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1.
Molecules ; 29(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38999156

ABSTRACT

Heavy metals and organic pollutants are prevalent in water bodies, causing great damage to the environment and human beings. Hence, it is urgent to develop a kind of adsorbent with good performance. Anion interlacing layered double hydroxides (LDHs) are a promising adsorbent for the sustainable removal of heavy metal ions and dyes from wastewater. Using aluminum chloride, zinc chloride and ammonium pentaborate tetrahydrate (NH4B5O8 · 4H2O, BA) as raw materials, the LDHs complex (BA-LDHs) of B5O8- intercalation was prepared by one-step hydrothermal method. The BA-LDHs samples were characterized by a X-ray powder diffractometer (XRD), scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR) and the Brunauer-Emmett-Teller (BET) method. The results showed that B5O8- was successfully intercalated. Adsorption experimental results suggested that BA-LDHs possess a maximum adsorption capacity of 18.7, 57.5, 70.2, and 3.12 mg·g-1 for Cd(II), Cu(II), Cr(VI) and Methylene blue (MB) at Cs = 2 g·L-1, respectively. The adsorption experiment conforms to the Langmuir and Freundlich adsorption models, and the kinetic adsorption data are well fitted by the pseudo-second-order adsorption kinetic equation. The as-prepared BA-LDHs have potential application prospects in the removal of heavy metals and dyes in wastewater. More importantly, they also provide a strategy for preparing selective adsorbents.

3.
Dalton Trans ; 53(27): 11242-11246, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38919991

ABSTRACT

Herein, we report a composite COF material loaded with a Pt nanoenzyme and an organic photosensitizer BODIPY, synthesized via a stepwise post-synthetic modification. The obtained Pt@COF-BDP nanoparticles can efficiently and continuously convert H2O2 to O2, thereby increasing the efficiency of single-linear oxygen production and achieving efficient tumor inhibition.


Subject(s)
Boron Compounds , Metal-Organic Frameworks , Photochemotherapy , Photosensitizing Agents , Platinum , Boron Compounds/chemistry , Boron Compounds/pharmacology , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Platinum/chemistry , Platinum/pharmacology , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Metal-Organic Frameworks/chemical synthesis , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Mice , Nanoparticles/chemistry , Tumor Hypoxia/drug effects , Hydrogen Peroxide/chemistry
4.
Biomed Opt Express ; 15(5): 2977-2999, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38855696

ABSTRACT

Accurate segmentation of polyp regions in gastrointestinal endoscopic images is pivotal for diagnosis and treatment. Despite advancements, challenges persist, like accurately segmenting small polyps and maintaining accuracy when polyps resemble surrounding tissues. Recent studies show the effectiveness of the pyramid vision transformer (PVT) in capturing global context, yet it may lack detailed information. Conversely, U-Net excels in semantic extraction. Hence, we propose the bilateral fusion enhanced network (BFE-Net) to address these challenges. Our model integrates U-Net and PVT features via a deep feature enhancement fusion module (FEF) and attention decoder module (AD). Experimental results demonstrate significant improvements, validating our model's effectiveness across various datasets and modalities, promising advancements in gastrointestinal polyp diagnosis and treatment.

5.
Adv Sci (Weinh) ; : e2401716, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840455

ABSTRACT

The demand for miniaturized and integrated multifunctional devices drives the progression of high-performance infrared photodetectors for diverse applications, including remote sensing, air defense, and communications, among others. Nonetheless, infrared photodetectors that rely solely on single low-dimensional materials often face challenges due to the limited absorption cross-section and suboptimal carrier mobility, which can impair sensitivity and prolong response times. Here, through experimental validation is demonstrated, precise control over energy band alignment in a type-II van der Waals heterojunction, comprising vertically stacked 2D Ta2NiSe5 and the topological insulator Bi2Se3, where the configuration enables polarization-sensitive, wide-spectral-range photodetection. Experimental evaluations at room temperature reveal that the device exhibits a self-powered responsivity of 0.48 A·W-1, a specific directivity of 3.8 × 1011 cm·Hz1/2·W-1, a response time of 151 µs, and a polarization ratio of 2.83. The stable and rapid photoresponse of the device underpins the utility in infrared-coded communication and dual-channel imaging, showing the substantial potential of the detector. These findings articulate a systematic approach to developing miniaturized, multifunctional room-temperature infrared detectors with superior performance metrics and enhanced capabilities for multi-information acquisition.

