The Role of MicroRNA-206 in the Regulation of Diabetic Wound Healing via Hypoxia-Inducible Factor 1-Alpha.

Successful wound healing in diabetic patients is hindered by dysregulated miRNA expression. This study aimed to investigate the abnormal expression of miRNAs in diabetic wound healing and the potential therapeutic role of modulating the miR-206/HIF-1α pathway. MicroRNA assays were used to identify differentially expressed miRNAs in diabetic wound sites and adjacent areas. In vitro models and a rat diabetic model were established to evaluate the effects of miR-206 on HIF-1α regulation and wound healing. The study revealed differential expression of miR-206 in diabetic wound tissues, its interaction with HIF-1α, and the inhibitory effect of miR-206 on cell growth under high glucose conditions. Modulating the miR-206/HIF-1α pathway using miR-206 antagomir promoted HIF-1α, CD34, and VEGF expression, ultimately enhancing diabetic wound healing.

A single immunization with core-shell structured lipopolyplex mRNA vaccine against rabies induces potent humoral immunity in mice and dogs.

The persistence and clinical consequences of rabies virus (RABV) infection have prompted global efforts to develop a safe and effective vaccines against rabies. mRNA vaccines represent a promising option against emerging and re-emerging infectious diseases, gaining particular interest since the outbreak of COVID-19. Herein, we report the development of a highly efficacious rabies mRNA vaccine composed of sequence-modified mRNA encoding RABV glycoprotein (RABV-G) packaged in core-shell structured lipopolyplex (LPP) nanoparticles, named LPP-mRNA-G. The bilayer structure of LPP improves protection and delivery of RABV-G mRNA and allows gradual release of mRNA molecules as the polymer degrades. The unique core-shell structured nanoparticle of LPP-mRNA-G facilitates vaccine uptake and demonstrates a desirable biodistribution pattern with low liver targeting upon intramuscular immunization. Single administration of low-dose LPP-mRNA-G in mice elicited potent humoral immune response and provided complete protection against intracerebral challenge with lethal RABV. Similarly, single immunization of low-dose LPP-mRNA-G induced high levels of virus-neutralizing antibody titers in dogs. Collectively, our data demonstrate the potential of LPP-mRNA-G as a promising next-generation rabies vaccine used in human and companion animals.

An application of stereo matching algorithm based on transfer learning on robots in multiple scenes.

Robot vision technology based on binocular vision holds tremendous potential for development in various fields, including 3D scene reconstruction, target detection, and autonomous driving. However, current binocular vision methods used in robotics engineering have limitations such as high costs, complex algorithms, and low reliability of the generated disparity map in different scenes. To overcome these challenges, a cross-domain stereo matching algorithm for binocular vision based on transfer learning was proposed in this paper, named Cross-Domain Adaptation and Transfer Learning Network (Ct-Net), which has shown valuable results in multiple robot scenes. First, this paper introduces a General Feature Extractor to extract rich general feature information for domain adaptive stereo matching tasks. Then, a feature adapter is used to adapt the general features to the stereo matching network. Furthermore, a Domain Adaptive Cost Optimization Module is designed to optimize the matching cost. A disparity score prediction module was also embedded to adaptively adjust the search range of disparity and optimize the cost distribution. The overall framework was trained using a phased strategy, and ablation experiments were conducted to verify the effectiveness of the training strategy. Compared with the prototype PSMNet, on KITTI 2015 benchmark, the 3PE-fg of Ct-Net in all regions and non-occluded regions decreased by 19.3 and 21.1% respectively, meanwhile, on the Middlebury dataset, the proposed algorithm improves the sample error rate at least 28.4%, which is the Staircase sample. The quantitative and qualitative results obtained from Middlebury, Apollo, and other datasets demonstrate that Ct-Net significantly improves the cross-domain performance of stereo matching. Stereo matching experiments in real-world scenes have shown that it can effectively address visual tasks in multiple scenes.

Pea-Tea Intercropping Improves Tea Quality through Regulating Amino Acid Metabolism and Flavonoid Biosynthesis.

