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1.
Nat Commun ; 15(1): 3869, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719933

ABSTRACT

Solving ill-posed inverse problems typically requires regularization based on prior knowledge. To date, only prior knowledge that is formulated mathematically (e.g., sparsity of the unknown) or implicitly learned from quantitative data can be used for regularization. Thereby, semantically formulated prior knowledge derived from human reasoning and recognition is excluded. Here, we introduce and demonstrate the concept of semantic regularization based on a pre-trained large language model to overcome this vexing limitation. We study the approach, first, numerically in a prototypical 2D inverse scattering problem, and, second, experimentally in 3D and 4D compressive microwave imaging problems based on programmable metasurfaces. We highlight that semantic regularization enables new forms of highly-sought privacy protection for applications like smart homes, touchless human-machine interaction and security screening: selected subjects in the scene can be concealed, or their actions and postures can be altered in the reconstruction by manipulating the semantic prior with suitable language-based control commands.

2.
Front Med ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806989

ABSTRACT

Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction (MI) can lead to heart failure. RNA N6-methyladenosine (m6A) methylation has been shown to play a pivotal role in the occurrence and development of many illnesses. In investigating the biological function of the m6A reader YTHDF1 in cardiac fibrosis, adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts, and MI surgery in vivo and transforming growth factor-ß (TGF-ß)-activated cardiac fibroblasts in vitro were performed to establish fibrosis models. Our results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis, whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic development. Mechanistically, zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene promoter. YTHDF1 augmented AXL translation and activated the TGF-ß-Smad2/3 signaling pathway, thereby aggravating the occurrence and development of cardiac dysfunction and myocardial fibrosis. Consistently, our data indicated that YTHDF1 was involved in activation, proliferation, and migration to participate in cardiac fibrosis in vitro. Our results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.

3.
Braz J Med Biol Res ; 57: e13437, 2024.
Article in English | MEDLINE | ID: mdl-38808889

ABSTRACT

Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.


Subject(s)
Animals, Newborn , Cognition , Hippocampus , Sevoflurane , Sevoflurane/pharmacology , Animals , Female , Male , Hippocampus/drug effects , Hippocampus/metabolism , Rats , Cognition/drug effects , Time Factors , Maze Learning/drug effects , Anesthetics, Inhalation/pharmacology , Anesthetics, Inhalation/adverse effects , Apoptosis/drug effects , Sex Factors , Rats, Sprague-Dawley , Methyl Ethers/pharmacology , Blotting, Western , Blood Gas Analysis , Cognitive Dysfunction/chemically induced
4.
Anal Chem ; 96(19): 7787-7796, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38702857

ABSTRACT

Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.


Subject(s)
Deep Learning , Humans , Stilbenes/chemistry , Gram-Positive Bacteria/isolation & purification , Fluorescent Dyes/chemistry , Gram-Negative Bacteria/isolation & purification , Wound Infection/microbiology , Wound Infection/diagnosis , Fungi/isolation & purification
5.
Insect Biochem Mol Biol ; 170: 104130, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38734116

ABSTRACT

Agmatine N-acetyltransferase (AgmNAT), which catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine, is a member of the GCN5-related N-acetyltransferase family. So far, knowledge of the physiological roles of AgmNAT in insects is limited. Here, we identified one gene encoding protein homologous to that of Drosophila AgmNAT using sequence information from an activity-verified Drosophila AgmNAT in a BLAST search of the Bactrocera dorsalis genome. We expressed and purified B. dorsalis AgmNAT in Escherichia coli and used the purified enzyme to define the substrate specificity for acyl-CoA and amine substrates. Our application of the screening strategy to BdorAgmNAT led to the identification of agmatine as the best amine substrate for this enzyme, with the highest kcat/Km value. We successfully obtained a BdorAgmNAT knockout strain based on a wild-type strain (WT) using the CRISPR/Cas9 technique. The ovary development of the BdorAgmNAT knockout mutants was delayed for 10 days compared with the WT specimens. Moreover, mutants had a much smaller mature ovary size and laid far fewer eggs than WT. Loss of function of BdorAgmNAT caused by RNAi with mature WT females did not affect their fecundity. These findings indicate that BdorAgmNAT is critical for oogenesis. Our data provide the first evidence for AgmNAT in regulating ovary development.