6.
Brain Behav ; 14(5): e3515, 2024 May.
Article in English | MEDLINE | ID: mdl-38702895

ABSTRACT

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.


Subject(s)
Hippocampus , Melatonin , Memory Disorders , Neuronal Plasticity , Sleep Deprivation , Animals , Melatonin/pharmacology , Melatonin/administration & dosage , Sleep Deprivation/complications , Sleep Deprivation/drug therapy , Sleep Deprivation/physiopathology , Mice , Male , Hippocampus/metabolism , Hippocampus/drug effects , Female , Memory Disorders/drug therapy , Memory Disorders/etiology , Memory Disorders/physiopathology , Neuronal Plasticity/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Pregnancy , Maternal Deprivation , Cognitive Dysfunction/etiology , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/physiopathology , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Brain-Derived Neurotrophic Factor/metabolism , Neuroinflammatory Diseases/drug therapy
7.
Nano Lett ; 24(20): 6043-6050, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38717152

ABSTRACT

Studying antiferromagnetic domains is essential for fundamental physics and potential spintronics applications. Despite their importance, few systematic studies have been performed on antiferromagnet (AFM) domains with high spatial resolution in van der Waals (vdW) materials, and direct probing of the Néel vectors remains challenging. In this work, we found multidomain states in the vdW AFM NiPS3, a material extensively investigated for its unique magnetic exciton. We employed photoemission electron microscopy combined with the X-ray magnetic linear dichroism (XMLD-PEEM) to image the NiPS3's magnetic structure. The nanometer-spatial resolution of XMLD-PEEM allows us to determine local Néel vector orientations and discover thermally fluctuating Néel vectors that are independent of the crystal symmetry even at 65 K, well below the TN of 155 K. We demonstrate that an in-plane orbital moment of the Ni ion is responsible for the weak magnetocrystalline anisotropy. The observed thermal fluctuations of the antiferromagnetic domains may explain the broadening of magnetic exciton peaks at higher temperatures.

8.
Article in English | MEDLINE | ID: mdl-38771689

ABSTRACT

Advancements in adapting deep convolution architectures for spiking neural networks (SNNs) have significantly enhanced image classification performance and reduced computational burdens. However, the inability of multiplication-free inference (MFI) to align with attention and transformer mechanisms, which are critical to superior performance on high-resolution vision tasks, imposes limitations on these gains. To address this, our research explores a new pathway, drawing inspiration from the progress made in multilayer perceptrons (MLPs). We propose an innovative spiking MLP architecture that uses batch normalization (BN) to retain MFI compatibility and introduce a spiking patch encoding (SPE) layer to enhance local feature extraction capabilities. As a result, we establish an efficient multistage spiking MLP network that blends effectively global receptive fields with local feature extraction for comprehensive spike-based computation. Without relying on pretraining or sophisticated SNN training techniques, our network secures a top-one accuracy of 66.39% on the ImageNet-1K dataset, surpassing the directly trained spiking ResNet-34 by 2.67%. Furthermore, we curtail computational costs, model parameters, and simulation steps. An expanded version of our network compares with the performance of the spiking VGG-16 network with a 71.64% top-one accuracy, all while operating with a model capacity 2.1 times smaller. Our findings highlight the potential of our deep SNN architecture in effectively integrating global and local learning abilities. Interestingly, the trained receptive field in our network mirrors the activity patterns of cortical cells.

