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BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.
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Dependovirus , Terapia Genética , Humanos , Terapia Genética/métodos , Dependovirus/genética , Criança , Masculino , Pré-Escolar , Feminino , Adolescente , Lactente , Vetores Genéticos , Resultado do Tratamento , Surdez/genética , Surdez/terapia , Mutação , Proteínas de MembranaRESUMO
Necrotic enteritis (NE) is a potentially fatal poultry disease that causes enormous economic losses in the poultry industry worldwide. The study aimed to evaluate the effects of dietary organic yeast-derived selenium (Se) on immune protection against experimental necrotic enteritis (NE) in commercial broilers. Chickens were fed basal diets supplemented with different Se levels (0.25, 0.50, and 1.00 Se mg/kg). To induce NE, Clostridium perfringens (C. perfringens) was orally administered at 14 days of age post hatch. The results showed that birds fed 0.25 Se mg/kg exhibited significantly increased body weight gain compared with the non-supplemented/infected birds. There were no significant differences in gut lesions between the Se-supplemented groups and the non-supplemented group. The antibody levels against α-toxin and NetB toxin increased with the increase between 0.25 Se mg/kg and 0.50 Se mg/kg. In the jejunal scrapings and spleen, the Se-supplementation groups up-regulated the transcripts for pro-inflammatory cytokines IL-1ß, IL-6, IL-8, iNOS, and LITAF and avian ß-defensin 6, 8, and 13 (AvBD6, 8 and 13). In conclusion, supplementation with organic yeast-derived Se alleviates the negative consequences and provides beneficial protection against experimental NE.
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Ração Animal , Galinhas , Infecções por Clostridium , Clostridium perfringens , Citocinas , Suplementos Nutricionais , Enterite , Doenças das Aves Domésticas , Selênio , Animais , Enterite/prevenção & controle , Enterite/veterinária , Enterite/imunologia , Enterite/microbiologia , Selênio/farmacologia , Selênio/administração & dosagem , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/imunologia , Clostridium perfringens/imunologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Infecções por Clostridium/imunologia , Citocinas/metabolismo , Toxinas Bacterianas/imunologia , Necrose , beta-Defensinas/metabolismo , Jejuno/efeitos dos fármacos , Jejuno/imunologia , Jejuno/microbiologia , Jejuno/patologia , Baço/imunologia , Leveduras , Óxido Nítrico Sintase Tipo II/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Interleucina-1beta/metabolismo , Anticorpos Antibacterianos/sangueRESUMO
H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.IMPORTANCEAvian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.
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Five novel chicken astrovirus (CAstV) strains, designated ZDF, MHC, WSC, WSW and MHW, were successfully isolated from chickens with gout, and were subjected to full genome sequencing characterization and tested for their pathogenic effects in specific pathogen-free (SPF) chicken embryos and chickens. The complete genomes of the five isolated strains were approximately 7436â nt to 7511â nt in length. Phylogenetic analysis revealed that strains ZDF and MHC were clustered in a clade with strains isolated in China and that the others were clustered with strains from other countries. Based on the amino acids of ORF2, strains MHW and WSW belonged to subgroup Ai, strain WSC belonged to Bii, and strains ZDF and MHC belonged to Bi. The pathogenicity of strains MHW, MHC and WSC, all belonging to different subgroups was studied. The results showed that the mortality of the chicken embryos was 100% when infected with any strain at a dose of more than 103 TCID50, 35% in SPF chickens infected with strain WSC, 25% with MHC and 15% with MHW. The body weights of chickens and embryos infected with 0.2 ml 10 TCID50 were significantly reduced after hatching. SPF chickens infected with any of the strains had similar lesions characterized by urate deposits on the epicardium and kidney, and necrotic spots on the liver. This study identified the three types of genotypic CAstV prevalent in China, with high mortality in embryonated chicken eggs and leading to white chick syndrome, retarded growth and visceral gout in infected chicks.
