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1.
Cell Biol Toxicol ; 40(1): 87, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39384651

ABSTRACT

BACKGROUND: The high prevalence and detrimental effects on patient outcomes make gastric cancer (GC) a significant health issue that persists internationally. Existing treatment modalities exhibit limited efficacy, prompting the exploration of immune checkpoint inhibitors as a novel therapeutic approach. However, resistance to immunotherapy poses a significant challenge in GC management, necessitating a profound grasp of the intrinsic molecular pathways. METHODS: This study focuses on investigating the immunosuppressive mechanisms of quiescent cancer cells (QCCs) in GC, particularly their resistance to T-cell-mediated immune responses. Utilizing mouse models, gene editing techniques, and transcriptome sequencing, we aim to elucidate the interactions between QCCs, immune cells, and key regulatory factors like HIF1A. Functional enrichment analysis will further underscore the role of glycolysis-related genes in mediating immunosuppression by QCCs. RESULTS: The cancer cells that survived GC treated with T-cell therapy lost their proliferative ability. QCCs, as the main resistance force to immunotherapy, exhibit stronger resistance to CD8+ T-cell attack and possess higher cancer-initiating potential. Single-cell sequencing analysis revealed that the microenvironment in the QCCs region harbors more M2-type tumor-associated macrophages and fewer T cells. This microenvironment in the QCCs region leads to the downregulation of T-cell immune activation and alters macrophage metabolic function. Transcriptome sequencing of QCCs identified upregulated genes related to chemo-resistance, hypoxia, and glycolysis. In vitro cell experiments illustrated that HIF1A promotes the transcription of glycolysis-related genes, and silencing HIF1A in QCCs enhances T-cell proliferation and activation in co-culture systems, induces apoptosis in QCCs, and increases QCCs' sensitivity to immune checkpoint inhibitors. In vivo, animal experiments showed that silencing HIF1A in QCCs can inhibit GC growth and metastasis. CONCLUSION: Unraveling the molecular mechanisms by which QCCs resist T-cell-mediated immune responses through immunosuppression holds promising implications for refining treatment strategies and enhancing patient outcomes in GC. By delineating these intricate interactions, this study contributes crucial insights into precision medicine and improved therapeutic outcomes in GC management.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit , Stomach Neoplasms , Tumor Microenvironment , Stomach Neoplasms/immunology , Stomach Neoplasms/genetics , Animals , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice , Humans , Tumor Microenvironment/immunology , Cell Line, Tumor , Immunotherapy/methods , Glycolysis/drug effects , Drug Resistance, Neoplasm/genetics , Tumor Escape/drug effects , Immune Evasion , Mice, Inbred C57BL
2.
Commun Eng ; 3(1): 122, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39223332

ABSTRACT

Optical coherence tomography (OCT) can be used to image microstructures of human kidneys. However, current OCT probes exhibit inadequate field-of-view, leading to potentially biased kidney assessment. Here we present a robotic OCT system where the probe is integrated to a robot manipulator, enabling wider area (covers an area of 106.39 mm by 37.70 mm) spatially-resolved imaging. Our system comprehensively scans the kidney surface at the optimal altitude with preoperative path planning and OCT image-based feedback control scheme. It further parameterizes and visualizes microstructures of large area. We verified the system positioning accuracy on a phantom as 0.0762 ± 0.0727 mm and showed the clinical feasibility by scanning ex vivo kidneys. The parameterization reveals vasculatures beneath the kidney surface. Quantification on the proximal convoluted tubule of a human kidney yields clinical-relevant information. The system promises to assess kidney viability for transplantation after collecting a vast amount of whole-organ parameterization and patient outcomes data.