9.
Plant Physiol Biochem ; 210: 108637, 2024 May.
Article in English | MEDLINE | ID: mdl-38670031

ABSTRACT

The MADS-box gene family is a transcription factor family that is widely expressed in plants. It controls secondary metabolic processes in plants and encourages the development of tissues like roots and flowers. However, the phylogenetic analysis and evolutionary model of MADS-box genes in Fagopyrum species has not been reported yet. This study identified the MADS-box genes of three buckwheat species at the whole genome level, and conducted systematic evolution and physicochemical analysis. The results showed that these genes can be divided into four subfamilies, with fragment duplication being the main way for the gene family expansion. During the domestication process from golden buckwheat to tartary buckwheat and the common buckwheat, the Ka/Ks ratio indicated that most members of the family experienced strong purification selection pressure, and with individual gene pairs experiencing positive selection. In addition, we combined the expression profile data of the MADS genes, mGWAS data, and WGCNA data to mine genes FdMADS28/48/50 that may be related to flavonoid metabolism. The results also showed that overexpression of FdMADS28 could increase rutin content by decreasing Kaempferol pathway content in hairy roots, and increase the resistance and growth of hairy roots to PEG and NaCl. This study systematically analyzed the evolutionary relationship of MADS-box genes in the buckwheat species, and elaborated on the expression patterns of MADS genes in different tissues under biotic and abiotic stresses, laying an important theoretical foundation for further elucidating their role in flavonoid metabolism.


Subject(s)
Evolution, Molecular , Fagopyrum , Flavonoids , Gene Expression Regulation, Plant , Genes, Plant , MADS Domain Proteins , Fagopyrum/genetics , Fagopyrum/metabolism , Flavonoids/metabolism , MADS Domain Proteins/genetics , MADS Domain Proteins/metabolism , Phylogeny
10.
Coron Artery Dis ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682469

ABSTRACT

BACKGROUND: The optimal timing for percutaneous coronary intervention (PCI) in patients undergoing transcatheter aortic valve replacement (TAVR) remains uncertain. This research aims to evaluate the results of patients diagnosed with severe aortic valve stenosis and coronary artery disease who undergo either simultaneous or staged PCI therapy during TAVR procedures. METHODS: We retrieved all relevant studies from our self-constructed databases up to January 2, 2024, encompassing databases such as Embase, Medline, Cochrane Library, and PubMed. RESULTS: A total of nine studies were included, and the results showed that both surgical modalities had good safety profiles in the early and long-term stages. For early endpoint events, the risk of all-cause mortality and major bleeding within 30 years was similar in the staged TAVR + PCI and the contemporaneous TAVR + PCI (P > 0.05). Additionally, the risk of myocardial infarction, stroke, acute kidney injury and pacemaker implantation within 30 days or perioperatively is similar (P > 0.05). For long-term endpoint events, the risk of all-cause mortality, myocardial infarction and stroke was similar in the two groups at ≥2 years (P > 0.05). CONCLUSION: In patients undergoing TAVR who required coronary revascularization, no significant differences were observed in the early and long-term outcomes between those receiving concurrent TAVR and PCI versus staged surgery.

11.
Brain Behav ; 14(5): e3508, 2024 May.
Article in English | MEDLINE | ID: mdl-38688894

ABSTRACT

BACKGROUND: The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. METHODS: Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. RESULTS: SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice. CONCLUSION: Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.


