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Although the gut microbiota can influence central nervous system (CNS) autoimmune diseases, the contribution of the intestinal epithelium to CNS autoimmunity is less clear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2) promoted sex-specific disease progression in an animal model of multiple sclerosis. Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory response in the CNS and reduced disease progression. In contrast, overexpression or activation of IEC DRD2 by phenylethylamine administration exacerbated disease severity. This was accompanied by altered lysozyme expression and gut microbiota composition, including reduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived from Lactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our study indicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increases susceptibility to CNS autoimmune diseases in a female-biased manner, opening up future avenues for sex-specific interventions of CNS autoimmune diseases.
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Enfermedades Autoinmunes del Sistema Nervioso , Esclerosis Múltiple , Masculino , Femenino , Ratones , Animales , Esclerosis Múltiple/metabolismo , Modelos Animales de Enfermedad , Transducción de Señal , Progresión de la Enfermedad , Receptores DopaminérgicosRESUMEN
Small-scale soft robots demonstrate intricate life-like behavior and allow navigation through arduous terrains and confined spaces. However, the primary challenges in soft robotics are 1) creating actuators capable of quick, reversible 22D-to-3D shape morphing with adjustable stiffness, 2) improving actuation force and robustness for wider applications, and 3) designing holistic systems for untethered manipulation and flexible multimodality in practical scenarios. Here, mechanically compliant paper-like robots are presented with multiple functionalities. The robots are based on photothermally activated polymer bimorph actuators that incorporate graphene for the photo-thermal conversion of energy and muscovite mica, with its high Young's modulus, providing the required stiffness. Conversion of light into heat leads to thermal expansion and bending of the stress-mismatched structures. The actuators are designed on the basis of a modified Timoshenko model, and numerical simulations are employed to evaluate their actuation performance. The membranes can be utilized for light-driven programmable shape-morphing. Localized control allows the implementation of active hinges at arbitrary positions within the membrane. Integrated into small-scale soft robots in mass production, the membrane facilitates locomotion, rolling, and flipping of the robots. Further, grasping and kicking mechanisms are demonstrated, highlighting the potential of such actuators for future applications.
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BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer. METHODS: In the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T. RESULTS: We found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48-72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal. CONCLUSIONS: In this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.
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Antígenos B7 , Inmunoterapia Adoptiva , Neoplasias Pancreáticas , Receptores Quiméricos de Antígenos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Humanos , Animales , Línea Celular Tumoral , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/inmunología , Inmunoterapia Adoptiva/métodos , Antígenos B7/metabolismo , Antígenos B7/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Proliferación Celular , Linfocitos T/inmunologíaRESUMEN
The glycocalyx is a proteoglycan-glycoprotein structure lining the luminal surface of the vascular endothelium and is susceptible to damage due to blast overpressure (BOP) exposure. The glycocalyx is essential in maintaining the structural and functional integrity of the vasculature and regulation of cerebral blood flow (CBF). Assessment of alterations in the density of the glycocalyx; its components (heparan sulphate proteoglycan (HSPG/syndecan-2), heparan sulphate (HS), and chondroitin sulphate (CS)); CBF; and the effect of hypercapnia on CBF was conducted at 2-3 h, 1, 3, 14, and 28 days after a high-intensity (18.9 PSI/131 kPa peak pressure, 10.95 ms duration, and 70.26 PSI·ms/484.42 kPa·ms impulse) BOP exposure in rats. A significant reduction in the density of the glycocalyx was observed 2-3 h, 1-, and 3 days after the blast exposure. The glycocalyx recovered by 28 days after exposure and was associated with an increase in HS (14 and 28 days) and in HSPG/syndecan-2 and CS (28 days) in the frontal cortex. In separate experiments, we observed significant decreases in CBF and a diminished response to hypercapnia at all time points with some recovery at 3 days. Given the role of the glycocalyx in regulating physiological function of the cerebral vasculature, damage to the glycocalyx after BOP exposure may result in the onset of pathogenesis and progression of cerebrovascular dysfunction leading to neuropathology.