3.
Eur J Pharmacol ; 983: 177012, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39304111

ABSTRACT

Membrane fusion is the main pathway for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to invade host cells. Harringtonine (HT), derived from cephalotaxus fortunei Hook. f., has been recognized as an effective antagonist of SARS-CoV-2. It can directly block the active binding of spike (S) protein to host angiotensin converting enzyme 2 (ACE2), as well as hinder the enzymolysis of transmembrane serine proteases 2 (TMPRSS2). This study examined the potential of HT metabolites, 5'-de-O-methylharringtonine and cephalotaxine, as the membrane fusion inhibitors for SARS-CoV-2. 5'-De-O-methylharringtonine was synthesized and subsequently characterized by high resolution mass spectrometry and nuclear magnetic resonance to be structurally consistent, with a purity of 92.677% determined by reverse phase high performance liquid chromatography. Both 5'-de-O-methylharringtonine and cephalotaxine can specifically bind to SARS-CoV-2 S protein and TMPRSS2 using cell membrane chromatography. They can form hydrogen bonds with key sites that correlated highly with the enhanced binding affinity of SARS-CoV-2 and its variants to ACE2 or nafamostat to TMPRSS2. Moreover, 5'-de-O-methylharringtonine and cephalotaxine can inhibit pseudotyped virus entry and membrane fusion in a dose-dependent manner, with enhanced effectiveness upon elevated expression of TMPRSS2. Importantly, they displayed low cytotoxic effects on human normal cell lines. Our study suggested that 5'-de-O-methylharringtonine and cephalotaxine were of low toxicity and safety for humans as potential antagonists of SARS-CoV-2 and its variants, which deserve further validation in a biosafety level 3 facility.


Subject(s)
Harringtonines , SARS-CoV-2 , Serine Endopeptidases , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Serine Endopeptidases/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Harringtonines/pharmacology , Membrane Fusion/drug effects , Virus Internalization/drug effects , Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Chlorocebus aethiops , Animals , Angiotensin-Converting Enzyme 2/metabolism , Vero Cells
4.
Nat Commun ; 15(1): 7977, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39266565

ABSTRACT

Despite the importance of cellular senescence in human health, how damaged cells undergo senescence remains elusive. We have previously shown that promyelocytic leukemia nuclear body (PML-NBs) translocation of the ciliary FBF1 is essential for senescence induction in stressed cells. Here we discover that an early cellular event occurring in stressed cells is the transient assembly of stress-induced nucleus-to-cilium microtubule arrays (sinc-MTs). The sinc-MTs are distinguished by unusual polyglutamylation and unique polarity, with minus-ends nucleating near the nuclear envelope and plus-ends near the ciliary base. KIFC3, a minus-end-directed kinesin, is recruited to plus-ends of sinc-MTs and interacts with the centrosomal protein CENEXIN1. In damaged cells, CENEXIN1 co-translocates with FBF1 to PML-NBs. Deficiency of KIFC3 abolishes PML-NB translocation of FBF1 and CENEXIN1, as well as senescence initiation in damaged cells. Our study reveals that KIFC3-mediated nuclear transport of FBF1 along polyglutamylated sinc-MTs is a prerequisite for senescence induction in mammalian cells.


Subject(s)
Cell Nucleus , Cellular Senescence , Cilia , Kinesins , Microtubules , Humans , Kinesins/metabolism , Kinesins/genetics , Cell Nucleus/metabolism , Microtubules/metabolism , Cilia/metabolism , Animals , Active Transport, Cell Nucleus , Mice
5.
Opt Lett ; 49(17): 4799-4802, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39207967

ABSTRACT

High-power laser diodes with a stable wavelength and narrow linewidth are crucial for many applications. In this study, we introduce a first-order distributed feedback (DFB) grating into an asymmetric large-cavity laser diode operating around 940 nm. This design maintains high output power and offers a wide temperature locking range. The nearly sinusoidal shape first-order grating is fabricated by ultraviolet (UV) nanoimprint lithography, inductively coupled plasma (ICP) dry etching, and wet polishing. At a heat sink temperature of 25°C, the DFB laser diode, with a 200 µm stripe width and 4 mm cavity length, achieves a maximum output power of 24.8 W and a full width at half maximum (FWHM) of 0.4 nm under continuous-wave (CW) conditions. The maximum slope efficiency is calculated to be 1.04 W/A. At an output power of 10.7 W, the device reaches a peak wall-plug efficiency of 56%. Under quasi-continuous operation at 20 A, the laser output spectrum remains locked to the DFB grating over a temperature range from -10°C to 110°C, with a temperature coefficient of 0.062 nm/°C.