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Infecções por Astroviridae , Avastrovirus , Gota , Doenças das Aves Domésticas , Animais , Infecções por Astroviridae/veterinária , Embrião de Galinha , Galinhas , China/epidemiologia , Variação Genética , Gota/veterinária , Filogenia , VirulênciaRESUMO
Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the underpinnings of a constellation of phenotypes that include prostate cancer (PCa) and sensorineural hearing loss (SNHL) in a human subject. Through interrogation of the subject's de novo, germline, balanced chromosomal translocation, we first identify a correlation between his disorders and a poorly annotated gene known as lipid droplet associated hydrolase (LDAH). Using data repositories of both germline and somatic variants, we identify convergent genomic evidence that substantiates a correlation between loss of LDAH and PCa. This correlation is validated through both in vitro and in vivo models that show loss of LDAH results in increased risk of PCa and, to a lesser extent, SNHL. By leveraging convergent evidence in emerging genomic data, we hypothesize that loss of LDAH is involved in PCa and other phenotypes observed in support of a genotype-phenotype association in an n-of-one human subject.
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Perda Auditiva Neurossensorial/genética , Neoplasias da Próstata/genética , Serina Proteases/genética , Translocação Genética/genética , Adulto , Idoso , Animais , Estudo de Associação Genômica Ampla , Células Germinativas/patologia , Perda Auditiva Neurossensorial/patologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Fenótipo , Neoplasias da Próstata/patologiaRESUMO
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.
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Galinhas/virologia , Evolução Molecular , Subtipo H7N9 do Vírus da Influenza A/genética , Vírus da Influenza A Subtipo H9N2/genética , Animais , Variação Antigênica/genética , Antígenos Virais/genética , China/epidemiologia , Genes Virais , Deriva Genética , Genótipo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Subtipo H7N9 do Vírus da Influenza A/imunologia , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Vírus da Influenza A Subtipo H9N2/imunologia , Vírus da Influenza A Subtipo H9N2/patogenicidade , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pandemias , Filogenia , Vírus Reordenados/genética , Vírus Reordenados/imunologia , Vírus Reordenados/patogenicidade , Estudos RetrospectivosRESUMO
SD/818 and SD/196 are H9N2 influenza virus strains isolated from chickens from the same farm at different times that exhibited similar genetic evolution. However, strain SD/818 exhibited higher pathogenicity in chickens than strain SD/196 and other H9N2 influenza virus epidemic strains from China. The expression of cytokines is an important host defence mechanism following viral infection and their intensity is a major determinant of viral pathogenicity. To elucidate the mechanism underlying the increased pathogenicity of strain SD/818 from the host's perspective, viral replication and cytokine expression were dynamically studied using real-time quantitative reverse transcription PCR in chickens infected with strain SD/818 compared with chickens infected with strain SD/196 in this study. The results showed that the replication of strain SD/818 and the expressions of IL-1ß, IL-6, TNF-α, IFN-α and IFN-ß induced by strain SD/818 were higher than those induced by strain SD/196 in the chicken host system. Expression of these cytokines in chickens coincided with or followed virus replication. These results suggested that high-level viral replication and pro-inflammatory cytokine expression (but not decreased type I IFN expression) were associated with the higher pathogenicity of strain SD/818 in chickens.
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Galinhas/imunologia , Citocinas/metabolismo , Vírus da Influenza A Subtipo H9N2/imunologia , Influenza Aviária/imunologia , Doenças das Aves Domésticas/imunologia , Animais , Embrião de Galinha , Galinhas/virologia , China , Citocinas/genética , Feminino , Interações Hospedeiro-Patógeno , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/patogenicidade , Vírus da Influenza A Subtipo H9N2/fisiologia , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Especificidade da Espécie , Organismos Livres de Patógenos Específicos , Replicação ViralRESUMO
Previous researches focusing on BC hearing mechanisms proved that the two routes, (1) EAC sound radiation and (2) inertial of ossicular chain, partially contribute to normal BC hearing. Therefore, the BC hearing for those patients with congenital aural atresia should partially decrease theoretically due to their abnormal anatomy. However, there are not many studies which mention these patients' BC hearing up till now. The objective of this study is to investigate congenital aural atresia patient's BC hearing by analysis of pre-surgical audiogram and to study their potential BC hearing mechanisms using animal modeling and their ABR measurements. The study methoed involves analyzing 75 patients' pre-operative audiogram. Then we produced an animal model by surgery to measure their BC hearing threshold changes. Clinical data showed that those patients had some BC hearing loss; and there were 25 cases (25/75, 33.3 %) which present with typical Carhart's Notch. The animal experiments proved that inertia of ossicular chain contribute to partial BC hearing, which demonstrated that the inertia produced more affects on high frequencies by comparing with low frequencies. The patients with congenital aural atresia present BC hearing loss, which could be mainly ascribed to the absence of inertia of ossicular chain.
