ABSTRACT
Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited the understanding of generalizable mechanisms of BAT regulation over physiology. Here, we perform deep quantitative proteomics of BAT across a cohort of 163 genetically defined diversity outbred mice, a model that parallels the genetic and phenotypic variation found in humans. We leverage this diversity to define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functions to 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify 638 proteins that correlate with protection from, or sensitivity to, at least one parameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, and ATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resource for understanding the conserved mechanisms of BAT regulation over metabolic physiology.
Subject(s)
Adipose Tissue, Brown , Proteome , Humans , Mice , Animals , Adipose Tissue, Brown/metabolism , Proteome/metabolism , Thermogenesis/physiology , Adiposity , Obesity/metabolism , Mice, Inbred C57BL , Proto-Oncogene Proteins/metabolismABSTRACT
It is imperative to devise effective removal strategies for high ionization potential (IP) organic pollutants in wastewater as their reduced electron-donating capacity challenges the efficiency of advanced oxidation systems in degradation. Against this backdrop, leveraging the metal-based carbon material structure meticulously, we employed metal-pyridine-N (M-N-C, M=Fe, Co, and Ni) as the electron transfer bridge. This distinctive design facilitated the ordered transfer of electrons from the adsorbent surface to the surface of high IP value pollutants, acting as a "supplement" to compensate for their deficient electron-donating capability, thereby culminating in the selective adsorption of these pollutants. Furthermore, this adsorbent also demonstrated effective removal of trace emerging contaminants (2 mg/L), displayed robust resistance to various salts, exhibited reusability, and maintained stability. These findings carry substantial implications for future carbon-based material design, offering a pathway toward exceptional adsorption performance in treating water pollution.
ABSTRACT
We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.
Subject(s)
Optical Fibers , Optogenetics , Mice , Animals , Hydrogels , Motor Activity , Sciatic Nerve/physiology , LocomotionABSTRACT
Activation of latent transforming growth factor (TGF)-ß2 is incompletely understood. Unlike TGF-ß1 and ß3, the TGF-ß2 prodomain lacks a seven-residue RGDLXX (L/I) integrin-recognition motif and is thought not to be activated by integrins. Here, we report the surprising finding that TGF-ß2 contains a related but divergent 13-residue integrin-recognition motif (YTSGDQKTIKSTR) that specializes it for activation by integrin αVß6 but not αVß8. Both classes of motifs compete for the same binding site in αVß6. Multiple changes in the longer motif underlie its specificity. ProTGF-ß2 structures define interesting differences from proTGF-ß1 and the structural context for activation by αVß6. Some integrin-independent activation is also seen for proTGF-ß2 and even more so for proTGF-ß3. Our findings have important implications for therapeutics to αVß6 in clinical trials for fibrosis, in which inhibition of TGF-ß2 activation has not been anticipated.
Subject(s)
Integrins , Transforming Growth Factor beta2 , Humans , Integrins/metabolism , Transforming Growth Factor beta1/metabolism , Antigens, Neoplasm/metabolism , Fibrosis , Transforming Growth Factor beta/metabolismABSTRACT
The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor (GPCR) with an ectodomain consisting of a low-density lipoprotein receptor class A (LDLa) module and leucine-rich repeats. The mechanism of RXFP1 signal transduction is clearly distinct from that of other GPCRs, but remains very poorly understood. In the present study, we determine the cryo-electron microscopy structure of active-state human RXFP1, bound to a single-chain version of the endogenous agonist relaxin-2 and the heterotrimeric Gs protein. Evolutionary coupling analysis and structure-guided functional experiments reveal that RXFP1 signals through a mechanism of autoinhibition. Our results explain how an unusual GPCR family functions, providing a path to rational drug development targeting the relaxin receptors.
Subject(s)
Relaxin , Humans , Relaxin/chemistry , Relaxin/metabolism , Cryoelectron Microscopy , Receptors, G-Protein-Coupled/metabolism , Receptors, Peptide/chemistryABSTRACT
It has been demonstrated that scar tissue and fibrosis may increase the likelihood of developing malignancies. Specifically, scar tissue has been linked to the occurrence and progression of lung cancer (LC), though the precise mechanisms necessitate further research for explanation. Lung scarring can stem from various causes, with carcinogenesis on scarring lesions in pulmonary tuberculosis (PTB) being the most frequent (accounting for approximately 75% of cases). Notably, having previously cured, PTB is the second most common risk factor for LC after smoking, with approximately 3% of PTB patients experiencing LC as a secondary condition. This essay will delve into the mechanisms, treatment, and prognosis of tuberculosis scar carcinoma (TSC).