6.
Article in English | MEDLINE | ID: mdl-39192640

ABSTRACT

OBJECTIVES: Non-Small Cell Lung Cancer (NSCLC) has attracted much attention on account of the high incidence and mortality of cancers. Vascular Endothelial Growth Factor Receptor 3 (VEGFR3/FLT4), which is a highly expressed receptor in NSCLC, greatly regulates cancer proliferation and migration. Pseudolaric Acid B (PAB) is a diterpenoid acid with antitumor activity isolated from Pseudolarix kaempferi. This study aimed to explore the inhibitory effect of PAB targeting FLT4 in NSCLC. METHODS: Cell membrane chromatography was used to evaluate the affinity of PAB binding on FLT4. NCIH1299 cells were used in this study, and an MTT assay was performed to determine the anti-proliferation effect of PAB. Cell cycle analysis was conducted to study the cycle arrest of PAB. Wound healing and Transwell assays assessed the rate of cell migration. Western blot analysis evaluated the expression of related proteins. RESULTS: PAB showed strong affinity to FLT4 with a KD value of 3.01 × 10- 6 M. Targeting FLT4 by PAB inactivated downstream P38MAPK and PI3K/AKT pathways, which inhibited the proliferation of NCI-H1299 cells. Meanwhile, PAB promoted G2/M phase arrest by influencing CyclinB1 and CDK1 complex formation to inhibit NCI-H1299 cell growth, but the effect was attenuated by knocking down the FLT4. Besides, PAB regulated MMP9 secretion through the Wnt/ß-catenin signaling pathway to inhibit NCI-H1299 cell migration. However, the ability of PAB to inhibit migration was significantly weakened by FLT4 knockdown in NCI-H1299 cells. CONCLUSION: PAB can inhibit the proliferation and migration of NSCLC cells through targeting FLT4 and is expected to be a promising FLT4 inhibitor for NSCLC treatment.

7.
J Proteome Res ; 23(9): 4005-4013, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39171377

ABSTRACT

Ribosome profiling and mass spectrometry have revealed thousands of previously unannotated small and alternative open reading frames (sm/alt-ORFs) that are translated into micro/alt-proteins in mammalian cells. However, their prevalence across human tissues and biological roles remains largely undefined. The placenta is an ideal model for identifying unannotated microproteins and alt-proteins due to its considerable protein diversity that is required to sustain fetal development during pregnancy. Here, we profiled unannotated microproteins and alt-proteins in human placental tissues from preeclampsia patients or healthy individuals by proteomics, identified 52 unannotated microproteins or alt-proteins, and demonstrated that five microproteins can be translated from overexpression constructs in a heterologous cell line, although several are unstable. We further demonstrated that one microprotein, XRCC6P1, associates with translation initiation factor eIF3 and negatively regulates translation when exogenously overexpressed. Thus, we revealed a hidden sm/alt-ORF-encoded proteome in the human placenta, which may advance the mechanism studies for placenta development as well as placental disorders such as preeclampsia.


Subject(s)
Placenta , Pre-Eclampsia , Protein Biosynthesis , Proteomics , Humans , Pregnancy , Female , Placenta/metabolism , Proteomics/methods , Pre-Eclampsia/metabolism , Pre-Eclampsia/genetics , Open Reading Frames , Eukaryotic Initiation Factor-3/metabolism , Eukaryotic Initiation Factor-3/genetics , Proteome/analysis , Proteome/metabolism , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Micropeptides
8.
J Ethnopharmacol ; 335: 118673, 2024 Dec 05.
Article in English | MEDLINE | ID: mdl-39121931

