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1.
Tissue Eng Part A ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832873

ABSTRACT

Xenotransplantation of adipose extracellular matrix (AAM) has come to prominence as an intriguing option for soft tissue reconstruction. However, the presence of immunogenic antigens within AAM can trigger unfavorable immune reactions, leading to inadequate in vivo regeneration outcomes. Therefore, the development of advanced technology capable of modulating immune responses is crucial for the therapeutic implementation of AAM xenografts. In this work, a innovative technique is created to bypass the immune system by covering the surface of both AAM and RGD peptide-modified AAM xenografts with autologous red blood cell (RBC) membrane. The RBC membrane coating remained persistent and exhibited no significant decline even after 21 days. Moreover, it effectively reduced the expression of antigen MHC1 on the AAM surface. Following xenogeneic transplantation, the RBC coated xenografts demonstrated increased expression of the adipogenic factor PPAR-γ and higher numbers of adipocytes. Additionally, they exhibited decreased expression of immunological factors including IL-6, IL-2, IFN-γ and TNF-α, and fewer inflammatory cells. These findings indicate that RBC membrane coating successfully suppressed immune responses and promoted increased adipogenesis in AAM xenografts. Therefore, AAM camouflage coating with RBC has a lot of potential as a biomaterial for soft tissue reconstruction in clinical settings.

2.
Cell Metab ; 36(6): 1287-1301.e7, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38838641

ABSTRACT

Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.


Subject(s)
Adipose Tissue, White , Skin , Wound Healing , Animals , Adipose Tissue, White/metabolism , Mice , Skin/metabolism , Skin/pathology , Mice, Inbred C57BL , Subcutaneous Fat/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Neuregulins/metabolism , Neuregulins/genetics , Male , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Adipose Tissue, Brown/metabolism , Adipocytes, Beige/metabolism , Macrophages/metabolism , Humans , Myofibroblasts/metabolism
3.
Int J Ophthalmol ; 17(3): 401-407, 2024.
Article in English | MEDLINE | ID: mdl-38721512

ABSTRACT

AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

4.
Zookeys ; 1200: 183-198, 2024.
Article in English | MEDLINE | ID: mdl-38756346

ABSTRACT

Six species of the ant-eating spider of the family Zodariidae are described from Xizang, China, including five new species: Asceuachayusp. nov. (♀), A.dawaisp. nov. (♂♀), Mallinellamigusp. nov. (♂), M.mеdogsp. nov. (♂♀), and M.yadongsp. nov. (♂♀). The female of Cydrelalinzhiensis (Hu, 2001) is described here for the first time. Descriptions and photographs of all the species are provided.

5.
Langmuir ; 40(19): 9975-9984, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38695640

ABSTRACT

Plasma membranes not only maintain the intracellular microenvironment through their phospholipid bilayer but also eliminate exogenous compounds outside the cell membranes. Most drugs especially with high polarity are prevented from entering into cells to exert their effects. Therefore, it is of great significance to design effective drug carriers with a penetrating ability toward plasma membranes. In this study, a dual-templated MIP (dt-MIPs) carrier with controllable microstructure and high drug loading capacity was prepared using highly expressed sphingomyelin on the plasma membrane and tenofovir (TFV), a first-line drug for HIV and chronic hepatitis B, as template molecules. The drug release experiments performed in vitro under simulated physiological conditions demonstrated that sustained and stable adsorption of TFV on dt-MIPs was more than 80% over 50 h. By a combination of flow cytometry and confocal microscopy, dt-MIPs were found to have efficient cell permeability. Furthermore, mass-spectrometry-based intracellular pharmacokinetic studies demonstrated that TFV was delivered completely into cells within 30 min with the delivery of dt-MIPs. The study presented above suggested that dt-MIPs are expected to be alternative nanoscale drug carriers for enhanced drug permeability and controlled release.


Subject(s)
Cell Membrane , Drug Carriers , Sphingomyelins , Sphingomyelins/chemistry , Drug Carriers/chemistry , Cell Membrane/metabolism , Cell Membrane/chemistry , Humans , Tenofovir/chemistry , Tenofovir/pharmacokinetics , Drug Liberation
6.
Environ Res ; 252(Pt 3): 119044, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38697599

ABSTRACT

Rising temperatures can increase the risk of mental disorders. As climate change intensifies, the future disease burden due to mental disorders may be underestimated. Using data on the number of daily emergency department visits for mental disorders at 30 hospitals in Beijing, China during 2016-2018, the relationship between daily mean temperature and such visits was assessed using a quasi-Poisson model integrated with a distributed lag nonlinear model. Emergency department visits for mental disorders attributed to temperature changes were projected using 26 general circulation models under four climate change scenarios. Stratification analyses were then conducted by disease subtype, sex, and age. The results indicate that the temperature-related health burden from mental disorders was projected to increase consistently throughout the 21st century, mainly driven by high temperatures. The future temperature-related health burden was higher for patients with mental disorders due to the use of psychoactive substances and schizophrenia as well as for women and those aged <65 years. These findings enhance our knowledge of how climate change could affect mental well-being and can be used to advance and refine targeted approaches to mitigating and adapting to climate change with a view on addressing mental disorders.