Subject(s)
Carcinoma , Lung Neoplasms , Tuberculosis, Pulmonary , Humans , Cicatrix/complications , Cicatrix/pathology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/epidemiology , Lung Neoplasms/pathology , Carcinoma/complications , Risk FactorsABSTRACT
Inverted flexible perovskite solar cells (fPSCs) are promising for commercialization due to their low cost, lightweight, and excellent stability. However, enhancing fPSCs' power conversion efficiency and stability remains challenging. Here, an unprecedented triple cross-linking engineering strategy is innovatively exhibit for efficient and stable inverted fPSCs. First, a carefully designed cross-linker, 4-fluorophenyl 5-(1,2-dithiolan-3-yl) pentanoate (FB-TA), is added to the perovskite precursor solution. During the perovskite film's crystallization at a low temperature, the cross-linking product of FB-TA can passivate the grain boundaries and reduce the film's residual strain and Young's module. Then, FB-TA is also introduced for the bottom- and top-interface modification of the perovskite film. The interfacial treating strategy protects the perovskite from water invasion and strengthens the interfaces. The combination of triple strategies affords highly efficient inverted fPSCs with a champion efficiency of 21.42% among the state-of-the-art inverted fPSCs based on nickel oxides. More importantly, the flexible devices also exhibit superior stabilities with T90 >4000 bending cycles, photostability with T90 >568 h, and ambient stability with T90 >2000 h, especially the stability with T80 >1120 h under harsh damp-heat conditions (i.e., 85 °C and 85% RH). The strategy provides new insights into the industrialization of high-performance and stable fPSCs.
ABSTRACT
BACKGROUND: Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear. METHODS: Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation. RESULTS: Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1. CONCLUSION: In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.
Subject(s)
Blood Glucose , Diabetes Mellitus, Experimental , Human Umbilical Vein Endothelial Cells , Ion Channels , Mice, Knockout , Nitric Oxide Synthase Type III , Oxidative Stress , Animals , Humans , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Diabetes Mellitus, Experimental/metabolism , Ion Channels/metabolism , Ion Channels/genetics , Blood Glucose/metabolism , Nitric Oxide Synthase Type III/metabolism , Mechanotransduction, Cellular , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/deficiency , Cells, Cultured , Cell Proliferation , Apoptosis , Male , Diabetic Angiopathies/metabolism , Diabetic Angiopathies/physiopathology , Diabetic Angiopathies/pathology , Diabetic Angiopathies/genetics , Diabetic Angiopathies/etiology , Cell Movement , Mice, Inbred C57BL , Reactive Oxygen Species/metabolism , Aorta, Thoracic/metabolism , Aorta, Thoracic/pathology , Aorta, Thoracic/physiopathology , Mice , Streptozocin , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Endothelium, Vascular/pathology , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/geneticsABSTRACT
Feline calicivirus (FCV) is a highly contagious virus in cats, which typically causes respiratory tract and oral infections. Despite vaccination against FCV being a regular practice in China, new FCV cases still occur. Antigenic diversity of FCV hinders the effective control by vaccination. This is first report which aims to investigate the molecular epidemiology and molecular characteristics of FCV in Kunshan, China. The nasopharyngeal swabs were collected from cats showing variable clinical signs from different animal clinics in Kunshan from 2022 to 2023. Preliminary detection and sequencing of the FCV capsid gene were performed to study genetic diversity and evolutionary characteristics. FCV-RNA was identified in 52 (26%) of the samples using RT-PCR. A significant association was found between FCV-positive detection rate, age, gender, vaccination status and living environment, while a non-significant association was found with breed of cats. Nucleotide analysis revealed two genotypes, GI and GII. GII predominated in Kunshan, with diverse strains and amino acid variations potentially affecting vaccination efficacy and FCV detection. Notably, analysis pinpointed certain strains' association with FCV-virulent systemic disease pathotypes. This investigation sheds light on FCV dynamics, which may aid in developing better prevention strategies and future vaccine designs against circulating FCV genotypes.