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVENACE: Sertoli cells are vital to maintain spermatogenesis and their function decline during aging. Epimedium has the effects of tonifying kidney-yang, strengthening bones and muscles, and expelling wind and dampness, and is commonly used in the treatment of kidney-yang deficiency, impotence and spermatorrhea. Icariin is the main active ingredients from Epimedium exhibiting delaying aging effects and improving male reproductive dysfunction. Whereas, it remains poorly understood how icariin alleviates age-associated decline in testicular function by protecting against the damage of junction function of Sertoli cells. AIM OF THE STUDY: This study aimed to evaluate the improvement effect of icariin on Sertoli cell junction function damage and explore the underlying mechanisms. MATERIALS AND METHODS: Male C57BL/6 mice and mouse Sertoli cell line TM4 cells were utilized to assess the improvement effect of icariin on aging-associated Sertoli cell junction function injury. H&E staining, transmission electron microscopy, qPCR, Western blot, molecular docking, siRNA transfection, and immunofluorescence were performed in this study. RESULTS: Dietary administration of icariin remarkly attenuated age-associated deterioration in spermatogenic function as evidenced by elevated testicular weight and index, sperm concentration and sperm viability. In addition, icariin protected Sertoli cell junction function from age-associated damage as proven by increased Sertoli cell numbers, improved tight junction ultrastructure, and upregulated junction-related proteins (ZO-1, Occludin and ß-Catenin). Moreover, icariin significantly upregulated ERα/c-fos signaling and PKR pathway in testicular Sertoli cells. Similarly, in vitro studies revealed that deletion of ERα, c-fos or PKR abolished the improvement effects of icariin on Sertoli cell junction function damage. CONCLUSIONS: Icariin effectively mitigates age-associated decline in testicular function by diminished Sertoli cell junction function damage through upregulating PKR pathway via ERα/c-fos signaling. Therefore, attenuating Sertoli cell junction function injury by the upregulation of PKR pathway via ERα/c-fos signaling probably indicates an effective target for the prevention and treatment of testicular spermatogenic function with aging.


Subject(s)
Aging , Flavonoids , Mice, Inbred C57BL , Proto-Oncogene Proteins c-fos , Sertoli Cells , Signal Transduction , Up-Regulation , Animals , Male , Sertoli Cells/drug effects , Sertoli Cells/metabolism , Flavonoids/pharmacology , Signal Transduction/drug effects , Mice , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-fos/genetics , Up-Regulation/drug effects , Aging/drug effects , Cell Line , Spermatogenesis/drug effects , Testis/drug effects , Testis/metabolism , Testis/pathology , Estrogen Receptor alpha
9.
J Stroke Cerebrovasc Dis ; 33(11): 107962, 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39191317

ABSTRACT

BACKGROUND AND PURPOSE: Post thrombolytic intracerebral hemorrhage (ICH) is associated with higher rate of death or disability in acute ischemic stroke patients. We investigated the relationship between post thrombolytic ICH volume and change in volume and death or disability at 90 days in acute ischemic stroke patients. METHODS: We analyzed 110 patents recruited in the Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY) trial who received intravenous tissue plasminogen activator (tPA) followed by mechanical thrombectomy (if indicated) and 3K3A-APC or placebo. ICH volume was measured at Day 2 and Day 7 using susceptibility weighted sequence (SWI) on magnetic resonance imaging (MRI). We also calculated the post thrombolytic ICH volume change between Day 2 and Day 7. Outcomes were determined by using utility weighted modified Rankin scale (UW-mRs) at 90-days, Outcomes were determined by using utility weighted modified Rankin scale (UW-mRS) at 90 days. To minimize interpretation bias, outcome assessors were blinded to the treatment allocation and clinical data.We adjusted for age, gender, National Institutes of Health Stroke Scale (NIHSS) score (<10,10-19 and ≥20), location of hemorrhage (single basal ganglia hemorrhage, single lobar, single cerebellum, and multiple sites) in multivariate regression analysis. RESULTS: A total of 88 (80%) of 110 patients had post thrombolytic ICH (mean volume 28.3 ml ± SD 62 ml). The strata of ICH volume were not associated with UW-mRs at 90 days: <20 cc (regression coefficient (RC)-0.05, p= 0.58), 20-39 cc (RC-0.22, p=0.17), or ≥40 cc (RC-0.34, p= 0.083) compared with no ICH after adjusting for potential confounders. Change in ICH mean volume 26.78 ml ±59.68, 52 had increase in volume) between Day 2 and day 7 was not associated with UW-mRS at 90 days (RC -67.71, p= 0.06). CONCLUSIONS: We did not observe any independent effect of post thrombolytic ICH volume on death or disability in acute ischemic stroke patients. Although further studies must be done, our data suggest that strategies to prevent ICH expansion such as antifibrinolytic medications and reduction in ICH volume such as surgical evacuation may not reduce death or disability in acute ischemic stroke patients with post thrombolytic ICH.

