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In the type III-E CRISPR-Cas system, a Cas effector (gRAMP) is associated with a TPR-CHAT to form Craspase (CRISPR-guided caspase). However, both the structural features of gRAMP and the immunity mechanism remain unknown for this system. Here, we report structures of gRAMP-crRNA and gRAMP:cRNA:target RNA as well as structures of Craspase and Craspase complexed with cognate target RNA (CTR) or non-cognate target RNA (NTR). Importantly, the 3' anti-tag region of NTR and CTR binds at two distinct channels in Craspase, and CTR with a non-complementary 3' anti-tag induces a marked conformational change of the TPR-CHAT, which allosterically activates its protease activity to cleave an ancillary protein Csx30. This cleavage then triggers an abortive infection as the antiviral strategy of the type III-E system. Together, our study provides crucial insights into both the catalytic mechanism of the gRAMP and the immunity mechanism of the type III-E system.
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Proteínas Asociadas a CRISPR , Proteínas Asociadas a CRISPR/genética , ARN/metabolismo , Antivirales , Sistemas CRISPR-Cas , Péptido Hidrolasas/genética , Péptido Hidrolasas/metabolismoRESUMEN
CRISPR-Cas systems are bacterial anti-viral systems, and phages use anti-CRISPR proteins (Acrs) to inactivate these systems. Here, we report a novel mechanism by which AcrIF11 inhibits the type I-F CRISPR system. Our structural and biochemical studies demonstrate that AcrIF11 functions as a novel mono-ADP-ribosyltransferase (mART) to modify N250 of the Cas8f subunit, a residue required for recognition of the protospacer-adjacent motif, within the crRNA-guided surveillance (Csy) complex from Pseudomonas aeruginosa. The AcrIF11-mediated ADP-ribosylation of the Csy complex results in complete loss of its double-stranded DNA (dsDNA) binding activity. Biochemical studies show that AcrIF11 requires, besides Cas8f, the Cas7.6f subunit for binding to and modifying the Csy complex. Our study not only reveals an unprecedented mechanism of type I CRISPR-Cas inhibition and the evolutionary arms race between phages and bacteria but also suggests an approach for designing highly potent regulatory tools in the future applications of type I CRISPR-Cas systems.
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Proteínas Asociadas a CRISPR/antagonistas & inhibidores , Sistemas CRISPR-Cas/fisiología , Proteínas Virales/metabolismo , ADP-Ribosilación/fisiología , Proteínas Bacterianas/genética , Bacteriófagos/genética , Proteínas Asociadas a CRISPR/genética , Proteínas Asociadas a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Microscopía por Crioelectrón/métodos , ADN/metabolismo , Modelos Moleculares , ARN Bacteriano/metabolismo , Proteínas Virales/genéticaRESUMEN
Chloroplast division involves the coordination of protein complexes from the stroma to the cytosol. The Min system of chloroplasts includes multiple stromal proteins that regulate the positioning of the division site. The outer envelope protein PLASTID DIVISION1 (PDV1) was previously reported to recruit the cytosolic chloroplast division protein ACCUMULATION AND REPLICATION OF CHLOROPLAST5 (ARC5). However, we show here that PDV1 is also important for the stability of the inner envelope chloroplast division protein PARALOG OF ARC6 (PARC6), a component of the Min system. We solved the structure of both the C-terminal domain of PARC6 and its complex with the C terminus of PDV1. The formation of an intramolecular disulfide bond within PARC6 under oxidized conditions prevents its interaction with PDV1. Interestingly, this disulfide bond can be reduced by light in planta, thus promoting PDV1-PARC6 interaction and chloroplast division. Interaction with PDV1 can induce the dimerization of PARC6, which is important for chloroplast division. Magnesium ions, whose concentration in chloroplasts increases upon light exposure, also promote the PARC6 dimerization. This study highlights the multilayer regulation of the PDV1-PARC6 interaction as well as chloroplast division.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Plastidios/metabolismo , Cloroplastos/metabolismo , Disulfuros/metabolismo , Dinaminas/metabolismoRESUMEN
Iron-based phosphate cathode of Na4Fe3(PO4)2(P2O7) has been regarded as a low-cost and structurally stable cathode material for Na-ion batteries (NIBs). However, their practical application is greatly hindered by the insufficient electrochemical performance and limited energy density. Here, we report a new iron-based phosphate cathode of Na4.5Fe3.5(PO4)2.5(P2O7) with the intergrown heterostructure of the maricite-type NaFePO4 and orthorhombic Na4Fe3(PO4)2(P2O7) phases at a mole ratio of 0.5:1. Benefited from the increased composition ratio and the spontaneous activation of the maricite-type NaFePO4 phase, the as-prepared Na4.5Fe3.5(PO4)2.5(P2O7) composites deliver a reversible capacity over 130 mA h g-1 and energy density close to 400 W h kg-1, which is far beyond that of the single-phase Na4Fe3(PO4)2(P2O7) cathode (â¼120 mA h g-1 and â¼350 W h kg-1). Moreover, the kg-level products from the scale-up synthesis demonstrate a stable cycling performance over 2000 times at 3 C in pouch cells. We believe that our findings could show the way forward the practical application of the iron-based phosphate cathodes for NIBs.
