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1.
Artigo em Inglês | MEDLINE | ID: mdl-39034764

RESUMO

This study evaluated the effects of different nutrient matrices, with or without phytase supplementation, on growth performance, nutrient digestibility, ileal amino acid (AA) digestibility, and blood inositol in pigs fed a complex diet based on corn-soybean meal. Four hundred newly weaned cross-bred (Landrace × Yorkshire × Duroc) 21-day-old piglets of initial body weight 6.35 ± 1.91 kg were allotted to one of the five dietary treatments: Control (CNT), a corn-soybean-based standard diet; negative control 1 (NC1), a standard diet with reduced available phosphorus (Av.P) (-0.125%), metabolizable energy (ME) (-40 kcal), and crude protein (CP) (-0.3%); NC1 with 500 phytase units per kilogramme (FTU/kg) (N1P5); negative control 2 (NC2), a standard diet with greater reduction of Av.P (-0.150%), ME (-55 kcal), and CP (-0.45%,); and NC2 with 1000 FTU/kg (N2P10). Piglets were housed in a random arrangement based on sex and body weight and data were analyzed as a randomized complete block design using analysis of variance. Results showed that the body weight and average daily gain of the NC2 treatment were lower (p < 0.05) compared to NC2. Gain to feed ratio was greater (p < 0.05) in the CNT and N1P5 treatments compared to the NC1, NC2, and N2P10 treatments. The CP digestibility was higher (p < 0.05) in N1P5 and N2P10 treatments compared to other treatments. Moreover, the digestibility of phosphorus and calcium was higher (p < 0.05) in N1P5 and N2P10 treatments than in CNT, NC1, and NC2 treatments. The digestibility of non-dispensable AA; histidine, isoleucine, leucine, phenylalanine, and valine were increased (p < 0.05) in N1P5 and N2P10 than in CNT, NC1, and NC2 treatments. Nevertheless, the digestibility of dispensable AA, glutamic acid, was higher (p < 0.05) in N1P5 and N2P10 treatments than in CNT, NC1, and NC2 treatments. Blood myo-inositol concentration was higher (p < 0.05) in N1P5 and N2P10 treatments compared to CNT, NC1, and NC2 treatments in phase 2. These results demonstrated enhanced outcomes under conditions of moderate deficiency, whereas more pronounced deficiencies necessitated increased phytase dosages to observe significant improvements. The efficacy of phytase was evident in its ability to elevate average daily gain, gain to feed ratio, phosphorus and calcium, CP, AA, and blood myo-inositol.

2.
Nat Commun ; 15(1): 5860, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997268

RESUMO

Lithium batteries with solid-state electrolytes are an appealing alternative to state-of-the-art non-aqueous lithium-ion batteries with liquid electrolytes because of safety and energy aspects. However, engineering development at the cell level for lithium batteries with solid-state electrolytes is limited. Here, to advance this aspect and produce high-energy lithium cells, we introduce a cell design based on advanced parametrization of microstructural and architectural parameters of electrode and electrolyte components. To validate the cell design proposed, we assemble and test (applying a stack pressure of 3.74 MPa at 45 °C) 10-layer and 4-layer solid-state lithium pouch cells with a solid polymer electrolyte, resulting in an initial specific energy of 280 Wh kg-1 (corresponding to an energy density of 600 Wh L-1) and 310 Wh kg-1 (corresponding to an energy density of 650 Wh L-1) respectively.

3.
Sci Rep ; 14(1): 16111, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997328

RESUMO

This retrospective study aimed to compare the outcomes of modified double-flanged sutureless scleral fixation versus sutured scleral fixation. Medical records of 65 eyes from 65 patients who underwent double-flanged scleral fixation (flange group) or conventional scleral fixation (suture group) between 2021 and 2022 were reviewed. Visual and refractive outcomes, as well as postoperative complications, were compared 1, 2, and 6 months after surgery. We included 31 eyes in the flange group and 34 eyes in the suture group. At 6 months postoperatively, the flange group showed better uncorrected visual acuity (0.251 ± 0.328 vs. 0.418 ± 0.339 logMAR, P = 0.041) and a smaller myopic shift (- 0.74 ± 0.93 vs. - 1.33 ± 1.15 diopter, P = 0.007) compared to the suture group. The flange group did not experience any instances of iris capture, while the suture group had iris capture in 10 eyes (29.4%; P < 0.001). In the flange group, all intraocular lenses remained centered, whereas in the suture group, they were decentered in 8 eyes (23.5%; P = 0.005). The double-flanged technique not only prevented iris capture and decentration of the intraocular lens but also reduced myopic shift by enhancing the stability of the intraocular lens.


