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New carbonyl sulfoxonium ylide glyco-reagents have been developed, enabling the synthesis of versatile heteroarene C-glycosides through a Ru-catalyzed C-H activation/annulation strategy. These reactions tolerate various saccharide donors and represent a significant advance in the stereoselective synthesis of heterocyclic C-glycosides. Furthermore, the strategy and methods could be applied to large-scale reactions and late-stage modifications of some structurally complex natural products or drugs.
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The natural abundance of stable carbon and nitrogen isotopes (δ13C and δ15N) in leaves can provide comprehensive information on the physiological and ecological processes of plants and has been widely used in ecological research. However, recent studies on leaf δ13C and δ15N have focused mainly on woody species, few studies have been conducted on herbs in different vegetation types, and their differences and driving factors are still unclear. In this study, we focused on the herbs in subalpine coniferous forests, alpine shrublands, and alpine mea-dows on the eastern Qinghai-Tibet Plateau, and investigated the differences in leaf δ13C and δ15N of herbs and the driving factors. The results showed that there were significant differences in leaf δ13C and δ15N values of herbs among different vegetation types, with the highest δ13C and δ15N values in alpine meadows, followed by alpine shrublands, and the lowest in subalpine coniferous forests. Using variation partitioning analysis, we revealed that differences in leaf δ13C and δ15N of herbs among various vegetation types were driven by both leaf functional traits and climate factors, with the contribution of leaf functional traits being relatively higher than that of climate factors. Hierarchical partitioning results indicated that mean annual temperature (MAT), chlorophyll content index, leaf nitrogen content per unit area (Narea), and leaf mass per area were the main drivers of leaf δ13C variations of herbs across different vegetation types, while the relative importance of Narea and MAT for variation in leaf δ15N of herbs was much higher than those other variables. There was a strong coupling relationship between leaf δ13C and δ15N as indicated by the result of the ordinary least squares regression. Our findings could provide new insights into understanding the key drivers of leaf δ13C and δ15N variations in herbs across different vegetation types.
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Isótopos de Carbono , Ecosistema , Isótopos de Nitrógeno , Hojas de la Planta , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Isótopos de Nitrógeno/análisis , Isótopos de Carbono/análisis , Tibet , China , Bosques , Altitud , Árboles/crecimiento & desarrollo , Árboles/metabolismo , Árboles/química , Tracheophyta/crecimiento & desarrollo , Tracheophyta/química , Tracheophyta/metabolismo , Pradera , Poaceae/crecimiento & desarrollo , Poaceae/química , Poaceae/metabolismoRESUMEN
The steroid hormone 17ß-estradiol (E2) has a significant impact on the development and progression of tumors. E2 stimulates tumor cell growth and metabolism, leading to an increase in reactive oxygen species (ROS) production. However, the rise in ROS levels is not sufficient to cause severe harm to cancer cells. and the mechanisms that regulate ROS are not well understood. Since FOXM1 plays a crucial role in the production of ROS, we aimed to investigate the impact of E2 on oxidative stress and the involvement of FOXM1 in the Ishikawa endometrial cancer cell line. Our research revealed that E2 controls the levels of ROS inside cells and safeguards them from apoptosis by promoting the expression of FOXM1. We observed a decrease in the expression of FOXM1 alongside an increase in oxidative damage. Moreover, cells demonstrated elevated levels of FOXM1 and ERα upon E2 treatment. Overall, our findings suggest that E2 prevents apoptosis induced by oxidative stress in endometrial cancer cells by encouraging the expression of FOXM1, potentially affecting ERα.
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Pseudoaneurysm is a rare but lethal complication of acute myocardial infarction. In this study, we present a unique case of a patient with left ventricular free wall rupture detected by cardiac magnetic resonance more than 1 year after a percutaneous transluminal coronary intervention.
