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1.
Ecol Evol ; 14(5): e11357, 2024 May.
Article in English | MEDLINE | ID: mdl-38694747

ABSTRACT

Ground-dwelling invertebrates are vital for soil biodiversity and function maintenance. Contemporary biodiversity assessment necessitates novel and automatic monitoring methods because of the threat of sharp reductions in soil biodiversity in farmlands worldwide. Using infrared camera traps (ICTs) is an effective method for assessing richness and abundance of ground-dwelling invertebrates. However, the influence that the shooting area of ICTs has on the diversity of ground-dwelling invertebrates has not been strongly considered during survey design. In this study, data from six ICTs with two shooting areas (A1, 38.48 cm2; A2, 400 cm2) were used to investigate ground-dwelling invertebrates in a farm in a city on the Eastern Coast of China from 20: 00 on July 31 to 00:00 on September 29, 2022. Over the course of 59 days and 1420 h, invertebrates within 9 taxa, 2447 individuals, and 112,909 ind./m2 were observed from 222,912 images. Our results show that ICTs with relatively large shooting areas recorded relatively high taxonomic richness and abundance of total ground-dwelling invertebrates, relatively high abundance of the dominant taxon, and relatively high daily and hourly abundance of most taxa. The shooting areas of ICTs significantly affected the recorded taxonomic richness and abundance of ground-dwelling invertebrates throughout the experimental period and at fine temporal resolutions. Overall, these results suggest that the shooting areas of ICTs should be considered when designing experiments, and ICTs with relatively large shooting areas are more favorable for monitoring the diversity of ground-dwelling invertebrates. This study further provides an automatic tool and high-quality data for biodiversity monitoring and protection in farmlands.

2.
Heliyon ; 10(8): e29291, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38644851

ABSTRACT

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and ß-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.

3.
Clin Anat ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38651194

ABSTRACT

As the cornerstone of medicine, the development of anatomy is related to many disciplines and fields and has received extensive attention from researchers. How to integrate and grasp the cutting-edge information in this field quickly is a challenge for researchers, so the aim of this study is to analyze research in anatomy using CiteSpace and VOSviewer in order to identify research hotspots and future directions. To offer a fresh viewpoint for assessing the academic influences of researchers, nations, or institutions on anatomy, and to examine the development of hotspots in anatomical study and to forecast future trends. A total of 4637 anatomy-related publications from 2013 to 2023 were collected from Web of Science Core Collection databases. Their temporal distribution, spatial distribution, cited authors, co-cited journals, keywords, and disciplinary connections in the literature were analyzed using CiteSpace and VOSviewer, and a knowledge graph was constructed. The temporal distribution shows a general fluctuation in the amount of literature published from 2013 to 2023. In spatial distribution, the total number of published articles was highest in the United States, the United Kingdom, and China, the United States leading. Tubbs, Rhoton, Iwanaga, and LaPrade are important authors in anatomy. Clinical Anatomy, Surgical and Radiologic Anatomy, and Journal of Anatomy were the most highly cited journals. Analysis of keywords and citation emergence showed that the research hotspots and trends in anatomy focused mainly on anatomy education, digital technology, and surgical management. At the same time, anatomy showed a trend toward multidisciplinary crossover, developing closer relationships with molecular biology, immunology, and clinical medicine. Current research in anatomy focuses on innovative reform of the educational model and the application and promotion of digital technology. Also, multidisciplinary cross-fertilization is an inevitable trend for the future development of anatomy.

