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2.
Mol Cancer ; 23(1): 117, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824567

Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.


Immunotherapy, Adoptive , Neoplasms , Receptors, Chimeric Antigen , Tumor Microenvironment , Humans , Neoplasms/therapy , Neoplasms/immunology , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Immunotherapy, Adoptive/methods , Tumor Microenvironment/immunology , Animals , Immunotherapy/methods
3.
J Am Chem Soc ; 2024 May 30.
Article En | MEDLINE | ID: mdl-38814730

Combining metal-organic frameworks (MOFs) with liquid crystals to construct liquid crystalline MOFs (LCMOF) offers the advantage of endowing and enhancing their functionality, yet it remains a challenging task. Herein, we report chiral liquid crystalline MOF (CLCMOF) thin films by cross-linking the chiral liquid crystals (CLC) with MOF thin films to realize highly circular polarization luminescence (CPL) performance with photo and thermal switching. By layer by layer cross-linking stilbene-containing CLC with stilbene-based MOF (CLC/MOF) thin film, the CLCMOF thin films were successfully obtained after UV irradiation due to the abundant [2 + 2] photocycloaddition. The resulted CLCMOF thin films have strong chirality, obvious photochromic fluorescent, and strong CPL performance (the asymmetry factor reaches to 0.4). Furthermore, due to the photochromic fluorescent MOF and thermotropic CLC, the CPL can be reversed and red-shifted after heating and UV irradiation treatment, showing photo- and thermal CPL switching. Such MOF-based CPL thin films with photo/thermal CPL switching were prepared to patterns and codes for the demonstration of potential application in advanced information anticounterfeit and encryption. This study not only opens a strategy for developing chiral thin films combining MOFs and liquid crystals but also offers a new route to achieve CPL switching in optical applications.

4.
Article En | MEDLINE | ID: mdl-38814824

AIMS: Asprosin, a newly discovered hormone, is linked to insulin resistance. This study shows the roles of asprosin in vascular smooth muscle cells (VSMCs) proliferation, migration, oxidative stress and neointima formation of vascular injury. METHODS: Mouse aortic VSMCs were cultured, and platelet-derived growth factor-BB (PDGF-BB) was used to induce oxidative stress, proliferation and migration in VSMCs. Vascular injury was induced by repeatedly moving a guidewire in the lumen of carotid artery in mice. RESULTS: Asprosin overexpression promoted VSMC oxidative stress, proliferation and migration, which were attenuated by toll-like receptor 4 (TLR4) knockdown, antioxidant NAC, NOX1 inhibitor ML171 or NOX2 inhibitor GSK2795039. Asprosin overexpression increased NOX1/2 expressions, while asprosin knockdown increased heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) expressions. Asprosin inhibited Nrf2 nuclear translocation. Nrf2 activator sulforaphane increased HO-1 and NQO-1 expressions, and prevented asprosin-induced NOX1/2 upregulation, oxidative stress, proliferation and migration. Exogenous asprosin protein had similar roles to asprosin overexpression. PDGF-BB increased asprosin expressions. PDGF-BB-induced oxidative stress, proliferation and migration were enhanced by Nrf2 inhibitor ML385, but attenuated by asprosin knockdown. Vascular injury increased asprosin expression. Local asprosin knockdown in the injured carotid artery promoted HO-1 and NQO-1 expressions, but attenuated the NOX1 and NOX2 upregulation, oxidative stress, neointima formation and vascular remodeling in mice. INNOVATION AND CONCLUSION: Asprosin promotes oxidative stress, proliferation and migration of VSMCs via TLR4-Nrf2-mediated redox imbalance. Inhibition of asprosin expression attenuates VSMC proliferation and migration, oxidative stress and neointima formation in the injured artery. Asprosin might be a promising therapeutic target for vascular injury.

