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1.
Antioxidants (Basel) ; 13(9)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39334728

RESUMO

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a critical enzyme that regulates nitric oxide (NO) signaling through the degradation of asymmetric dimethylarginine (ADMA). Previous studies have revealed a link between the beneficial effects of aerobic exercise and the upregulation of DDAH1 in bones and hearts. We previously reported that skeletal muscle DDAH1 plays a protective role in cardiotoxin (CTX)-induced skeletal muscle injury and regeneration. To determine the effects of aerobic exercise on CTX-induced skeletal muscle injury and the role of DDAH1 in this process, wild-type (WT) mice and skeletal muscle-specific Ddah1-knockout (Ddah1MKO) mice were subjected to swimming training for 8 weeks and then injected with CTX. In WT mice, swimming training for 8 weeks significantly promoted skeletal muscle regeneration and attenuated inflammation, oxidative stress, and apoptosis in the gastrocnemius (GA) muscle after CTX injection. These phenomena were associated with increases in the protein expression of PAX7, myogenin, MEF2A, eNOS, SOD2, and peroxiredoxin 5 and decreases in iNOS expression in GA muscles. Swimming training also decreased serum ADMA levels and increased serum nitrate/nitrite (NOx) levels and skeletal muscle DDAH1 expression. Interestingly, swimming training in Ddah1MKO mice had no obvious effect on CTX-induced skeletal muscle injury or regeneration and did not repress the CTX-induced inflammatory response, superoxide generation, or apoptosis. In summary, our data suggest that DDAH1 is important for the protective effect of aerobic exercise on skeletal muscle injury and regeneration.

2.
Se Pu ; 42(10): 935-942, 2024 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-39327657

RESUMO

Receptor chromatography is an efficient analytical technique that combines the high separation ability of chromatography with the high specificity of receptors for drug recognition. In addition, this technique offers the advantages of active recognition, online separation, and convenient multidimensional target tracking. This strategy allows target active ingredients in complex systems, such as traditional Chinese medicines, to be efficiently screened and accurately identified. Furthermore, the interactions between ligands and immobilized proteins can be studied. To avoid a loss in function, receptor chromatography requires efficient, mild, and simple immobilization methods that do not damage the structure of the immobilized receptors. Improvements in the activity, stability, and ligand-recognition specificity of immobilized functional proteins can be achieved by selecting appropriate immobilization conditions. Notably, the protein immobilization method is not only closely related to the recognition ability of receptor chromatography but also determines the accuracy of the technique. Common methods for immobilizing functional proteins include physical adsorption, chemical reactions, biological affinity reactions, and click chemistry. Despite being easy to operate under mild reaction conditions, these methods have shortcomings, including poor reaction specificity and the necessity of using high-purity functional proteins to prepare chromatography columns. Maintaining the high activity of immobilized receptors and ensuring excellent identification and separation abilities are key challenges in the further development of receptor chromatography. In this work, these issues were addressed by introducing a specific bioorthogonal reaction involving haloalkane dehalogenase (Halo) and 6-chlorohexanoic acid for the immobilization of the α1A-adrenergic receptor (α1A-AR). Specifically, Halo-α1A-AR was immobilized on the surface of 6-chlorohexanoic acid-modified aminopropyl silica gel in one step. The stationary phase with immobilized Halo-α1A-AR was characterized using scanning electron microscopy. Moreover, the activity of the Halo-α1A-AR chromatographic column was evaluated using specific ligands (terazosin hydrochloride, phentolamine mesylate, tamsulosin hydrochloride, and urapidil) and nonspecific ligands (yohimbe and metoprolol) for α1A-AR. Halo-α1A-AR was successfully immobilized on the silica gel surface with good stability over 30 days, and the Halo-α1A-AR chromatographic column exhibited good ligand-recognition activity. The nonlinear chromatography results indicated that prazosin hydrochloride, terazosin hydrochloride, and urapidil interacted with immobilized Halo-α1A-AR through one type of binding site, with association constants of 3.85×105, 5.00×105, and 5.90×105L/mol, respectively. In contrast, phentolamine mesylate and tamsulosin hydrochloride interacted with immobilized Halo-α1A-AR through two types of binding site. The association constants with the high- and low-affinity binding sites were 3.12×106 and 6.01×105L/mol, respectively, for phentolamine mesylate and 9.98×105 and 0.21×105L/mol, respectively, for tamsulosin hydrochloride. Compared with the traditional carbonyldiimidazole method, the immobilization method developed in this work did not require receptor purification and thus minimized the loss of receptor activity. The affinity constants obtained with immobilized Halo-α1A-AR were consistent with the values determined for receptor-ligand binding in solution, indicating that the Halo-α1A-AR chromatography column is suitable for studying drug-protein interactions. This approach also provides a foundation for the efficient screening and accurate determination of target active ingredients in complex systems.