Pea-tea intercropping is an excellent cultivation method that can improve tea quality. However, the underlying mechanism is still unclear. The present study was aimed at elucidating the mechanism of the effect of pea-tea intercropping on tea quality through a high-throughput method. Transcriptome and metabolome analyses were conducted to identify the changes in gene expression and metabolites changes intercropping, respectively. In addition, the amino acids and catechins were detected using the LC-MS method and quantified absolutely. The results showed that total polyphenols and catechins decreased but amino acids increased in pea intercropped tea shoots. Correspondingly, genes related to amino acid metabolism and flavonoid biosynthesis were differentially expressed. For amino acid metabolism, 11 differentially expressed genes were identified, including 5 upregulated and 6 downregulated genes. Meanwhile, three genes involved in carbohydrate transport and metabolism were upregulated in pea intercropped tea plants. These genes were also involved in amino acid metabolism. For flavonoid biosynthesis, two downregulated genes were identified, which were the flavonol synthase and anthocyanidin synthase genes and followed a similar pattern to changes in catechins and polyphenols. These advances have opened new horizons for understanding the biochemical mechanisms of amino acids and flavonoids in improving tea quality in the pea-tea intercropping cultivation model.

Inter-Fighting between Influenza A Virus NS1 and ß-TrCP: A Novel Mechanism of Anti-Influenza Virus.

Influenza A virus (IAV) prevents innate immune signaling during infection. In our previous study, the production of pro-inflammatory cytokines was associated with Cullin-1 RING ligase (CRL1), which was related to NF-κB activation. However, the underlying mechanism is unclear. Here, an E3 ligase, ß-transducin repeat-containing protein (ß-TrCP), was significantly downregulated during IAV infection. Co-IP analysis revealed that non-structural 1 protein (NS1) interacts with ß-TrCP. With co-transfection, an increase in NS1 expression led to a reduction in ß-TrCP expression, affecting the level of IκBα and then resulting in repression of the activation of the NF-κB pathway during IAV infection. In addition, ß-TrCP targets the viral NS1 protein and significantly reduces the replication level of influenza virus. Our results provide a novel mechanism for influenza to modulate its immune response during infection, and ß-TrCP may be a novel target for influenza virus antagonism.

Molecular Link in Flavonoid and Amino Acid Biosynthesis Contributes to the Flavor of Changqing Tea in Different Seasons.

The present study was aimed to elucidate the flavor formation mechanism of Changqing tea. High-performance liquid chromatography (HPLC) analysis showed that the total catechins of Changqing tea was 65-160 mg/g, with 16-34 mg/g non-galloyated catechins and 49-126 mg/g galloylated catechins. Tea polyphenols and free amino acids account for 286-312 mg/g and 35-89 mg/g, respectively. Transcriptome of Changqing tea during different seasons revealed 316, 130 and 12 DEGs in comparisons of spring vs. autumn, spring vs. summer, and summer vs. autumn, respectively. Compared to spring, the genes involved in flavonoid biosynthesis and bitter imparted amino acids were up-regulated in summer and autumn. Metabolome analysis was conducted by using HPLC-MS; the result indicated that umami and kokumi contributing amino acids were decreased in summer and autumn compared with spring. It could be concluded that the coordination of flavonoid biosynthesis and amino acids biosynthesis resulted in the special flavor of Changqing tea.

The effect of coupled inhibitory-facilitatory repetitive transcranial magnetic stimulation on shaping early reorganization of the motor network after stroke.

Neural plasticity is a major factor driving cortical reorganization after stroke. This study aimed to evaluate functional connectivity (FC) changes in the cortical motor network after coupled inhibitory-facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment and to assess the correlation between FC changes and functional recovery, further characterizing the neural mechanisms underlying the beneficial effects of rTMS. We randomly divided 63 patients with acute stroke into four groups: (1) Group A received coupled inhibitory-facilitatory rTMS [1 Hz over the contralesional primary motor cortex (M1) and 10 Hz over ipsilesional M1]; (2) Group B received a contralesional sham stimulation and ipsilesional 10 Hz stimulation; (3) Group C received a contralesional 1 Hz rTMS and ipsilesional sham stimulation; and (4) Group D received bilateral sham stimulation only. Standardized rehabilitation therapy was performed immediately after rTMS, and each group was treated with their respective treatment modalities for 4 weeks. Twenty-four hours before and after the intervention, participants underwent resting-state functional magnetic resonance imaging. Additional functional assessments were conducted at baseline, after treatment, and at the 3 month follow-up. The rTMS treatment significantly changed the FCs of intra- and inter-hemispheric cortical motor networks in the rTMS groups (A and B) compared with the sham group (Group D). This effect was more pronounced in Group A, which displayed a changed FC between the contralesional postcentral gyrus and contralesional superior parietal gyrus, between the contralesional precentral gyrus and contralesional postcentral gyrus, and between the ipsilesional postcentral gyrus and contralesional superior parietal gyrus, when compared with Groups B and C. Importantly, FC changes were significantly correlated with improvement of motor function. In the early stages of ischemic stroke, coupled rTMS was more conducive to motor recovery by modulating the FCs of intra-hemispheric and inter-hemispheric motor networks. Our results suggested that FC changes were related to motor function recovery for early-stage cerebral stroke patients treated with coupled rTMS. These findings could help to understand the mechanism of coupled rTMS and further the use of this therapy as an adjunct rehabilitation technique in motor recovery.

