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We isolated novel reassortant avian influenza A(H5N6) viruses containing genes from clade 2.3.4.4b H5N1 virus and low pathogenicity avian influenza viruses in carcasses of whooper swans and bean geese in South Korea during December 2023. Neuraminidase gene was from a clade 2.3.4.4b H5N6 virus infecting poultry and humans in China.
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Animales Salvajes , Aves , Virus de la Influenza A , Gripe Aviar , Filogenia , Animales , Gripe Aviar/virología , Gripe Aviar/epidemiología , República de Corea/epidemiología , Animales Salvajes/virología , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Aves/virología , Virus Reordenados/genética , Historia del Siglo XXI , Humanos , Neuraminidasa/genéticaRESUMEN
Clade 2.3.4.4b highly pathogenic avian influenza A (HPAI) viruses have been detected in wild birds worldwide, causing recurrent outbreaks since 2016. During the winter of 2021-2022, we detected one H5N8 and forty-three H5N1 clade 2.3.4.4b HPAI viruses from wild birds in South Korea. Phylogenetic analysis revealed that HA gene of H5N1 viruses was divided into two genetically distinct groups (N1.G1 and N1.G2). Bayesian phylodynamic analysis demonstrated that wild birds play a vital role in viral transmission and long-term maintenance. We identified five genotypes (N1.G1.1, N1.G2, N1.G2.1, N1.G2.2, and N1.G2.2.1) having distinct gene segment constellations most probably produced by reassortments with low-pathogenic avian influenza viruses. Our results suggest that clade 2.3.4.4b persists in wild birds for a long time, causing continuous outbreaks, compared with previous clades of H5 HPAI viruses. Our study emphasizes the need for enhancing control measures in response to the changing viral epidemiology.
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Promising advances in membrane technology can lead to energy-saving and eco-friendly solutions in industrial sectors. This work demonstrates a highly selective membrane with ultrathin and highly interconnected organosiloxane polymer nanolayers by initiated chemical vapor deposition to effectively separate solutes within the molecular weight range of 150-300 g mol-1. We optimize the poly(1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasiloxane) membrane by adjusting both the thickness of the selective layer and the pore sizes of its support membranes. Notably, the 29 nm selective layer imparts a uniformly narrow molecular sieving property, providing a record-high solute-solute selectivity of 39.88 for different-sized solutes. Furthermore, a solute-solute selectivity of 11.04 was demonstrated using the real-world active pharmaceutical ingredient mixture of Acyclovir and Valacyclovir, key components for Herpes virus treatment, despite their molecular weight difference of less than 100 g mol-1. The highly interconnected membrane is expected to meet rigorous requirements for high-standard active pharmaceutical ingredient separation.
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Alzheimer's disease (AD) is a neurodegenerative disorder with complex pathogenesis and effective clinical treatment strategies for this disease remain elusive. Interestingly, nanomedicines are under extensive investigation for AD management. Currently, existing redox molecules show highly bioactive property but suffer from instability and high production costs, limiting clinical application for neurological diseases. Compared with natural enzymes, artificial enzymes show high stability, long-lasting catalytic activity, and versatile enzyme-like properties. Further, the selectivity and performance of artificial enzymes can be modulated for neuroinflammation treatments through external stimuli. In this review, we focus on the latest developments of metal, metal oxide, carbon-based and polymer based nanozymes and their catalytic mechanisms. Recent developments in nanozymes for diagnosing and treating AD are emphasized, especially focusing on their potential to regulate pathogenic factors and target sites. Various applications of nanozymes with different stimuli-responsive features were discussed, particularly focusing on nanozymes for treating oxidative stress-related neurological diseases. Noninvasiveness and focused application to deep body regions makes ultrasound (US) an attractive trigger mechanism for nanomedicine. Since a complete cure for AD remains distant, this review outlines the potential of US responsive nanozymes to develop future therapeutic approaches for this chronic neurodegenerative disease and its emergence in AD management.
