ABSTRACT
The tumor suppressor p53 is critical for tumor suppression, but the regulatory role of p53 in alcohol-induced fatty liver remains unclear. Here, we show a role for p53 in regulating ethanol metabolism via acetaldehyde dehydrogenase 2 (ALDH2), a key enzyme responsible for the oxidization of alcohol. By repressing ethanol oxidization, p53 suppresses intracellular levels of acetyl-CoA and histone acetylation, leading to the inhibition of the stearoyl-CoA desaturase-1 (SCD1) gene expression. Mechanistically, p53 directly binds to ALDH2 and prevents the formation of its active tetramer and indirectly limits the production of pyruvate that promotes the activity of ALDH2. Notably, p53-deficient mice exhibit increased lipid accumulation, which can be reversed by ALDH2 depletion. Moreover, liver-specific knockdown of SCD1 alleviates ethanol-induced hepatic steatosis caused by p53 loss. By contrast, overexpression of SCD1 in liver promotes ethanol-induced fatty liver development in wild-type mice, while it has a mild effect on p53-/- or ALDH2-/- mice. Overall, our findings reveal a previously unrecognized function of p53 in alcohol-induced fatty liver and uncover pyruvate as a natural regulator of ALDH2.
Subject(s)
Aldehyde Dehydrogenase, Mitochondrial , Fatty Liver, Alcoholic , Fatty Liver , Tumor Suppressor Protein p53 , Animals , Mice , Aldehyde Dehydrogenase, Mitochondrial/genetics , Aldehyde Dehydrogenase, Mitochondrial/metabolism , Ethanol/toxicity , Ethanol/metabolism , Fatty Liver/genetics , Fatty Liver/metabolism , Fatty Liver, Alcoholic/genetics , Fatty Liver, Alcoholic/metabolism , Liver/metabolism , Pyruvates/metabolism , Pyruvates/pharmacology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
Ribbon synapses of inner hair cells (IHCs) are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles (SVs), however, remains elusive. This study showed that hair cell knock-out of murine Dmxl2, whose human homolog is responsible for nonsyndromic sensorineural hearing loss DFNA71, resulted in auditory synaptopathy by impairing synaptic endocytosis and recycling. The mutant mice in the C57BL/6J background of either sex had mild hearing loss with severely diminished wave I amplitude of the auditory brainstem response. Membrane capacitance measurements of the IHCs revealed deficiency in sustained synaptic exocytosis and endocytic membrane retrieval. Consistent with the electrophysiological findings, 3D electron microscopy reconstruction showed reduced reserve pool of SVs and endocytic compartments, while the membrane-proximal and ribbon-associated vesicles remain intact. Our results propose an important role of DMXL2 in hair cell endocytosis and recycling of the SVs.
Subject(s)
Endocytosis , Hair Cells, Auditory, Inner , Nerve Tissue Proteins , Synaptic Vesicles , Animals , Female , Male , Mice , Endocytosis/physiology , Evoked Potentials, Auditory, Brain Stem/physiology , Exocytosis/physiology , Hair Cells, Auditory, Inner/physiology , Mice, Inbred C57BL , Mice, Knockout , Synaptic Vesicles/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolismABSTRACT
BACKGROUND: Lower respiratory tract infection (LRTI) has long been an important threat to people's life and health, so the rapid diagnosis of LRTI is of great significance in clinical treatment. In recent years, the development of the sequencing technology provides a new direction for the rapid diagnosis of LRTI. In this review, the advantages and disadvantages of second-generation sequencing techniques represented by metagenomics next-generation sequencing (mNGS) and droplet digital polymerase chain reaction (ddPCR) in LRTI were reviewed. Furthermore, it offers insights into the future trajectory of this technology, highlighting its potential to revolutionise the field of respiratory infection diagnostics. OBJECTIVE: This review summarises developments in mechanistic research of second-generation sequencing technology their relationship with clinical practice, providing insights for future research. METHODS: Authors conducted a search on PubMed and Web of Science using the professional terms 'Lower respiratory tract infection' and 'droplet digital polymerase chain reaction' and 'metagenomics next generation sequencing'. The obtained literature was then roughly categorised based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. RESULTS: Different studies discussed the application of second-generation sequencing technology in LRTI from different angles, including the detection of pathogens of LRTI by mNGS and ddPCR, the prediction ability of drug-resistant bacteria, and comparison with traditional methods. We try to analyse the advantages and disadvantages of the second-generation sequencing technology by combing the research results of mNGS and ddPCR. In addition, the development direction of the second-generation sequencing technology is prospected.
Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Respiratory Tract Infections , Humans , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/microbiology , High-Throughput Nucleotide Sequencing/methods , Metagenomics/methods , Polymerase Chain Reaction/methodsABSTRACT
The previous research has focused on the suppressive effects of Erianin on tumor progression, but its impact on cancer stemness has not been reported. This study aimed to investigate the effects of Erianin on lung cancer stemness. First, we screened various concentrations Erianin to ensure that it did not affect lung cancer cell viability. Subsequently, we found that Erianin significantly attenuated lung cancer stemness through various analyses, including qRT-PCR, western blot, sphere-formation, and ALDH activity detection. Furthermore, Erianin was shown to enhance chemosensitivity of lung cancer cells. Mechanistically, three inhibitors (cell apoptosis inhibitor, necrosis inhibitor, and ferroptosis inhibitor) were added into lung cancer cells with Erianin treatment, respectively, and we found that Erianin mainly suppressed lung cancer stemness through ferroptosis. Taken together, this study reveals that Erianin has the potential to suppress lung cancer stemness and could be a valuable chemotherapeutic enhancer for lung cancer.
Subject(s)
Bibenzyls , Ferroptosis , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Cell Line, Tumor , Bibenzyls/pharmacology , Cell ProliferationABSTRACT
Studies have shown that vehicle trajectory data are effective for calibrating microsimulation models. Light Detection and Ranging (LiDAR) technology offers high-resolution 3D data, allowing for detailed mapping of the surrounding environment, including road geometry, roadside infrastructures, and moving objects such as vehicles, cyclists, and pedestrians. Unlike other traditional methods of trajectory data collection, LiDAR's high-speed data processing, fine angular resolution, high measurement accuracy, and high performance in adverse weather and low-light conditions make it well suited for applications requiring real-time response, such as autonomous vehicles. This research presents a comprehensive framework for integrating LiDAR sensor data into simulation models and their accurate calibration strategies for proactive safety analysis. Vehicle trajectory data were extracted from LiDAR point clouds collected at six urban signalized intersections in Lubbock, Texas, in the USA. Each study intersection was modeled with PTV VISSIM and calibrated to replicate the observed field scenarios. The Directed Brute Force method was used to calibrate two car-following and two lane-change parameters of the Wiedemann 1999 model in VISSIM, resulting in an average accuracy of 92.7%. Rear-end conflicts extracted from the calibrated models combined with a ten-year historical crash dataset were fitted into a Negative Binomial (NB) model to estimate the model's parameters. In all the six intersections, rear-end conflict count is a statistically significant predictor (p-value < 0.05) of observed rear-end crash frequency. The outcome of this study provides a framework for the combined use of LiDAR-based vehicle trajectory data, microsimulation, and surrogate safety assessment tools to transportation professionals. This integration allows for more accurate and proactive safety evaluations, which are essential for designing safer transportation systems, effective traffic control strategies, and predicting future congestion problems.
