RESUMO
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Células T de Memória , Reinfecção , SARS-CoV-2 , Humanos , Adolescente , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Masculino , Reinfecção/imunologia , Reinfecção/virologia , Feminino , Células T de Memória/imunologia , Estudos Prospectivos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Formação de Anticorpos , Glicoproteína da Espícula de Coronavírus/imunologia , Memória Imunológica , Criança , Linfócitos T/imunologiaRESUMO
After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , SARS-CoV-2 , Humanos , Idoso , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Masculino , Feminino , Estudos Longitudinais , China/epidemiologia , SARS-CoV-2/classificação , SARS-CoV-2/fisiologia , Anticorpos Neutralizantes , Cinética , Anticorpos Antivirais/sangue , Reinfecção/epidemiologiaRESUMO
Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.
Assuntos
Bartonella , Coinfecção , Leptospira , Animais , Bartonella/genética , China/epidemiologia , Filogenia , Roedores/microbiologia , Musaranhos/microbiologiaRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.
Assuntos
Anticorpos Neutralizantes , Vacinas contra COVID-19 , COVID-19 , Imunidade Humoral , Humanos , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/prevenção & controle , Testes de Neutralização , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Vacinas contra COVID-19/imunologiaRESUMO
The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.
Assuntos
Vacinas contra a AIDS , COVID-19 , Vacinas contra Influenza , Vacinas contra Papillomavirus , Vacinas contra Vírus Sincicial Respiratório , Vacinas contra a SAIDS , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BCG , Vacinas contra COVID-19 , Vacina contra Difteria, Tétano e Coqueluche , Humanos , Vacina contra Sarampo-Caxumba-Rubéola , SARS-CoV-2 , SobreviventesRESUMO
BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.
Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Imunidade Celular/imunologia , Adulto , Linfócitos B/imunologia , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/imunologia , Memória Imunológica/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologiaRESUMO
We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity.
Assuntos
COVID-19/sangue , Quimiocina CXCL10/sangue , Interleucina-7/sangue , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.
Assuntos
Infecções Assintomáticas , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Adulto , Idoso , Betacoronavirus/genética , COVID-19 , China/epidemiologia , Busca de Comunicante , Infecções por Coronavirus/epidemiologia , Saúde da Família , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Filogenia , Pneumonia Viral/epidemiologia , Quarentena , SARS-CoV-2RESUMO
BACKGROUND: China is thought to be a hotspot for zoonotic influenza virus emergence, yet there have been few prospective studies examining the occupational risks of such infections. METHODS: We present the first 2 years of data collected from a 5-year, prospective, cohort study of swine-exposed and -unexposed participants at 6 swine farms in China. We conducted serological and virological surveillance to examine evidence for swine influenza A virus infection in humans. RESULTS: Of the 658 participants (521 swine-exposed and 137 swine-unexposed), 207 (31.5%) seroconverted against at least 1 swine influenza virus subtype (swine H1N1 or H3N2). Swine-exposed participants' microneutralization titers, especially those enrolled at confined animal feeding operations (CAFOs), were higher against the swine H1N1 virus than were other participants at 12 and 24 months. Despite elevated titers, among the 187 study subjects for whom we had complete follow-up, participants working at swine CAFOs had significantly greater odds of seroconverting against both the swine H1N1 (odds ratio [OR] 19.16, 95% confidence interval [CI] 3.55-358.65) and swine H3N2 (OR 2.97, 95% CI 1.16-8.01) viruses, compared to unexposed and non-CAFO swine workers with less intense swine exposure. CONCLUSIONS: While some of the observed increased risk against swine viruses may have been explained by exposure to human influenza strains, study data suggest that even with elevated preexisting antibodies, swine-exposed workers were at high risk of infection with enzootic swine influenza A viruses.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções por Orthomyxoviridae , Doenças dos Suínos , Animais , Anticorpos Antivirais , China/epidemiologia , Estudos de Coortes , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/epidemiologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Estudos Prospectivos , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/epidemiologia , Zoonoses/epidemiologiaAssuntos