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Proteoglicanos de Heparán Sulfato , Sindecano-2 , Animales , Ratas , Glicocálix , Hipercapnia , Circulación Cerebrovascular , Heparitina Sulfato , Sulfatos de CondroitinaRESUMEN
CRISPR/Cas9 gene editing technology, as a highly efficient genome editing method, has been extensively employed in the realm of animal husbandry for genetic improvement. With its remarkable efficiency and precision, this technology has revolutionized the field of animal husbandry. Currently, CRISPR/Cas9-based gene knockout, gene knock-in and gene modification techniques are widely employed to achieve precise enhancements in crucial production traits of livestock and poultry species. In this review, we summarize the operational principle and development history of CRISPR/Cas9 technology. Additionally, we highlight the research advancements utilizing this technology in muscle growth and development, fiber growth, milk quality composition, disease resistance breeding, and animal welfare within the livestock and poultry sectors. Our aim is to provide a more comprehensive understanding of the application of CRISPR/Cas9 technology in gene editing for livestock and poultry.
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Sistemas CRISPR-Cas , Ganado , Animales , Ganado/genética , Aves de Corral/genética , Edición Génica/métodos , Técnicas de Sustitución del GenRESUMEN
BACKGROUND: Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis. METHODS: This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques. RESULTS: The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis. CONCLUSIONS: This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.
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Multiómica , Piel , Animales , Piel/metabolismo , Cabras/genéticaRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing and multiple studies have elucidated its pathogenesis, however, the related- microbiome imbalance caused by SARS-CoV-2 is still not clear. In this study, we have comprehensively compared the microbiome composition and associated function alterations in the oropharyngeal swabs of healthy controls and coronavirus disease 2019 (COVID-19) patients with moderate or severe symptoms by metatranscriptomic sequencing. We did observe a reduced microbiome alpha-diversity but significant enrichment of opportunistic microorganisms in patients with COVID-19 compared with healthy controls, and the microbial homeostasis was rebuilt following the recovery of COVID-19 patients. Correspondingly, less functional genes in multiple biological processes and weakened metabolic pathways such as carbohydrate metabolism, energy metabolism were also observed in COVID-19 patients. We only found higher relative abundance of limited genera such as Lachnoanaerobaculum between severe patients and moderate patients while no worthy-noting microbiome diversity and function alteration were observed. Finally, we noticed that the co-occurrence of antibiotic resistance and virulence was closely related to the microbiome alteration caused by SRAS-CoV-2. Overall, our findings demonstrate that microbial dysbiosis may enhance the pathogenesis of SARS-CoV-2 and the antibiotics treatment should be critically considered.
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COVID-19 , Microbiota , Humanos , SARS-CoV-2 , Disbiosis , Farmacorresistencia MicrobianaRESUMEN
Optical frequency metrology in atoms and ions can probe hypothetical fifth forces between electrons and neutrons by sensing minute perturbations of the electronic wave function induced by them. A generalized King plot has been proposed to distinguish them from possible standard model effects arising from, e.g., finite nuclear size and electronic correlations. Additional isotopes and transitions are required for this approach. Xenon is an excellent candidate, with seven stable isotopes with zero nuclear spin, however it has no known visible ground-state transitions for high resolution spectroscopy. To address this, we have found and measured twelve magnetic-dipole lines in its highly charged ions and theoretically studied their sensitivity to fifth forces as well as the suppression of spurious higher-order standard model effects. Moreover, we identified at 764.8753(16) nm a E2-type ground-state transition with 500 s excited state lifetime as a potential clock candidate further enhancing our proposed scheme.