4.
Environ Technol ; : 1-11, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623611

ABSTRACT

Tobacco (Nicotiana tabacum L.) shows promise for remediating Cd-contaminated soil due to its significant Cd accumulation capabilities. Although various tobacco varieties exhibit distinct Cd bioaccumulation capacities, a comprehensive understanding of the underlying mechanisms is lacking. This study, conducted using hydroponics, explores differences in Cd accumulation and tolerance mechanisms between two tobacco varieties, Basma and Yunyan 87. The results showed that Cd stress reduced the dry weight, tolerance index, and root morphology for both varieties. Basma exhibited a relatively smaller decline in these indices compared to Yunyan 87. Moreover, Basma demonstrated a higher Cd bioconcentration factor (BCF), concentration, and accumulated content, signifying its superior tolerance and bioaccumulation capacity to Cd compared to Yunyan 87. The Carbonyl Cyanide3-ChloroPhenylhydrazone (CCCP) addition resulted in reduced Cd accumulation and BCFs in both tobacco species. This effect was more pronounced in Basma, suggesting that Basma relies more on an active transport process than Yunyan 87. This could potentially explain its enhanced bioaccumulation ability. Subcellular Cd distribution analysis revealed Basma's preference for distributing Cd in soluble fractions, while Yunyan 87 favoured the cell wall fractions. Transmission electron microscope showed that Basma's organelles were less damaged than Yunyan 87's under Cd stress, possibly contributing to the superior tolerance of Basma. Therefore, these results provided a theoretical foundation for development of Cd-contaminated soil tobacco remediation technology.

5.
bioRxiv ; 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38559075

ABSTRACT

Hypertranscription is widespread in aggressive human cancers. However detection relies on mRNAs, which are heavily processed and have variable half-lives, and on accurate cell number estimations. Previously we introduced FFPE-CUTAC, a genome-wide method for mapping RNA Polymerase II in formalin-fixed paraffin-embedded (FFPE) sections. Here we apply FFPE-CUTAC on slides and curls to demonstrate hypertranscription at regulatory elements and replication-coupled histone genes. We find that hypertranscription differs between transgene-driven mouse gliomas and scales with enhanced proliferation and reduced mitochondrial DNA. We also apply FFPE-CUTAC to identify tumor-specific patterns in assorted human tumor-normal pairs. We analyze the top-ranked 100 annotated regulatory elements that are hypertranscribed in most of the tumors and identify multiple loci around ERBB2 on Chromosome 17q12-21 in the breast and colon cancer samples, mapping likely HER2 amplifications punctuated by selective sweeps. Our results demonstrate that FFPE-CUTAC measurement of hypertranscription provides an affordable and sensitive genome-wide strategy for cancer diagnosis.

6.
Front Immunol ; 15: 1337129, 2024.
Article in English | MEDLINE | ID: mdl-38650924

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) rank among the most prevalent types of head and neck cancer globally. Unfortunately, a significant number of patients receive their diagnoses at advanced stages, limiting the effectiveness of available treatments. The tumor microenvironment (TME) is a pivotal player in HNSCC development, with macrophages holding a central role. Macrophages demonstrate diverse functions within the TME, both inhibiting and facilitating cancer progression. M1 macrophages are characterized by their phagocytic and immune activities, while M2 macrophages tend to promote inflammation and immunosuppression. Striking a balance between these different polarization states is essential for maintaining overall health, yet in the context of tumors, M2 macrophages typically prevail. Recent efforts have been directed at controlling the polarization states of macrophages, paving the way for novel approaches to cancer treatment. Various drugs and immunotherapies, including innovative treatments based on macrophages like engineering macrophages and CAR-M cell therapy, have been developed. This article provides an overview of the roles played by macrophages in HNSCC, explores potential therapeutic targets and strategies, and presents fresh perspectives on the future of HNSCC treatment.


Subject(s)
Head and Neck Neoplasms , Macrophages , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/diagnosis , Tumor Microenvironment/immunology , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/immunology , Macrophages/immunology , Animals , Immunotherapy/methods , Cell Plasticity/immunology
7.
Nat Commun ; 15(1): 1861, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38424087

ABSTRACT

O-Sulfation is a vital post-translational modification in bioactive molecules, yet there are significant challenges with their synthesis. Dialkyl sulfates, such as dimethyl sulfate and diisopropyl sulfate are commonly used as alkylation agents in alkaline conditions, and result in the formation of sulfate byproducts. We report herein a general and robust approach to O-sulfation by harnessing the tunable reactivity of dimethyl sulfate or diisopropyl sulfate under tetrabutylammonium bisulfate activation. The versatility of this O-sulfation protocol is interrogated with a diverse range of alcohols, phenols and N-OH compounds, including carbohydrates, amino acids and natural products. The enhanced electrophilicity of the sulfur atom in dialkyl sulfates, facilitated by the interaction with bisulfate anion (HSO4-), accounts for this pioneering chemical reactivity. We envision that our method will be useful for application in the comprehension of biological functions and discovery of drugs.

