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The gene family known as the Lateral Organ Boundary Domain (LBD) is responsible for producing transcription factors unique to plants, which play a crucial role in controlling diverse biological activities, including their growth and development. This research focused on examining Cerasus humilis'ChLBD gene, owing to its significant ecological, economic, and nutritional benefits. Examining the ChLBD gene family's member count, physicochemical characteristics, phylogenetic evolution, gene configuration, and motif revealed 41 ChLBD gene family members spread across 8 chromosomes, with ChLBD gene's full-length coding sequences (CDSs) ranging from 327 to 1737 base pairs, and the protein sequence's length spanning 109 (ChLBD30)-579 (ChLBD35) amino acids. The molecular weights vary from 12.068 (ChLBD30) to 62.748 (ChLBD35) kDa, and the isoelectric points span from 4.74 (ChLBD20) to 9.19 (ChLBD3). Categorizing them into two evolutionary subfamilies: class I with 5 branches, class II with 2, the majority of genes with a single intron, and most members of the same subclade sharing comparable motif structures. The results of collinearity analysis showed that there were 3 pairs of tandem repeat genes and 12 pairs of fragment repeat genes in the Cerasus humilis genome, and in the interspecific collinearity analysis, the number of collinear gene pairs with apples belonging to the same family of Rosaceae was the highest. Examination of cis-acting elements revealed that methyl jasmonate response elements stood out as the most abundant, extensively dispersed in the promoter areas of class 1 and class 2 ChLBD. Genetic transcript analysis revealed that during Cerasus humilis' growth and maturation, ChLBD developed varied control mechanisms, with ChLBD27 and ChLBD40 potentially playing a role in managing color alterations in fruit ripening. In addition, the quality of calcium fruit will be affected by the environment during transportation and storage, and it is particularly important to use appropriate means to preserve the fruit. The research used salicylic acid-treated Cerasus humilis as the research object and employed qRT-PCR to examine the expression of six ChLBD genes throughout storage. Variations in the expression of the ChLBD gene were observed when exposed to salicylic acid, indicating that salicylic acid could influence ChLBD gene expression during the storage of fruits. This study's findings lay the groundwork for additional research into the biological role of the LBD gene in Cerasus humilis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01438-5.
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BACKGROUND: Gut bacterial microbiota is altered in patients with chronic kidney disease (CKD) and those on dialysis. However, it is not yet clear what bacterial composition changes occur in patients with idiopathic nephrotic syndrome (INS). We present in this report the changes in gut bacterial microbiota in INS patients with membranous nephropathy. METHODS: A total of 158 individuals were recruited for this study. Of these, 80 patients had stage 3-5 CKD without nephrotic syndrome (CKD group), 48 patients had INS and pathological diagnosis of membranous nephropathy (INS group), and 30 were age- and sex-matched healthy controls (HC group). The gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol. RESULTS: The results indicate that the nephrotic syndrome patients had a significantly different alpha and beta diversity compared with the CKD group and HC group (P < 0.01). At the phylum level, the INS patients showed increased Fusobacteria and Proteobacteria but reduced Firmicutes when compared with the HC group. At the genus level, Megamonas, Megasphaera, Akkermansia, and the butyrate-producing bacteria Lachnospira, Roseburia, and Fusobacterium were more abundant in the HC group (LDA score > 3) than the CKD and INS group. Fecal organic acid analysis revealed significantly lower quantities of propionate acid and butyric acid in INS than the HC group (P < 0.05). Compared with the HC group, we found that Parabacteroides was increased in CKD and INS patients. In addition, Oscillospira and Ruminococcus were more abundant in CKD patients than in the other two groups (LDA score > 3). At the genus level, ten bacterial taxa were more prevalent in the HC group. Providencia and Myroides were more prevalent in INS patients. CONCLUSION: Our findings highlight that, INS patients had a significantly different alpha and beta diversity and decreased gut microbiota-derived short-chain fatty acids, such as butyrate. However, large-scale prospective studies should be performed to identify the cause and effect factors of these changes in the microbiota in INS patients.
