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African swine fever, caused by the African swine fever virus (ASFV), is a viral hemorrhagic disease that affects domestic pigs and wild boars. ASFV infection causes extensive tissue damage, and the associated mechanism is poorly understood. Pyroptosis is characterized by the activation of inflammatory caspases and pore formation in the cellular plasma membrane, resulting in the release of inflammatory cytokines and cell damage. How ASFV infection regulates pyroptosis remains unclear. Here, using siRNA assay and overexpression methods, we report that ASFV infection regulated pyroptosis by cleaving the pyroptosis execution protein gasdermin A (GSDMA). ASFV infection activated caspase-3 and caspase-4, which specifically cleaved GSDMA at D75-P76 and D241-V242 to produce GSDMA into five fragments, including GSDMA-N1-75, GSDMA-N1-241, and GSDMA-N76-241 fragments at the N-terminal end of GSDMA. Only GSDMA-N1-241, which was produced in the late stage of ASFV infection, triggered pyroptosis and inhibited ASFV replication. The fragments, GSDMA-N1-75 and GSDMA-N76-241, lose the ability to induce pyroptosis. Overall ASFV infection differentially regulates pyroptosis by GSDMA in the indicated phase, which may be conducive to its own replication. Our findings reveal a novel molecular mechanism for the regulation of pyroptosis.
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Vírus da Febre Suína Africana , Febre Suína Africana , Caspase 3 , Caspases Iniciadoras , Piroptose , Vírus da Febre Suína Africana/metabolismo , Animais , Febre Suína Africana/metabolismo , Febre Suína Africana/virologia , Febre Suína Africana/patologia , Suínos , Caspase 3/metabolismo , Caspase 3/genética , Caspases Iniciadoras/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Ligação a Fosfato/metabolismo , Células HEK293 , Replicação ViralRESUMO
African swine fever (ASF) is a highly contagious infectious disease of domestic pigs and wild boars caused by African swine fever virus (ASFV), with a mortality rate of up to 100%. In order to replicate efficiently in macrophages and monocytes, ASFV has evolved multiple strategies to evade host antiviral responses. However, the underlying molecular mechanisms by which ASFV-encoded proteins execute immune evasion are not fully understood. In this study, we found that ASFV pH240R strongly inhibits transcription, maturation, and secretion of interleukin-1ß (IL-1ß). Importantly, pH240R not only targeted NF-κB signaling but also impaired NLRP3 inflammasome activation. In this mechanism, pH240R interacted with NF-kappa-B essential modulator (NEMO), a component of inhibitor of kappa B kinase (IKK) complex and subsequently reduced phosphorylation of IκBα and p65. In addition, pH240R bonded to NLRP3 to inhibit NLRP3 inflammasome activation, resulting in reduced IL-1ß production. As expected, infection with H240R-deficient ASFV (ASFV-ΔH240R) induced more inflammatory cytokine expression both in vitro and in vivo than its parental ASFV HLJ/18 strain. Consistently, H240R deficiency reduced the viral pathogenicity in pigs compared with its parental strain. These findings reveal that the H240R gene is an essential virulence factor, and deletion of the H240R gene affects the pathogenicity of ASFV HLJ/18 by enhancing antiviral inflammatory responses, which provides insights for ASFV immune evasion mechanisms and development of attenuated live vaccines and drugs for prevention and control of ASF. IMPORTANCE African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious and acute hemorrhagic viral disease of domestic pigs, with a high mortality approaching 100%. ASFV has spread rapidly worldwide and caused huge economic losses and ecological consequences. However, the pathogenesis and immune evasion mechanisms of ASFV are not fully understood, which limits the development of safe and effective ASF attenuated live vaccines. Therefore, investigations are urgently needed to identify virulence factors that are responsible for escaping the host antiviral innate immune responses and provide a new target for development of ASFV live-attenuated vaccine. In this study, we determined that the H240R gene is an essential virulence factor, and its depletion affects the pathogenicity of ASFV by enhancing NLRP3-mediated inflammatory responses, which provides theoretical support for the development of an ASFV attenuated live vaccine.