ABSTRACT
BACKGROUND: Potentilla anserina L. is rich in various nutrients, active ingredients and unique flavor, comprising a natural nutrition and health food. However, its application in aquatic food has been rarely reported. Therefore, the effects of Potentilla anserina L. powder (PAP) on gel properties and volatile flavor profile of silver carp surimi were investigated. RESULTS: The gel strength and water-holding capacity of the surimi gels were significantly improved (P < 0.05), and the whiteness and cooking loss of all the samples decreased slightly with the increase in PAP content. The addition of PAP shortened the relaxation time (T2) of the surimi gels and converted some of the free water into immobile or bound water, which resulted in a better immobilization of water in the surimi. Scanning electron microscopy images demonstrated that the network of surimi gels with PAP added was denser and had a smoother surface compared to the control. Volatile components (VCs) analysis showed that 33 VCs were identified in the surimi gel samples with different additions of PAP, among which aldehydes, alcohols and esters were the major VCs, accounting for more than 50% of the VCs in the surimi gels. PAP addition reduced the fishy and rancid flavor compounds in surimi gels, such as 1-propanol, 1-octen-3-ol, etc., and promoted the production of aldehydes, alcohols, esters and other flavor substances. CONCLUSION: These results of the present study provide theoretical support for the investigation and development of new nutrient-health-flavored surimi products. © 2024 Society of Chemical Industry.
Subject(s)
Carps , Fish Products , Flavoring Agents , Gels , Potentilla , Taste , Volatile Organic Compounds , Animals , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/analysis , Fish Products/analysis , Gels/chemistry , Flavoring Agents/chemistry , Potentilla/chemistry , Powders/chemistry , Plant Extracts/chemistry , Cooking , HumansABSTRACT
Searching for high effective catalysts has been an endless effort to improve the efficiency of green energy harvesting and degradation of pollutants. In the past decades, tremendous strategies are explored to achieve high effective catalysts, and various theoretical understandings are proposed for the improved activity. As the catalytic reaction occurs at the surface or edge, the unsaturated ions may lead to the fluctuation of spin. Meanwhile, transition metals in catalysts have diverse spin states and may yield the spin effects. Therefore, the role of spin or magnetic moment should be carefully examined. In this review, the recent development of spin catalysts is discussed to give an insightful view on the origins for the improved catalytic activity. First, a brief introduction on the applications and advances in spin-related catalytic phenomena, is given, and then the fundamental principles of spin catalysts and magnetic fields-radical reactions are introduced in the second part. The spin-related catalytic performance reported in oxygen evolution/reduction reaction (OER/ORR) is systematically discussed in the third part, and general rules are summarized accordingly. Finally, the challenges and perspectives are given. This review may provide an insightful understanding of the microscopic mechanisms of catalytic phenomena and guide the design of spin-related catalysts.
ABSTRACT
The identification of structural variations (SVs) and viral integrations in circulating tumor DNA (ctDNA) is a key step in precision oncology that may assist clinicians in treatment selection and monitoring. However, due to the short fragment size of ctDNA, it is challenging to accurately detect low-frequency SVs or SVs involving complex junctions in ctDNA sequencing data. Here, we describe Aperture, a new fast SV caller that applies a unique strategy of $k$-mer-based searching, binary label-based breakpoint detection and candidate clustering to detect SVs and viral integrations with high sensitivity, especially when junctions span repetitive regions. Aperture also employs a barcode-based filter to ensure specificity. Compared with existing methods, Aperture exhibits superior sensitivity and specificity in simulated, reference and real data tests, especially at low dilutions. Additionally, Aperture is able to predict sites of viral integration and identify complex SVs involving novel insertions and repetitive sequences in real patient data. Aperture is freely available at https://github.com/liuhc8/Aperture.
Subject(s)
Circulating Tumor DNA/chemistry , Nucleic Acid Conformation , Virus Integration , Algorithms , Humans , Neoplasms/blood , Neoplasms/geneticsABSTRACT
On the basis of computational ghost imaging (CGI), we present a new imaging technique, feature ghost imaging (FGI), which can convert the color information into distinguishable edge features in retrieved grayscale images. With the edge features extracted by different order operators, FGI can obtain the shape and the color information of objects simultaneously in a single-round detection using one single-pixel detector. The feature distinction of rainbow colors is presented in numerical simulations and the verification of FGI's practical performance is conducted in experiments. Furnishing a new perspective to the imaging of colored objects, our FGI extends the function and the application fields of traditional CGI while sustaining the simplicity of the experimental setup.
ABSTRACT
Owing to the chirality of Weyl nodes characterized by the first Chern number, a Weyl system supports one-way chiral zero modes under a magnetic field, which underlies the celebrated chiral anomaly. As a generalization of Weyl nodes from three-dimensional to five-dimensional physical systems, Yang monopoles are topological singularities carrying nonzero second-order Chern numbers c_{2}=±1. Here, we couple a Yang monopole with an external gauge field using an inhomogeneous Yang monopole metamaterial and experimentally demonstrate the existence of a gapless chiral zero mode, where the judiciously designed metallic helical structures and the corresponding effective antisymmetric bianisotropic terms provide the means for controlling gauge fields in a synthetic five-dimensional space. This zeroth mode is found to originate from the coupling between the second Chern singularity and a generalized 4-form gauge field-the wedge product of the magnetic field with itself. This generalization reveals intrinsic connections between physical systems of different dimensions, while a higher-dimensional system exhibits much richer supersymmetric structures in Landau level degeneracy due to the internal degrees of freedom. Our study offers the possibility of controlling electromagnetic waves by leveraging the concept of higher-order and higher-dimensional topological phenomena.
ABSTRACT
As an emerging imaging technique, computational ghost imaging (CGI) has its unique application in image encryption. However, the long imaging time and high requirement of transmitting data, both in the size of data and vulnerability of lossy compression, limit its application in the practical communications. Using discrete cosine transform to sparse bucket signals of CGI, we here propose a method by transforming the bucket signals from the sensing matrix domain to the space domain, enhancing the ability of the bucket signals (i.e., encrypted image) to resist the lossy compression. Based on the principle of CGI, we first propose to use gradient descent to find an orthogonal matrix as the encryption key, then test the performance of our method at different quality factors and undersampling rates. Both simulations and experimental results demonstrate that our encryption method shows great resistance to the traditional lossy compression methods and has good performance in the undersampling conditions. Our method provides a convenient way to transmit the bucket signals of CGI by the format that involves lossy compression and thus camouflages itself while significantly reducing the amount of data being transmitted.
ABSTRACT
The principle of computational ghost imaging (GI) offers a potential application in optical encryption. Nevertheless, large numbers of keys composed of random or specific patterns set an obstacle to its application. Here, we propose a series of pattern compression methods based on computational GI, in which thousands of patterns are replaced by a single standard image (i.e., two-dimensional data), a sequence of numbers (i.e., one-dimensional data) or the fractional part of an irrational number (i.e., zero-dimensional data). Different pattern compression methods are tested in both simulations and experiments, and their error tolerances in encryption are further discussed. Our proposed methods can greatly reduce the pattern amount and enhance encryption security, which pushes forward the application of computational GI, especially in optical encryption.
ABSTRACT
Single-pixel imaging (SPI) can perceive the world using only a single-pixel detector, but long sampling times with a series of patterns are inevitable for SPI, which is the bottleneck for its practical application. Developing new patterns to reduce the sampling times might provide opportunities to address this challenge. Based on the Kronecker product of Hadamard matrix, we here design a complete set of new patterns, called Gao-Boole patterns, for SPI. Compared to orthogonal Hadamard basis patterns with elements valued as +1 or -1, our Gao-Boole patterns are non-orthogonal ones and the element values are designed as +1 or 0. Using our Gao-Boole patterns, the reconstructed quality of a target image (N × N pixels) is as high as the Hadamard one but only with half pattern numbers of the Hadamard ones, for both full sampling (N2 for Gao-Boole patterns, 2N2 for Hadamard basis patterns) and undersampling cases in experiment. Effectively reducing the patterns numbers and sampling times without sacrificing imaging quality, our designed Gao-Boole patterns provide a superior option for structural patterns in SPI and help to steer SPI toward practical imaging application.
