ABSTRACT
Exosomes are small vesicles containing proteins, nucleic acids, and biological lipids, which are responsible for intercellular communication. Studies have shown that exosomes can be utilized as effective drug delivery vehicles to accurately deliver therapeutic substances to target tissues, enhancing therapeutic effects and reducing side effects. Mesenchymal stem cells (MSCs) are a class of stem cells widely used for tissue engineering, regenerative medicine, and immunotherapy. Exosomes derived from MSCs have special immunomodulatory functions, low immunogenicity, the ability to penetrate tumor tissues, and high yield, which are expected to be engineered into efficient drug delivery systems. Despite the promising promise of MSC-derived exosomes, exploring their optimal preparation methods, drug-loading modalities, and therapeutic potential remains challenging. Therefore, this article reviews the related characteristics, preparation methods, application, and potential risks of MSC-derived exosomes as drug delivery systems in order to find potential therapeutic breakthroughs.
Subject(s)
Drug Delivery Systems , Exosomes , Mesenchymal Stem Cells , Exosomes/metabolism , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Drug Delivery Systems/methods , Animals , Drug Carriers/chemistry , Neoplasms/therapyABSTRACT
Machine learning enabled auscultating diagnosis can provide promising solutions especially for prescreening purposes. The bottleneck for its potential success is that high-quality datasets for training are still scarce. An open auscultation dataset that consists of samples and annotations from patients and healthy individuals is established in this work for the respiratory diagnosis studies with machine learning, which is of both scientific importance and practical potential. A machine learning approach is examined to showcase the use of this new dataset for lung sound classifications with different diseases. The open dataset is available to the public online.
Subject(s)
Auscultation , Machine Learning , Respiratory Sounds , Humans , Auscultation/methods , Respiratory Sounds/classificationABSTRACT
Background: Percutaneous atrial septal defect (ASD) closure is the preferred treatment for patients with suitable ASD anatomy. The safety and effectiveness of transcatheter closure have been established. However, reports on transesophageal echocardiography (TEE)-guided percutaneous closure of ASD via the right internal jugular vein (RIJV) are limited. The study aims to discuss the safety and effectiveness of percutaneous trans-jugular vein closure of ASD. Methods: We conducted a retrospective analysis of patients (n=103) with secondary ASD who underwent surgical treatment in the Department of Cardiovascular Surgery, the Second Hospital of Jilin University between July 2015 to July 2022. The article is a cross-sectional study. Clinical data, including age, gender, weight, defect diameter, tricuspid regurgitation, left atrial (LA) size, and the operation results, were collected and evaluated. Nonparametric rank sum tests were used to assess tricuspid regurgitation before and after surgery, while paired sample t-tests were used to compare LA size before and after surgery. Results: TEE-guided percutaneous closure of ASD via the RIJV was successfully performed in 97 out of 103 (94.2%) cases. The average procedure time was 34.48±13.06 min, and the mean age at the time of the procedure and ASD size were 36±18 years and 15.45±5.82 mm, respectively. On analyzing medical records and echocardiographic images, postoperative complications were found to occur in four (3.9%) patients. Among these, three patients had residual shunt as indicated by echocardiography during the operation, which subsequently disappeared at the three-month follow-up. One patient developed atrial fibrillation after surgery but returned to normal sinus rhythm with medication. Percutaneous closure of ASD via the RIJV was unsuccessful in 6 patients (5.8%), with 5 of them undergoing transthoracic ASD closure and achieving satisfactory results. One patient refused further surgical treatment. No pericardial effusion, thrombosis, atrioventricular block, or other complications were observed during the 3-month to 1-year follow-up period. Conclusions: ASD closure via the RIJV is a safe and effective therapeutic approach. The initial results are satisfactory, but further studies with large sample sizes and long-term follow-up are warranted to assess the long-term outcomes.
