RESUMO
Quasi-2D perovskites have attracted much attention in perovskite photovoltaics due to their excellent stability. However, their photoelectric conversion efficiency (PCE) still lags 3D counterparts, particularly with high short-circuit current (JSC) loss. The quantum confinement effect is pointed out to be the sole reason, which introduces widened bandgap and poor exciton dissociation, and undermines the light capture and charge transport. Here, the gradient incorporation of formamidinium (FA) cations into quasi-2D perovskite is proposed to address this issue. It is observed that FA prefers to incorporate into the larger n value phases near the film surface compared to the smaller n value phases in the bulk, resulting in a narrow bandgap and gradient structure within the film. Through charge dynamic analysis using in situ light-dark Kelvin probe force microscopy and transient absorption spectroscopy, it is demonstrated that incorporating 10% FA significantly facilitates efficient charge transfer between low n-value phases in the bulk and high n-value nearby film surface, leading to reduced charge accumulation. Ultimately, the device based on (AA)2(MA0.9FA0.1)4Pb5I16, where AA represents n-amylamine renowned for its exceptional environmental stability as a bulky organic ligand, achieves an impressive power conversion efficiency (PCE) of 18.58% and demonstrates enhanced illumination and thermal stability.
RESUMO
BACKGROUND: Senecavirus A (SVA) causes an emerging vesicular disease (VD) with clinical symptoms indistinguishable from other vesicular diseases, including vesicular stomatitis (VS), foot-and-mouth disease (FMD), and swine vesicular disease (SVD). Currently, SVA outbreaks have been reported in Canada, the U.S.A, Brazil, Thailand, Vietnam, Colombia, and China. Based on the experience of prevention and control of FMDV, vaccines are the best means to prevent SVA transmission. RESULTS: After preparing an SVA inactivated vaccine (CH-GX-01-2019), we evaluated the immunogenicity of the SVA inactivated vaccine mixed with Imject® Alum (SVA + AL) or Montanide ISA 201 (SVA + 201) adjuvant in mice, as well as the immunogenicity of the SVA inactivated vaccine combined with Montanide ISA 201 adjuvant in post-weaned pigs. The results of the mouse experiment showed that the immune effects in the SVA + 201 group were superior to that in the SVA + AL group. Results from pigs immunized with SVA inactivated vaccine combined with Montanide ISA 201 showed that the immune effects were largely consistent between the SVA-H group (200 µg) and SVA-L group (50 µg); the viral load in tissues and blood was significantly reduced and no clinical symptoms occurred in the vaccinated pigs. CONCLUSIONS: Montanide ISA 201 is a better adjuvant choice than the Imject® Alum adjuvant in the SVA inactivated vaccine preparation, and the CH-GX-01-2019 SVA inactivated vaccine can provide effective protection for pigs.
Assuntos
Adjuvantes Imunológicos , Compostos de Alúmen , Manitol/análogos & derivados , Óleo Mineral , Ácidos Oleicos , Picornaviridae , Animais , Camundongos , Suínos , Vacinas de Produtos InativadosRESUMO
Excess salt consumption contributes to hypertension and arterial dysfunction in humans living in industrialized societies. However, this arterial phenotype is not typically observed in inbred, genetically identical mouse strains that consume a high-salt (HS) diet. Therefore, we sought to determine the effects of HS diet consumption on systolic blood pressure (BP) and arterial function in UM-HET3 mice, an outbred, genetically diverse strain of mice. Male and female UM-HET3 mice underwent a low-salt [LS (1% NaCl)] or HS (4% NaCl) diet for 12 wk. Systolic BP and aortic stiffness, determined by pulse wave velocity (PWV), were increased in HS after 2 and 4 wk, respectively, compared with baseline and continued to increase through week 12 (P < 0.05). Systolic BP was higher from weeks 2-12 and PWV was higher from weeks 4-12 in HS compared with LS mice (P < 0.05). Aortic collagen content was â¼81% higher in HS compared with LS (P < 0.05), whereas aortic elastin content was similar between groups (P > 0.05). Carotid artery endothelium-dependent dilation (EDD) was â¼10% lower in HS compared with LS (P < 0.05), endothelium-independent dilation was similar between groups (P > 0.05). Finally, there was a strong relationship between systolic BP and PWV (r2 = 0.40, P < 0.05), as well as inverse relationship between EDD and systolic BP (r2 = 0.21, P < 0.05) or PWV (r2 = 0.20, P < 0.05). In summary, HS diet consumption in UM-HET3 mice increases systolic BP, which is accompanied by aortic stiffening and impaired EDD. These data suggest that outbred, genetically diverse mice may provide unique translational insight into arterial adaptations of humans that consume an HS diet.NEW & NOTEWORTHY Excess salt consumption is a contributor to hypertension and arterial dysfunction in humans living in industrialized societies, but this phenotype is not observed in inbred, genetically identical mice that consume a high-salt (HS) diet. This study reveals that a HS diet in outbred, genetically diverse mice progressively increases systolic blood pressure and induce arterial dysfunction. These data suggest that genetically diverse mice may provide translational insight into arterial adaptations in humans that consume an HS diet.
