomodulatory effects rather than direct antimicrobial activity. In summation, our findings underscored the potential of Ecn as an innovative therapeutic remedy for sepsis-induced injury, particularly through the regulation of the NF-κB and MEK/ERK signaling pathway. This exploration unveiled a promising therapeutic approach for treating sepsis, supplementing existing interventions and addressing their constraints.

Background: Pyroptosis is an inflammatory form of regulated necrosis that has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the role of lipid peroxidation in pyroptosis and its underlying mechanisms in COPD remain unclear. Methods: In vitro, human bronchial epithelial cells (Beas-2b cells) were exposed to cigarette smoke extract (CSE) for 24 h. In vivo, mice were exposed to cigarette smoke (CS) for 4 weeks. To investigate the role of xCT, we used siRNA and AAV6 to conditionally knock down xCT in vitro and in vivo, respectively. Results: The administration of ferrostatin-1 (Fer-1), a ferroptosis inhibitor that inhibits lipid peroxidation, significantly reduced the cytotoxicity of CSE to Beas-2b cells and mitigated inflammatory exudation, lung injury and mucus hypersecretion in mice with CS-induced COPD. Fer-1 suppressed gasdermin D (GSDMD)-mediated pyroptosis caused by CS in vitro and in vivo. However, in Beas-2b cells and the lung epithelial cells of mice, conditional knockdown of xCT (a negative regulatory factor of lipid peroxidation) inhibited the xCT/GPx4 axis, leading to more severe lipid peroxidation and GSDMD-mediated pyroptosis during cigarette smoke exposure. Moreover, we found that CS promoted the degradation of xCT through the ubiquitin proteasome system (UPS) and that treatment with MG132 significantly inhibited the degradation of xCT and downregulated the expression of pyroptosis-related proteins. Conclusion: The results of this study suggested that the ubiquitination-mediated degradation of xCT drives GSDMD-mediated pyroptosis in COPD and is a potential therapeutic target for COPD.

As a highly conserved, multifunctional protein with multiple domains, p62/SQSTM1 plays a crucial role in several essential cellular activities, particularly selective autophagy. Recent research has shown that p62 is crucial in eradicating intracellular bacteria by xenophagy, a selective autophagic process that identifies and eliminates such microorganisms. This review highlights the various roles of p62 in intracellular bacterial infections, including both direct and indirect, antibacterial and infection-promoting aspects, and xenophagy-dependent and independent functions, as documented in published literature. Additionally, the potential applications of synthetic drugs targeting the p62-mediated xenophagy mechanism and unresolved questions about p62's roles in bacterial infections are also discussed.

ABSTRACT As a member of the enteroviruses, coxsackievirus A6 (CV-A6) has been a major cause of hand, foot, and mouth disease (HFMD) since 2008. It can infect both pediatric and adult populations, often leading to atypical HFMD. The host innate immune system plays a vital role in the development of enteroviral infections. However, the interplay between the host antiviral response and CV-A6 has not been well investigated. In the present study, we demonstrated that the 2C protein from CV-A6 (2C CV-A6 ) suppresses interferon beta (IFN-β) production in HEK293T cells. Further results indicated that 2C CV-A6 interacts with both melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) and induces the degradation of these RNA sensors through proteases in the lysosomal pathway. This function also applies to 2C proteins from enterovirus A71 (2C EV-A71 ) and coxsackievirus B3 (2C CV-B3 ) but not CV-A16 2C (2C CV-A16 ) for its incompetence in MDA5 and RIG-I recognition. Partial depletion and amino acid substitution analyses indicated that the F28A, V75A, and I96V mutations significantly compromised 2C CV-A6 -induced MDA5/RIG-I depletion. Surprisingly, unlike V75A and I96V that interrupt the 2C CV-A6 -MDA5/RIG-I interaction, 2C CV-A6 F28A remained competent in MDA5/RIG-I binding, suggesting that the interaction alone is not sufficient for 2C-mediated reduction. Additional tests indicated that CV-A6 viruses containing the 2C F28A mutation were less efficient in IFN-β suppression, which is associated with compromised viral replication and release in infected rhabdomyosarcoma (RD) cells, suggesting that 2C-mediated immune regulation plays a vital role in enteroviral replication. Taken together, our data reveal a novel mechanism by which enteroviral 2C proteins antagonize the host innate antiviral immune response. IMPORTANCE Coxsackievirus A6 (CV-A6) is a major emerging pathogen associated with atypical hand, foot, and mouth disease and can cause serious complications such as encephalitis, acute flaccid paralysis, and neurorespiratory syndrome. Therefore, revealing the associated pathogenic mechanisms could benefit the control of CV-A6 infections. In this study, we demonstrate that the nonstructural 2C CV-A6 suppresses IFN-β production, which supports CV-A6 infection. This is achieved by depleting RNA sensors such as melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I (RIG-I) through the lysosomal pathway. Such a function is shared by 2C EV-A71 and 2C CV-B3 but not 2C CV-A16 , suggesting the latter might have an alternative way to promote viral replication. This study broadens our understanding of enterovirus 2C protein regulation of the RIG-I-like receptor signaling pathway and reveals a novel mechanism by which CV-A6 and other enteroviruses evade the host innate immune response. These findings on 2C may provide new therapeutic targets for the development of effective inhibitors against CV-A6 and other enterovirus infections.

