The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant’s internal genes. However, it is ...not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010–2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.
Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment ...is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.
This single-arm, single-centre trial enrolled children (aged 1–18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing.
Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes vg and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1–2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40–57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5–4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery.
AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9.
National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.
Chronic subjective tinnitus poses significant challenges in clinical practice, and it is usually associated with hearing impairment, particularly with high-frequency sensorineural hearing loss ...(SNHL). Patients suffering from tinnitus with SNHL experience one of the most severe sensory disabilities, and this has devastating effects on their quality of life. Nowadays, mild to moderate SNHL can be managed with a properly fitted hearing aid (HA) that provides sound amplification, and several studies suggest that HAs may also benefit those with tinnitus. However, inadequate attention has been paid by medical personnel to the impact of HA use in residual hearing protection for patients with tinnitus and coexisting SNHL, and existing evidence is still at a preliminary stage. This study aims to identify and evaluate the efficacy of the use of HAs in both sound perception and residual hearing preservation among patients with tinnitus and coexisting SNHL.
The present study is a prospective, single-center, outcome assessor and data analyst-blinded, randomized, controlled trial. Eligible participants will be recruited and randomly allocated into the HA intervention group and the waiting list control group at a ratio of 1:1. The primary outcome is to evaluate the severity of tinnitus using the Tinnitus Handicap Inventory as a continuous variable at 6 months from randomization. Secondary outcome measures include changes in hearing status and mental states. The trial will last 6 months, with follow-up visits at 3 months and 6 months.
This will be the first randomized, controlled trial to identify and evaluate HAs' efficacy on residual hearing preservation among tinnitus patients with coexisting high-frequency SNHL in China. We are aiming for novelty and generalizability, and strengths of this study are that it will examine the effectiveness of HA in patients with tinnitus and hearing impairment and will further explore the residual hearing protection provided by HA treatment in the tinnitus group.
ClinicalTrials.gov NCT05343026. Registered on April 25, 2022.
•Four-three fowl adenovirus strains isolated between 2007 to 2014 in China were characterized, using molecular methods.•This is the first finding of FAdV4 infection and HPS cases in ...ostriches.•Serotype 11 were dominant over this period.•The pathogens were mainly distributed in north and east of China.•Strict biosecurity protection measures are necessary to control FAdV.
Forty-three fowl adenovirus (FAdV) strains were isolated in China from 2007 to 2014 from poultry and ostriches with inclusion body hepatitis (IBH) and hydropericardium syndrome (HPS). Phylogenetic analysis showed that 28/43 strains clustered into Fowl aviadenovirus D (FAdV-D) and 9/43 strains clustered into FAdV-E. FAdV-C included three isolates of ostrich origin, one of goose origin and two of chicken origin. Based on hexon loop 1 gene sequencing analysis, these viruses were genetically related to FAdV-4, FAdV-8a, FAdV-8b and FAdV-11, of which FAdV-11 was dominant. The isolation in 2014 of three FAdV strains belonging to serotype 4 from ostrich flocks is to our knowledge the first finding of FAdV-4 infection and HPS cases in ostriches. Epidemiological analysis showed that FAdV has been circulating in northern and eastern China, where more than 50% of layers and broilers are raised. The hosts of this pathogen included broilers, layers, geese and ostriches. IBH and HPS cases had a sporadic or cluster distribution from 2007 to 2013; however, since 2014 the number of cases has increased sharply. To control FAdV, strict biosecurity protection measures are necessary and a multivalent vaccine may be needed.
Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was ...identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.3.2.1c HA gene and a H9N2-derived PB2 gene. Sanmenxia Clade 2.3.2.1c-like H5N1 viruses possess the closest genetic identity to A/Alberta/01/2014 (H5N1), which recently caused a fatal respiratory infection in Canada with signs of meningoencephalitis, a highly unusual symptom with influenza infections in humans. Furthermore, this virus was shown to be highly pathogenic to both birds and mammals, and demonstrate tropism for the nervous system. Due to the geographical location of Sanmenxia, these novel H5N1 viruses also have the potential to be imported to other regions through the migration of wild birds, similar to the H5N1 outbreak amongst migratory birds in Qinghai Lake during 2005. Therefore, further investigation and monitoring is required to prevent this novel reassortant virus from becoming a new threat to public health.
