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1.
Appl Environ Microbiol ; : e0104724, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028195

RESUMO

Phloroglucinol (1,3,5-trihydroxybenzene) is a key intermediate in the degradation of polyphenols such as flavonoids and hydrolysable tannins and can be used by certain bacteria as a carbon and energy source for growth. The identification of enzymes that participate in the fermentation of phloroglucinol to acetate and butyrate in Clostridia was recently reported. In this study, we present the discovery and characterization of a novel metabolic pathway for phloroglucinol degradation in the bacterium Collinsella sp. zg1085, from marmot respiratory tract. In both the Clostridial and Collinsella pathways, phloroglucinol is first reduced to dihydrophoroglucinol by the NADPH-dependent phloroglucinol reductase (PGR), followed by ring opening to form (S)-3-hydroxy-5-oxohexanoate by a Mn2+-dependent dihydrophloroglucinol cyclohydrolase (DPGC). In the Collinsella pathway, (S)-3-hydroxy-5-oxohexanoate is then cleaved to form malonate semialdehyde and acetone by a newly identified aldolase (HOHA). Finally, a NADP+-dependent malonate-semialdehyde dehydrogenase converts malonate semialdehyde to CO2 and acetyl-CoA, an intermediate in carbon and energy metabolism. Recombinant expression of the Collinsella PGR, DPGC, and HOHA in E. coli enabled the conversion of phloroglucinol into acetone, providing support for the proposed pathway. Experiments with Olsenella profusa, another bacterium containing the gene cluster of interest, show that the PGR, DPGC, HOHA, and MSDH are induced by phloroglucinol. Our findings add to the variety of metabolic pathways for the degradation of phloroglucinol, a widely distributed phenolic compound, in the anaerobic microbiome.IMPORTANCEPhloroglucinol is an important intermediate in the bacterial degradation of polyphenols, a highly abundant class of plant natural products. Recent research has identified key enzymes of the phloroglucinol degradation pathway in butyrate-producing anaerobic bacteria, which involves cleavage of a linear triketide intermediate by a beta ketoacid cleavage enzyme, requiring acetyl-CoA as a co-substrate. This paper reports a variant of the pathway in the lactic acid bacterium Collinsella sp. zg1085, which involves cleavage of the triketide intermediate by a homolog of deoxyribose-5-phosphate aldolase, highlighting the variety of mechanisms for phloroglucinol degradation by different anaerobic bacterial taxa.

2.
Plant Cell Environ ; 47(6): 2192-2205, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38481108

RESUMO

Physiological water stress induced by low root temperatures might contribute to species-specific climatic limits of tree distribution. We investigated the low temperature sensitivity of root water uptake and transport in seedlings of 16 European tree species which reach their natural upper elevation distribution limits at different distances to the alpine treeline. We used 2H-H2O pulse-labelling to quantify the water uptake and transport velocity from roots to leaves in seedlings exposed to constant 15°C, 7°C or 2°C root temperature, but identical aboveground temperatures between 20°C and 25°C. In all species, low root temperatures reduced the water transport rate, accompanied by reduced stem water potentials and stomatal conductance. At 7°C root temperature, the relative water uptake rates among species correlated positively with the species-specific upper elevation limits, indicating an increasingly higher sensitivity to lower root zone temperatures, the lower a species' natural elevational distribution limit. Conversely, 2°C root temperature severely inhibited water uptake in all species, irrespective of the species' thermal elevational limits. We conclude that low temperature-induced hydraulic constraints contribute to the cold distribution limits of temperate tree species and are a potential physiological cause behind the low temperature limits of plant growth in general.


Assuntos
Temperatura Baixa , Raízes de Plantas , Especificidade da Espécie , Árvores , Água , Água/metabolismo , Raízes de Plantas/fisiologia , Raízes de Plantas/metabolismo , Árvores/fisiologia , Árvores/metabolismo , Altitude , Folhas de Planta/fisiologia , Folhas de Planta/metabolismo , Plântula/fisiologia , Plântula/metabolismo , Transporte Biológico , Estômatos de Plantas/fisiologia
3.
Haematologica ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961734