Isolation and pathogenic characterization of duck adenovirus 3 mutant circulating in China.

Duck adenoviruses (DAdVs) include serotype 1 (DAdV-1) in the genus Atadenovirus and serotypes 2-4 (DAdV-2, 3, and 4) in the genus Aviadenovirus. DAdV-3 was initially isolated from Chinese Muscovy ducks in 2014, whereby the infected ducks exhibited yellowing and hemorrhaging in the liver, along with slight pericardial effusion, swelling, and hemorrhaging in the kidneys. In recent years, duck adenovirus infections have appeared in Muscovy duck farms in Fujian, Zhejiang, Anhui, Guangdong, and other places in China. They have an incidence rate of 40 to 55% and a mortality rate of 35 to 43%, resulting in great losses to the duck breeding industry. In this study, 7 DAdV-3 strains, designated as TZ193, FJPT20161124, GX20170519, FJZZ, GDMM, AHAQ, and GDHS were isolated from Muscovy ducks in different provinces of China during 2016-2019, and their complete genomics were sequenced. Their genomes all exhibited significant deletions in ORF67, which also had G to A transitions at the 41st and 977th nt positions, resulting in a stop codon. The pathogenicity of TZ193, a novel isolate of DAdV-3, was investigated in Muscovy ducks. TZ193 caused characteristic lesions of swelling as well as hemorrhagic liver and kidney in the infected ducklings. Moreover, the mortality rate of TZ193 in 5-day-old domestic ducks was 100%. Our data provide concrete evidence for the identification of the DAdV-3 novel variant mutant in China, which effects increased mortality in ducks. This highlights the necessity for monitoring the specific molecular epidemiology of novel DAdV-3 mutants and the development of new vaccines in the future.

Combining inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment improves motor function by modulating GABA in acute ischemic stroke patients.

BACKGROUND: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. OBJECTIVES: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. METHODS: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. RESULTS: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). CONCLUSIONS: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.

[Changes of regional saturation of cerebral oxygenation and neuron specific enolase in patients after cardiopulmonary resuscitation].

OBJECTIVE: To observe the changes of regional saturation of cerebral oxygenation (rScO2) and blood neuron specific enolase (NSE) in patients after cardiopulmonary resuscitation (CPR), and to explore its value in evaluating the prognosis of patients' neurological function. METHODS: From January 2012 to December 2020, 97 patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA) treated in the intensive care unit (ICU) of the Second Affiliated Hospital of Soochow University were selected. According to the prognosis, the patients were divided into two groups: good neurological function group [Glasgow-Pittsburgh Cerebral Performance Categories (CPC) 1-2, 20 cases] and neurological dysfunction group (CPC classification 3-5, 77 cases). The clinical data of gender, age, the number of patients with defibrillable rhythm, time of ROSC, the number of CA patients outside the hospital, acute physiology and chronic health evaluation II (APACHE II), Glasgow coma scale (GCS), global non-response scale (FOUR), body temperature, mean arterial pressure (MAP), blood lactic acid (Lac) and GCS at discharge, as well as the length of ICU stay, rScO2 and blood NSE were collected. The differences of rScO2 and NSE between the two groups were compared; and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of rScO2 and NSE alone or in combination in predicting the prognosis of patients with ROSC after CA. RESULTS: The rScO2 of good neurological function group was significantly higher than that of neurological dysfunction group at 1, 3, 6, 12, 24 and 48 hours (all P < 0.05). At 24 hours after admission, the rScO2 on the left and right sides of good neurological function group was significantly higher than that in neurological dysfunction group [left: 0.65 (0.59, 0.76) vs. 0.55 (0.44, 0.67), right: 0.62 (0.61, 0.73) vs. 0.50 (0.30, 0.69), both P < 0.05], and NSE was significantly lower than that in the neurological dysfunction group [ng/L: 21.42 (15.38, 29.69) vs. 45.82 (24.05, 291.26), P < 0.05]. ROC curve analysis showed that both rScO2 and NSE alone and combined detection had a certain value in predicting the prognosis of neurological function in patients with ROSC after CA, and the area under the ROC curve (AUC) detected by the combination was the largest, which was higher than the AUC predicted by rScO2 or NSE (0.904 vs. 0.884, 0.792). When the cut-off value of combination was 0.83, the sensitivity and specificity were 75.7% and 100% respectively. CONCLUSIONS: Monitoring rScO2 and NSE can predict the prognosis of neurological function after CPR, especially the combined evaluation of the two indexes, which can greatly improve the accuracy of diagnosis.

Key Amino Acids of M1-41 and M2-27 Determine Growth and Pathogenicity of Chimeric H17 Bat Influenza Virus in Cells and in Mice.

Based on our previous studies, we show that the M gene is critical for the replication and pathogenicity of the chimeric H17 bat influenza virus (Bat09:mH1mN1) by replacing the bat M gene with those from human and swine influenza A viruses. However, the key amino acids of the M1 and/or M2 proteins that are responsible for virus replication and pathogenicity remain unknown. In this study, replacement of the PR8 M gene with the Eurasian avian-like M gene from the A/California/04/2009 pandemic H1N1 virus significantly decreased viral replication in both mammalian and avian cells in the background of the chimeric H17 bat influenza virus. Further studies revealed that M1 was more crucial for viral growth and pathogenicity than M2 and that the amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins identified in this study might be important for influenza virus surveillance and could be used to produce live attenuated vaccines in the future. IMPORTANCE The M1 and M2 proteins influence the morphology, replication, virulence, and transmissibility of influenza viruses. Although a few key residues in the M1 and M2 proteins have been identified, whether other residues of the M1 and M2 proteins are involved in viral replication and pathogenicity remains to be discovered. In the background of the chimeric H17 bat influenza virus, the Eurasian avian-like M gene from the A/California/04/2009 virus significantly decreased viral growth in mammalian and avian cells. Further study showed that M1 was implicated more than M2 in viral growth and pathogenicity in vitro and in vivo and that the key amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins could be used for influenza virus surveillance and live attenuated vaccine applications in the future. These findings provide important contributions to knowledge of the genetic basis of the virulence of influenza viruses.

Effects of mirror therapy on motor aphasia after acute cerebral infarction: A randomized controlled trial.

BACKGROUND: Mirror therapy (MT) has proven to be beneficial for treating patients suffering from motor aphasia after stroke. However, the impacts of MT on neuroplasticity remain unexplored. OBJECTIVE: In this paper we conducted a randomized controlled trial to evaluate the treatment using the MT on motor aphasia following acute cerebral infarction. METHODS: We randomly assigned 30 patients into test and control groups, with test group patients treated with MT, whereas control group patients were treated with sham MT. At 24 hours prior to and after the intervention, we obtained functional magnetic resonance imaging (fMRI) data from study subjects. At baseline, after treatment and 12-week follow-up, we additionally evaluated patients with the Modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the aphasia quotient (AQ) in the western aphasia test. RESULTS: After 2 weeks of treatment, the test group demonstrated significant improvements in AQ values, naming, repetition, spontaneous speech, and mRS scores compared to the control group (P < 0.05). Furthermore, in the follow-up time point (12 weeks), we found that the test group exhibited significantly better NIHSS scores and AQ evaluation indicators than the control group (P < 0.05). Specifically, the fMRI study shows that functional connectivity significantly improved in test group patients mainly among frontal, temporal, and parietal lobes of the left hemisphere with each other than controls group. Meanwhile, we found significantly enhanced functional connectivity with the hippocampus (P < 0.01). CONCLUSIONS: Our results indicate that the MT can expedite the recovery of language function during the early phases of stroke recovery. These findings may elucidate the underlying mechanism of MT and the application of this therapy as an adjunct rehabilitation technique in language recovery.

Red Light Regulates the Metabolite Biosynthesis in the Leaves of "Huangjinya" Through Amino Acid and Phenylpropanoid Metabolisms.

"Huangjinya" is a light-sensitive albino variety and is widely cultivated in China. It has been proved that red light could promote the vegetable growth of plants. However, the mechanism of "Huangjinya" in response to a red light is unclear. This study used high-throughput sequencing technology to analyze the transcriptome of tender shoots of "Huangjinya" under the white and red light supplement conditions. At the same time, liquid chromatography tandem mass spectrometry (LC-MS) was used to analyze metabolite changes under different light conditions. Transcriptome analysis revealed that a total of 174 differentially expressed genes (DEGs) were identified after the red light supplement. Kyoto encyclopedia of genes and genomes (KEGG) classification indicated that amino acid metabolism enriched the most DEGs. In addition, two phenylpropanoid metabolism-related genes and five glutathione S-transferase genes (CsGSTs) were found to be expressed differently. Metabolome analysis revealed that 193 differential metabolites were obtained. Being the same as transcriptome analysis, most differential metabolites were enriched in amino acids, sweet and umami tasting amino acids were increased, and bitter-tasting amino acids were decreased after the red light supplement. In summary, red light supplementary treatment may be propitious to the quality of "Huangjinya" due to its regulatory effect on amino acid metabolism. Also, CsGSTs involved phenylpropanoid metabolism contributed to tea quality changes in "Huangjinya."

Effects of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation on motor recovery in patients following acute cerebral infarction.

BACKGROUND: The treatment for patients suffering from motor dysfunction following stroke using continuous repetitive transcranial magnetic stimulation (rTMS) has the potential to be beneficial for recovery. However, the impact of explicit results on the coupling of various rTMS protocols on motor treatment in patients following acute cerebral infarction remain unexplored. OBJECTIVE: The current study aims to design a sham-controlled randomized report to explore the capability of consecutive suppressive-facilitatory rTMS method to increase the motor results following acute stroke. METHODS: A hundred ischemic stroke patients suffering from motor disorder were randomly assigned to obtain 4 week sessions of (1)10 Hz over the ipsilesional primary motor cortex (M1) and next 1 Hz over the contralesional M1; (2) contralesional sham stimulation and next ipsilesional real 10 Hz; (3) contralesional real 1 Hz rTMS and next ipsilesional sham stimulation; or (4) bilateral sham-control procedures. At 24 hours before and after the intervention, we obtained cortical excitability data from study subjects. At baseline, after treatment and 3 months follow up, we additionally evaluated patients with the clinical assessments. RESULTS: At post-intervention, group A showed greater motor improvements in FMA, FMA-UL, NIHSS, ADL and mRS values than group B, group C and group D, that were continued for at least 3 months after the completion of the treatment time. Specifically, it is shown in the cortical excitability study that the motor-evoked potential (MEP) amplitude and resting motor threshold (rMT) more significantly improved in group A than other groups. The improvement in motor function and change in motor cortex excitability exhibit a significant correlation in the affected hemisphere. The combined 1 Hz and 10 Hz stimulation treatment showed a synergistic effect. CONCLUSIONS: Facilitatory rTMS and coupling inhibitory produced extra satisfactory results in facilitating the motor's recovery in the subacute and acute phase following stroke compared to that acquired from alone single-course modulation.

Metabolic Regulation Profiling of Carbon and Nitrogen in Tea Plants [Camellia sinensis (L.) O. Kuntze] in Response to Shading.

Manipulating light transmission by shading is the most effective method of improving the nutritional value and sensory qualities of tea. In this study, the metabolic profiling of two tea cultivars ("Yulv" and "Maotouzhong") in response to different shading periods during the summer season was performed using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS) and gas chromatography-mass spectrometry (GC-MS). The metabolic pathway analyses showed that the glycolytic pathway and the tricarboxylic acid cycle (TCA cycle) in the leaves and shoots of "Maotouzhong" were significantly inhibited by long-term shading. The nitrogen metabolism in the leaves of the two cultivars was promoted by short-term shading, while it was inhibited by long-term shading. However, the nitrogen metabolism in the shoots of the two cultivars was always inhibited by shading, whether for short or long-term periods. In addition, the intensity of the flavonoid metabolism in both tea cultivars could be reduced by shading. These results revealed that shading could regulate the carbon and nitrogen metabolism and short-term shading could improve the tea quality to some extent.

GABA-induced motor improvement following acute cerebral infarction.