Subject(s)
Climate Change , Emergency Service, Hospital , Mental Disorders , Humans , Mental Disorders/epidemiology , Beijing/epidemiology , Emergency Service, Hospital/statistics & numerical data , Female , Middle Aged , Male , Adult , Aged , Young Adult , Adolescent , Temperature , China/epidemiology , Emergency Room Visits
7.
Aesthet Surg J ; 2024 May 26.
Article in English | MEDLINE | ID: mdl-38796831

ABSTRACT

BACKGROUND: Owing to the delicate structure of the adipose tissue, fat necrosis accounts for 43.7% of all complications after autologous fat grafting; however, its regulation remains unclear. OBJECTIVES: The purpose of this study was to examine the role of necroptosis in fat graft remodeling after grafting. METHODS: Clinical fat graft necrosis samples were collected, and the expression levels of the necroptosis marker phosphorylated(p)-MLKL were analyzed. Transcriptome analysis was performed on fat grafts before and one week after transplantation in C57BL/6 mouse fat grafting models. Additionally, the in vivo effects of RIPK1 inhibitor Nec-1s or RIPK3 inhibitor GSK'872 on the fat grafting complications including fat necrosis and fibrosis were investigated. RESULTS: Necroptosis markers were observed and associated with higher occurrence of fibrosis in clinical fat graft necrosis samples compared to normal fat tissue. Amplification and RNA-Seq were conducted on RNA isolated from fat grafts before and after grafting. MLKL, RIPK1 and RIPK3 expression levels were significantly upregulated in comparison to controls. Higher expression levels of necroptotic RNAs were associated with higher levels of DAMPs, including Cxcl2, HMGB1, S100a8, S100a9, Nlrp3 and IL33, and activated pro-inflammatory signaling pathways, including the TNF, NF-kappa B and chemokine signaling pathways. Necroptotic inhibitor Nec-1s and GSK'872 robustly suppressed the p-MLKL expression level and significantly inhibited necroptotic cell death, especially in adipocytes. Moreover, administration of Nec-1s and GSK'872 significantly alleviated fat necrosis and subsequent fibrosis in fat grafts. CONCLUSIONS: Collectively, our study findings highlight the potential therapeutic applications of necroptosis inhibitors in preventing fat necrosis and fibrosis after grafting.

8.
Acta Pharmacol Sin ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719954

ABSTRACT

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

9.
Int J Gen Med ; 17: 1665-1676, 2024.
Article in English | MEDLINE | ID: mdl-38706753

ABSTRACT

Purpose: This study aimed to investigate the clinical characteristics of acute epiglottitis (AE) patients in East China and examine the correlation between the incidence of AE and the 24 solar terms (24 STs). Methods: A retrospective, observational study was conducted on patients diagnosed with AE between January 2014 and December 2021 at a single-center medical institution in East China. The clinical characteristics of patients with AE and their correlation with the 24 STs were investigated. Results: A total of 287 patients with AE were included in this study, among which there were 179 males (62.37%) and 108 females (37.63%), with a mean age of 47.79 ± 13.83 years (range 16-87 years). Of these patients, 100 (34.84%) had at least one comorbidity and the most common comorbidities were hypertension, smoking and type 2 diabetes. The duration of hospitalization was 3 days (IQR, 1-16 days). All patients, except for one who required tracheal intubation, were cured with intravenous antibiotic administration and the combined use of corticosteroids. The incidence of AE showed significant fluctuations between the 24 STs and the highest number of cases occurred during the Summer solstice (24 cases, 8.36%). Conclusion: The incidence of AE was seen to increase annually in this study. The main features of AE are sore throat, dysphagia, odynophagia and fever, which may be accompanied by inflammation in surrounding areas. A clear correlation exists between the incidence of AE and the fluctuations within the 24 STs, notably with the peak incidence observed during the Summer solstice, which approximately corresponds to June 21 to July 7 in the Gregorian calendar.