5.
Diabetes Metab Syndr Obes ; 17: 2107-2120, 2024.
Article En | MEDLINE | ID: mdl-38799279

Introduction: Cardiac fibrosis is one of the important causes of heart failure and death in diabetic cardiomyopathy (DCM) patients. Circular RNAs (circRNAs) are covalently closed RNA molecules in eukaryotes and have high stability. Their role in myocardial fibrosis with diabetic cardiomyopathy (DCM) remain to be fully elucidated. This study aimed to understand the expression profiles of circRNAs in myocardial fibrosis with DCM, exploring the possible biomarkers and therapeutic targets for DCM. Methods: At 21 weeks of age, db/db mice established the type 2 DCM model measured by echocardiography, and the cardiac tissue was extracted for Hematoxylin-eosin, Masson's trichrome staining, and transmission electron microscopy. Subsequently, the expression profile of circRNAs in myocardial fibrosis of db/db mice was constructed using microarray hybridization and verified by real-time quantitative polymerase chain reaction. A circRNA-microRNA-messenger RNA coexpression network was constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were done. Results: Compared with normal control mice, db/db mice had 77 upregulated circRNAs and 135 downregulated circRNAs in their chromosomes (fold change ≥1.5, P ≤ 0.05). Moreover, the enrichment analysis of circRNA host genes showed that these differentially expressed circRNAs were mainly involved in mitogen-activated protein kinase signaling pathways. CircPHF20L1, circCLASP1, and circSLC8A1 were the key circRNAs. Moreover, circCLASP1/miR-182-5p/Wnt7a, circSLC8A1/miR-29b-1-5p/Col12a1, and most especially circPHF20L1/miR-29a-3p/Col6a2 might be three novel axes in the development of myocardial fibrosis in DCM. Conclusion: The findings will provide some novel circRNAs and molecular pathways for the prevention or clinical treatment of DCM through intervention with specific circRNAs.

6.
Sci Rep ; 14(1): 12149, 2024 05 27.
Article En | MEDLINE | ID: mdl-38802416

Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo-keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.


Aldo-Keto Reductase Family 1 member B10 , Carcinoma, Hepatocellular , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Liver Neoplasms/mortality , Liver Neoplasms/metabolism , Male , Female , Prognosis , Aldo-Keto Reductase Family 1 member B10/genetics , Aldo-Keto Reductase Family 1 member B10/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Middle Aged , Kaplan-Meier Estimate , Aldo-Keto Reductases/genetics , Aldo-Keto Reductases/metabolism , Gene Expression Profiling , Computational Biology/methods
7.
Clin Breast Cancer ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38821744

BACKGROUND: Chlamydia trachomatis (C. trachomatis) infection has been implicated in various cancers, yet its association with breast cancer remains unexplored. This infection triggers a cascade of immune responses primarily regulated by Interleukins-12 (IL-12). Thus, the objective of this case-control study was to investigate the link between C. trachomatis infection and breast cancer risk, as well as the modification effect of IL-12. METHODS: We assessed IgG levels against C. trachomatis in serum of 1,121 women with breast cancer (861 with estrogen receptor-positive (ER+) and 260 with estrogen receptor-negative (ER-) tumors) and 400 controls in Guangzhou, China. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer risk in association with C. trachomatis infection. The interaction between C. trachomatis infection and IL-12 on breast cancer risk was estimated by the product terms in the logistic regression models. RESULTS: Seropositivity of C. trachomatis IgG showed a slight association with an increased risk of breast cancer (OR = 1.20; 95% CI: 0.86∼1.78). This association was more pronounced among women with a higher (OR = 5.82; 95% CI: 1.31∼25.94) than a lower (OR = 0.73; 95% CI: 0.41∼1.30) level of IL-12, with a statistically significant interaction observed (Pinteraction = 0.013). In addition, C. trachomatis IgG seropositivity was related to an increased risk of breast cancer among PR+ patients (OR = 1.53; 95% CI: 1.04∼2.23). CONCLUSIONS: C. trachomatis infection may contribute to the development of hormone-responsive breast cancer in women with high levels of IL-12. Further studies are needed to uncover the underlying mechanisms.

8.
Comput Biol Med ; 177: 108601, 2024 May 14.
Article En | MEDLINE | ID: mdl-38776728

Automated karyotyping is of great importance for cytogenetic research, as it speeds up the process for cytogeneticists through incorporating AI-driven automated segmentation and classification techniques. Existing frameworks confront two primary issues: Firstly the necessity for instance-level data annotation with either detection bounding boxes or semantic masks for training, and secondly, its poor robustness particularly when confronted with domain shifts. In this work, we first propose an accurate segmentation framework, namely KaryoXpert. This framework leverages the strengths of both morphology algorithms and deep learning models, allowing for efficient training that breaks the limit for the acquirement of manually labeled ground-truth mask annotations. Additionally, we present an accurate classification model based on metric learning, designed to overcome the challenges posed by inter-class similarity and batch effects. Our framework exhibits state-of-the-art performance with exceptional robustness in both chromosome segmentation and classification. The proposed KaryoXpert framework showcases its capacity for instance-level chromosome segmentation even in the absence of annotated data, offering novel insights into the research for automated chromosome segmentation. The proposed method has been successfully deployed to support clinical karyotype diagnosis.

