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BACKGROUND: Bariatric surgery is one of the most effective ways to treat morbid obesity, and postoperative nausea and vomiting (PONV) is one of the common complications after bariatric surgery. At present, the mechanism of the high incidence of PONV after weight-loss surgery has not been clearly explained, and this study aims to investigate the effect of surgical position on PONV in patients undergoing bariatric surgery. AIM: To explore the effect of the operative position during bariatric surgery on PONV. METHODS: Data from obese patients, who underwent laparoscopic sleeve gastrectomy (LSG) in the authors' hospital between June 2020 and February 2022 were divided into 2 groups and retrospectively analyzed. Multivariable logistic regression analysis and the t-test were used to study the influence of operative position on PONV. RESULTS: There were 15 cases of PONV in the supine split-leg group (incidence rate, 50%) and 11 in the supine group (incidence rate, 36.7%) (P = 0.297). The mean operative duration in the supine split-leg group was 168.23 ± 46.24 minutes and 140.60 ± 32.256 minutes in the supine group (P < 0.05). Multivariate analysis revealed that operative position was not an independent risk factor for PONV (odds ratio = 1.192, 95% confidence interval: 0.376-3.778, P = 0.766). CONCLUSION: Operative position during LSG may affect PONV; however, the difference in the incidence of PONV was not statistically significant. Operative position should be carefully considered for obese patients before surgery.
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BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.
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Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Recidiva , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Feminino , Masculino , Estudos Prospectivos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Fatores de Tempo , Fatores de Risco , Pontuação de Propensão , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Índice de Gravidade de Doença , Prevenção Secundária/métodosRESUMO
N6-methyladenosine (m6A) is the most prevalent modification in cellular RNA which orchestrates diverse physiological and pathological processes during stress response. However, the differential m6A modifications that cope with herbivore stress in resistant and susceptible crop varieties remain unclear. Here, we found that rice stem borer (RSB) larvae grew better on indica rice (e.g., MH63, IR64, Nanjing 11) than on japonica rice varieties (e.g., Nipponbare, Zhonghua 11, Xiushui 11). Then, transcriptome-wide m6A profiling of representative resistant (Nipponbare) and susceptible (MH63) rice varieties were performed using a nanopore direct RNA sequencing approach, to reveal variety-specific m6A modifications against RSB. Upon RSB infestation, m6A methylation occurred in actively expressed genes in Nipponbare and MH63, but the number of methylation sites decreased across rice chromosomes. Integrative analysis showed that m6A methylation levels were closely associated with transcriptional regulation. Genes involved in herbivorous resistance related to mitogen-activated protein kinase, jasmonic acid (JA), and terpenoid biosynthesis pathways, as well as JA-mediated trypsin protease inhibitors, were heavily methylated by m6A, and their expression was more pronounced in RSB-infested Nipponbare than in RSB-infested MH63, which may have contributed to RSB resistance in Nipponbare. Therefore, dynamics of m6A modifications act as the main regulatory strategy for expression of genes involved in plant-insect interactions, which is attributed to differential responses of resistant and susceptible rice varieties to RSB infestation. These findings could contribute to developing molecular breeding strategies for controlling herbivorous pests.
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Carexqingyuanensis, a new species of Cyperaceae from Guangdong Province, China, is described and illustrated. The new species is morphologically similar to Carexpeliosanthifolia F. T. Wang & Tang ex P. C. Li, but it can be distinguished by the racemose inflorescence branches appearing single (rarely binate or ternate) (vs. binate or ternate), one (rarely two or three) (vs. 1-3) spiked, male part of linear-cylindrical spikes much longer than the female part (vs. just male part short-cylindrical and slightly longer than female part), style base thickened (vs. not thickened) and perigynium horizontally patent with a short (vs. long and excurved) beak. Phylogenetic analysis, based on the two nuclear DNA regions (ETS 1f and ITS) and three chloroplast DNA regions (matK, ndhF and rps16), suggests that the new species belongs to sect. Siderostictaes.s. of subg. Siderosticta and shows a closer phylogenetic relationship to Carexscaposa C. B. Clarke.