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OBJECTIVE: Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been associated with several fatal adverse events, such as pneumonia, interstitial lung disease, and infection. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted ADCs. METHODS: We performed a systematic search in Embase, PubMed, Web of Science, and Scopus databases from inception to February 1, 2022, and the last search was updated to July 1, 2023. The eligible studies for inclusion in our analysis were limited to RCTs of HER2-targeted ADCs that were approved by the US Food and Drug Administration and examined on cancer patients with available data on fatal adverse events. The protocol for this study was registered in PROSPERO (No. CRD42022331627). RESULTS: Fifteen studies (13 RCTs) involving 7,277 patients were finally included for meta-analysis. Of these patients, 4,246 received HER2-targeted ADCs and 3,481 received the control treatment. The data were combined using Bayesian hierarchical modeling, which allowed for the estimation of the mean incidence of fatal adverse events to be 0.78% (95% CrI: 0.28-1.37%, τ = 0.006) for the patients treated with HER2-targeted ADCs. The relative risk was 0.80 (95% CrI, 0.5-1.26, τ = 0.17) compared to control patients. Among 43 reported deaths caused by HER2-targeted ADCs, the most common fatal adverse event was respiratory toxicity, including pneumonia, pneumonitis, and interstitial lung disease. On subgroup analysis, no difference in the risk of fatal adverse events was found between different HER2-targeted ADCs or cancer types. CONCLUSION: Our findings suggest that the risk of fatal adverse events with HER2-targeted ADCs may be lower compared to standard control therapies in cancer patients, and there is no significant difference in risk observed between different HER2-targeted ADCs or cancer types. However, the most common fatal adverse event was respiratory toxicity, suggesting that cancer patients who use the above drugs should strengthen respiratory system monitoring and take preventive measures in some severe cases.
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Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Neoplasias , Neumonía , Humanos , Inmunoconjugados/efectos adversos , Incidencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/epidemiologíaRESUMEN
Determine the association of lean body mass (LBM) on the incidence and severity of peripheral neurotoxicity in cancer patients who received nab-paclitaxel alone or combined with cisplatin or carboplatin. This prospective clinical study examined 32 cancer patients classified into a sarcopenia or non-sarcopenia group according to the Asian L3 vertebra skeletal muscle index (L3-SMI) at Ordos Central Hospital (China) from December 2020-2021, to compare the incidence and severity of neurotoxicity and analizing the relationship between nab-paclitaxel dose per kg LBM and neurotoxicity. There were 18 patients (56.25%) in the sarcopenia group and 14 (43.75%) in the non-sarcopenia group. The incidences of peripheral and severe neurotoxicity were higher in the sarcopenia group (both P < 0.05). Patients in three different body surface area (BSA) groups received the same nab-paclitaxel dose (260 mg/m2 BSA). However, when patients were divided into three groups according to LBM, they received different doses (low-LBM: 15.18 mg/kg LBM, middle-LBM: 12.82 mg/kg LBM, and high-LBM: 11.14 mg/kg LBM). The incidence of grade-C or higher neurotoxicity of these three groups was 61.54% (8/13), 20.00% (1/5), and 11.11% (1/9). Sarcopenia and a higher dose of nab-paclitaxel per kg LBM were associated with peripheral and severe neurotoxicity. Chemotherapy dosing based on body composition may reduce neurotoxicity in patients receiving nab-paclitaxel.Registration number of Clinical Trial: ChiCTR2000040918.
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Neoplasias , Sarcopenia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Composición Corporal , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Paclitaxel/efectos adversos , Estudios Prospectivos , Sarcopenia/inducido químicamente , Sarcopenia/epidemiologíaRESUMEN
Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and N-acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS-5) and its N-acetylated derivative (N-5) showed the best protective activity. Pretreatment with COS-5 or N-5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N-5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.