Assuntos
Hidrolases , Hidrolases/química , Receptores Adrenérgicos alfa 1/química , Receptores Adrenérgicos alfa 1/metabolismo , Humanos , Enzimas Imobilizadas/química
3.
Heliyon ; 10(17): e36733, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39281597

RESUMO

The soaking and fermentation of the stems and leaves is an important intermediate step in the processing of Indigo Naturalis. However, the relationship between microbiota and Indigo Naturalis yields is still poorly understood. This study aimed to compare microbial communities and metabolite profiles at various stages of soaking fermentation, followed by validation of the results using HPLC. A total of 731 compounds were identified through metabolite analysis, with the levels of indigo and indirubin peaking after 36 h of fermentation. Metagenomes revealed Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were identified as the most abundant microbial phyla in soaking fermentation. Correlation analysis indicated that the yields of indigo and indirubin may be affected by Lactococcus, Clostridium, and Enterobacter through the regulation of related synthetic enzymes. The findings offered novel perspectives on the relationship of microorganisms and Indigo Naturalis yields.

4.
Opt Lett ; 49(16): 4689-4692, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146136

RESUMO

Based on polarization holography, circular polarization beam splitters with separation angles of up to 100° have been fabricated. The left- and right-handed circularly polarized waves can be reconstructed by the two holograms that were designed by the tensor theory of polarization holography, respectively. In the fabrication of circular polarization beam splitters, two holograms were recorded only by the interference method in the same area of the polarization-sensitive material. This method is simple, inexpensive, and easy to adjust the separation angles and element size. The diffraction efficiency and the polarization state of the reconstructed waves were tested under different incident waves, and the experimental results are in good agreement with the theory. This work not only deepens our understanding of polarization holography but also expands the applications of polarization holography.

5.
PLoS One ; 19(8): e0309092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39190650

RESUMO

The Silurian system in Tazhong area is characterized by extensive, low-abundance lithological reservoirs with strong diagenesis, resulting in significant heterogeneity. The complex pore structure in this area significantly impacts fluid control, making accurate characterization and classification of pore structures crucial for understanding reservoir properties and their influence on oil and gas distribution. Based on 314 Mercury Injection Capillary Pressure (MICP) samples in combination with core slices and thin casting slices observation, a pipeline of characterization and classification scheme by data-mining analytics of strong diagenesis sandstone pore structure types in the study zone is established, and the characteristics of different pore structures are clarified. According to the pore structure parameter abstracted by MICP data compression and variable analysis based on hierarchical clustering and principal component analysis (PCA) analysis, the variables are reasonably evaluated and screened, and the screened variables can be divided into three groups: mean pore throat radius-maximum pore throat radius-median pore throat radius-pore throat diameter mean variable group, microscopic mean coefficient variable group, and median pressure displacement pressure-relative sorting coefficient variable group. The combination of classification schemes analysed by decision tree model and linear discriminant analysis (LDA) model was determined. In the two-dimensional projection diagram of LDA model, a relatively obvious distribution of low displacement pressure, middle displacement pressure and high displacement pressure was obtained, and three distribution lines were nearly parallel. Based on the relevant information, 6 combined classification schemes suitable for final pore structure modelling were determined verified by microscopic observation. The correct characterization and classification of pore structure can be applied to the prediction of pore type, which can be used to improve the prediction of oil and gas distribution and oil and gas recovery in the future.