Assuntos
Hipertensão , Cloreto de Sódio , Humanos , Masculino , Feminino , Camundongos , Animais , Pressão Sanguínea , Cloreto de Sódio/farmacologia , Análise de Onda de Pulso , Cloreto de Sódio na Dieta , DietaRESUMO
OBJECTIVE: Oncolytic adenoviruses are capable of exerting anticancer effects via a variety of mechanisms, including apoptosis and autophagy. In the present study, the dual-specific antitumor oncolytic adenovirus, Ad-Apoptin-hTERT-E1a (ATV), was used to infect cervical cancer cell lines to test its antitumor effects. METHODS: To explore the use of apoptin in tumor gene therapy, a recombinant adenovirus ATV expressing the apoptin protein was assessed to determine its lethal and growth-inhibitory effects on human cervical cancer cell line (HeLa) cells in vitro . Nonapoptotic autophagy of HeLa cells infected with ATV was assessed by examining the cell morphology, development of acidic vesicular organelles and the conversion of microtubule-associated protein 1 light chain 3 (LC3) from its cytoplasmic to autophagosomal membrane form. Using gene silencing (knockdown of LC3 and Belin-1), autophagy-associated molecules (e.g. ATG5, ATG12 and ULK1) were monitored by real-time PCR and western blot. RESULTS: A series of experiments demonstrated that ATV could significantly induce apoptosis and autophagy in cervical cancer cells, and provided evidence that ATV not only induced apoptosis but also autophagy and ATG5, ATG12 and ULK1 related pathways were not entirely dependent on LC3 and Beclin-1. CONCLUSION: These results indicate that ATV may have a potential application in tumor gene therapy.
Assuntos
Morte Celular Autofágica , Terapia Viral Oncolítica , Neoplasias do Colo do Útero , Feminino , Humanos , Adenoviridae/genética , Células HeLa , Linhagem Celular Tumoral , Apoptose , Autofagia , Terapia Viral Oncolítica/métodosRESUMO
In this study, we compared the inhibitory effects of recombinant oncolytic adenovirus (Ad-apoptin-hTERTp-E1a, Ad-VT) with that of doxorubicin (DOX), a first-line chemotherapy drug, and tamoxifen (TAM), an endocrine therapy drug, on the proliferation of breast cancer cells. We found that Ad-VT could effectively inhibit the proliferation of breast cancer cells (p < 0.01); the inhibition rate of Ad-VT on normal mammary epithelial MCF-10A cells was less than 20%. DOX can effectively inhibit the proliferation of breast cancer cells and also has a strong inhibitory effect on MCF-10A cells (p < 0.01). TAM also has a strong inhibitory effect on breast cancer cells, among which the oestrogen-dependent MCF-7 cell inhibition was stronger (p < 0.01), At higher concentrations, TAM also had a high rate of inhibition (>70%) on the proliferation of MCF-10A cells. We also found that both recombinant adenovirus and both drugs could successfully induce tumour cell apoptosis. Further Western blot results showed that the recombinant adenovirus killed breast cancer cells through the endogenous apoptotic pathway. Analysis of the nude mouse subcutaneous breast cancer model showed that Ad-VT significantly inhibited tumour growth (the luminescence rate of cancer cells was reduced by more than 90%) and improved the survival rate of tumour-bearing mice (p < 0.01). Compared with DOX and TAM, Ad-VT has a significant inhibitory effect on breast cancer cells, but almost no inhibitory effect on normal breast epithelial cells, and this inhibitory effect is mainly through the endogenous apoptotic pathway. These results indicate that Ad-VT has significant potential as a drug for the treatment of breast cancer.
Assuntos
Adenoviridae , Neoplasias , Adenoviridae/genética , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Doxorrubicina/farmacologia , Estrogênios/farmacologia , Camundongos , Tamoxifeno/farmacologiaRESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) and Porcine circovirus (PCV) are two important pathogens, which caused respiratory disease in pigs. PRRSV and PCV2 had caused great economic losses to the pig industry. Pigs coinfection with PCV2 and PRRSV were common in the clinic, PCV2 antibodies can be detected in most of the pigs. PCV2d and HP-PRRSV(JXA1-like) were two major viruses circulating in the pigs in China. In this study, HP-PRRSV (JXA1-like) and PCV2d were used to coinfect and (or) sequential infect 5-week-old weaned PCV2-antibody positive pigs and the clinical indications, pathological, virus load, and specific antibodies of the challenged post-weaned piglets were evaluated. Thirty 5-week-old post-weaned pigs were divided into six groups infected with PBS, PCV2, PRRSV, PCV2-PRRSV, PRRSV-PCV2, and Co-PRRSV-PCV2 according to the PCV2 specific antibodies. Pigs infected with PRRSV can experience diarrhea, increased body temperature, weight loss, and even death. The pigs in the PRRSV infected group and PRRSV-PCV2 infected group showed severe clinical symptoms, high mortality, and low average daily gain. The main pathological changes were widening of the lung interstitium, lung adhesion, and so on. The PRRSV-PCV2 infected group showed high levels of TNF-α and IL-2. In conclusion, PRRSV and PRRSV-PCV2 sequential infected pigs showed most pathogenic signs, and PCV2-PRRSV sequential infected pigs showed less pathogenicity than pigs of PCV2 and PRRSV coinfection and PRRSV monoinfection from day 10-14, partially suppressing the cytokine storm produced by PRRSV.
Assuntos
Infecções por Circoviridae , Coinfecção , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Doenças dos Suínos , Suínos , Animais , Coinfecção/veterinária , Virulência , Anticorpos AntiviraisRESUMO
The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.
Assuntos
COVID-19 , Vacinas de DNA , Animais , Humanos , Camundongos , Adjuvantes Imunológicos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Imunidade Celular , Camundongos Transgênicos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Vacinas de DNA/genéticaRESUMO
Photothermal therapy (PTT) is a promising treatment that efficiently suppresses local cancer, but fails to induce a robust antitumor immune response against tumor metastasis and recurrence. In this study, a NIR responsive nano-immunostimulant (Mn/A-HP NI) is fabricated by entrapping manganese and azo-initiator (AIPH) into hyaluronic acid-based polypyrrole nanoparticle. The as-prepared Mn/A-HP NIs with a high photothermal conversion efficiencey of 20.17% dramatically induced the imunogenic cell death of tumor cells and triggered the release ATP and HMGB1. Meanwhile, the hyperthermia induced AIPH decomposition to produce alkyl radicals which further destroyed cancer cells. Furthermore, the Mn/A-HP NIs were capable of promoting the maturation and antigen cross-presentation ability of dendritic cells. Consequently, the multifunctional Mn/A-HP NIs provided a combined treatment via integrating PTT/chemo-dynamic therapy and immune activation for tumor therapy.