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Microbioma Gastrointestinal , Glomerulonefrite Membranosa , Síndrome Nefrótica , Adulto , Disbiose , Fezes , Humanos , Síndrome Nefrótica/complicações , Estudos Prospectivos , RNA Ribossômico 16S/genética , Diálise RenalRESUMO
Whether the abnormal circadian rhythm of urinary sodium excretion is associated with hypertension in chronic kidney disease (CKD) is poorly understood. In this study, we assessed the relationship between the circadian rhythm of urinary sodium excretion and hypertension. Urinary samples were collected during both the day (07:00 to 22:00) and night (22:00 to 07:00) to estimate night/day urinary sodium excretion ratios. Blood pressure (BP) and clinical data were also measured. A total of 1,099 Chinese CKD patients were recruited, 308 patients were excluded, and 791 patients were final enrolled in this study. Among them, 291 patients were normotensive and 500 were hypertensive CKD patients. A 1:1 propensity score matching (PSM) analysis was performed with age and estimated glomerular filtration rate (eGFR) matched between 190 normotensive and hypertensive patients. In the full cohort and PSM cohort, multivariate regression analysis showed that the night/day urinary sodium excretion ratio was an independent risk factor for clinical hypertension, whereas 24 h urinary sodium excretion, diurnal and nocturnal urinary sodium excretion were not. When the night/day urinary sodium excretion ratios were further divided into tertiles (tertile 1 < 0.47, tertile 2, 0.47-0.84 and tertile 3 > 0.84), multivariate analysis showed that tertile 3 was independently associated with hypertension in the full and PSM cohorts. In addition, tertile 3 was also independently associated with eGFR ≤ 60 mL/min/1.73 m2 and left ventricular hypertrophy. These data suggested that an abnormal circadian rhythm of urinary sodium excretion was independently associated with hypertension and target-organ damage. Individualized salt intake and therapeutic strategies should be used to normalize the natriuretic dipping profile in CKD patients.
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Hipertensão Renal/urina , Hipertensão/urina , Nefrite/urina , Insuficiência Renal Crônica/urina , Sódio/urina , Adulto , Biomarcadores/urina , Pressão Sanguínea , China/epidemiologia , Ritmo Circadiano/fisiologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertensão Renal/complicações , Hipertensão Renal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefrite/complicações , Nefrite/fisiopatologia , Pontuação de Propensão , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores de RiscoRESUMO
Early diagnosis of head and neck cancer can improve therapeutic outcomes but remains a challenge. The blood proteome can comprise a key source of biomarkers that enable the early diagnosis and precision medicine in head and neck cancer, but blood protein biomarkers of head and neck cancer are not well delineated. Here we applied two-sample Mendelian randomization to a GWAS dataset of 1478 blood proteins and large dataset of head and neck cancer cases and controls to identify blood proteome traits associated with head and neck cancer. Multiple two-sample Mendelian randomization (MR) methods were used to assess causal effects of the exposures, including: Inverse-variance weighted (IVW), Mendelian randomization-Egger method, Weight Median method, simple mode, weight mode. Sensitivity analysis was performed by using heterogeneity test, pleiotropy test and one-by-one exclusion test. Multivariable MR analyses were performed to assess the effects of obesity, diabetes mellitus, and smoking. A significant causal association between A Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23) and head and neck cancer was noted. The sensitivity analysis indicated no significant bias. Multivariate analysis showed that the effect for ADAM23 remained significant after adjusting for the indirect effects of obesity, diabetes mellitus and smoking. In sum, this study showed a significant causal role of genetically dysregulated ADAM23 protein with head and neck cancer risk. The specific mechanisms underlying the role of ADAM23 in mediating head and neck cancer risk, and its role as a potential therapeutic target and biomarker, need further investigation.
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The method of partial differential equations for image inpainting achieves better repair results and is economically feasible with fast repair time. Addresses the inability of Curvature-Driven Diffusion (CDD) models to repair complex textures or edges when the input image is affected by severe noise or distortion, resulting in discontinuous repair features, blurred detail textures, and an inability to deal with the consistency of global image content, In this paper, we have the CDD model of P-Laplace operator term to image inpainting. In this method, the P-Laplace operator is firstly introduced into the diffusion term of CDD model to regulate the diffusion speed; then the improved CDD model is discretized, and the known information around the broken region is divided into two weighted average iterations to get the inpainting image; finally, the final inpainting image is obtained by weighted averaging the two image inpainting images according to the distancing. Experiments show that the model restoration results in this paper are more rational in terms of texture structure and outperform other models in terms of visualization and objective data. Comparing the inpainting images with 150, 1000 and 100 iterations respectively, Total Variation(TV) model and the CDD model inpainting algorithm always has inpainting traces in details, and TV model can't meet the visual connectivity, but the algorithm in this paper can remove the inpainting traces well, TV model and the CDD model inpainting algorithm always have inpainting traces in details, and TV model can't meet the visual connectivity, but the algorithm in this paper can remove the inpainting traces well. Of the images used for testing, the highest PSNR reached 38.7982, SSIM reached 0.9407, and FSIM reached 0.9781, the algorithm not only inpainting the effect and, but also has fewer iterations.
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Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Modelos Teóricos , DifusãoRESUMO
OBJECTIVE: The objective of this study was to evaluate the growth performance, rumen fermentation parameters and bacterial community of post-weaning dairy calves in response to five diets varying in corn silage (CS) inclusion. METHODS: A total of forty Holstein weaned bull calves (80±3 days of age;128.2±5.03 kg at study initiation) were randomized into five groups (8 calves/group) with each receiving one of five dietary treatments offered as total mixed ration in a 123-d feeding study. Dietary treatments were control diet (CON; 0% CS dry matter [DM]); Treatment 1 (T1; 27.2% CS DM); Treatment 2 (T2; 46.5% CS DM); Treatment 3 (T3; 54.8% CS DM); and Treatment 4 (T4; 67.2% CS DM) with all diets balanced for similar protein and energy concentration. RESULTS: Results showed that calves offered CS had greater average daily gain, body length and chest depth growth, meanwhile altered rumen fermentation indicated by decreased rumen acetate concentrations. Principal coordinate analysis showed the rumen bacterial community structure was affected by varying CS inclusion diets. Bacteroidetes and Firmicutes were the predominant bacterial phyla in the calf rumens across all treatments. At the genus level, the abundance of Bacteroidales_RF16_group was increased, whereas Unclassified_ Lachnospiraceae was decreased for calves fed CS. Furthermore, Spearman's correlation test between the rumen bacteria and rumen fermentation parameters indicated that Bacteroidales_RF16_group and Unclassified Lachnospiraceae were positively correlated with propionate and acetate, respectively. CONCLUSION: The results of the current study suggested that diet CS inclusion was beneficial for post-weaning dairy calf growth, with 27.2% to 46.5% CS of diet DM recommended to achieve improved growth performance. Bacteroidales_RF16_group and Unclassified Lachnospiraceae play an important role in the rumen fermentation pattern for post-weaning calves fed CS.
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Here, a novel paired electrolysis system is constructed, where fluorine-doped tin oxide glass serves as the anode for the water oxidation reaction to produce hydrogen peroxide (H2O2), and cobalt phthalocyanine (CoPc)/carbon nanotube (CNT) loaded carbon paper as the cathode for CO2 reduction to generate CO. This system demonstrates a high overall energy efficiency of 34%, where a faradaic efficiency exceeding 90% for CO2 reduction and 60% for water oxidation to H2O2 have been achieved, demonstrating significant energy savings of nearly 40% compared to the respective half-reaction systems.
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Taraxaci herba, as a traditional Chinese medicine, is the name of the Taraxacum genus in the Asteraceae family. Documented in the Tang Herbal Medicine (Tang Dynasty, AD 657-659), its medicinal properties cover a wide range of applications such as acute mastitis, lung abscess, conjunctival congestion, sore throat, damp-heat jaundice, and vision improvement. In the Chinese Pharmacopoeia (Edition 2020), more than 40 kinds of China-patented drugs containing Taraxaci herba were recorded. This review explores the evolving scientific understanding of Taraxaci herba, covering facets of ethnopharmacology, botany, phytochemistry, pharmacology, artificial cultivation, and quality control. In particular, the chemical constituents and pharmacological research are reviewed. Taraxaci herba has been certified as a traditional medicine plant, and its flavonoids, phenolic acids, and terpenoids have been identified and separated, which include Chicoric acid, taraxasterol, Taraxasteryl acetate, Chlorogenic acid, isorhamnetin, and luteolin; they are responsible for anti-inflammatory, antioxidant, antibacterial, anti-tumor, and anti-cancer activities. These findings validate the traditional uses of Taraxaci herba and lay the groundwork for further scientific exploration. The sources used in this study include Web of Science, Pubmed, the CNKI site, classic monographs, the Chinese Pharmacopoeia, the Chinese Medicine Dictionary, and doctoral and master's theses.
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BACKGROUND: Prostate cancer (PCa) is the most common cancer and the second leading cause of cancer-related death in men. Previous studies have shown that the poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPis) improve the treatment response of patients with metastatic castration-resistant PCa (mCRPC). However, the efficacy and safety of various PARPis in mCRPC patients remain unclear, presenting a significant challenge for clinicians when making treatment decisions. To address this, this study conducted two indirect comparisons to evaluate the efficacy and safety of four PARPis (olaparib, niraparib, rucaparib, and talazoparib) in patients with mCRPC. METHODS: A systematic review and network meta-analysis (NMA) using Bayesian statistics was conducted. A comprehensive literature search was performed of the PubMed, Web of Science, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) databases to identify relevant studies from the inception to November 8, 2023, using search terms such as "PARP inhibitor", "olaparib", "rucaparib", "niraparib", "talazoparib", and "mCRPC". Phase 2/3 randomized controlled trials (RCTs) related to PARPi therapy and novel hormonal therapy in patients with mCRPC were included in the analysis. The targeted outcomes included radiographic progression-free survival (rPFS), overall survival (OS), adverse events (AEs), and grade ≥3 AEs. Four reviewers screened the titles and abstracts independently to assess the eligibility of each article. Two researchers independently extracted data from the included studies. The risk of bias and quality of the studies were assessed using the Risk-of-Bias 2 tool. RESULTS: Six high-quality phase 2/3 clinical trials, comprising 3,205 individuals, were selected for the systematic review and NMAs. Two NMAs were conducted due to the different designs of the six clinical trials. The indirect comparison with a random-effects model of olaparib, niraparib, and talazoparib showed that olaparib significantly improved rPFS with a hazard ratio (HR) of 0.67 [95% confidence interval (CI): 0.46-0.96]; however, no such significant difference was observed in relation to olaparib and rucaparib. In terms of OS, no significant difference was observed among olaparib, niraparib, and talazoparib. In relation to the AEs, the PARPi interventions using olaparib, niraparib, and talazoparib increased the rates of grade ≥3 AEs with odds ratios (ORs) of 2.0 (95% CI: 0.89-5.3), 3.0 (95% CI: 1.3-7.4), and 3.7 (95% CI: 1.1-12.0), respectively. In the rank probability analysis, according to the surface under the cumulative ranking (SUCRA), olaparib ranked first, followed by niraparib, and talazoparib. Most of the included studies were assessed to be at low risk of bias. CONCLUSIONS: Olaparib significantly improved rPFS among olaparib, niraparib, and talazoparib. Talazoparib exhibited the highest SUCRA value. Regarding safety, olaparib and rucaparib did not significantly increase the incidence of grade ≥3 AEs. When making personalized treatment decisions, clinicians should consider individual patient characteristics, treatment efficacy, and potential AEs.
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Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Humanos , Masculino , Metanálise em Rede , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidadeRESUMO
During plant growth and development, the YABBY gene plays a crucial role in the morphological structure, hormone signaling, stress resistance, crop breeding, and agricultural production of plant lateral organs, leaves, flowers, and fruits. Astragalus mongholicus is a perennial herbaceous plant in the legume family, widely used worldwide due to its high medicinal and edible value. However, there have been no reports of the YABBY gene family in A. mongholicus. This study used bioinformatics methods, combined with databases and analysis websites, to systematically analyze the AmYABBY gene family in the entire genome of A. mongholicus and verified its expression patterns in different tissues of A. mongholicus through transcriptome data and qRT-PCR experiments. A total of seven AmYABBY genes were identified, which can be divided into five subfamilies and distributed on three chromosomes. Two pairs of AmYABBY genes may be involved in fragment duplication on three chromosomes. All AmYABBY proteins have a zinc finger YABBY domain, and members of the same group have similar motif composition and intron - exon structure. In the promoter region of the genes, light-responsive and MeJa-response cis-elements are dominant. AmYABBY is highly expressed in stems and leaves, especially AmYABBY1, AmYABBY2, and AmYABBY3, which play important roles in the growth and development of stems and leaves. The AmYABBY gene family regulates the growth and development of A. mongholicus. In summary, this study provides a theoretical basis for in-depth research on the function of the AmYABBY gene and new insights into the molecular response mechanism of the growth and development of the traditional Chinese medicine A. mongholicus.
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Astrágalo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Astrágalo/genética , Astrágalo/metabolismo , Genoma de Planta/genética , Família Multigênica , Filogenia , Genes de Plantas , Regiões Promotoras Genéticas/genéticaRESUMO
The electrocatalytic reduction of CO2 to high-value fuels by renewable electricity is a sustainable strategy, which can substitute for fossil fuels and circumvent climate changes induced by elevated CO2 emission levels, making the rational design of versatile electrocatalysts highly desirable. Among all the electrocatalytic materials used in the CO2 reduction reaction, nickel phthalocyanine (NiPc)-based electrocatalysts have attracted considerable attention recently because of their high CO selectivity and catalytic activity. Herein, we review the latest advances in CO2 electroreduction to CO catalyzed by immobilized NiPc and its derivatives on diverse surfaces. Specific strategies, the structure-performance relationship and the CO2-to-CO reaction mechanism of these NiPc-based electrocatalysts are analyzed. Future opportunities and challenges for this series of powerful heterogeneous electrocatalysts are also highlighted.
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Silybum marianum (L.) Gaertn, a herbaceous plant with a long history in traditional medicine for the treatment of hepatobiliary diseases, particularly in Europe, which has attracted attention for its remarkable therapeutic effect. This review systematically summarizes the research progress in the botany, phytochemistry, pharmacology, comprehensive utilization and synthetic biology of S. marianum. Up to now, more than 20 types of flavonolignan components have been isolated from S. marianum. In addition, the rearch on fatty acids and triterpenoids is also constantly improving. Among them, silybin is the most active compound in flavonolignans components. Its pharmacological effects in vivo and in vitro include anti-inflammatory, antioxidant, anti-tumour, hypoglycaemic, neuroprotective and immunoregulatory properties. The use of coniferyl alcohol and taxifolin as substrates to produce silybin and isosilybin under the action of enzyme catalysis is the commonly used biosynthetic pathway of silymarin, which provides support for a comprehensive analysis of the synthetic pathway of silymarin. In addition to medicinal use, the extracts of plants also have broad application prospects in the production of food, healthcare products, cosmetics and other aspects. In addition, the chemical composition, pharmacological mechanism and synthetic biology of S. marianum need to be further studied, which is very important for its clinical efficacy and resource development.
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Proverbs are usually regarded as structurally fixed expressions. However, in daily communication, language users often change them to suit their communicative purposes in many ways, resulting in proverb variations. Using the data from the Corpus of Contemporary American English (COCA corpus), this study attempts to present varieties of the English proverb "There are two sides to every coin" and explain the variations from the perspective of linguistic creativity. This study also explores the variations of this proverb in EFL learners' use via the data from Chinese EFL learners' corpus TECCL. The study shows that, first proverb use can roughly be divided into two types: canonical and non-canonical uses, each having three ways of alteration, i.e., addition of modifiers, substitution of content words, and reduction. Second, Chinese EFL learners tend to use the proverb in a mechanical way with little variation, which shows their inflexible use of proverbs. Finally, proverb variation by nature is the creative manipulation of language use to fit the context, which is a form of linguistic creativity that reflects the cognitive creativity of human beings.
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The photocatalytic technique has drawn far-ranging interests in addressing the current issues; however, its property suffers from the limited visible light response and rapid recombination of carriers. To address these issues, two specific approaches have been proposed to enhance the photocatalytic activity: (1) ultrasound-assisted synthesis has been utilized to prepare photocatalysts, resulting in refined grain size, increased specific surface area, and reduced photogenerated carrier recombination; (2) sonophotocatalysis and piezoelectric enhanced photocatalysis have been developed to accelerate the reaction, which utilizes the synergism between ultrasound and light. On one side, sonophotocatalysis generates cavitation bubbles which induce more reactive radicals for redox reactions. On the other side, ultrasound induces deformation of the piezoelectric material structure, which changes the internal piezoelectric potential and improves the photocatalytic performance. Currently, intensive efforts have been devoted to related research and great progress has been reached with applications in pollutant degradation, new energy production, and other fields. This work starts by elucidating the fundamental concept of ultrasound-assisted photocatalyst synthesis and photocatalysis. Then, the synergistic behavior between ultrasonic and light in ultrasonic-assisted photocatalysis has been thoroughly discussed, including pollutant degradation, water splitting, and bacterial sterilization. Finally, the challenge and outlook are investigated and proposed.