Assuntos
Mineração de Dados , Mineração de Dados/métodos , Análise de Componente Principal , Campos de Petróleo e Gás , Análise Discriminante , China , Porosidade , Análise por Conglomerados
6.
Exp Aging Res ; : 1-12, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39003730

RESUMO

BACKGROUND: Cognitive models of depression assert that attentional biases play an important role in the maintenance of depression. However, few studies have explored attentional bias in depressed older adults, and no consistent conclusions have been reached. METHODS: In the current study, we investigated attentional bias in older adults with non-clinical depression. Older adults aged over 60 with non-clinical depression and without depression were instructed to perform a free viewing task while their eye movements were tracked. RESULTS: The results showed that, compared to older adults without depression, non-clinically depressed older adults had longer total fixation durations and a greater number of fixations on sad stimuli. Moreover, non-depressed older adults exhibited a preference for pleasant images, whereas this effect was not observed in older adults with non-clinical depression. CONCLUSION: This study suggested that non-clinically depressed older adults have attentional bias, which is manifested as increased attention to sad stimuli and decreased attention to pleasant stimuli.The current study has functional and potential functional implications.

7.
J Chromatogr A ; 1730: 465141, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38986402

RESUMO

Functional protein immobilization forms the basis for bio-detections. A series of one-point, site-specific immobilization methods have been developed, however, it still remains as a challenge how to avoid the proteins to move in all directions as well as conveniently regenerate the bio-devices. Herein, we have developed a bivalent affinity binding-inspired method for PPARγ immobilization using DNA aptamer and nickel-nitrilotriacetic acid (Ni2+-NTA) chelation. The specific DNA aptamer (Apt 2) was selected by an on-column systematic evolution of ligands by exponential enrichment (SELEX) method with affinity of (1.57 ± 0.15) × 105 M-1, determined by isothermal titration calorimetry (ITC). Apt 2 and nickel-nitrilotriacetic acid (Ni2+-NTA) were modified on macroporous silica gels via L-α-allylglycine as a linker. They respectively interacted with PPARγ and 6×His tag via bivalent affinity binding for the receptor immobilization. After comprehensive surface characterization, PPARγ was proved to be successful immobilized. Chromatographic studies revealed that the immobilized PPARγ has conformation selectivity, which discriminated agonist and antagonist of the receptor. Ligand-binding parameters (affinity and rate constant) of four agonists (rosiglitazone, pioglitazone, troglitazone, and magnolol) with PPARγ were determined. Troglitazone showed the lowest dissociation rate constant. The binding affinities (3.28 × 107, 1.91 × 106, 2.25 × 107, and 2.43 × 107 M-1) were highly consistent with the data obtained using purified receptor in solution (2.16 × 107, 4.52 × 106, 1.20 × 107, and 1.56 × 107 M-1), offering reliable bio-detection method for PPARγ and its ligands. Due to the biocompatibility of nuclear receptor with DNA, it is conceivable that the bivalent affinity-based method will be a general method for the immobilization of other nuclear receptors, which may provide selective conformation and improved ligand-binding activity for the receptors.


Assuntos
Aptâmeros de Nucleotídeos , PPAR gama , PPAR gama/química , PPAR gama/metabolismo , Ligantes , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Ligação Proteica , Proteínas Imobilizadas/química , Proteínas Imobilizadas/metabolismo , Ácido Nitrilotriacético/química , Ácido Nitrilotriacético/análogos & derivados , Humanos , Calorimetria
8.
Sci Adv ; 10(24): eadn6211, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38865453

