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1.
Plant J ; 117(6): 1815-1835, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37967090

RESUMEN

Developing climate-resilient crops is critical for future food security and sustainable agriculture under current climate scenarios. Of specific importance are drought and soil salinity. Tolerance traits to these stresses are highly complex, and the progress in improving crop tolerance is too slow to cope with the growing demand in food production unless a major paradigm shift in crop breeding occurs. In this work, we combined bioinformatics and physiological approaches to compare some of the key traits that may differentiate between xerophytes (naturally drought-tolerant plants) and mesophytes (to which the majority of the crops belong). We show that both xerophytes and salt-tolerant mesophytes have a much larger number of copies in key gene families conferring some of the key traits related to plant osmotic adjustment, abscisic acid (ABA) sensing and signalling, and stomata development. We show that drought and salt-tolerant species have (i) higher reliance on Na for osmotic adjustment via more diversified and efficient operation of Na+ /H+ tonoplast exchangers (NHXs) and vacuolar H+ - pyrophosphatase (VPPases); (ii) fewer and faster stomata; (iii) intrinsically lower ABA content; (iv) altered structure of pyrabactin resistance/pyrabactin resistance-like (PYR/PYL) ABA receptors; and (v) higher number of gene copies for protein phosphatase 2C (PP2C) and sucrose non-fermenting 1 (SNF1)-related protein kinase 2/open stomata 1 (SnRK2/OST1) ABA signalling components. We also show that the past trends in crop breeding for Na+ exclusion to improve salinity stress tolerance are counterproductive and compromise their drought tolerance. Incorporating these genetic insights into breeding practices could pave the way for more drought-tolerant and salt-resistant crops, securing agricultural yields in an era of climate unpredictability.


Asunto(s)
Productos Agrícolas , Fitomejoramiento , Productos Agrícolas/genética , Productos Agrícolas/metabolismo , Sulfonamidas , Naftalenos , Ácido Abscísico/metabolismo , Sequías
2.
J Virol ; 98(2): e0168223, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38289117

RESUMEN

Porcine deltacoronavirus (PDCoV) has caused enormous economic losses to the global pig industry. However, the immune escape mechanism of PDCoV remains to be fully clarified. Transcriptomic analysis revealed a high abundance of interferon (IFN)-induced protein with tetratricopeptide repeats 3 (IFIT3) transcripts after PDCoV infection, which initially implied a correlation between IFIT3 and PDCoV. Further studies showed that PDCoV nsp5 could antagonize the host type I interferon signaling pathway by cleaving IFIT3. We demonstrated that PDCoV nsp5 cleaved porcine IFIT3 (pIFIT3) at Gln-406. Similar cleavage of endogenous IFIT3 has also been observed in PDCoV-infected cells. The pIFIT3-Q406A mutant was resistant to nsp5-mediated cleavage and exhibited a greater ability to inhibit PDCoV infection than wild-type pIFIT3. Furthermore, we found that cleavage of IFIT3 is a common characteristic of nsp5 proteins of human coronaviruses, albeit not alphacoronavirus. This finding suggests that the cleavage of IFIT3 is an important mechanism by which PDCoV nsp5 antagonizes IFN signaling. Our study provides new insights into the mechanisms by which PDCoV antagonizes the host innate immune response.IMPORTANCEPorcine deltacoronavirus (PDCoV) is a potential emerging zoonotic pathogen, and studies on the prevalence and pathogenesis of PDCoV are ongoing. The main protease (nsp5) of PDCoV provides an excellent target for antivirals due to its essential and conserved function in the viral replication cycle. Previous studies have revealed that nsp5 of PDCoV antagonizes type I interferon (IFN) production by targeting the interferon-stimulated genes. Here, we provide the first demonstration that nsp5 of PDCoV antagonizes IFN signaling by cleaving IFIT3, which affects the IFN response after PDCoV infection. Our findings reveal that PDCoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by deltacoronaviruses.