Subject(s)
Caliciviridae Infections , Calicivirus, Feline , Cat Diseases , Cats , Animals , Phylogeny , Calicivirus, Feline/genetics , Molecular Epidemiology , Caliciviridae Infections/epidemiology , Caliciviridae Infections/veterinary , Capsid Proteins/genetics , RNA , Cat Diseases/epidemiologyABSTRACT
Transgenerational plasticity (TGP) allows a plant to acclimate to external variable environments and is a potential mechanism that explains the range expansion and invasion success of some exotic plants. Most studies explored the traits of TGP associated with the success of exotic plant invasions by comparison studies among exotic, native, invasive, and noninvasive species. However, studies on the TGP of invasive plants in different resource environments are scarce, and the biological mechanisms involved are not well understood. This study aimed to determine the role of TGP in the invasiveness of Xanthium strumarium in northeast China. We measured the plant morphology of aboveground parts and the growth of three generations of the invader under different environmental conditions. The results showed that the intergenerational plasticity of X. strumarium was stronger under stress conditions. We found that the X. strumarium parent generation (F0) grown under water and/or nutrient deficiency conditions transferred the environmental information to their offspring (F1 and F2). The F1 generation grown under high-resource conditions has greater height with larger crown sizes, thicker basal diameters, and higher biomass. Both water and nutrients can affect the intergenerational transmission of plant plasticity, nutrients play a more important role compared with water. The high morphological intergenerational plasticity of X. strumarium under a pressure environment can help it quickly adapt to the new environment and accelerate the rapid expansion of the population in the short term. The root:shoot ratio and reproductive and nutrient distribution of the X. strumarium F0 and F1 generations showed high stability when the growth environment of the F0 generation differed from that of the F1 generation. The stable resource allocation strategy can ensure that the obtained resources are evenly distributed to each organ to maintain the long-term existence of the community. Therefore, the study of intergenerational transmission plasticity is of great significance for understanding the invasion process, mechanism, and prevention of invasive plants.
Subject(s)
Xanthium , Biomass , Plants , Adaptation, Physiological , WaterABSTRACT
BACKGROUND: Oncology databases that integrate genomic and clinical data have become valuable resources for precision medicine. However, the generalizability of these databases has not been comprehensively assessed. OBJECTIVES: To describe the demographics, clinical characteristics, treatments, and overall survival of breast cancer cohorts in GENIE-BPC and three other databases. METHODS: This study utilized GENIE-BPC, SEER, SEER-Medicare, and Merative MarketScan Research Databases. Women with invasive breast cancer were identified through EHR, cancer registries or ICD-9/10-CM codes. The ages were 18+ years or per database requirement. Treatments were based on EHR or HCPCS/NDC codes in claims. Overall survival was estimated as time from diagnosis to death. RESULTS: Of female breast cancer patients in GENIE-BPC (n = 775), SEER (n = 548 336), SEER-Medicare (n = 68 914), and Marketscan (n = 109 499) databases, the median ages at initial diagnosis were 44, 62, 74, and 57 years, respectively. A greater proportion of patients in GENIE-BPC, compared to SEER/SEER-Medicare, had higher nuclear grades (%III-%IV: 57% vs. 26%/24%), advanced disease stage (%IV: 25.3% vs. 5%/3.6%), percent of triple negative breast cancer (19.7% vs. 10.2%/8.5%), and receipt of chemotherapy (85.0% vs. NA/22.3%). The 1-, 3-, and 5-year overall survival rates were lower in GENIE-BPC (78.5%, 60.5%, 55.5%) than in SEER (95.8%, 89.5%, 85.5%) and SEER-Medicare (91.6%, 81.4%, 75.0%). CONCLUSION: Breast cancer patients in GENIE-BPC were younger, had more advanced disease, had a higher proportion of triple negative breast cancer and recipients of chemotherapy, and had poorer overall survival. Researchers must use statistical adjustment when extrapolating results (e.g., biomarker prevalence) from GENIE-BPC to the larger breast cancer population.