RESUMO

Semi-artificial Z-scheme systems offer promising potential toward efficient solar-to-chemical conversion, yet sustainable and stable designs are currently lacking. Here, we developed a sustainable hybrid Z-scheme system capable for visible light-driven overall water splitting by integrating the durability of inorganic photocatalysts with the interfacial adhesion and regenerative property of bacterial biofilms. The Z-scheme configuration is fabricated by drop casting a mixture of photocatalysts onto a glass plate, followed by the growth of biofilms for conformal conductive paste through oxidative polymerization of pyrrole molecules. Notably, the system exhibited scalability indicated by consistent catalytic efficiency across various sheet areas, resistance observed by remarkable maintaining of photocatalytic efficiency across a range of background pressures, and high stability as evidenced by minimal decay of photocatalytic efficiency after 100-hour reaction. Our work thus provides a promising avenue toward sustainable and high-efficiency artificial photosynthesis, contributing to the broader goal of sustainable energy solutions.

9.
Biomed Chromatogr ; 38(8): e5931, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38881185

RESUMO

As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT1R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT1R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT1R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT1R. The association constants were (2.40 ± 0.02) × 104 M-1 for naringenin (5.22 ± 0.26) × 104 M-1 for pinocembrin, and (4.27 ± 0.14) × 104 M-1 for chrysin, respectively. These compounds can bind with AT1R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT1R column for screening and analyzing bioactive compounds in Tibetan medicines.


Assuntos
Simulação de Acoplamento Molecular , Extratos Vegetais , Receptor Tipo 1 de Angiotensina , Extratos Vegetais/química , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 1 de Angiotensina/química , Cromatografia Líquida de Alta Pressão/métodos
10.
Life Sci ; 344: 122452, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38462226

RESUMO

The intestinal tract plays a vital role in both digestion and immunity, making its equilibrium crucial for overall health. This equilibrium relies on the dynamic interplay among intestinal epithelial cells, macrophages, and crypt stem cells. Intestinal epithelial cells play a pivotal role in protecting and regulating the gut. They form vital barriers, modulate immune responses, and engage in pathogen defense and cytokine secretion. Moreover, they supervise the regulation of intestinal stem cells. Macrophages, serving as immune cells, actively influence the immune response through the phagocytosis of pathogens and the release of cytokines. They also contribute to regulating intestinal stem cells. Stem cells, known for their self-renewal and differentiation abilities, play a vital role in repairing damaged intestinal epithelium and maintaining homeostasis. Although research has primarily concentrated on the connections between epithelial and stem cells, interactions with macrophages have been less explored. This review aims to fill this gap by exploring the roles of the intestinal epithelial-macrophage-crypt stem cell axis in maintaining intestinal balance. It seeks to unravel the intricate dynamics and regulatory mechanisms among these essential players. A comprehensive understanding of these cell types' functions and interactions promises insights into intestinal homeostasis regulation. Moreover, it holds potential for innovative approaches to manage conditions like radiation-induced intestinal injury, inflammatory bowel disease, and related diseases.


Assuntos
Mucosa Intestinal , Células-Tronco , Macrófagos , Células Epiteliais , Homeostase
11.
Plant Cell ; 36(10): 4212-4233, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-38299372

RESUMO

Alternative complex III (ACIII) couples quinol oxidation and electron acceptor reduction with potential transmembrane proton translocation. It is compositionally and structurally different from the cytochrome bc1/b6f complexes but functionally replaces these enzymes in the photosynthetic and/or respiratory electron transport chains (ETCs) of many bacteria. However, the true compositions and architectures of ACIIIs remain unclear, as do their structural and functional relevance in mediating the ETCs. We here determined cryogenic electron microscopy structures of photosynthetic ACIII isolated from Chloroflexus aurantiacus (CaACIIIp), in apo-form and in complexed form bound to a menadiol analog 2-heptyl-4-hydroxyquinoline-N-oxide. Besides 6 canonical subunits (ActABCDEF), the structures revealed conformations of 2 previously unresolved subunits, ActG and I, which contributed to the complex stability. We also elucidated the structural basis of menaquinol oxidation and subsequent electron transfer along the [3Fe-4S]-6 hemes wire to its periplasmic electron acceptors, using electron paramagnetic resonance, spectroelectrochemistry, enzymatic analyses, and molecular dynamics simulations. A unique insertion loop in ActE was shown to function in determining the binding specificity of CaACIIIp for downstream electron acceptors. This study broadens our understanding of the structural diversity and molecular evolution of ACIIIs, enabling further investigation of the (mena)quinol oxidoreductases-evolved coupling mechanism in bacterial energy conservation.


Assuntos
Chloroflexus , Microscopia Crioeletrônica , Complexo III da Cadeia de Transporte de Elétrons , Chloroflexus/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Oxirredução , Hidroxiquinolinas/metabolismo , Transporte de Elétrons , Fotossíntese
12.
Clin Chem Lab Med ; 62(6): 1092-1100, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38253403

RESUMO

OBJECTIVES: The standardization of cystatin C (CysC) measurement has received increasing attention in recent years due to its importance in estimating glomerular filtration rate (GFR). Mass spectrometry-based assays have the potential to provide an accuracy base for CysC measurement. However, a precise, accurate and sustainable LC-MS/MS method for CysC is still lacking. METHODS: The developed LC-MS/MS method quantified CysC by detecting signature peptide (T3) obtained from tryptic digestion. Stable isotope labeled T3 peptide (SIL-T3) was spiked to control matrix effects and errors caused by liquid handling. The protein denaturation, reduction and alkylation procedures were combined into a single step with incubation time of 1 h, and the digestion lasted for 3.5 h. In the method validation, digestion time-course, imprecision, accuracy, matrix effect, interference, limit of quantification (LOQ), carryover, linearity, and the comparability to two routine immunoassays were evaluated. RESULTS: No significant matrix effect or interference was observed with the CysC measurement. The LOQ was 0.21 mg/L; the within-run and total imprecision were 1.33-2.05 % and 2.18-3.90 % for three serum pools (1.18-5.34 mg/L). The LC-MS/MS method was calibrated by ERM-DA471/IFCC and showed good correlation with two immunoassays traceable to ERM-DA471/IFCC. However, significant bias was observed for immunoassays against the LC-MS/MS method. CONCLUSIONS: The developed LC-MS/MS method is robust and simpler and holds the promise to provide an accuracy base for routine immunoassays, which will promote the standardization of CysC measurement.


Assuntos
Cistatina C , Espectrometria de Massa com Cromatografia Líquida , Humanos , Cistatina C/sangue , Imunoensaio/métodos , Limite de Detecção , Espectrometria de Massa com Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos
13.
New Phytol ; 241(4): 1605-1620, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38179647

RESUMO

Dynamic DNA methylation regulatory networks are involved in many biological processes. However, how DNA methylation patterns change during flower senescence and their relevance with gene expression and related molecular mechanism remain largely unknown. Here, we used whole genome bisulfite sequencing to reveal a significant increase of DNA methylation in the promoter region of genes during natural and ethylene-induced flower senescence in carnation (Dianthus caryophyllus L.), which was correlated with decreased expression of DNA demethylase gene DcROS1. Silencing of DcROS1 accelerated while overexpression of DcROS1 delayed carnation flower senescence. Moreover, among the hypermethylated differentially expressed genes during flower senescence, we identified two amino acid biosynthesis genes, DcCARA and DcDHAD, with increased DNA methylation and reduced expression in DcROS1 silenced petals, and decreased DNA methylation and increased expression in DcROS1 overexpression petals, accompanied by decreased or increased amino acids content. Silencing of DcCARA and DcDHAD accelerates carnation flower senescence. We further showed that adding corresponding amino acids could largely rescue the senescence phenotype of DcROS1, DcCARA and DcDHAD silenced plants. Our study not only demonstrates an essential role of DcROS1-mediated remodeling of DNA methylation in flower senescence but also unravels a novel epigenetic regulatory mechanism underlying DNA methylation and amino acid biosynthesis during flower senescence.


Assuntos
Dianthus , Syzygium , Dianthus/genética , Syzygium/metabolismo , Senescência Vegetal , Metilação de DNA/genética , Aminoácidos/metabolismo , Flores/genética , Flores/metabolismo
14.
Comput Biol Med ; 167: 107597, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37875042

RESUMO

BACKGROUND: Cancer-associated fibroblasts (CAFs) play pivotal roles in tumor invasion and metastasis. However, studies on CAF biomarkers in Cutaneous Melanoma (CM) are still scarce. This study aimed to explore the potential CAF biomarkers in CM, propose the potential therapeutic targets, and provide new insights for targeted therapy of CAFs in CM. METHODS: We utilized weighted gene co-expression network analysis to identify CAF signature genes in CM, and conducted comprehensive bioinformatics analysis on the CAF risk score established by these genes. Moreover, single-cell sequencing analysis, spatial transcriptome analysis, and cell experiments were utilized for verifying the expression and distribution pattern of signature genes. Furthermore, molecular docking was employed to screen potential target drugs. RESULTS: FBLN1 and COL5A1, two crucial CAF signature genes, were screened to establish the CAF risk score. Subsequently, a comprehensive bioinformatic analysis of the CAF risk score revealed that high-risk score group was significantly enriched in pathways associated with tumor progression. Besides, CAF risk score was significantly negatively correlated with clinical prognosis, immunotherapy response, and tumor mutational burden in CM patients. In addition, FBLN1 and COL5A1 were further identified as CAF-specific biomarkers in CM by multi-omics analysis and experimental validation. Eventually, based on these two targets, Mifepristone and Dexamethasone were screened as potential anti-CAFs drugs. CONCLUSION: The findings indicated that FBLN1 and COL5A1 were the CAF signature genes in CM, which were associated with the progression, treatment, and prognosis of CM. The comprehensive exploration of CAF signature genes is expected to provide new insight for clinical CM therapy.


Assuntos
Fibroblastos Associados a Câncer , Melanoma , Neoplasias Cutâneas , Humanos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Melanoma/tratamento farmacológico , Melanoma/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Simulação de Acoplamento Molecular , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Melanoma Maligno Cutâneo
15.
Reproduction ; 166(6): 473-484, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37732584

RESUMO

In brief: Post-ovulatory aging (POA) results in a decline in oocyte quality and embryonic developmental capacity although the underlying mechanisms remain elusive. This study provides comprehensive mRNA expression profiles of fresh and aging oocytes in mice for the first time. Abstract: POA impairs the quality of mammalian oocytes with harmful effects on the developmental potential of the embryo. This is a major problem for humans since it is associated with low rate of natural fertility, with high rate of spontaneous abortion and low efficiency of in vitro fertilization. However, the molecular mechanisms underlying this process remain unclear and new methods are demanded to control POA. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis on fresh and aging MII mouse oocytes and compared their global RNA transcription patterns. Nine hundred and twenty-one differentially expressed genes (DEGs) were identified. Five hundred and sixty-nine genes were downregulated, while 356 were upregulated in the group of aging oocytes. Gene ontology (GO) enrichment analysis demonstrated that a series of DEGs were significantly enriched involving mitochondrial functions, spindle functions and protein metabolism. The results of qPCR and a series of functional tests further confirmed that the disorder of mitochondrial functions, spindle functions and impairment of protein metabolism were actually involved in the progression of POA. In this study, panoramic mRNA expression profiles of fresh and aging oocytes were depicted and fully validated. Our data will provide a useful resource for further research on the regulation of gene expression of POA and suggest potential strategies to delay and reverse POA.