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Vírus da Febre Suína Africana , Febre Suína Africana , Proteínas Virais , Animais , Febre Suína Africana/imunologia , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/patogenicidade , Deleção de Genes , Inflamassomos/genética , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Sus scrofa , Suínos , Proteínas Virais/genética , Proteínas Virais/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/imunologiaRESUMO
IMPORTANCE: African swine fever (ASF) caused by ASF virus (ASFV) is a highly contagious and acute hemorrhagic viral disease in domestic pigs. Until now, no effective commercial vaccine and antiviral drugs are available for ASF control. Here, we generated a new live-attenuated vaccine candidate (ASFV-ΔH240R-Δ7R) by deleting H240R and MGF505-7R genes from the highly pathogenic ASFV HLJ/18 genome. Piglets immunized with ASFV-ΔH240R-Δ7R were safe without any ASF-related signs and produced specific antibodies against p30. Challenged with a virulent ASFV HLJ/18, the piglets immunized with high-dose group (105 HAD50) exhibited 100% protection without clinical symptoms, showing that low levels of virus replication with no observed pathogenicity by postmortem and histological analysis. Overall, our results provided a new strategy by designing live-attenuated vaccine candidate, resulting in protection against ASFV infection.
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Vírus da Febre Suína Africana , Deleção de Genes , Genes Virais , Vacinas Atenuadas , Vacinas Virais , Animais , Febre Suína Africana/imunologia , Febre Suína Africana/prevenção & controle , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/classificação , Vírus da Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/patogenicidade , Sus scrofa/virologia , Vacinas Atenuadas/imunologia , Proteínas Virais/genética , Vacinas Virais/genética , Vacinas Virais/imunologia , Virulência , Replicação Viral , Genes Virais/genéticaRESUMO
African swine fever (ASF) is a viral hemorrhagic disease that affects domestic pigs and wild boar and is caused by the African swine fever virus (ASFV). The ASFV virion contains a long double-stranded DNA genome, which encodes more than 150 proteins. However, the immune escape mechanism and pathogenesis of ASFV remain poorly understood. Here, we report that the pyroptosis execution protein gasdermin D (GSDMD) is a new binding partner of ASFV-encoded protein S273R (pS273R), which belongs to the SUMO-1 cysteine protease family. Further experiments demonstrated that ASFV pS273R-cleaved swine GSDMD in a manner dependent on its protease activity. ASFV pS273R specifically cleaved GSDMD at G107-A108 to produce a shorter N-terminal fragment of GSDMD consisting of residues 1 to 107 (GSDMD-N1-107). Interestingly, unlike the effect of GSDMD-N1-279 fragment produced by caspase-1-mediated cleavage, the assay of LDH release, cell viability, and virus replication showed that GSDMD-N1-107 did not trigger pyroptosis or inhibit ASFV replication. Our findings reveal a previously unrecognized mechanism involved in the inhibition of ASFV infection-induced pyroptosis, which highlights an important function of pS273R in inflammatory responses and ASFV replication.