Asunto(s)
Proteasas 3C de Coronavirus , Infecciones por Coronavirus , Deltacoronavirus , Interferón Tipo I , Péptidos y Proteínas de Señalización Intracelular , Enfermedades de los Porcinos , Porcinos , Animales , Humanos , Proteasas 3C de Coronavirus/metabolismo , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Deltacoronavirus/enzimología , Deltacoronavirus/metabolismo , Deltacoronavirus/patogenicidad , Inmunidad Innata , Interferón Tipo I/antagonistas & inhibidores , Interferón Tipo I/biosíntesis , Interferón Tipo I/inmunología , Péptidos y Proteínas de Señalización Intracelular/química , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteolisis , Transducción de Señal/inmunología , Porcinos/inmunología , Porcinos/virología , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/metabolismo , Enfermedades de los Porcinos/virología , Factores de Transcripción/metabolismo , Zoonosis Virales/inmunología , Zoonosis Virales/virología , Replicación Viral
3.
J Immunol ; 211(9): 1426-1437, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37712758

RESUMEN

Allogeneic hematopoietic stem cell transplantation (alloSCT) is, in many clinical settings, the only curative treatment for acute myeloid leukemia (AML). The clinical benefit of alloSCT greatly relies on the graft-versus-leukemia (GVL) effect. However, AML relapse remains the top cause of posttransplant death; this highlights the urgent need to enhance GVL. Studies of human GVL have been hindered by the lack of optimal clinically relevant models. In this article, we report, the successful establishment of a novel (to our knowledge) humanized GVL model system by transplanting clinically paired donor PBMCs and patient AML into MHC class I/II knockout NSG mice. We observed significantly reduced leukemia growth in humanized mice compared with mice that received AML alone, demonstrating a functional GVL effect. Using this model system, we studied human GVL responses against human AML cells in vivo and discovered that AML induced T cell depletion, likely because of increased T cell apoptosis. In addition, AML caused T cell exhaustion manifested by upregulation of inhibitory receptors, increased expression of exhaustion-related transcription factors, and decreased T cell function. Importantly, combined blockade of human T cell-inhibitory pathways effectively reduced leukemia burden and reinvigorated CD8 T cell function in this model system. These data, generated in a highly clinically relevant humanized GVL model, not only demonstrate AML-induced inhibition of alloreactive T cells but also identify promising therapeutic strategies targeting T cell depletion and exhaustion for overcoming GVL failure and treating AML relapse after alloSCT.

4.
Small ; : e2311702, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456371

RESUMEN

The PD1/PD-L1 immune checkpoint blocking is a promising therapy, while immunosuppressive tumor microenvironment (TME) and poor tumor penetration of therapeutic antibodies limit its efficacy. Repolarization of tumor-associated macrophages (TAMs) offers a potential method to ameliorate immunosuppression of TME and further boost T cell antitumor immunity. Herein, hybrid cell membrane biomimetic nanovesicles (hNVs) are developed by fusing M1 macrophage-derived nanovesicles (M1-NVs) and PD1-overexpressed tumor cell-derived nanovesicles (PD1-NVs) to improve cancer immunotherapy. The M1-NVs promote the transformation of M2-like TAMs to M1-like phenotype and further increase the release of pro-inflammatory cytokines, resulting in improved immunosuppressive TME. Concurrently, the PD1-NVs block PD1/PD-L1 pathway, which boosts cancer immunotherapy when combined with M1-NVs. In a breast cancer mouse model, the hNVs efficiently accumulate at the tumor site after intravenous injection and significantly inhibit the tumor growth. Mechanically, the M1 macrophages and CD8+ T lymphocytes in TME increase by twofold after the treatment, indicating effective immune activation. These results suggest the hNVs as a promising strategy to integrate TME improvement with PD1/PD-L1 blockade for cancer immunotherapy.

5.
Small ; : e2402649, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949403

RESUMEN

The utilization of the organic-inorganic hybrid photocatalysts for water splitting has gained significant attention due to their ability to combine the advantages of both materials and generate synergistic effects. However, they are still far from practical application due to the limited understanding of the interactions between these two components and the complexity of their preparation process. Herein, a facial approach by combining a glycolated conjugated polymer with a TiO2-X mesoporous sphere to prepare high-efficiency hybrid photocatalysts is presented. The functionalization of conjugated polymers with hydrophilic oligo (ethylene glycol) side chains can not only facilitate the dispersion of conjugated polymers in water but also promote the interaction with TiO2-X forming stable heterojunction nanoparticles. An apparent quantum yield of 53.3% at 365 nm and a hydrogen evolution rate of 35.7 mmol h-1 g-1 is achieved by the photocatalyst in the presence of Pt co-catalyst. Advanced photophysical studies based on femtosecond transient absorption spectroscopy and in situ, XPS analyses reveal the charge transfer mechanism at type II heterojunction interfaces. This work shows the promising prospect of glycolated polymers in the construction of hybrid heterojunctions for photocatalytic hydrogen production and offers a deep understanding of high photocatalytic performance by such heterojunction photocatalysts.

6.
Theor Appl Genet ; 137(4): 86, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38512498

RESUMEN

KEY MESSAGE: Recent developments in understanding the distribution and distinctive features of recombination hotspots are reviewed and approaches are proposed to increase recombination frequency in coldspot regions. Recombination events during meiosis provide the foundation and premise for creating new varieties of crops. The frequency of recombination in different genomic regions differs across eukaryote species, with recombination generally occurring more frequently at the ends of chromosomes. In most crop species, recombination is rare in centromeric regions. If a desired gene variant is linked in repulsion with an undesired variant of a second gene in a region with a low recombination rate, obtaining a recombinant plant combining two favorable alleles will be challenging. Traditional crop breeding involves combining desirable genes from parental plants into offspring. Therefore, understanding the mechanisms of recombination and factors affecting the occurrence of meiotic recombination is important for crop breeding. Here, we review chromosome recombination types, recombination mechanisms, genes and proteins involved in the meiotic recombination process, recombination hotspots and their regulation systems and discuss how to increase recombination frequency in recombination coldspot regions.


Asunto(s)
Recombinación Homóloga , Fitomejoramiento , Genoma , Centrómero , Productos Agrícolas/genética , Meiosis/genética
7.
Theor Appl Genet ; 137(3): 50, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363421

RESUMEN

KEY MESSAGE: Two new major QTL were identified for powdery mildew resistance. We confirmed that the QTL on 7HS contributed mainly to the adult-plant resistance, while another one on chromosome arm 1HS made a significant contribution to the seedling resistance. Powdery mildew (PM), caused by Blumeria hordei, can occur at all post emergent stages of barley and constantly threatens crop production. To identify more genes for effective resistance to powdery mildew for use in breeding programs, 696 barley accessions collected from different regions of the world were evaluated for PM resistance at seedling and adult growth stages in three different states of Australia. These barley accessions were genotyped using DArTSeq with over 18,000 markers for a genome-wide association study (GWAS). Using the FarmCPU model, 54 markers showed significant associations with PM resistance scored at the seedling and adult-plant stages in different states of Australia. Another 40 markers showed tentative associations (LOD > 4.0) with resistance. These markers are distributed across all seven barley chromosomes. Most of them were grouped into eleven QTL regions, coinciding with the locations of most of the reported resistance genes. Two major MTAs were identified on chromosome arms 3HS and 5HL, with one on 3HS contributing to adult plant resistance and the one on 5HL to both seedling and adult plant resistance. An MTA on 7HS contributed mainly to the adult-plant resistance, while another one on chromosome arm 1HS made a significant contribution to the seedling resistance.


Asunto(s)
Ascomicetos , Hordeum , Hordeum/genética , Estudio de Asociación del Genoma Completo , Plantones/genética , Marcadores Genéticos , Ascomicetos/genética , Fitomejoramiento , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética
8.
Physiol Plant ; 176(2): e14259, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38511474

RESUMEN

Proteins of the armadillo repeat gene family play important roles in plant pathogen response. Here, 169 armadillo (ARM) genes were identified in upland cotton (Gossypium hirsutum). Phylogenetic analysis grouped these into 11 subfamilies, with conserved protein structures within each subfamily. The results signify that the expansion of the gene family occurred via whole genome duplication and dispersed duplication. Expression profiling and network analysis suggest that GhARM144 may regulate cotton resistance to Verticillium dahliae. GhARM144 was upregulated in roots by V. dahliae infection or salicylic acid treatment. This upregulation indicates a negative regulatory role of GhARM144' in the cotton immune responses, potentially by manipulating salicylic acid biosynthesis. Protein interaction studies found that GhARM144 associates with an osmotin-like protein, GhOSM34, at the plasma membrane. Silencing GhOSM34 reduced the resistance to V. dahliae, suggesting it may play a positive regulatory role. The results demonstrate that GhARM144 modulates cotton immunity through interaction with GhOSM34 and salicylic acid signalling. Further study of these proteins may yield insights into disease resistance mechanisms in cotton and other plants.


Asunto(s)
Acremonium , Ascomicetos , Verticillium , Filogenia , Verticillium/metabolismo , Gossypium/genética , Gossypium/metabolismo , Ácido Salicílico/metabolismo , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
9.
Phytopathology ; : PHYTO01240043R, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38451589

RESUMEN

Scald is one of the major economically important foliar diseases in barley, causing up to 40% yield loss in susceptible varieties. The identification of quantitative trait loci and elite alleles that confer resistance to scald is imperative in reducing the threats to barley production. In this study, genome-wide association studies were conducted using a panel of 697 barley genotypes to identify quantitative trait loci for scald resistance. Field experiments were conducted over three consecutive years. Among different models used for genome-wide association studies analysis, FarmCPU was shown to be the best-suited model. Nineteen significant marker-trait associations related to scald resistance were identified across six different chromosomes. Eleven of these marker-trait associations correspond to previously reported scald resistance genes Rrs1, Rrs4, and Rrs2, respectively. Eight novel marker-trait associations were identified in this study, with the candidate genes encoding a diverse class of proteins, including region leucine-rich repeats, AP2/ERF transcription factor, homeodomain-leucine zipper, and protein kinase family proteins. The combination of identified superior alleles significantly reduces disease severity scores. The results will be valuable for marker-assisted breeding for developing scald-resistant varieties.

10.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34675076

RESUMEN

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.


Asunto(s)
Ácidos Grasos Omega-3/administración & dosificación , Miopía/prevención & control , Administración Oral , Animales , Transdiferenciación Celular , Células Cultivadas , Coroides/irrigación sanguínea , Suplementos Dietéticos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Cobayas , Humanos , Hipoxia/dietoterapia , Hipoxia/fisiopatología , Hipoxia/prevención & control , Ratones , Miofibroblastos/patología , Miopía/dietoterapia , Miopía/fisiopatología , Adulto Joven
11.
J Am Chem Soc ; 145(44): 23948-23962, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37886816

RESUMEN

Assembling macroscopic helices with controllable chirality and understanding their formation mechanism are highly desirable but challenging tasks for artificial systems, especially coordination polymers. Here, we utilize solvents as an effective tool to induce the formation of macroscopic helices of chiral coordination polymers (CPs) and manipulate their helical sense. We chose the Ni/R-,S-BrpempH2 system with a one-dimensional tubular structure, where R-,S-BrpempH2 stands for R-,S-(1-(4-bromophenyl)ethylaminomethylphosphonic acid). The morphology of the self-assemblies can be controlled by varying the cosolvent in water, resulting in the formation of twisted ribbons of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-2T) in pure H2O; needle-like crystals of R-,S-Ni(Brpemp)(H2O)2·1/3CH3CN (R-,S-1C) in 20 vol % CH3CN/H2O; nanofibers of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-3F) in 20-40 vol % methanol/H2O or ethanol/H2O; and superhelices of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-4H or 5H) in 40 vol % propanol/H2O. Interestingly, the helicity of the superhelix can be controlled by using a propanol isomer in water. For the Ni/R-BrpempH2 system, a left-handed superhelix of R-4H(M) was obtained in 40 vol % NPA/H2O, while a right-handed superhelix of R-5H(P) was isolated in 40 vol % IPA/H2O. These results were rationalized by theoretical calculations. Adsorption studies revealed the chiral recognition behavior of these compounds. This work may contribute to the development of chiral CPs with a macroscopic helical morphology and interesting functionalities.

12.
Biochem Cell Biol ; 101(2): 148-159, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36861809

RESUMEN

Nuclear receptor 4A1 (NR4A1), a member of the NR4A subfamily, acts as a gene regulator in a wide range of signaling pathways and responses to human diseases. Here, we provide a brief overview of the current functions of NR4A1 in human diseases and the factors involved in its function. A deeper understanding of these mechanisms can potentially improve drug development and disease therapy.


Asunto(s)
Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Transducción de Señal , Humanos , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética
13.
Theor Appl Genet ; 136(1): 9, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36656369

RESUMEN

KEY MESSAGE: A major QTL (qS7.1) for salinity damage score and Na+ exclusion was identified on chromosome 7H from a barley population derived from a cross between a cultivated variety and a wild accession. qS7.1 was fine-mapped to a 2.46 Mb physical interval and HvNCX encoding a sodium/calcium exchanger is most likely the candidate gene. Soil salinity is one of the major abiotic stresses affecting crop yield. Developing salinity-tolerant varieties is critical for minimizing economic penalties caused by salinity and providing solutions for global food security. Many genes/QTL for salt tolerance have been reported in barley, but only a few of them have been cloned. In this study, a total of 163 doubled haploid lines from a cross between a cultivated barley variety Franklin and a wild barley accession TAM407227 were used to map QTL for salinity tolerance. Four significant QTL were identified for salinity damage scores. One (qS2.1) was located on 2H, determining 7.5% of the phenotypic variation. Two (qS5.1 and qS5.2) were located on 5H, determining 5.3-11.7% of the phenotypic variation. The most significant QTL was found on 7H, explaining 27.8% of the phenotypic variation. Two QTL for Na+ content in leaves under salinity stress were detected on chromosomes 1H (qNa1.1) and 7H(qNa7.1). qS7.1 was fine-mapped to a 2.46 Mb physical interval using F4 recombinant inbred lines. This region contains 23 high-confidence genes, with HvNCX which encodes a sodium/calcium exchanger being most likely the candidate gene. HvNCX was highly induced by salinity stress and showed a greater expression level in the sensitive parent. Multiple nucleotide substitutions and deletions/insertions in the promoter sequence of HvNCX were found between the two parents. cDNA sequencing of the HvNCX revealed that the difference between the two parents is conferred by a single Ala77/Pro77 amino acid substitution, which is located on the transmembrane domain. These findings open new prospects for improving salinity tolerance in barley by targeting a previously unexplored trait.


Asunto(s)
Hordeum , Sitios de Carácter Cuantitativo , Tolerancia a la Sal/genética , Hordeum/genética , Calcio/metabolismo , Sodio/metabolismo , Salinidad
14.
J Dairy Sci ; 106(12): 9186-9199, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37641277

RESUMEN

When ketosis occurs, supraphysiological concentrations of nonesterified fatty acids (NEFA) display lipotoxicity and are closely related to the occurrence of hepatic lipid accumulation, oxidative stress, and inflammation, resulting in hepatic damage and exacerbating the progression of ketosis. However, the mechanism of these lipotoxic effects caused by high concentrations of NEFA in ketosis is still unclear. Cluster antigen 36 (CD36), a fatty acid transporter, plays a vital role in the development of hepatic pathological injury in nonruminants. Thus, the aim of this study was to investigate whether CD36 plays a role in NEFA-induced hepatic lipotoxicity in dairy cows with clinical ketosis. Liver tissue and blood samples were collected from healthy (n = 10) and clinically ketotic (n = 10) cows at 3 to 15 d in milk. In addition, hepatocytes isolated from healthy calves were treated with 0, 0.6, 1.2, or 2.4 mM NEFA for 12 h; or infected with CD36 expressing adenovirus or CD36 silencing small interfering RNA for 48 h and then treated with 1.2 mM NEFA for 12 h. Compared with healthy cows, clinically ketotic cows had greater concentrations of serum NEFA and ß-hydroxybutyrate and activities of aspartate aminotransferase and alanine aminotransferase but lower serum glucose. In addition, dairy cows with clinical ketosis displayed excessive hepatic lipid accumulation. More importantly, these alterations were accompanied by an increased abundance of hepatic CD36. In the cell culture model, exogenous NEFA (0, 0.6, 1.2, or 2.4 mM) treatment could dose-dependently increase the abundance of CD36. Meanwhile, NEFA (1.2 mM) increased the content of triacylglycerol, reactive oxygen species and malondialdehyde, and decreased the activities of glutathione peroxidase and superoxide dismutase. Moreover, NEFA upregulated phosphorylation levels of nuclear factor κB (NF-κB) and the inhibitor of NF-κB (IκB) α, along with the upregulation of protein abundance of NLR family pyrin domain containing 3 (NLRP3) and caspase-1, and mRNA abundance of IL1B, IL6, and tumor necrosis factor α (TNFA). These alterations induced by NEFA in bovine hepatocytes were associated with increased lipid accumulation, oxidative stress and inflammation, which could be further aggravated by CD36 overexpression. Conversely, silencing CD36 attenuated these NEFA-induced detriments. Overall, these data suggest that CD36 may be a potential therapeutic target for NEFA-induced hepatic lipid accumulation, oxidative stress, and inflammation in dairy cows.


Asunto(s)
Enfermedades de los Bovinos , Cetosis , Femenino , Bovinos , Animales , Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados , FN-kappa B/metabolismo , Hepatocitos/metabolismo , Inflamación/veterinaria , Inflamación/metabolismo , Estrés Oxidativo , Cetosis/veterinaria , Ácido 3-Hidroxibutírico , Enfermedades de los Bovinos/metabolismo
15.
J Dairy Sci ; 106(8): 5763-5774, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37268562

RESUMEN

During the transition period in dairy cows, high circulating concentrations of nonesterified fatty acids (NEFA) increase hepatic lipid deposits and are considered a major pathological factor for liver damage. We investigated whether AdipoRon, a synthetic small-molecule agonist of adiponectin receptors 1 and 2 shown to prevent liver lipid accumulation in nonruminants, could alleviate NEFA-induced lipid accumulation and mitochondrial dysfunction. Bovine hepatocytes were isolated from 5 healthy Holstein female newborn calves (1 d of age, 30-40 kg, fasting), and independently isolated hepatocytes from at least 3 different calves were used for each subsequent experiment. The composition and concentration of NEFA used in this study were selected according to hematological criteria of dairy cows with fatty liver or ketosis. First, hepatocytes were cultured with various concentrations of NEFA (0, 0.6, 1.2, or 2.4 mM) for 12 h. In a second experiment, hepatocytes were treated with AdipoRon at different concentrations (0, 5, 25, or 50 µM for 12 h) and times (25 µM for 0, 6, 12, or 24 h) with or without NEFA (1.2 mM) treatment. In the last experiment, hepatocytes were treated with AdipoRon (25 µM), NEFA (1.2 mM), or both for 12 h after treatment with or without the autophagy inhibitor chloroquine. Hepatocytes treated with NEFA had increased protein abundance of sterol regulatory element-binding protein 1c (SREBP-1c) and mRNA abundance of acetyl-CoA carboxylase 1 (ACACA), and decreased protein abundance of peroxisome proliferator-activated receptor α (PPARA), proliferator-activated receptor gamma coactivator-1 α (PGC-1α), mitofusin 2 (MFN2), cytochrome c oxidase subunit IV (COX IV), and mRNA abundance of carnitine palmitoyltransferase 1A (CPT1A), along with lower ATP concentrations. AdipoRon treatment reversed these effects, suggesting this compound had a positive effect on lipid metabolism and mitochondrial dysfunction during the NEFA challenge. In addition, upregulated expression of microtubule-associated protein 1 light chain 3-II (LC3-II, encoded by MAP1LC3) and downregulated expression of sequestosome-1 (SQSTM1, also called p62) indicated that AdipoRon enhanced autophagic activity in hepatocytes. The fact that chloroquine impeded the beneficial effects of AdipoRon on lipid accumulation and mitochondrial dysfunction suggested a direct role for autophagy during NEFA challenge. Our results suggest that autophagy is an important cellular mechanism to prevent NEFA-induced lipid accumulation and mitochondrial dysfunction in bovine hepatocytes, which is consistent with other studies. Overall, AdipoRon may represent a promising therapeutic agent to maintain hepatic lipid homeostasis and mitochondrial function in dairy cows during the transition period.


Asunto(s)
Enfermedades de los Bovinos , Hígado Graso , Bovinos , Animales , Femenino , Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Hepatocitos/metabolismo , Hígado/metabolismo , Hígado Graso/veterinaria , Metabolismo de los Lípidos , Mitocondrias/metabolismo , Autofagia , ARN Mensajero/metabolismo , Enfermedades de los Bovinos/metabolismo
16.
J Dairy Sci ; 106(8): 5626-5635, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37291038

RESUMEN

Fatty liver is a major metabolic disorder of high-producing dairy cows during the transition period. In nonruminants, it is well established that insulin-induced gene 1 (INSIG1) plays a crucial role in regulating hepatic lipogenesis by controlling the anchoring of sterol regulatory element-binding protein 1 (SREBP-1) on the endoplasmic reticulum along with SREBP cleavage-activating protein (SCAP). Whether the INSIG1-SCAP-SREBP-1c transport axis is affected in cows experiencing fatty liver is unknown. Thus, the aim of this study was to investigate the potential role of INSIG1-SCAP-SREBP-1c axis in the progression of fatty liver in dairy cows. For in vivo experiments, 24 dairy cows at the start of their fourth lactation (median; range 3-5) and 8 d in milk (median; range 4-12 d) were selected into a healthy group [n = 12; triglyceride (TG) content <1%] and a severe fatty liver group (n = 12; TG content >10%) according to their hepatic TG content. Blood samples were collected for detecting serum concentrations of free fatty acids, ß-hydroxybutyrate, and glucose. Compared with healthy cows, cows with severe fatty liver had higher serum concentrations of ß-hydroxybutyrate and free fatty acids and lower concentration of glucose. Liver biopsies were used to detect the status of INSIG1-SCAP-SREBP-1c axis, and the mRNA expression of SREBP-1c-target lipogenic genes acetyl-CoA carboxylase α (ACACA), fatty acid synthase (FASN), and diacylglycerol acyltransferase 1 (DGAT1). Cows with severe fatty liver had lower protein expression of INSIG1 in the hepatocyte endoplasmic reticulum fraction, greater protein expression of SCAP and precursor SREBP-1c in the hepatocyte Golgi fraction, and greater protein expression of mature SREBP-1c in the hepatocyte nuclear fraction. In addition, the mRNA expression of SREBP-1c-target lipogenic genes ACACA, FASN, and DGAT1 was greater in the liver of dairy cows with severe fatty liver. In vitro experiments were conducted on hepatocytes isolated from 5 healthy 1-d-old female Holstein calves, and hepatocytes from each calf were run independently. First, hepatocytes were treated with 0, 200, or 400 µM palmitic acid (PA) for 12 h. Exogenous PA treatment decreased INSIG1 protein abundance, enhanced the endoplasmic reticulum to Golgi export of SCAP-precursor SREBP-1c complex and the nuclear translocation of mature SREBP-1c, all of which was associated with increased transcriptional activation of lipogenic genes and TG synthesis. Second, hepatocytes were transfected with INSIG1-overexpressing adenovirus for 48 h and treated with 400 µM PA 12 h before the end of transfection. Overexpressing INSIG1 inhibited PA-induced SREBP-1c processing, upregulation of lipogenic genes, and TG synthesis in hepatocytes. Overall, the present in vivo and in vitro results indicated that the low abundance of INSIG1 contributed to SREBP-1c processing and hepatic steatosis in dairy cows. Thus, the INSIG1-SCAP-SREBP-1c axis may be a novel target for treatment of fatty liver in dairy cows.


Asunto(s)
Enfermedades de los Bovinos , Hígado Graso , Bovinos , Animales , Femenino , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Ácidos Grasos no Esterificados , Ácido 3-Hidroxibutírico , Hígado Graso/metabolismo , Hígado Graso/veterinaria , Hígado/metabolismo , Hepatocitos/metabolismo , Triglicéridos/metabolismo , Insulina/metabolismo , ARN Mensajero/metabolismo , Glucosa/metabolismo , Enfermedades de los Bovinos/metabolismo
17.
J Environ Manage ; 344: 118482, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37413729

RESUMEN

In recent years, urban flood disasters caused by sudden heavy rains have become increasingly severe, posing a serious threat to urban public infrastructure and the life and property safety of residents. Rapid simulation and prediction of urban rain-flood events can provide timely decision-making reference for urban flood control and disaster reduction. The complex and arduous calibration process of urban rain-flood models has been identified as a major obstacle affecting the efficiency and accuracy of simulation and prediction. This study proposes a multi-scale urban rain-flood model rapid construction method framework, BK-SWMM, focusing on urban rain-flood model parameters and based on the basic architecture of Storm Water Management Model (SWMM). The framework comprises two main components: 1) constructing a SWMM uncertainty parameter sample crowdsourcing dataset and coupling Bayesian Information Criterion (BIC) and K-means clustering machine learning algorithm to discover clustering patterns of SWMM model uncertainty parameters in urban functional areas; 2) coupling BIC and K-means with SWMM model to form BK-SWMM flood simulation framework. The applicability of the proposed framework is validated by modeling three different spatial scales in the study regions based on observed rainfall-runoff data. The research findings indicate that the distribution pattern of uncertainty parameters, such as depression storage, surface Manning coefficient, infiltration rate, and attenuation coefficient. The distribution patterns of these seven parameters in urban functional zones indicate that the values are highest in the Industrial and Commercial Areas (ICA), followed by Residential Areas (RA), and lowest in Public Areas (PA). All three spatial scales' REQ, NSEQ, and RD2 indices were superior to the SWMM and less than 10%, greater than 0.80, and greater than 0.85, respectively. However, when the study area's geographical scale expands, the simulation's accuracy will decline. Further research is required on the scale dependency of urban storm flood models.


Asunto(s)
Colaboración de las Masas , Inundaciones , Agua , Incertidumbre , Teorema de Bayes , Movimientos del Agua , Lluvia , Modelos Teóricos , Ciudades , China
18.
J Environ Manage ; 330: 117163, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36603255

RESUMEN

A series of goethite-modified montmorillonite (GMt) materials was synthesized for the amelioration of cationic cadmium (Cd) and anionic arsenic (As) complex contaminants in soil and water bodies. The results showed that goethite (Gt) was successfully loaded onto the surface of montmorillonite (Mt), which possessed more functional groups (such as Fe-O, and Fe-OH) and a larger specific surface area. GMt-0.5 (Mt loaded with Gt at a ratio of 0.5:1) showed the highest adsorption capacity for Cd(II) and As(III) with the maximum of 50.61 mg/g and 57.58 mg/g, respectively. The removal rate of Cd(II) was highly pH dependent, while the removal rate of As(III) showed little dependence on pH. The goethite on montmorillonite might contribute to the formation of surface complexes with As(III) and oxidation of As(III) to As(V). In the binary system, both, synergistic and competitive adsorption existed simultaneously. Importantly, in the binary system, the removal of As(III) was more favorable because of the electrostatic interaction, formation of a ternary complex, and co-precipitation. In addition, the amendment of GMt-0.5 significantly reduced the availability of Cd and As in the soil. This study suggests that GMt-0.5 is a promising candidate for the simultaneous immobilization of metal (loid)s in both, aqueous solution and mine soil.


Asunto(s)
Arsénico , Cadmio , Cadmio/química , Bentonita/química , Adsorción , Suelo , Agua
19.
Molecules ; 28(6)2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36985540

RESUMEN

Combining biomass, a clean and renewable energy source, with waste plastic, which serves as a good auxiliary fuel, can produce high-quality clean fuel. The performance of biomass-derived fuel can be improved by torrefaction. This study optimized the co-torrefaction of fungus bran and polypropylene (PP) waste plastic to obtain clean solid biofuel with high calorific value and low ash content (AC) using response surface methodology. Two sets of mixed biochars were investigated using a multiobjective optimization method: mass yield-higher heating value-ash content (MY-HHV-AC) and energy yield-ash content (EY-AC). PP increased the heat value, decreased AC, and acted as a binder. The optimal operating conditions regarding reaction temperature, reaction time, and PP blending ratio were 230.68 °C, 30 min, and 20%, respectively, for the MY-HHV-AC set and 220 °C, 30 min, 20%, respectively, for the EY-AC set. The MY-HHV-AC set had properties close to those of peat and lignite. Furthermore, compared with that of the pure biochar, the AC of the two sets decreased by 15.71% and 14.88%, respectively, indicating that the prepared mixed biochars served as ideal biofuels. Finally, a circular economy framework for biobriquette fuel was proposed and prospects for preparing pellets provided.

20.
Molecules ; 28(2)2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36677840

RESUMEN

Co-hydrothermal carbonization (Co-HTC) of sewage sludge (SS) and corn straw (CS) for fuel preparation is a waste treatment method that reduces the pre-treatment cost of solid waste and biomass fuel. Based on the response surface methodology (RSM), a test was designed to prepare SS and CS hydrochars using a hydrothermal high-pressure reactor. The test examined the higher heating value (HHV) and the concentrations of alkali metals and alkaline earth metals (AAEMs) and Cl. The HHV of SS-hydrochar decreased with an increase in reaction temperature, but that of CS-hydrochar increased. The yield of CS-hydrochar was at 26.74−61.26%, substantially lower than that of SS-hydrochar. Co-hydrochar has the advantages of HHV and an acceptable yield. The HHV of co-hydrochar was 9215.51−12,083.2 kJ/kg, representing an increase of 12.6−47.6% over single component hydrochar, while the yield of co-hydrochar was 41.46−72.81%. In addition, the stabilities of AAEM and Cl in the co-hydrochar were Mg > Ca > K > Na > Cl. SS and CS had a synergistic effect on dechlorination efficiency (DE), which had a negative effect on the removal efficiency (RE) of Ca and Na. The optimal hydrocharization conditions were a temperature of approximately 246.14 °C, a residence time of approximately 90 min, and a mixing ratio of SS−CS of approximately 57.18%. The results offer a way to utilize SS and CS by Co-HTC and convert them into low-chlorine and low-alkali fuel, thus pushing the improvement of this promising waste-to-energy technology.

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