Subject(s)
Antioxidants , Mice, Inbred C57BL , Mitochondria , Oligopeptides , Sleep Deprivation , Animals , Mice , Sleep Deprivation/drug therapy , Sleep Deprivation/complications , Sleep Deprivation/metabolism , Oligopeptides/pharmacology , Oligopeptides/administration & dosage , Male , Mitochondria/drug effects , Mitochondria/metabolism , Antioxidants/pharmacology , Hippocampus/metabolism , Hippocampus/drug effects , Memory Disorders/drug therapy , Memory Disorders/etiology , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Sirtuin 1/metabolism , Disease Models, Animal
12.
J Biochem Mol Toxicol ; 38(4): e23698, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38501767

ABSTRACT

Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti-inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation-induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty-two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro-inflammatory cytokines and Sirt1/miR-134 pathway-related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation-induced learning and memory impairment, elevated interleukin-1ß, interleukin-6, and tumor necrosis factor-α levels, and decreased brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin levels by activating the Sirt1/miR-134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation-induced cognitive dysfunction by reducing pro-inflammatory cytokines and improving synaptic function via the Sirt1/miR-134 pathway.


Subject(s)
Cognitive Dysfunction , MicroRNAs , Male , Mice , Animals , Resveratrol/pharmacology , Sleep Deprivation/complications , Sleep Deprivation/metabolism , Sirtuin 1/metabolism , Dimethyl Sulfoxide/metabolism , Dimethyl Sulfoxide/pharmacology , Mice, Inbred C57BL , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/prevention & control , Hippocampus/metabolism , MicroRNAs/metabolism , Cytokines/metabolism , Cognition
13.
J Phys Condens Matter ; 36(23)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38417165

ABSTRACT

Perpendicular magnetic anisotropy (PMA) of magnets is paramount for electrically controlled spintronics due to their intrinsic potentials for higher memory density, scalability, thermal stability and endurance, surpassing an in-plane magnetic anisotropy (IMA). Nickel film is a long-lived fundamental element ferromagnet, yet its electrical transport behavior associated with magnetism has not been comprehensively studied, hindering corresponding spintronic applications exploiting nickel-based compounds. Here, we systematically investigate the highly versatile magnetism and corresponding transport behavior of nickel films. As the thickness reduces within the general thickness regime of a magnet layer for a memory device, the hardness of nickel films' ferromagnetic loop of anomalous Hall effect increases and then decreases, reflecting the magnetic transitions from IMA to PMA and back to IMA. Additionally, the square ferromagnetic loop changes from a hard to a soft one at rising temperatures, indicating a shift from PMA to IMA. Furthermore, we observe a butterfly magnetoresistance resulting from the anisotropic magnetoresistance effect, which evolves in conjunction with the thickness and temperature-dependent magnetic transformations as a complementary support. Our findings unveil the rich magnetic dynamics and most importantly settle down the most useful guiding information for current-driven spintronic applications based on nickel film: The hysteresis loop is squarest for the ∼8 nm-thick nickel film, of highest hardness withRxyr/Rxys∼ 1 and minimumHs-Hc, up to 125 K; otherwise, extra care should be taken for a different thickness or at a higher temperature.

14.
IEEE Trans Image Process ; 33: 1614-1626, 2024.
Article in English | MEDLINE | ID: mdl-38358876

ABSTRACT

We present a systematic approach for training and testing structural texture similarity metrics (STSIMs) so that they can be used to exploit texture redundancy for structurally lossless image compression. The training and testing is based on a set of image distortions that reflect the characteristics of the perturbations present in natural texture images. We conduct empirical studies to determine the perceived similarity scale across all pairs of original and distorted textures. We then introduce a data-driven approach for training the Mahalanobis formulation of STSIM based on the resulting annotated texture pairs. Experimental results demonstrate that training results in significant improvements in metric performance. We also show that the performance of the trained STSIM metrics is competitive with state of the art metrics based on convolutional neural networks, at substantially lower computational cost.