6.
Medicine (Baltimore) ; 103(19): e38131, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728449

ABSTRACT

OBJECTIVE: This study aims to investigate the current research trends and focal points in the field of pelvic floor reconstruction for the management of pelvic organ prolapse (POP). METHODS: To achieve this objective, a bibliometric analysis was conducted on relevant literature using the Citespace database. The analysis led to the creation of a knowledge map, offering a comprehensive overview of scientific advancements in this research area. RESULTS: The study included a total of 607 publications, revealing a consistent increase in articles addressing pelvic floor reconstruction for POP treatment. Most articles originated from the United States (317 articles), followed by Chinese scholars (40 articles). However, it is important to note that the overall number of articles remains relatively low. The organization with the highest publication frequency was the Cleveland Clinic in Ohio, where Matthew D. Barber leads the academic group. Barber himself has the highest number of published articles (18 articles), followed by Zhu Lan, a Chinese scholar (10 articles). Key topics with high frequency and mediated centrality include stress urinary incontinence, quality of life, impact, and age. The journal with the largest number of papers from both domestic and international researchers is INT UROGYNECOL J. The study's hotspots mainly focus on the impact of pelvic floor reconstruction on the treatment and quality of life of POP patients. The United States leads in this field, but there is a lack of cooperation between countries, institutions, and authors. Moving forward, cross-institutional, cross-national, and cross-disciplinary exchanges and cooperation should be strengthened to further advance the field of pelvic floor reconstructive surgery for POP research.


Subject(s)
Bibliometrics , Pelvic Floor , Pelvic Organ Prolapse , Pelvic Organ Prolapse/surgery , Humans , Pelvic Floor/surgery , Female , Plastic Surgery Procedures/methods , Plastic Surgery Procedures/statistics & numerical data , Quality of Life
7.
Se Pu ; 42(5): 410-419, 2024 Apr 08.
Article in Chinese | MEDLINE | ID: mdl-38736384

ABSTRACT

Protein A affinity chromatographic materials are widely used in clinical medicine and biomedicine because of their specific interactions with immunoglobulin G (IgG). Both the characteristics of the matrix, such as its structure and morphology, and the surface modification method contribute to the affinity properties of the packing materials. The specific, orderly, and oriented immobilization of protein A can reduce its steric hindrance with the matrix and preserve its bioactive sites. In this study, four types of affinity chromatographic materials were obtained using agarose and polyglycidyl methacrylate (PGMA) spheres as substrates, and multifunctional epoxy and maleimide groups were used to fix protein A. The effects of the ethylenediamine concentration, reaction pH, buffer concentration, and other conditions on the coupling efficiency of protein A and adsorption performance of IgG were evaluated. Multifunctional epoxy materials were prepared by converting part of the epoxy groups of the agarose and PGMA matrices into amino groups using 0.2 and 1.6 mol/L ethylenediamine, respectively. Protein A was coupled to the multifunctional epoxy materials using 5 mmol/L borate buffer (pH 8) as the reaction solution. When protein A was immobilized on the substrates by maleimide groups, the agarose and PGMA substrates were activated with 25% (v/v) ethylenediamine for 16 h to convert all epoxy groups into amino groups. The maleimide materials were then converted into amino-modified materials by adding 3 mg/mL 3-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) dissolved in dimethyl sulfoxide (DMSO) and then suspended in 5 mmol/L borate buffer (pH 8). The maleimide groups reacted specifically with the C-terminal of the sulfhydryl group of recombinant protein A to achieve highly selective fixation on both the agarose and PGMA substrates. The adsorption performance of the affinity materials for IgG was improved by optimizing the bonding conditions of protein A, such as the matrix type, matrix particle size, and protein A content, and the adsorption properties of each affinity material for IgG were determined. The column pressure of the protein A affinity materials prepared using agarose or PGMA as the matrix via the maleimide method was subsequently evaluated at different flow rates. The affinity materials prepared with PGMA as the matrix exhibited superior mechanical strength compared with the materials prepared with agarose. Moreover, an excellent linear relationship between the flow rate and column pressure of 80 mL/min was observed for this affinity material. Subsequently, the effect of the particle size of the PGMA matrix on the binding capacity of IgG was investigated. Under the same protein A content, the dynamic binding capacity of the affinity materials on the PGMA matrix was higher when the particle size was 44-88 µm than when other particle sizes were used. The properties of the affinity materials prepared using the multifunctional epoxy and maleimide-modified materials were compared by synthesizing affinity materials with different protein A coupling amounts of 1, 2, 4, 6, 8, and 10 mg/mL. The dynamic and static binding capacities of each material for bovine IgG were then determined. The prepared affinity material was packed into a chromatographic column to purify IgG from bovine colostrum. Although all materials showed specific adsorption selectivity for IgG, the affinity material prepared by immobilizing protein A on the PGMA matrix with maleimide showed significantly better performance and achieved a higher dynamic binding capacity at a lower protein grafting amount. When the protein grafting amount was 15.71 mg/mL, the dynamic binding capacity of bovine IgG was 32.23 mg/mL, and the dynamic binding capacity of human IgG reached 54.41 mg/mL. After 160 cycles of alkali treatment, the dynamic binding capacity of the material reached 94.6% of the initial value, indicating its good stability. The developed method is appropriate for the production of protein A affinity chromatographic materials and shows great potential in the fields of protein immobilization and immunoadsorption material synthesis.