Subject(s)
Breast Neoplasms , Databases, Factual , Genomics , SEER Program , Humans , Female , Breast Neoplasms/therapy , Breast Neoplasms/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Middle Aged , Aged , Adult , United States/epidemiology , Cohort Studies , Precision Medicine/methods , Aged, 80 and over , Young AdultABSTRACT
BACKGROUND: Sugammadex was initially approved for reversal of neuromuscular blockade in adults in the United States in 2015. Limited data suggest sugammadex is widely used in pediatric anesthesia practice however the factors influencing use are not known. We explore patient, surgical, and institutional factors associated with the decision to use sugammadex versus neostigmine or no reversal, and the decision to use 2 mg/kg vs 4 mg/kg dosing. METHODS: Using data from the Multicenter Perioperative Outcomes Group (MPOG) database, an EHR-derived registry, we conducted a retrospective cross-sectional study. Eligible cases were performed between January 1, 2016 and December 31, 2020, for children 0 to 17 years at US hospitals. Cases involved general anesthesia with endotracheal intubation and administration of rocuronium or vecuronium. Using generalized linear mixed models with institution and anesthesiologist-specific random intercepts, we measured the importance of a variety of patient, clinician, institution, anesthetic, and surgical risk factors in the decision to use sugammadex versus neostigmine, and the decision to use a 2 mg/kg vs 4 mg/kg dose. We then used intraclass correlation statistics to evaluate the proportion of variance contributed by institution and anesthesiologist specifically. RESULTS: There were 97,654 eligible anesthetics across 30 institutions. Of these 47.1% received sugammadex, 43.1% received neostigmine, and 9.8% received no reversal agent. Variability in the choice to use sugammadex was attributable primarily to institution (40.4%) and attending anesthesiologist (27.1%). Factors associated with sugammadex use (compared to neostigmine) include time from first institutional use of sugammadex (odds ratio [OR], 1.08, 95% confidence interval [CI], 1.08-1.09, per month, P < .001), younger patient age groups (0-27 days OR, 2.59 [2.00-3.34], P < .001; 28 days-1 year OR, 2.72 [2.16-3.43], P < .001 vs 12-17 years), increased American Society of Anesthesiologists [ASA] physical status (ASA III: OR, 1.32 [1.23-1.42], P < .001 ASA IV OR, 1.71 [1.46-2.00], P < .001 vs ASA I), neuromuscular disease (OR, 1.14 (1.04-1.26], P = .006), cardiac surgery (OR, 1.76 [1.40-2.22], P < .001), dose of neuromuscular blockade within the hour before reversal (>2 ED95s/kg OR, 4.58 (4.14-5.07], P < .001 vs none), and shorter case duration (case duration <60 minutes OR, 2.06 [1.75-2.43], P < .001 vs >300 minutes). CONCLUSIONS: Variation in sugammadex use was primarily explained by institution and attending anesthesiologist. Patient factors associated with the decision to use sugammadex included younger age, higher doses of neuromuscular blocking agents, and increased medical complexity.
ABSTRACT
To date, only some cancer patients can benefit from chemotherapy and targeted therapy. Drug resistance continues to be a major and challenging problem facing current cancer research. Rapidly accumulated patient-derived clinical transcriptomic data with cancer drug response bring opportunities for exploring molecular determinants of drug response, but meanwhile pose challenges for data management, integration, and reuse. Here we present the Cancer Treatment Response gene signature DataBase (CTR-DB, http://ctrdb.ncpsb.org.cn/), a unique database for basic and clinical researchers to access, integrate, and reuse clinical transcriptomes with cancer drug response. CTR-DB has collected and uniformly reprocessed 83 patient-derived pre-treatment transcriptomic source datasets with manually curated cancer drug response information, involving 28 histological cancer types, 123 drugs, and 5139 patient samples. These data are browsable, searchable, and downloadable. Moreover, CTR-DB supports single-dataset exploration (including differential gene expression, receiver operating characteristic curve, functional enrichment, sensitizing drug search, and tumor microenvironment analyses), and multiple-dataset combination and comparison, as well as biomarker validation function, which provide insights into the drug resistance mechanism, predictive biomarker discovery and validation, drug combination, and resistance mechanism heterogeneity.