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Condução Óssea , Ossículos da Orelha/fisiopatologia , Perda Auditiva Condutiva , Procedimentos Cirúrgicos Otológicos/métodos , Adolescente , Animais , Gatos , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/fisiopatologia , Modelos Animais de Doenças , Orelha/anormalidades , Orelha/fisiopatologia , Feminino , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/etiologia , Perda Auditiva Condutiva/fisiopatologia , Perda Auditiva Condutiva/cirurgia , Testes Auditivos/métodos , Humanos , Masculino , Resultado do TratamentoRESUMO
Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. Here, we subjected a recombinant virus (rH1N1) with the same constellation makeup as the pandemic H1N1/2009 virus to nine serial passages in pigs. The severity of infection sequentially increased with each passage. Deep sequencing of viral quasispecies from the ninth passage found five consensus amino acid mutations: PB1 A469T, PA 1129T, NA N329D, NS1 N205K, and NEP T48N. Mutations in the hemagglutinin (HA) protein, however, differed greatly between the upper and lower respiratory tracts. Three representative viral clones with the five consensus mutations were selected for functional evaluation. Relative to the parental virus, the three viral clones showed enhanced replication and polymerase activity in vitro and enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets in vivo. Specifically, two mutants of rH1N1 (PB1 A469T and a combination of NS1 N205K and NEP T48N) were identified as determinants of transmissibility in guinea pigs. Crucially, one mutant viral clone with the five consensus mutations, which also carried D187E, K211E, and S289N mutations in its HA, additionally was able to infect ferrets by airborne transmission as effectively as the pandemic virus. Our findings demonstrate that influenza virus can acquire viral characteristics that are similar to those of the pandemic virus after limited serial passages in pigs. Importance: We demonstrate here that an engineered reassortant swine influenza virus, with the same gene constellation pattern as the pandemic H1N1/2009 virus and subjected to only nine serial passages in pigs, acquired greatly enhanced virulence and transmissibility. In particular, one representative pathogenic passaged virus clone, which carried three mutations in the HA gene and five consensus mutations in PB1, PA, NA, NS1, and NEP genes, additionally was able to confer respiratory droplet transmission as effectively as the pandemic H1N1/2009 virus. Our findings suggest that pigs can readily induce adaptive mutational changes to a precursor pandemic-like virus to transform it into a highly virulent and infectious form akin to that of the pandemic H1N1/2009 virus, which underlines the potential direct role of pigs in promoting influenza A virus pathogenicity and transmissibility.
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Vírus da Influenza A/patogenicidade , Suínos/virologia , Animais , Líquido da Lavagem Broncoalveolar , Linhagem Celular , Cães , Feminino , Cobaias , Vírus da Influenza A/genética , Mutação , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Inoculações Seriadas , VirulênciaRESUMO
H9N2 influenza viruses with an A316S substitution in hemagglutinin (HA) and a shorter neuraminidase (NA) stalk have become predominant in China. The A316S was shown to increase HA cleavage efficiency when combined with short stalk NA, and the short stalk NA improved NA enzyme activity and release of virus from erythrocytes. Single mutations or combinations of these mutations strengthened the virulence of H9N2 virus in chickens and mice.