15.
Cancers (Basel) ; 16(3)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38339378

ABSTRACT

In the absence of early detection and initial treatment, prostate cancer often progresses to an advanced stage, frequently spreading to the bones and significantly impacting patients' well-being and healthcare resources. Therefore, managing patients with prostate cancer that has spread to the bones often involves using bone-targeted medications like bisphosphonates and denosumab to enhance bone structure and minimize skeletal complications. Additionally, researchers are studying the tumor microenvironment and biomarkers to understand the mechanisms and potential treatment targets for bone metastases in prostate cancer. A literature search was conducted to identify clinical studies from 2013 to 2023 that focused on pain, performance status, or quality of life as primary outcomes. The analysis included details such as patient recruitment, prior palliative therapies, baseline characteristics, follow-up, and outcome reporting. The goal was to highlight the advancements and trends in bone metastasis research in prostate cancer over the past decade, with the aim of developing strategies to prevent and treat bone metastases and improve the quality of life and survival rates for prostate cancer patients.

16.
Genome Biol ; 25(1): 61, 2024 02 27.
Article in English | MEDLINE | ID: mdl-38414075

ABSTRACT

BACKGROUND: Tartary buckwheat, Fagopyrum tataricum, is a pseudocereal crop with worldwide distribution and high nutritional value. However, the origin and domestication history of this crop remain to be elucidated. RESULTS: Here, by analyzing the population genomics of 567 accessions collected worldwide and reviewing historical documents, we find that Tartary buckwheat originated in the Himalayan region and then spread southwest possibly along with the migration of the Yi people, a minority in Southwestern China that has a long history of planting Tartary buckwheat. Along with the expansion of the Mongol Empire, Tartary buckwheat dispersed to Europe and ultimately to the rest of the world. The different natural growth environments resulted in adaptation, especially significant differences in salt tolerance between northern and southern Chinese Tartary buckwheat populations. By scanning for selective sweeps and using a genome-wide association study, we identify genes responsible for Tartary buckwheat domestication and differentiation, which we then experimentally validate. Comparative genomics and QTL analysis further shed light on the genetic foundation of the easily dehulled trait in a particular variety that was artificially selected by the Wa people, a minority group in Southwestern China known for cultivating Tartary buckwheat specifically for steaming as a staple food to prevent lysine deficiency. CONCLUSIONS: This study provides both comprehensive insights into the origin and domestication of, and a foundation for molecular breeding for, Tartary buckwheat.


Subject(s)
Fagopyrum , Domestication , Fagopyrum/genetics , Gene Expression Profiling , Genome-Wide Association Study , Genomics , Phylogeny
17.
Viral Immunol ; 37(1): 44-56, 2024.
Article in English | MEDLINE | ID: mdl-38324005

ABSTRACT

Hantaan virus (HTNV) is prevalent in Eurasia. It causes hemorrhagic fever with renal syndrome (HFRS). Long noncoding RNAs (lncRNAs) play key roles in regulating innate immunity. Among these, lncRNA negative regulator of interferon response (NRIR) was reported as an inhibitor of several interferon (IFN)-stimulated genes. Our results showed that: NRIR expression was upregulated by HTNV infection in a type I IFN-dependent manner. The expression of NRIR in CD14+ monocytes from HFRS patients in acute phase was significantly higher than that in convalescent phase and healthy controls. HTNV infection in some HTNV-compatible cells was promoted by NRIR. NRIR negatively regulated innate immunity, especially IFITM3 expression. Localized in the nucleus, NRIR bound with HNRNPC, and knockdown of HNRNPC significantly weakened the effect of NRIR in promoting HTNV infection and restored IFITM3 expression. These results indicated that NRIR regulates the innate immune response against HTNV infection possibly through its interaction with HNRNPC and its influence on IFITM3.