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Vírus da Febre Suína Africana , Febre Suína Africana , Cisteína Proteases , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros , Proteínas Virais , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/enzimologia , Vírus da Febre Suína Africana/metabolismo , Animais , Cisteína Proteases/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Piroptose , Sus scrofa , Suínos , Proteínas Virais/metabolismoRESUMO
Inflammatory factors and type I interferons (IFNs) are key components of host antiviral innate immune responses, which can be released from the pathogen-infected macrophages. African swine fever virus (ASFV) has developed various strategies to evade host antiviral innate immune responses, including alteration of inflammatory responses and IFNs production. However, the molecular mechanism underlying inhibition of inflammatory responses and IFNs production by ASFV-encoded proteins has not been fully understood. Here we report that ASFV infection only induced low levels of IL-1ß and type I IFNs in porcine alveolar macrophages (PAMs), even in the presence of strong inducers such as LPS and poly(dA:dT). Through further exploration, we found that several members of the multigene family 360 (MGF360) and MGF505 strongly inhibited IL-1ß maturation and IFN-ß promoter activation. Among them, pMGF505-7R had the strongest inhibitory effect. To verify the function of pMGF505-7R in vivo, a recombinant ASFV with deletion of the MGF505-7R gene (ASFV-Δ7R) was constructed and assessed. As we expected, ASFV-Δ7R infection induced higher levels of IL-1ß and IFN-ß compared with its parental ASFV HLJ/18 strain. ASFV infection-induced IL-1ß production was then found to be dependent on TLRs/NF-κB signaling pathway and NLRP3 inflammasome. Furthermore, we demonstrated that pMGF505-7R interacted with IKKα in the IKK complex to inhibit NF-κB activation and bound to NLRP3 to inhibit inflammasome formation, leading to decreased IL-1ß production. Moreover, we found that pMGF505-7R interacted with and inhibited the nuclear translocation of IRF3 to block type I IFN production. Importantly, the virulence of ASFV-Δ7R is reduced in piglets compared with its parental ASFV HLJ/18 strain, which may due to induction of higher IL-1ß and type I IFN production in vivo. Our findings provide a new clue to understand the functions of ASFV-encoded pMGF505-7R and its role in viral infection-induced pathogenesis, which might help design antiviral agents or live attenuated vaccines to control ASF.
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Vírus da Febre Suína Africana/patogenicidade , Febre Suína Africana/imunologia , Evasão da Resposta Imune/imunologia , Macrófagos Alveolares/imunologia , Proteínas Virais/imunologia , Vírus da Febre Suína Africana/imunologia , Animais , Imunidade Inata , Interferon Tipo I/biossíntese , Interleucina-1beta/biossíntese , Família Multigênica , Suínos , Virulência/imunologiaRESUMO
The state of growth of invasive species has a significant impact on the microbial regulation of the soil carbon (C) cycle. This study focused on the growth of Spartina alterniflora treated with imazapyr in the Tiaozini wetland of Jiangsu Province, China. The changes in soil bacterial structure, bacterial C metabolic activity, soil C, and regulation mechanism of soil C metabolic activity by biotic and abiotic factors were investigated. The results showed that soil bacterial diversity eventually decreased significantly (p < 0.05) along with significant changes in microbial structure (p < 0.05). Significant changes in soil physicochemical properties due to S. alterniflora growth inhibition were the key factors affecting the changes in the soil bacterial taxa composition (p < 0.05). Abiotic factors showed a greater effect on metabolic activities related to C fixation and biosynthesis of bacterial taxa than biotic factors (self-regulation). Additionally, bacterial taxa regulated soil C emission and degradation to a greater extent than abiotic factors. This study provides important information for understanding the regulators of C cycling in coastal wetland soil during the control of S. alterniflora invasion by imazapyr; moreover, it provides a scientific basis for the government to establish a prevention and control policy for S. alterniflora invasion. Understanding the complex interplay between abiotic and biotic factors is essential for developing effective strategies to manage soil C and mitigate the impacts of climate change.
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The leaf surfaces of plants are important organs for retaining particulate matter (PM). They can be renewed via washout processes (e.g., rainfall), thereby restoring the ability to retain new PM. Most of the current studies have focused on the mechanisms of rainfall characteristics on the renewal of PM on plant leaf surfaces and interspecific differences, while the effects of different leaf heights on PM renewal within the same plant canopy have been less studied. In addition, the dynamics of PM during rainfall, especially the water-soluble ions (WSII) component, are often neglected. This research used Salix matsudana, a tree species with a significant natural height difference between the upper and lower leaves of its canopy, as its study object. Using artificially simulated rainfall, the rainfall intensity was quantified as low, medium, and high (i.e., 30 mm/h, 45 mm/h, and 60 mm/h), and the rainfall process was divided into three sub-stages: pre (0-20 min), mid (20-40 min), and post (40-60 min). The experimental setup was divided into upper (2 m) and lower leaves (1 m) according to the height of the canopy. The concentration and distribution of water-insoluble PM (WIPM) were obtained using the elution weighing method, whereas WSII were obtained using ion chromatography. The dynamics of WIPM and WSII during the removal of PM from the leaf surface by rainfall were studied at different canopy heights, and the results showed that the composition and proportions of WIPM and WSII varied at different stages of the rainfall process and that the concentrations of WIPM and WSII removed from the upper leaves differed slightly from those of the lower leaves. In particular, the concentrations of WIPM and WSII removed from the lower leaves were greater than those from the upper leaves at high rainfall intensity (60 mm/h), showing consistency between rainfall removal of PM from the leaf surface at different heights within the plant canopy and deposition of PM, while at low (30 mm/h) and medium (45 mm/h) rainfall intensities the performance was slightly different.
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Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Íons/análise , Material Particulado/análise , Folhas de Planta/química , Plantas , Árvores/química , Água/análiseRESUMO
Precipitation is considered the most effective way to remove particulate matter from the leaves of plants. Changes in rainfall characteristics can affect the scavenging processes of particulate matter from leaves. In order to better understand the dynamics of PM scavenging during rainfall, especially the water-soluble ions components, leaves from the 11 plant species (trees, shrubs, terrestrial herbs, wetland plants) from the Olympic park were sampled and used in indoor experiments. During the experiments, the rainfall intensity was set at 30 mm/h, 45 mm/h, and 60 mm/h, and the duration was divided into 0-20 min, 20-40 min, and 40-60 min. The sampled plant leaves were set in the experiments at 1 m and 3 m height from the ground. Concentrations and compositions of nine water-soluble ions of rainfall samples were analyzed in this experiment. The results revealed that SO42-, Ca2+, and Na+ were the most abundant ionic species removed from the leaves, and NO3- ranked fourth, followed by Cl-, Mg2+ K+, NH4+, and F-. The ions concentration of rainfall samples decreased when the rain intensity increased from 30 to 45 mm/h and when the rain intensity increased to 60 mm/h. The efficiency of scavenging during different rainfall durations depends on the ionic species. Na+, Mg2+, Ca2+, and SO42- concentrations increased with the increase in rainfall duration, whereas those of NH4+, K+, and Cl- decreased. The effect of leaf height on ions concentration of rainfall samples was also different among the ionic species: Na+, Mg2+, Ca2+, NO3-, and F- concentrations were significantly higher at 1 m compared with 3 m. The principal component analysis of ions in rainfall samples revealed two main sources of particulate matter in our study. One is from vehicle exhaust and industrial and agricultural pollution. The other is agricultural combustion and ground dust sources. The results of the above study can provide a basis and theoretical support for the establishment of urban cleaning systems and the prevention of air pollution.
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Folhas de Planta , Água , Íons , Árvores , Material ParticuladoRESUMO
Lead pollution has attracted significant attention over the years. However, research on the transfer of lead between urban atmospheric particles, soils, and plants remains rare. We measured lead concentrations and lead isotope ratios in total suspended particles (TSP), soil, and plants in an urban wetland in Beijing. The study period was September 2016-August 2017- covering all four seasons. The concentrations of lead in the atmospheric particles vary from 3.13 to 6.68 mg/m3. It is significantly higher in autumn than that in spring and summer (P < 0.05). There is also a significant difference between summer and winter (P < 0.05). The soil lead concentrations range from 57 to 114 mg/kg, with the highest concentration in spring, followed by summer, winter and autumn. The lead concentrations are 1.28-7.75 mg/kg in plants. The concentration was highest in spring and significantly higher than in summer. The bioaccumulation factor of Phragmites australis was 0.064 (<0.1), indicating that lead is not easily transferred to plants. Unlike the bioaccumulation factors, translocation factors have much higher values, indicating a higher transfer within the plants. Results also indicate an interesting seasonal pattern with almost 97% of lead in plants during spring being of atmospheric origin, whereas in autumn, soilborne sources contribute almost 94%. The isotopic compositions of lead in the urban atmosphere-soil-plant system show that lead pollution results from the mixing of geogenic and anthropogenic materials. Vehicle exhaust, crustal rocks and ore deposits are likely primary sources of lead pollution within the study domain.
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Arabis paniculata Franch (Brassicaceae) has been widely used for the phytoremediation of heavy mental, owing to its hyper tolerance of extreme Pb, Zn, and Cd concentrations. However, studies on its genome or plastid genome are scarce. In the present study, we obtained the complete chloroplast (cp) genome of A. paniculata via de novo assembly through the integration of Illumina reads and PacBio subreads. The cp genome presents a typical quadripartite cycle with a length of 153,541 bp, and contains 111 unigenes, with 79 protein-coding genes, 28 tRNAs and 4 rRNAs. Codon usage analysis showed that the codons for leucine were the most frequent codons and preferentially ended with A/U. Synonymous (Ks) and non-synonymous (Ka) substitution rate analysis indicated that the unigenes, ndhF and rpoC2, related to "NADH-dehydrogenase" and "RNA polymerase" respectively, underwent the lowest purifying selection pressure. Phylogenetic analysis demonstrated that Arabis flagellosa and A. hirsuta are more similar to each other than to A. paniculata, and Arabis is the closest relative of Draba among all Brassicaceae genera. These findings provide valuable information for the optimal exploitation of this model species as a heavy-metal hyperaccumulator. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01151-1.
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Today, particulate-matter (PM) pollution has become one of the most severe air-pollution problems. As the most commonly used method in daily life, phytoremediation can use plant organs (such as leaves) as biological filters for pollutants to repair the atmosphere. At the same time, rainfall can remove PM from plant-leaf surfaces and enable them to adsorb PM again. By simulating natural rainfall, the rainfall characteristics are quantified as rainfall intensity and rainfall duration, and we use the washout-weighing method to obtain the amount of PM removed from the leaf surface. Then, use a scanner to scan the leaves after rain to get their images, and use Image J software to process the images to obtain leaf area. Finally, the amount of PM removed by rain per unit leaf area can be calculated. It will be used to explore the impact of different rainfall intensity and duration on the removal of PM from the leaf surface of wetland plants. The results showed that under three rainfall intensities used in this experiment, the removal of PM from plant-leaf surfaces all increased with an increase in rainfall duration. When the particle size is 10-100-µm, and the rainfall intensity is 30 mm/h, the removal amount of plant particles tested in this experiment is the largest. With increased rainfall duration, the removal of PM from plant-leaf surfaces increased sharply at first, then slowly, and finally tended to be stable. The removal efficiency of PM on the blade surface is most apparent at the early stage of rainfall, and then gradually weakens. Among the four wetland plants tested in this experiment, in the range of 10-100-µm, the number of PM on the leaf surface of Scirpus validus is the largest, and the optimum rainfall intensity is 30 mm/h; in the range of 2.5-10-µm, the number of PM on the leaf surface of Typha orientalis is the largest, and the optimal rainfall intensity is 30 mm/h; in the range of 0.45-2.5-µm, the number of PM on the leaf surface of Iris wilsonii is the largest, and the optimal rainfall intensity is 15 mm/h. Wetland species with high particle accumulation capacity can provide references for vegetation restoration of degraded wetland plants and plant cultivation in constructed wetlands. At the same time, the best rainfall intensity and duration for removing particulate matter on the surface of plant leaves were obtained through experiments, which provided a reference for the design of automatic plant irrigation systems and dust removers in different scenarios.
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Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Folhas de Planta/química , Áreas AlagadasRESUMO
OBJECTIVE: This study explored the technical characteristics and effectiveness of sling retraction technique in microvascular decompression for hemifacial spasm. METHODS: Between January 2008 and May 2016, 158 patients affected by hemifacial spasm underwent microvascular decompression. Among them, the traditional technique was performed in 86 patients (A Group) and the sling retraction technique was used in 72 patients (B Group). The authors conducted a retrospective study and compared the surgical outcome of the 2 groups. The authors measured cure rate at 3 months and 5 years after microvascular decompression. RESULTS: In the traditional technique group, the cure rate of microvascular decompression was 94.2% and 83.3%. While in the sling retraction technique group, the cure rate of microvascular decompression was 95.8% and 94.4%. Facial nerve palsy, hearing loss, meningitis, and ataxia were frequent complications in both 2 groups. CONCLUSIONS: The sling technique using biomedical glue is an effective and safe option for patients of hemifacial spasm. During the long-term follow-up, the sling retraction technique of microvascular decompression was more effective than the traditional technique, while there were no significant differences in the incidences of complications.
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Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ataxia/etiologia , Paralisia de Bell/etiologia , Feminino , Perda Auditiva/etiologia , Humanos , Masculino , Meningite/etiologia , Cirurgia de Descompressão Microvascular/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This study aimed to investigate the effect of miR-423-5p on the sensitivity of glioma stem cells to apigenin and to explore the potential mechanism. Previous research indicated that apigenin can effectively inhibit the proliferation of many cancer cells, including glioma cells, though our data unexpectedly showed that apigenin had no effect on glioma stem cell apoptosis. As many studies have reported that malignant transformation and progression of glioma are due to glioma stem cells, an anti-glioma stem cell approach has become an important direction for glioma treatment. In this study, we found miR-423-5p to be overexpressed in glioma tissues and corresponding glioma stem cells. Downregulation of miR-423-5p repressed glioma stem cell growth but did not cause apoptosis. Based on the concept of "Pharmaco-miR," this study further demonstrated that the combination of miR-423-5p knockdown and apigenin had a notable additive effect on inhibiting proliferation and promoting apoptosis in glioma stem cells. Hoechst staining showed higher apoptosis rates and typical apoptotic morphological changes of the cell nucleus, and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocya-nine iodide) staining revealed reduced mitochondrial membrane potential. Further research demonstrated that the mechanism is associated with a shift in the Bax/Bcl-2 ratio, an increased cytochrome c level, Apaf-1 induction, and caspase-3 activation. In conclusion, this study indicates that downregulation of miR-423-5p enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.
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Apigenina/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , MicroRNAs/fisiologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glioma/patologia , Humanos , Potencial da Membrana Mitocondrial/fisiologia , MicroRNAs/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/fisiologiaRESUMO
In the field of image descattering, the image formation models employed for restoration approaches are often simplified. In these models, scattering distribution is uniform in homogeneous media when transmission is fixed. Through specifically designed experiments, we discover that scattering exhibits non-uniform characteristics even in homogeneous media. Neglecting non-uniform scattering in these models limits their accuracy in representing scattering distribution, resulting in existing image descattering approaches inadequate. To tackle these issues, this paper proposes a novel image formation model for image descattering, considering more physical parameters, such as zenith angle, azimuth angle, scattering phase function, and camera focal length. Our model describes the light transfer process in scattering media more accurately. For image descattering, we introduce corresponding algorithms for parameter estimation in our model and simultaneous restoration from degraded images. Experimental evaluations demonstrate the effectiveness of our proposed model in various tasks, including physical parameter estimation, pure-scattering removal, image dehazing, and underwater image restoration. In terms of calculating parameters, our results are close to the real values; in terms of underwater image restoration, our work outperforms the state-of-art methods; in terms of image dehazing, our work promotes the performance of existing methods by replacing previous models with our model.
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We aimed to detect neopterin concentrations in serum and synovial fluid (SF) of knee osteoarthritis (OA) patients and to clarify their relationship with clinical severity of the disease. We cross-sectionally enrolled 176 knee OA patients and 63 age- and sex-matched controls. We measured neopterin concentrations by enzyme-linked immunosorbent assay (ELISA) and investigated the correlation between serum/SF neopterin concentrations and Kellgren-Lawrence (KL) grades as well as Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores in OA patients. Our results demonstrated that increased SF neopterin concentrations were independently correlated with greater symptomatic and radiographic severity in OA patients. These results suggested a crucial role of neopterin activation in the development and progression of knee OA. Assessment of neopterin levels in SF is a potential biomarker to evaluate disease severity in OA patients.
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Neopterina/metabolismo , Osteoartrite do Joelho/metabolismo , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/diagnóstico por imagem , Índice de Gravidade de Doença , Líquido Sinovial/metabolismoRESUMO
BACKGROUND: Mounting evidence suggests that there is a complex regulatory relationship between long non-coding RNAs (lncRNAs) and the glycolytic process during glioma development. This study aimed to investigate the prognostic role of glycolysis-related lncRNAs in glioma and their impact on the tumor microenvironment. METHODS: This study utilized glioma transcriptome data from public databases to construct, evaluate, and validate a prognostic signature based on differentially expressed (DE)-glycolysis-associated lncRNAs through consensus clustering, DE-lncRNA analysis, Cox regression analysis, and receiver operating characteristic (ROC) curves. The clusterProfiler package was applied to reveal the potential functions of the risk score-related differentially expressed genes (DEGs). ESTIMATE and Gene Set Enrichment Analysis (GSEA) were utilized to evaluate the relationship between prognostic signature and the immune landscape of gliomas. Furthermore, the sensitivity of patients to immune checkpoint inhibitor (ICI) treatment based on the prognostic feature was predicted with the assistance of the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in glioma cells and normal cell. RESULTS: By consensus clustering based on glycolytic gene expression profiles, glioma patients were divided into two clusters with significantly different overall survival (OS), from which 2 DE-lncRNAs, AL390755.1 and FLJ16779, were obtained. Subsequently, Cox regression analysis demonstrated that all of these lncRNAs were associated with OS in glioma patients and constructed a prognostic signature with a robust prognostic predictive efficacy. Functional enrichment analysis revealed that DEGs associated with risk scores were involved in immune responses, neurons, neurotransmitters, synapses and other terms. Immune landscape analysis suggested an extreme enrichment of immune cells in the high-risk group. Moreover, patients in the low-risk group were likely to benefit more from ICI treatment. qRT-PCR results showed that the expression of AL390755.1 and FLJ16779 was significantly different in glioma and normal cells. CONCLUSION: We constructed a novel prognostic signature for glioma patients based on glycolysis-related lncRNAs. Besides, this project had provided a theoretical basis for the exploration of new ICI therapeutic targets for glioma patients.
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BACKGROUND: There are a few models for predicting the outcomes of patients with severe fever with thrombocytopenia syndrome (SFTS) based on single-center data, but clinicians need more reliable models based on multicenter data to predict the clinical outcomes and effectiveness of drug therapy. METHODOLOGY/PRINCIPAL FINDINGS: This retrospective multicenter study analyzed data from 377 patients with SFTS, including a modeling group and a validation group. In the modeling group, the presence of neurologic symptoms was a strong predictor of mortality (odds ratio: 168). Based on neurologic symptoms and the joint indices score, which included age, gastrointestinal bleeding, and the SFTS virus viral load, patients were divided into double-positive, single-positive, and double-negative groups, which had mortality rates of 79.3%, 6.8%, and 0%, respectively. Validation using data on 216 cases from two other hospitals yielded similar results. A subgroup analysis revealed that ribavirin had a significant effect on mortality in the single-positive group (P = 0.006), but not in the double-positive or double-negative group. In the single-positive group, prompt antibiotic use was associated with reduced mortality (7.2% vs 47.4%, P < 0.001), even in individuals without significant granulocytopenia and infection, and early prophylaxis was associated with reduced mortality (9.0% vs. 22.8%, P = 0.008). The infected group included SFTS patients with pneumonia or sepsis, while the noninfected group included patients with no signs of infection. The white blood cell count and levels of C-reactive protein and procalcitonin differed significantly between the infection and non-infection groups (P = 0.020, P = 0.011, and P = 0.003, respectively), although the absolute difference in the medians were small. CONCLUSIONS/SIGNIFICANCE: We developed a simple model to predict mortality in patients with SFTS. Our model may help to evaluate the effectiveness of drugs in these patients. In patients with severe SFTS, ribavirin and antibiotics may reduce mortality.
Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Humanos , Ribavirina/uso terapêutico , Estudos Retrospectivos , Proteína C-ReativaRESUMO
Mixing different kind inhalation medications for simultaneous inhalation is widely used in the treatment of chronic respiratory diseases, and it can minimize the administration time and improve patient adherence. To our knowledge, it is unclear whether beclomethasone (BDP, Clenil®) can bemixed with acetylcysteine (NAC, Fluimucil®), because the in vitro physico-chemical compatibility and aerosol characteristics of the mixture are unknown. In this study, we investigated physical compatibility, including the appearance, pH, osmotic pressure and chemical stability, as well as aerosol characteristics, including particle size corresponding to 10%/50%/90% of the cumulative percentage of total particle volume (X10/X50/X90), volume median droplet diameter (VMD), mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD) and geometric standard deviation (GSD), delivery rate, and total delivery of the above solutions. After mixing, there were no significant changes in visual appearance, pH, osmolality and drug content of the mixtures at room temperature for 12 h. The FDP of BDP in the mixture decreased by 16.49%, whereas the NAC increased by 10.85%. The delivery rates of BDP and NAC in the mixture decreased by 66.05% and 45.54%, and total delivery increased by 13.20% and 25.29%, respectively. However, the MMAD, FPF, particle size and GSD of the mixture were almost unchanged. We demonstrated that these admixtures are physico-chemically compatible but that coadministration of beclomethasone with acetylcysteine can markedly affect output and aerosol characteristics.
RESUMO
RATIONALE: Meningiomas are mostly benign brain tumors with minimal malignant cases. Anaplastic meningioma has malignant morphological characteristics and a World Health Organization grade of III. PATIENT CONCERNS: The present study reports a case of an occipital meningioma in a patient who initially chose observation and follow-up after diagnosis. The patient ultimately underwent surgery due to the enlargement of the tumor and the development of visual field defects after a decade of imaging follow-up. The postoperative pathology slides indicated the presence of an anaplastic meningioma (World Health Organization-grade III). DIAGNOSES: The patient's diagnosis was established through cranial magnetic resonance imaging, which revealed an irregular mixed mass in the right occipital region with isointense T1 and hypointense T2 signal, irregular lobulation, and a maximum diameter of approximately 5.4 cm. Heterogenous enhancement was observed in the contrast-enhanced scan. INTERVENTIONS: The patient opted for surgical intervention to remove the tumor, and the pathology slides of the tumor sample confirmed the diagnosis of anaplastic meningioma. The patient also received radiotherapy (40Gy/15fr). OUTCOMES: No recurrence was observed during the 9-month follow-up. LESSONS: This case highlights the potential for low-grade meningiomas to undergo malignant transformation, particularly in the presence of irregular lobulation, peritumoral brain edema, and heterogeneous enhancement on contrast-enhanced scans. Total excision (Simpson grade I) is the preferred treatment option, and long-term imaging follow-up is recommended.
Assuntos
Edema Encefálico , Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
In recent years, scholars have paid increased attention to the ecological role of crab burrows, particularly their impact on the hydrological processes of saltmarsh wetlands. This study aims to investigate the influence of crab burrows on soil water and salt transport and to understand the ecological significance of crab burrows in coastal wetlands from the perspective of ecohydrological processes. We combined a field sample survey and an indoor soil column infiltration experiment to analyze the differences in infiltration time, soil water content, and soil electrical conductivity (EC) between different experimental groups. Consequently, the results showed that the size of crab burrow diameter varies significantly in different areas of the coastal wetland, influenced by tidal creek and sea-land distances, with larger burrow diameters in areas around 5 m from the tidal creek. Large-diameter burrows (2.5 cm × 6) are more conducive to salt transport due to their preferential water conductivity to the underlying soil vertically, small-diameter burrows (0.5 cm × 6) could promote water infiltration uniformly and maintain good soil water retention capacity. This study's results provide insights into the hydrological connectivity and spatial distribution of salinity in coastal wetlands. Additionally, the positive impact of burrows on the water-salt environment of coastal wetland sediments may also provide new ideas for coastal wetland restoration.