Objectives: Lung cancer is a major public health concern and represents the most common cause of cancer-related death worldwide. Among eukaryotes, the G protein-coupled receptor (GPCR) family stands as the largest group of membrane proteins. Alterations in GPCR gene expression and dysregulation of signal transduction have been recognized as the markers of malignancy. As a member of the GPCR family, G protein-coupled receptor 37 (GPR37) exhibits unknown functions in tumors, particularly in non-small-cell lung cancer (NSCLC)Methods: We explored the expression and prognosis of GPR37 in NSCLC through TCGA, GTEx, GEO, and GEPIA2. We detected the expression of GPR37 in NSCLC tissues and cell lines. The study explored the influence of GPR37 on tumor cell proliferation. Furthermore, we examined the effects of GPR37 on tumor cell apoptosis and invasion. Most importantly, we investigated whether GPR37 affects cisplatin-induced drug resistance in NSCLC. Furthermore, by conducting animal experiments, we assessed the impact of GPR37 on NSCLC and delved into underlying mechanisms.Results: (1) In NSCLC, the expression of GPR37 is markedly higher than that in corresponding normal tissues. We found that elevated GPR37 expression predicts an unfavorable prognosis. (2) It was demonstrated that GPR37 positively regulates NSCLC cell invasion, migration, and proliferation, suppresses cell apoptosis, heightens resistance to cisplatin, and promotes tumor formation and growth. Conversely, we observed that GPR37 knockdown suppresses NSCLC cell invasion, migration, and proliferation, promotes cell apoptosis, increases sensitivity to cisplatin, and affects tumor formation and growth. (3) GPR37 activates PI3K/Akt/mTOR signal transduction pathways to mediate epithelial-mesenchymal transition (EMT), thereby promoting the progression of NSCLC.Conclusions: It was suggested that GPR37 acts a crucial role in promoting the occurrence and development of NSCLC. Knockdown of GPR37 significantly inhibits the occurrence and development of NSCLC. Therefore, our findings demonstrated that GPR37 may represent a viable therapeutic target for NSCLC.

[Purpose/Significance]To give full play to the leading role of intelligence personnel, provide theoretical guidance for the management optimization, analysis and refinement of electronic medical record data from the perspective of“data potential energy”,expand the application scenarios of information science, increase the means of hospital knowledge service, and improve the efficiency of knowledge service.[Method/Process]Based on the concept of“data potential energy”and related theories of information science, the potential energy accumulation and release model of electronic medical records was constructed, and the potential energy accumulation dimension and release process of electronic medical records data were analyzed.The potential energy model was verified by case study and machine learning algorithm.[Result/Conclusion]Taking the information science perspective as the starting point and the end result, this paper uses the concept of“data potential energy”to elaborate the mode of organization, integration, analysis and application of electronic medical record data, and uses real-world case data and electronic medical record data to verify the validity and rationality of the theory.

In recent years, the role of ferroptosis in pulmonary fibrosis has garnered increasing interest as a potential therapeutic target. Pulmonary fibrosis is a pathological process characterized by the accumulation of extracellular matrix in affected lung tissues, and currently, there are no effective therapies for preventing or reversing the fibrotic lesions. Ferroptosis is a form of programmed cell death that is regulated by a network of enzymes and signaling pathways. Dysregulation of ferroptosis has been implicated in several diseases, including pulmonary fibrosis. The accumulation of lipid peroxides in the course of ferroptosis causes damage to cell membranes and other cellular components, leading ultimately to cell death. Relevant targets for therapeutic intervention in ferroptosis include key enzymes, such as glutathione peroxidase 4, transcription factors like nuclear factor erythroid 2-related factor 2, and iron chelation. This review provides an overview of the emerging role of ferroptosis in pulmonary fibrosis and highlights potential therapeutic targets in this pathway. Further research is needed to develop safe and effective approaches targeting ferroptosis in treatment of pulmonary fibrosis.