Assuntos
Hipertermia Induzida , Nanopartículas , Polímeros/química , Terapia Fototérmica , Pirróis/farmacologia , Nanopartículas/química , Linhagem Celular Tumoral , FototerapiaRESUMO
The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) cause a huge economic loss around the pig industry worldwide; the NADC30-like PRRSV have attracted much attention outbreaks in China in recent years. Recombination between PRRSV subtypes, point mutations, insertions and deletions that contribute to the emergence of new variants in the genome. In this study, the PRRSV-HB-16-China-2019 strain's full-length genomic sequence shares 93.0% nucleotide similarity to NADC30 PRRSV without any gene insertion. Compared with VR-2332, it has an NSP2 coding region that is different from NADC30, which has a discontinuous 206-aa (111-aa from position 323 to 433 and 95-aa from position 476 to 570) deletion. Compared with other NADC30-Like strains, it has a discontinuous 75-amino acid (75-aa from position 476 to 552) deletion, which was first reported. Notably, the strain, PRRSV-HB-16-China-2019, contained an addition a 1-aa deletion in ORF5 and a unique 3-nt deletion in 3'-UTR similar to NADC30, the strain is recombined between a NADC30-like strain and a vaccine strain named RespPRRS MLV(parental strain VR-2332). Our findings indicate that PRRSV-HB-16-China-2019 is a new NSP2-deletion NADC30-like strain with certain deletions and mutations. Our results show that the emergence of the new NADC30-like strain has increased the difficulty of PRRSV prevention in China.
Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , China , Variação Genética , Genoma Viral , Filogenia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Recombinação Genética , SuínosRESUMO
BACKGROUND: Porcine vesicular disease is caused by the Seneca Valley virus (SVV), it is a novel Picornaviridae, which is prevalent in several countries. However, the pathogenicity of SVV on 5-6 week old pigs and the transmission routes of SVV remain unknown. METHODS: This research mainly focuses on the pathogenicity of the CH-GX-01-2019 strain and the possible vector of SVV. In this study, 5-6 week old pigs infected with SVV (CH-GX-01-2019) and its clinical symptoms (including rectal temperatures and other clinical symptoms) were monitored, qRT-PCR were used to detect the viremia and virus distribution. Neutralization antibody assay was set up during this research. Mosquitoes and Culicoides were collected from pigsties after pigs challenge with SVV, and SVV detection within mosquitoes and Culicoides was done via RT-PCR. RESULTS: The challenged pigs presented with low fevers and mild lethargy on 5-8 days post infection. The viremia lasted more than 14 days. SVV was detected in almost all tissues on the 14th day following the challenge, and it was significantly higher in the hoofs (vesicles) and lymph nodes in comparison with other tissues. Neutralizing antibodies were also detected and could persist for more than 28 days, in addition neutralizing antibody titers ranged from 1:128 to 1:512. Mosquitoes and Culicoides were collected from the pigsty environments following SVV infection. Although SVV was not detected in the mosquitoes, it was present in the Culicoides, however SVV could not be isolated from the positive Culicoides. CONCLUSIONS: Our work has enriched the knowledge relating to SVV pathogenicity and possible transmission routes, which may lay the foundation for further research into the prevention and control of this virus.
Assuntos
Ceratopogonidae , Infecções por Picornaviridae , Picornaviridae , Doenças dos Suínos , Animais , Fazendas , Mosquitos Vetores , Infecções por Picornaviridae/veterinária , Suínos , VirulênciaRESUMO
A novel circovirus designated "porcine circovirus type 4" (PCV4) was recently reported in pigs with severe clinical disease in Hunan Province, China. Relatively little is known about the molecular epidemiology of this recently discovered virus. In order to assess the prevalence of PCV4 infection in pigs and to analyze its genomic characteristics, 1683 clinical samples were collected in Inner Mongolia, China, from 2016 to 2018. The overall infection rate of PCV4 was 1.6% (27/1683) at the sample level and 21.6% (11/51) at the farm level, with rates ranging from 3.2% (1/31) to 20.0% (6/30) on different PCV4-positive pig farms. In addition, the PCV4 infection rates at both the sample and farm level increased from 2016 to 2018. This also showed that PCV4 was present in pigs in 2016 in China and therefore did not arrive later than this date. Additionally, our findings showed that PCV4 infections had no association with PCV2 or PCV3 infections. We sequenced the complete genomes of three PCV4 strains and found that the PCV4 strains had a high degree of genetic stability but shared less than 80% sequence identity with other circoviruses. We identified six amino acid mutations in the Rep protein and seven in the Cap protein. Phylogenetic analysis based on Cap and Rep sequences confirmed that the PCV4 strains grouped in an independent branch. Our findings provide important information about the prevalence and genetic characteristics of PCV4 strains.