Subject(s)
Chromatography, Affinity , Staphylococcal Protein A , Chromatography, Affinity/methods , Staphylococcal Protein A/chemistry , Adsorption , Immunoglobulin G/chemistry , Polymethacrylic Acids/chemistry , Sepharose/chemistry
8.
Inflammopharmacology ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753222

ABSTRACT

Alzheimer's disease (AD) is a fatal neurological illness that worsens with time. Preventing the aggregate formation of amyloid beta protein is a promising approach to treat Alzheimer's disease. This article describes an amiable procedure for the synthesis of Olesoxime-Resveratrol (OLX-RSV) encapsulated in exosomes. By suppressing Aß1-42 aggregation and crossing the blood-brain barrier also known as BBB after intravenous treatment without resulting in any discernible damage, the nanocomposite demonstrated good biocompatibility. A variety of characterization technique including particle size, TEM, and in vitro drug release experiments, were used to characterize the exosomes. Human Neuroblastoma (SHSY5Y) cells were used to test the cytotoxicity and viability of cells of the formulation using the Cell Counting Kit-8 assay. The prepared OLX-RSV-loaded exosomes were tested for their ability to suppress Aß1-42 in SHSY5Y Cells by analyzing the amyloid samples using CD spectra. The effects of apoptosis on Human neuroblastoma cells were studied using cytofluorometry. The parameters of SOD, caspase-3 and the ability to scavenge reactive oxygen species (ROS) were also evaluated. The behavioral outcomes of Morris water maze test demonstrated that OLX-RSV-loaded exosomes significantly enhanced the APP/PS1 mice's capacity to learn and remember spatial cues. Therefore, we hypothesized that OLX-RSV-loaded exosomes could be a useful and efficient method in the treatment of AD.