8.
J Org Chem ; 89(4): 2759-2763, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38308650

ABSTRACT

On the basis of steric hindrance, one carbonyl group in a diketone can be reduced in a regioselective manner, with high enantioselectivity. The methodology can be extended to ketones with varied length of hydrocarbon chain spacing, and the products can be converted by oxidation to hydroxy esters or lactones without loss of enantiopurity.

9.
Insects ; 15(1)2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38249034

ABSTRACT

We evaluated the hourly dynamics of ground-dwelling invertebrate communities in farmland using infrared camera traps between August and September 2022. No significant variations within 24 h nor between any two time points of each day were observed in the taxonomic richness and abundance of the entire community. However, the periods from 4:00 to 7:00 and 13:00 to 20:00 showed relatively high taxonomic richness, while those from 2:00 to 6:00 and 16:00 to 21:00 showed relatively high abundance. Millipede abundance varied significantly in a 24 h period, with higher abundance from 3:00 to 4:00 and 1:00 to 2:00. Additionally, slug, beetle, and grasshopper abundances were significantly higher from 22:00 to 23:00, 17:00 to 18:00, and 23:00 to 24:00, respectively. The abundance of other taxa did not show significant variations between any two time points of a day. Predominant generalist predators showed positive correlation in their activity times. These results suggest that significant variations within each 24 h period are uncommon at either community or taxa (except for millipedes) levels in farmland ground-dwelling invertebrates. Further, while most taxa had significantly preferred active hours, the total community did not. Therefore, hourly dynamics should be considered to understand biodiversity maintenance.

10.
Pestic Biochem Physiol ; 198: 105713, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38225071

ABSTRACT

The application of different types of pesticides can result in the coexistence of multiple pesticide residues in our food and the environment. This can have detrimental effects on the health of offspring across generations when parents are exposed to these pesticides. Therefore, it is imperative to understand the long-term effects that can be inherited by future generations when assessing the risks associated with pesticides. To study the genotoxic effects of commonly used pesticides, prochloraz (PRO) and chlorpyrifos (CHL), and assess whether their combined exposures have a different toxic effect, we modeled the transgenerational effects of parental (F0-generation) and/or offspring (F1-generation) exposures on zebrafish embryos in the F1-generation. Following the exposures, we proceeded to assess the impacts of these exposures on a range of biological processes in F1-generation zebrafish. Our results revealed that exposure to PRO and CHL altered multiple biological processes, such as inflammation, apoptosis, oxidative stress, and thyroid hormone synthesis, and detoxification system, providing molecular targets for subsequent studies on toxicity mechanisms. Notably, our study also found that the biological processes of F1-generation zebrafish embryos were altered even though they were not exposed to any pesticide when F0-generation zebrafish were exposed to PRO or CHL, suggesting potential genotoxicity. In conclusion, we provided in-vivo evidence that parental exposure to PRO and/or CHL can induce genotoxicity in the offspring. Moreover, we observed that the toxic effects resulting from the combined exposure were interactive, suggesting a potential synergistic impact on the offspring.


Subject(s)
Chlorpyrifos , Endocrine Disruptors , Imidazoles , Pesticides , Water Pollutants, Chemical , Animals , Chlorpyrifos/toxicity , Zebrafish , Endocrine Disruptors/toxicity , Water Pollutants, Chemical/toxicity , Pesticides/toxicity
12.
J Clin Densitom ; 27(1): 101463, 2024.
Article in English | MEDLINE | ID: mdl-38157729

ABSTRACT

Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.