RESUMO

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

4.
Hum Genomics ; 17(1): 26, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949502

RESUMO

BACKGROUND: G6PD deficiency is a common inherited disorder worldwide and has a higher incidence rate in southern China. Many variants of G6PD result from point mutations in the G6PD gene, leading to decreased enzyme activity. This study aimed to analyse the genotypic and phenotypic characteristics of G6PD deficiency in Guangzhou, China. METHODS: In this study, a total of 20,208 unrelated participants were screened from 2020 to 2022. G6PD deficiency was further analysed by quantitative enzymatic assay and G6PD mutation analysis. The unidentified genotype of the participants was further ascertained by direct DNA sequencing. RESULTS: A total of 12 G6PD mutations were identified. Canton (c.1376G>T) and Kaiping (c.1388G>A) were the most common variants, and different mutations led to varying levels of G6PD enzyme activity. Comparing the enzyme activities of the 6 missense mutations between the sexes, we found significant differences (P < 0.05) in the enzyme activities of both male hemizygotes and female heterozygotes. Two previously unreported mutations (c.1438A>T and c.946G>A) were identified. CONCLUSIONS: This study provided detailed genotypes of G6PD deficiency in Guangzhou, which could be valuable for diagnosing and researching G6PD deficiency in this area.


Assuntos
Deficiência de Glucosefosfato Desidrogenase , Feminino , Humanos , Masculino , China/epidemiologia , Genótipo , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , Heterozigoto , Mutação
5.
Environ Toxicol ; 39(5): 3026-3039, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38317508

RESUMO

Long noncoding RNAs have been reported to be involved in the development of breast cancer. LINC01572 was previously reported to promote the development of various tumors. However, the potential biological function of LINC01572 in breast cancer remains largely unknown. R language was used to perform bioinformatic analysis of The Cancer Genome Atlas data. The expression level of RNAs was examined by RT-qPCR. The effect of knocking down or overexpression LINC01572 in triple-negative breast cancer (TNBC) cell lines was evaluated by detecting cell proliferation, migrant action. RNA immunoprecipitation assay and RNA pull-down assay were performed to explore the regulatory relationship between LINC01572, EIF4A3, and ß-catenin. Bioinformatics analysis identifies LINC01572 as an oncogene of breast cancer. LINC01572 is over-expressed in TNBC tissues and cell lines, correlated with poor clinical prognosis in BC patients. Cell function studies confirmed that LINC01572 facilitated the proliferation and migration of TNBC cells in both vivo and vitro. Mechanistically, ß-catenin mRNA and EIF4A3 combine spatially to form a complex, LINC01572 helps transport this complex from the nucleus to the cytoplasm, thereby facilitating the translation of ß-catenin. Our findings confirm that LINC01572 acts as a tumor promoter and may act as a biomarker in TNBC. In addition, novel molecular regulatory relationships involving LINC01572/EIF4A3/ß-catenin are critical to the development of TNBC, which led to a new understanding of the mechanisms of TNBC progression and shows a new target for precision treatment for TNBC.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias de Mama Triplo Negativas/genética , RNA Mensageiro/genética , Linhagem Celular Tumoral , RNA , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo
6.
J Asian Nat Prod Res ; : 1-8, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780916

RESUMO

A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7-9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 µM and compounds 1, 9-11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.

7.
J Integr Plant Biol ; 66(6): 1106-1125, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558522

RESUMO

It is generally accepted that jasmonate-ZIM domain (JAZ) repressors act to mediate jasmonate (JA) signaling via CORONATINE-INSENSITIVE1 (COI1)-mediated degradation. Here, we report a cryptic signaling cascade where a JAZ repressor, FvJAZ12, mediates multiple signaling inputs via phosphorylation-modulated subcellular translocation rather than the COI1-mediated degradation mechanism in strawberry (Fragaria vesca). FvJAZ12 acts to regulate flavor metabolism and defense response, and was found to be the target of FvMPK6, a mitogen-activated protein kinase that is capable of responding to multiple signal stimuli. FvMPK6 phosphorylates FvJAZ12 at the amino acid residues S179 and T183 adjacent to the PY residues, thereby attenuating its nuclear accumulation and relieving its repression for FvMYC2, which acts to control the expression of lipoxygenase 3 (FvLOX3), an important gene involved in JA biosynthesis and a diverse array of cellular metabolisms. Our data reveal a previously unreported mechanism for JA signaling and decipher a signaling cascade that links multiple signaling inputs with fruit trait development.