10.
J Nanobiotechnology ; 22(1): 219, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38698419

ABSTRACT

BACKGROUND: Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration. METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system. RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration. CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.


Subject(s)
Adipose Tissue , Chemokine CXCL12 , Receptors, CXCR4 , Regeneration , Stem Cells , rhoA GTP-Binding Protein , Chemokine CXCL12/metabolism , Animals , Receptors, CXCR4/metabolism , Mice , Adipose Tissue/cytology , Adipose Tissue/metabolism , rhoA GTP-Binding Protein/metabolism , Stem Cells/metabolism , Stem Cells/cytology , Mice, Inbred C57BL , Feedback, Physiological , Cell Movement , Cells, Cultured , Male , Signal Transduction
11.
Front Endocrinol (Lausanne) ; 15: 1365156, 2024.
Article in English | MEDLINE | ID: mdl-38686209

ABSTRACT

Obesity is a chronic disease that affects the energy balance of the whole body. In addition to increasing fat mass, tissue fibrosis occurred in white adipose tissue in obese condition. Fibrosis is the over-activation of fibroblasts leading to excessive accumulation of extracellular matrix, which could be caused by various factors, including the status of adipocytes. The morphology of adipocytes responds rapidly and dynamically to nutrient fluctuations. Adaptive hypertrophy of normal adipocytes protects peripheral organs from damage from lipotoxicity. However, the biological behavior of hypertrophic adipocytes in chronic obesity is abnormally altered. Adipocytes lead to fibrotic remodeling of the extracellular matrix by inducing unresolved chronic inflammation, persistent hypoxia, and increasing myofibroblast numbers. Moreover, adipocyte-induced fibrosis not only restricts the flexible expansion and contraction of adipose tissue but also initiates the development of various diseases through cellular autonomic and paracrine effects. Regarding anti-fibrotic therapy, dysregulated intracellular signaling and epigenetic changes represent potential candidate targets. Thus, modulation of adipocytes may provide potential therapeutic avenues for reversing pathological fibrosis in adipose tissue and achieving the anti-obesity purpose.


Subject(s)
Adipocytes , Fibrosis , Obesity , Humans , Obesity/pathology , Obesity/metabolism , Adipocytes/pathology , Adipocytes/metabolism , Animals , Adipose Tissue/pathology , Adipose Tissue/metabolism
12.
Chem Commun (Camb) ; 60(40): 5322-5325, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38666540

ABSTRACT

A small molecule-based NIR-II type-I photosensitizer (IT-IC) with a strong push-pull effect and good planar π-conjugated structure was synthesized. The IT-IC NPs exhibited strong light absorption, outstanding NIR-II fluorescence emission, excellent photothermal conversion and efficient type-I/II ROS generation, showing encouraging therapeutic outcomes for hypoxic tumors.


Subject(s)
Infrared Rays , Photosensitizing Agents , Theranostic Nanomedicine , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Humans , Animals , Mice , Cell Line, Tumor , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Reactive Oxygen Species/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Molecular Structure , Photochemotherapy , Tumor Hypoxia/drug effects , Cell Survival/drug effects , Nanoparticles/chemistry
13.
Psych J ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632076

ABSTRACT

Based on the functional assessment concept and embodied assessment requirements, the present study aimed to design and develop an assessment tool for children with intellectual disabilities with the help of somatosensory interactive (SI) technology. The sample in this study consisted of 73 children with intellectual disabilities and 70 children with typical development. Data were collected through three SI tasks, four traditional executive function tasks, and user experience interviews to analyse the effectiveness of the SI assessment tool. The results showed that the SI assessment tool had good scale validity, discriminant validity, and the ability to identify intellectual disabilities. Children preferred SI tasks and showed higher involvement and more positive emotions. The SI tool with three SI tasks is a more scientific, effective, and advanced tool for assessing children with intellectual disabilities.

14.
Clin Lab ; 70(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38623668

ABSTRACT

BACKGROUND: Platelet (PLT) count is one of the most important parameters of automated hematology, as spurious PLT reports could affect medical judgement and bring significant risks. In most cases, spurious PLT will not be reported for review criteria, which will be triggered by abnormal PLT histograms and PLT flag(s). Here, we present a case of severe aplastic anemia after hematopoietic stem cell transplantation with spurious high platelet count with normal histogram and no PLT flag(s). METHODS: The electrical impedance channel (PLT-I) and the fluorescence channel (PLT-F) of Sysmex XN-series hematology analyzer was used to obtain PLT results. Then, the sample was retested by another hematology analyzer MINDRAY BC-7500 [NR] CRP, and incubation was performed to rule out cryoglobulin interference. Furthermore, a microscope was used to estimate the PLT count by the ratio of platelets to red blood cells and observe the morphology of cells. RESULTS: Both PLT-I and PLT-F test results were spuriously high, and microscopically assessed platelet counts were relatively reliable. The observed spiny cells and ghost cells caused by hemolysis may have contributed to the inaccuracy of instrumental counting in this case. CONCLUSIONS: For special hematologic patients, PLT-I with flags may not be sufficient for screening purposes and PLT-F is not always accurate. Multiple testing methods including manual microscopy are needed.