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Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.
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Ciclina D2 , Megalencefalia , Polidactilia , Polimicrogiria , Feminino , Humanos , Masculino , Códon sem Sentido/genética , Ciclina D2/genética , Sequenciamento do Exoma , Hidrocefalia , Malformações do Desenvolvimento Cortical , Megalencefalia/genética , Megalencefalia/diagnóstico , Polidactilia/genética , Polidactilia/diagnóstico , Polimicrogiria/genética , Polimicrogiria/diagnóstico , Pré-EscolarRESUMO
Background: Congenital cataracts stand as the primary cause of childhood blindness globally, characterized by clouding of the eye's lens at birth or shortly thereafter. Previous investigations have unveiled that a variant in the V-MAF avian musculoaponeurotic-fibrosarcoma oncogene homolog (MAF) gene can result in Ayme-Gripp syndrome and solitary cataract. Notably, MAF mutations have been infrequently reported in recent years. Methods: In this investigation, we recruited a Chinese family with non-syndromic cataracts. Whole exome sequencing and Sanger sequencing were applied to scrutinize the genetic anomaly within the family. Results: Through whole exome sequencing and subsequent data filtration, a new mutation (NM_005360, c.901T>C/p.Y301H) in the MAF gene was detected. Sanger sequencing validated the presence of this mutation in another affected individual. The p.Y301H mutation, situated in an evolutionarily preserved locus, was not detected in our 200 local control cohorts and various public databases. Additionally, multiple bioinformatic programs predicted that the mutation was deleterious and disrupted the bindings between MAF and its targets. Conclusion: Hence, we have documented a new MAF mutation within a Chinese family exhibiting isolated congenital cataracts. Our study has the potential to broaden the spectrum of MAF mutations, offering insights into the mechanisms underlying cataract formation and facilitating genetic counseling and early diagnosis for congenital cataract patients.
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BACKGROUND: Cockayne syndrome is an inherited heterogeneous defect in transcription-coupled DNA repair (TCR) cause severe clinical syndromes, which may affect the nervous system development of infants and even lead to premature death in some cases. ERCC8 diverse critical roles in the nucleotide excision repair (NER) complex, which is one of the disease-causing genes of Cockayne syndrome. METHODS AND RESULTS: The mutation of ERCC8 in the patient was identified and validated using WES and Sanger sequencing. Specifically, a compound heterozygous mutation (c.454_460dupGTCTCCA p. T154Sfs*13 and c.755_759delGTTTT p.C252Yfs*3) of ERCC8 (CSA) was found, which could potentially be the genetic cause of Cockayne syndrome in the proband. CONCLUSION: In this study, we identified a novel heterozygous mutation of ERCC8 in a Chinese family with Cockayne syndrome, which enlarging the genetic spectrum of the disease.
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Síndrome de Cockayne , Humanos , Povo Asiático , Núcleo Celular , Síndrome de Cockayne/genética , Enzimas Reparadoras do DNA/genética , Reparo por Excisão , Mutação/genética , Fatores de TranscriçãoRESUMO
BACKGROUND: Firmiana danxiaensis is a critically endangered and ecologically important tree currently only found in four locations in Danxia or Karst habitats in northern Guangdong Province, China. The specialized habitat preference makes it an ideal model species for study of adaptive evolution. Meanwhile, the phylogenetic relationships of F. danxiaensis in four locations under two landforms are unclear. Therefore, we sequenced its complete chloroplast (cp.) genomes and conducted comprehensive interspecific and intrageneric plastome studies. RESULTS: The F. danxiaensis plastomes in four locations showed a typical quadripartite and circular structure that ranged from 160,832 to 161,206 bp in size, with 112 unique genes encoded. Comparative genomics showed that the plastomes of F. danxiaensis were relatively conserved with high similarity of genome organization, gene number, GC content and SSRs. While the genomes revealed higher biased codon preferences in Karst habitat than those in Danxia habitats. Eighteen and 11 divergent hotpots were identified at interspecific and intrageneric levels for species identification and further phylogenetic studies. Seven genes (clpP, accD, ccsA, ndhH, rpl20, rpoC2, and rps4) were under positive selection and may be related to adaptation. Phylogenetic analysis revealed that F. danxiaensis is sister to F. major and F. simplex. However, the interspecific relationships are not consistent with the habitat types. CONCLUSIONS: The characteristics and interspecific relationship of F. danxiaensis plastomes provide new insights into further integration of geographical factors, environmental factors, and genetic variations on the genomic study of F. danxiaensis. Together, our study will contribute to the study of species identification, population genetics, and conservation biology of F. danxiaensis.
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Genoma de Cloroplastos , Filogenia , Genoma de Cloroplastos/genética , Genômica , Sequência de Bases , Genética PopulacionalRESUMO
Insensitivity to external optical feedback is experimentally demonstrated in a self-chaotic deformed square microcavity laser for the first time, to the best of our knowledge. Both the optical and radio frequency (RF) spectra of the microlaser remain unaffected for external optical feedback with feedback strength as high as 9.9â dB. In addition, the autocorrelation function curve exhibits no time-delayed peaks. The insensitivity makes the self-chaotic microcavity laser promising for applications in feedback-insensitive optical sources.
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Video object removal aims at erasing a target object in the entire video and filling holes with plausible contents, given an object mask in the first frame as input. Existing solutions mostly break down the task into (supervised) mask tracking and (self-supervised) video completion, and then separately tackle them with tailored designs. In this paper, we introduce a new setup, coined as unified video object removal, where mask tracking and completion are addressed within a unified framework. Despite introducing more challenges, the setup is promising for future practical usage. We embrace the observation that these two sub-tasks have strong inherent connections in terms of pixel-level temporal correspondence. Making full use of the connections could be beneficial considering the complexity of both algorithm and deployment. We propose a single network linking the two sub-tasks by inferring temporal correspondences across multiple frames, i.e., correspondences between valid-valid (V-V) pixel pairs for mask tracking and correspondences between valid-hole (V-H) pixel pairs for video completion. Thanks to the unified setup, the network can be learned end-to-end in a totally unsupervised fashion without any annotations. We demonstrate that our method can generate visually pleasing results and perform favorably against existing separate solutions in realistic test cases.
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We explored the relationship between climate factors (mean annual precipitation and mean annual temperature) and the contents and stoichiometry of soil carbon (C), nitrogen (N), and phosphorus (P) at different soil depths (0-5, 5-10, 10-20, 20-30, 30-50, 50-70, and 70-100 cm) temperate steppe of Longzhong. The results showed with the increases of soil depth, soil C, N contents, C:P, and N:P gradually decreased from 21.88 g·kg-1, 1.84 g·kg-1, 33.6 and 3.1 to 7.67 g·kg-1, 0.59 g·kg-1, 12.5 and 1.0, respectively. Soil C:N showed an increasing trend from 12.2 to 13.9, while soil P content remained stable with an average of 0.61 g·kg-1. Soil C, N, C:P, and N:P were significantly positively correlated with mean annual precipitation and negatively correlated with mean annual temperature. Soil P content and C:N were not correlated with mean annual precipita-tion and mean annual temperature. With the increases of soil depth, the total explanatory power of the changes in soil C, N and P contents by mean annual precipitation and mean annual temperature decreased and then increased, and that in soil C:P, N:P and C:N did not change significantly. The changes of soil C, N and P contents on the temperature steppe were mainly influenced by mean annual precipitation. The effects and relative contributions of mean annual precipitation and mean annual temperature on the variations of soil nutrient contents and stoichiometry of C, N and P differed at different soil depths.
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Nitrogênio , Solo , Temperatura , China , Nitrogênio/análise , Carbono/análise , Fósforo/análiseRESUMO
OBJECTIVE: Bioequivalence (BE) studies support the approval and clinical use of both new and generic drug products. Narrow therapeutic index (NTI) drugs have relatively high costs and low success rates of BE evaluation clinical trials as high-risk drugs. A physiologically-based pharmacokinetic (PBPK) model can be used to evaluate the BE of two preparations. METHODS: This study inputs the basic physical and chemical property parameters of warfarin sodium available at the present stage into GastroPlus™ software, and combined it with the Advanced Compartmental Absorption and Transit (ACAT™) model built into the software. The PBPK model of Chinese individuals taking 2.5 mg of warfarin sodium orally while fasted condition was developed using the disposal parameters calculated from the clinically measured PK data of the reference preparations. The model was tested using the PK data of other reference preparations and tested preparations from different domestic manufacturers. RESULTS: The results revealed that at least 30% of drugs are released in 30 min under a pH of 4.5 condition, and at least 80% are released in 30 min under a pH of 6.8 condition, which can be used as bioequivalent dissolution limits under fasted conditions. The risk of BE failure in the fed condition will be significantly reduced for the clinical study on the BE of warfarin sodium, which is a NTI drug if the fasted condition is bioequivalent. CONCLUSION: The results revealed that the PBPK models were successfully developed for 2.5 mg of warfarin sodium tablets in Chinese individuals. Developing a PBPK model for NTI drugs based on in vitro dissolution data in software is a promising method for BE evaluation, which can provide great help for developing new drugs and the clinical trial research of BE of generic drugs.
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Software , Varfarina , Humanos , Equivalência Terapêutica , Solubilidade , Jejum , Modelos Biológicos , ComprimidosRESUMO
Wild rice (Zizania spp.), an aquatic grass belonging to the subfamily Gramineae, has a high economic value. Zizania provides food (such as grains and vegetables), a habitat for wild animals, and paper-making pulps, possesses certain medicinal values, and helps control water eutrophication. Zizania is an ideal resource for expanding and enriching a rice breeding gene bank to naturally preserve valuable characteristics lost during domestication. With the Z. latifolia and Z. palustris genomes completely sequenced, fundamental achievements have been made toward understanding the origin and domestication, as well as the genetic basis of important agronomic traits of this genus, substantially accelerating the domestication of this wild plant. The present review summarizes the research results on the edible history, economic value, domestication, breeding, omics research, and important genes of Z. latifolia and Z. palustris over the past decades. These findings broaden the collective understanding of Zizania domestication and breeding, furthering human domestication, improvement, and long-term sustainability of wild plant cultivation.
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Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, IFN-α and IFN-ß, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD.
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Doença de Alzheimer , Estilbenos , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Inflamassomos/metabolismo , Glicosídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Lipopolissacarídeos , Citocinas/metabolismo , Nucleotidiltransferases/metabolismo , Camundongos Transgênicos , Estilbenos/farmacologia , Estilbenos/uso terapêuticoRESUMO
We propose and demonstrate deformed square cavity microlasers for realizing highly efficient output from a connected waveguide. The square cavities are deformed asymmetrically by replacing two adjacent flat sides with circular arcs to manipulate the ray dynamics and couple the light to the connected waveguide. The numerical simulations show that the resonant light can efficiently couple to the fundamental mode of the multi-mode waveguide by carefully designing the deformation parameter utilizing global chaos ray dynamics and internal mode coupling. An enhancement of approximately six times in the output power is realized in the experiment compared to the non-deformed square cavity microlasers, while the lasing thresholds are reduced by about 20%. The measured far-field pattern shows highly unidirectional emission agreeing well with the simulation, which confirms the feasibility of the deformed square cavity microlasers for practical applications.
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Postharvest chilling injury (CI) of fruit, including peaches, is a huge challenge to horticultural product preservation. Microwave irradiation can be used as a physiological regulator due to the thermal effects; however, its non-thermal effects on the CI of postharvest fruit remain unclear. Thus, the physiological attributes and metabolisms involving phenolics, fatty acids, and sugars were compared between 'Zhongtao No.9' peaches treated with microwave irradiation at 45.5 W for different durations and control. Microwave treatment especially at 45.5 W for 7 min without inducing thermal effects could significantly inhibit internal browning caused by CI, concomitant with reduced total phenolic content. Moreover, the maintenance of membrane stability was indicated by a boosted double bond index, which may be attributed to the inhibition of membrane lipid degradation, and sucrose accumulation. In summary, the non-thermal effects of microwave irradiation contribute to CI alleviation through restraining phenolic content and maintaining membrane stability in peach fruit.
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Prunus persica , Prunus persica/metabolismo , Frutas/química , Micro-Ondas , Açúcares/análise , Ácidos Graxos/análise , Temperatura BaixaRESUMO
This study aimed to investigate whether lactating Hu sheep's dietary protein levels could generate dynamic effects on the performance of their offspring. Twelve ewes with similar parity were fed iso-energy diets which contained different protein levels (P1: 9.82%, P2: 10.99%) (n = 6), and the corresponding offspring were divided into SP1 and SP2 (n = 12). At 60 days, half of the lambs were harvested for further study: the carcass weight (p = 0.043) and dressing percentage (p = 0.004) in the SP2 group were significantly higher than SP1. The acetic acid (p = 0.007), propionic acid (p = 0.003), butyric acid (p < 0.001) and volatile fatty acids (p < 0.001) in rumen fluid of SP2 were significantly lower than SP1. The expression of MCT2 (p = 0.024), ACSS1 (p = 0.039) and NHE3 (p = 0.006) in the rumen of SP2 was lower than SP1, while the HMGCS1 (p = 0.026), HMGCR (p = 0.024) and Na+/K+-ATPase (p = 0.020) was higher than SP1. The three dominant phyla in the rumen are Bacteroidetes, Proteobacteria and Firmicutes. The membrane transport, amino acid metabolism and carbohydrate metabolism of SP1 were relatively enhanced, the replication and repair function of SP2 was relatively enhanced. To sum up, the increase of dietary protein level significantly increased the carcass weight and dressing percentage of offspring and had significant effects on rumen volatile fatty acids, acetic acid activation and cholesterol synthesis related genes. HIGHLIGHTSIn the early feeding period, the difference in ADG of lambs was mainly caused by the sucking effect.The increase in dietary protein level of ewes significantly increased the carcass weight and dressing percentage of offspring.The dietary protein level of ewes significantly affected the volatile fatty acids (VFAs) and genes related to acetic acid activation and cholesterol synthesis in the rumen of their offspring.The membrane transport, amino acid metabolism and carbohydrate metabolism of the offspring of ewes fed with a low protein diet were relatively enhanced.The replication and repair function of the offspring of ewes fed with a high protein diet was relatively strengthened.
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Lactação , Rúmen , Gravidez , Animais , Ovinos , Feminino , Rúmen/metabolismo , Dieta/veterinária , Ácidos Graxos Voláteis , Acetatos/análise , Acetatos/metabolismo , Proteínas Alimentares/análise , Proteínas Alimentares/metabolismo , Aminoácidos/análise , Aminoácidos/metabolismo , Colesterol/metabolismo , Ração Animal/análise , Leite/química , Suplementos NutricionaisRESUMO
Along with the extensive application of radiation in medical, military and other fields, human beings carry a greater risk of exposure to radiation environment that causes a range of physical injure, particularly to the brain in cognition. However, the radiation-associated cognitive disability is poorly understood and there is no effective prevention or long-term treatment. Here, we demonstrate that neurogenesis and neuroinflammation disorder are primarily involved in the pathophysiological basis of irradiation-induced cognitive decline. Furthermore, we discovered that tetrahydroxy stilbene glucoside (TSG), a natural active ingredient from Heshouwu that has been well known for its unique anti-aging effect as the Chinese herb, can be a promising mitigator to improve learning-memory ability by facilitating the neurogenesis in the proliferation and differentiation of the surviving neural progenitor cells via AMPK/Tet2, and attenuating the neuroinflammation in the microglial NLRP3 inflammasomes activation via AMPK in vivo. Additionally, TSG was also revealed to activate AMPK by molecular docking and kinase enzyme system assay in vitro. Taken together, our findings identify TSG, as the AMPK activator, prevents radiation-induced cognitive dysfunction by regulating neurogenesis and neuroinflammation via AMPK/Tet2 in rodents, and represents a very promising candidate for developing drugs that can be used for radiation-associated brain injury.