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Enfermedad de Alzheimer , Nanoestructuras , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/terapia , Catálisis , MetalesRESUMEN
For ethylene/ethane separation, a CMS (carbon molecular sieve) membrane was developed with a PAN (polyacrylonitrile) polymer precursor on an alumina support. To provide an excellent thermal property to PAN precursor prior to the pyrolysis, the stabilization as a pre-treatment process was carried out. Tuning the stabilization condition was very important to successfully preparing the CMS membrane derived from the PAN precursor. The stabilization and pyrolysis processes for the PAN precursor were finely tuned, and optimized in terms of stabilization temperature and time, as well as pyrolysis temperature, heating rate, and soaking time. The PAN stabilized at >250 °C showed improved thermal stability and carbon yield. The CMS membrane derived from stabilized PAN showed reasonable separation performance for ethylene permeance (0.71 GPU) and ethylene/ethane selectivity (7.62), respectively. Increasing the pyrolysis temperature and soaking time gave rise to an increase in the gas permeance, and a reduction in the membrane selectivity. This trend was opposite to that for the CMS membranes derived from other polymer precursors. The optimized separation performance (ethylene permeance of 2.97 GPU and ethylene/ethane selectivity of 7.25) could be achieved at the pyrolysis temperature of 650 °C with a soaking time of 1 h. The separation performance of the CMS membrane derived from the PAN precursor was comparable to that of other polymer precursors, and surpassed them regarding the upper bound trade off.
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Carbon molecular sieve (CMS) membranes have been developed to replace or support energy-intensive cryogenic distillation for olefin/paraffin separation. Olefin and paraffin have similar molecular properties, but can be separated effectively by a CMS membrane with a rigid, slit-like pore structure. A variety of polymer precursors can give rise to different outcomes in terms of the structure and performance of CMS membranes. Herein, for olefin/paraffin separation, the CMS membranes derived from a number of polymer precursors (such as polyimides, phenolic resin, and polymers of intrinsic microporosity, PIM) are introduced, and olefin/paraffin separation properties of those membranes are summarized. The effects from incorporation of inorganic materials into polymer precursors and from a pyrolysis process on the properties of CMS membranes are also reviewed. Finally, the prospects and future directions of CMS membranes for olefin/paraffin separation and aging issues are discussed.
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BACKGROUND: Intracellular lipid accumulation is associated with various diseases, particularly cancer. Mitochondrial dysfunction is considered as a cause of lipid accumulation; however, the related underlying mechanism remains unclear. FINDINGS: We found that Von Hippel-Lindau (VHL)-deficiency led to lipid accumulation and mitochondrial dysfunction in renal cell carcinoma cells. Moreover, VHL downregulated ATP-citrate lyase (ACLY), a key enzyme in de novo lipid synthesis, at the transcriptional level, which inhibited intracellular lipid accumulation in human renal carcinoma tissues. We identified PPARγ as the transcription factor regulating ACLY expression by binding to the cis-regulatory site PPRE on its promoter. VHL directly interacted with and promoted ubiquitination of PPARγ, leading to its degradation both in vitro and in vivo, resulting in the downregulation of ACLY. Furthermore, adenovirus-mediated VHL overexpression substantially ameliorated hepatic steatosis induced by a high-fat diet in db/db mice. Importantly, low VHL expression was associated with high ACLY expression and poor prognosis in human liver carcinoma in a dataset in The Cancer Genome Atlas. CONCLUSIONS: VHL plays role in cellular lipid metabolism via regulating mitochondria and targeting PPARγ, a transcription factor for ACLY independent of hypoxia-inducible factor 1α. A novel VHL-PPARγ-ACLY axis and its implication in fatty liver disease and cancer were uncovered.