ABSTRACT
Polypropylene (PP) is one of the most extensively used commodity plastics. In terms of eco-friendliness, it is worth considering preparing high-lignin-filled PP. This study explores the incorporation of high lignin content, derived from acetic acid lignin (AAL) and Kraft lignin (KL), into PP through twin-screw extrusion and injection molding. The challenge lies in maintaining mechanical performance. A compatibilizer-specifically, maleic anhydride-grafted polypropylene (MAPP)-is employed to enhance lignin-PP compatibility by chemically bonding with lignin and physically associating with the PP phase. Results indicate that KL maintains better dispersity than AAL. Compatibilizers with a high maleic anhydride (MA) level (≥0.8 wt.%) and moderate melt flow index (MFI) in the range of 60-100 g 10 min⻹ prove favorable in constructing a reinforced PP/KL network. Optimizing with 40 wt.% lignin content and 10 parts per hundred (pph) of compatibilizer yields blends with mechanical performance comparable to neat PP, exhibiting a notable increase in modulus and heat deflection temperature (HDT). Furthermore, utilizing PP/lignin blends can lead to a 20% reduction in expenses and approximately 40% reduction in PP-induced greenhouse gas (GHG) emissions. This approach not only reduces PP costs but also adds value to lignin utilization in a sustainable and cost-effective manner.
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Wuxiang virus (WUXV) is the first sandfly-borne Phlebovirus isolated from Phlebotomus chinensis collected in China and has been established as a consistent viral presence in the local sandfly populations of both Wuxiang County and Yangquan City. However, its distribution in the Shanxi Province remains unclear. In this study, three novel WUXV strains were isolated from sandflies collected from Jiexiu City, Shanxi Province, China, in 2022. Subsequently, whole-genome sequences of these novel strains were generated using next-generation sequencing. The open reading frame (ORF) sequences of the WUXV strains from the three locations were subjected to gene analysis. Phylogenetic analysis revealed that WUXV belongs to two distinct clades with geographical differences. Strains from Wuxiang County and Yangquan City belonged to clade 1, whereas strains from Jiexiu City belonged to clade 2. Reassortment and recombination analyses indicated no gene reassortment or recombination between the two clades. However, four reassortments or recombination events could be detected in clade 1 strains. By aligning the amino acid sequences, eighty-seven mutation sites were identified between the two clades, with seventeen, sixty, nine, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Additionally, selection pressure analysis identified 17 positively selected sites across the entire genome of WUXV, with two, thirteen, one, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Notably, sites M-312 and M-340 in the M segment not only represented mutation sites but also showed positive selective pressure effects. These findings highlight the need for continuous nationwide surveillance of WUXV.
Subject(s)
High-Throughput Nucleotide Sequencing , Psychodidae , Animals , Phylogeny , China/epidemiology , Amino Acid Sequence , RNA-Dependent RNA PolymeraseABSTRACT
Goose astroviruses (GoAstVs) are causative agents that account for fatal infection of goslings characterized by visceral urate deposition, resulting in severe economic losses in major goose-producing regions in China since 2017. In this study, we sought to unravel the intrinsic properties associated with adaptation and evolution in the host environment of GoAstVs. Consistent results from phylogenetic analysis and correspondence analysis performed on the codon usage patterns (CUPs) reveal 2 clusters of GoAstVs, namely, GoAstV-1 and GoAstV-2. However, multiple similar compositional characteristics were found, despite the high divergence between GoAstV-1 and GoAstV-2. Studies on the base composition of GoAstVs reveal an A/U bias, indicating a compositional constraint, while natural selection prevailed in determining the CUPs in the virus genome based on our neutrality plot analysis, reflecting high adaptive pressure to fit the host environment. Codon adaptation index (CAI) analysis revealed a higher degree of fitness to the CUPs of the corresponding host for GoAstVs than avian influenza virus and betacoronaviruses, which may be a favorable factor contributing to the high pathogenicity and wide distribution of GoAstVs in goslings. In addition, GoAstVs were less adapted to ducks and chickens, with significantly lower CAI values than to geese, which may be a reason for the different prevalence of GoAstVs among these species. Extensive investigations on dinucleotide distribution revealed a significant suppression of the CpG and UpA motifs in the virus genome, which may facilitate adaptation to the host's innate immune system by evading surveillance. In addition, our study reported the trends of increasing fitness to the host's microenvironment for GoAstVs through increasing adaptation to host CUPs and ongoing reduction of CpG motifs in the virus genome. The present analysis deepens our understanding of the basic biology, pathogenesis, adaptation and evolutionary pattern of GoAstVs, and contributes to the development of novel antiviral strategies.