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Autophagy plays an important role in plant antiviral defense. Several plant viruses are reported to encode viral suppressor of autophagy (VSA) to prevent autophagy for effective virus infection. However, whether and how other viruses, in particular DNA viruses, also encode VSAs to affect viral infection in plants is unknown. Here, we report that the C4 protein encoded by Cotton leaf curl Multan geminivirus (CLCuMuV) inhibits autophagy by binding to the autophagy negative regulator eukaryotic translation initiation factor 4A (eIF4A) to enhance the eIF4A-Autophagy-related protein 5 (ATG5) interaction. By contrast, the R54A or R54K mutation in C4 abolishes its capacity to interact with eIF4A, and neither C4R54A nor C4R54K can suppress autophagy. However, the R54 residue is not essential for C4 to interfere with transcriptional gene silencing or post-transcriptional gene silencing. Moreover, plants infected with mutated CLCuMuV-C4R54K develop less severe symptoms with decreased levels of viral DNA. These findings reveal a molecular mechanism underlying how the DNA virus CLCuMuV deploys a VSA to subdue host cellular antiviral autophagy defense and uphold viral infection in plants.
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Begomovirus , Virosis , Nicotiana/genética , Begomovirus/genética , Proteínas/metabolismo , ADN Viral/genética , ADN Viral/metabolismo , Autofagia/genética , Antivirales/metabolismo , Enfermedades de las PlantasRESUMEN
The commercial applications of lead halide perovskites are hindered by their negative environmental impact and inherent instability. Consequently, developing environmentally friendly copper-based perovskite materials is crucial for future solid-state lighting and display applications. In this study, an ultrafast high-power ultrasonic synthesis strategy was utilized to achieve uniform nucleation and growth of Cs3Cu2X5 (X = Cl, Br, I) nanocrystals (NCs) that possess remarkable luminescence properties, hydroxyl protection, and ligand-free characteristics. These Cs3Cu2X5 NCs exhibited a tunable spectral range spanning from 446 to 525 nm, accompanied by photoluminescence quantum yields (PLQYs) varying from 0.2% to 79.2%. The spectral attributes of the NCs were effectively controlled by modulating the halide type and composition. It is worth noting that density functional theory (DFT) calculations offer valuable insights into the synthesis of NCs and the selection of suitable alcohol solvents. Moreover, we successfully fabricated an efficient and stable white light-emitting diode (WLED) with a high luminous efficiency of 23 lm W-1 and CIE color coordinates of (0.3266, 0.3487). Our work provides a new strategy to synthesize Cs3Cu2X5 NCs and holds promise for their potential application in display and lighting devices.
