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"Chen, Zelin"
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Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents
The pathological mechanisms of radiation ulcer remain unsolved and there is currently no effective medicine. Here, we demonstrate that persistent DNA damage foci and cell senescence are involved in radiation ulcer development. Further more, we identify cordycepin, a natural nucleoside analogue, as a potent drug to block radiation ulcer (skin, intestine, tongue) in rats/mice by preventing cell senescence through the increase of NRF2 nuclear expression (the assay used is mainly on skin). Finally, cordycepin is also revealed to activate AMPK by binding with the α1 and γ1 subunit near the autoinhibitory domain of AMPK, then promotes p62-dependent autophagic degradation of Keap1, to induce NRF2 dissociate from Keap1 and translocate to the nucleus. Taken together, our findings identify cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents, and activation of AMPK or NRF2 may thus represent therapeutic targets for preventing cell senescence and radiation ulcer.
Radiation damage causes DNA foci to form and senescence, causing ulcers. Here, the authors show that a naturally occurring adenosine analogue, cordycepin, prevents cell senescence via an increase in AMPK/NRF2, so blocking ulcers caused by radiation on skin/intestine/tongue damage in rodents.
Journal Article
A Two-Stage Framework for Sensor Selection and Geolocation for eVTOL Emergency Localization Using HF Skywaves
High-Frequency (HF) geolocation is crucial for emergency search and rescue operations and for re-geolocation of missing targets. This paper proposes a two-stage (Receiver selection then geolocation with Random Spatial Spectrum (RSS)) framework with HF skywave propagation as the main link, which is suitable for scenarios where the electric Vertical Take-off and Landing (eVTOL) aircraft loses contact, crashes, or has communication interruption after a malfunction. First, stage A employs two receiver selection paths. One is selection with unknown biases, which combines geometric observability to determine receiver selection. The other is selection with bias priors, which introduces non-line-of-sight bias priors and robust weighting to improve availability. Secondly, stage B constructs RSS-based geolocation using grid objective function matching to alleviate the sensitivity of explicit time difference estimation to noise and model mismatch, thereby maintaining robustness under non-line-of-sight (NLOS) conditions. Finally, simulation and actual measurements demonstrate that the “select first, geolocation later” approach achieves superior overall performance compared to direct geolocation without receiver selection. This study provides a methodological basis and initial field evidence for HF skywave-based emergency eVTOL geolocation.
Journal Article
The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation
Inflammation plays a significant role in the occurrence and development of multiple diseases. This study comprehensively reviews and presents literature from the last five years, showing that acupuncture indeed exerts strong anti-inflammatory effects in multiple biological systems, namely, the immune, digestive, respiratory, nervous, locomotory, circulatory, endocrine, and genitourinary systems. It is well known that localized acupuncture-mediated anti-inflammatory effects involve the regulation of multiple populations and functions of immune cells, including macrophages, granulocytes, mast cells, and T cells. In acupuncture stimulation, macrophages transform from the M1 to the M2 phenotype and the negative TLR4 regulator PPARγ is activated to inhibit the intracellular TLR/MyD88 and NOD signaling pathways. The downstream IκBα/NF-κB and P38 MAPK pathways are subsequently inhibited by acupuncture, followed by suppressed production of inflammasome and proinflammatory mediators. Acupuncture also modulates the balance of helper T cell populations. Furthermore, it inhibits oxidative stress by enhancing SOD activity via the Nrf2/HO-1 pathway and eliminates the generation of oxygen free radicals, thereby preventing inflammatory cell infiltration. The anti-inflammatory effects of acupuncture on different biological systems are also specific to individual organ microenvironments. As part of its anti-inflammatory action, acupuncture deforms connective tissue and upregulates the secretion of various molecules in acupoints, further activating the NF-κB, MAPK, and ERK pathways in mast cells, fibroblasts, keratinocytes, and monocytes/macrophages. The somatic afferents present in acupuncture-activated acupoints also convey sensory signals to the spinal cord, brainstem, and hypothalamic neurons. Upon information integration in the brain, acupuncture further stimulates multiple neuro-immune pathways, including the cholinergic anti-inflammatory, vagus-adrenal medulla-dopamine, and sympathetic pathways, as well as the hypothalamus-pituitary-adrenal axis, ultimately acting immune cells via the release of crucial neurotransmitters and hormones. This review provides a scientific and reliable basis and viewpoints for the clinical application of acupuncture in various inflammatory conditions.
Journal Article
A high-throughput functional genomics workflow based on CRISPR/Cas9-mediated targeted mutagenesis in zebrafish
The Burgess laboratory describes their functional genomics pipeline based on CRISPR/Cas9-targeted mutagenesis in zebrafish. The system is scalable, enabling phenotypic screening of hundreds of targeted mutants.
The zebrafish is a popular model organism for studying development and disease, and genetically modified zebrafish provide an essential tool for functional genomic studies. Numerous publications have demonstrated the efficacy of gene targeting in zebrafish using CRISPR/Cas9, and they have included descriptions of a variety of tools and methods for guide RNA synthesis and mutant identification. However, most of the published techniques are not readily scalable to increase throughput. We recently described a CRISPR/Cas9-based high-throughput mutagenesis and phenotyping pipeline in zebrafish. Here, we present a complete workflow for this pipeline, including target selection; cloning-free single-guide RNA (sgRNA) synthesis; microinjection; validation of the target-specific activity of the sgRNAs; founder screening to identify germline-transmitting mutations by fluorescence PCR; determination of the exact lesion by Sanger or next-generation sequencing (including software for analysis); and genotyping in the F
1
or subsequent generations. Using these methods, sgRNAs can be evaluated in 3 d, zebrafish germline-transmitting mutations can be identified within 3 months and stable lines can be established within 6 months. Realistically, two researchers can target tens to hundreds of genes per year using this protocol.