9.
Surgery ; 2024 May 21.
Article En | MEDLINE | ID: mdl-38777658

BACKGROUND: To explore the diameter of lymph nodes with metastatic thyroid carcinoma and the effectiveness and safety of thermal ablation. METHODS: Several databases were searched for literature on the treatment of thyroid carcinoma metastatic lymph nodes by thermal ablation. A subgroup analysis was performed according to the diameter of the metastatic lymph nodes. The measures included pooled estimates of mean volume reduction, pooled proportions of total disappearance and recurrence, and the pooled proportions of overall complications. RESULTS: There were 20 studies with 372 patients and 620 metastatic lymph nodes included. Based on the average maximum diameter of the metastatic lymph nodes, they were divided into three groups: A (≤ 10 mm), B (10 < diameter ≤ 20 mm), and C (> 20 mm). The study results indicated a significant decrease in the average volume only in groups A and B. The ratio of tumor disappearance showed that group A had the highest percentage, followed by group B and then group C. The recurrence rates were comparable between groups A and B, but slightly lower than in group C. Moreover, the overall complication rates for the three groups were ranked as follows: group A > group C > group B. CONCLUSION: Overall, thermal ablation is an effective and safe treatment for thyroid cancer metastatic lymph nodes with diameters of 10-20mm.

11.
Zhongguo Gu Shang ; 37(5): 487-91, 2024 May 25.
Article Zh | MEDLINE | ID: mdl-38778533

OBJECTIVE: To investigate the effect of remote ischemic preconditioning (RIPC) on major adverse cardiovascular events (MACE) in elderly patients with hip fracture 1 year after operation. METHODS: Total of 314 elderly patients with hip fracture of gradeⅡand Ⅲ for American Society of Anesthesiologists (ASA) were treated by surgical operation from April 2015 to May 2020 including 116 males and 198 females, the age ranged from 60 to 76 years old. The subjects were divided into intervention group and control group according to whether received RIPC. Among them, 157 cases in intervention group included 56 males and 101 females with an average age of (68.12±7.13) years old and 157 cases in control group included 60 males and 97 females with an average age of (68.24±7.05) years old. Both groups were given routine anesthesia. The intervention group was treated with RIPC on the basis of routine anesthesia. The MACE events 1 year after operation in two groups were compared and analyzed. RESULTS: The OR values of RIPC for myocardial infarction, heart failure, stroke, nonfatal cardiac arrest, coronary revascularization, severe arrhythmia, peripheral artery thrombosis, readmission of cardiovascular disease, and all-cause death in patients with hip fracture one year after operation were 1.269, 1.304, 0.977, 1.089, 1.315, 1.335, 0.896, 0.774, 1.191, respectively, but there was no significant difference (P>0.05). CONCLUSION: RIPC did not significantly affect and change the occurrence of major cardiovascular adverse events within 1 year after hip fracture surgery. The long term impact of RIPC on clinical cardiovascular outcomes in non cardiac surgery needs to be confirmed in appropriate randomized clinical trials.


Hip Fractures , Ischemic Preconditioning , Humans , Male , Female , Hip Fractures/surgery , Aged , Ischemic Preconditioning/methods , Middle Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/surgery , Postoperative Complications/etiology , Postoperative Complications/prevention & control
12.
Front Immunol ; 15: 1357378, 2024.
Article En | MEDLINE | ID: mdl-38720885

Exosomes carry proteins, metabolites, nucleic acids and lipids from their parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes.


Diabetes Mellitus , Exosomes , Immunomodulation , Exosomes/immunology , Exosomes/metabolism , Humans , Diabetes Mellitus/immunology , Diabetes Mellitus/therapy , Animals , Macrophages/immunology , Macrophages/metabolism
13.
Schizophr Res ; 269: 36-47, 2024 May 08.
Article En | MEDLINE | ID: mdl-38723519