Subject(s)
Biomarkers, Pharmacological , Databases, Genetic , Drug Resistance, Neoplasm/genetics , Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neoplasms/genetics , Transcriptome/genetics , Tumor Microenvironment/drug effects , Tumor Microenvironment/geneticsABSTRACT
OBJECTIVES: This study aimed to investigate the involvement of the cell cycle-related protein centromere protein F (CENPF) in the development of ovarian cancer (OC) and explored its relationship with ferroptosis. DESIGN: The databases were analysed to identify differential expression of cell cycle-related proteins between individuals with OC and normal individuals. Immunohistochemistry and statistical analysis were conducted on ovarian tissues obtained from 40 patients with epithelial OC and 20 normal individuals. In vitro experiments were performed using SKOV3 and HEY epithelial OC cell lines. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mRNA microarray dataset, consisting of GSE14001, GSE54388, GSE40595, and GSE14407, was downloaded from the Gene Expression Omnibus (GEO) database to investigate the genes associated with cell cycle regulation in OC cells. CENPF was selected as the subject of study through differential analysis.Assessed the expression of CENPF in both OC patients and normal ovarian tissues using immunohistochemistry. Lentivirus infection was employed to downregulate CENPF expression, and subsequent experiments including Cell Counting Kit-8 assay, cell cycle analysis, transwell assay, and wound-healing assay were conducted to investigate the effects of CENPF on proliferation, invasion, migration, and cell cycle regulation in OC cells. The reactive oxygen species (ROS) and the malondialdehyde (MDA) assays were performed to assess the involvement of CENPF in cellular redox reactions. Western blot analysis was conducted to examine the expression levels of ferroptosis-related proteins (GPX4, SLC7A11, DMT1, and protein 53 [p53]). RESULTS: By querying and integrating cell cycle-related genes from the GEO database, in silico analyses using The Cancer Genome Atlas database combined with immunohistochemical studies, we discovered that CENPF is upregulated in OC tissues and is related to survival. Downregulation of CENPF inhibited biological function of OC cells, increased intracellular ROS and MDA levels, and downregulated the GPX4 protein and the SLC7A11/xCT protein, but upregulated the DMT1 protein and the tumour p53 expression to induce ferroptosis. LIMITATIONS: This study did not investigate ferroptosis-related studies following CENPF overexpression, and the findings have not been validated in animal studies. CONCLUSIONS: Our findings demonstrated that the deficiency of CENPF played a crucial anti-oncogenic role in the progression of OC through the mechanism of ferroptosis.
ABSTRACT
Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes' (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.
Subject(s)
Adenosine/analogs & derivatives , Benzene , Methyltransferases , Benzene/toxicity , Animals , Methyltransferases/genetics , Methyltransferases/metabolism , Mice , Cell Transformation, Neoplastic/chemically induced , Cell Transformation, Neoplastic/genetics , Myeloid Cells/drug effects , Myeloid Cells/pathology , Mice, Inbred C57BL , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , MaleABSTRACT
A motor imagery brain-computer interface connects the human brain and computers via electroencephalography (EEG). However, individual differences in the frequency ranges of brain activity during motor imagery tasks pose a challenge, limiting the manual feature extraction for motor imagery classification. To extract features that match specific subjects, we proposed a novel motor imagery classification model using distinctive feature fusion with adaptive structural LASSO. Specifically, we extracted spatial domain features from overlapping and multi-scale sub-bands of EEG signals and mined discriminative features by fusing the task relevance of features with spatial information into the adaptive LASSO-based feature selection. We evaluated the proposed model on public motor imagery EEG datasets, demonstrating that the model has excellent performance. Meanwhile, ablation studies and feature selection visualization of the proposed model further verified the great potential of EEG analysis.
Subject(s)
Brain-Computer Interfaces , Electroencephalography , Signal Processing, Computer-Assisted , Electroencephalography/methods , Humans , Algorithms , Brain/physiology , Brain/diagnostic imaging , Imagination/physiologyABSTRACT
Wireless Sensor Networks (WSNs) have emerged as an efficient solution for numerous real-time applications, attributable to their compactness, cost-effectiveness, and ease of deployment. The rapid advancement of 5G technology and mobile edge computing (MEC) in recent years has catalyzed the transition towards large-scale deployment of WSN devices. However, the resulting data proliferation and the dynamics of communication environments introduce new challenges for WSN communication: (1) ensuring robust communication in adverse environments and (2) effectively alleviating bandwidth pressure from massive data transmission. In response to the aforementioned challenges, this paper proposes a semantic communication solution. Specifically, considering the limited computational and storage resources of WSN devices, we propose a flexible Attention-based Adaptive Coding (AAC) module. This module integrates window and channel attention mechanisms, dynamically adjusts semantic information in response to the current channel state, and facilitates adaptation of a single model across various Signal-to-Noise Ratio (SNR) environments. Furthermore, to validate the effectiveness of this approach, the paper introduces an end-to-end Joint Source Channel Coding (JSCC) scheme for image semantic communication, employing the AAC module. Experimental results demonstrate that the proposed scheme surpasses existing deep JSCC schemes across datasets of varying resolutions; furthermore, they validate the efficacy of the proposed AAC module, which is capable of dynamically adjusting critical information according to the current channel state. This enables the model to be trained over a range of SNRs and obtain better results.