Anticorpos Neutralizantes/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/imunologia , Reações Cruzadas , Farmacorresistência Viral , Humanos , Técnicas Microbiológicas , Mutação , Testes de Neutralização , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Estomatite/virologia , Vacinas de Produtos Inativados/imunologiaRESUMO
Background: Our understanding of influenza A virus transmission between humans and pigs is limited. Methods: Beginning in 2015, we used a One Health approach and serial sampling to prospectively study 299 swine workers and 100 controls, their 9000 pigs, and 6 pig farm environments in China for influenza A viruses (IAVs) using molecular, culture, and immunological techniques. Study participants were closely monitored for influenza-like illness (ILI) events. Results: Upon enrollment, swine workers had higher serum neutralizing antibody titers against swine H1N1 and higher nasal wash total immunoglobulin A (IgA) and specific IgA titers against swine H1N1 and H3N2 viruses. Over a period of 12 months, IAVs were detected by quantitative reverse-transcription polymerase chain reaction in 46 of 396 (11.6%) environmental swabs, 235 of 3300 (7.1%) pig oral secretion, 23 of 396 (5.8%) water, 20 of 396 (5.1%) aerosol, and 19 of 396 (4.8%) fecal-slurry specimens. Five of 32 (15.6%) participants with ILI events had nasopharyngeal swab specimens that were positive for IAV, and 17 (53.1%) demonstrated 4-fold rises in neutralization titers against a swine virus. Reassorted Eurasian avian-lineage H1N1, A(H1N1)pdm09-like, and swine-lineage H3N2 viruses were identified in pig farms. The A(H1N1)pdm09-like H1N1 viruses identified in swine were nearly genetically identical to the human H1N1 viruses isolated from the participants with ILI. Conclusions: There was considerable evidence of A(H1N1)pdm09-like, swine-lineage H1N1, and swine-lineage H3N2 viruses circulating, likely reassorting, and likely crossing species within the pig farms. These data suggest that stronger surveillance for novel influenza virus emergence within swine farms is imperative.
Assuntos
Influenza Humana/transmissão , Infecções por Orthomyxoviridae/transmissão , Vírus Reordenados/patogenicidade , Doenças dos Suínos/transmissão , Adolescente , Adulto , Idoso , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Fazendeiros , Fazendas/estatística & dados numéricos , Feminino , Humanos , Imunidade nas Mucosas , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Masculino , Pessoa de Meia-Idade , Saúde Única , Infecções por Orthomyxoviridae/imunologia , Estudos Prospectivos , Fatores de Risco , Suínos/virologia , Zoonoses/transmissãoRESUMO
We conducted a 3-year longitudinal serologic survey on an open cohort of poultry workers, swine workers, and general population controls to assess avian influenza A virus (AIV) seroprevalence and seroincidence and virologic diversity at live poultry markets (LPMs) in Wuxi City, Jiangsu Province, China. Of 964 poultry workers, 9 (0.93%) were seropositive for subtype H7N9 virus, 18 (1.87%) for H9N2, and 18 (1.87%) for H5N1. Of 468 poultry workers followed longitudinally, 2 (0.43%), 13 (2.78%), and 7 (1.5%) seroconverted, respectively; incidence was 1.27, 8.28, and 4.46/1,000 person-years for H7N9, H9N2, and H5N1 viruses, respectively. Longitudinal surveillance of AIVs at 9 LPMs revealed high co-circulation of H9, H7, and H5 subtypes. We detected AIVs in 726 (23.3%) of 3,121 samples and identified a high diversity (10 subtypes) of new genetic constellations and reassortant viruses. These data suggest that stronger surveillance for AIVs within LPMs and high-risk populations is imperative.
Assuntos
Fazendeiros , Vírus da Influenza A , Influenza Humana/epidemiologia , Influenza Humana/virologia , Adulto , Idoso , Animais , China/epidemiologia , Feminino , Geografia , História do Século XXI , Humanos , Incidência , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/virologia , Influenza Humana/história , Influenza Humana/transmissão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Aves Domésticas/virologia , Vigilância em Saúde Pública , Fatores de Risco , Estudos Soroepidemiológicos , SuínosRESUMO
Avian influenza A(H7N9) virus has caused 5 epidemic waves in China since its emergence in 2013. We investigated the dynamic changes of antibody response to this virus over 1 year postinfection in 25 patients in Suzhou City, Jiangsu Province, China, who had laboratory-confirmed infections during the fifth epidemic wave, October 1, 2016-February 14, 2017. Most survivors had relatively robust antibody responses that decreased but remained detectable at 1 year. Antibody response was variable; several survivors had low or undetectable antibody titers. Hemagglutination inhibition titer was >1:40 for <40% of the survivors. Measured in vitro in infected mice, hemagglutination inhibition titer predicted serum protective ability. Our findings provide a helpful serologic guideline for identifying subclinical infections and for developing effective vaccines and therapeutics to counter H7N9 virus infections.