Subject(s)
Avastrovirus , Geese , Animals , Geese/genetics , Base Composition , Phylogeny , Chickens/genetics , Codon , Avastrovirus/geneticsABSTRACT
Achieving high atomic utilization and low cost of desirable Pt/TiO2 catalysts is a major challenge for room temperature HCHO oxidation. Here, the strategy of anchoring stable Pt single atoms by abundant oxygen vacancies over TiO2-nanosheet-assembled hierarchical spheres (Pt1/TiO2-HS) was designed to eliminate HCHO. A superior HCHO oxidation activity and CO2 yield (â¼100% CO2 yield) at relative humidity (RH) > 50% over Pt1/TiO2-HS is achieved for long-term run. We attribute the excellent HCHO oxidation performance to the stable isolated Pt single atoms anchored on the defective TiO2-HS surface. The Ptδ+ on the Pt1/TiO2-HS surface has a facile intense electron transfer with the support by forming Pt-O-Ti linkages, driving HCHO oxidation effectively. Further in situ HCHO-DRIFTS revealed that the dioxymethylene (DOM) and HCOOH/HCOO- intermediates were further degraded via active OH- and adsorbed oxygen on the Pt1/TiO2-HS surface, respectively. This work may pave the way for the next generation of advanced catalytic materials for high-efficiency catalytic HCHO oxidation at room temperature.
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Lignin-based carbon fibers (LCFs) with graphitized structures decorated on their surfaces were successfully prepared using the simultaneous catalyst loading and chemical stabilization of melt-spun lignin fibers, followed by quick carbonization functionalized as catalytic graphitization. This technique not only enables surficial graphitized LCF preparation at a relatively low temperature of 1200 °C but also avoids additional treatments used in conventional carbon fiber production. The LCFs were then used as electrode materials in a supercapacitor assembly. Electrochemical measurements confirmed that LCF-0.4, a sample with a relatively low specific surface area of 89.9 m2 g-1, exhibited the best electrochemical properties. The supercapacitor with LCF-0.4 had a specific capacitance of 10.7 F g-1 at 0.5 A g-1, a power density of 869.5 W kg-1, an energy density of 15.7 Wh kg-1, and a capacitance retention of 100% after 1500 cycles, even without activation.
ABSTRACT
The problem of drug resistance due to long-term use of antibiotics has been a concern for years. As this problem grows worse, infections caused by multiple bacteria are expanding rapidly and are extremely detrimental to human health. Antimicrobial peptides (AMPs) are a good alternative to current antimicrobials with potent antimicrobial activity and unique antimicrobial mechanisms, which have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections. Currently, researchers have conducted clinical investigations on AMPs for drug-resistant bacterial infections while integrating new technologies in the development of AMPs, such as changing amino acid structure of AMPs and using different delivery methods for AMPs. This article introduces the basic properties of AMPs, deliberates the mechanism of drug resistance in bacteria and the therapeutic mechanism of AMPs. The current disadvantages and advances of AMPs in combating drug-resistant bacterial infections are also discussed. This article provides important insights into the research and clinical application of new AMPs for drug-resistant bacterial infections.