Schizophrenia patients with tardive dyskinesia (TD) are associated with accelerated biological aging, immunological dysfunction, and premature morbidity and mortality. Older individuals are particularly vulnerable to TD development. As a characteristic of immunosenescence, alterations in the relative proportions of naïve or memory T cell subpopulations may be negatively or positively associated with brain structure abnormalities; however, whether these changes are correlated with TD remains unclear. In this study, we investigated correlations between distributions of T cell phenotypes and brain structure abnormalities (especially white matter) in schizophrenia patients with (TD) and without (NTD) TD (n = 50 and 58, respectively) relative to healthy controls (HC, n = 41). Immune markers, including naïve (CD45RA+), memory (CD45RO+), and apoptotic (CD95+) CD4+ and CD8+ T cells, were examined by flow cytometry, as were the intracellular levels of cytokines (interferon (IFN)-γ, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α) in CD8 + CD45RA + CD95+ and CD8 + CD45RO + CD95+ T cells. MRI was employed to evaluate the fractional anisotropy (FA) of white matter tracts and subcortical volumes, following published routines. The percentage of CD8 + CD45RO + CD95+ T cells was higher in TD compared with NTD and HC groups and correlated with the choroid plexus volume in TD group. The intracellular level of IFN-γ in CD8 + CD45RO + CD95+ T cells, the FA of the fornix/stria terminalis, and the pallidum volume were correlated with orofacial TD, whereas the FAs of the inferior fronto-occipital fasciculus, cingulum, and superior longitudinal fasciculus were correlated with limb-truncal TD. These findings provide preliminary evidence that the association between immunosenescence-related T cell subpopulations and brain structure may underline the pathological process of TD.

14.
Biomater Sci ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38726643

The current treatment for venous thrombosis during pregnancy is ineffective, primarily, due to the unique physiology of pregnant women. Most clinical medications have fetal side effects when they circulate in the body. We first synthesized nanomaterials (Cur-PFP@PC) using poly lactic-co-glycolic acid (PLGA) as the base material, with curcumin (Cur) and perfluoropentane (PFP) as core components. Subsequently, we encapsulated Cur-PFP@PC into the platelet membrane to synthesize P-Cur-PFP@PC. Under ultrasound guidance, in combination with low-intensity focused ultrasound (LIFU), PFP underwent a phase change, resulting in thrombolysis. The generated microbubbles enhanced the signal impact of ultrasound, and P-Cur-PFP@PC showed better performance than Cur-PFP@PC. P-Cur-PFP@PC can target thrombosis treatment, achieve visually and precisely controlled drug release, and repair damaged blood vessels, thus avoiding the adverse effects associated with traditional long-term drug administration.

15.
iScience ; 27(5): 109748, 2024 May 17.
Article En | MEDLINE | ID: mdl-38706838

We previously reported that loss of function of TYW1 led to cerebral palsy with severe intellectual disability through reduced neural proliferation. However, whether TYW1 loss affects neural differentiation is unknown. In this study, we first demonstrated that TYW1 loss blocked the formation of OHyW in tRNAphe and therefore affected the translation efficiency of UUU codon. Using the brain organoid model, we showed impaired neuron differentiation when TYW1 was depleted. Interestingly, retrotransposons were differentially regulated in TYW1-/- hESCs (human embryonic stem cells). In particular, one kind of human-specific endogenous retrovirus-K (HERVK/HML2), whose reactivation impaired human neurodevelopment, was significantly up-regulated in TYW1-/- hESCs. Consistently, a UUU codon-enriched protein, SMARCAD1, which was a key factor in controlling endogenous retroviruses, was reduced. Taken together, TYW1 loss leads to up-regulation of HERVK in hESCs by down-regulated SMARCAD1, thus impairing neuron differentiation.

16.
Heliyon ; 10(9): e30337, 2024 May 15.
Article En | MEDLINE | ID: mdl-38707349

The biological function and prognostic value of efferocytosis in cancer remains unclear. In this study, we systematically analysed the expression profiles and genetic variations of 50 efferocytosis-related regulator genes in 33 cancer types. Using data from The Cancer Genome Atlas, we established an efferocytosis potential index (EPI) model to represent the efferocytosis level in each cancer type. The relationship between the EPI and prognosis, immune-related molecules, specific pathways, and drug sensitivity was determined. We found that efferocytosis regulator genes were abnormally expressed in cancer tissue, perhaps owing to copy number variations, gene alterations, and DNA methylation. For the most part, the EPI was higher in tumour vs. normal tissues. In most of the 33 cancer types, it positively correlated with cell death- and immune-related pathway enrichment, the tumour microenvironment, immune infiltration, and drug sensitivity. For specific cancers, a high EPI may be a prognostic risk factor and, in patients treated receiving immune checkpoint therapy, a predictor of poor prognosis. Our study reveals the biological functions of efferocytosis-related regulator genes in distinct cancers and highlights the potential of efferocytosis intervention in cancer therapy.