ABSTRACT
The angle-sensitive photonic bandgap (PBG) is one of the typical features of one-dimensional photonic crystals. Based on the phase-variation compensation effect between the dielectric and hyperbolic metamaterials (HMMs), angle-insensitive PBGs can be realized in photonic hypercrystals. However, since hypercrystals are usually constructed using metal components, these angle-insensitive PBGs are mostly limited to narrow bandwidths in visible range. Here, we replace metal with indium tin oxide (ITO) to construct HMMs in the near-infrared range. In these ITO-based HMMs, we experimentally demonstrate the negative refraction of light in transverse magnetic polarization. With this HMM component, we realize a photonic hypercrystal with an angle-insensitive PBG in the wavelength range of 1.15-2.02 µm. These ITO-based hypercrystals with large angle-insensitive PBGs can find applications in near-infrared reflectors or filters.
ABSTRACT
Desulfurization sorbent with a high active component utilization is of importance for the removal of H2S from coal gas at high temperatures. Thus, the hypothesis for producing ZnxCo3-xO4/carbon nanofiber sorbents via the combinations of electrospinning, in situ hydrothermal growth, and carbonization technique has been rationally constructed in this study. ZnxCo3-xO4 nanoparticles derived from metal-organic frameworks are uniformly loaded on the electrospun carbon nanofibers (CNFs) with high dispersion. ZnxCo3-xO4/CNFs sorbents possess the highest breakthrough sulfur adsorption capacity (12.4 g S/100 g sorbent) and an excellent utilization rate of the active component (83.2%). The excellent performance of ZnxCo3-xO4/CNFs can be attributed to the synergetic effect of the hierarchical structure and widely distributed ZnxCo3-xO4 on the CNFs supporter. The decomposition of Zn/Co-ZIFs not only generates the nucleus of oxides but also realizes their physical isolation through the formation of carbon grids on the surface of CNFs, avoiding the aggregation of oxides. Furthermore, ZnxCo3-xO4/CNFs sorbents show an overwhelming superiority over the ZnO/CNFs sorbent, which is attributed to the introduction of Co and then the promotion of the stability of Zn at high temperatures. The presence of Co also accelerates the adsorption of H2S on the active site of the oxide surface. The presented method is beneficial for promoting desulfurization performances and producing sorbents with high utilization of active components.
ABSTRACT
The transformation of methane into high value-added chemicals such as aromatics provides a more desired approach towards sustainable chemistry but remains a critical challenge due to the low selectivity of aromatics and poor stability. Herein, we first report a coupling reaction of CH3 Cl and CO (CCTA) based on methane conversion, which achieves extremely high aromatics selectivity (82.2 %) with the selectivity of BTX up to ca. 60 % over HZSM-5. The promoting effects have been demonstrated on other zeolites especially 10-membered rings (10 MR) zeolites. Multiple characterizations show that 2,3-dimethyl-2-cyclopentene-1-one (DMCPO) is generated from acetyl groups and olefins. Furthermore, isotopic labeling analysis confirms that CO is inserted into the DMCPO and aromatics rings. A new aromatization mechanism is proposed, including the formation of the above intermediates, which conspicuously weakens the hydrogen transfer reaction, leading to a considerable increase of aromatics selectivity and a dramatic drop in alkanes.
ABSTRACT
The selective conversion of methane to high value-added chemicals under mild conditions is of great significance for the commercially viable and sustainable utilization of methane but remains a formidable challenge. Herein, we report a strategy for efficiently converting methane to acetic acid via CH3 Cl as an intermediate. Up to 99.3 % acetic acid and methyl acetate (AA+MA) selectivity was achieved over pyridine-pretreated MOR (MOR-8) under moderate conditions of 523â K and 2.0â MPa. Water, conventionally detrimental to carbonylation reaction over zeolite catalysts, was conducive to the production of AA in the current reaction system. In the 100â h continuous test with the MOR-8 catalyst, the average AA+MA selectivity remained over 98 %. AA was formed by carbonylation of methoxy groups within 8-membered rings of MOR followed by hydrolysis. This strategy provided an approach for highly efficient utilization of methane to oxygenates under mild reaction conditions.