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The present experiment was carried out to analyze the longitudinal changes in milk microorganisms. For this purpose, milk samples were collected from 12 healthy cows (n = 96; six primiparous cows and six multiparous cows) at eight different time points. The characteristics and variations in microbial composition were analyzed by 16S rRNA gene high-throughput sequencing. In the primiparous group, higher and more stable alpha diversity was observed in transitional and mature milk compared with the colostrum, with no significant difference in alpha diversity at each time point in the multiparous group. Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota were the most dominant phyla, and Pseudomonas, UCG-005, Acinetobacter, Vibrio, Lactobacillus, Bacteroides, Serratia, Staphylococcus, and Glutamicibacter were the most dominant genera in both primiparous and multiparous cow milk. Some typically gut-associated microbes, such as Bacteroides, UCG-005, and Rikenellaceae_RC9_gut_group, etc., were enriched in the two groups. Biomarker taxa with the day in time (DIM) were identified by a random forest algorithm, with Staphylococcus showing the highest degree of interpretation, and the difference in milk microbiota between the two groups was mainly reflected in 0 d-15 d. Additionally, network analysis suggested that there were bacteria associated with the total protein content in milk. Collectively, our results disclosed the longitudinal changes in the milk microbiota of primiparous and multiparous cows, providing further evidence in dairy microbiology.
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Accumulation of misfolded proteins leads to many neurodegenerative diseases that can be treated by lowering or removing mutant proteins. Huntington's disease (HD) is characterized by the intracellular accumulation of mutant huntingtin (mHTT) that can be soluble and aggregated in the central nervous system and causes neuronal damage and death. Here, an intracellular antibody (intrabody) fragment is generated that can specifically bind mHTT and link to the lysosome for degradation. It is found that delivery of this peptide by either brain injection or intravenous administration can efficiently clear the soluble and aggregated mHTT by activating the lysosomal degradation pathway, resulting in amelioration of gliosis and dyskinesia in HD knock-in (KI-140Q) mice. These findings suggest that the small intrabody peptide linked to lysosomes can effectively lower mutant proteins and provide a new approach for treating neurodegenerative diseases that are caused by the accumulation of mutant proteins.
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Doença de Huntington , Doenças Neurodegenerativas , Animais , Camundongos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Lisossomos/metabolismo , Proteínas Mutantes , Proteínas do Tecido Nervoso , PeptídeosRESUMO
Severe combined immunodeficiency (SCID) encompasses a range of inherited disorders that lead to a profound deterioration of the immune system. Among the pivotal genes associated with SCID, RAG1 and IL2RG play crucial roles. IL2RG is essential for the development, differentiation, and functioning of T, B, and NK cells, while RAG1 critically contributes to adaptive immunity by facilitating V(D)J recombination during the maturation of lymphocytes. Animal models carrying mutations in these genes exhibit notable deficiencies in their immune systems. Non-human primates (NHPs) are exceptionally well-suited models for biomedical research due to their genetic and physiological similarities to humans. Cytosine base editors (CBEs) serve as powerful tools for precisely and effectively modifying single-base mutations in the genome. Their successful implementation has been demonstrated in human cells, mice, and crop species. This study outlines the creation of an immunodeficient monkey model by deactivating both the IL2RG and RAG1 genes using the CBE4max system. The base-edited monkeys exhibited a severely compromised immune system characterized by lymphopenia, atrophy of lymphoid organs, and a deficiency of mature T cells. Furthermore, these base-edited monkeys were capable of hosting and supporting the growth of human breast cancer cells, leading to tumor formation. In summary, we have successfully developed an immunodeficient monkey model with the ability to foster tumor growth using the CBE4max system. These immunodeficiency monkeys show tremendous potential as valuable tools for advancing biomedical and translational research.
