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1.
J Agric Food Chem ; 72(19): 11205-11220, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38708789

RESUMEN

Chlorpyrifos (CPF), dichlorvos (DDV), and cypermethrin (CP), as commonly used pesticides, have been implicated in inducing neuropsychiatric disorders, such as anxiety, depression-like behaviors, and locomotor activity impairment. However, the exact molecular mechanisms of these adverse effects, particularly in both sexes and their next-generation effects, remain unclear. In this study, we conducted behavioral analysis, along with cellular assays (monodansylcadaverine staining) and molecular investigations (qRT-PCR and western blotting of mTOR, P62, and Beclin-1) to clear the potential role of autophagy in pesticide-induced behavioral alterations. For this purpose, 42 adult female and 21 male inbred ICR mice (F0) were distributed into seven groups. Maternal mice (F0) and 112 F1 offspring were exposed to 0.5 and 1 ppm of CPF, DDV, and CP through drinking water. F1 male and female animals were studied to assess the sex-specific effects of pesticides on brain tissue. Our findings revealed pronounced anxiogenic effects and impaired locomotor activity in mice. F1 males exposed to CPF (1 ppm) exhibited significantly elevated depression-like behaviors compared to other groups. Moreover, pesticide exposure reduced mTOR and P62 levels, while enhancing the Beclin-1 gene and protein expression. These changes in autophagy signaling pathways, coupled with oxidative and neurogenic damage in the cerebral cortex and hippocampus, potentially contribute to heightened locomotor activity, anxiety, and depression-like behaviors following pesticide exposure. This study underscores the substantial impact of pesticides on both physiological and behavioral aspects, emphasizing the necessity for comprehensive assessments and regulatory considerations for pesticide use. Additionally, the identification of sex-specific responses presents a crucial dimension for pharmaceutical sciences, highlighting the need for tailored therapeutic interventions and further research in this field.


Asunto(s)
Ansiedad , Autofagia , Conducta Animal , Depresión , Ratones Endogámicos ICR , Estrés Oxidativo , Plaguicidas , Animales , Femenino , Masculino , Ratones , Autofagia/efectos de los fármacos , Ansiedad/inducido químicamente , Ansiedad/fisiopatología , Ansiedad/metabolismo , Depresión/metabolismo , Depresión/genética , Depresión/inducido químicamente , Depresión/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Plaguicidas/toxicidad , Plaguicidas/efectos adversos , Conducta Animal/efectos de los fármacos , Locomoción/efectos de los fármacos , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Cloropirifos/toxicidad , Cloropirifos/efectos adversos
2.
Plant Biotechnol J ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713743

RESUMEN

CRISPR-Cas9 is widely used for genome editing, but its PAM sequence requirements limit its efficiency. In this study, we explore Faecalibaculum rodentium Cas9 (FrCas9) for plant genome editing, especially in rice. FrCas9 recognizes a concise 5'-NNTA-3' PAM, targeting more abundant palindromic TA sites in plant genomes than the 5'-NGG-3' PAM sites of the most popular SpCas9. FrCas9 shows cleavage activities at all tested 5'-NNTA-3' PAM sites with editing outcomes sharing the same characteristics of a typical CRISPR-Cas9 system. FrCas9 induces high-efficiency targeted mutagenesis in stable rice lines, readily generating biallelic mutants with expected phenotypes. We augment FrCas9's ability to generate larger deletions through fusion with the exonuclease, TREX2. TREX2-FrCas9 generates much larger deletions than FrCas9 without compromise in editing efficiency. We demonstrate TREX2-FrCas9 as an efficient tool for genetic knockout of a microRNA gene. Furthermore, FrCas9-derived cytosine base editors (CBEs) and adenine base editors (ABE) are developed to produce targeted C-to-T and A-to-G base edits in rice plants. Whole-genome sequencing-based off-target analysis suggests that FrCas9 is a highly specific nuclease. Expression of TREX2-FrCas9 in plants, however, causes detectable guide RNA-independent off-target mutations, mostly as single nucleotide variants (SNVs). Together, we have established an efficient CRISPR-FrCas9 system for targeted mutagenesis, large deletions, C-to-T base editing, and A-to-G base editing in plants. The simple palindromic TA motif in the PAM makes the CRISPR-FrCas9 system a promising tool for genome editing in plants with an expanded targeting scope.