ABSTRACT
The first synthesis of highly strained spirocyclobutane-pyrrolines via a palladium-catalyzed tandem Narasaka-Heck/C(sp3 or sp2)-H activation reaction is reported here. The key step in this transformation is the activation of a δ-C-H bond via an in situ generated σ-alkyl-Pd(II) species to form a five-membered spiro-palladacycle intermediate. The concerted metalation-deprotonation (CMD) process, rate-determining step, and energy barrier of the entire reaction were explored by density functional theory (DFT) calculations. Moreover, a series of control experiments was conducted to probe the rate-determining step and reversibility of the C(sp3)-H activation step.
ABSTRACT
BACKGROUND: Osteosarcoma is a common malignant tumor in adolescents with a low 5-year survival rate. Dexmedetomidine (DEX) has been widely used for surgery of osteosarcoma patients. MiR-520a-3p and YOD1 expression was abnormal in osteosarcoma cells. However, whether DEX affects osteosarcoma progression via miR-520a-3p-YOD1 interactome needs to be explored. METHODS: We detected osteosarcoma cells biological behavior by CCK-8 assay, BrdU assay, cell adhesion assay, and apoptosis assay, respectively. The miR-520a-3p and YOD1 levels was explored in osteosarcoma cell lines by RT-qPCR or western blotting assay. RESULTS: In this study, we found that DEX treating osteosarcoma cells inhibited cell viability, proliferation and adhesion, while it promoted cell apoptosis. Moreover, miR-520a-3p targeting to YOD1 also functionally repressed cell malignancy in osteosarcoma cells. Notably, DEX treatment could inhibit YOD1 expression via upregulating miR-520a-3p, thereby suppressing cell malignancy in osteosarcoma. CONCLUSIONS: Our study first revealed that DEX inhibited malignancy of osteosarcoma cells via miR-520a-3p/YOD1 axis.
Subject(s)
Bone Neoplasms/drug therapy , Dexmedetomidine/pharmacology , MicroRNAs/genetics , Osteosarcoma/drug therapy , Thiolester Hydrolases/antagonists & inhibitors , Analgesics, Non-Narcotic/pharmacology , Apoptosis/drug effects , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Endopeptidases/metabolism , Humans , MicroRNAs/metabolism , Osteosarcoma/genetics , Osteosarcoma/metabolism , Signal Transduction/drug effects , Thiolester Hydrolases/metabolismABSTRACT
Current lithium-ion battery technology is approaching the theoretical energy density limitation, which is challenged by the increasing requirements of ever-growing energy storage market of electric vehicles, hybrid electric vehicles, and portable electronic devices. Although great progresses are made on tailoring the electrode materials from methodology to mechanism to meet the practical demands, sluggish mass transport, and charge transfer dynamics are the main bottlenecks when increasing the areal/volumetric loading multiple times to commercial level. Thus, this review presents the state-of-the-art developments on rational design of the commercialization-driven electrodes for lithium batteries. First, the basic guidance and challenges (such as electrode mechanical instability, sluggish charge diffusion, deteriorated performance, and safety concerns) on constructing the industry-required high mass loading electrodes toward commercialization are discussed. Second, the corresponding design strategies on cathode/anode electrode materials with high mass loading are proposed to overcome these challenges without compromising energy density and cycling durability, including electrode architecture, integrated configuration, interface engineering, mechanical compression, and Li metal protection. Finally, the future trends and perspectives on commercialization-driven electrodes are offered. These design principles and potential strategies are also promising to be applied in other energy storage and conversion systems, such as supercapacitors, and other metal-ion batteries.