17.
Microbiol Spectr ; : e0379623, 2024 May 07.
Article En | MEDLINE | ID: mdl-38712963

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

18.
Materials (Basel) ; 17(9)2024 Apr 29.
Article En | MEDLINE | ID: mdl-38730910

The development of efficient catalysts with longevity to remove chlorobenzene is challenging due to Cl poisoning. Herein, a series of Mn-Cr/ZrOx catalysts supported by Zr-based metal-organic framework (UiO-66)-derived ZrOx was prepared and investigated for chlorobenzene (CB) catalytic oxidation. MnCr/ZrOx-M prepared via a wet impregnation method presented an amorphous structure, indicating the homogeneous dispersion of Cr and Mn, which improved acid and redox properties. 40Mn7Cr3/ZrOx-M exhibited the best catalytic activity for chlorobenzene oxidation with T90 of 293 °C, which is mainly due to the strong interaction between manganese and chromium promoted by the large specific surface area of the ZrOx support. Furthermore, 40Mn7Cr3/ZrOx-M presented excellent stability for chlorobenzene oxidation.

19.
iScience ; 27(5): 109793, 2024 May 17.
Article En | MEDLINE | ID: mdl-38736547

Vesicular fusion plays a pivotal role in cellular processes, involving stages like vesicle trafficking, fusion pore formation, content release, and membrane integration or separation. This dynamic process is regulated by a complex interplay of protein assemblies, osmotic forces, and membrane tension, which together maintain a mechanical equilibrium within the cell. Changes in cellular mechanics or external pressures prompt adjustments in this equilibrium, highlighting the system's adaptability. This review delves into the synergy between intracellular proteins, structural components, and external forces in facilitating vesicular fusion and release. It also explores how cells respond to mechanical stress, maintaining equilibrium and offering insights into vesicle fusion mechanisms and the development of neurological disorders.

20.
Transl Cancer Res ; 13(4): 2064-2072, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38737686

Background: Tracheobronchopathia osteochondroplastica (TPO) is a rare, benign, chronic disorder of unknown etiology. It is characterized by submucosal nodules, often calcified, which predominantly affect the anterolateral aspects of the trachea and main bronchi, while sparing the posterior bronchial wall. The co-occurrence of TPO and lung cancer is exceedingly rare. This report presents a case of TPO association with early-stage lung cancer, which was managed through surgical intervention. No active treatment was undertaken for the TPO. Case Description: A patient presented with a nodule in the right upper lobe, which was identified during a computed tomography (CT) scan of the chest, suggestive of early-stage lung cancer. Concurrently, multiple calcifications in the cartilaginous rings of the trachea were noted. Bronchoscopy revealed distinctive "pebblestone" nodules along the anterior and lateral tracheal walls, indicative of extensive TPO. The patient underwent bronchofiberscopy, which showed patency in the bronchial lumen of the right lung's upper lobe. A biopsy was not undertaken during this procedure. Comprehensive preoperative tests, including a blood biochemical examination, tumor-marker tests, lung-function tests, head-enhanced magnetic resonance imaging, abdominal ultrasound, and whole-body bone emission CT revealed no significant abnormalities. Despite this, the patient declined a whole-body positron emission tomography (PET)-CT scan. Given the potential malignancy of nodules in the right lung's upper lobe, the lobectomy for lung cancer was carried out, a procedure that would have proceeded irrespective of the presence or absence of TPO. Preoperative planning for potential tracheal intubation difficulties involved consultation with the anesthesiologist, resulting in a smooth intraoperative process. The pathology confirmed invasive adenocarcinoma. Post-surgery, the patient developed an infection in the right lung's lower lobe, identified as pseudomonas aeruginosa and Klebsiella pneumoniae through sputum culture and bronchoscopic lavage. Treatment with meropenem for 2 weeks, as guided by drug sensitivity results and respiratory advice, led to an improvement, allowing for discharge. A follow-up lung CT four months post-operation showed inflammation absorption in the right lower lobe. Conclusions: Surgical resection in cases of TPO association with lung cancer may have an increased risk of postoperative pulmonary infection. Proactive intraoperative sputum aspiration by anesthesiologists and the postoperative reinforcement of anti-infection measures, guided by drug sensitivity results, are recommended.

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