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Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H9N2/química , Vírus da Influenza A Subtipo H9N2/patogenicidade , Neuraminidase/química , Neuraminidase/genética , Infecções por Orthomyxoviridae/virologia , Substituição de Aminoácidos , Animais , Embrião de Galinha , Galinhas , Cães , Eritrócitos/virologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A Subtipo H9N2/genética , Células Madin Darby de Rim Canino , Camundongos , Mutação , Neuraminidase/metabolismo , Doenças das Aves Domésticas/virologia , Liberação de VírusRESUMO
OBJECTIVE: To investigate the audiological characteristics of vestibular schwannoma (VS) patients with normal pure-tone audiometry (PTA) results. STUDY DESIGN: A retrospective study. SETTING: Forty-two VS patients with normal PTA results from October 2016 to October 2022 were included. METHODS: Normal PTA was defined when the hearing threshold is ≤25 dB hearing loss (HL) in each test frequency and the PTA is ≤25 dB HL. Results of multiple audiological tests such as the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), multiple auditory steady-state responses threshold (ASSR), and speech discrimination score were retrospectively reviewed. Demographic data of these patients were also been collected. RESULTS: According to our results, the ABR and average ASSR threshold of the affected side were statistically significantly higher in VS patients with normal PTA. ABR waveforms on the affected side also showed more abnormalities. The DPOAE pass rates of the affected side were lower than the unaffected side while the amplitude and signal-to-noise ratio rate was also lower. In addition, we used magnetic resonance imaging 3-dimensional reconstruction images to measure the volume of tumors in these patients. We also found that higher ABR threshold means lager tumor size in patients with normal PTA. CONCLUSION: VS patients with normal PTA result cannot be assumed to have no impairment of hearing function. ABR, DPOAE, and ASSR results showed the characteristic changes in the affect ear. ABR threshold has the highest sensitivity for hearing abnormalities and is strong relative with tumor size in patients with normal PTA.
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Audiometria de Tons Puros , Limiar Auditivo , Potenciais Evocados Auditivos do Tronco Encefálico , Neuroma Acústico , Humanos , Neuroma Acústico/complicações , Neuroma Acústico/fisiopatologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Idoso , Emissões Otoacústicas Espontâneas/fisiologiaRESUMO
To understand the epizootiologic characteristics of pathogens and opportunistic infections in one Beagle dog production colony and three research facilities, viruses and mycoplasma were detected in 1777 samples collected from Beagle dogs in China by polymerase chain reaction/reverse transcription polymerase chain reaction, and bacteria were isolated and identified by 16S rRNA sequence analysis. In addition, genotyping of the major circulating viruses was carried out by amplification of gene fragments and homology analysis. Canine coronavirus (CCoV), Escherichia coli, canine parvovirus (CPV), Bordetella bronchiseptica, Clostridium perfringens, Mycoplasma cynos, Klebsiella pneumoniae, Streptococcus canis, canine astrovirus (CaAstV), canine kobuvirus (CaKV), Pseudomonas aeruginosa, Proteus mirabilis, Macrococcus canis, Pasteurella canis, canine bocavirus (CBoV) and canine adenovirus (CAdV) were detected in the samples. Single, double, triple and quadruple infections accounted for 6.6%, 1.4%, 1.2% and 0.96% of samples, respectively. CCoV strains in 81 samples included three genotypes, CCoV-I, CCoV-IIa and CCoV-IIb, by analysis of S gene. The rate of single infection of CCoV-I, CCoV-IIa or CCoV-IIb was 19%, 38% or 7.4% respectively. The double and triple infection rates of CCoV were 32.8% and 2.5% respectively. All CPV strains in 36 samples belonged to CPV-2c. There were three amino acid differences in the Fiber protein of CAdV-positive sample QD2022, compared with the reference strain Toronto A26/61 and the vaccine strain YCA-18. These results suggest that CCoV and CPV are primary infectious agents, and that these two viruses were often identified in mixed infections, or coinfections alongside mycoplasma or other bacteria. These results will provide the basis for improvements in prevention and control of naturally occurring infectious diseases in Beagle dog production colonies and research facilities.