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Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide prokaryotes with nucleic acid-based adaptive immunity against infections of mobile genetic elements, including phages. To counteract this immune process, phages have evolved various anti-CRISPR (Acr) proteins which deactivate CRISPR-Cas-based immunity. However, the mechanisms of many of these Acr-mediated inhibitions are not clear. Here, we report the crystal structure of AcrIF13 and explore its inhibition mechanism. The structure of AcrIF13 is unique and displays a negatively charged surface. Additionally, biochemical studies identified that AcrIF13 interacts with the type I-F CRISPR-Cas surveillance complex (Csy complex) to block target DNA recognition and that the Cas5f-8f tail and Cas7.6f subunit of the Csy complex are specific binding targets of AcrIF13. Further mutational studies demonstrated that several negatively charged residues of AcrIF13 and positively charged residues of Cas8f and Cas7f of the Csy complex are involved in AcrIF13-Csy binding. Together, our findings provide mechanistic insights into the inhibition mechanism of AcrIF13 and further suggest the prevalence of the function of Acr proteins as DNA mimics.
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Bacteriófagos , Proteínas Asociadas a CRISPR , Bacteriófagos/metabolismo , Proteínas Asociadas a CRISPR/metabolismo , Sistemas CRISPR-Cas , ADN/metabolismo , Proteínas Virales/metabolismoRESUMEN
Electrochemical exfoliation starting with graphite powder as the raw material for graphene production shows superiority in cost effectiveness over the popular bulk graphite. However, the crucial conductive network inside the graphite powder electrode along with its formation and influence mechanisms remains blank. Here, an adjustable-pressure graphite powder electrode with a sandwich structure was designed for this. Appropriate encapsulation pressure is necessary and conducive to constructing a continuous and stable conductive network, but overloaded encapsulation pressure is detrimental to the exfoliation and graphene quality. With an initial encapsulation pressure (IEP) of 4 kPa, the graphite powders expand rapidly to a final stable expansion pressure of 49 kPa with a final graphene yield of 46.3%, where 84% of the graphene sheets are less than 4 layers with ID/IG values between 0.22 and 1.24. Increasing the IEP to 52 kPa, the expansion pressure increases to 73 kPa, but the graphene yield decreases to 39.3% with a worse graphene quality including higher layers and ID/IG values of 1.68-2.13. In addition, small-size graphite powders are not suitable for the electrochemical exfoliation. With the particle size decreasing from 50 to 325 mesh, the graphene yield decreases almost linearly from 46.3% to 5.5%. Conductive network and electrolyte migration synergize and constrain each other, codetermining the electrochemical exfoliation. Within an encapsulated structure, the electrochemical exfoliation of the graphite powder electrode proceeds from the outside to the inside. The insights revealed here will provide direction for further development of electrochemical exfoliation of graphite powder to produce graphene.
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BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic respiratory disease. This study investigated the global, regional and country burden of COPD based on gender, age and socio-demographic indices (SDIs) in the last 30-year period from 1990 to 2019. METHODS: The COPD data, including incidence, mortality and disability-adjusted life years (DALYs), were obtained from the 2019 Global Burden of Disease Study. If age-standardized incidence rate (ASIR) or death rate (ASDR) remains almost constant or decreases, the number of cases will still increase as the global population increases substantially. Estimated annual percentage change (EAPC) was calculated to assess incidence, mortality and DALY trends. RESULTS: The incidence of COPD increased by 85.89% from 8,722,966 cases in 1990 to 16,214,828 cases in 2019, and the ASIR decreased from 216.48/100,000 persons in 1990 (95%UI, 204.56-227.33) to 200.49 per 100,000 persons (95%UI, 188.63-212.57) in 2019. The ASIR increased (EAPC = 0.05, 95%CI, 0.01-0.10) in the low SDI region, was stable in the high SDI region, and fell in the other three SDI regions. Men had a higher ASIR than women over the past 30 years, and there were differences in the incidence rates for different age groups. Male mortality and DALYs were higher than female mortality. ASDR decreased by 2.13% (95%CI, -2.23% to -2.02%) per year and the annual age-standardized DALY rate decreased by 1.97% (95%CI, -2.05% to -1.89%). CONCLUSIONS: The ASIR, ASDR and age-standardized DALY rate of COPD declined overall in the last 30 years, and were highest in the low-middle SDI region.
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Carga Global de Enfermedades , Enfermedad Pulmonar Obstructiva Crónica , Femenino , Masculino , Humanos , Adulto , Años de Vida Ajustados por Calidad de Vida , Salud Global , Incidencia , Enfermedad Pulmonar Obstructiva Crónica/epidemiologíaRESUMEN
CRISPR-Cas systems are bacterial adaptive immune systems, and phages counteract these systems using many approaches such as producing anti-CRISPR (Acr) proteins. Here, we report the structures of both AcrIF14 and its complex with the crRNA-guided surveillance (Csy) complex. Our study demonstrates that apart from interacting with the Csy complex to block the hybridization of target DNA to the crRNA, AcrIF14 also endows the Csy complex with the ability to interact with non-sequence-specific dsDNA as AcrIF9 does. Further structural studies of the Csy-AcrIF14-dsDNA complex and biochemical studies uncover that the PAM recognition loop of the Cas8f subunit of the Csy complex and electropositive patches within the N-terminal domain of AcrIF14 are essential for the non-sequence-specific dsDNA binding to the Csy-AcrIF14 complex, which is different from the mechanism of AcrIF9. Our findings highlight the prevalence of Acr-induced non-specific DNA binding and shed light on future studies into the mechanisms of such Acr proteins.
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Sistemas CRISPR-Cas/genética , Proteínas de Unión al ADN/metabolismo , ADN/metabolismo , Endodesoxirribonucleasas/metabolismo , Pseudomonas aeruginosa/genética , Bacteriófagos/genética , Bacteriófagos/crecimiento & desarrollo , Proteínas Asociadas a CRISPR/metabolismo , ADN/genética , Proteínas de Unión al ADN/antagonistas & inhibidores , Conformación Proteica , Pseudomonas aeruginosa/virología , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: Primary brain and central nervous system cancer (collectively called CNS cancers) cause a significant burden to society. The purpose of this study was to evaluate the trends in the burden of CNS cancers from 1990 to 2019 and to predict the incidence and mortality rates and the corresponding numbers for the next 25 years to help countries to understand the trends in its incidence and mortality, and to make better adjustments or formulation of policies and allocation of resources thereby reducing the burden of the disease. METHODS: The 2019 Global Burden of Disease Study provided incidence rates, death rates, and disability-adjusted life year (DALY) data in Asia from 1990 to 2019. To reflect the trends in the age-standardized incidence, mortality, and DALY rates, the estimated annual percentage change (EAPC) was determined. The Bayesian age-period cohort (BAPC) model was employed to predict the burden of CNS cancers in the next 25 years. RESULTS: The incidence, death, and DALY rates of CNS cancers all increased from 1990 to 2019. The age-standardized incidence rate (ASIR) for CNS cancers increased from 9.89/100,000 in 1990 to 12.14/100,000 in 2019, with an EAPC of 0.69 (95% confidence interval (CI): 0.65, 0.73). The ASDR and the age-standardized DALY rate both decreased, with EAPCs of - 0.08 and - 0.52, respectively. Before 2005, the age-standardized DALY rate in East Asia was much greater in females than in males, while in Central Asia, the age-standardized death and DALY rates in males both increased sharply after 2000. In contrast to 1990, the caseload increased for the 55-70 years age group. The number of deaths decreased sharply among individuals aged younger than 20 years, especially in East Asia, accounting for only 5.41% of all deaths. The age group with the highest mortality rate was > 60 years, especially in Japan. The ASIR will continue to increase in Asia from 2020 to 2044, and the ASDR will gradually diminish. The incidence and number of deaths from CNS cancers in Asia are expected to increase over the next 25 years, especially among females. CONCLUSIONS: The study identified an increasing trend in morbidity, mortality and disability-adjusted life-years (DALYs), with differences in age-standardized morbidity rates for different population groups. In addition, it is noteworthy that the burden of disease (as measured by disability-adjusted life-years (DALYs)) is higher among women in Central Asia compared with other regions. ASIR will continue to increase over the next 25 years, with the increase in female cases and mortality expected to be more pronounced. This may need to be further substantiated by additional research, on the basis of which health authorities and policymakers can better utilize limited resources and develop appropriate policies and preventive measures.
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Neoplasias , Muerte Perinatal , Masculino , Humanos , Femenino , Anciano , Adulto , Persona de Mediana Edad , Teorema de Bayes , Años de Vida Ajustados por Calidad de Vida , Carga Global de Enfermedades , Asia/epidemiología , Incidencia , Salud Global , Neoplasias/epidemiología , Encéfalo , Sistema Nervioso CentralRESUMEN
BACKGROUND: Syphilis is a sexually transmitted disease caused by Treponema pallidum, and the infection source is syphilis patients. This study aimed to estimate the incidence, mortality rate, and disability-adjusted life years (DALYs) of syphilis to improve the understanding of the current global situation of syphilis. METHODS: This study collected data on syphilis incidence, mortality, and DALYs from the 2019 Global Burden of Disease database. RESULTS: The global number of incident cases and age-standardized incidence rate (ASIR) increased from 8,845,220 (95% UI: 6,562,510-11,588,860) in 1990 to 14,114,110 (95% UI: 10,648,490-18,415,970) in 2019 and 160.03/100,000 persons (95% UI: 120.66-208.1) to 178.48/100,000 persons (95% UI: 134.94-232.34), respectively. The estimated annual percentage change (EAPC) in the ASIR was 0.16 (95% CI: 0.07-0.26). The EAPC in the ASIR associated with high and high-middle sociodemographic indices increased. The ASIR increased among males but decreased among females, and the incidence peaked among males and females between the ages of 20 and 30 years. The EAPCs in the age-standardized death rate and age-standardized DALY rate decreased. CONCLUSIONS: The incidence and ASIR of syphilis increased worldwide from 1990 to 2019. Only the regions with high and high-middle sociodemographic indices showed an increase in the ASIR. Moreover, the ASIR increased among males but decreased among females. The age-standardized death rate and DALY rate both declined worldwide. The increase in the global ASIR of syphilis is a challenge.
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Carga Global de Enfermedades , Sífilis , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Años de Vida Ajustados por Calidad de Vida , Salud Global , IncidenciaRESUMEN
Milk fat globules (MFGs) surround the triacylglycerol core that composes milk fat. The aim of this study is to induce milk fat depression via dietary conjugated linoleic acid (CLA) supplementation to study MFG size parameters, number and glycerophospholipid composition. Eighteen Holstein dairy cows (136 ± 28 days in milk, 571 ± 37.9 kg body weight, 27.6 ± 2.1 kg milk/day) were selected and randomly assigned to a control or CLA group for a 14-day period. Cows were fed a basal diet (control, n = 8) or the control plus 400 g/day CLA (C18:2 cis-9, trans-11 38.1% and C18:2 trans-10, cis-12 36.8%) (n = 10) for 7 days after which the CLA group was switched to the basal diet for another 7 days along with the control group. Cow performance, milk composition, MFG size and numbers were measured daily. On the seventh day after the start of the experiment, milk samples were identified and the quantification of glycerophospholipid compounds, and RNA were isolated from milk fat samples for a real-time polymerase chain reaction. Compared with control, at Day 7 from the start of feeding, supplemental CLA did not affect milk production (28.09 vs. 28.50 kg/day), dry matter intake (14.9 vs. 15.4 kg/day), or milk protein (3.55/100 vs. 3.70 g/100 ml) and lactose contents (5.11/100 vs. 5.17 g/100 ml). However, although the specific surface area of MFG (2138 vs. 1815 m²/kg) was greater, CLA reduced milk fat content (1.95/100 vs 3.64 g/100 ml on Day 7) and particle size parameters of MFG. The number of MFG gradually decreased until Day 7 of feeding, and then increased by Day 14 (2.96 × 109 on Day 1, 1.63 × 109 on Day 7 and 2.28 × 109 on Day 14) in the CLA group. Compared with control, glycerophospholipid analysis revealed that concentrations of phosphatidylcholine (PC) (e.g., PC [16:0/18:1] 20322 vs. 29793 nmol/L), lysophosphatidylethanolamine (LPE) (e.g., LPE [18:1] 956 vs. 4610 nmol/L) and phosphatidylethanolamine (PE) (e.g., PE [16:0/18:1] 7000 vs. 9769 nmol/L) in milk lipids decreased during CLA feeding. In contrast, concentrations of phosphatidylinositol (PI) (e.g., PI [18:0/18:1] 4052 vs. 1799 nmol/L) and phosphatidylserine (PS) (e.g., PS [18:1/18:2] 9500 vs. 6843 nmol/L) increased. The messenger RNA abundance of fatty acid synthase, diacylglycerol O-acyltransferase 1, glycerol-3-phosphate acyltransferase 4 and phosphate cytidylyltransferase 1, choline, alpha (PCYT1A) were downregulated in the CLA group, confirming published data demonstrating a negative effect of CLA on lipogenesis in the mammary gland. Overall, these results provided evidence for the important role of lipogenic gene expression in the regulation of MFG size, number and glycerophospholipid composition.
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Ácidos Linoleicos Conjugados , Femenino , Animales , Bovinos , Ácidos Linoleicos Conjugados/farmacología , Lactancia/fisiología , Ácidos Grasos/metabolismo , Fosfolípidos , Dieta/veterinaria , Glicerofosfolípidos/farmacología , Suplementos Dietéticos/análisisRESUMEN
This study investigated pesticide residues in market-sold vegetables and fruits in Hebei Province, China, over 5 years (2018-2022). A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method was applied to gas chromatography with triple-quadrupole mass spectrometer (GC-MS/MS). The analytical methods were validated with respect to matrix effect (ME), recovery rate (78.9~105.5%), limit of quantitation (LOQ, 2.93~9.73 µg/kg), and linear correlation coefficient (0.9982~0.9997). Residues of 10 pesticides in 12 categories of vegetable and fruit were detected. 31.9% of the samples were detected pesticide residues; 15.5% of samples were detected multi-component pesticide residues. Twenty-seven positive detections of pesticide residues exceeded the corresponding maximum residue limit (MRL), accounting for 2.33%. The most types of pesticide residues were detected in cherry, with the number of 7. Procymidone was the most detected pesticide, and it was detected in 8 categories of samples. The hazard index (HI) of omethoate was the highest and the procymidone was the lowest. The HI of all the vegetables and fruits were less than 100%. The effects of pesticide residues are within an acceptable range for human. Adequate attention and further monitoring are still needed.
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Residuos de Plaguicidas , Plaguicidas , Humanos , Residuos de Plaguicidas/análisis , Espectrometría de Masas en Tándem/métodos , Monitoreo del Ambiente , Plaguicidas/análisis , Frutas/química , Medición de Riesgo , Contaminación de Alimentos/análisis , Verduras/químicaRESUMEN
Runs of homozygosity (ROH) are a powerful tool to explore patterns of genomic inbreeding in animal populations and detect signatures of selection. The present study used ROH analysis to evaluate the genome-wide patterns of homozygosity, inbreeding levels, and distribution of ROH islands using the SNP data sets from 899 Mediterranean buffaloes. A total of 42,433 ROH segments were identified, with an average of 47.20 segments per individual. The ROH comprising mostly shorter segments (1-4 Mb) accounted for approximately 72.29% of all ROH. In contrast, the larger ROH (>8 Mb) class accounted for only 7.97% of all ROH segments. Estimated inbreeding coefficients from ROH (FROH) ranged from 0.0201 to 0.0371. Pearson correlations between FROH and genomic relationship matrix increased with the increase of ROH length. We identified ROH hotspots in 12 genomic regions, located on chromosomes 1, 2, 3, 5, 17, and 19, harboring a total of 122 genes. Protein-protein interaction (PPI) analysis revealed the clustering of these genes into 7 PPI networks. Many genes located in these regions were associated with different production traits. In addition, 5 ROH islands overlapped with cattle quantitative trait loci that were mainly associated with milk traits. These findings revealed the genome-wide autozygosity patterns and inbreeding levels in Mediterranean buffalo. Our study identified many candidate genes related to production traits that could be used to assist in selective breeding for genetic improvement of buffalo.