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As the most senstitive plant organs to environmental changes, leaves serve as crucial indicators of plant survival strategies. We measured the morphology, anatomical traits, gas exchange parameters, and chlorophyll fluorescence parameters of Quercus aquifolioides (evergreen broad-leaved) and Sorbus rehderiana (deciduous broad-leaved) at altitudes of 2600, 2800, 3000, 3200 and 3400 m on the eastern edge of the Qinghai-Tibet Plateau, China. We explored the similarity and difference in their responses to altitude change and the ecological adaptation strategy. The results showed that as the altitude increased, leaf dry matter content of Q. aquifolioides decreased, that of S. rehderiana increased, leaf size for both species gradually decreased, and the palisade coefficient of Q. aquifolioides showed a decreasing trend, contrasting with the increasing trend in S. rehderiana. As the altitude increased, the thickness of leaves, palisade tissue, spongy tissue, upper epidermis, and lower epidermis of both species increased significantly, with the increment of 22.4%, 4.9%, 45.1%, 23.3%, 19.6%, and 28.2%, 46.9%, 8.9%, 25.9%, 20.8% at altitude of 3400 m, respectively, compared with the altitude of 2600 m. The gas exchange and chlorophyll fluorescence parameters of S. rehderiana significantly increased with increasing altitude, while Q. aquifolioides showed the opposite trend. Leaf anatomical traits, gas exchange, and chlorophyll fluorescence parameters of both species displayed considerable plasticity. There were significant correlations among most leaf traits and between leaf traits and altitude. The survival strategy of Q. aquifolioides was more conservative in response to altitude changes, while that of S. rehderiana was more active. Both species adapted to different altitudes by adjusting their own traits.
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Altitud , Hojas de la Planta , Quercus , Sorbus , Quercus/fisiología , Quercus/crecimiento & desarrollo , China , Ecosistema , Tibet , Adaptación FisiológicaRESUMEN
BACKGROUND: Peiminine (PMI) is an active alkaloid sourced from Fritillaria thunbergii, which has been shown to suppress the development of a variety of tumors. Whereas, the roles and precise mechanism of PMI in breast cancer (BC) development remain not been clarified. METHODS: The cytotoxic effect of PMI on MCF-10A and BC cell lines (MCF-7 and BT-549) were assessed by MTT and LDH release assay. Cell proliferation was evaluated by EdU staining. Levels of Malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH) activity and iron assay were measured by Enzyme linked immunosorbent assay (ELISA) kits, respectively. Transmission Electron Microscope was performed to observe mitochondrial morphological structure. Immunofluorescence, immunohistochemistry, and western blot were conducted to examine protein levels, respectively. Xenograft model was used to confirm cellular findings. RESULTS: PMI treatment reduced the viability and enhanced LDH level of MCF-7 and BT-549 cells in a time- and concentration-dependent manner, and further suppressed cell proliferation in vitro and tumor growth in vivo. Subsequently, PMI administration resulted in significant increases of ROS, MDA and iron levels, reduction of GSH activity as well as mitochondrial shrinkage and GPX4 reduction, while all these phenomena could be rescued by ferrostatin-1. Mechanistically, PMI treatment led to promoted Nrf2 expression and its nuclear translocation, as well as it's downstream protein HO-1 and NQO1 expressions. Notably, ML-385, a Nrf2 specific inhibitor, greatly reversed the anti-tumor effects and pro-ferroptosis role of PMI in BC cells. CONCLUSION: Taking these finding together, PMI could stimulate ferroptosis to inhibit BC tumor growth by activating Nrf2-HO-1 signaling pathway.
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Neoplasias de la Mama , Cevanas , Ferroptosis , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Transducción de Señal , HierroRESUMEN
Anterior cruciate ligament (ACL) tear is a common sports-related injury, and cartilage injury always emerges as a serious complication following ACL tear, significantly impacting the physical and psychological well-being of affected individuals. Over the years, efforts have been directed toward finding strategies to repair cartilage injury after ACL tear. In recent times, procyanidins, known for their anti-inflammatory and antioxidant properties, have emerged as potential key players in addressing this concern. This article focuses on summarizing the research progress of procyanidins in repairing cartilage injury after ACL tear. It covers the roles, mechanisms, and clinical significance of procyanidins in repairing cartilage injury following ACL tear and explores the future prospects of procyanidins in this domain. This review provides novel insights and hope for the repair of cartilage injury following ACL tear.