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Infecções por Coronavirus , Coronavirus Canino , Doenças do Cão , Parvovirus Canino , Cães , Animais , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , RNA Ribossômico 16S/genética , Doenças do Cão/epidemiologia , Reação em Cadeia da Polimerase , China/epidemiologia , Coronavirus Canino/genética , Parvovirus Canino/genéticaRESUMO
Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .
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Dependovirus , Terapia Genética , Humanos , Terapia Genética/métodos , Criança , Masculino , Feminino , Dependovirus/genética , Pré-Escolar , Surdez/genética , Surdez/terapia , Adolescente , Resultado do Tratamento , Genes Recessivos , Vetores Genéticos/genética , Potenciais Evocados Auditivos do Tronco EncefálicoRESUMO
Organic pollutants pose a serious threat to water environment, thus it is essential to develop high-performance adsorbent to remove them from wastewater. Herein, nitrogen-doped magnetic porous carbon (M-PLAC) with three-dimensional porous structure was synthesized from lignin to adsorb methylene blue (MB) and tetracycline (TC) in wastewater. The calculated equilibrium adsorption amount by M-PLAC for MB and TC was 645.52 and 1306.00 mg/g, respectively. The adsorption of MB and TC on M-PLAC conformed to the pseudo-second-order kinetic model. The removal of MB by M-PLAC showed fast and efficient characteristics and exhibited high selectivity for TC in a binary system. In addition, M-PLAC was suitable for a variety of complex water environments and had good regeneration performance, demonstrating potential advantages in practical wastewater treatment. The organic pollutant adsorption by M-PLAC was attributed to electrostatic interaction, hole filling effect, hydrogen bonding, and the π-π interaction.
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Poluentes Ambientais , Poluentes Químicos da Água , Carbono , Lignina/química , Adsorção , Águas Residuárias , Porosidade , Nitrogênio , Tetraciclina/química , Antibacterianos , Água/química , Fenômenos Magnéticos , Poluentes Químicos da Água/química , CinéticaRESUMO
Amine-functionalized magnetic microspheres (LS-Fe-NMA) were successfully prepared from lignosulfonate by magnetization and amine modification to remove Cr(VI) from industrial wastewater. In addition to SEM, FTIR, XPS, magnetic hysteresis curves and other characterizations, the adsorption tests were performed in real Cr(VI)-containing industrial wastewater. The experimental influencing factors, such as adsorbent types, LS content in the composites, adsorption time, dosages of adsorbent and adsorption temperature were systematically explored. The results of adsorption models fitting proved that the adsorption conformed to the Langmuir model and the pseudo-second-order kinetic model. At 45 °C, the calculated equilibrium adsorption amount by LS-Fe-NMA in industrial wastewater was 642.11 mg/g. In addition, the adsorption process followed the principle of spontaneous endothermic reaction. It was found that electrostatic interaction, redox and complexation existed during the adsorption process. The excellent adsorption performance and reusability of LS-Fe-NMA for Cr(VI) demonstrates its practical application value in real Cr(VI)-containing industrial wastewater.
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Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Microesferas , Poluentes Químicos da Água/análise , Cromo/análise , Adsorção , Purificação da Água/métodos , Cinética , Fenômenos Magnéticos , Concentração de Íons de HidrogênioRESUMO
To detect the antibody against fowl adenovirus serotype 4 (FAdV-4) in clinical practice, the latex agglutination test (LAT) was developed by using the Fiber-2 protein of FAdV-4 as an antigen bound to sensitized latex microspheres. The concentration, time, and temperature of sensitization latex microspheres by the Fiber-2 protein were studied and optimized; the specificity, sensitivity, and repeatability of LAT were tested; and the method developed in the study was applied. The results showed that the optimum sensitization concentration of Fiber-2 protein was 0.8 mg/mL, the time was 120 min, and the temperature was 37 â. Except for antiserum against FAdV-4 and FAdV-10, LAT developed in the study could not agglutinate antisera against FAdV-1, FAdV-2, FAdV-3, FAdV-4, FAdV-5, FAdV-6, FAdV-8a, FAdV-8b, FAdV-11, Newcastle disease virus, infectious bronchitis virus, egg drop syndrome virus and Clostridium perfringens. Compared with the commercial FAdV-4 ELISA Kit, the titers in 21 clinical samples were low when tested by the developed LAT method, but there was no significant difference. The coefficients of variation among different batches and the same batch of latex-sensitized particles were between 0 % and 13.3 % and 0-8.7 %, respectively. The critical value of immune protective antibody against FAdV-4 was 25, and the titers in 40.9 % of clinical samples were higher than the immune critical point. The results showed that the Fiber-2-based LAT developed in the study has the characteristics of high specificity, sensitivity and repeatability, has the advantages of free equipment, long shelf life, and fast and easy operation, and is an effective and convenient method for serological diagnosis of FAdV-4 infection and evaluating the efficacy of vaccines.