10.
Org Lett ; 26(34): 7139-7143, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39146026

ABSTRACT

We report an efficient perfluoroalkoxylation reaction of alkyl halides catalyzed by copper(I) iodide (CuI), which facilitates the simultaneous activation of both perfluoroalkoxide and alkyl halides. This methodology is tolerant of a wide range of functional groups and eliminates the need for costly metal reagents. The reaction is conducted in a single step under mildly practical conditions.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1258-1263, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39192428

ABSTRACT

OBJECTIVE: To understand the effect of collagen peptides on the function of mouse lymphocytes under simulated microgravity. METHODS: The splenocytes of mice were isolated, and the rotary cell culture system was used to simulate the microgravity. The T lymphocytes were stimulated with mitotic agents, concanavalin A (ConA), and the cells were treated with different concentrations of collagen peptides. The proliferation of lymphocytes and the levels of cytokines in the supernatant were detected. RESULTS: Simulated microgravity could inhibit the proliferation of spleen T lymphocytes and decrease the level of cytokines in the supernatant. Collagen peptides could promote the lymphocyte proliferation and cytokine production in cells cultured under simulated microgravity. CONCLUSION: Collagen peptides may attenuate the inhibitory effect of simulated microgravity on T lymphocytes by regulating the cell proliferation and the secretion of cytokines.


Subject(s)
Cell Proliferation , Collagen , Cytokines , Peptides , Spleen , T-Lymphocytes , Weightlessness Simulation , Animals , Mice , Spleen/cytology , Peptides/pharmacology , Cytokines/metabolism , Concanavalin A/pharmacology , Weightlessness
12.
Cell Biochem Biophys ; 82(3): 2297-2319, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39174865

ABSTRACT

This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora.


Subject(s)
Apolipoproteins E , Atherosclerosis , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Inflammation , Myeloid Differentiation Factor 88 , Toll-Like Receptor 4 , Animals , Mice , Gastrointestinal Microbiome/drug effects , Atherosclerosis/prevention & control , Atherosclerosis/drug therapy , Atherosclerosis/pathology , Toll-Like Receptor 4/metabolism , RAW 264.7 Cells , Myeloid Differentiation Factor 88/metabolism , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Lipopolysaccharides , Disease Models, Animal , Male , Signal Transduction/drug effects , Macrophages/metabolism , Macrophages/drug effects , Mice, Knockout
13.
Cell Rep ; 43(9): 114662, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39178116

ABSTRACT

Ferroptosis is a form of nonapoptotic cell death characterized by iron-dependent peroxidation of polyunsaturated phospholipids. However, much remains unknown about the regulators of ferroptosis. Here, using CRISPR-Cas9-mediated genetic screening, we identify protein arginine methyltransferase 1 (PRMT1) as a crucial promoter of ferroptosis. We find that PRMT1 decreases the expression of solute carrier family 7 member 11 (SLC7A11) to limit the abundance of intracellular glutathione (GSH). Moreover, we show that PRMT1 interacts with ferroptosis suppressor protein 1 (FSP1), a GSH-independent ferroptosis suppressor, to inhibit the membrane localization and enzymatic activity of FSP1 through arginine dimethylation at R316, thus reducing CoQ10H2 content and inducing ferroptosis sensitivity. Importantly, genetic depletion or pharmacological inhibition of PRMT1 in mice prevents ferroptotic events in the liver and improves the overall survival under concanavalin A (ConA) exposure. Hence, our findings suggest that PRMT1 is a key regulator of ferroptosis and a potential target for antiferroptosis therapeutics.