3.
Plant Sci ; 340: 111974, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38199385

RESUMEN

The AGL6 (AGMOUSE LIKE 6) gene is a member of the SEP subfamily and functions as an E-class floral homeotic gene in the development of floral organs. In this study, we cloned IiAGL6, the orthologous gene of AGL6 in Isatis indigotica. The constitutive expression of IiAGL6 in Arabidopsis thaliana resulted in a late-flowering phenotype and the development of curly leaves during the vegetative growth period. Abnormal changes in floral organ development were observed during the reproductive stage. In woad plants, suppression of IiAGL6 using TRV-VIGS (tobacco rattle virus-mediated virus-induced gene silencing) decreased the number of stamens and led to the formation of aberrant anthers. Similar changes in stamen development were also observed in miRNA-AGL6 transgenic Arabidopsis plants. Yeast two-hybrid and BiFC tests showed that IiAGL6 can interact with other MADS-box proteins in woad; thus, playing a key role in defining the identities of floral organs, particularly during stamen formation. These findings might provide novel insights and help investigate the biological roles of MADS transcription factors in I. indigotica.


Asunto(s)
Arabidopsis , Isatis , Isatis/genética , Isatis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Flores , Arabidopsis/metabolismo , Polen/genética , Polen/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo , Filogenia
4.
Int J Biol Macromol ; 253(Pt 6): 127393, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37827404

RESUMEN

Cellulose is an economical, biodegradable, widely available, and eco-friendly natural macromolecule. But its utilization has been restricted due to its insolubility in water and common organic solvents. In this work, soluble fluorescent probes based on cellulose were synthesized. Firstly, the primary hydroxyl group in glucose units was reacted with SOCl2 to introduce Cl and obtain chloro-cellulose (Cell-Cl). This operation breaks down the regular structure and hydrogen bonding of the original cellulose, enabling it to dissolve in DMSO. Secondly, the Cell-Cl reacted with CS2 and 2-mercaptobenzothiazole to obtain a cellulose-based macromolecular RAFT reagent (Cell-CTA). Finally, the fluorescent monomers which bears -C=C- and naphthalimide, and methacrylic acid (MAA) were grafted onto the main chain of cellulose through RAFT polymerization. Thus, cellulose-based readily soluble macromolecular fluorescent probes were obtained. The cellulose-based probes can specifically recognize Fe3+ in pure water and can be recycled and regenerated. Additionally, the cellulose-based probes exhibit remarkable adsorption and separation properties for Fe3+ ions. The modification of cellulose decreases its crystallinity and introduces hydrophilic groups and fluorophores, which enables cellulose to be soluble in both pure water and the organic solvent DMSO. This work expands the application range of cellulose-based copolymers.


Asunto(s)
Celulosa , Colorantes Fluorescentes , Celulosa/química , Dimetilsulfóxido , Polímeros/química , Solventes , Agua
5.
Materials (Basel) ; 16(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37687654

RESUMEN

In this paper, a multilayer ultra-wideband transparent metamaterial wave absorber is proposed, which has the characteristics of ultra-wideband wave absorption, light transmission and flexible bending; in addition, due to the complete symmetry of the structure, the absorber has polarization insensitivity to incident electromagnetic waves. Both simulation and experimental results show that the frequency range of the microwave absorption rate is higher than 90% between 8.7 GHz and 38.9 GHz (between which most of the absorption rate can reach more than 95%), the total bandwidth is 30.2 GHz, and the relative bandwidth is 126.9%, realizing microwave broadband absorption and covering commonly used communication frequency bands such as X-band, Ku-band, and K-band. A sample was processed and tested. The test results are in good agreement with the results of the theoretical analysis, which proves the correctness of the theoretical analysis. In addition, through the selection and oxidation of indium tin (ITO) materials, the metamaterial also has the characteristics of optical transparency and flexibility, so it has potential application value in the window radar stealth and conformal radar stealth of weapons and equipment.