Assuntos
Infecções por Adenoviridae , Aviadenovirus , Doenças das Aves Domésticas , Animais , Sorogrupo , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/veterinária , Testes de Fixação do Látex , Anticorpos Antivirais , Galinhas , Adenoviridae , Doenças das Aves Domésticas/diagnósticoRESUMO
Magnetic porous adsorbent materials are widely favored for their large specific surface area, good adsorption performance, and ease of separation. This work provided a magnetic biochar derived from furfural residue (M-FRAC) with excellent adsorption properties for various pollutants, including Congo red (CR), Tetracycline (TC), Bisphenol A (BPA), and Cr6+. The influence of experimental parameters, such as pollutant concentration, contact time, and pH, on the adsorption properties of M-FRAC was studied in detail. The adsorption process was highly dependent on pH and initial contaminant concentration. All pollutant adsorption was favorable under acidic conditions. The optimal pH of the CR, TC, and Cr6+ adsorption was 5, 4, and 2, respectively, while that of BPA was in the range of 2-5. The experimental equilibrium adsorption amount of CR, TC, BPA, and Cr6+ by M-FRAC was 110.89, 602.81, 157.76, and 265.31 mg/g, respectively. The adsorption processes of pollutants on M-FRAC were in accordance with the Langmuir isotherm model. The adsorption kinetics fitted the pseudo-second-order (PSO) kinetics model. In addition, M-FRAC could be readily separated from solution by applying an external magnetic field. Therefore, the M-FRAC has a good application prospect in practical industrial wastewater treatment.
Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Vermelho Congo , Adsorção , Furaldeído , Tetraciclina , Antibacterianos , Carvão Vegetal/química , Fenômenos Magnéticos , Cinética , Poluentes Químicos da Água/análise , Concentração de Íons de HidrogênioRESUMO
During a tracing investigation of blue ear disease in China conducted from January to November 2008, 11 porcine reproductive and respiratory syndrome virus (PRRSV) isolates were collected from eight provinces including Liaoning, Jilin, Hebei, Shandong, Henan, Shanghai, Zhejiang, and Guangxi. The complete gene sequences of the NSP2, ORF5, and ORF7 genes from these 11 PRRSV isolates were amplified, cloned and detected by RT-PCR and then compared with the published sequences of other strains. The results showed that all of the isolates genotypically belonged to an American strain, but shared high homology with JXA1, the highly pathogenic strain endemic to China. All of the 11 PRRSV isolates demonstrated a 90-nucleotide deletion in the NSP2 gene, suggesting that the main epidemic of PRRSV in 2008 was due to this gene deletion isolate. More consistent mutations were found in specific regions of the ORF5 and ORF7 genes of the 11 PRRSV isolates, such as the signal peptide and transmembrane regions of GP5 and the Pat 7 motif of the N protein. Whether these mutations influence nuclear localization of PRRSV requires confirmation by future studies.
Assuntos
Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/classificação , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , RNA Viral/genética , Proteínas Virais/genética , Animais , China , Análise por Conglomerados , Genótipo , Dados de Sequência Molecular , Mutação , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Análise de Sequência de DNA , Deleção de Sequência , Homologia de Sequência de Aminoácidos , SuínosRESUMO
BACKGROUND: 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. METHODS AND DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT05343026. Registered on April 25, 2022.