Assuntos
Anticorpos Antivirais/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Idoso , Animais , Anticorpos Antivirais/sangue , Feminino , História do Século XXI , Hospitalização , Humanos , Subtipo H7N9 do Vírus da Influenza A/classificação , Influenza Humana/história , Influenza Humana/virologia , Masculino , Camundongos , Pessoa de Meia-Idade , Testes Sorológicos , SobreviventesRESUMO
Critical and major operations are often accompanied by brain ischemic complications. Previous studies found that propofol post-conditioning provided neuroprotective functions through upregulating the expression of potassium chloride cotransporter 2 (KCC2) in gamma-aminobutyric acid (GABA) interneurons. Membrane expression and phosphorylation represents KCC2 activity, which were modulated by a protein kinase C (PKC)-dependent mechanism. However, the role of propofol in increasing KCC2 phosphorylation and the involvement of protein kinase Mζ (PKMζ), a major subtype of PKC, in the KCC2 pathway remained unclear. In this study, we established middle cerebral artery occlusion model in rats to evaluate the long-term recovery of brain functions using behavioral experiments. KCC2 and PKMζ were assessed via western blot. We used the selective inhibitor, zeta inhibitory peptide (ZIP), to investigate the relationship between KCC2 and PKMζ. Intracellular chloride concentration in the hippocampal CA1 area was measured to determine KCC2 activity. We found that propofol, infused at a speed of 20 mg kg-1 h-1 for 2 h at the onset of reperfusion, improved neurological deficits and cognitive dysfunction following ischemia/reperfusion injury. PKMζ expression was significantly upregulated, which improved KCC2 membrane expression and phosphorylation in the ischemic hippocampal CA1 area, and these effects could last up to 28 days. But ZIP inhibited this process. Ultimately, we showed that propofol increased KCC2 phosphorylation and PKMζ was the upstream of KCC2. Propofol led to long-term recovery of brain functions by upregulating the activity of the PKMζ/KCC2 pathway.
Assuntos
Neuroproteção/efeitos dos fármacos , Propofol/farmacologia , Proteína Quinase C/efeitos dos fármacos , Simportadores/efeitos dos fármacos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Masculino , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia , Cotransportadores de K e Cl-RESUMO
With Two-photon absorption laser-induced fluorescence(TALIF) technology, leads pulse laser in pure high-enthply flow field from the direction of perpendicular to flow field, and obtains the two-dimension atom O fluorescent signal with ICCD setting outside of test section on the vertical direction of flat made with flow field and laser, this signal reflects the relative concentration of atom O. In paper, given the experimental environment and experimental equipment, to ensure that excitation laser wavelength in experiment is the best one, different angular quantum number on ground state of atom O are tested; finally, it is determined that J=2, wavelength 225.584 nm shall be experimental excitation laser wavelength. To make sure that the obtaining atom O fluorescent signal is in unsaturated linear region, in same condition, changing the excitation laser energy from small to large to test fluorescent signal, ultimately acquiring laser energy linear region is below 3.4 mJ. To record ICCD fluorescent image clearly with optimum contrast, Nikon f=105 mm F/2.8 lens is chosen as experimental lens, and the results are got with an accumulation of 50 times exposure. By analyzing the experimental fluorescent signal, we can get two peak positions on left and right of central line about ±50 mm wide which are generated with compressional wave in supersonic flow field, and atom O concentration has 60 mm wide uniform area in central zone of subsonic flow field, the concentration decreases dramatically. This phenomenon is consistent with flow characteristics of wind tunnel, so the method can be applied to flow parameters measurement in the future.