Assuntos
Infecções por Circoviridae/epidemiologia , Circovirus/genética , Doenças dos Suínos/epidemiologia , Animais , China/epidemiologia , Infecções por Circoviridae/virologia , Fazendas , Genoma Viral/genética , Genômica/métodos , Epidemiologia Molecular/métodos , Filogenia , Prevalência , Estudos Retrospectivos , Suínos , Doenças dos Suínos/virologiaRESUMO
Ferroptosis as an iron-dependent lipid peroxidation process causes sevely oxidative damage of cell, but lack of highly efficient and recycable antioxidant agents. To this end, cerium doped carbon dots (Ce-doped CDs) with radical scavenging activity were synthesized using a simple microwave-assisted hydrothermal carbonization. The resultant Ce-doped CDs exhibited an ultra-small size of only approximately 2.6 nm, excellent dispersion in water as well as optical performance. Taking advantage of inherent ultra-small size, Ce-doped CDs were endowed with high Ce3+/Ce4+ratio, which significantly enhanced their radical scavenging activity. Meanwhile, the Ce-doped CDs with superior biocompatibility could enter cells quickly and then localized in the cytoplasm. As we expected, the Ce-doped CDs strongly protected cells from oxidative damage of erastin-mediated ferroptosis. These findings suggest that the as-prepared Ce-doped CDs have the potential to be antioxidant drugs against for ferroptosis-induced oxidative damage.
Assuntos
Cério , Ferroptose/efeitos dos fármacos , Sequestradores de Radicais Livres , Estresse Oxidativo/efeitos dos fármacos , Pontos Quânticos/química , Animais , Carbono/química , Carbono/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cério/química , Cério/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Camundongos , Células NIH 3T3RESUMO
BACKGROUND: Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not adequately disentangled their effects. OBJECTIVE: To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PATIENTS: Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020. MEASUREMENTS: Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex. RESULTS: Among 6916 patients with COVID-19, there was a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a BMI of 18.5 to 24 kg/m2, those with BMIs of 40 to 44 kg/m2 and greater than 45 kg/m2 had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino race/ethnicity or other sociodemographic characteristics was not detected. LIMITATION: Deaths occurring outside a health care setting and not captured in membership files may have been missed. CONCLUSION: Obesity plays a profound role in risk for death from COVID-19, particularly in male patients and younger populations. Our capitated system with more equalized health care access may explain the absence of effect of racial/ethnic and socioeconomic disparities on death. Our data highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention. PRIMARY FUNDING SOURCE: Roche-Genentech.
Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Obesidade/epidemiologia , Pneumonia Viral/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Índice de Massa Corporal , COVID-19 , California/epidemiologia , Estudos de Coortes , Comorbidade , Prestação Integrada de Cuidados de Saúde , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Fatores Sexuais , Adulto JovemRESUMO
A series of perylene diimide (PDI) derivatives have been investigated at the CAM-B3LYP/6-31G(d) and the TD-B3LYP/6-31+G(d,p) levels to design solar cell acceptors with high performance in areas such as suitable frontier molecular orbital (FMO) energies to match oligo(thienylenevinylene) derivatives and improved charge transfer properties. The calculated results reveal that the substituents slightly affect the distribution patterns of FMOs for PDI-BI. The electron withdrawing group substituents decrease the FMO energies of PDI-BI, and the electron donating group substituents slightly affect the FMO energies of PDI-BI. The di-electron withdrawing group substituents can tune the FMOs of PDI-BI to be more suitable for the oligo(thienylenevinylene) derivatives. The electron withdrawing group substituents result in red shifts of absorption spectra and electron donating group substituents result in blue shifts for PDI-BI. The -CN substituent can improve the electron transport properties of PDI-BI. The -CH3 group in different positions slightly affects the electron transport properties of PDI-BI.
Assuntos
Imidas/química , Perileno/análogos & derivados , Energia Solar , Simulação por Computador , Perileno/químicaRESUMO
Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.
Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Doenças Musculares , Sepse , Animais , Sepse/complicações , Camundongos , Masculino , Doenças Musculares/etiologia , Doenças Musculares/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Músculo Esquelético , Elevação dos Membros PosterioresRESUMO
Senecavirus A (SVA) is constantly associated with vesicular disease in pigs, and the clinical symptoms of pig infection with SVA are indistinguishable from other porcine vesicular diseases. Vaccine is one of the best methods to eliminate and control the spread of SVA. Virus-like particles (VLPs) can play important roles in prevention for infectious diseases. Here, the SVA VLPs was assembled by the baculovirus expression vector system, and the immunogenicity of the SVA VLPs mixed with different adjuvants were evaluated in mice and pigs. Two recombinant baculoviruses (rPFBD-VP1-VP3 and rPFBD-VP2-VP4) were constructed, which co-infected with Sf9 suspension cells to assemble SVA VLPs successfully. SVA VLPs mixed with ISA201 adjuvant and ISA201 +Poly(I:C) adjuvant produced higher levels of neutralizing antibody, specific antibody (total IgG, IgG1, IgG2a and IgG2b) and cytokines in the T cells. And there was no significant difference between SVA VLPs+ 201 group and SVA VLPs+Poly(I:C)+ 201 group. Pigs immunized with high dose of SVA VLPs mixed with ISA201 adjuvant could produce higher titers of neutralizing antibody and SVA-specific antibody. Furthermore, the protection rates of SVA VLPs-H and SVA VLPs-L were 100% and 80%, and the viral load of SVA VLPs-H group is the lowest in all SVA VLPs groups. It is the first time to develop the SVA VLPs using the baculovirus expression vector system, which may lay the foundation for the research and development of SVA vaccine.
Assuntos
Picornaviridae , Vacinas de Partículas Semelhantes a Vírus , Camundongos , Animais , Suínos , Anticorpos Antivirais , Adjuvantes Imunológicos , Anticorpos NeutralizantesRESUMO
The extracellular matrix of cartilage primarily constitutes of collagen and aggrecan. Cartilage degradation starts with aggrecan loss in osteoarthritis (OA). Vitamin D (VD) plays an essential role in several inflammation-related diseases and can protect the collagen in cartilage during OA. The present study focused on the role of VD in aggrecan turnover of human articular chondrocytes treated with tumor necrosis factor α (TNF-α) and the possible mechanism. Treatment with different doses of VD and different periods of intervention with TNF-α and TGF-ß1 receptor (TGFßR1) inhibitor SB525334 were investigated. The viability of human chondrocytes and extracellular secretion of TGF-ß1 were measured. The expression of intracellular TGFßR1 and VD receptor was examined. Transcriptional and translational levels of aggrecan and the related metabolic factors were analyzed. The results showed that TNF-α markedly reduced the viability, TGFßR1 expressions and aggrecan levels of human chondrocytes, and increased disintegrin and metalloproteinase with thrombospondin motifs. The alterations were partially inhibited by VD treatment. Furthermore, the effects of VD were blocked by the TGFßR1 inhibitor SB525334 in TNF-α-treated cells. VD may prevent proteoglycan loss due to TNF-α via TGF-ß1 signaling in human chondrocytes.
Assuntos
Agrecanas , Cartilagem Articular , Condrócitos , Proteoglicanas , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa , Vitamina D , Humanos , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Agrecanas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Vitamina D/farmacologia , Proteoglicanas/metabolismo , Proteoglicanas/farmacologia , Cartilagem Articular/metabolismo , Cartilagem Articular/efeitos dos fármacos , Células Cultivadas , Sobrevivência Celular/efeitos dos fármacos , Osteoartrite/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptores de Calcitriol/metabolismoRESUMO
OBJECTIVE: Identifying the gut microbiota associated with host immunity in the AIDS stage. DESIGN: We performed a cross-sectional study. METHODS: We recruited people with HIV (PWH) in the AIDS or non-AIDS stage and evaluated their gut microbiota and metabolites by using 16S ribosomal RNA (rRNA) sequencing and liquid chromatography-mass spectrometry (LC-MS). Machine learning models were used to analyze the correlations between key bacteria and CD4 + T cell count, CD4 + T cell activation, bacterial translocation, gut metabolites, and KEGG functional pathways. RESULTS: We recruited 114 PWH in the AIDS stage and 203 PWH in the non-AIDS stage. The α-diversity of gut microbiota was downregulated in the AIDS stage ( P â<â0.05). Several machine learning models could be used to identify key gut microbiota associated with AIDS, including the logistic regression model with area under the curve (AUC), sensitivity, specificity, and Brier scores of 0.854, 0.813, 0.813, and 0.160, respectively. The decreased key bacteria ASV1 ( Bacteroides sp.), ASV8 ( Fusobacterium sp.), ASV30 ( Roseburia sp.), ASV37 ( Bacteroides sp.), and ASV41 ( Lactobacillus sp.) in the AIDS stage were positively correlated with the CD4 + T cell count, the EndoCAb IgM level, 4-hydroxyphenylpyruvic acid abundance, and the predicted cell growth pathway, and negatively correlated with the CD3 + CD4 + CD38 + HLA-DR + T cell count and the sCD14 level. CONCLUSION: Machine learning has the potential to recognize key gut microbiota related to AIDS. The key five bacteria in the AIDS stage and their metabolites might be related to CD4 + T cell reduction and immune activation.