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Antioxidantes , Degeneración Macular , Humanos , Anciano , Antioxidantes/farmacología , Antioxidantes/metabolismo , Acroleína/toxicidad , Supervivencia Celular , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Degeneración Macular/inducido químicamente , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/prevención & controlRESUMEN
Liaoning cashmere goat (LCG) is a famous cashmere goat breed in China. Cashmere fineness, as an important index to evaluate cashmere quality, is also one of the problems to be improved for Liaoning cashmere goats. Transcriptome studies all mRNA transcribed by a specific tissue or cell in a certain period. It is a key link in the study of gene expression regulation. It plays an important role in the analysis of biological growth and disease. Transcriptome is spatio-temporal specific, that is, gene expression varies in different tissues or at different times. Three coarser and three fine LCG skin samples were sequenced by RNA-seq technology, and a total of 427 differentially expressed genes were obtained, including 291 up-regulated genes and 136 down-regulated genes. In the experiment, we screened out 16 genes that had significant differences in the expression of coarse and fine cashmere of Liaoning cashmere goats, so it was inferred that these 16 genes might have regulatory effects on cashmere fineness. Moreover, GO gene set enrichment analysis revealed that differential genes mainly consist of immune response, MHC protein complex, Heme binding and other pathways. KEGG analysis showed that transplant-versus-host disease and allograft rejection were the main pathways of differential genes.
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Regulación de la Expresión Génica , Transcriptoma , Animales , Perfilación de la Expresión Génica/veterinaria , Secuencia de Bases , Cabras/genética , Folículo Piloso/metabolismoRESUMEN
This study aimed to investigate the relationship between the polymorphism of bile acid-CoA: amino acid N-acyltransferase (BAAT) and collagen type I alpha 1 chain (COL1A1) genes and the production performance of Liaoning Cashmere goat (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence comparison of BAAT and COL1A1 genes and PCR-Seq polymorphism, and the effect of SNPs on production performance was analyzed by SPSS software. The results showed that three SNPs loci were detected in BAAT gene: G7900A, T7967C, C7998T, and one SNP locus T6716C was detected in COL1AL gene. At G7900A locus, the dominant genotype for cashmere performance was GG, and the dominant genotype for body measurement traits and milk production traits was AG. At T7967C locus, the dominant genotype for cashmere performance was TT, and the dominant genotype for body measurement traits and milk production traits was CC. At C7998T locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. At the T6716C locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. H1H1: AACC is the dominant haplotype combination. Therefore, this study will provide a reliable reference for future research on cashmere production performance, body measurement traits, and milk production traits of LCG.
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Cabras , Polimorfismo de Nucleótido Simple , Animales , Polimorfismo de Nucleótido Simple/genética , Cabras/genética , Fenotipo , Genotipo , Reacción en Cadena de la PolimerasaRESUMEN
Reproductive traits have a high economic value in goat breeding, and increasing the number of lambs produced by ewes is of great importance to improve the production efficiency of goat farming. Lambing traits in goats are low heritability traits, but their genetic basis is ultimately determined by genes. This study aimed to investigate the relationship between INHA, RARG, and PGR gene polymorphisms and production performance, such as lambing, cashmere production, milk production, and body size in Liaoning cashmere goats. A total of six single nucleotide polymorphisms (SNPs) loci were identified in these three genes, G144A and T504C on the INHA gene, A56G, G144A, G490C on the RARG gene, and G109519T on the PGR gene. For lambing and cashmere production traits, the AA genotype of G144A on the INHA gene, TT on the T504C genotype, GG genotype of G144A on the INHA gene, A56G, G144A, and T504C on RARG and G109519T on PGR gene are dominant genotypes. AATT is a dominant haplotype combination. Allele G can be used as a molecular marker for lambing, cashmere, and milk production traits in Liaoning cashmere goats. Marker-assisted selection can be used for early selection to achieve improvement of genetic traits in Liaoning cashmere goats.