Subject(s)
Bone Diseases , Fractures, Bone , Fractures, Spontaneous , Liver Transplantation , Humans , Fractures, Spontaneous/diagnostic imaging , Fractures, Spontaneous/etiology , Bone Density , Liver Transplantation/adverse effects , Retrospective Studies , Fractures, Bone/etiology , Bone Diseases/complications , Biomarkers
13.
J Stomatol Oral Maxillofac Surg ; 125(4): 101728, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38070674

ABSTRACT

BACKGROUND AND OBJECTIVES: The resorption of flap's volume can be frequently observed in the transplantation of microvascular free flaps, which could significantly affect postoperative function. Therefore, it's essential to comprehend the postoperative flap volume and the mechanisms behind before making clinical decisions. METHODS: Literature search was conducted from database on PubMed, EMBASE, Cochrane Library, Chinese database and Google Scholar. A random effects model meta-analyses and descriptive systematic review were performed. RESULTS: The search identified 420 articles, of which 9 studies included in meta-analysis and 14 studies included in descriptive systematic review. Postoperative flap volume maintenance rate is used to represent the volume change. The pooled mean postoperative flap volume maintenance rate was 62.82 % for soft tissue flap (95 %CI: 58.83 to 66.82, p = 0.076, I2=56.3 %) and 85.96 % for bone flap (95 %CI: 84.19 to 87.73, p = 0.274, I2=20.4 %). Weight loss, muscle atrophy, and decreased serum albumin levels are risk factors for postoperative volume reduction of soft tissue flaps. The bone resorption rate of bone flaps in women is higher than that in men. CONCLUSION: When designing microvascular free flaps for oral and maxillofacial surgery, soft tissue flaps should consider an anticipated postoperative shrinkage of 37 %, while bone flaps should consider an anticipated postoperative shrinkage of 14 %.

14.
Oral Maxillofac Surg ; 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38038839

ABSTRACT

OBJECTIVES: The use of miR-21 expression remains vague in diagnosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to systematically evaluate the diagnostic potential of the miR-21 expression in patients with HNSCCs through investigating and summarizing the results reported in the literature. METHODS: Extant medical databases were examined for articles of clinical study assessing the miR-21 expression in HNSCC cases, published in the past 20 years. Bioinformatics research was also performed for finding miR-21 targets differentially expressed in HNSCC so as to present their biological behaviors. RESULTS: Our meta-analysis comprised 11 studies including 622/450 cases in HNSCC/control group. Forest plots displayed miR-21 which possessed significantly good specificity (0.76, p < 0.001) and sensitivity (0.80, p < 0.001). Diagnostic odds ratio was 2.46 (95% CI 1.87-3.24). Positive and negative likelihood ratio was 3.40 (95% CI 1.94-5.97) and 0.26 (95% CI 0.18-0.38), respectively. Area under the receiver operating characteristic curve was 0.85. CONCLUSION: This study is the highest level of evidence presently available in diagnosing HNSCC. This PRISMA meta-analysis indicated that the pooled results were robust, confirming the oncogenic potential of miR-21 that could be used successfully as a screening biomarker in HNSCC patients. Specifically, the overexpression of miR-21 in these patients presents a worse survival outcome.

15.
Nature ; 624(7991): 255-256, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38030764
16.
Ear Nose Throat J ; : 1455613231210388, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37994533