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In this work, 0.75 wt 2,3-pyridinedicarboxylic anhydride (PDA) as a novel dopant was utilized to obtain modified graphitic carbon nitride with ultratrace doping (3MCN-PDA3) by facile thermal polymerization. Characterization of the microstructure, surface state, and porosity properties of the samples indicated that 3MCN-PDA3 has a thinner sheet-like, larger-scale, and tighter lamellar stacking structure than that of pristine graphitic carbon nitride (3MCN). Based on photo/electrochemical analysis, the PDA dopant formed an extended coplanar conjugated system by anhydride-amine thermal condensation with heptazine rings, and the channels of amide covalent bonds and superconjugation of the solitary pair of electrons of the nitrogen atoms of PDA synergistically promoted the charge transport performance of 3MCN-PDA3. Under visible light, the photodegradation efficiency of Rhodamine B (RhB) over 3MCN-PDA3 reached 92.4% in 60 min and realized almost entire removal in 200 min (99.2%), 1.43 times that of 3MCN. Furthermore, the experimental results and generalized density theory calculations confirmed that PDA acts as an intermediate molecular island and constructs an efficient carrier transfer pathway between different heptazine units. The results indicate that PDA is a promising candidate to enhance the charge transfer performance through ultratrace doping in the large-scale preparation and application of the graphitic carbon nitride photocatalyst.
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A new Cp*Rh(III)-catalyzed regioselective cyclization reaction of aromatic amides with allenes is reported. The use of allenyl derivatives bearing a directing-group assistant as a reaction promoter was the key to the success of this protocol. In this catalytic system, N-(pivaloyloxy)benzamide substrates react with allenes via Rh-σ-alkenyl intermediates, while N-(pivaloyloxy) indol substrates react via Rh-π-allyl intermediates. These reactions were characterized by mild reaction conditions, a broad substrate scope, and high functional-group compatibility to yield several high-value isoquinolinone and pyrimido[1,6-a]indol-1(2H)-one skeleton-containing compounds. The synthetic applications and primary mechanisms were also investigated.
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Alpha-Momorcharin (α-MMC), as one of the most important type I RIPs, has been reported to exert inhibitory effects against various tumour cells through its N-glycosidase activity. The present study was designed to propose an efficient purification strategy and explored its mechanism of apoptosis signalling pathway against human liver cancer cells SK-Hep-1. α-MMC can be successfully obtained by our purification strategy combining ion-exchange and gel-filtration chromatography. The functional studies revealed that α-MMC obviously increased the level of ROS and apoptosis rate, induced cell cycle arrest in the G1 phase, and depolarised MMP of SK-Hep-1 cells. To further confirm whether α-MMC could induce mitochondria involved apoptosis, we found that PARP-1, Caspase-3, Caspase-9, and BCL-2 were downregulated upon α-MMC. Taken together, these results suggested that this natural purified α-MMC can induce apoptosis involved mitochondria and may serve as a potential novel therapeutic drug in the treatment of human liver cancer in the future.
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Developing efficient oxygen evolution reaction (OER) electrocatalysts can greatly advance the commercialization of proton exchange membrane (PEM) water electrolysis. However, the unclear and disputed reaction mechanism and structure-activity relationship of OER pose significant obstacles. Herein, the active site and intermediate for OER on AuIr nanoalloys are simultaneously identified and correlated with the activity, through the integration of in situ shell-isolated nanoparticle-enhanced Raman spectroscopy and X-ray absorption spectroscopy. The AuIr nanoalloys display excellent OER performance with an overpotential of only 246 mV to achieve 10 mA cm-2 and long-term stability under strong acidic conditions. Direct spectroscopic evidence demonstrates that * OO adsorbed on IrOx sites is the key intermediate for OER, and it is generated through the O-O coupling of adsorbed oxygen species directly from water, providing clear support for the adsorbate evolution mechanism. Moreover, the Raman information of the * OO intermediate can serve as a universal "in situ descriptor" that can be obtained both experimentally and theoretically to accelerate the catalyst design. It unveils that weakening the interactions of * OO on the catalysts and facilitating its desorption would boost the OER performance. This work deepens the mechanistic understandings on OER and provides insightful guidance for the design of more efficient OER catalysts.