Subject(s)
Ferroptosis , Protein-Arginine N-Methyltransferases , Protein-Arginine N-Methyltransferases/metabolism , Protein-Arginine N-Methyltransferases/genetics , Animals , Ferroptosis/genetics , Humans , Mice , CRISPR-Cas Systems/genetics , Mice, Inbred C57BL , Glutathione/metabolism , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Male , Liver/metabolism , Repressor Proteins/metabolism , Repressor Proteins/genetics , HEK293 Cells
14.
Biomol Biomed ; 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39151094

ABSTRACT

Cardiovascular diseases (CVDs) are a major challenge in global health. Despite significant advances in treatment and management, the incidence and mortality rates of CVDs have been rising in recent years, particularly in the United States. With continuous advancements in medical technology, perioperative transesophageal echocardiography (TEE) has become a key technology in cardiac surgery, enhancing surgical success rates and patient safety. The application of TEE spans preoperative planning, intraoperative monitoring, and postoperative evaluation, especially in complex procedures such as mitral valve repair and aortic valve replacement, where it plays an indispensable role. Simultaneously, the introduction of artificial intelligence (AI) brings new prospects for TEE image analysis and diagnostic support, significantly improving diagnostic accuracy and real-time decision-making capabilities. However, the application of TEE technology faces challenges such as high costs, uneven technological diffusion, and the high skill requirements for medical personnel. Therefore, establishing standardized training protocols and strengthening multidisciplinary collaboration are crucial. This paper reviews the application of TEE in cardiac surgery and its path toward educational and practical standardization from a global perspective, emphasizing its importance in improving the postoperative quality of life for patients and exploring future directions in technological innovation and educational optimization.

15.
Neuro Oncol ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093693

ABSTRACT

BACKGROUND: Self-renewal of glioma stem cells (GSCs) is responsible for glioblastoma (GBM) therapy-resistant and recurrence. Tumor necrosis factor α (TNFα) and TNF signaling pathway display an antitumor activity in preclinical models and in tumor patients. However, TNFα exhibits no significance for glioma clinical prognosis based on Glioma Genome Atlas database. This study aimed to explore whether TNFα of tumor microenvironment maintains self-renewal of GSCs and promotes worse prognosis in glioma patient. METHODS: Spatial transcriptomics, immunoblotting, sphere formation assay, extreme limiting dilution, and gene expression analysis were used to determine the role of TNFα on GSC's self-renewal. Mass spectrometry, RNA-sequencing detection, bioinformatic analyses, qRT-RNA, immunofluorescence, immunohistochemistry, single cell RNA sequencing, in vitro and in vivo models were used to uncover the mechanism of TNFα-induced GSC self-renewal. RESULTS: Low level of TNFα displays a promoting effect on GSC self-renewal and worse glioma prognosis. Mechanistically, Vasorin (VASN) mediated TNFα-induced self-renewal by potentiating glycolysis. Lactate produced by glycolysis inhibits the TNFα secretion of tumor-associated macrophages (TAMs) and maintains TNFα in a low level. CONCLUSIONS: TNFα-induced GSC self-renewal mediated by VASN provides a possible explanation for the failures of endogenous TNFα effect on GBM. Combination of targeting VASN and TNFα anti-tumor effect may be an effective approach for treating GBM.

16.
Sci Data ; 11(1): 882, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143093

ABSTRACT

Recent advances in computer vision and deep learning techniques have facilitated significant progress in video scene understanding, thus helping film and television practitioners achieve accurate video editing. However, so far, publicly available semantic segmentation datasets are mostly limited to indoor scenes, city streets, and natural images, often ignoring example objects in action movies, which is a research gap that needs to be urgently filled. In this paper, we introduce a large-scale, high-precision semantic segmentation dataset of props in Chinese martial arts movie clips, named ChineseMPD. Specifically, this dataset first establishes segmentation rules and general review criteria for audiovisual data, and then provides semantic segmentation annotations for six weapon props (Gun, Sword, Stick, Knife, Hook, and Arrow) with a summary of 32,992 objects.To the best of our knowledge, this dataset is the largest semantic segmentation dataset for movie props to date. ChineseMPD dataset not only significantly expands the application of traditional tasks of computer vision such as object detection and scene understanding, but also opens up new avenues for interdisciplinary research.