Subject(s)
Anti-Infective Agents , Bacterial Infections , Humans , Antimicrobial Peptides , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/therapeutic use , Bacterial Infections/drug therapy , Anti-Infective Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria/metabolismABSTRACT
The Tembusu virus (TMUV), a member of the Flaviviridae family, can be transmitted via mosquitoes and cause poultry disease. In 2020, a strain of TMUV (YN2020-20) was isolated from mosquito samples collected in Yunnan province, China. In vitro experiments showed that TMUV-YN2020-20 produced a significant cytopathic effect (CPE) in BHK, DF-1, and VERO cells, while the CPE in C6/36 cells was not significant. Phylogenetic analysis revealed that the strain belonged to Cluster 3.2 and was closely related to the Yunnan mosquito-derived isolates obtained in 2012 and the Shandong avian-derived isolate obtained in 2014. Notably, TMUV-YN2020-20 developed five novel mutations (E-V358I, NS1-Y/F/I113L, NS4A-T/A89V, NS4B-D/E/N/C22S, and NS5-E638G) at loci that were relatively conserved previously. The results of this study demonstrate the continuous circulation and unique evolution of TMUV in mosquitoes in Yunnan province and suggest that appropriate surveillance should be taken.
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@#Abstract: Objective To elucidate the antigenic antibody reaction of recombinant expression of non-structural protein 1 (NS1) of Japanese encephalitis (JE) virus with various mosquito-borne flaviviruses, including JE virus, and the antigenic antibody reaction of serum samples of patients infected with JE virus in acute stage. Methods In this study, Escherichia coli prokaryotic expression vector (pET) system was used to recombinant express Japanese encephalitis virus NS1 gene. Western Blot assay was performed to detect the antibody responses of the recombinantly expressed protein against a variety of mosquito-transmitted flaviviruses, including JE virus, as well as antigen-antibody reactions of serum from patients with acute JE virus infection. Results The NS1 gene expression product of JE virus (P3 strain) was in the form of an inclusion body, and the denatured and renatured expression product was displayed as a single band in the denatured gel (polyacrylamide gel electrophoresis, PAGE), with a molecular weight of about 45 000. The results of further antigen-antibody analysis showed that the antigen/antibody hybridization reaction of the expression product with polyclonal or monoclonal antibody of JE virus (mosquito isolates, encephalitis isolates) and serum samples of patients with acute JE virus infection could be completely consistent. The recombinant product showed negative antigen/antibody hybridization reactions with mosquito-transmitted flaviviruses, such as dengue virus and yellow fever virus polyclonal antibodies, but positive reactions with polyclonal antibodies to West Nile virus and Murray Valley encephalitis virus. Conclusions In this study, the recombinant expression of the NS1 protein of JE virus was successfully obtained, and the antigen/antibody reaction between the recombinant protein and samples of patients infected with mosquito-borne flavivirus and JE virus was analyzed. The study results provide important basic data for elucidating the antigen-antibody reaction between the NS1 protein of JE virus and mosquito-borne flavivirus. The recombinant expression protein obtained in this study provides an important material basis for further research on the function of JE virus NS1 protein.
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In recent years, numerous viruses have been identified from ticks, and some have been linked to clinical cases of emerging tick-borne diseases. Chinese northeast frontier is tick infested. However, there is a notable lack of systematic monitoring efforts to assess the viral composition in the area, leaving the ecological landscape of viruses carried by ticks not clear enough. Between April and June 2017, 7101 ticks were collected to perform virus surveillance on the China-North Korea border, specifically in Tonghua, Baishan, and Yanbian. A total of 2127 Ixodes persulcatus were identified. Further investigation revealed the diversity of tick-borne viruses by transcriptome sequencing of Ixodes persulcatus. All ticks tested negative for tick-borne encephalitis virus. Transcriptome sequencing expanded 121 genomic sequence data of 12 different virus species from Ixodes persulcatus. Notably, a new segmented flavivirus, named Baishan Forest Tick Virus, were identified, closely related to Alongshan virus and Harz mountain virus. Therefore, this new virus may pose a potential threat to humans. Furthermore, the study revealed the existence of seven emerging tick-borne viruses dating back to 2017. These previously identified viruses included Mudanjiang phlebovirus, Onega tick phlebovirus, Sara tick phlebovirus, Yichun mivirus, and three unnamed viruses (one belonging to the Peribunyaviridae family and the other two belonging to the Phenuiviridae family). The existence of these emerging tick-borne viruses in tick samples collected in 2017 suggests that their history may extend further than previously recognized. This study provides invaluable insights into the virome of Ixodes persulcatus in the China-North Korea border region, enhancing our ongoing efforts to manage the risks associated with tick-borne viruses.