Assuntos
Esclera , Técnicas de Sutura , Acuidade Visual , Humanos , Esclera/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Suturas , Implante de Lente Intraocular/métodos , Implante de Lente Intraocular/efeitos adversos , Procedimentos Cirúrgicos sem Sutura/métodos , Adulto , Complicações Pós-Operatórias/etiologia
4.
BMC Cancer ; 24(1): 784, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951803

RESUMO

INTRODUCTION: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. METHODS: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. DISCUSSION: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. TRIAL REGISTRATION: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.


Assuntos
Estudos Cross-Over , Exercício Físico , Vesículas Extracelulares , Miocinas , Neoplasias da Próstata , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Vesículas Extracelulares/metabolismo , Músculo Esquelético/metabolismo , Miocinas/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Estudos Clínicos como Assunto
5.
J Anim Sci Technol ; 66(3): 493-503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38975576

RESUMO

The aim of this experiment was to evaluate the effects of low crude protein (CP) level with essential amino acids (AA) addition on growth performance, nutrient digestibility, microbiota, and volatile fatty acid composition in growing pigs. A total of 160 growing pigs (Landrace × Yorkshire × Duroc [LYD]; average initial body weight 16.68 ± 0.12 kg) were randomly allotted to one of the four treatments on the basis of initial body weight. A randomized complete block design was used to conduct this experiment in the Research Center of Animal Life Sciences at Kangwon National University. There were ten pigs/replicate with four replicates in each treatment. The treatments include; CON (Control, 17.2% dietary CP level), low protein (LP)-1.10 (15.7% dietary CP level + 1.10% lysine level), LP-1.15 (15.7% dietary CP level + 1.15% lysine level), LP1.2 (15.7% dietary CP level + 1.20% lysine level). The pigs fed CON and LP-1.2 diet showed greater final body weight than that of LP-1.1 diet (p < 0.05). Although average daily gain, average daily feed intake, and feed efficiency did not show any difference in phase 2 and 3, average daily gain and feed efficiency was significantly greater in CON and LP-1.20 in phase 1. However, the average daily feed intake did not show any difference during the experimental period. Isobutyric acid and isovaleric acid composition of LP treatments were lower than CON treatment in phase 2. Total branched chain fatty acid composition was significantly lower in LP treatment in phases 1 and 2. However, there was no significant difference among treatments in phase 3. The results of this study underscore the importance of AA supplementation when implementing a low-protein diet during the early growth phase (16-50 kg) in pigs.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38855926

RESUMO

This study evaluated the efficacy of a multi-protease on the performance, egg quality and digestibility of laying hen. The study had four treatments: Control (without multi-protease, CON), Pro 1.2 (CON + 0.1% multi-protease), Pro 2.4 (CON + 0.2% multi-protease) and Pro 3.6 (CON + 0.3% multi-protease). Each treatment was replicated six times (replicate = experimental unit = one pen with 15 hens) to give a total of 360 layer hens of the Hy-line breed. The study lasted for a total of 3 months (14 day adaptation period + 84 days experimental period). The effects of the additive were assessed on: the performance variables, egg quality and ileal amino acid (AA) digestibility. At the end of the study, dietary supplementation with Pro 2.4 and Pro 3.6 improved (p < 0.05) hen-day egg production, egg mass and eggshell thickness compared with CON at the peak phase. Further improvements (p < 0.05) were observed in the digestibility of crude protein and AAs such as isoleucine, lysine, threonine and cysteine at Pro 2.4 and Pro 3.6 protease supplementation levels compared with CON, while arginine and alanine were higher (p < 0.05) at Pro 3.6 compared with CON. No differences were reported for other performances such as body weight, average daily feed intake, average egg weight, feed conversion ratio, eggshell hardness and all the egg qualities measured. Overall, the results from this study showed better efficacy at Pro 2.4 and Pro 3.6 on the performance of laying hen during the peak phase.

7.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892160

RESUMO

Capmatinib and savolitinib, selective MET inhibitors, are widely used to treat various MET-positive cancers. In this study, we aimed to determine the effects of these inhibitors on MET-amplified gastric cancer (GC) cells. Methods: After screening 37 GC cell lines, the following cell lines were found to be MET-positive with copy number variation >10: SNU-620, ESO51, MKN-45, SNU-5, and OE33 cell lines. Next, we assessed the cytotoxic response of these cell lines to capmatinib or savolitinib alone using cell counting kit-8 and clonogenic cell survival assays. Western blotting was performed to assess the effects of capmatinib and savolitinib on the MET signaling pathway. Xenograft studies were performed to evaluate the in vivo therapeutic efficacy of savolitinib in MKN-45 cells. Savolitinib and capmatinib exerted anti-proliferative effects on MET-amplified GC cell lines in a dose-dependent manner. Savolitinib inhibited the phosphorylation of MET and downstream signaling pathways, such as the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) pathways, in MET-amplified GC cells. Additionally, savolitinib significantly decreased the number of colonies formed on the soft agar and exerted dose-dependent anti-tumor effects in an MKN-45 GC cell xenograft model. Furthermore, a combination of trastuzumab and capmatinib exhibited enhanced inhibition of AKT and ERK activation in human epidermal growth factor receptor-2 (HER2)- and MET-positive OE33 cells. Targeting MET with savolitinib and capmatinib efficiently suppressed the growth of MET-amplified GC cells. Moreover, these MET inhibitors exerted synergistic effects with trastuzumab on HER2- and MET-amplified GC cells.


Assuntos
Proteínas Proto-Oncogênicas c-met , Neoplasias Gástricas , Triazinas , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Animais , Triazinas/farmacologia , Camundongos , Benzamidas/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular , Feminino , Imidazóis
8.
Biomol Ther (Seoul) ; 32(4): 481-491, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38835145

RESUMO

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

10.
Int J Pharm ; 657: 124177, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38697582

RESUMO

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs-Empagliflozin, Furosemide, and Ilaprazole-are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.


Assuntos
Nebulizadores e Vaporizadores , Tamanho da Partícula , Polímeros , Polímeros/química , Estabilidade de Medicamentos , Solubilidade , Composição de Medicamentos/métodos , Resinas Acrílicas/química , Povidona/química , Ultrassom , Ácidos Polimetacrílicos/química , Furosemida/química , Química Farmacêutica/métodos
11.
Virus Genes ; 60(3): 251-262, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38587722

RESUMO

SARS-CoV-2 Omicron has the largest number of mutations among all the known SARS-CoV-2 variants. The presence of these mutations might explain why Omicron is more infectious and vaccines have lower efficacy to Omicron than other variants, despite lower virulence of Omicron. We recently established a long-term in vivo replication model by infecting Calu-3 xenograft tumors in immunodeficient mice with parental SARS-CoV-2 and found that various mutations occurred majorly in the spike protein during extended replication. To investigate whether there are differences in the spectrum and frequency of mutations between parental SARS-CoV-2 and Omicron, we here applied this model to Omicron. At 30 days after infection, we found that the virus was present at high titers in the tumor tissues and had developed several rare sporadic mutations, mainly in ORF1ab with additional minor spike protein mutations. Many of the mutant isolates had higher replicative activity in Calu-3 cells compared with the original SARS-CoV-2 Omicron virus, suggesting that the novel mutations contributed to increased viral replication. Serial propagation of SARS-CoV-2 Omicron in cultured Calu-3 cells resulted in several rare sporadic mutations in various viral proteins with no mutations in the spike protein. Therefore, the genome of SARS-CoV-2 Omicron seems largely stable compared with that of the parental SARS-CoV-2 during extended replication in Calu-3 cells and xenograft model. The sporadic mutations and modified growth properties observed in Omicron might explain the emergence of Omicron sublineages. However, we cannot exclude the possibility of some differences in natural infection.


Assuntos
COVID-19 , Neoplasias Pulmonares , Mutação , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Replicação Viral , Animais , Replicação Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Camundongos , Humanos , COVID-19/virologia , Neoplasias Pulmonares/virologia , Neoplasias Pulmonares/genética , Glicoproteína da Espícula de Coronavírus/genética , Modelos Animais de Doenças , Linhagem Celular Tumoral
12.
Cancer Res Treat ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38637966

RESUMO

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and 3 patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6, 12.4, and 18.1 months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

13.
J Sport Health Sci ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604409

RESUMO

BACKGROUND: The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle-organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment. METHODS: A systematic search was undertaken in PubMed, Medline, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on interleukin15 (IL-15), irisin, secreted protein acidic and rich in cysteine (SPARC), oncostatin M (OSM), and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change. RESULTS: Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn. CONCLUSION: Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

14.
J Child Neurol ; 39(3-4): 138-146, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38528770

RESUMO

Objective: We examined the yield of routine epilepsy panel genetic testing in pediatric patients. Methods: We retrospectively reviewed epilepsy genetic panel results routinely performed in the hospital or clinic on patients <8 years old from July 2021 to July 2023. We evaluated demographics, family history, seizure type, severity, and frequency, development, tone and movement abnormalities, dysmorphism, and electroencephalography (EEG) or magnetic resonance imaging (MRI) results as predictors of results. Results: 65 patients were included with mean age 4.5 years. Sixty percent of patients were male; 11 patients had pathogenic variants (16.9%), 7 were carriers for autosomal recessive conditions (10.8%), 36 had variants of uncertain significance (55.4%), and 11 tested negative (16.9%). Pathogenic variants and variants of uncertain significance were unassociated with demographics, clinical features, imaging, or family history. Conclusion: Variants identified have potential implications for treatment (SCN1), comorbidity screening (TSC1), reproduction (ATAD1, PSAT1, and CLN8), and prognostication (FOXG1). Patients not routinely screened for a genetic cause of epilepsy by our standard practices had clinically relevant results.


Assuntos
Epilepsia , Testes Genéticos , Convulsões , Humanos , Masculino , Feminino , Testes Genéticos/métodos , Pré-Escolar , Estudos Retrospectivos , Criança , Epilepsia/genética , Epilepsia/diagnóstico , Convulsões/genética , Convulsões/diagnóstico , Eletroencefalografia , Lactente , Imageamento por Ressonância Magnética
15.
J Med Virol ; 96(2): e29459, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38345153

RESUMO

We recently established a long-term SARS-CoV-2 infection model using lung-cancer xenograft mice and identified mutations that arose in the SARS-CoV-2 genome during long-term propagation. Here, we applied our model to the SARS-CoV-2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS-CoV-2. We observed limited mutations in SARS-CoV-2 Delta during long-term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta-10 and Delta-12, with both predominant mutations and some additional mutations. Delta-10 and Delta-12 showed lower replication capacity compared with SARS-CoV-2 Delta in cultured cells; however, Delta-12 was more lethal in K18-hACE2 mice compared with SARS-CoV-2 Delta and Delta-10. Mice infected with Delta-12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta-12 was associated with lung and brain pathology. Our long-term infection model can provide mutant viruses derived from SARS-CoV-2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Animais , Camundongos , Xenoenxertos , SARS-CoV-2/genética , Encéfalo
16.
Poult Sci ; 103(3): 103467, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295502

RESUMO

In this study, a total of 312 Hyline brown laying hen of 1.92 ± 0.12 kg acquired at 24-wk old were employed to evaluate the pharmaceutical effect of Korean wild ginseng residue extract administered via drinking water on the performance, microbiota quality, cytokine expression, and the ginsenoside saponin (GS) content of laying hen for 12 wk. In the experiments, basic feed (CON) was compared with basic feed + 0.05% wild ginseng in drinking water (WGD1), basic feed + 0.1% wild ginseng in drinking water (WGD2), and basic feed + 0.5% wild ginseng in drinking water (WGD3). At the end of study, hen-day egg production (HDEP), average egg weight (AEW), and egg mass (EM) were linearly higher (p < 0.05) in WGD3 at wk 30 to 33, 34 to 37 wk, and the cumulative wk compared with CON. Feed conversion ratio (FCR) was linearly lower in WGD3 at 34 to 37 wk, and the cumulative wk compared with CON. Relative expression of tumor necrosis factor alpha (TNF-α) was linearly lower (p < 0.05) in the WGD3 at wk 30 to 33, and 34 to 37 wk compared with CON. The GS in egg yolk was linearly higher (p < 0.05) in laying hens supplemented the WGD3 treatment at wk 34 to 37, while the fecal microflora quantity of Lactobacillus was linearly higher (p < 0.05) in WGD3 at wk 30 to 33, till 34 to 37 wk, and Escherichia coli (E. coli) was linearly lower (p < 0.05) in the WGD2 and WGD3 from 2637 wk compared with CON. We concluded the result in HDEP, AEW, EM, and FCR were due to the increase in GS content, tentatively leading to an improvement in the TNF-α, and fecal microflora quality such as Lactobacillus and E. coli in the WGD3. We therefore recommend the use of WGD3 at application level 0.5% in drinking water for optimum laying performance from 30 to 37 wk.


Assuntos
Água Potável , Ginsenosídeos , Microbiota , Panax , Saponinas , Animais , Feminino , Citocinas/genética , Saponinas/farmacologia , Fator de Necrose Tumoral alfa , Galinhas , Escherichia coli , Óvulo , Ginsenosídeos/farmacologia , Lactobacillus , Preparações Farmacêuticas , Extratos Vegetais/farmacologia , República da Coreia
17.
Cell ; 187(1): 95-109.e26, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38181745

RESUMO

DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) catalyze targeted base editing of mitochondrial DNA (mtDNA) in eukaryotic cells, a method useful for modeling of mitochondrial genetic disorders and developing novel therapeutic modalities. Here, we report that A-to-G-editing TALEDs but not C-to-T-editing DdCBEs induce tens of thousands of transcriptome-wide off-target edits in human cells. To avoid these unwanted RNA edits, we engineered the substrate-binding site in TadA8e, the deoxy-adenine deaminase in TALEDs, and created TALED variants with fine-tuned deaminase activity. Our engineered TALED variants not only reduced RNA off-target edits by >99% but also minimized off-target mtDNA mutations and bystander edits at a target site. Unlike wild-type versions, our TALED variants were not cytotoxic and did not cause developmental arrest of mouse embryos. As a result, we obtained mice with pathogenic mtDNA mutations, associated with Leigh syndrome, which showed reduced heart rates.


Assuntos
DNA Mitocondrial , Efetores Semelhantes a Ativadores de Transcrição , Animais , Humanos , Camundongos , Adenina , Citosina , DNA Mitocondrial/genética , Edição de Genes , RNA , Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Engenharia de Proteínas
18.
Nat Med ; 30(1): 177-185, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38182783

RESUMO

Freezing of gait (FoG) is a profoundly disruptive gait disturbance in Parkinson's disease, causing unintended stops while walking. Therapies for FoG reveal modest and transient effects, resulting in a lack of effective treatments. Here we show proof of concept that FoG can be averted using soft robotic apparel that augments hip flexion. The wearable garment uses cable-driven actuators and sensors, generating assistive moments in concert with biological muscles. In this n-of-1 trial with five repeated measurements spanning 6 months, a 73-year-old male with Parkinson's disease and substantial FoG demonstrated a robust response to robotic apparel. With assistance, FoG was instantaneously eliminated during indoor walking (0% versus 39 ± 16% time spent freezing when unassisted), accompanied by 49 ± 11 m (+55%) farther walking compared to unassisted walking, faster speeds (+0.18 m s-1) and improved gait quality (-25% in gait variability). FoG-targeting effects were repeatable across multiple days, provoking conditions and environment contexts, demonstrating potential for community use. This study demonstrated that FoG was averted using soft robotic apparel in an individual with Parkinson's disease, serving as an impetus for technological advancements in response to this serious yet unmet need.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Robótica , Masculino , Humanos , Idoso , Doença de Parkinson/complicações , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/terapia , Marcha/fisiologia , Caminhada/fisiologia
19.
Pediatr Pulmonol ; 59(4): 825-833, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38197494