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Proteínas Quinases Ativadas por AMP , Dioxigenases , Cognição , Proteínas de Ligação a DNA , Dioxigenases/farmacologia , Glucosídeos , Humanos , Simulação de Acoplamento Molecular , Neurogênese , Doenças Neuroinflamatórias , EstilbenosRESUMO
Although feline coronavirus (FCoV) infection is extremely common in cats, there are currently few effective treatments. A peptide derived from the heptad repeat 2 (HR2) domain of the coronavirus (CoV) spike protein has shown effective for inhibition of various human and animal CoVs in vitro, but further use of FCoV-HR2 in vivo has been limited by lack of practical delivery vectors and small animal infection model. To overcome these technical challenges, we first constructed a recombinant Bacillus subtilis (rBSCotB-HR2P) expressing spore coat protein B (CotB) fused to an HR2-derived peptide (HR2P) from a serotype II feline enteric CoV (FECV). Immunogenic capacity was evaluated in mice after intragastric or intranasal administration, showing that recombinant spores could trigger strong specific cellular and humoral immune responses. Furthermore, we developed a novel mouse model for FECV infection by transduction with its primary receptor (feline aminopeptidase N) using an E1/E3-deleted adenovirus type 5 vector. This model can be used to study the antiviral immune response and evaluate vaccines or drugs, and is an applicable choice to replace cats for the study of FECV. Oral administration of rBSCotB-HR2P in this mouse model effectively protected against FECV challenge and significantly reduced pathology in the digestive tract. Owing to its safety, low cost, and probiotic features, rBSCotB-HR2P is a promising oral vaccine candidate for use against FECV/FCoV infection in cats.
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Infecções por Coronavirus , Coronavirus Felino , Animais , Bacillus subtilis/genética , Antígenos CD13/metabolismo , Gatos , Coronavirus Felino/genética , Coronavirus Felino/metabolismo , Modelos Animais de Doenças , Humanos , Imunidade , Camundongos , Peptídeos/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Esporos Bacterianos/genéticaRESUMO
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is responsible for the COVID-19 pandemic that has caused unprecedented loss of life and economic trouble all over the world, though the mechanism of its replication remains poorly understood. In this study, antibodies were generated and used to systematically determine the expression profile and subcellular distribution of 11 SARS-CoV-2 nonstructural replicase proteins (nsp1, nsp2, nsp3, nsp5, nsp7, nsp8, nsp9, nsp10, nsp13, nsp14, and nsp15) by Western blot and immunofluorescence assay. Nsp3, nsp5, and nsp8 were detected in perinuclear foci at different time points, with diffusion and stronger fluorescence observed over time. In particular, colocalization of nsp8 and nsp13 with different replicase proteins suggested viral protein-protein interaction, which may be key to understanding their functions and potential molecular mechanisms. Viral intermediate dsRNA was detected in perinuclear foci as early as 2-h postinfection, indicating the initiation of virus replication. With the passage of time, these perinuclear dsRNA foci became larger and brighter, and nearly all colocalized with N protein, consistent with viral growth over time. Thus, the development of these anti-nsp antibodies provides basic tools for the further study of replication and diagnosis of SARS-CoV-2. IMPORTANCE The intracellular localization of SARS-CoV-2 replicase nonstructural proteins (nsp) during infection has not been fully elucidated. In this study, we systematically analyzed the expression and subcellular localization of 11 distinct viral nsp and dsRNA over time in SARS-CoV-2-infected cells by using individual antibody against these replicase proteins. The data indicated that nsp gene expression is highly regulated in space and time, which could be useful to understand the function of viral replicases and future development of diagnostics and potential antiviral strategies against SARS-CoV-2.