ABSTRACT

Objective: The treatment of oral squamous cell carcinoma (OSCC) is dominated by surgery and radiochemotherapy, but its prognosis is still unsatisfactory, with around five tenths of 5-year survival. This study aimed to assess the prognosis of OSCC patients treated with surgery with and without postoperative radiotherapy. Study Design: Retrospective study. Methods: The clinicopathological information and follow-up datasets on patients with OSCC (T1-4 and/or N+) registered from 2010 to 2015 were downloaded from the Surveillance, Epidemiology, and End Results database. Totally 7231 enrolled subjects were divided into a case group (surgery alone, n = 4167) and a control group (surgery combined with postoperative radiotherapy, n = 3064). One-to-one matching was performed by propensity score matching to make the baseline data comparable between the 2 subgroups. Multivariate Cox regression analysis was used to calculate hazard ratios (HR) of various clinicopathological features. The Kaplan-Meier method and log-rank test were used to plot the survival curves. Results: The majority of patients in case group were tumor stage I (n = 2569, 61.7%), whereas most patients in control group were stages III to IV (n = 2360, 77.1%). In the case group, the 1-, 3-, and 5-year overall survival (OS; 76%, 59.5%, 53.7%) were significantly lower than those of the control group (85.1%, 64.1%, 55.8%; P < .0001). Similarly, the 1-, 3-, and 5-year cancer-specific survival (CSS) of the case group (80.2%, 66.6%, 63.3%) were significantly lower than those of the control group (87.2%, 69.3%, 63.9%, respectively; P < .0001). Cox multivariate analysis indicated that age, differentiation, clinical stage, and tumor-node-metastasis stage affected the prognosis of OSCC patients, while postoperative radiotherapy was a protective factor (OS: HR = 0.649, P < .001; CSS: HR = 0.702, P < .001). Conclusions: Postoperative radiation was an independent protective factor, hence, the combination of surgery plus radiotherapy is more beneficial for the survival of patients with OSCC, particularly for advanced cases.

17.
Nat Commun ; 14(1): 6943, 2023 11 06.
Article in English | MEDLINE | ID: mdl-37932264

ABSTRACT

Chromatin conformation reorganization is emerging as an important layer of regulation for gene expression and lineage specification. Yet, how lineage-specific transcription factors contribute to the establishment of cell type-specific 3D chromatin architecture in the immune cells remains unclear, especially for the late stages of T cell subset differentiation and maturation. Regulatory T cells (Treg) are mainly generated in the thymus as a subpopulation of T cells specializing in suppressing excessive immune responses. Here, by comprehensively mapping 3D chromatin organization during Treg cell differentiation, we show that Treg-specific chromatin structures were progressively established during its lineage specification, and highly associated with Treg signature gene expression. Additionally, the binding sites of Foxp3, a Treg lineage specifying transcription factor, were highly enriched at Treg-specific chromatin loop anchors. Further comparison of the chromatin interactions between wide-type Tregs versus Treg cells from Foxp3 knock-in/knockout or newly-generated Foxp3 domain-swap mutant mouse revealed that Foxp3 was essential for the establishment of Treg-specific 3D chromatin architecture, although it was not dependent on the formation of the Foxp3 domain-swapped dimer. These results highlighted an underappreciated role of Foxp3 in modulating Treg-specific 3D chromatin structure formation.


Subject(s)
Chromatin , T-Lymphocytes, Regulatory , Mice , Animals , Chromatin/metabolism , Forkhead Transcription Factors/metabolism , Gene Expression Regulation , Cell Differentiation/genetics
18.
Front Immunol ; 14: 1259562, 2023.
Article in English | MEDLINE | ID: mdl-37781367

ABSTRACT

Gliomas account for the majority of brain malignant tumors. As the most malignant subtype of glioma, glioblastoma (GBM) is barely effectively treated by traditional therapies (surgery combined with radiochemotherapy), resulting in poor prognosis. Meanwhile, due to its "cold tumor" phenotype, GBM fails to respond to multiple immunotherapies. As its capacity to prime T cell response, dendritic cells (DCs) are essential to anti-tumor immunity. In recent years, as a therapeutic method, dendritic cell vaccine (DCV) has been immensely developed. However, there have long been obstacles that limit the use of DCV yet to be tackled. As is shown in the following review, the role of DCs in anti-tumor immunity and the inhibitory effects of tumor microenvironment (TME) on DCs are described, the previous clinical trials of DCV in the treatment of GBM are summarized, and the challenges and possible development directions of DCV are analyzed.


Subject(s)
Brain Neoplasms , Cancer Vaccines , Glioblastoma , Glioma , Humans , Dendritic Cells , Cancer Vaccines/therapeutic use , Tumor Microenvironment
19.
Head Neck ; 45(10): 2515-2524, 2023 10.
Article in English | MEDLINE | ID: mdl-37548087

ABSTRACT

IMPORTANCE: Venous thromboembolism (VTE) is closely relevant to head and neck cancer (HNC) prognosis, but little data exist on the risk prediction of VTE in patients with HNC. OBJECTIVE: To study the risk factors regarding VTE in HNC patients and construct a nomogram model for its prediction. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional retrospective study was implemented to comparatively analyze 220 HNC patients from January 2018 to December 2021. The Lasso algorithm was used to optimize the selection of variables. A nomogram model for predicting HNC-associated VTE was established using multivariate logistic regression analysis. Internal validation of the model was performed by bootstrap resampling (1000 times). Calibration plot and decision curve analysis (DCA) were applied to evaluate the calibration capability of the prediction model. MAIN OUTCOME AND MEASURE: The demographics, medical history, blood biochemical indicators, and modalities of treatment were included for analysis. RESULTS: The incidence of HNC-associated VTE was 2.8% (55/1967) in authors' affiliation. Five variables of risk factors, including surgery, radiochemotherapy, D-dimer, aspartate transaminase, and globulin, were screened and selected as predictors by Lasso algorithm. A prediction model that incorporated these independent predictors was developed and presented as the nomogram. The model showed good discrimination with a C-index of 0.972 (95% CI: 0.934-0.997), and had an area under the receiver operating characteristic curve value of 0.981 (p < 0.001, 95% CI: 0.964-0.998). The calibration curve displayed good agreement of the predicted probability with the actual observed probability for HNC-associated VTE. The DCA plot showed that the application of this nomogram was associated with net benefit gains in clinical practice. CONCLUSIONS AND RELEVANCE: The high-performance nomogram model developed in this study may help early diagnose the risk of VTE in HNC patients and to guide individualized decision-making on thromboprophylaxis.


Subject(s)
Head and Neck Neoplasms , Venous Thromboembolism , Humans , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Retrospective Studies , Anticoagulants/therapeutic use , Cross-Sectional Studies , Risk Assessment , Nomograms , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/therapy
20.
Immunity ; 56(9): 2086-2104.e8, 2023 09 12.
Article in English | MEDLINE | ID: mdl-37572655

ABSTRACT

The limited efficacy of immunotherapies against glioblastoma underscores the urgency of better understanding immunity in the central nervous system. We found that treatment with αCTLA-4, but not αPD-1, prolonged survival in a mouse model of mesenchymal-like glioblastoma. This effect was lost upon the depletion of CD4+ T cells but not CD8+ T cells. αCTLA-4 treatment increased frequencies of intratumoral IFNγ-producing CD4+ T cells, and IFNγ blockade negated the therapeutic impact of αCTLA-4. The anti-tumor activity of CD4+ T cells did not require tumor-intrinsic MHC-II expression but rather required conventional dendritic cells as well as MHC-II expression on microglia. CD4+ T cells interacted directly with microglia, promoting IFNγ-dependent microglia activation and phagocytosis via the AXL/MER tyrosine kinase receptors, which were necessary for tumor suppression. Thus, αCTLA-4 blockade in mesenchymal-like glioblastoma promotes a CD4+ T cell-microglia circuit wherein IFNγ triggers microglia activation and phagocytosis and microglia in turn act as antigen-presenting cells fueling the CD4+ T cell response.


Subject(s)
Glioblastoma , Mice , Animals , Glioblastoma/drug therapy , Glioblastoma/metabolism , CTLA-4 Antigen , Th1 Cells , Microglia , CD8-Positive T-Lymphocytes , Phagocytosis , Dendritic Cells , CD4-Positive T-Lymphocytes
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