Assuntos
Senescência Celular , Mitocôndrias , Oócitos , Animais , Feminino , Camundongos , Gravidez , Mitocôndrias/metabolismo , Oócitos/metabolismo , RNA , RNA Mensageiro/metabolismo
16.
Elife ; 122023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737710

RESUMO

Carotenoid (Car) pigments perform central roles in photosynthesis-related light harvesting (LH), photoprotection, and assembly of functional pigment-protein complexes. However, the relationships between Car depletion in the LH, assembly of the prokaryotic reaction center (RC)-LH complex, and quinone exchange are not fully understood. Here, we analyzed native RC-LH (nRC-LH) and Car-depleted RC-LH (dRC-LH) complexes in Roseiflexus castenholzii, a chlorosome-less filamentous anoxygenic phototroph that forms the deepest branch of photosynthetic bacteria. Newly identified exterior Cars functioned with the bacteriochlorophyll B800 to block the proposed quinone channel between LHαß subunits in the nRC-LH, forming a sealed LH ring that was disrupted by transmembrane helices from cytochrome c and subunit X to allow quinone shuttling. dRC-LH lacked subunit X, leading to an exposed LH ring with a larger opening, which together accelerated the quinone exchange rate. We also assigned amino acid sequences of subunit X and two hypothetical proteins Y and Z that functioned in forming the quinone channel and stabilizing the RC-LH interactions. This study reveals the structural basis by which Cars assembly regulates the architecture and quinone exchange of bacterial RC-LH complexes. These findings mark an important step forward in understanding the evolution and diversity of prokaryotic photosynthetic apparatus.


Photosynthesis is a biological process that converts energy from sunlight into a form of chemical energy that supports almost all life on Earth. Over the course of evolution, photosynthesis has gone from being only performed by bacteria to appearing in algae and green plants. While this has given rise to a range of different machineries for photosynthesis, the process always begins the same way: with a structure called the reaction center-light harvesting (RC-LH) complex. Two pigments in the light-harvesting (LH) region ­ known as chlorophyll and carotenoids ­ absorb light energy and transfer it to another part of the complex known as the quinone-type reaction center (RC). This results in the release of electrons that interact with a molecule called quinone converting it to hydroquinone. The electron-bound hydroquinone then shuttles to other locations in the cell where it initiates further steps that ultimately synthesize forms of chemical energy that can power essential cellular processes. In photosynthetic bacteria, hydroquinone must first pass through a ring structure in the light harvesting region in order to leave the reaction center. Previous studies suggest that carotenoids influence the architecture of this ring, but it remains unclear how this may affect the ability of hydroquinone to move out of the RC-LH complex. To investigate, Xin, Shi, Zhang et al. used a technique called cryo-electron microscopy to study the three-dimensional structure of RC-LH complexes in one of the first bacterial species to employ photosynthesis, Roseiflexus castenholzii. The experiments found that fully assembled complexes bind two groups of carotenoids: one nestled in the interior of the LH ring and the other on the exterior. The exterior carotenoids work together with bacteriochlorophyll molecules to form a closed ring that blocks hydroquinone from leaving the RC-LH complex. To allow hydroquinone to leave, two groups of regulatory proteins, including a cytochrome and subunit X, then disrupt the structure of the ring to 'open' it up. These findings broaden our knowledge of the molecules involved in photosynthesis. A better understanding of this process may aid the development of solar panels and other devices that use RC-LH complexes rather than silicon or other inorganic materials to convert energy from sunlight into electricity.


Assuntos
Carotenoides , Quinonas , Citoplasma
17.
Plant Biotechnol J ; 21(11): 2307-2321, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37626478