Subject(s)
Agmatine/analogs & derivatives , Anemia, Aplastic , Oxamic Acid/analogs & derivatives , Humans , Platelet Count/methods , Anemia, Aplastic/diagnosis , Reproducibility of Results , Blood Platelets
15.
Article in English | MEDLINE | ID: mdl-38662567

ABSTRACT

Human gaze provides valuable information on human focus and intentions, making it a crucial area of research. Recently, deep learning has revolutionized appearance-based gaze estimation. However, due to the unique features of gaze estimation research, such as the unfair comparison between 2D gaze positions and 3D gaze vectors and the different pre-processing and post-processing methods, there is a lack of a definitive guideline for developing deep learning-based gaze estimation algorithms. In this paper, we present a systematic review of the appearance-based gaze estimation methods using deep learning. Firstly, we survey the existing gaze estimation algorithms along the typical gaze estimation pipeline: deep feature extraction, deep learning model design, personal calibration and platforms. Secondly, to fairly compare the performance of different approaches, we summarize the data pre-processing and post-processing methods, including face/eye detection, data rectification, 2D/3D gaze conversion and gaze origin conversion. Finally, we set up a comprehensive benchmark for deep learning-based gaze estimation. We characterize all the public datasets and provide the source code of typical gaze estimation algorithms. This paper serves not only as a reference to develop deep learning-based gaze estimation methods, but also a guideline for future gaze estimation research. The project web page can be found at https://phi-ai.buaa.edu.cn/Gazehub/.

16.
PLoS One ; 19(4): e0299285, 2024.
Article in English | MEDLINE | ID: mdl-38662713

ABSTRACT

OBJECTIVE: To investigate the association between the visceral adiposity index and the prevalence of diabetes and prediabetes in the US adult population. METHOD: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 for ten consecutive years, including 18745 eligible participants. The weighted multivariate logistic model and fitting curve were used to explore the correlation and dose-response relationship between visceral adiposity index (VAI) and diabetes (DM) and prediabetes in the general population and the prevalence of different subgroups. RESULTS: In the fully adjusted continuous model, the risk of diabetes and prediabetes in the general population increased 0.15 times [1.15 (1.10,1.20), p<0.0001] with every increase of 1 unit of VAI. In the fully adjusted classification model, with the lowest quartile array Q1 of VAI as the reference group, Q2 of the second Quantile group, Q3 of the third Quantile group, and Q4 of the Quartile group increased 0.26 times [1.26 (1.10,1.44), p<0.001], 0.65 times [1.65 (1.43,1.89), p<0.0001], 1.60 times [2.60 (2.28,2.97), p<0.0001] respectively with the risk of diabetes and prediabetes. The above results showed that VAI was positively associated with the prevalence of diabetes and prediabetes, and the fitted curves showed a non-linear trend. (P for non-linear = 0<0.05). The results of the subgroup population were consistent with the total population and a significant interaction was found in gender (P for interaction<0.0001). CONCLUSION: In conclusion, we found a non-linear positive association between VAI and the risk of diabetes and prediabetes in the US adult population and found that women have a higher risk of diabetes and prediabetes than men; therefore, we should focus on the female population, and we call for the use of VAI to manage the development of diabetes and prediabetes in the clinical setting.


Subject(s)
Intra-Abdominal Fat , Nutrition Surveys , Prediabetic State , Humans , Prediabetic State/epidemiology , Male , Female , Middle Aged , Adult , Cross-Sectional Studies , Risk Factors , Prevalence , Diabetes Mellitus/epidemiology , United States/epidemiology , Adiposity , Aged , Obesity, Abdominal/epidemiology , Obesity, Abdominal/complications
17.
Front Oncol ; 14: 1367008, 2024.
Article in English | MEDLINE | ID: mdl-38638851