γ-Aminobutyric acid (GABA) plays a key role in motor learning. In the aftermath of stroke, we monitored GABA+ content of primary motor cortex by magnetic resonance spectroscopy (MRS), assessing its relation to functional motor recovery following a standardized 4-week program of rehabilitation. The cohort included 20 patients, each experiencing stroke within 2 weeks of symptom onset. Twenty age-matched healthy subjects were also recruited as controls. GABA+ levels were determined at baseline and following rehabilitation, performed only once in sex- and age-matched control subjects. Motor functions were then measured via Fugl-Meyer Assessment (FMA). Processing of MRS data was driven by open-source Gannet software. Because GABA, macromolecules, and homocarnosine jointly contribute to MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) signals, the designation GABA+ (rather than GABA) was applied. Baseline GABA+/creatine (Cr) ratios proved significantly lower in patients with strokes than in control subjects (P<0.05). Following the 4-week rehabilitative regimen, significant improvement in FMA indices was evident across the test group. FMA scores and GABA+/Cr ratios correlated significantly at baseline, the GABA+/Cr ratio displaying a significant association with motor function (P=0.025). In the setting of acute stroke, GABA+/Cr ratios of primary motor cortex fell significantly below levels found in healthy subjects. The observed association between GABA+/Cr ratio and motor recovery underscores the utility of MRS-measured GABA as a key motor recuperative biomarker.

Characterization and pathogenicity of fowl adenovirus serotype 4 isolated from eastern China.

BACKGROUND: Fowl adenovirus outbreaks have occurred in China since June 2015. This virus is an emerging infectious disease that causes hydropericardium syndrome and inclusion body hepatitis (HPS-IBH), resulting in significant economic loss to poultry farmers. Five fowl adenovirus (FAdV) strains (HN, AQ, AH726, JS07 and AH712) were isolated from Jiangsu and Anhui provinces. RESULTS: Phylogenetic analysis revealed that the five isolates belonged to species C fowl adenovirus serotype 4. An 11 amino-acid deletion in ORF29, relative to an older viral isolate, JSJ13, was observed for all five strains described here. In chicken experiments, 80-100% birds died after intramuscular inoculation and displayed lesions characteristic of HPS-IBH. The viral DNA copies were further detected by hexon-probe based real-time polymerase chain reaction (PCR) in the chicken samples. The viral loads and cytokine profiles were recorded in all the organs after infections. Despite minor genetic differences, the 5 strains displayed significantly different tissue tropisms and cytokine profiles. CONCLUSIONS: Our data enhance the current understanding some of the factors involved in the pathogenicity and genetic diversity of the FAdV serotype 4 (FAdV-4) in China. Our work provides theoretical support for the prevention and control of HPS-IBH in chickens.

H9N2 Viruses Isolated From Mammals Replicated in Mice at Higher Levels Than Avian-Origin Viruses.

H9N2 subtype influenza A virus (IAV) has more than 20 genotypes that are able to cross species barriers and expand from birds to mammals and humans. To better understand the impact of different H9N2 genotypes and their characteristics, five H9N2 viruses from different hosts including chickens, geese, pigs, mink, and humans representing the B69 88(Gs/14, Ck/15, and Mi/14), B35 (Sw/08) and G9 genotypes (Hu/04) were infected in chicken and mice. In mice, mammal-origin viruses replicated at higher levels in the lungs compared to avian viruses. The goose-virus replicated at the lowest levels indicating poor adaptation. Increased pro-inflammatory cytokines were positively correlated with viral loads in the lung. In chickens, all viruses were excreted from cloacal and/or oropharyngeal swabs. Interestingly, Mink-origin virus exhibited higher virulence and replication in mice and chickens. Our data indicate that mammal-origin H9N2 viruses are more adapted and virulent in mice than the avian-origin viruses.

A novel linear epitope crossing Group 1 and Group 2 influenza A viruses located in the helix A of HA2 derived from H7N9.

In this research, four monoclonal antibodies (mAbs) were first generated as an immunogen by using the GST fusion protein that carries the fusion peptide and helix A derived from H7N9 influenza A virus (IAV). These mAbs could react with HA of H7N9, H3N2, and H9N2 with neutralizing activity. A novel linear epitope recognized by these mAbs was identified by peptide-based ELISA, and this epitope was located in TAADYKSTQSAIDQITGKLN at the C terminus of the helix A of H7N9. 3 A11, which is one of the four mAbs, could efficiently recognize the corresponding epitopes derived from H9, H7, H5, H3, and H1. Analysis of sera against the corresponding epitope from different HAs revealed that the C terminus of helix A in H9, H7, and H3 possessed dominant B cell epitopes that cross both Group 1 and Group 2 IAV, whereas the C terminus of helix A in H5 possessed only dominant B cell epitopes that cross subtypes in Group 1 virus. All these results demonstrated that the linear epitope identified in the helix A of H7N9 could be a novel target for developing broad-spectrum influenza diagnostics or vaccine candidates.