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Búfalos , Polimorfismo de Nucleótido Simple , Animales , Búfalos/genética , Bovinos , Diarrea/veterinaria , Genotipo , Homocigoto , Endogamia , Italia , Sitios de Carácter CuantitativoRESUMEN
Hanper ewes that were either monotocous or polytocous provided ovarian follicles of diameter >3 mm in the follicular phase and, in the luteal phase, samples of corpora lutea that had developed from follicles of diameter >3 mm. Differentially expressed mRNAs (monotocous versus polytocous) were then identified, and their functions were predicted. Results showed that 1508 mRNAs were differentially expressed in the follicular phase, with 885 being in the luteal tissues. Those which were differentially expressed in the follicular phase were mainly involved in the regulation of the ferroptosis and lysosome signalling pathways, whereas, for the luteal tissue, the differentially expressed mRNAs were mainly involved in the regulation of steroid biosynthesis. Based on the results, it was inferred that these pathways could explain variations in the fecundity of sheep.
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Folículo Ovárico , Ovario , Ovinos/genética , Femenino , Animales , Ovario/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Folículo Ovárico/fisiología , Cuerpo Lúteo/fisiología , Fertilidad/genéticaRESUMEN
In clinic, perioperative neurocognitive disorder is becoming a common complication of surgery in old patients. Neuroinflammation and blood-brain barrier (BBB) disruption are important contributors for cognitive impairment. Atorvastatin, as a strong HMG-CoA reductase inhibitor, has been widely used in clinic. However, it remains unclear whether atorvastatin could prevent anesthesia and surgery-induced BBB disruption and cognitive injury by its anti-inflammatory property. In this study, aged C57BL/6J mice were used to address this question. Initially, the mice were subject to atorvastatin treatment for 7 days (10 mg/kg). After a simple laparotomy under 1.5% isoflurane anesthesia, Morris water maze was performed to assess spatial learning and memory. Western blot analysis, immunohistochemistry, and enzyme-linked immunosorbent assay were used to examine the inflammatory response, BBB integrity, and cell apoptosis. Terminal-deoxynucleotidyl transferase mediated nick end labeling assay was used to assess cell apoptosis. The fluorescein sodium and transmission electron microscopy were used to detect the permeability and structure of BBB. The results showed that anesthesia and surgery significantly injured hippocampal-dependent learning and memory, which was ameliorated by atorvastatin. Atorvastatin could also reverse the surgery-induced increase of systemic and hippocampal cytokines, including IL-1ß, TNF-α, and IL-6, accompanied by inhibiting the nuclear factor kappa-B (NF-κB) pathway and Nucleotide-Binding Oligomerization Domain, or Leucine Rich Repeat and Pyrin Domain Containing 3 (NLRP3) inflammasome activation, as well as hippocampal neuronal apoptosis. In addition, surgery triggered an increase of BBB permeability, paralleled by a decrease of the ZO-1, occludin, and Claudin 5 proteins in the hippocampus. However, atorvastatin treatment could protect the BBB integrity from the impact of surgery, by up-regulating the expressions of ZO-1, occludin, and Claudin 5. These findings suggest that atorvastatin exhibits neuroprotective effects on cognition in aged mice undergoing surgery.
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Envejecimiento/metabolismo , Atorvastatina/efectos adversos , Barrera Hematoencefálica/metabolismo , Disfunción Cognitiva/metabolismo , Inflamasomas/metabolismo , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal , Procedimientos Quirúrgicos Operativos/efectos adversos , Envejecimiento/patología , Animales , Atorvastatina/farmacología , Barrera Hematoencefálica/patología , Disfunción Cognitiva/etiología , RatonesRESUMEN
As an important application of functional biomaterials, neural probes have contributed substantially to studying the brain. Bioinspired and biomimetic strategies have begun to be applied to the development of neural probes, although these and previous generations of probes have had structural and mechanical dissimilarities from their neuron targets that lead to neuronal loss, neuroinflammatory responses and measurement instabilities. Here, we present a bioinspired design for neural probes-neuron-like electronics (NeuE)-where the key building blocks mimic the subcellular structural features and mechanical properties of neurons. Full three-dimensional mapping of implanted NeuE-brain interfaces highlights the structural indistinguishability and intimate interpenetration of NeuE and neurons. Time-dependent histology and electrophysiology studies further reveal a structurally and functionally stable interface with the neuronal and glial networks shortly following implantation, thus opening opportunities for next-generation brain-machine interfaces. Finally, the NeuE subcellular structural features are shown to facilitate migration of endogenous neural progenitor cells, thus holding promise as an electrically active platform for transplantation-free regenerative medicine.
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Materiales Biocompatibles/química , Interfaces Cerebro-Computador , Electrodos Implantados , Electrónica , Neuronas/fisiología , Animales , Animales Recién Nacidos , Astrocitos/citología , Biomimética , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Mapeo Encefálico , Fenómenos Electrofisiológicos , Proteínas Fluorescentes Verdes/metabolismo , Hipocampo/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Inflamación , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Nanomedicina , Neuritas , Refractometría , Proyectos de Investigación , Técnicas Estereotáxicas , Estrés MecánicoRESUMEN
BACKGROUND: Rectus sheath block (RSB) is known to attenuate postoperative pain and reduce perioperative opioid consumption. Thus, a retrospective study was performed to examine the effects of bilateral rectus sheath block (BRSB) in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A total of 178 patients undergoing CRS/HIPEC at our hospital were included. Patient information and anaesthesia-related indicators were collected from the electronic medical record (EMR) system. All subjects were divided into the following two groups: the G group (general anaesthesia) and the GR group (RSB combined with general anaesthesia). Patients in the GR group received 0.375% ropivacaine for BRSB before surgery. The primary outcomes included the total amount of remifentanil and rocuronium, the total consumption of dezocine after surgery, the visual analogue scale (VAS) score and the patient-controlled intravenous analgesia (PCIA) input dose at 1 h (T6), 6 h (T7), 12 h (T8), 24 h (T9) and 48 h (T10) after surgery. Other outcomes were also recorded, such as patient demographic data, the intraoperative heart rate (HR) and mean arterial pressure (MAP), and postoperative complications. RESULTS: Compared with the G group, the GR group showed a shorter time to tracheal extubation (P < 0.05), a decreased total amount of remifentanil and rocuronium (P < 0.05), and a reduced VAS score, PCIA input dose and number of PCIA boluses at 1 h, 6 h and 12 h after surgery (P < 0.05). However, at 24 h and 48 h after surgery, there were no differences in the VAS score of pain at rest or during motion between the two groups (P > 0.05). Moreover, the incidence of hypertension, emergence agitation, delayed recovery, hypercapnia, and nausea and vomiting was lower in the GR group than in the G group (P < 0.05). There were no differences in the changes in MAP and HR during the surgery between the two groups (P > 0.05). No complications associated with nerve block occurred. CONCLUSION: BRSB could provide short-term postoperative analgesia, reduce perioperative opioid consumption and reduce the incidence of postoperative complications. It is an effective and safe procedure in CRS/HIPEC.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción/métodos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Bloqueo Nervioso/métodos , Recto del Abdomen/diagnóstico por imagen , Recto del Abdomen/inervación , Ultrasonografía Intervencional/métodos , Adulto , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Femenino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efectos adversos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Recto del Abdomen/efectos de los fármacos , Estudios RetrospectivosRESUMEN
Human-vehicle classification is an essential component to avoiding accidents in autonomous driving. The classification technique based on the automotive radar sensor has been paid more attention by related researchers, owing to its robustness to low-light conditions and severe weather. In the paper, we propose a hybrid support vector machine-convolutional neural network (SVM-CNN) approach to address the class-imbalance classification of vehicles and pedestrians with limited experimental radar data available. A two-stage scheme with the combination of feature-based SVM technique and deep learning-based CNN is employed. In the first stage, the modified SVM technique based on these distinct physical features is firstly used to recognize vehicles to effectively alleviate the imbalance ratio of vehicles to pedestrians in the data level. Then, the residual unclassified images will be used as inputs to the deep network for the subsequent classification, and we introduce a weighted false error function into deep network architectures to enhance the class-imbalance classification performance at the algorithm level. The proposed SVM-CNN approach takes full advantage of both the locations of underlying class in the entire Range-Doppler image and automatical local feature learning in the CNN with sliding filter bank to improve the classification performance. Experimental results demonstrate the superior performances of the proposed method with the F 1 score of 0.90 and area under the curve (AUC) of the receiver operating characteristic (ROC) of 0.99 over several state-of-the-art methods with limited experimental radar data available in a 77 GHz automotive radar.