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ATP Citrato (pro-S)-Liasa/genética , Metabolismo de los Lípidos/efectos de los fármacos , Neoplasias/metabolismo , PPAR gamma/metabolismo , Ubiquitinación , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/fisiología , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Hígado Graso/metabolismo , Humanos , Ratones , Complejo de la Endopetidasa Proteasomal/fisiología , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genéticaRESUMEN
Ginsenoside Rg3 is a steroidal saponin abundant in Korean red ginseng that has high anti-inflammatory activity. Rg3 exerts an immunomodulatory effect in acute inflammatory conditions such as bacterial infections. In this study, we determined the effect of Rg3 on bacterial uptake by macrophages and the related intracellular signaling pathways. Rg3 increased macrophage phagocytosis of IgG-opsonized Escherichia coli and IgG-opsonized beads (IgGbeads), but not of non-opsonized beads. Rg3 also enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (p38 MAPK), but not that of Akt. The inclusion of IgGbeads in macrophage cultures also increased the phosphorylation of ERK1/2 and p38, but co-culture of macrophages with non-opsonized beads did not affect the phosphorylation of ERK1/2 and p38. The Rg3-induced promotion of phagocytosis was inhibited by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. PD98059 inhibited Rg3-induced p38 MAPK phosphorylation, but SB203580 did not suppress ERK1/2 phosphorylation. Culture of macrophages with Rg3 increased actin polymerization, and this effect was inhibited by SB203580 and PD98059. The Rg3-induced increase in phagocytosis was also inhibited by NSC23766, a Rac1 inhibitor and CASIN, a Cdc42 inhibitor. Intraperitoneal injection of Rg3 increased the phosphorylation of ERK1/2 and p38 as well as the phagocytosis of bacteria by lung cells. These results demonstrate that ginsenoside Rg3 enhances macrophage phagocytosis of bacteria by activating the ERK1/2 and p38 MAPK pathways.
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Bacterias/patogenicidad , Ginsenósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Receptores de IgG/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Células Cultivadas , Imidazoles/farmacología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Piridinas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
This paper addresses the problem of multi-object tracking in complex scenes by a single, static, uncalibrated camera. Tracking-by-detection is a widely used approach for multi-object tracking. Challenges still remain in complex scenes, however, when this approach has to deal with occlusions, unreliable detections (e.g., inaccurate position/size, false positives, or false negatives), and sudden object motion/appearance changes, among other issues. To handle these problems, this paper presents a novel online multi-object tracking method, which can be fully applied to real-time applications. First, an object tracking process based on frame-by-frame association with a novel affinity model and an appearance update that does not rely on online learning is proposed to effectively and rapidly assign detections to tracks. Second, a two-stage drift handling method with novel track confidence is proposed to correct drifting tracks caused by the abrupt motion change of objects under occlusion and prolonged inaccurate detections. In addition, a fragmentation handling method based on a track-to-track association is proposed to solve the problem in which an object trajectory is broken into several tracks due to long-term occlusions. Based on experimental results derived from challenging public data sets, the proposed method delivers an impressive performance compared with other state-of-the-art methods. Furthermore, additional performance analysis demonstrates the effect and usefulness of each component of the proposed method.
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Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The synthetic routes rely on amide formation with secondary amines and chloro-acid chlorides; SN2 reaction with sodium azide; and the selective [3 + 2] Hüisgen cycloaddition with appropriate terminal alkynes. The target secondary and tertiary 1,2,3-triazoloamide derivatives were obtained with three-diversity points in excellent overall yields and purities using the reported solid- and solution-phase synthetic routes, respectively.