ABSTRACT

Background: In contemporary study, the death of esophageal squamous cell carcinoma (ESCC) patients need precise and expedient prognostic methodologies. Objective: To develop and validate a prognostic model tailored to ESCC patients, leveraging the power of machine learning (ML) techniques and drawing insights from comprehensive datasets of laboratory-derived blood parameters. Methods: Three ML approaches, including Gradient Boosting Machine (GBM), Random Survival Forest (RSF), and the classical Cox method, were employed to develop models on a dataset of 2521 ESCC patients with 27 features. The models were evaluated by concordance index (C-index) and time receiver operating characteristics (Time ROC) curves. We used the optimal model to evaluate the correlation between features and prognosis and divide patients into low- and high-risk groups by risk stratification. Its performance was analyzed by Kaplan-Meier curve and the comparison with AJCC8 stage. We further evaluate the comprehensive effectiveness of the model in ESCC subgroup by risk score and KDE (kernel density estimation) plotting. Results: RSF's C-index (0.746) and AUC (three-year AUC 0.761, five-year AUC 0.771) had slight advantage over GBM and the classical Cox method. Subsequently, 14 features such as N stage, T stage, surgical margin, tumor length, age, Dissected LN number, MCH, Na, FIB, DBIL, CL, treatment, vascular invasion, and tumor grade were selected to build the model. Based on these, we found significant difference for survival rate between low-(3-year OS 81.8%, 5-year OS 69.8%) and high-risk (3-year OS 25.1%, 5-year OS 11.5%) patients in training set, which was also verified in test set (all P < 0.0001). Compared with the AJCC8th stage system, it showed a greater discriminative ability which is also in good agreement with its staging ability. Conclusion: We developed an ESCC prognostic model with good performance by clinical features and laboratory blood parameters.

19.
FASEB J ; 38(5): e23520, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38430369

ABSTRACT

Fat grafting is a promising technique for correcting soft tissue abnormalities, but oil cyst formation and graft fibrosis frequently impede the therapeutic benefit of fat grafting. The lipolysis of released oil droplets after grafting may make the inflammation and fibrosis in the grafts worse; therefore, by regulating adipose triglyceride lipase (ATGL) via Atglistatin (ATG) and Forskolin (FSK), we investigated the impact of lipolysis on fat grafts in this study. After being removed from the mice and chopped into small pieces, the subcutaneous fat from wild-type C57BL/6J mice was placed in three different solutions for two hours: serum-free cell culture medium, culture medium+FSK (50 µM), and culture medium+ATG (100 µM). Following centrifugation to remove water and free oil droplets, 0.3 mL of the fat particles per mouse was subcutaneously injected into the back of mice. Additionally, the subcutaneous fat grafting area was immediately injected with PBS (control group), ATG (30 mg/kg), and FSK (15 mg/kg) following fat transplantation. Detailed cellular events after grafting were investigated by histological staining, real-time polymerase chain reaction, immunohistochemistry/immunofluorescent staining, and quantification. Two weeks after grafting, grafts treated with ATG showed lower expression of ATGL and decreased mRNA levels of TNFα and IL-6. In contrast, grafts treated with ATG showed elevated expression levels of IL-4 and IL-13 compared to the control grafts. In addition, fewer apoptotic cells and oil cysts were observed in ATG grafts. Meanwhile, a higher CD206+/CD68+ ratio of macrophages and more CD31+ vascular endothelial cells existed in the 2-month ATG grafts. In comparison to the control, ATG treatment improved the volume retention of grafts, and decreased graft fibrosis and oil cyst formation. By preventing oil droplet lipolysis, pharmacological suppression of ATGL shielded adipocytes from lipotoxicity following grafting. Additionally, ATG ameliorated the apoptosis and inflammation brought on by adipocyte death and oil droplet lipolysis in grafted fat. These all indicate that lipolysis inhibition improved transplanted fat survival and decreased the development of oil cysts and graft fibrosis, offering a potential postoperative pharmacological intervention for bettering fat grafting.


Subject(s)
Adipose Tissue , Cysts , Animals , Mice , Lipolysis , Endothelial Cells , Mice, Inbred C57BL , Fibrosis , Inflammation
20.
Front Cell Infect Microbiol ; 14: 1354880, 2024.
Article in English | MEDLINE | ID: mdl-38465236

ABSTRACT

Plasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of Plasmodium parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria.


Subject(s)
Malaria, Vivax , Malaria , Parasites , Plasmodium , Animals , Humans , Plasmodium vivax/genetics , Parasites/metabolism , Merozoites , Thrombospondins/metabolism , Plasmodium/metabolism , Malaria/parasitology , Malaria, Vivax/parasitology , Protozoan Proteins/metabolism , Mammals/metabolism
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