Assuntos
Ciclopentanos , Frutas , Regulação da Expressão Gênica de Plantas , Oxilipinas , Proteínas de Plantas , Transdução de Sinais , Fosforilação , Ciclopentanos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Frutas/metabolismo , Frutas/crescimento & desenvolvimento , Oxilipinas/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Fragaria/metabolismo , Fragaria/genética , Núcleo Celular/metabolismo
8.
J Anesth ; 38(3): 377-385, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38441686

RESUMO

PURPOSE: More literature studies have reported that alfentanil is safe and effective for labor analgesia. However, there is no unified consensus on the optimal dosage of alfentanil used for epidural analgesia. This study explored the concentration at 90% of minimum effective concentration (EC90) of alfentanil combined with 0.075% ropivacaine in patients undergoing epidural labor analgesia to infer reasonable drug compatibility and provide guidance for clinical practice. METHODS: In this prospective, single-center, double-blind study, a total of 45 singleton term primiparas with vaginal delivery who volunteered for epidural labor analgesia were recruited. The first maternal was administered with 3 µg/mL alfentanil combined with 0.075% ropivacaine with the infusion of 10 mL of the mixture every 50 min at a background dose of 3 mL/h. In the absence of PCEA, a total of 15 mL of the mixture is injected per hour. The subsequent alfentanil concentration was determined on the block efficacy of the previous case, using an up-down sequential allocation with a bias-coin design. 30 min after epidural labor analgesia, the block of patient failed with visual analog score (VAS) > 3, the alfentanil concentration was increased in a 0.5 µg/mL gradient for the next patient, while the block was successful with VAS ≤ 3, the alfentanil concentration was remained or decreased in a gradient according to a randomized response list for the next patient. EC90 and 95% confidence interval were calculated by linear interpolation and prediction model with R statistical software. RESULTS: In this study, the estimated EC90 of alfentanil was 3.85 µg/mL (95% confidence interval, 3.64-4.28 µg/mL). CONCLUSION: When combined with ropivacaine 0.075%, the EC90 of alfentanil for epidural labor analgesia is 3.85 µg/mL in patients undergoing labor analgesia.


Assuntos
Alfentanil , Analgesia Epidural , Analgesia Obstétrica , Analgésicos Opioides , Anestésicos Locais , Ropivacaina , Humanos , Ropivacaina/administração & dosagem , Feminino , Método Duplo-Cego , Alfentanil/administração & dosagem , Gravidez , Analgesia Epidural/métodos , Estudos Prospectivos , Adulto , Anestésicos Locais/administração & dosagem , Analgesia Obstétrica/métodos , Analgésicos Opioides/administração & dosagem , Relação Dose-Resposta a Droga , Medição da Dor/métodos , Medição da Dor/efeitos dos fármacos
9.
Biochem Biophys Res Commun ; 671: 229-235, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37307706

RESUMO

The process of erythroid differentiation is orchestrated at the molecular level by a complex network of transcription factors. Erythroid Krüppel-like factor (EKLF/KLF1) is a master erythroid gene regulator that directly regulates most aspects of terminal erythroid differentiation. However, the underlying regulatory mechanisms of EKLF protein stability are still largely unknown. In this study, we identified Vacuolar protein sorting 37 C (VPS37C), a core subunit of the Endosomal sorting complex required for transport-I (ESCRT-I) complex, as an essential regulator of EKLF stability. Our study showed that VPS37C interacts with EKLF and prevents K48-linked polyubiquitination of EKLF and proteasome-mediated EKLF degradation, thus enhancing EKLF protein stability and transcriptional activity. VPS37C overexpression in murine erythroleukemia (MEL) cells promotes hexamethylene bisacetamide (HMBA)-induced erythroid differentiation manifested by up-regulating erythroid-specific EKLF target genes and increasing benzidine-positive cells. In contrast, VPS37C knockdown inhibits HMBA-induced MEL cell erythroid differentiation. Particularly, the restoration of EKLF expression in VPS37C-knockdown MEL cells reverses erythroid-specific gene expression and hemoglobin production. Collectively, our study demonstrated VPS37C is a novel regulator of EKLF ubiquitination and degradation, which plays a positive role in erythroid differentiation of MEL cells by enhancing EKLF protein stability.


Assuntos
Fatores de Transcrição Kruppel-Like , Proteína C , Animais , Camundongos , Proteína C/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Diferenciação Celular/genética , Transporte Proteico , Células Eritroides/metabolismo
10.
Biol Reprod ; 109(5): 720-735, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37552055

RESUMO

Trophoblast plays a crucial role in gestation maintenance and embryo implantation, partly due to the synthesis of progesterone. It has been demonstrated that hypoxia regulates invasion, proliferation, and differentiation of trophoblast cells. Additionally, human trophoblasts display rhythmic expression of circadian clock genes. However, it remains unclear if the circadian clock system is present in goat trophoblast cells (GTCs), and its involvement in hypoxia regulation of steroid hormone synthesis remains elusive. In this study, immunofluorescence staining revealed that both BMAL1 and NR1D1 (two circadian clock components) were highly expressed in GTCs. Quantitative real-time PCR analysis showed that several circadian clock genes were rhythmically expressed in forskolin-synchronized GTCs. To mimic hypoxia, GTCs were treated with hypoxia-inducing reagents (CoCl2 or DMOG). Quantitative real-time PCR results demonstrated that hypoxia perturbed the mRNA expression of circadian clock genes and StAR. Notably, the increased expression of NR1D1 and the reduction of StAR expression in hypoxic GTCs were also detected by western blotting. In addition, progesterone secretion exhibited a notable decline in hypoxic GTCs. SR9009, an NR1D1 agonist, significantly decreased StAR expression at both the mRNA and protein levels and markedly inhibited progesterone secretion in GTCs. Moreover, SR8278, an NR1D1 antagonist, partially reversed the inhibitory effect of CoCl2 on mRNA and protein expression levels of StAR and progesterone synthesis in GTCs. Our results demonstrate that hypoxia reduces StAR expression via the activation of NR1D1 signaling in GTCs, thus inhibiting progesterone synthesis. These findings provide new insights into the NR1D1 regulation of progesterone synthesis in GTCs under hypoxic conditions.


Assuntos
Progesterona , Trofoblastos , Animais , Humanos , Trofoblastos/metabolismo , Cabras/genética , Hipóxia , RNA Mensageiro , Cobalto , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo
11.
J Med Virol ; 95(10): e29168, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37815403

RESUMO

Ocular manifestations have been well recognized in coronavirus disease 2019 (COVID-19) outbreak. Several studies have detected ocular manifestations in patients after COVID-19. However, little is known about the retinal and vitreal alterations in patients before and after COVID-19 infection. This study aimed to investigate the retinal and vitreal alterations in patients before and after contracting COVID-19 infection using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). A total of 38 participants (76 eyes) were enrolled and followed-up 1 month after COVID-19 infection. Then, 26 patients (52 eyes) were evaluated 3 months after COVID-19 infection. Compared with the pre-COVID-19 status, patients with 1- and 3-month post-COVID-19 statuses had significant thinning of ganglion cell and inner plexiform layer, thickening of inner nuclear layer, a decrease in the vessel density (VD) of superficial vascular complex, and an increase in the VD of deep vascular complex. Meanwhile, alteration in parameters of foveal avascular zone (all p < 0.05) and hyper-reflective dots in the vitreous of 27 patients (54 eyes) (71.1% vs. pre-COVID-19, 34.2%, p = 0.006) were observed. These findings suggest significantly retinal and vitreal alterations occurred in patients after COVID-19 infection, possibly due to direct or indirect virus-induced injuries. Further longitudinal studies are required to investigate the long-term effects of COVID-19 infection on the human eyes.


Assuntos
COVID-19 , Vasos Retinianos , Humanos , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , COVID-19/diagnóstico por imagem , Retina/diagnóstico por imagem
12.
J Neuroophthalmol ; 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37624772

RESUMO

BACKGROUND: For patients with multiple sclerosis (MS), both structure and microvasculature alterations in the inner retina have been investigated in several studies. However, little is known about the alterations in the outer retina and choroid. Hence, this study aimed to assess the outer retinal and choroidal changes in patients with MS with no history of optic neuritis (ON). METHODS: Patients with MS and healthy control participants were enrolled in this cross-sectional study. Quantitative analyses were performed using swept source optical coherence tomography and swept source optical coherence tomography angiography images to assess outer retina thickness (ORT) and choroid thickness (CT), vessel density (VD) of choriocapillaris, and choroidal vascularity index (CVI), which were then compared between the groups. RESULTS: A total of 37 participants with MS (72 eyes) and 74 healthy control participants (148 eyes) were included in this study. Compared with healthy controls, patients with MS with no history of ON showed reduced VD of the choriocapillaris and CVI. There was no significant difference in ORT and CT between 2 groups. Meanwhile, in patients with MS, no correlation between OCTA parameters and expanded disability status scale score were found in this study. CONCLUSIONS: Our study indicates that patients with MS with no history of optical neuritis have reduced choriocapillaris vessel density and decreased choroidal vascularity index without detectable alteration in outer retina thickness and choroid thickness. The findings complement the outer retinal and choroidal component of MS, providing deeper insight into the pathophysiology of MS.

13.
Ecotoxicol Environ Saf ; 262: 115315, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37542983

RESUMO

Salinity is detrimental to soil health, plant growth, and crop productivity. Understanding salt tolerance mechanisms offers the potential to introduce superior crops, especially in coastal regions. Root system architecture (RSA) plasticity is vital for plant salt stress adaptation. Tall fescue is a promising forage grass in saline regions with scarce RSA studies. Here, we used the computer-integrated and -automated programs EZ-Rhizo II and ROOT-Vis II to analyze and identify natural RSA variations and adaptability to high salt stress at physiological and genetic levels in 17 global tall fescue accessions. Total root length rather than the number of lateral roots contribute more to water uptake and could be used to separate salt-tolerant (LS-11) and -sensitive accessions (PI531230). Comparative evaluation of LS-11 and PI531230 demonstrated that the lateral root length rather than the main root contributed more towards the total root length in LS-11. Also, high water uptake was associated with a larger lateral root vector and position while low water intake was associated with an insignificant correlation between root length, vector, and position. To examine candidate gene expression, we performed transcriptome and transcription analyses using high-throughput RNA sequencing and real-time quantitative PCR, respectively of the lateral and main roots. The main root displayed more differentially expressed genes than the lateral root. A Poisson comparison of LS-11 vs PI531230 demonstrated significant upregulation of PLASMA MEMBRANE AQUAPORIN 1 and AUXIN RESPONSE FACTOR 22 in both the main and lateral root, which are associated with transmembrane water transport and the auxin-activated signaling system, respectively. There is also an upregulation of BASIC HELIX-LOOP-HELIX 5 in the main root and a downregulation in the lateral root, which is ascribed to sodium ion transmembrane transport, as well as an upregulation of THE MEDIATOR COMPLEX 1 assigned to water transport in the lateral root and a downregulation in the main root. Gene-protein interaction analysis found that more genes interacting with aquaporins proteins were upregulated in the lateral root than in the main root. We inferred that deeper main roots with longer lateral roots emanating from the bottom of the main root were ideal for tall fescue water uptake and salt tolerance, rather than many shallow roots, and that, while both main lateral roots may play similar roles in salt sensing and water uptake, there are intrinsic genomic differences.

14.
Phytother Res ; 37(8): 3195-3210, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37013717

RESUMO

Elevations in circling branched-chain amino acids (BCAAs) levels associated with insulin resistance and type 2 diabetes mellitus (T2DM). Morus alba L. water extracts (MLE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of MLE with the BCAAs co-metabolism modulated by host and gut microbiota. Tissue-specific expressions of BCAA-catabolizing enzymes were detected by RT-PCR and western blot, respectively. The components of the intestinal microflora were analyzed by high-throughput 16S rRNA gene sequencing. The results showed that MLE administration improved blood glucose and insulin level, decreased inflammatory cytokines expression, and lowered serum and feces BCAAs levels. Furthermore, MLE reversed the abundance changes of the bacterial genera correlated with serum and feces BCAAs, such as Anaerovorax, Bilophila, Blautia, Colidextribacter, Dubosiella, Intestinimonas, Lachnoclostridium, Lachnospiraceae_NK4A136, Oscillibacter, and Roseburia. Functionality prediction indicated that MLE potentially inhibited bacterial BCAAs biosynthesis, and promoted the tissue-specific expression of BCAAs catabolic enzyme. More importantly, MLE had obvious impacts on BCAA catabolism in germ-free-mimic T2DM mice. Those results indicated that MLE improving T2DM-related biochemical abnormalities is associated with not only gut microbiota modification but also the tissue-specific expression of BCAAs catabolic enzyme.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistência à Insulina , Morus , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Morus/química , RNA Ribossômico 16S/análise , Aminoácidos de Cadeia Ramificada/análise , Aminoácidos de Cadeia Ramificada/metabolismo , Folhas de Planta/química
15.
Int J Mol Sci ; 24(6)2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36982927

RESUMO

The enzyme encoded by slr1022 gene from Synechocystis sp. PCC6803 was reported to function as N-acetylornithine aminotransferase, γ-aminobutyric acid aminotransferase, and ornithine aminotransferase, which played important roles in multiple metabolic pathways. Among these functions, N-acetylornithine aminotransferase catalyzes the reversible conversion of N-acetylornithine to N-acetylglutamate-5-semialdehyde with PLP as cofactor, which is a key step in the arginine biosynthesis pathway. However, the investigation of the detailed kinetic characteristics and catalytic mechanism of Slr1022 has not been carried out yet. In this study, the exploration of kinetics of recombinant Slr1022 illustrated that Slr1022 mainly functioned as N-acetylornithine aminotransferase with low substrate specificity to γ-aminobutyric acid and ornithine. Kinetic assay of Slr1022 variants and the model structure of Slr1022 with N-acetylornithine-PLP complex revealed that Lys280 and Asp251 residues were the key amino acids of Slr1022. The respective mutation of the above two residues to Ala resulted in the activity depletion of Slr1022. Meanwhile, Glu223 residue was involved in substrate binding and it served as a switch between the two half reactions. Other residues such as Thr308, Gln254, Tyr39, Arg163, and Arg402 implicated a substrate recognition and catalytic process of the reaction. The results of this study further enriched the understanding of the catalytic kinetics and mechanism of N-acetylornithine aminotransferase, especially from cyanobacteria.


Assuntos
Synechocystis , Synechocystis/genética , Synechocystis/metabolismo , Transaminases/metabolismo , Ornitina-Oxo-Ácido Transaminase , Ácido gama-Aminobutírico
16.
Arch Orthop Trauma Surg ; 143(11): 6753-6762, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37344688

RESUMO

PURPOSE: Oxycodone-acetaminophen is a synergic combination of semisynthetic opioid agonis and analgesic/antipyretic agent, which improves analgesic efficacy. This randomized, controlled study intended to evaluate the analgesic efficacy and tolerance of oxycodone-acetaminophen compared to celecoxib alone in post-total knee arthroplasty (TKA) knee osteoarthritis patients. METHODS: One hundred and six knee osteoarthritis patients were randomized into oxycodone-acetaminophen group (N = 54) and celecoxib group (N = 52) at a 1:1 ratio. Each patient orally received oxycodone-acetaminophen (5 mg/325 mg, four times per day) or celecoxib (200 mg, twice per day) from 2 h to day (D) 3 after TKA; meanwhile, each patient received 2-day patient-controlled analgesia (PCA). The primary outcome was pain visual analog scale (VAS) score at rest; other assessments were the secondary outcomes. RESULTS: Pain VAS scores at rest at D1, D2, D3, and pain VAS scores at flexion at D0.5, D1, D2, D3 were lower in oxycodone-acetaminophen group compared to celecoxib group (all P < 0.050). Besides, extra (P < 0.001) and total (P < 0.001) PCA consumption were declined in oxycodone-acetaminophen group compared with celecoxib group. Furthermore, patients' satisfaction score at D3 (P = 0.012) and D7 (P = 0.043) was higher in oxycodone-acetaminophen group versus celecoxib group. Hospital for special surgery knee score (HSS) at preoperation, M1, and M3 did not differ between the two groups (all P > 0.050). The incidences of all adverse events were not varied between oxycodone-acetaminophen and celecoxib groups (all P > 0.050). CONCLUSION: Oxycodone-acetaminophen exerts superior analgesic efficacy, patients' satisfaction, and similar tolerance compared to celecoxib in post-TKA knee osteoarthritis patients.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Celecoxib/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Osteoartrite do Joelho/complicações , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Analgésicos , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego
17.
Angew Chem Int Ed Engl ; 62(47): e202309957, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37596841