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BACKGROUND: Digital subtraction angiography (DSA), the gold standard of cerebrovascular disease diagnosis, is limited in its diagnostic ability to evaluate arterial diameter. Intravascular ultrasonography (IVUS) has advantages in assessing stenosis and plaque nature and improves the evaluation and effectiveness of carotid artery stenting (CAS). CASE SUMMARY: Case 1: A 65-year-old man presented with a five-year history of bilateral lower limb weakness due to stroke. Physical examination showed decreased strength (5-/5) in both lower limbs. Carotid artery ultrasound, magnetic resonance angiography, and computed tomography angiography (CTA) showed a right proximal internal carotid artery (ICA) stenosis (70%-99%), acute cerebral infarction, and severe right ICA stenosis, respectively. We performed IVUS-assisted CAS to measure the stenosis and detected a low-risk plaque at the site of stenosis prior to stent implantation. Post-stent balloon dilatation was performed and postoperative IVUS demonstrated successful expansion and adherence. CTA six months postoperatively showed no significant increase in in-stent stenosis. Case 2: A 36-year-old man was admitted with a right common carotid artery (CCA) dissection detected by ultrasound. Physical examination showed no positive neurological signs. Carotid ultrasound and CTA showed lumen dilation in the proximal CCA with an intima-like structure and bulging in the proximal segment of the right CCA with strip-like low-density shadow (dissection or carotid web). IVUS-assisted DSA confirmed right CCA dissection. CAS was performed and intraoperative IVUS suggested a large residual false lumen. Post-stent balloon dilatation was performed reducing the false lumen. DSA three months postoperatively indicated good stent expansion with mild stenosis. CONCLUSION: IVUS aids decision-making during CAS by accurately assessing carotid artery wall lesions and plaque nature preoperatively, dissection and stenosis morphology intraoperatively, and visualizing and confirming CAS postoperatively.
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Exploring the resource limitation of soil microbial metabolism is essential to understand ecosystem functions and processes. However, the spatially divergent patterns and drivers of soil microbial nutrient limitation cha-racteristics in montane ecosystems at small scales, especially at the slope aspect scale, are still unclear. In this study, we measured soil enzyme activities involved in carbon (C), nitrogen (N) and phosphorus (P) cycle and quantified the microbial nutrient limitations by enzyme stoichiometry in two representative mountain sites in subalpine region of western Sichuan, including the sunny and shady slopes with different vegetation types (shrubland and forest, respectively) in Miyaluo of Lixian County, and with the same vegetation type (shrubland) in Yakexia of Heishui County. The results showed that soil enzyme activities and their stoichiometric ratios were significantly different between slope aspects in Miyaluo, while the differences were not significant in Yakexia. The stoichiometry ratio of C-, N- and P-acquiring enzymes on the sunny slope of Miyaluo was 1:0.96:0.92, approaching the 1:1:1 ratio at the global scale, but deviated from 1:1:1 on the shady slope of Miyaluo (1:1.39:0.75) and the different slopes of Yakexia (1:1.09:1.35). There was no significant difference in vector length between slope aspects at both sites, indicating no significant effect of slope aspect on the microbial C limitation. The vector angle was significantly higher on the sunny slope (43.6°) than that on the shady slope (28.7°) in Miyaluo, suggesting that the microorganisms were mainly N-limited. Partial least squares path model showed that the vector angle was mainly directly influenced by the soil nutrient ratios. The vector angle ranged from 50.3° to 51.4°, and did not differ between slope aspects in Yakexia. Therefore, differences in vegetation types between slope aspects drove variations in soil enzyme activity and microbial nutrient limitation through soil properties. It would provide a scientific basis for predicting the spatial pattern of soil enzyme activity and microbial nutrient limitation.
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Charadriiformes , Ecosistema , Animales , Charadriiformes/metabolismo , Suelo , China , Microbiología del Suelo , Nutrientes , Fósforo/análisis , Nitrógeno/análisis , CarbonoRESUMEN
Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.