RESUMO

There is a lack of research that has focused on attention-deficit hyperactivity disorder (ADHD) in people with cystic fibrosis (pwCF). Given ADHD is associated with executive functioning impairments, exploring ADHD in the context of living with cystic fibrosis (CF) is of great importance. The purpose of the current systematic review was to examine ADHD in pwCF across the lifespan in terms of its prevalence, its impact on various health outcomes, and treatments for managing ADHD. This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles reporting studies of any design that focused on ADHD in pwCF were included. Studies were excluded if they did not meet this criterion and if they were written in languages other than English. PsycINFO, MEDLINE, EMBASE, and CINAHL databases were searched. Search items were based on three concepts: (1) terms related to CF, (2) terms related to ADHD, and (3) terms related to age. Ten studies were included in this systematic review. Reported prevalence rates of ADHD in pwCF ranged from 5.26% to 21.9%. The reported relationships between ADHD and CF and other health outcomes is inconsistent. In terms of treatment considerations, pharmacological interventions and behavioural strategies for managing ADHD in the context of living with CF have been reported as being successful. Additional research is needed to further explore ADHD in the CF population and health variables that may be associated with CF prognosis.

20.
J Glaucoma ; 33(5): 361-369, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38194280

RESUMO

PRCIS: This nationwide analysis identified the prevalence and incidence of childhood glaucoma for an 18-year period. The prevalence and incidence of primary congenital glaucoma showed increasing trends. Juvenile open angle glaucoma, meanwhile, showed a decreasing tendency. PURPOSE: We aimed to determine the trends in the prevalence and incidence of childhood glaucoma in the entire population of South Korea. PATIENTS AND METHODS: A nationwide retrospective cohort study was performed with an age-specific and sex-specific population of South Korea. The Korean National Health Insurance Service claims database for 2002 to 2019 was accessed to identify cases of ophthalmologist-confirmed primary childhood glaucoma [ie, primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG)]. Incidence for PCG was estimated for a same-birth-year population, while that for JOAG was estimated using age-specific and sex-specific population figures. To verify the glaucoma cases, we also analyzed the diagnostic codes as well as any information on medication prescriptions and/or ocular-surgery history. RESULTS: During the 18-year observational period, totals of 505 and 7538 patients were diagnosed with PCG and JOAG, respectively. The mean prevalences of PCG and JOAG were 3.96±0.72 and 14.17±5.18, respectively. The prevalence of PCG showed an overall increasing trend during the study period, but the pattern was not significant ( ß =0.049, P =0.143); that of JOAG, meanwhile, showed a significant decreasing tendency ( ß =-0.713, P =0.001). PCG prevalence showed no difference between urban and rural areas, but JOAG showed a higher prevalence in rural areas ( P <0.001). As for mean incidence, the rates for PCG and JOAG were 1.54±0.49 and 5.02±1.95 (per 100,000 person-years), respectively, and were higher in males ( P <0.001 and P =0.013). CONCLUSION: This study identified childhood glaucoma prevalence and incidence in a general population of East Asian ethnicity. This data could help to promote a better understanding of the typical epidemiological features and clinical courses of childhood glaucoma patients.


Assuntos
Glaucoma de Ângulo Aberto , Humanos , República da Coreia/epidemiologia , Incidência , Masculino , Feminino , Prevalência , Estudos Retrospectivos , Criança , Pré-Escolar , Adolescente , Lactente , Distribuição por Idade , Distribuição por Sexo , Glaucoma de Ângulo Aberto/epidemiologia , Pressão Intraocular/fisiologia , Glaucoma/epidemiologia , Recém-Nascido , Bases de Dados Factuais
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