Monolepta hieroglyphica (Motschulsky) (Coleoptera: Chrysomelidae) is an important agricultural insect pest. In this study, the complete mitochondrial genome of M. hieroglyphica was sequenced using ...Illumina HiSeq X Ten. The mitogenome was 16,213 bp long and comprised 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs) and a putative control region (CR). The nucleotide composition of the M. hieroglyphica mitochondrial genome was significantly biased (A, G, C and T accounted for 41.04%, 8.01%, 11.76% and 39.18%, respectively) with 80.23% A + T content. Two rRNAs were located between tRNA-Leu and the CR, separated by tRNA-Val. The CR, located between 12 s rRNA and tRNA-Ile, was 1661 bp long. The length of the 22 tRNAs ranged from 61 to 71 bp. Phylogenetic analyses of 29 Chrysomelidae-Galerucinae species based on 13 mitochondrial protein-coding genes reconstructed using Bayesian 3.2.0 showed that the M. hieroglyphica mitogenome was clustered with the existing three different species of the Monolepta genus mitogenomes in a monophyletic manner. The M. hieroglyphica mitogenome provides an important data resource for further studies and contributes to our understanding of the phylogeny of this group.
Ouabain application to the round window can selectively destroy type-I spiral ganglion cells, producing an animal model of auditory neuropathy. To assess the long-term effects of this deafferentation ...on synaptic organization in the organ of Corti and cochlear nucleus, and to ask whether surviving cochlear neurons show any post-injury plasticity in the adult, we quantified the peripheral and central synapses of type-I neurons at posttreatment times ranging from 1 to 3 months. Measures of normal DPOAEs and greatly reduced auditory brainstem responses (ABRs) confirmed the neuropathy phenotype. Counts of presynaptic ribbons and postsynaptic glutamate receptor patches in the inner hair cell area decreased with post-exposure time, as did counts of cochlear nerve terminals in the cochlear nucleus. Although these counts provided no evidence of new synapse formation via branching from surviving neurons, the regular appearance of ectopic neurons in the inner hair cell area suggested that neurite extension is not uncommon. Correlations between pathophysiology and histopathology showed that ABR thresholds are very insensitive to even massive neural degeneration, whereas the amplitude of ABR wave 1 is a better metric of synaptic degeneration.
Monolepta hieroglyphica (Motschulsky) (Coleoptera: Chrysomelidae) is an important agricultural insect pest. In this study, the complete mitochondrial genome of M. hieroglyphica (GenBank accession ...number MW732714) was sequenced using Illumina HiSeq X Ten. The mitogenome was 16,213 bp long and comprised 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs) and a putative control region (CR). The nucleotide composition of the M. hieroglyphica mitochondrial genome was significantly biased (A, G, C and T accounted for 41.04%, 8.01%, 11.76% and 39.18%, respectively) with 80.23% A + T content. Two rRNAs were located between tRNA-Leu and the CR, separated by tRNA-Val. The CR, located between 12 s rRNA and tRNA-Ile, was 1,661 bp long. The length of the 22 tRNAs ranged from 61 to 71 bp. Phylogenetic analyses of 29 Chrysomelidae-Galerucinae species based on 13 mitochondrial protein-coding genes reconstructed using Bayesian 3.2.0 showed that the M. hieroglyphica mitogenome was clustered with the existing three different species of the Monolepta genus mitogenomes in a monophyletic manner. The M. hieroglyphica mitogenome provides an important data resource for further studies and contributes to our understanding of the phylogeny of this group.
Electrocatalytic CO2 reduction to valued products is a promising way to mitigate the greenhouse effect, as this reaction makes use of the excess CO2 in the atmosphere and at the same time forms ...valued fuels to partially fulfill the energy demand for human beings. Among these valued products, methane is considered a high-value product with a high energy density. This review systematically summarizes the recently studied reaction mechanisms for CO2 electroreduction to CH4. It guides us in designing effective electrocatalysts with an improved electrocatalytic performance. In addition, we briefly summarize the recent progress on CO2 electroreduction into CH4 from the instructive catalyst design, including catalyst structure engineering and catalyst component engineering, and then briefly discuss the electrolyte effect. Furthermore, we also provide a simplified techno-economic analysis of this technology. These summaries are helpful for beginners to rapidly master the contents related to the electroreduction of carbon dioxide to methane and also help to promote the further development of this field.
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