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Cabras , Polimorfismo de Nucleótido Simple , Ovinos/genética , Animales , Femenino , Cabras/genética , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Genotipo , Oveja Doméstica , Reproducción/genéticaRESUMEN
Liaoning cashmere goat (LCG) have tall bones, high cashmere production and outstanding meat production performance. In recent years, good breeding progress has not been made in terms of body size, meat yield, milk yield and other properties in terms of production. The study focused on the correlation between the SNPs of MSTN and IGFBP-3 genes with the body size performance, cashmere production and milk performance. The MSTN and IGFBP-3 gene sequence alignment and PCR-Seq polymorphism were used to detect the potential SNPs, and the correlation with production performance was analyzed by SPSS and SHEsis software. The results showed that the TT genotype at the T1662G locus of the MSTN gene is dominant and has significant advantages in body measurements such as sacrum height, chest width, and waist height. The C allele at the C4021T locus of IGFBP-3 gene shows an advantage in the body measurement performance. Among the haplotype combinations, H2H2:TGTC is preponderant combination for body size performance, H2H2:TGTC and H1H2:TGCC are preponderant combinations for cashmere production performance, H1H3:GGCC is preponderant combination for milk production performance. It may be a molecular marker for future selection and breeding.
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Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Polimorfismo de Nucleótido Simple , Animales , Polimorfismo de Nucleótido Simple/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Cabras/genética , Genotipo , Tamaño Corporal/genéticaRESUMEN
Cashmere fineness is getting thicker, which is one of the key problems in cashmere breeding, however, there have been no systematic studies on the molecular regulation of cashmere fineness. The aim of this study was to investigate the relationship between KRT26 and TCHH gene polymorphism and production performance in Liaoning cashmere goats (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence alignment and PCR-Seq polymorphism of KRT26 and TCHH genes and analyzed the effect of SNPs on production performance by SPSS software. Two SNPs sites (A559T and A6839G) of two genes were detected. The AA genotype of KRT26 A559T locus was the dominant genotype. AG and GG at TCHH A6839G locus were the dominant genotypes. AAAA was the dominant haplotype combination. The results showed that KRT26 and TCHH genes were associated with cashmere fineness of LCG, and A559T (AA) and A6839G (GG) genotypes were the preferred marker genotypes for cashmere fineness, which provided more theoretical basis for further research on cashmere fineness.
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Cabras , Polimorfismo de Nucleótido Simple , Animales , Polimorfismo de Nucleótido Simple/genética , Cabras/genética , Leche , Fenotipo , Reacción en Cadena de la PolimerasaRESUMEN
Liaoning cashmere goat (LCG) is one of the excellent cashmere goat breeds in China. Because of its larger size, better cashmere, and better cashmere production performance, people pay special attention to it. This article mainly studied the relationship between SNP loci of LIPE gene and ITGB4 gene and milk production, cashmere production and body measurement traits of LCGs. We further identified potential SNP loci by PCR-Seq polymorphism detection and gene sequence comparison of LIPE and ITGB4 genes. Further, we use SPSS and SHEsis software to analyze their relationship to production performance. The consequence indicated that CC genotype of LIPE gene T16409C locus was dominant genotype in milk production and cashmere production, while CT genotype of LIPE gene T16409C locus was dominant in body size. The CT genotype of C168T locus of ITGB4 gene is the dominant genotype of body type and cashmere production, while the dominant genotype of milk production is TT genotype. Through joint analysis, in haploid combinations, H1H2:CCCT is the dominant haplotype combination in cashmere fineness. H3H4:TTCT is a dominant haplotype combination of milk production traits and body measurement traits. These dominant genotypes can provide a reliable basis for the study of production performance of LCG.