9.
Article in English | MEDLINE | ID: mdl-38735658

ABSTRACT

PURPOSE: To investigate the role of coexisting RET/PTC rearrangement and TERT promoter mutation in the prognosis and therapeutic targeting in papillary thyroid cancer (PTC). METHODS: A total of 669 PTC patients with complete clinical follow-up and genetic data were pooled from thyroid cancer datasets TCGA, MSK MetTropism, and MSK-IMPACT, from whom 163 patients (112 women and 47 men, 4 unknown) with wild-type BRAF/RAS were identified, with median age (IQR) of 46.00 (33.00, 61.00) years and median follow-up time (IQR) of 16.13 (8.09, 27.91) months for comparative genotype cohort analysis of mortality. RESULTS: There was a significant concurrence index between RET/PTC and TERT promoter mutations, being 2.040 (95% CI 1.110-3.747, P = 0.023). Mortality occurred in 5/100 (5%) patients harboring neither mutation, 2/18 (11.1%) patients harboring TERT promoter mutation alone, 0/31 (0%) patients harboring RET/PTC alone, and 7/14 (50%) patients harboring both genetic alterations, corresponding to HRs (95% CI) of 1 (Reference), 2.469 (0.405-14.02), 3.296e-09 (0-inf), and 9.019 (2.635-30.87), respectively, which remained essentially unchanged after adjustment for patient race, sex, and age. Similar results were observed with BRAF/RAS and TERT promoter mutations. Mechanistically, RET/PTC used the MAP kinase pathway to upregulate the mutated TERT, but not the wild-type TERT, and, correspondingly, targeting RET and MEK could suppress mutated TERT but not the wild-type TERT. CONCLUSION: Coexisting RET/PTC and TERT promoter mutation identify PTC as a unique clinical entity with high mortality, providing new implications for genetic-based prognostication and potential therapeutic targeting of RET and MEK guided by RET/PTC and TERT status.

10.
Technol Cancer Res Treat ; 23: 15330338241254075, 2024.
Article in English | MEDLINE | ID: mdl-38720626

ABSTRACT

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% (P = .042), and the 3-year DFS rates were 70.4% and 47.4% (P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS (P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS (P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients (P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.


Subject(s)
Chemoradiotherapy , Neoplasm Staging , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/mortality , Female , Middle Aged , Prognosis , Adult , Aged , Retrospective Studies , Lymphatic Metastasis , Kaplan-Meier Estimate , Treatment Outcome , Proportional Hazards Models , Survival Rate
11.
J Org Chem ; 89(10): 6966-6973, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38691095

ABSTRACT

The arylation of C(sp2)-H and C(sp3)-H bonds in carboxylic acids catalyzed by Pd(II) with 4-aminobentriazole as the directing group was investigated. In addition to activation of the C(sp2)-H bond, selective arylation of alkyl carboxylic acids and amino acids in the ß position can also be achieved. This strategy involved a 5,5-bicyclic Pd intermediate complex whose structure was determined by X-ray single crystal diffraction analysis. Importantly, the DG (directing group) can be easily removed under mild conditions.

12.
Int J Biol Macromol ; : 132439, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38761907

ABSTRACT

This study explored the immunomodulatory impact and potential mechanisms on macrophages RAW264.7 using a purified macromolecular sulfate glycosaminoglycan (SBSG) from the swim bladder, whose structure was similar to chondroitin sulfate A. The results showed that SBSG at 0.25-1 mg/mL increased the viability and phagocytosis of RAW264.7 cells. Meanwhile, SBSG promoted the secretion of tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and nitric oxide (NO), as well as the production of reactive oxygen species (ROS). According to the RT-PCR and Western blot data, SBSG activated TLR4-nuclear factor kappa B (NF-κB) signaling pathways, which decreased the relative mRNA and protein levels of Toll-like receptor 4 (TLR4), IκB kinase ß (IKKß), NF-κB p65, and p-NF-κB p65. The molecular docking and molecular dynamic simulation findings revealed that the main binding force between TLR4 and SBSG was conventional hydrogen bond interaction, resulting in more stable ligand receptor complexes. In summary, SBSG exhibits significant immunomodulatory potential, similar to chondroitin sulfate C. The underlying molecular mechanism involved the binding of SBSG through hydrogen bonding to TLR4 receptors, triggering the NF-κB signaling pathway to downregulate the expression of related genes and proteins. This, in turn, regulated the secretion of various cytokines that were mediated by macrophages to exert the immunity of the body.