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Aminas/química , Técnicas de Química Sintética , Aminas/síntesis química , Resonancia Magnética Nuclear Biomolecular , Técnicas de Síntesis en Fase Sólida , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
BACKGROUND DATA: In patients with chronic low back pain, the center of gravity (COG) is abnormally located posterior to the center in most cases. OBJECTIVE: The purpose of this study was to examine the effects of posterior-located COG on the functions (lumbar extension strength, and static and dynamic balance) and structure (lumbar lordosis angle and lumbosacral angle) of the lumbar spine. MATERIAL AND METHODS: In this study, the COG of chronic low back pain patients who complained of only low back pain were examined using dynamic body balance equipment. A total of 164 subjects participated in the study (74 males and 90 females), and they were divided into two groups of 82 patients each. One group (n=82) consisted of patients whose COG was located at the center (C-COG); the other group (n=82) consisted of patients whose COG was located posterior to the center (P-COG). The following measures assessed the lumber functions and structures of the two groups: lumbar extension strength, moving speed of static and dynamic COGs, movement distance of the static and dynamic COGs, lumbar lordosis angle, and lumbosacral angle. The measured values were analyzed using independent t-tests. RESULTS: The group of patients with P-COG showed more decreases in lumbar extension strength, lumbar lordosis angle, and lumbosacral angle compared to the group of patients with C-COG. Also this group showed increases in moving speed and movement distance of the static COG. However, there were no differences in moving speed and movement distance of the dynamic COG between the two groups. CONCLUSIONS: These findings suggest that chronic LBP patients with P-COG have some disadvantages to establish lumbar extension strength and static and dynamic balance, which require specific efforts to maintain a neutral position and to control posture.
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Lordosis/fisiopatología , Dolor de la Región Lumbar/fisiopatología , Vértebras Lumbares/fisiología , Modalidades de Fisioterapia/instrumentación , Equilibrio Postural/fisiología , Postura/fisiología , Adulto , Músculos de la Espalda/fisiología , Dolor Crónico/diagnóstico por imagen , Dolor Crónico/fisiopatología , Femenino , Gravitación , Humanos , Lordosis/diagnóstico por imagen , Dolor de la Región Lumbar/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Radiografía , Torso/fisiologíaRESUMEN
BACKGROUND: The skin has many important functions such as protection, preservation, temperature regulation, and vitamin D synthesis. It is composed of a variety of cell types including keratinocytes, melanocytes and fibroblasts. OBJECTIVE: We attempted to compare the gene expression profiles between keratinocytes, melanocytes and fibroblast, using cDNA microarray. METHODS: Keratinocytes, melanocytes and fibroblasts were primary cultured from five foreskin specimens. Total RNAs were extracted and pooled to reduce the individual variations, and then used for cDNA microarray. RESULTS: Total 12,028 genes were selected as the reliable genes whose expression was detected in at least one of the three cell types. By comparing the relative expression levels with cutoff limitation as a fourfold change, we obtained 126 fibroblast-specific, 179 keratinocyte-specific and 173 melanocyte-specific genes, many of which are known to be characteristically expressed in each cell type. In addition, we identified many genes whose skin-specific functions have not yet been determined. CONCLUSION: Our data provide important information on which to base further investigation into the specification of skin cell types.
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BACKGROUND: Ionizing radiation is used to treat many of cancers, however, it also produces unwanted side effect on normal tissues, such as radiodermatitis. We previously established an animal model for radiodermatitis, and found that X-ray irradiation induced the expression of ID3 in hairless mouse skin by cDNA microarray. OBJECTIVE: The aim of this study is to investigate the functional role of ID3 in X-ray irradiated keratinocytes. METHODS: Immunohistochemistry, RT-PCR and Western blot were performed to demonstrate the ID3 induction by X-ray irradiation. HaCaT keratinocytes were transduced with the recombinant adenovirus expressing HA-ID3, and then effects on apoptosis were analyzed. RESULTS: X-ray irradiation increased markedly the ID3 protein level in epidermis of mouse skin. X-ray irradiation also induced the expression of ID3 in HaCaT keratinocytes cultured in vitro, at both mRNA and protein levels. When ID3 was overexpressed by recombinant adenovirus, apoptosis of keratinocytes were induced even in the absence of X-ray irradiation. Furthermore, overexpression of ID3 sensitized X-ray-induced apoptosis. Interestingly, X-ray irradiation significantly reduced the endogenous ß-catenin level, which was related with induction of apoptosis. Similarly, overexpression of ID3 led to remarkable reduction in ß-catenin level. CONCLUSION: These results suggest that ID3 plays a role as an apoptosis inducer in response to X-ray irradiation via the regulation of endogenous ß-catenin level.