17.
Front Med (Lausanne) ; 11: 1418048, 2024.
Article in English | MEDLINE | ID: mdl-39175821

ABSTRACT

Background: The assessment of image quality (IQA) plays a pivotal role in the realm of image-based computer-aided diagnosis techniques, with fundus imaging standing as the primary method for the screening and diagnosis of ophthalmic diseases. Conventional studies on fundus IQA tend to rely on simplistic datasets for evaluation, predominantly focusing on either local or global information, rather than a synthesis of both. Moreover, the interpretability of these studies often lacks compelling evidence. In order to address these issues, this study introduces the Local and Global Attention Aggregated Deep Neural Network (LGAANet), an innovative approach that integrates both local and global information for enhanced analysis. Methods: The LGAANet was developed and validated using a Multi-Source Heterogeneous Fundus (MSHF) database, encompassing a diverse collection of images. This dataset includes 802 color fundus photography (CFP) images (302 from portable cameras), and 500 ultrawide-field (UWF) images from 904 patients with diabetic retinopathy (DR) and glaucoma, as well as healthy individuals. The assessment of image quality was meticulously carried out by a trio of ophthalmologists, leveraging the human visual system as a benchmark. Furthermore, the model employs attention mechanisms and saliency maps to bolster its interpretability. Results: In testing with the CFP dataset, LGAANet demonstrated remarkable accuracy in three critical dimensions of image quality (illumination, clarity and contrast based on the characteristics of human visual system, and indicates the potential aspects to improve the image quality), recording scores of 0.947, 0.924, and 0.947, respectively. Similarly, when applied to the UWF dataset, the model achieved accuracies of 0.889, 0.913, and 0.923, respectively. These results underscore the efficacy of LGAANet in distinguishing between varying degrees of image quality with high precision. Conclusion: To our knowledge, LGAANet represents the inaugural algorithm trained on an MSHF dataset specifically for fundus IQA, marking a significant milestone in the advancement of computer-aided diagnosis in ophthalmology. This research significantly contributes to the field, offering a novel methodology for the assessment and interpretation of fundus images in the detection and diagnosis of ocular diseases.

18.
Phytomedicine ; 132: 155854, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39032276

ABSTRACT

BACKGROUND: Recent investigations underscore the capacity of photodynamic therapy (PDT) to induce adipocyte apoptosis, thereby mitigating obesity. Nonetheless, extant synthetic photosensitizers manifest limitations that hinder their clinical viability. PURPOSE: In the current study, we used Hypericum perforatum-derived exosomes-like nanovesicles (HPExos) as a novel photosensitizer, and investigated its PDT effects in adipose tissue during obesity. METHOD: HPExos-were administered to high fat diet mice via intraperitoneal injection, followed by targeted irradiation with specialized LED lights. Mass spectrometric analysis was analyzed in adipose tissues. CCK8 assay and Oil Red O staining were used to investigate lipid accumulation in 3T3-L1 cells to clarify adipocyte differentiation. The expression levels of related markers associated with adipogenesis and lipogenesis were assessed by RT-PCR. Apoptosis analysis was performed by TUNEL staining of and western blotting. RESULTS: HPExos combined with PDT accumulated in visceral white adipose tissues results in a reduced body weight and improved insulin sensitivity. HPExos combined with PDT induced apoptosis by driving high levels of ROS. In addition, HPExos combined with PDT significantly downregulated the expression of transcription factors, PPARγ, C/EBPα, and SREBP and lipogenesis protein FABP4 both in vitro and in vivo, associated with a decreased FFA levels. CONCLUSION: These findings suggest that HPExos could act as an effective photosensitizer in regulating glucose hemostasis by inhibiting adipocyte differentiation and lipogenesis, offering a promising approach for obesity treatment.