13.
FASEB J ; 38(10): e23678, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38780199

ABSTRACT

Melatonin (MLT), a conserved small indole compound, exhibits anti-inflammatory and antioxidant properties, contributing to its cardioprotective effects. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with atherosclerosis disease risk, and is known as an atherosclerosis risk biomarker. This study aimed to investigate the impact of MLT on Lp-PLA2 expression in the atherosclerotic process and explore the underlying mechanisms involved. In vivo, ApoE-/- mice were fed a high-fat diet, with or without MLT administration, after which the plaque area and collagen content were assessed. Macrophages were pretreated with MLT combined with ox-LDL, and the levels of ferroptosis-related proteins, NRF2 activation, mitochondrial function, and oxidative stress were measured. MLT administration significantly attenuated atherosclerotic plaque progression, as evidenced by decreased plaque area and increased collagen. Compared with those in the high-fat diet (HD) group, the levels of glutathione peroxidase 4 (GPX4) and SLC7A11 (xCT, a cystine/glutamate transporter) in atherosclerotic root macrophages were significantly increased in the MLT group. In vitro, MLT activated the nuclear factor-E2-related Factor 2 (NRF2)/SLC7A11/GPX4 signaling pathway, enhancing antioxidant capacity while reducing lipid peroxidation and suppressing Lp-PLA2 expression in macrophages. Moreover, MLT reversed ox-LDL-induced ferroptosis, through the use of ferrostatin-1 (a ferroptosis inhibitor) and/or erastin (a ferroptosis activator). Furthermore, the protective effects of MLT on Lp-PLA2 expression, antioxidant capacity, lipid peroxidation, and ferroptosis were decreased in ML385 (a specific NRF2 inhibitor)-treated macrophages and in AAV-sh-NRF2 treated ApoE-/- mice. MLT suppresses Lp-PLA2 expression and atherosclerosis processes by inhibiting macrophage ferroptosis and partially activating the NRF2 pathway.


Subject(s)
Atherosclerosis , Ferroptosis , Melatonin , NF-E2-Related Factor 2 , Animals , Ferroptosis/drug effects , NF-E2-Related Factor 2/metabolism , Melatonin/pharmacology , Mice , Atherosclerosis/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , Atherosclerosis/pathology , Male , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Diet, High-Fat/adverse effects , Macrophages/metabolism , Macrophages/drug effects , Mice, Inbred C57BL , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effects , 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , Lipoproteins, LDL/metabolism , Antioxidants/pharmacology
14.
Transl Oncol ; 46: 101996, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38795560

ABSTRACT

Recent studies indicate that circular RNAs (circRNAs) are crucial in the progression of colorectal cancer (CRC). Eukaryotic translation initiation factor 4A3 (EIF4A3) has been identified as a promoter of circRNA production. The biological roles and mechanisms of EIF4A3-derived circRNA (circEIF4A3) in CRC cell autophagy remain poorly understood. This study explores the effects of circEIF4A3 on CRC cell growth and autophagy, aiming to elucidate the underlying molecular mechanisms. We discovered that EIF4A3 and circEIF4A3 synergistically enhance CRC cell growth. CircEIF4A3 sequesters miR-3126-5p, consequently upregulating EIF4A3. Further, circEIF4A3 increases EIF4A3 expression, which promotes autophagy by stabilizing ATG5 mRNA and enhances ATG7 protein stability through the stabilization of USP14 mRNA, a deubiquitinating enzyme. Upregulation of ATG5 and ATG7 counteracts the growth-inhibitory effects of EIF4A3 knockdown on CRC cells. Moreover, our findings demonstrate that EIF4A3 induces the formation of circEIF4A3 in CRC cells. In conclusion, a positive feedback loop between circEIF4A3 and EIF4A3 supports CRC cell growth by facilitating autophagy.