Assuntos
Síndrome da Imunodeficiência Adquirida , Microbioma Gastrointestinal , Infecções por HIV , Humanos , Disbiose , Estudos Transversais , Linfócitos T CD4-Positivos , Bactérias/genética , RNA Ribossômico 16S/genéticaRESUMO
The phase segregation of wide-bandgap perovskite is detrimental to a device's performance. We find that Sodium Benzenesulfonate (SBS) can improve the interface passivation of PTAA, thus addressing the poor wettability issue of poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine](PTAA). This improvement helps mitigate interface defects caused by poor contact between the perovskite and PTAA, reducing non-radiative recombination. Additionally, enhanced interface contact improves the crystallinity of the perovskite, leading to higher-quality perovskite films. By synergistically controlling the crystallization and trap passivation to reduce the phase segregation, SBS-modified perovskite solar cells (PSCs) achieved a power conversion efficiency (PCE) of 20.27%, with an open-circuit voltage (Voc) of 1.18 V, short-circuit current density (Jsc) of 20.93 mA cm-2, and fill factor (FF) of 82.31%.
RESUMO
BACKGROUND: SMS text messaging- and internet-based self-reporting systems can supplement existing vaccine safety surveillance systems, but real-world participation patterns have not been assessed at scale. OBJECTIVE: This study aimed to describe the participation rates of a new SMS text messaging- and internet-based self-reporting system called the Kaiser Permanente Side Effect Monitor (KPSEM) within a large integrated health care system. METHODS: We conducted a prospective cohort study of Kaiser Permanente Southern California (KPSC) patients receiving a COVID-19 vaccination from April 23, 2021, to July 31, 2023. Patients received invitations through flyers, SMS text messages, emails, or patient health care portals. After consenting, patients received regular surveys to assess adverse events up to 5 weeks after each dose. Linkage with medical records provided demographic and clinical data. In this study, we describe KPSEM participation rates, defined as providing consent and completing at least 1 survey within 35 days of COVID-19 vaccination. RESULTS: Approximately, 8% (164,636/2,091,975) of all vaccinated patients provided consent and completed at least 1 survey within 35 days. The lowest participation rates were observed for parents of children aged 12-17 years (1349/152,928, 0.9% participation rate), and the highest participation was observed among older adults aged 61-70 years (39,844/329,487, 12.1%). Persons of non-Hispanic White race were more likely to participate compared with other races and ethnicities (13.1% vs 3.9%-7.5%, respectively; P<.001). In addition, patients residing in areas with a higher neighborhood deprivation index were less likely to participate (5.1%, 16,503/323,122 vs 10.8%, 38,084/352,939 in the highest vs lowest deprivation quintiles, respectively; P<.001). Invitations through the individual's Kaiser Permanente health care portal account and by SMS text message were associated with the highest participation rate (19.2%, 70,248/366,377 and 10.5%, 96,169/914,793, respectively), followed by email (19,464/396,912, 4.9%) and then QR codes on flyers (25,882/2,091,975, 1.2%). SMS text messaging-based surveys demonstrated the highest sustained daily response rates compared with internet-based surveys. CONCLUSIONS: This real-world prospective study demonstrated that a novel digital vaccine safety self-reporting system implemented through an integrated health care system can achieve high participation rates. Linkage with participants' electronic health records is another unique benefit of this surveillance system. We also identified lower participation among selected vulnerable populations, which may have implications when interpreting data collected from similar digital systems.