ABSTRACT
When photographing objects underwater, it is important to utilize an optical window to isolate the imaging device from the water. The properties of the entire imaging system will change, and the imaging quality will decrease due to the refraction impact of the water and the window. The theoretical calculation method for air imaging is no longer relevant in this context. To analyze the unique rule, this research derives the formulas for key parameters of underwater imaging systems under paraxial circumstances. First, the optical window is modeled, then the formula for the optical window's focal length in the underwater environment is derived, and the change rule for the focal length of various window forms underwater is condensed. For the ideal imaging system using a domed optical window, the equivalent two-optical group model of the imaging system is established, and the formula for calculating the focal length, working distance, and depth of field of the underwater imaging system is derived through paraxial ray tracing. The accuracy of the formula is verified through the comparative analysis of the formula calculation results and the Zemax modeling simulation results. It provides an important theoretical basis for the in-depth study of underwater imaging technology.
ABSTRACT
Isoliquiritigenin (ISL) is a chalcone that has shown great potential in the treatment of cancer. However, its relatively weak activity and low water solubility limit its clinical application. In this study, we designed and synthesized 21 amino acid ester derivatives of ISL and characterized the compounds using 1H NMR and 13C NMR. Among them, compound 9 (IC50 = 14.36 µM) had a better inhibitory effect on human cervical cancer (Hela) than ISL (IC50 = 126.5 µM), and it was superior to the positive drug 5-FU (IC50 = 33.59 µM). The mechanism of the action experiment showed that compound 9 could induce Hela cell apoptosis and autophagy through the PI3K/Akt/mTOR pathway.
Subject(s)
Amino Acids , Antineoplastic Agents , Apoptosis , Chalcones , Drug Design , Esters , Chalcones/pharmacology , Chalcones/chemistry , Chalcones/chemical synthesis , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , HeLa Cells , Amino Acids/chemistry , Amino Acids/pharmacology , Esters/chemistry , Esters/pharmacology , Esters/chemical synthesis , Apoptosis/drug effects , TOR Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Cell Proliferation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Structure-Activity Relationship , Phosphatidylinositol 3-Kinases/metabolism , Autophagy/drug effects , Molecular StructureABSTRACT
BACKGROUND: Dendrobium officinale flos (DOF), a novel food raw material, is used in Chinese folk medicine to nourish the stomach. However, there is still no available study to evaluate the effects of DOF on animal models of acute gastric injury and its mechanism by modern pharmacological research. RESULTS: Herein, we characterized the major components of an aqueous extract of DOF and assessed its potential ameliorative effects in a rat model of acute gastric mucosal injury. The DOF water extract showed significant protective effects on the gastric mucosa and exhibited excellent antioxidant and anti-inflammatory activities. Acute gastric injury rat models induced by ethanol (6 mL kg-1) were pretreated with different doses of DOF water extract (50-100 mg kg-1 day-1), and the biological effects of DOF extract in gastric tissues were evaluated. DOF extract alleviated the symptoms of ethanol-stimulated acute gastric mucosal injury, as evidenced by a significant reduction in gastric injury index and the degree of gastric pathological changes. Additionally, treatment with DOF extract upregulated mucin expression in the gastric mucosa, attenuated oxidative stress, decreased the release of inflammatory mediators (TNF-α, IL-6), suppressed the expression of key proinflammatory enzymes (COX-2 and iNOS), reduced the phosphorylation of p38 MAPK and p65 NF-κB and increased the level of PGE2 in gastric tissues. CONCLUSION: DOF exerts protective effects against ethanol-induced acute gastric mucosal injury, mainly by inhibiting inflammation and oxidative stress. © 2024 Society of Chemical Industry.