15.
Int J Biol Macromol ; 269(Pt 1): 132073, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705328

ABSTRACT

Selenium nanoparticles (SeNPs) are a potential tumor therapeutic drug and have attracted widespread attention due to their high bioavailability and significant anticancer activity. However, the poor water solubility and degradability of selenium nanoparticles severely limit their application. In this study, spherical selenium nanoparticles with a particle size of approximately 50 nm were prepared by using Sargassum fusiforme polysaccharide (SFPS) as a modifier and Tween-80 as a stabilizer. The results of in vitro experiments showed that Sargassum fusiforme polysaccharide-Tween-80-Selenium nanoparticles (SFPS-Tw-SeNPs) had a significant inhibitory effect on A549 cells, with an IC50 value of 6.14 µg/mL, and showed antitumor cell migration and invasion ability against A549 cells in scratch assays and cell migration and invasion assays (transwell assays). Western blot experiments showed that SFPS-Tw-SeNPs could inhibit the expression of tumor migration- and invasion-related proteins. These results suggest that SFPS-Tw-SeNPs may be potential tumor therapeutic agents, especially for the treatment of human lung cancer.


Subject(s)
Cell Movement , Nanoparticles , Polysaccharides , Sargassum , Selenium , Sargassum/chemistry , Humans , Selenium/chemistry , Cell Movement/drug effects , Polysaccharides/chemistry , Polysaccharides/pharmacology , A549 Cells , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Particle Size , Cell Proliferation/drug effects , Edible Seaweeds
16.
Int Immunopharmacol ; 132: 111953, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38599097

ABSTRACT

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is an important cause of early dysfunction and exacerbation of immune rejection in transplanted hearts. The integrin-related protein CD47 exacerbates myocardial ischemia-reperfusion injury by inhibiting the nitric oxide signaling pathway through interaction with thrombospondin-1 (TSP-1). In addition, the preservation quality of the donor hearts is a key determinant of transplant success. Preservation duration beyond four hours is associated with primary graft dysfunction. We hypothesized that blocking the CD47-TSP-1 system would attenuate ischemia-reperfusion injury in the transplanted heart and, thus, improve the preservation of donor hearts. METHODS: We utilized a syngeneic mouse heart transplant model to assess the effect of CD47 monoclonal antibody (CD47mAb) to treat MIRI. Donor hearts were perfused with CD47mAb or an isotype-matched control immunoglobulin (IgG2a) and were implanted into the abdominal cavity of the recipients after being stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C for 4 h or 8 h. RESULTS: At both the 4-h and 8-h preservation time points, mice in the experimental group perfused with CD47mAb exhibited prolonged survival in the transplanted heart, reduced inflammatory response and oxidative stress, significantly decreased inflammatory cell infiltration, and fewer apoptosis-related biomarkers. CONCLUSION: The application of CD47mAb for the blocking of CD47 attenuates MIRI as well as improves the preservation and prognosis of the transplanted heart in a murine heart transplant model.


Subject(s)
CD47 Antigen , Heart Transplantation , Mice, Inbred C57BL , Animals , CD47 Antigen/antagonists & inhibitors , CD47 Antigen/metabolism , CD47 Antigen/immunology , Mice , Male , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Organ Preservation/methods , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/immunology , Myocardial Reperfusion Injury/metabolism , Thrombospondin 1/metabolism , Oxidative Stress/drug effects , Disease Models, Animal , Apoptosis/drug effects
17.
Sensors (Basel) ; 24(8)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38676207

ABSTRACT

Teaching gesture recognition is a technique used to recognize the hand movements of teachers in classroom teaching scenarios. This technology is widely used in education, including for classroom teaching evaluation, enhancing online teaching, and assisting special education. However, current research on gesture recognition in teaching mainly focuses on detecting the static gestures of individual students and analyzing their classroom behavior. To analyze the teacher's gestures and mitigate the difficulty of single-target dynamic gesture recognition in multi-person teaching scenarios, this paper proposes skeleton-based teaching gesture recognition (ST-TGR), which learns through spatio-temporal representation. This method mainly uses the human pose estimation technique RTMPose to extract the coordinates of the keypoints of the teacher's skeleton and then inputs the recognized sequence of the teacher's skeleton into the MoGRU action recognition network for classifying gesture actions. The MoGRU action recognition module mainly learns the spatio-temporal representation of target actions by stacking a multi-scale bidirectional gated recurrent unit (BiGRU) and using improved attention mechanism modules. To validate the generalization of the action recognition network model, we conducted comparative experiments on datasets including NTU RGB+D 60, UT-Kinect Action3D, SBU Kinect Interaction, and Florence 3D. The results indicate that, compared with most existing baseline models, the model proposed in this article exhibits better performance in recognition accuracy and speed.