Background and Objectives In the midst of the pandemic, new coronavirus mutants continue to emerge; the most relevant variant worldwide is omicron. Here, patients who recovered from the disease living in Jilin Province were analyzed to identify factors affecting the severity of omicron infection and to provide insights into its spread and early indication. Methods In this study, 311 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were divided into two groups. Data on the patients’ demographic characteristics and laboratory tests, including platelet count (PLT), neutrophil count (NE), C-reactive protein (CRP), serum creatinine (SCR), and neutrophil-to-lymphocyte ratio (NLR), were collected. The biomarkers for moderate and severe coronavirus disease 2019 (COVID-19) and factors affecting the incubation period and time to subsequent negative nucleic acid amplification test (NAAT) were also investigated. Results Age, gender, vaccination, hypertension, stroke, chronic obstructive pulmonary disease (COPD)/chronic bronchitis/asthma, and some laboratory tests were statistically different between the two groups. In the receiver operating characteristic (ROC) analysis, PLT and CRP had higher area under the ROC curve values. In the multivariate analysis, age, hypertension, COPD/chronic bronchitis/asthma, and CRP were correlated with moderate and severe COVID-19. Moreover, age was correlated with longer incubation. In the Kaplan-Meier curve analysis, gender (male), CRP, and NLR were associated with longer time to subsequent negative NAAT. Conclusions Older patients with hypertension and lung diseases were likely to have moderate or severe COVID-19, and younger patients might have a shorter incubation. A male patient with high CRP and NLR levels might take more time to turn back negative in the NAAT.

BACKGROUND:Blood vessels that contain endothelial cells (ECs) on the surface are in direct contact with host blood and are the first target of xenograft rejection. Currently, our understanding of human anti-pig vessel immune responses is primarily based on in vitro assays using pig ECs. Therefore, it is necessary to develop an animal model that permits in vivo study of human immunological rejection of pig vessels. METHODS:Pig artery tissues (PAT) were transplanted into human immune system (HIS) mice or immunodeficient NSG mice (as controls). Intragraft human immune cell infiltration and antibody deposition were quantified using histology and immunohistochemistry. Donor antigen-specific immune responses were quantified using a mixed lymphocyte reaction and a complement-dependent killing assay. RESULTS:Pig CD31+ ECs were detected and increased 2-fold from weeks 3 to 5 in PAT xenografts from immunodeficient NSG mice. However, compared with NSG mice, PAT xenografts in HIS mice had significantly lower numbers of porcine CD31+ ECs and showed a marked reduction from week 3 to week 5. PAT xenograft rejection in HIS mice is associated with intensive infiltration of human immune cells, deposition of human IgM and IgG antibodies, and the formation of a tertiary lymphoid structure. Robust donor pig antigen-specific human T cells and antibody responses were detected in PAT-transplanted HIS mice. CONCLUSION:We have developed a humanized mouse model to evaluate human anti-pig xenoimmune responses by PAT transplantation in vivo. This model is expected to facilitate the refinement of pig gene-editing strategies (the expression on EC surface) and the testing of local immunosuppressive strategies for clinical pig organ xenotransplantation.

Three-prime repair exonuclease 1 (TREX1) is a major 3 '-5 ' DNA exonuclease, which digests cytosolic DNA to avoid inappropriate activation of the innate immune system. Besides the most studied exonuclease activity, the recently discovered functions of TREX1, such as regulating the oligosaccharyltransferase complex and triggering proteasome-mediated degradation, are also indispensable to prevent innate immune activation. However, mounting evidence indicates a dual role of TREX1 in human diseases. In cancer and radiotherapy, the digestion of immunogenic DNA by TREX1 inhibits antitumor immunity. Moreover, TREX1 also processes specific chromosomal abnormalities upon nuclear membrane rupture, which induces DNA damage. In this review, we summarize previous studies assessing the function and mechanisms of TREX1 in autoimmune diseases, inflammatory diseases, and cancer and discuss the relationship between the function and its associated diseases. By analyzing the various roles of TREX1 under different conditions, we explored the remaining questions regarding the molecular mechanism of TREX1.

To determine the efficacy and safety of Endostar combined with gemcitabine and cisplatin in the treatment of NSCLC, and provide evidence-based reference for clinical drug use. Retrieved from Cochrane Library, PubMed, Embase, ClinicalTrials, CNKI, Wanfang and VIP database, randomized controlled trials (RCT) were collected. Pooled standard mean differences (SMD) and 95% confidence intervals (CI) were analyzed using R software with a random-effects model. Data from a total of 27 RCTs were included, involving 1646 patients were analyzed. Results of meta-analysis showed that response rate and clinical benefit rate of trial group were significantly higher than those of control group. There was no statistical significance in the incidence of leucopenia, thrombocytopenia and gastrointestinal reaction between 2 groups. The results showed that Endostar combined with gemcitabine and cisplatin may generally improve therapeutic efficacy of NSCLC patients, without increasing the incidence of adverse reactions.