Subject(s)
Ixodes , Thogotovirus , Humans , Animals , Democratic People's Republic of Korea , Virome/genetics , China/epidemiology , RNAABSTRACT
Introduction: The Hedi virus (HEDV) and Wuxiang virus (WUXV) are newly discovered Bunyaviruses transmitted by sandflies. The geographical distribution of isolation of these two viruses continues to expand and it has been reported that WUXV causes neurological symptoms and even death in suckling mice. However, little is known about the prevalence of the two viruses in mammalian infections. Methods: In order to understand the infection status of HEDV and WUXV in humans and animals from regions where the viruses have been isolated, this study used Western blotting to detect the positive rates of HEDV and WUXV IgG antibodies in serum samples from febrile patients, dogs, and chickens in the forementioned regions. Results: The results showed that of the 29 human serum samples, 17.24% (5/29) tested positive for HEDV, while 68.96% (20/29) were positive for WUXV. In the 31 dog serum samples, 87.10% (27/31) were positive for HEDV and 70.97% (22/31) were positive for WUXV, while in the 36 chicken serum samples, 47.22% (17/36) were positive for HEDV, and 52.78% (19/36) were positive for WUXV. Discussion: These findings suggest there are widespread infections of HEDV and WUXV in mammals (dogs, chickens) and humans from the regions where these viruses have been isolated. Moreover, the positive rate of HEDV infections was higher in local animals compared to that measured in human specimens. This is the first seroepidemiological study of these two sandfly-transmitted viruses. The findings of the study have practical implications for vector-borne viral infections and related zoonotic infections in China, as well as providing an important reference for studies on the relationship between sandfly-transmitted viruses and zoonotic infections outside of China.
Subject(s)
Phlebotomus , Psychodidae , Sandfly fever Naples virus , Humans , Animals , Dogs , Mice , Chickens , Zoonoses/epidemiology , Mammals , Antibodies, Viral , China/epidemiologyABSTRACT
The development of anodes with highly efficient electrochemical catalysis and good durability is crucial for solid oxide fuel cells (SOFCs). This paper reports a superior Ru-doped La0.4Sr0.4Ti0.85Ni0.15O3-δ (L0.4STN) anode material with excellent catalytic activity and good stability. The doping of Ru can inhibit the agglomeration of in situ-exsolved Ni nanoparticles on the surface and induce the formation of abundant multiple-twinned defects in the perovskite matrix, which significantly increase the concentration of oxygen vacancies. The reduced L0.4STRN (R-L0.4STRN) anode shows an area-specific resistance (ASR) of 0.067 Ω cm2 at 800 °C, which is only about one-third of that of stochiometric R-L0.6STN (0.212 Ω cm2). A single cell with the R-L0.4STRN anode shows excellent stability (â¼50 h at 650 °C) in both H2 and CH4. Furthermore, R-L0.4STRN exhibits outstanding resistance to carbon deposition, which can be attributed to the synergistic effect of highly dispersed Ni nanoparticles and active twinned defects induced by Ru doping.
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The sluggish oxygen reduction reaction (ORR) is a central issue for energy conversion technologies, particularly in the cathodes of solid oxide fuel cells. The recognition of atomic-level kinetics of the ORR is the key solution. Herein, we take BaCo0.75Fe0.25O3 (BCF) perovskite cathode as a model to investigate the ambiguous ORR mechanism by density function theory and ab initio molecular dynamics. The oxygen dissociation process was found as the rate-determining step, and the performance of BCF series perovskite could be well-characterized by the dissociation barrier energy. Further electronic structure analysis demonstrated that the Pr (Nd)-Odis bond accepted electrons during the oxygen dissociation process, resulting in reduction of the barrier energy. Finally, strong correlations between rare earth 4f electrons and B-site transition metal 3d electrons were found to be another underlying descriptor to determine the electrochemical activity. We expected that the method could be universally applied to design or screen other high-performance perovskite cathodes.
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The dynamic kinetic resolution of C-N atropisomeric pyridones was achieved via asymmetric phase-transfer catalysis, exploiting a rotational barrier-lowering hydrogen bond in the starting materials. X-ray and NMR experiments revealed the presence of a barrier-raising ground state CHâ¯π interaction in the product, supported by DFT calculations. A co-crystal of the quinidine-derived phase-transfer catalyst and substrate reveals key substrate-catalyst non-covalent interactions.
Subject(s)
Pyridones , Catalysis , Hydrogen Bonding , Kinetics , Magnetic Resonance SpectroscopyABSTRACT
BACKGROUND: Early gut microbial colonization is important for postnatal growth and immune development of the chicken. However, at present, commercial chickens are hatched and raised without adult hens, thus are cut off from the microbiota transfer between hens and chicks. In this study, we compared the gut microbiota composition between hen-reared and separately reared chicks, and its impact on the resistance to H9N2 avian influenza virus, with the motive of investigating the impact of this cutoff in microbiota transfer. RESULTS: We used the 16SrRNA sequencing method to assess the composition of the gut microbiota in chicks represented by three hen-reared groups and one separately reared group. We found that the diversity of gut microbes in the chicks from the three hen-reared groups was more abundant than in the separately reared group, both at the phylum and genus levels. Our findings highlight the importance of early parental care in influencing the establishment of gut microbiota in the early life of chicks. SourceTracker analysis showed that the feather and cloaca microbiota of hens are the main sources of gut microbiota of chicks. After H9N2 exposure, the viral infection lasted longer in the separately reared chicks, with the viral titers in their oropharyngeal swabs being higher compared to the hen-reared chicks at day 5 post-infection. Interestingly, our results revealed that the gut microbiota of the hen-reared chicks was more stable after H9N2 infection in comparison to that of the separately reared chicks. CONCLUSIONS: Microbiota transfer between the hens and their chicks promotes the establishment of a balanced and diverse microbiota in the early life of the chicks and improves microbiota stability after H9N2 challenge. These findings advance our understanding of the protective role of gut microbiota in the early life of chicks and should be instrumental in improving chick rearing in the commercial poultry industry. Video Abstract.
Subject(s)
Gastrointestinal Microbiome , Influenza A Virus, H9N2 Subtype , Microbiota , Animals , Chickens , Cloaca , FemaleABSTRACT
Canine distemper virus (CDV) is a highly contagious virus that causes multi-systemic, sub-clinical to fatal diseases in a wide range of carnivore species. Based on the sequences of the haemagglutinin (H) gene, CDV strains have been classified into 18 major genetic lineages. In this study, we characterized the genomes of CDV isolated from the lungs of two dead red pandas in China. Histopathological and immunohistochemical analyses revealed damage due to viral infection in these lungs. The two strains showed a deep genetic distance from the other 18 recognized lineages (>4.6% at nucleotide level and >5.0% at amino acid level). The maximum clade credibility tree of the H- gene sequences showed that they belonged to an independent clade and had diverged a relatively long time ago from the Asia-4 lineage (since 1884). These results suggest that the analyzed strains belong to a new CDV lineage, which we designate as Asia-6. Our finding indicates that CDV infections in wildlife in China are complex and are a threat to endangered carnivores.
Subject(s)
Carnivora , Distemper Virus, Canine , Distemper , Dog Diseases , Animals , China/epidemiology , Distemper/epidemiology , Distemper Virus, Canine/genetics , Dogs , Hemagglutinins, Viral/genetics , PhylogenyABSTRACT
Since its first isolation in around 2007, the avian-origin H3N2 canine influenza virus (CIV) has become established and continues to circulate in dog populations. This virus serves as a useful model for deciphering the complex evolutionary process of interspecies transmission of influenza A virus (IAV) from one species to its subsequent circulation in another mammalian host. The present investigation is a comprehensive effort to identify and characterize genetic changes that accumulated in the avian-origin H3N2 CIV during its circulation in the dog. We revealed that H3N2 CIV experiences greater selection pressure with extremely high global non-synonymous to synonymous substitution ratios per codon (dN/dS ratio) for each gene compared to the avian reservoir viruses. A total of 54 amino acid substitutions were observed to have accumulated and become fixed in the H3N2 CIV population based on our comprehensive codon-based frequency diagram analysis. Of these substitutions, 11 sites also display high prevalence in H3N8 CIV, indicating that convergent evolution has occurred on different lineages of CIV. Notably, six substitutions, including HA-G146S, M1-V15I, NS1-E227K, PA-C241Y, PB2-K251R, and PB2-G590S, have been reported to play imperative roles in facilitating the transmission and spillover of IAVs across species barriers. Most of these substitutions were found to have become fixed in around 2015, which might have been a favorable factor that facilitating the spread of these CIV lineages from South Asia to North America and subsequent further circulation in these areas. We also detected 12 sites in six viral genes with evidence for positive selection by comparing the rates of non-synonymous and synonymous substitutions at each site. Besides, our study reports trends of enhanced ongoing adaptation of H3N2 CIV to their respective host cellular systems, based on the codon adaptation index analysis, which points toward increasing fitness for efficient viral replication. In addition, a reduction in the abundance of the CpG motif, as evident from an analysis of relative dinucleotide abundance, may contribute to the successful evasion of host immune recognition. The present study provides key insights into the adaptive changes that have accumulated in the avian-origin H3N2 viral genomes during its establishment and circulation into dog populations.
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Interstitial fibrosis is a typical feature of all progressive renal diseases. The process of fibrosis is frequently coupled with the presence of pro-fibrotic factors and inflammation. Naringin is a dihydroflavone compound that has been previously reported to exhibit anti-fibrotic effects in the liver, where it prevents oxidative damage. In the present study, a rat model of renal interstitial fibrosis and fibrosis cell model were established to evaluate the effects of naringin on inflammatory proteins and fibrosis markers in kidney of rats and NRK-52E cells, and to elucidate the role of the TGF-ß/Smad signaling pathway in this mechanism. Compared with those in fibrotic NRK-52E cells that were stimulated by transforming growth factor-ß (TGF-ß), gene expression levels of α-smooth muscle actin (α-SMA), collagen 1 (COL1A1), collagen 3 (COL3A1), interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) were all found to be significantly decreased in fibrotic NRK-52E cells following treatment with naringin (50, 100 and 200 ng/ml). Results from the histopathological studies showed that naringin treatment preserved the renal tissue structure and reduced the degree of fibrosis in the kidney tissues of rats that underwent unilateral ureteral obstruction (UUO). In addition, naringin administration reduced the expression of α-SMA, COL1A1, COL3A1, IL-1ß, IL-6 and TNF-α in the kidneys of rats following UUO. The current study, using western blot analysis, indicated that naringin also downregulated the activation of Smad2/3 and the expression of Smad4, high-mobility group protein B1, activator protein-1, NF-κB and cyclooxygenase-2 whilst upregulating the expression of Smad7 in fibrotic NRK-52E cells and rats in the UUO group. In conclusion, naringin could antagonize renal interstitial fibrosis by regulating the TGF-ß/Smad pathway and the expression of inflammatory factors.