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Linfopenia , Imunodeficiência Combinada Severa , Animais , Camundongos , Imunodeficiência Combinada Severa/genética , Haplorrinos , Edição de Genes , Proteínas de Homeodomínio/genéticaRESUMO
Biological activities require a delicate balance between excitatory and inhibitory signals in the brain. Disruption of this balance could lead to neurological disorders, such as epilepsydue to a relative enhancement of excitatory signals. In general, cytosolic calcium plays a key role in the transmission of excitatory signals mainly by promoting the release of synaptic vesicles containing neurotransmitters. A series of molecular components responsible for maintaining intracellular calcium homeostasis, including voltage-gated calcium (CaV) channels, the endoplasmic reticulum (ER) calcium sensor stromal interaction molecule (STIM), the PM calcium channel Orai, ER-resident inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), sarco-endoplasmic reticulum calcium ATPase (SERCA), and transmembrane and coiled-coil domains 1 (TMCO1), have been demonstrated to be involved in calcium dysregulation that underlies epileptic seizures. More importantly, epileptic phenotypes were confirmed in several molecular components by transgenic animal models, including CACNA1A, CACNA1E, CACNA1G, CACNA2D1, ORAI1 and IP3R1. Calcium-binding proteins (CaBPs), such as calmodulin, parvalbumin, calretinin, and calbindin, provide an additional layer of defense by acting as calcium reservoirs to buffer rapid increases in cytosolic calcium concentrations and participate in cellular functions by regulating the activities of ion channels or acting as calcium-modulated sensors, and a series of lines of evidence support their implication with epileptic activities. Overall, stroke represents the most common environmental cause of acquired epilepsy in older adults, and preventing calcium disruption due to reperfusion injury might be an effective way to treat acute symptomatic seizures and decrease the risk for acquired poststroke epilepsy.
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Cálcio , Epilepsia , Animais , Convulsões , Epilepsia/etiologia , Canal de Liberação de Cálcio do Receptor de Rianodina , HomeostaseRESUMO
BACKGROUND: To improve droplet deposition rates at the base of rice, an electrical vortex air-assisted spraying system for small- and medium-sized high-clearance boom sprayers was developed. This system uses vortex airflows to guide droplets to the base of rice and the back of leaves, as well as to increase leaf perturbation and droplet penetration and deposition. RESULTS: The spatial distribution of the airflow field generated by this system and the effects of the canopy on the airflow field were described. An orthogonal experiment was performed in a rice field based on fan speed, auxiliary airflow angle, and spray height as the experimental factors. It was discovered that a fan speed of 4000 rpm, auxiliary airflow angle of 0°, and spray height of 30 cm were optimal for droplet deposition at the base of the canopy. These settings resulted in droplet coverage of 54.5% and 35.9% on the front and back of the leaves, respectively, which are 48% and 104% higher than that on the front and back sides of leaves without an auxiliary airflow, respectively. CONCLUSION: Compared with the traditional application method, vortex air-assisted application significantly improved the rate of droplet coverage in rice canopy of different area. Hence, vortex air-assisted application enables new approaches and methods for rice crop protection. © 2022 Society of Chemical Industry.
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OryzaRESUMO
The G protein-coupled receptor 37 (GPR37) has been reported to be expressed in macrophages and the activation of GPR37 by its ligand/agonist, and it can regulate macrophage-associated functions and inflammatory responses. Since our previous work identified that osteocalcin (OCN) acts as an endogenous ligand for GPR37 and can elicit various intracellular signals by interacting with GPR37, we thus hypothesized that OCN may also play a functional role in macrophage through the activation of GPR37. To verify the hypothesis, we conducted a series of in vivo and in vitro studies in lipopolysaccharide (LPS)-challenged mice and primary cultured macrophages. Our results reveal that the OCN gene deletion (OCN-/-) and wild type (WT) mice showed comparable death rates and inflammatory cytokines productions in response to a lethal dose of LPS exposure. However, the detrimental effects caused by LPS were significantly ameliorated by exogenous OCN treatments in both WT and OCN-/- mice. Notably, the protective effects of OCN were absent in GPR37-/- mice. In coordination with the in vivo results, our in vitro studies further illustrated that OCN triggered intracellular responses via GPR37 in peritoneal macrophages by regulating the release of inflammatory factors and macrophage phagocytic function. Finally, we exhibited that the adoptive transfer of OCN-treated macrophages from WT mice significantly inhibits the release of pro-inflammatory cytokines in GPR37-/- mice exposed to LPS. Taken together, these findings suggest a protective role of OCN against LPS-caused acute inflammation, by the activation of GPR37 in macrophages, and provide a potential application of the activation of the OCN/GPR37 regulatory axis as a therapeutic strategy for inflammatory diseases.