Subject(s)
3T3-L1 Cells , Apoptosis , Exosomes , Hypericum , Obesity , Photochemotherapy , Hypericum/chemistry , Animals , Mice , Exosomes/metabolism , Photochemotherapy/methods , Male , Apoptosis/drug effects , Obesity/drug therapy , Diet, High-Fat , Mice, Inbred C57BL , Adipose Tissue/drug effects , Photosensitizing Agents/pharmacology , PPAR gamma/metabolism , Adipocytes/drug effects , Adipogenesis/drug effects , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Lipogenesis/drug effects , Reactive Oxygen Species/metabolism , Plant Extracts/pharmacology , Insulin Resistance , CCAAT-Enhancer-Binding Proteins , Fatty Acid-Binding Proteins , Sterol Regulatory Element Binding Protein 1
19.
Sci Total Environ ; 948: 174983, 2024 Oct 20.
Article in English | MEDLINE | ID: mdl-39047834

ABSTRACT

NASA has released the latest Moderate Resolution Imaging Spectroradiometer (MODIS) Multi-Angle Implementation of Atmospheric Correction (MAIAC) Collection 6 (C6) and Collection 6.1 (C6.1) aerosol optical depth (AOD) products with 1 km spatial resolution. This study validated and compared C6 and C6.1 MAIAC AOD products with AERONET observations in terms of accuracy and stability, and analyzed the spatiotemporal characteristics of AOD at different scales in China. The results show that the overall accuracy of MAIAC products is good, with correlation coefficient (R) > 0.9, mean bias (BIAS) < 0.015, and the fraction within the expected error (EE) > 68 %. However, after the algorithm update, the accuracy of Terra MAIAC aerosol products C6.1 has significantly decreased. The accuracy of the products varies with the region. The accuracy of C6.1 in North China, Central East China, and West China, is comparable to or even exceeds that of C6, but performs poorly in South China. In addition, the stability of the updated C6.1 MAIAC aerosol products has not seen significantly improvement. The metrics of no product can all meet the stability goals of the Global Climate Observing System (GCOS, 0.02 per decade) in China. C6.1 improves the retrieval frequency in many regions and temporarily solves the problem of AOD discontinuity at the boundaries of different aerosol models in C6, but there are some fixed climatological AOD blocks (AOD = 0.014) in the eastern Tibetan Plateau region. Both C6 and C6.1 can capture similar annual variation characteristics of AOD to those observed at the AERONET sites. The study provides possible references for improving the MAIAC algorithm and building long-term stable aerosol records.

20.
Sci Total Environ ; 946: 174455, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38964392

ABSTRACT

With the development of industrialization and urbanization, heavy metal (HM) pollution has become an urgent problem in many countries. The use of microorganisms to control HM pollution has attracted the attention of many scholars due to its advantages of mild conditions, low process cost, and no secondary pollution. In this context, this review aimed to compile recent advances on the potential of lactic acid bacteria (LAB) as HMs biosorbents. As a food-safe class of probiotic, LAB can not only be used for HM remediation in soil and wastewater, but most importantly, can be used for metal removal in food. The extracellular adsorption and intracellular accumulation are the main mechanisms of HM removal by LAB. Lactic acid (LA) fermentation is also one of the removal mechanisms, especially in the food industry. The pH, temperature, biomass, ion concentration and adsorption time are the essential parameters to be considered during the bioremediation. Although the LAB remediation is feasible in theory and lab-scale experiments, it is limited in practical applications due to its low efficiency. Therefore, the commonly used methods to improve the adsorption efficiency of LAB, including pretreatment and mixed-cultivation, are also summarized in this review. Finally, based on the review of literature, this paper presents the emerging strategies to overcome the low adsorption capacity of LAB. This review proposes the future investigations required for this field, and provides theoretical support for the practical application of LAB bioremediation of HMs.


Subject(s)
Biodegradation, Environmental , Metals, Heavy , Metals, Heavy/metabolism , Lactobacillales/metabolism , Adsorption , Soil Pollutants/metabolism
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