6.
Environ Sci Pollut Res Int ; 30(36): 86352-86364, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37402917

RESUMEN

Arsenic contamination in drinking water causes a global public health problem. Emerging evidence suggests that arsenic may act as an environmental risk factor for anxiety disorders. However, the exact mechanism underlying the adverse effects has not been fully elucidated. This study aimed to evaluate the anxiety-like behaviors of mice exposed to arsenic trioxide (As2O3), to observe the neuropathological changes, and to explore the link between the GABAergic system and behavioral manifestations. For this purpose, male C57BL/6 mice were exposed to various doses of As2O3 (0, 0.15, 1.5, and 15 mg/L) through drinking water for 12 weeks. Anxiety-like behaviors were assessed using the open field test (OFT), light/dark choice test, and elevated zero maze (EZM). Neuronal injuries in the cerebral cortex and hippocampus were assessed by light microscopy with H&E and Nissl staining. Ultrastructural alteration in the cerebral cortex was assessed by transmission electron microscope (TEM). The expression levels of GABAergic system-related molecules (i.e., glutamate decarboxylase, GABA transporter, and GABAB receptor subunits) in the prefrontal cortex (PFC) were determined by qRT-PCR and western blotting. Arsenic exposure showed a striking anxiogenic effect on mice, especially in the group exposed to 15 mg/L As2O3. Light microscopy showed neuron necrosis and reduced cell counts. TEM revealed marked ultrastructural changes, including the vacuolated mitochondria, disrupted Nissl bodies, an indentation in the nucleus membrane, and delamination of myelin sheath in the cortex. In addition, As2O3 influenced the GABAergic system in the PFC by decreasing the expression of the glutamate decarboxylase 1 (GAD1) and the GABAB2 receptor subunit, but not the GABAB1 receptor subunit. To sum up, sub-chronic exposure to As2O3 is associated with increased anxiety-like behaviors, which may be mediated by altered GABAergic signaling in the PFC. These findings shed light on the mechanisms responsible for the neurotoxic effects of arsenic and therefore more cautions should be taken.


Asunto(s)
Arsénico , Agua Potable , Masculino , Ratones , Animales , Arsénico/toxicidad , Ratones Endogámicos C57BL , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Ansiedad/inducido químicamente , Ácido gamma-Aminobutírico/metabolismo
7.
Environ Sci Pollut Res Int ; 30(19): 56879-56892, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36929255

RESUMEN

Green credit policy is the primary means for financial institutions to fulfill their environmental responsibilities. It is an issue worthy of attention whether green credit policy can achieve the effect of energy conservation, efficiency improvement, pollution reduction, and carbon reduction. This study uses the difference-in-difference method to test the impact of green credit policy on energy efficiency. The results show that green credit policy led to a significant decrease in energy intensity of green credit-restricted sectors while impeding the advancement of green total factor energy efficiency. The heterogeneity results show that the energy efficiency of large-scale, light textile manufacturing, resource processing industries, and clean industries are more significantly affected. Green credit policy can achieve energy conservation and has a linkage effect on pollution and carbon reduction. Although the constraint effect of green credit policy has effectively suppressed energy intensity, it also leads some industries to face a vicious cycle of "enhanced financing constraints-weakened innovation impetus," which in turn makes it challenging to improve green total factor energy efficiency. The above findings confirm the effectiveness of green credit policy in energy conservation and emission reduction. Also, they indicate the necessity of further improvement of the green financial policy system.


Asunto(s)
Conservación de los Recursos Energéticos , Política Fiscal , Políticas , China , Carbono , Desarrollo Económico
8.
Reprod Sci ; 30(6): 1891-1910, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36484981

RESUMEN

Lead (Pb) is a highly toxic heavy metal. Pb exposure could adversely affect many organs, including the male reproductive system. Oxidative stress and mitochondrial impairment play a fundamental role in the pathogenesis of Pb-induced male reproductive system injury. Taurine (TAU) is abundantly found in mammalian bodies. The positive effects of TAU on oxidative stress biomarkers and mitochondrial function have been reported. The current study evaluated the effects of TAU on Pb-induced reproductive toxicity. Mice received Pb (20 mg/kg/day; gavage, 35 consecutive days). Then, sperm indices (quality and quantity) together with sperm kinetics, sperm mitochondrial parameters, testicular and sperm oxidative stress biomarkers, testis and plasma testosterone levels, and the expression of genes involved in the steroidogenesis process have been evaluated. Pb caused significant histopathological alterations and oxidative stress in male mice's reproductive system and sperm. Moreover, significant mitochondrial function impairment was evident in sperm isolated from Pb-treated mice. Pb exposure also suppressed the expression of StAR, 17ß-HSD, CYP11A, and 3ß-HSD genes in the male gonad. It was found that TAU (500 and 1000 mg/kg) significantly improved oxidative stress biomarkers in both male gonads and gametes of Pb-treated mice. TAU also significantly restored sperm mitochondrial function and kinetics. The expression of genes involved in steroidogenesis was also higher in TAU-treated animals. These data suggest TAU as an effective agent against Pb-induced reproductive toxicity. The effects of TAU on oxidative stress markers, mitochondrial function, and the steroidogenesis process seem to play a fundamental role in its protective properties. Further studies are warranted to detect the precise protective effects of this amino acid in the reproductive system. Lead (Pb) is a toxic element that adversely affects the male reproductive system. Mitochondrial impairment and oxidative stress have a crucial role in the Pb-induced reproductive toxicity. Taurine (TAU) could considerably improve the reproductive toxicity induced by Pb via enhancing mitochondrial function and mitigating oxidative stress indices. ΔΨ, mitochondrial membrane potential; ATP, adenosine triphosphate.


Asunto(s)
Plomo , Taurina , Masculino , Ratones , Animales , Taurina/farmacología , Taurina/metabolismo , Fenómenos Biomecánicos , Plomo/toxicidad , Plomo/metabolismo , Semen/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo , Estrés Oxidativo , Mitocondrias/metabolismo , Biomarcadores/metabolismo , Testosterona , Mamíferos/metabolismo
9.
Naunyn Schmiedebergs Arch Pharmacol ; 395(12): 1557-1572, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36097067

RESUMEN

Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28 days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.


Asunto(s)
Colestasis , Lesión Pulmonar , Neumonía , Ratas , Animales , Taurina/farmacología , Taurina/uso terapéutico , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Lesión Pulmonar/prevención & control , Estrés Oxidativo , Conductos Biliares/cirugía , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Ligadura/efectos adversos , Antioxidantes/uso terapéutico , Cirrosis Hepática/patología , Fibrosis , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Neumonía/patología , Hígado
10.
PeerJ ; 10: e13034, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35251790

RESUMEN

BACKGROUND: The architecture of inflorescence and the development of floral organs can influence the yield of seeds and have a significant impact on plant propagation. E-class floral homeotic MADS-box genes exhibit important roles in regulation of floral transition and differentiation of floral organs. Woad (Isatis indigotica) possesses unique inflorescence, floral organs and fruit. However, very little research has been carried out to determine the function of MADS-box genes in this medicinal cruciferous plant species. RESULTS: SEPALLATA orthologs in I. indigotica were cloned by degenerate PCR. The sequence possessing the highest identity with SEP2 and SEP4 of Arabidopsis were named as IiSEP2 and IiSEP4, respectively. Constitutive expression of IiSEP2 in Columbia (Col-0) ecotype of Arabidopsis led to early flowering, and the number of the flowers and the lateral branches was reduced, indicating an alteration in architecture of the inflorescences. Moreover, the number of the floral organs was declined, the sepals were turned into carpelloid tissues bearing stigmatic papillae and ovules, and secondary flower could be produced in apetalous terminal flowers. In 35S::IiSEP4-GFP transgenic Arabidopsis plants in Landsberg erecta (Ler) genetic background, the number of the floral organs was decreased, sepals were converted into curly carpelloid structures, accompanied by generation of ovules. Simultaneously, the size of petals, stamens and siliques was diminished. In 35S::IiSEP4-GFP transgenic plants of apetalous ap1 cal double mutant in Ler genetic background, the cauliflower phenotype was attenuated significantly, and the petal formation could be rescued. Occasionally, chimeric organs composed of petaloid and sepaloid tissues, or petaloid and stamineous tissues, were produced in IiSEP4 transgenic plants of apl cal double mutant. It suggested that overexpression of IiSEP4 could restore the capacity in petal differentiation. Silencing of IiSEP4 by Virus-Induced Gene Silencing (VIGS) can delay the flowering time, and reduce the number and size of the floral organs in woad flowers. CONCLUSION: All the results showed that SEPALLATA-like genes could influence the architecture of the inflorescence and the determinacy of the floral meristems, and was also related to development of the floral organs.


Asunto(s)
Arabidopsis , Isatis , Inflorescencia/genética , Arabidopsis/genética , Isatis/genética , Proteínas de Plantas/genética , Flores/genética
11.
Int J Biol Macromol ; 205: 410-418, 2022 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-35202630

RESUMEN

Hyaluronic acid (HA), a high-value biomacromolecule, has wide applications in medical, cosmetic and food fields. Currently, employing the safe-grade microorganisms for de novo biosynthesis of HA from renewable substrates has become a promising alternative. In this study, we established a Bacillus amyloliquefaciens strain as platform for HA production from Jerusalem artichoke inulin. Firstly, the different HA and UDP-GlcUA synthase genes were introduced into B. amyloliquefaciens to construct the HA synthesis pathway. Secondly, the byproduct polysaccharides were removed by knocking sacB and epsA-O using CRISPR/Cas9n system, resulting in a 13% increase in HA production. Finally, 2.89 g/L HA with a high molecular weight of 1.5 MDa was obtained after optimizing fermentation conditions and adding osmotic agents. This study demonstrates the engineered B. amyloliquefaciens can effectively synthesize HA with Jerusalem artichoke inulin and provides a green route for HA production.


Asunto(s)
Bacillus amyloliquefaciens , Helianthus , Bacillus amyloliquefaciens/genética , Bacillus amyloliquefaciens/metabolismo , Fermentación , Helianthus/genética , Helianthus/metabolismo , Ácido Hialurónico/metabolismo , Inulina/metabolismo
12.
Front Bioeng Biotechnol ; 10: 824859, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35145959

RESUMEN

Ectoine, an osmotic pressure-compensated solute, is used in the food, agriculture, medicine, and cosmetics industries due to its ability to protect macromolecules. In this study, an ectoine-producing variant of Escherichia coli, ET08, was genetically constructed by introducing the ectABC gene cluster and eliminating metabolic pathways involving lysine and pyruvate. Medium optimization enhanced ectoine production from 1.87 to 10.2 g/L. Analysis of the transcriptional levels revealed that supplementation with ammonium sulfate enhanced the metabolic flux towards the biosynthesis of ectoine. Furthermore, by optimizing the copy number of ectA, ectB, and ectC, the recombinant E. coli ET11 (ectA:ectB:ectC = 1:2:1) produced 12.9 g/L ectoine in the shake flask and 53.2 g/L ectoine in a fed-batch fermenter, representing the highest ectoine titer produced by E. coli, which has great industrial prospects.

13.
Clin Exp Hepatol ; 8(3): 195-210, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36685263

RESUMEN

Taurine (TAU) is a free amino acid abundant in the human body. Various physiological roles have been attributed to TAU. At the subcellular level, mitochondria are the primary targets for TAU function. Meanwhile, it has been found that TAU depletion is associated with severe pathologies. Cholestasis is a severe clinical complication that can progress to liver fibrosis, cirrhosis, and hepatic failure. Bile duct ligation (BDL) is a reliable model for assessing cholestasis/cirrhosis and related complications. The current study was designed to investigate the effects of cholestasis/cirrhosis on tissue and mitochondrial TAU reservoirs. Cholestatic rats were monitored (14 and 42 days after BDL surgery), and TAU levels were assessed in various tissues and isolated mitochondria. There was a significant decrease in TAU in the brain, heart, liver, kidney, skeletal muscle, intestine, lung, testis, and ovary of the BDL animals (14 and 42 days after surgery). Mitochondrial levels of TAU were also significantly depleted in BDL animals. Tissue and mitochondrial TAU levels in cirrhotic animals (42 days after the BDL operation) were substantially lower than those in the cholestatic rats (14 days after BDL surgery). These data indicate an essential role for tissue and mitochondrial TAU in preventing organ injury induced by cholestasis/cirrhosis and could justify TAU supplementation for therapeutic purposes.

14.
Front Microbiol ; 12: 717387, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34475866

RESUMEN

Petit Manseng is widely used for fermenting sweet wine and is popular among younger consumers because of its sweet taste and attractive flavor. To understand the mechanisms underlying spontaneous fermentation of Petit Manseng sweet wine in Xinjiang, the dynamic changes in the microbial population and volatile compounds were investigated through high-throughput sequencing (HTS) and headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS) technology, respectively. Moreover, the relationship between the microbial population and volatile compounds was deduced via multivariate data analysis. Candida and Mortierella were dominant genera in Petit Manseng wine during spontaneous fermentation. Many fermentative aroma compounds, including ethyl octanoate, isoamyl acetate, ethyl butyrate, ethyl decanoate, isoamyl alcohol, ethyl laurate, isopropyl acetate, hexanoic acid, and octanoic acid, were noted and found to be responsible for the strong fruity and fatty aroma of Petit Manseng sweet wine. Multivariate data analysis indicated that the predominant microorganisms contributed to the formation of these fermentative aroma compounds. Hannaella and Neomicrosphaeropsis displayed a significantly positive correlation with the 6-methylhept-5-en-2-one produced. The current results provide a reference for producing Petit Manseng sweet wine with desirable characteristics.

15.
Carbohydr Polym ; 269: 118320, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34294332

RESUMEN

Hyaluronic acid (HA) is a naturally formed acidic mucopolysaccharide, with excellent moisturising properties and used widely in the medicine, cosmetics, and food industries. The industrial production of specific molecular weight HA has become imperative. Different biological activities and physiological functions of HA mainly depend on the degree of polymerisation. This article reviews the research status and development prospects of the green biosynthesis and molecular weight regulation of HA. There is an application-based prerequisite of specific molecular weight of HA that could be regulated either during the fermentation process or via a controlled HA degradation process. This work provides an important theoretical basis for the downstream efficient production of diversified HA, which will further accelerate the research applications of HA and provide a good scientific basis and method reference for the study of the molecular weight regulation of similar biopolymers.


Asunto(s)
Ácido Hialurónico/biosíntesis , Secuencia de Aminoácidos , Bacterias/genética , Bacterias/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Secuencia de Carbohidratos , Fermentación , Hialuronano Sintasas/genética , Hialuronano Sintasas/metabolismo , Ácido Hialurónico/química , Ácido Hialurónico/aislamiento & purificación , Ácido Hialurónico/metabolismo , Hialuronoglucosaminidasa/metabolismo , Hidrólisis , Peso Molecular , Ingeniería de Proteínas
16.
Cell Death Dis ; 12(2): 196, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608505