RESUMO

Problems of zinc anode including dendrite and hydrogen evolution seriously degrade the performance of zinc batteries. Solid electrolyte interphase (SEI), which plays a key role in achieving high reversibility of lithium anode in aprotic organic solvent, is also beneficial to performance improvement of zinc anode in aqueous electrolyte. However, various studies about interphase for zinc electrode is quite fragmented, and lack of deep understanding on root causes or general design rules for SEI construction. And water molecules with high reactivity brings serious challenge to the effective SEI construction. Here, we reviewed the brief development history of zinc batteries firstly, then summarized the approaches to construct SEI in aqueous electrolyte. Furthermore, the formation mechanisms behind approaches are systematically analyzed, together with discussion on the SEI components and evaluation on electrochemical performance of zinc anode with various types of SEI. Meanwhile, the challenge between lab and industrialization are also discussed.

18.
Educ Inf Technol (Dordr) ; : 1-20, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37361795

RESUMO

Online teacher professional development (OTPD) opportunities are made available to teachers and draw increasing research attention. As the key characteristics of teachers' participation in OTPD, the frequency and quality of participation are increasingly concerned. However, the relationship between teacher participation frequency and participation quality is still unclear. Addressing this problem not only helps reveal teachers' participation patterns in OTPD, but also provides support for promoting teachers' online professional learning and improving OTPD organization and management. To identify teachers' participation patterns and the relationship between participation frequency and participation quality in OTPD, this study analyzed 5,064 log records of 415 teachers using lag sequential analysis, t-test, and Chi-square test. The findings indicated that teachers preferred shallow participation behaviors, such as sharing resources and experience, and seldom carried out deep participation/engagement behaviors (e.g., proposing knowledge topics, establishing teaching and research practices). Teachers with higher participation frequency had lower participation quality in OTPD and tended to repeat shallow participation behaviors. Finally, the study proposed some suggestions for better supporting teachers' participation in online professional development, such as strengthening the links between information sharing activities, knowledge construction activities, and teaching and research practices.

19.
Am J Physiol Cell Physiol ; 322(2): C231-C245, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34936504

RESUMO

Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes (Bmal1, Per2, Nr1d1, and Dbp) and an autophagy-related gene (Atg5) exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of Bmal1, Per2, and Dbp in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, Nr1d1 knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of Bmal1-/- mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited Atg5 transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.


Assuntos
Proteína 5 Relacionada à Autofagia/biossíntese , Autofagia/fisiologia , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Células da Granulosa/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/biossíntese , Animais , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proteína 5 Relacionada à Autofagia/genética , Células Cultivadas , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/biossíntese , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Feminino , Células da Granulosa/patologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética
20.
J Neurosci Res ; 100(12): 2187-2200, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36069656

RESUMO

There is solid evidence for the prominent involvement of the central autonomic and default mode systems in shaping personality. However, whether functional connectivity of these systems can represent neural correlates and predictors of individual variation in personality traits is largely unknown. Resting-state functional magnetic resonance imaging data of 215 healthy young adults were used to construct the sympathetic (SN), parasympathetic (PN), and default mode (DMN) networks, with intra- and internetwork functional connectivity measured. Personality factors were assessed using the five-factor model. We examined the associations between personality factors and functional network connectivity, followed by performance of personality prediction based on functional connectivity using connectome-based predictive modeling (CPM), a recently developed machine learning approach. All personality factors (neuroticism, extraversion, conscientiousness, and agreeableness) other than openness were significantly correlated with intra- and internetwork functional connectivity of the SN, PN, and DMN. Moreover, the CPM models successfully predicted conscientiousness and agreeableness at the individual level using functional network connectivity. Our findings may expand existing knowledge regarding the neural substrates underlying personality.


Assuntos
Conectoma , Rede Nervosa , Adulto Jovem , Humanos , Rede Nervosa/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Personalidade , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico
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