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Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Humanos , Lactante , Anticuerpos Antivirales , Método Doble Ciego , Pueblos del Este de Asia , Inmunogenicidad Vacunal , Inmunoglobulina A , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/efectos adversos , Vacunas contra Rotavirus/uso terapéutico , Vacunas Atenuadas , Vacunas CombinadasRESUMEN
OBJECTIVE: To observe the effects of electroacupuncture ï¼EAï¼ on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of kisspeptin and kiss1r in rats with polycystic ovarian syndrome ï¼PCOSï¼, so as to explore the mechanism of EA for relieving ovarian dysfunction in PCOS rats. METHODS: Forty-eight SD female rats were randomly divided into control group, model group, EA group and flutamide group, with 12 rats in each group. PCOS rat model was replicated with the gavage of letrozole ï¼0.1 mg/mL, 10 mLâ¢kg-1â¢d-1ï¼. In the EA group, EA ï¼2 Hz, 2 mAï¼ was used to stimulate "Guanyuan" ï¼CV4ï¼ for 20 min each time. In the flutamide group, flutamide solution ï¼50 mgâ¢kg-1â¢d-1ï¼ was administrated by gavage. The treatments were given once daily for 14 days in each group. After the modeling and treatment, the body and ovarian weights of the rats were measured, and the ovarian index was calculated. Using HE staining, the morphological changes of ovary were observed. ELISA was adopted to detect the contents of testosterone ï¼Tï¼, luteinizing hormone ï¼LHï¼ and estradiol ï¼E2ï¼ in serum, the contents of E2 and T in the culture medium of ovarian granulosa cells and theca cells, as well as the content of kisspeptin in the ovarian tissue. The positive expression of kisspeptin in ovary was observed by immunohistochemical method, and the protein expression of its receptor kiss1r was detected by Western blot. RESULTS: Compared with the control group, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and positive expression of kisspeptin in ovary were all increased ï¼P<0.01, P<0.05ï¼ï¼ and the content of E2 in the culture medium of granulosa cells was decreased ï¼P<0.01ï¼ in the model group. When compared with the model group, in the EA and flutamide groups, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and expression of kisspeptin in ovary were all decreased ï¼P<0.01, P<0.05ï¼ï¼ and the content of E2 in the culture medium of granulosa cells was increased ï¼P<0.05, P<0.01ï¼. CONCLUSION: EA regulates the serum sex hormone levels, the secretion function of the ovarian granulosa cells and theca cells, and the ovarian kisspeptin/kiss1r protein expression in PCOS rats, showing the similar effect as receptor blockade intervention. It is suggested that the improvement of EA in ovarian dysfunction of PCOS rats may be related to the kisspeptin/kiss1r system.
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Electroacupuntura , Síndrome del Ovario Poliquístico , Animales , Femenino , Humanos , Ratas , Flutamida , Kisspeptinas/genética , Hormona Luteinizante , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/terapiaRESUMEN
Cp*Rh(III)-catalyzed nitro-directed C-H alkylation/alkenylation of nitroarenes has been reported for the first time. This protocol is associated with the features of high efficiency, broad substrate scope, and good functional group compatibility. Additionally, gram-scale experiments and synthetic applications proved the practicability of the method. Moreover, preliminary mechanistic investigations consistently revealed C-H bond cleavage as the rate-limiting step.
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The bat coronaviruses (CoV) BANAL-20-52 and BANAL-20-236 are two newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely related coronaviruses (SC2r-CoV) and the genome of BANAL-20-52 shares the highest homology with SARS-CoV-2. However, the risk of their potential zoonotic transmission has not been fully evaluated. Here, we determined their potential host susceptibility among 13 different bat species and 26 different animal species, and found that both might have extensive host ranges, indicating high zoonotic transmission potential. We also determined the cryo-EM structures of BANAL-20-52 and BANAL-20-236 S proteins at pH 5.5 and the complex of BANAL-20-236 S1 and Rhinolophus affinis ACE2, and found that both trimeric S proteins adopt all three receptor binding domains (RBDs) in "closed" conformation and are more compact than SARS-CoV-2. Strikingly, the unique sugar moiety at N370 of bat SC2r-CoVs acts like a "bolt" and crosses over two neighboring subunits, facilitating the S proteins in the locked conformation and underpinning the architecture stability. Removal of the glycosylation at N370 by a T372A substitution substantially enhances virus infectivity but becomes highly sensitive to trypsin digestion at pH 5.5, a condition roughly mimicking the insectivorous bat's stomach digestion. In contrast, WT S proteins of SC2r-CoVs showed considerable resistance to trypsin digestion at pH 5.5, indicating that the highly conserved T372 in bat CoVs might result from the selective advantages in stability during the fecal-oral transmission over A372. Moreover, the results of cross-immunogenicity among S proteins of SARS-CoV-2, BANAL-20-52, and BANAL-20-236 showed that A372 pseudoviruses are more sensitive to anti-S sera than T372, indicating that immune evasion might also play a role in the natural selection of T372 over A372 during evolution. Finally, residues 493 and 498 of the S protein affect host susceptibility, and residue 498 also influences the immunogenicity of the S protein. Together, our findings aid a better understanding of the molecular basis of CoV entry, selective evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts of these viruses to prevent potential outbreaks.