Journal Article
Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages
Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.
Adipose tissue macrophages are central to controlling inflammation in the context of obesity. Here the authors present a new infrared dye (IR-61) that accumulates in the mitochondria of these cells resulting in anti-inflammatory effects that counter obesity-associated pathology in mice.
Journal Article
Femtosecond Laser Fabrication of Wettability-Functional Surfaces: A Review of Materials, Structures, Processing, and Applications
Wettability-functional surfaces are crucial in both theoretical investigation and engineering applications. Compared to traditional micro/nano fabrication methods (such as ion etching, sol–gel, chemical vapor deposition, template techniques, and self-assembly), femtosecond laser processing has unique advantages, such as unmatched precision, flexible controllability, and material adaptability, widely used for the fabrication of wettability-functional surfaces. This paper systematically discusses the principle and advancement of femtosecond laser micro/nano processing in regulating surface wettability and analyzes the laser modulation mechanisms and structural design strategies for wettability-functional surfaces on various materials. Additionally, this paper reviews the practical applications of femtosecond laser-based wettability-functional surfaces in environmental engineering, aerospace, and biomedical fields, while highlighting the challenges and future directions for femtosecond laser processing of wettability-functional surfaces.
Journal Article
Design and Research on the Variable Polar Distance of the Double-Sided Linear Induction Motor for Electromagnetic Catapult
According to the special technical requirements of carrier-based aircraft catapults, this paper describes the design of a variable pole distance bilateral linear induction motor. When the traditional constant pole motor is used as the catapult of carrier-based aircraft, the current frequency continues to increase during the catapult process, which greatly aggravates the burden of the motor. Therefore, we propose a variable pole length primary double-sided linear induction motor structure. Compared with the traditional constant pole motor structure, this structure can gradually increase the pole distance with an increase in speed when the current frequency remains unchanged. In contrast, the variable pole distance method with a current frequency of 200 Hz has a pole distance of 0.262 m when the displacement is 10 m, and the pole distance increases to 0.352 m when the displacement is 100 m. By maintaining a constant current frequency, this method effectively reduces the control complexity at high speed. Through the theoretical analysis and research calculation conducted on the designed motor, a finite element simulation model was also established by ANSYS 14.0, and the influence of the change in the pole distance on the performance of the motor was analyzed. The magnetic field line and magnetic density distribution of the motor are simulated and analyzed, and the validity of the theoretical calculation is verified.
Journal Article
Global tissue transcriptomic analysis to improve genome annotation and unravel skin pigmentation in goldfish
Goldfish is an ornamental fish with diverse phenotypes. However, the limited genomic resources of goldfish hamper our understanding of the genetic basis for its phenotypic diversity. To provide enriched genomic resources and infer possible mechanisms underlying skin pigmentation, we performed a large-scale transcriptomic sequencing on 13 adult goldfish tissues, larvae at one- and three-days post hatch, and skin tissues with four different color pigmentation. A total of 25.52 Gb and 149.80 Gb clean data were obtained using the PacBio and Illumina platforms, respectively. Onto the goldfish reference genome, we mapped 137,674 non-redundant transcripts, of which 5.54% was known isoforms and 78.53% was novel isoforms of the reference genes, and the remaining 21,926 isoforms are novel isoforms of additional new genes. Both skin-specific and color-specific transcriptomic analyses showed that several significantly enriched genes were known to be involved in melanogenesis, tyrosine metabolism, PPAR signaling pathway, folate biosynthesis metabolism and so on. Thirteen differentially expressed genes across different color skins were associated with melanogenesis and pteridine synthesis including
mitf
,
ednrb
,
mc1r
,
tyr
,
mlph
and
gch1
, and xanthophore differentiation such as
pax7
,
slc2a11
and
slc2a15
. These transcriptomic data revealed pathways involved in goldfish pigmentation and improved the gene annotation of the reference genome.
Journal Article
Establishment of reverse genetics systems for Colorado tick fever virus
The Colorado tick fever virus (CTFV), which has 12-segmented double-stranded RNA genomes, is a pathogenic arbovirus that causes severe diseases in humans. However, little progress has been made in the analysis of replication mechanisms and pathogenicity. This virological constraint is due to the absence of a reverse genetics system for CTFV; therefore, we aimed to establish the system. Initially, the efficacy of CTFV replication was investigated in various cell lines. CTFV was found to grow in many cell types derived from different hosts and organs. Subsequently, BHK-T7 cells stably expressing T7 RNA polymerase were transfected with plasmids encoding each of the 12 CTFV gene segments, expression plasmids encoding all CTFV proteins, and a vaccinia virus RNA-capping enzyme. Following transfection, the cells were co-cultured with Vero or HeLa cells. Using this system, we rescued monoreassortants and recombinant viruses harboring peptide-tagged viral proteins. Furthermore, an improved system using Expi293F cells expressing T7 RNA polymerase was established, which enabled the generation of recombinant reporter CTFVs. In conclusion, these reverse genetics systems for CTFV will greatly contribute to the understanding of viral replication mechanisms, pathogenesis, and transmission, ultimately facilitating the development of rational treatments and candidate vaccines.
Journal Article