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Cabras , Polimorfismo de Nucleótido Simple , Animales , Polimorfismo de Nucleótido Simple/genética , Cabras/genética , Leche , Fenotipo , GenotipoRESUMEN
Objective: This study aims to investigate the effectiveness of levosimendan in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection complicated by cardiac insufficiency and myocardial injury. Methods: A total of 22 patients with SARS-CoV-2 infection and myocardial injury, admitted to the Cardiology Department of our hospital between December 2022 and February 2023, are randomly divided into two groups: a dobutamine general treatment group and a levosimendan observation treatment group. The treatment outcomes of the two groups are compared and analyzed. Results: The overall improvement rate in the general treatment group is 80%, while the levosimendan treatment group shows a 100% improvement rate. There is a statistically significant difference between the two groups (P < .05). Post-treatment, the left ventricular ejection fraction for the general treatment group and the levosimendan treatment group are (48 ± 7)% and (54 ± 6)%, respectively. Additionally, the left ventricular end-diastolic diameter is (55.0 ± 3.0) mm in the general treatment group and (51 ± 5.0) mm in the levosimendan group, with a statistically significant difference (P < .05). After active treatment, the plasma levels of B-type natriuretic peptide (Brain Natriuretic Peptide, NT-proBNP) are significantly lower in the levosimendan treatment group than in the general treatment group (P < .05). Moreover, the plasma levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the levosimendan group decrease slightly faster than those in the general treatment group, with a statistically significant difference (P < .05). The length of hospital stay in the levosimendan group is (12 ± 3) days, significantly lower than the general treatment group (16 ± 5) days, with a statistically different result (P < .05). Conclusions: Levosimendan demonstrates significant efficacy in patients with novel coronavirus infection complicated by myocardial injury, resulting in improved clinical symptoms, enhanced cardiac function, shorter hospital stays, early discharge, and cost savings.
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Natural dual farnesyl X receptor (FXR)/G protein-coupled bile acid receptor 1 (TGR5) activators have received little attention in the management of metabolic diseases. Deoxyschizandrin (DS), a natural lignan, occurs in S. chinensis fruit and has potent hepatoprotective effects, whereas its protective roles and mechanisms against obesity and non-alcoholic fatty liver disease (NAFLD) are largely elusive. Here, we identified DS as a dual FXR/TGR5 agonist using luciferase reporter and cyclic adenosine monophosphate (cAMP) assays. DS was orally or intracerebroventricularly administrated to high-fat diet-induced obesity (DIO) mice, and methionine and choline-deficient L-amino acid diet (MCD diet)-induced non-alcoholic steatohepatitis to evaluate its protective effects. Exogenous leptin treatment was employed to investigate the sensitization effect of DS on leptin. The molecular mechanism of DS was explored by Western blot, quantitative real-time PCR analysis, and ELISA. The results showed that DS activated FXR/TGR5 signaling and effectively reduced NAFLD in DIO and MCD diet-fed mice. DS countered obesity in DIO mice by promoting anorexia and energy expenditure and reversing leptin resistance, involving both peripheral and central TGR5 activation and leptin sensitization. Our findings indicate that DS may be a novel therapeutic approach for alleviating obesity and NAFLD through regulating FXR and TGR5 activities and leptin signaling.
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Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Leptina/uso terapéutico , Receptores Acoplados a Proteínas G/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ácidos y Sales Biliares/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/farmacología , Proteínas de Unión al GTP/uso terapéutico , Ratones Endogámicos C57BL , HígadoRESUMEN
When COVID-19 suddenly broke out, the epidemic areas are short of basic emergency relief which need to be transported from surrounding areas. To make transportation both time-efficient and cost-effective, we consider a multimodal hub-and-spoke transportation network for emergency relief schedules. Firstly, we establish a mixed integer nonlinear programming (MINLP) model considering multi-type emergency relief and multimodal transportation. The model is a bi-objective one that aims at minimizing both transportation time consumption and transportation costs. Due to its NP-hardness, devising an efficient algorithm to cope with such a problem is challenging. This study thus employs and redesigns Grey Wolf Optimizer (GWO) to tackle it. To benchmark our algorithm, a real-world case is tested with three solution methods which include other two state-of-the-art meta-heuristics. Results indicate that the customized GWO can solve such a problem in a reasonable time with higher accuracy. The research could provide significant practical management insights for related government departments and transportation companies on designing an effective transportation network for emergency relief schedules when faced with the unexpected COVID-19 pandemic.