RESUMEN

Fibroblast growth factor 9 (FGF9) has long been assumed to modulate multiple biological processes, yet very little is known about the impact of FGF9 on neurodevelopment. Herein, we found that loss of Fgf9 in olig1 progenitor cells induced epilepsy in mice, with pathological changes in the cortex. Then depleting Fgf9 in different neural populations revealed that epilepsy was associated with GABAergic neurons. Fgf9 CKO in GABAergic neuron (CKOVGAT) mice exhibited not only the most severe seizures, but also the most severe growth retardation and highest mortality. Fgf9 deletion in CKOVGAT mice caused neuronal apoptosis and decreased GABA expression, leading to a GABA/Glu imbalance and epilepsy. The adenylate cyclase/cyclic AMP and ERK signaling pathways were activated in this process. Recombinant FGF9 proteoliposomes could significantly decrease the number of seizures. Furthermore, the decrease of FGF9 was commonly observed in serum of epileptic patients, especially those with focal seizures. Thus, FGF9 plays essential roles in GABAergic neuron survival and epilepsy pathology, which could serve as a new target for the treatment of epilepsy.


Asunto(s)
Corteza Cerebral/metabolismo , Epilepsia/metabolismo , Factor 9 de Crecimiento de Fibroblastos/deficiencia , Neuronas GABAérgicas/metabolismo , Células-Madre Neurales/metabolismo , Adenilil Ciclasas/metabolismo , Adulto , Animales , Anticonvulsivantes/farmacología , Apoptosis , Estudios de Casos y Controles , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Epilepsia/patología , Epilepsia/fisiopatología , Epilepsia/prevención & control , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Factor 9 de Crecimiento de Fibroblastos/sangre , Factor 9 de Crecimiento de Fibroblastos/genética , Factor 9 de Crecimiento de Fibroblastos/farmacología , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/patología , Predisposición Genética a la Enfermedad , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/patología , Proteínas Recombinantes/farmacología , Transducción de Señal , Adulto Joven
17.
Mol Neurobiol ; 58(5): 2435-2446, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33439438

RESUMEN

BACKGROUND: TANK-binding kinase1 (TBK1) haploinsufficiency has been shown to cause both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); however, the mechanism is unclear. METHODS: Myeloid Tbk1 knockout mice (Tbk1-LKO mice) were established and motor function and pathological analyses were also performed. The level of p-TBK1 was analyzed in the ALS animal model and in patient samples using flow cytometry. The expression of inflammatory proteins and mRNAs was analyzed via western blotting and RT-PCR, respectively. RESULTS: The latency to fall in seven-month-old Tbk1-LKO mice was significantly reduced in evaluations conducted on two consecutive days. Overall, 25.6% of Tbk1-LKO mice presented paralysis symptoms and signs, along with a loosened myelin sheath and axon degeneration at 14-16 months of age. Furthermore, the Tbk1 deficiency in myeloid cells induced inflammatory cell infiltration and dysbacteriosis in the digestive tract. Additionally, p-TBK1 levels were reduced by 29.5% and 14.8% in monocytes of patients with definite ALS and probable ALS and decreased by 27.6% and 45.5% in monocytes and microglia of ALS animals, respectively. The use of PEI-mannose-TBK1 or PEI-mannose-SaCas9-sgRNA to delete mutant SOD1 in macrophages significantly delayed disease onset and prolonged survival in the mouse model of ALS. CONCLUSIONS: Based on these data, inflammatory monocyte and macrophage infiltration and impaired innate immune defenses contribute to ALS and FTD.


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Axones/metabolismo , Actividad Motora/fisiología , Degeneración Nerviosa/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Animales , Axones/patología , Línea Celular , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Noqueados , Microglía/metabolismo , Microglía/patología , Monocitos/metabolismo , Monocitos/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Degeneración Nerviosa/patología , Fosforilación , Proteínas Serina-Treonina Quinasas/genética
18.
Plant Cell Environ ; 44(1): 114-129, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32860452

RESUMEN

Melatonin (N-acetyl-5-methoxytryptamine) plays important roles in plant defences against a variety of biotic and abiotic stresses, including UV-B stress. Molecular mechanisms underlying functions of melatonin in plant UV-B responses are poorly understood. Here, we show that melatonin effect on molecular signalling pathways, physiological changes and UV-B stress resistance in Arabidopsis. Both exogenous and endogenous melatonin affected expression of UV-B signal transduction pathway genes. Experiments using UV-B signalling component mutants cop1-4 and hy5-215 revealed that melatonin not only acts as an antioxidant to promote UV-B stress resistance, but also regulates expression of several key components of UV-B signalling pathway, including ubiquitin-degrading enzyme (COP1), transcription factors (HY5, HYH) and RUP1/2. Our findings indicate that melatonin delays and subsequently enhances expression of COP1, HY5, HYH and RUP1/2, which act as central effectors in UV-B signalling pathway, thus regulating their effects on antioxidant systems to protect the plant from UV-B stress.


Asunto(s)
Arabidopsis/efectos de la radiación , Melatonina/metabolismo , Transducción de Señal , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiología , Peróxido de Hidrógeno/metabolismo , Malondialdehído/metabolismo , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genética , Transducción de Señal/efectos de la radiación , Estrés Fisiológico , Rayos Ultravioleta/efectos adversos
19.
J Cereb Blood Flow Metab ; 41(4): 723-730, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32615886

RESUMEN

Salvinorin A (SA) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. In this study, we investigated whether intranasal SA administration could improve neurological outcomes in a monkey ischemic stroke model. The stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery M2 segment with an autologous blood clot. Eight adult rhesus monkeys were randomly administered SA or 10% dimethyl sulfoxide as control 20 min after ischemia. Magnetic resonance imaging was used to confirm the ischemia and extent of injury. Neurological function was evaluated using the Non-Human Primate Stroke Scale (NHPSS) over a 28-day observation period. SA significantly reduced infarct volume (3.9 ± 0.7 cm3 vs. 7.2 ± 1.0 cm3; P = 0.002), occupying effect (0.3 ± 0.2% vs. 1.4 ± 0.3%; P = 0.002), and diffusion limitation in the lesion (-28.2 ± 11.0% vs. -51.5 ± 7.1%; P = 0.012) when compared to the control group. SA significantly reduced the NHPSS scores to almost normal in a 28-day observation period as compared to the control group (P = 0.005). Intranasal SA reduces infarct volume and improves neurological outcomes in a rhesus monkey ischemic stroke model using autologous blood clot.


Asunto(s)
Diterpenos de Tipo Clerodano/uso terapéutico , Accidente Cerebrovascular Isquémico/complicaciones , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Animales , Coagulación Sanguínea , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/prevención & control , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Resultado del Tratamiento
20.
Plant Physiol Biochem ; 154: 229-237, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32563851

RESUMEN

E-class MADS-box genes, SEPALLATA (SEP), participate in various aspects of plant development together with B-, C- and D-class MADS-box genes. IiSEP4, a homologous gene of SEP4, was cloned from Isatis indigotica. IiSEP4 was highly expressed in sepals, and its mRNA was mildly detected in leaves, inflorescences, flowers, stamens and young silicles. Constitutive expression of IiSEP4 in Arabidopsis thaliana caused early flowering, accompanied by the reduction of flowers and floral organs. Moreover, the sepals in some flowers were transformed into carpelloid structures with stigmatic papillae, and obviously accompanied by ovule formation. Yeast two-hybrid assays demonstrated that IiSEP4 interacts with other woad MADS proteins to determine the identity of floral organs. These findings reveal the important roles of IiSEP4 in floral development of I. indigotica. The results of this study can lay a foundation for further study on biological functions of MADS transcriptional factors in I. indigotica.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Isatis , Proteínas de Dominio MADS/genética , Proteínas de Plantas/genética , Arabidopsis/genética , Clonación Molecular , Flores/fisiología , Isatis/genética , Proteínas de Dominio MADS/fisiología , Filogenia , Proteínas de Plantas/fisiología , Plantas Modificadas Genéticamente
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