Subject(s)
Hantaan virus , Hemorrhagic Fever with Renal Syndrome , Interferon Type I , RNA, Long Noncoding , Humans , Hantaan virus/genetics , RNA, Long Noncoding/genetics , Immunity, Innate , Membrane Proteins , RNA-Binding Proteins/genetics
18.
Cell Commun Signal ; 22(1): 45, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38233864

ABSTRACT

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Lung Neoplasms/pathology , Mutation/genetics , Protein Kinase Inhibitors/pharmacology , Retinoblastoma Binding Proteins/genetics , Smad4 Protein/genetics , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Ubiquitin-Protein Ligases/genetics
19.
Aging (Albany NY) ; 16(2): 1128-1144, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38231482

ABSTRACT

BACKGROUND: Early life stress can cause cognitive impairment in aged offspring. Environmental enrichment (EE) is considered to be an effective non-pharmacological treatment for improving cognitive decline. The aim of this research was to evaluate the effect of EE, on cognitive impairment in aged offspring induced by maternal sleep deprivation (MSD) and the underlying mechanisms involved to investigate its potential value in clinical practice. METHODS: CD-1 damns were subjected or not to sleep deprivation during late gestation. Twenty-one days after birth, the offspring were assigned to standard or EE cages. At 18 months-old, the learning and memory function of the offspring mice was evaluated using Morris water maze. The hippocampal and prefrontal cortical levels of protein, gene, proinflammation cytokines, and oxidative stress indicators was examined by Western blot, real-time polymerase chain reaction, enzyme linked immunosorbent assay, and biochemical assays. RESULTS: Offspring in MSD group exhibited declined learning and memory abilities compared with control animals. Moreover, the hippocampal and prefrontal cortical levels of Sirtuin1 (Sirt1), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), postsynaptic density protein-95, and synaptophysin were lower and those of proinflammation cytokines higher in the MSD group; meanwhile, the superoxide dismutase content was higher and the malondialdehyde and reactive oxygen species contents were lower. However, these deleterious changes were ameliorated by exposure to EE. CONCLUSIONS: EE attenuates MSD-induced cognitive impairment, oxidative stress, and neuroinflammation and reverses the reduction in synaptic protein levels in aged offspring mice via the Sirt1/PGC-1α pathway.


Subject(s)
Cognitive Dysfunction , Sleep Deprivation , Mice , Animals , Pregnancy , Female , Sleep Deprivation/complications , Sleep Deprivation/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/therapy , Cognitive Dysfunction/metabolism , Mitochondria/metabolism , Cytokines/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
20.
Sci Total Environ ; 915: 170129, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38242456

ABSTRACT

Decabromodiphenyl ether (BDE-209) is one of the most widely used flame retardants that can infect domestic and wildlife through contaminated feed. Nano­selenium (Nano-Se) has the advantage of enhancing the anti-oxidation of cells. Nonetheless, it remains uncertain whether Nano-Se can alleviate vascular Endothelial cells damage caused by BDE-209 exposure in chickens. Therefore, we established a model with 60 1-day-old chickens, and administered BDE-209 intragastric at a ratio of 400 mg/kg bw/d, and mixed Nano-Se intervention at a ratio of 1 mg/kg in the feed. The results showed that BDE-209 could induce histopathological and ultrastructural changes. Additionally, exposure to BDE-209 led to cardiovascular endoplasmic reticulum stress (ERS), oxidative stress and thioredoxin-interacting protein (TXNIP)-pyrin domain-containing protein 3 (NLRP3) pathway activation, ultimately resulting in pyroptosis. Using the ERS inhibitor 4-PBA in Chicken arterial endothelial cells (PAECs) can significantly reverse these changes. The addition of Nano-Se can enhance the body's antioxidant capacity, inhibit the activation of NLRP3 inflammasome, and reduce cellular pyroptosis. These results suggest that Nano-Se can alleviate the pyroptosis of cardiovascular endothelial cells induced by BDE-209 through ERS-TXNIP-NLRP3 pathway. This study provides new insights into the toxicity of BDE-209 in the cardiovascular system and the therapeutic effects of Nano-Se.


Subject(s)
Cardiovascular System , Halogenated Diphenyl Ethers , Selenium , Animals , Endothelial Cells/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Chickens/metabolism , Pyroptosis , Selenium/metabolism , Endoplasmic Reticulum Stress
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