RESUMO
BACKGROUND: Hyperalgesia is one of the negative consequences following intraoperative analgesia with remifentanil. Peroxynitrite is a critical determinant in nociceptive process. Peroxynitrite inactivates iron-sulfur cluster that results in mitochondrial dysfunction and the release of iron, leading to mitochondrial iron accumulation. Iron accumulation mediated by divalent metal transporter 1 (DMT1) plays a key role in N-methyl-D-aspartate neurotoxicity. This study aims to determine whether peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via DMT1-mediated iron accumulation. METHODS: Behavior testing was performed in rat model at different time points. Three-nitrotyrosine, nitrated manganese superoxide dismutase, and DMT1 with/without iron-responsive element [DMT1(+)IRE and DMT1(-)IRE] in spinal cord were detected by Western blot and immunohistochemistry. Spinal iron concentration was measured using the Perl stain and atomic absorption spectrophotometer. Hydrogen-rich saline imparting selectivity for peroxynitrite decomposition and iron chelator was applied in mechanistic study on the roles of peroxynitrite and iron, as well as the prevention of hyperalgesia. RESULTS: Remifentanil induced thermal and mechanical hyperalgesia at postoperative 48 h. Compared with control, there were higher levels of 3-nitrotyrosine (mean ± SD, hyperalgesia vs. control, 1.22 ± 0.18 vs. 0.25 ± 0.05, n = 4), nitrated manganese superoxide dismutase (1.01 ± 0.1 vs. 0.19 ± 0.03, n = 4), DMT1(-)IRE (1.42 ± 0.19 vs. 0.33 ± 0.06, n = 4), and iron concentration (12.87 ± 1.14 vs. 5.26 ± 0.61 µg/g, n = 6) in remifentanil-induced postoperative hyperalgesia, while DMT1(+)IRE was unaffected. Eliminating peroxynitrite with hydrogen-rich saline protected against hyperalgesia and attenuated DMT1(-)IRE overexpression and iron accumulation. Iron chelator prevented hyperalgesia in a dose-dependent manner. CONCLUSIONS: Our study identifies that spinal peroxynitrite activates DMT1(-)IRE, leading to abnormal iron accumulation in remifentanil-induced postoperative hyperalgesia, while providing the rationale for the development of molecular hydrogen and "iron-targeted" therapies.
Assuntos
Proteínas de Transporte de Cátions/biossíntese , Hiperalgesia/metabolismo , Proteínas Reguladoras de Ferro/biossíntese , Ácido Peroxinitroso/biossíntese , Piperidinas/toxicidade , Medula Espinal/metabolismo , Animais , Hiperalgesia/induzido quimicamente , Ferro/metabolismo , Masculino , Dor Pós-Operatória/metabolismo , Ratos , Ratos Sprague-Dawley , RemifentanilRESUMO
BACKGROUND: Many studies have confirmed that brief remifentanil exposure can enhance pain sensitivity. We previously reported that activation of glycogen synthase kinase-3ß (GSK-3ß) contributes to remifentanil-induced hyperalgesia via regulating N-methyl-D-aspartate receptor plasticity in the spinal dorsal horn. In this study, we demonstrated that GSK-3ß inhibition prevented remifentanil-induced postoperative hyperalgesia via regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and function in the spinal dorsal horn. METHODS: Using a rat model of remifentanil-induced incision hyperalgesia, mechanical and thermal pain was tested 1 day before infusion and 2 hours, 6 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after infusion. Western blot analysis was used to detect AMPAR subunit (GluR1 and GluR2) trafficking, AMPAR phosphorylation status, and GSK-3ß activity in the spinal dorsal horn. Furthermore, whole-cell patch-clamp recording was used to analyze the effect of GSK-3ß inhibition on AMPAR-induced current in the spinal dorsal horn. RESULTS: Membrane AMPAR subunit GluR1 was upregulated in the spinal cord in remifentanil-induced postoperative hyperalgesia rats (275 ± 36.54 [mean ± SD] vs 100 ± 9.53, P = 0.0009). Selective GSK-3ß inhibitors, LiCl and TDZD, treatment ameliorates remifentanil-induced postoperative hyperalgesia, and this was associated with the downregulated GluR1 subunit in the membrane fraction (254 ± 23.51 vs 119 ± 14.74, P = 0.0027; 254 ± 23.51 vs 124 ± 9.35, P = 0.0032). Moreover, remifentanil incubation increased the amplitude and the frequency of AMPAR-induced current in dorsal horn neurons (61.09 ± 9.34 pA vs 32.56 ± 6.44 pA, P = 0.0009; 118.32 ± 20.33 milliseconds vs 643.67 ± 43.29 milliseconds, P = 0.0002), which was prevented with the application of LiCl and TDZD, respectively. Remifentanil-induced postoperative pain induced an increase in pGluR1 Ser845 and Rab5, which was prevented with the application of LiCl and TDZD. CONCLUSIONS: These results indicate that amelioration of remifentanil-induced postoperative hyperalgesia by GSK-3ß inhibition is attributed to downregulated AMPAR GluR1 expression in the membrane fraction and inhibition of AMPAR function via altering pGluR1 and Rab5 expression in the spinal dorsal horn.