Subject(s)
Gestures , Humans , Pattern Recognition, Automated/methods , Algorithms , Teaching
18.
Genome Biol ; 25(1): 107, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671502

ABSTRACT

Long-read sequencing data, particularly those derived from the Oxford Nanopore sequencing platform, tend to exhibit high error rates. Here, we present NextDenovo, an efficient error correction and assembly tool for noisy long reads, which achieves a high level of accuracy in genome assembly. We apply NextDenovo to assemble 35 diverse human genomes from around the world using Nanopore long-read data. These genomes allow us to identify the landscape of segmental duplication and gene copy number variation in modern human populations. The use of NextDenovo should pave the way for population-scale long-read assembly using Nanopore long-read data.


Subject(s)
DNA Copy Number Variations , Genome, Human , Humans , High-Throughput Nucleotide Sequencing/methods , Software , Nanopore Sequencing/methods , Sequence Analysis, DNA/methods , Genomics/methods
19.
Talanta ; 275: 126076, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38663070

ABSTRACT

Raman spectroscopy serves as a powerful and reliable tool for the characterization of pathogenic bacteria. The integration of Raman spectroscopy with artificial intelligence techniques to rapidly identify pathogenic bacteria has become paramount for expediting disease diagnosis. However, the development of prevailing supervised artificial intelligence algorithms is still constrained by costly and limited well-annotated Raman spectroscopy datasets. Furthermore, tackling various high-dimensional and intricate Raman spectra of pathogenic bacteria in the absence of annotations remains a formidable challenge. In this paper, we propose a concise and efficient deep clustering-based framework (RamanCluster) to achieve accurate and robust unsupervised Raman spectral identification of pathogenic bacteria without the need for any annotated data. RamanCluster is composed of a novel representation learning module and a machine learning-based clustering module, systematically enabling the extraction of robust discriminative representations and unsupervised Raman spectral identification of pathogenic bacteria. The extensive experimental results show that RamanCluster has achieved high accuracy on both Bacteria-4 and Bacteria-6, with ACC values of 77 % and 74.1 %, NMI values of 75 % and 73 %, as well as AMI values of 74.6 % and 72.6 %, respectively. Furthermore, compared with other state-of-the-art methods, RamanCluster exhibits the superior accuracy on handling various complicated pathogenic bacterial Raman spectroscopy datasets, including situations with strong noise and a wide variety of pathogenic bacterial species. Additionally, RamanCluster also demonstrates commendable robustness in these challenging scenarios. In short, RamanCluster has a promising prospect in accelerating the development of low-cost and widely applicable disease diagnosis in clinical medicine.


Subject(s)
Bacteria , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Bacteria/isolation & purification , Cluster Analysis , Algorithms
20.
PeerJ Comput Sci ; 10: e1962, 2024.
Article in English | MEDLINE | ID: mdl-38660153

ABSTRACT

Data sharing is increasingly important across various industries. However, issues such as data integrity verification during sharing, encryption key leakage, and difficulty sharing data between different user groups have been identified. To address these challenges, this study proposes a multi-group data sharing network model based on Consortium Blockchain and IPFS for P2P sharing. This model uses a dynamic key encryption algorithm to provide secure data sharing, avoiding the problems associated with existing data transmission techniques such as key cracking or data leakage due to low security and reliability. Additionally, the model establishes an IPFS network for users within the group, allowing for the generation of data probes to verify data integrity, and the use of the Fabric network to record log information and probe data related to data operations and encryption. Data owners retain full control over access to their data to ensure privacy and security. The experimental results show that the system proposed in this study has wide applicability.

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