RESUMO

Petal senescence is the final stage of flower development. Transcriptional regulation plays key roles in this process. However, whether and how post-transcriptional regulation involved is still largely unknown. Here, we identified an ethylene-induced NAC family transcription factor DcNAP in carnation (Dianthus caryophyllus L.). One allele, DcNAP-dTdic1, has an insertion of a dTdic1 transposon in its second exon. The dTdic1 transposon disrupts the structure of DcNAP and causes alternative splicing, which transcribes multiple domain-deleted variants (DcNAP2 and others). Conversely, the wild type allele DcNAP transcribes DcNAP1 encoding an intact NAC domain. Silencing DcNAP1 delays and overexpressing DcNAP1 accelerates petal senescence in carnation, while silencing and overexpressing DcNAP2 have the opposite effects, respectively. Further, DcNAP2 could interact with DcNAP1 and interfere the binding and activation activity of DcNAP1 to the promoters of its downstream target ethylene biosynthesis genes DcACS1 and DcACO1. Lastly, ethylene signalling core transcriptional factor DcEIL3-1 can activate the expression of DcNAP1 and DcNAP2 in the same way by binding their promoters. In summary, we discovered a novel mechanism by which DcNAP regulates carnation petal senescence at the post-transcriptional level. It may also provide a useful strategy to manipulate the NAC domains of NAC transcription factors for crop genetic improvement.


Assuntos
Dianthus , Syzygium , Dianthus/genética , Syzygium/metabolismo , Flores , Etilenos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Sci Adv ; 9(31): eadh8442, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37531428

RESUMO

El Niño-Southern Oscillation (ENSO) is the strongest interannual climate variability with far-reaching socioeconomic consequences. Many studies have investigated ENSO-projected changes under future greenhouse warming, but its responses to plausible mitigation behaviors remain unknown. We show that ENSO sea surface temperature (SST) variability and associated global teleconnection patterns exhibit strong hysteretic responses to carbon dioxide (CO2) reduction based on the 28-member ensemble simulations of the CESM1.2 model under an idealized CO2 ramp-up and ramp-down scenario. There is a substantial increase in the ensemble-averaged eastern Pacific SST anomaly variance during the ramp-down period compared to the ramp-up period. Such ENSO hysteresis is mainly attributed to the hysteretic response of the tropical Pacific Intertropical Convergence Zone meridional position to CO2 removal and is further supported by several selected single-member Coupled Model Intercomparison Project Phase 6 (CMIP6) model simulations. The presence of ENSO hysteresis leads to its amplified and prolonged impact in a warming climate, depending on the details of future mitigation pathways.

19.
Life Sci ; 331: 122059, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37652154

RESUMO

DNA damage caused by internal or external factors lead to increased genomic instability and various diseases. The DNA damage response (DDR) is a crucial mechanism that maintaining genomic stability through detecting and repairing DNA damage timely. Post-translational modifications (PTMs) play significant roles in regulation of DDR. Among the present PTMs, crotonylation has emerged as a novel identified modification that is involved in a wide range of biological processes including gene expression, spermatogenesis, cell cycle, and the development of diverse diseases. In the past decade, numerous crotonylation sites have been identified in histone and non-histone proteins, leading to a more comprehensive and deep understanding of the function and mechanisms in protein crotonylation. This review provides a comprehensive overview of the regulatory mechanisms of protein crotonylation and the effect of crotonylation in DDR. Furthermore, the effect of protein crotonylation in tumor development and progression is presented, to inspire and explore the novel strategies for tumor therapy.


Assuntos
Fenômenos Biológicos , Histonas , Masculino , Humanos , Ciclo Celular , Divisão Celular , Dano ao DNA , Instabilidade Genômica
20.
iScience ; 26(8): 107392, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37554464

RESUMO

Numerosity perception is a fundamental cognitive function in humans and animals. Using an individual difference approach with a comprehensive dataset (N = 249), we performed a voxel-based morphometry analysis to unravel the neuroanatomical substrates associated with individual differences in numerosity perception sensitivity, measured by a classical non-symbolic numerical judgment task. Results showed that greater gray matter volume (GMV) in the left cerebellum, right temporal pole, and right parahippocampal was positively correlated to higher perceptual sensitivity to numerosity. In contrast, the GMV in the left intraparietal sulcus, and bilateral precentral/postcentral gyrus was negatively correlated to the sensitivity of numerosity perception. These findings indicate that a wide range of brain structures, rather than a specific anatomical structure or circuit, forms the neuroanatomical basis of numerosity perception, lending support to the emerging network view of the neural representation of numerosity. This work contributes to a more comprehensive understanding of how the brain processes numerical information.

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