Assuntos
Regulação da Expressão Gênica , Quinase 3 da Glicogênio Sintase/metabolismo , Hiperalgesia/metabolismo , Dor Pós-Operatória/metabolismo , Piperidinas/efeitos adversos , Receptores de AMPA/biossíntese , Animais , Inibidores Enzimáticos/farmacologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta , Hiperalgesia/induzido quimicamente , Hiperalgesia/prevenção & controle , Masculino , Técnicas de Cultura de Órgãos , Dor Pós-Operatória/induzido quimicamente , Dor Pós-Operatória/prevenção & controle , Piperidinas/antagonistas & inibidores , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/antagonistas & inibidores , RemifentanilRESUMO
This paper introduces the experiment technology for measuring the radiation of high temperature gas in the high frequency plasma wind tunnel. The infrared radiation of carbon dioxide at high temperature has been measured using this technology. We introduced the principium, flow field and the working gas of the high frequency plasma wind tunnel. The experiment condition, equipment, method of data processing and the analyse of the experiment results were introduced. We had measured the infrared radiation of carbon dioxide at four different temperatures between 1500 and 3000 K using this technology for measuring the radiation of high temperature gas which had been developed by ourselves. Measuring the spatial distribution of the infrared radiation of carbon dioxide using Able-transform were also introduced. We have analyzed the emission spectrum at 4.3 µm of carbon dioxide at high temperature. The conclusion had been obtained that the center wavelength of the emission spectrum moved to the long wave when the temperature risen. The authors also had analyzed and contrasted the experiment results and the data obtained from literatures.
RESUMO
BACKGROUND: The recent discovery of emerging relapsing fever group Borrelia (RFGB) species, such as Borrelia miyamotoi, poses a growing threat to public health. However, the global distribution and associated risk burden of these species remain uncertain. We aimed to map the diversity, distribution, and potential infection risk of RFGB. METHODS: We searched PubMed, Web of Science, GenBank, CNKI, and eLibrary from Jan 1, 1874, to Dec 31, 2022, for published articles without language restriction to extract distribution data for RFGB detection in vectors, animals, and humans, and clinical information about human patients. Only articles documenting RFGB infection events were included in this study, and data for RFGB detection in vectors, animals, or humans were composed into a dataset. We used three machine learning algorithms (boosted regression trees, random forest, and least absolute shrinkage and selection operator logistic regression) to assess the environmental, ecoclimatic, biological, and socioeconomic factors associated with the occurrence of four major RFGB species: Borrelia miyamotoi, Borrelia lonestari, Borrelia crocidurae, and Borrelia hermsii; and mapped their worldwide risk level. FINDINGS: We retrieved 13 959 unique studies, among which 697 met the selection criteria and were used for data extraction. 29 RFGB species have been recorded worldwide, of which 27 have been identified from 63 tick species, 12 from 61 wild animals, and ten from domestic animals. 16 RFGB species caused human infection, with a cumulative count of 26 583 cases reported from Jan 1, 1874, to Dec 31, 2022. Borrelia recurrentis (17 084 cases) and Borrelia persica (2045 cases) accounted for the highest proportion of human infection. B miyamotoi showed the widest distribution among all RFGB, with a predicted environmentally suitable area of 6·92 million km2, followed by B lonestari (1·69 million km2), B crocidurae (1·67 million km2), and B hermsii (1·48 million km2). The habitat suitability index of vector ticks and climatic factors, such as the annual mean temperature, have the most significant effect among all predictive models for the geographical distribution of the four major RFGB species. INTERPRETATION: The predicted high-risk regions are considerably larger than in previous reports. Identification, surveillance, and diagnosis of RFGB infections should be prioritised in high-risk areas, especially within low-income regions. FUNDING: National Key Research and Development Program of China.
Assuntos
Borrelia , Febre Recorrente , Borrelia/isolamento & purificação , Humanos , Febre Recorrente/epidemiologia , Febre Recorrente/microbiologia , Febre Recorrente/diagnóstico , AnimaisRESUMO
The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS+ T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8+ T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants.