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Flowering time and maturity are crucial agronomic traits that affect the regional adaptability of soybean plants. The development of soybean cultivars with early maturity adapted to longer days and colder climates of high latitudes is very important for ensuring normal ripening before frost begins. FUL belongs to the MADS-box transcription factor family and has several duplicated members in soybeans. In this study, we observed that overexpression of GmFULc in the Dongnong 50 cultivar promoted soybean maturity, while GmFULc knockout mutants exhibited late maturity. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that GmFULc could bind to the CArG, bHLH and homeobox motifs. Further investigation revealed that GmFULc could directly bind to the CArG motif in the promoters of the GmZTL3 and GmZTL4 genes. Overexpression of GmZTL4 promoted soybean maturity, whereas the ztl4 mutants exhibited delayed maturity. Moreover, we found that the cis element box 4 motif of the GmZTL4 promoter, a motif of light response elements, played an important role in controlling the growth period. Deletion of this motif shortened the growth period by increasing the expression levels of GmZTL4. Functional investigations revealed that short-day treatment promoted the binding of GmFULc to the promoter of GmZTL4 and inhibited the expression of E1 and E1Lb, ultimately resulting in the promotion of flowering and early maturation. Taken together, these findings suggest a novel photoperiod regulatory pathway in which GmFULc directly activates GmZTL4 to promote earlier maturity in soybean.
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Regulação da Expressão Gênica de Plantas , Glycine max , Proteínas de Domínio MADS , Proteínas de Plantas , Glycine max/genética , Glycine max/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica , Plantas Geneticamente Modificadas/genéticaRESUMO
BACKGROUND: This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. METHODS: Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10-4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period. RESULTS: Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I. CONCLUSION: The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.
With advancements in science and technology, ovarian transplantation techniques have become increasingly mature. However, there are still many questions that need to be addressed. For instance, the large size of the transplanted ovarian tissues may cause over-recruitment of the primordial follicles. When the transplanted ovarian tissue is too small, it can only exert limited functionality and may not meet the patient's needs. This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function in rats after oophorectomy, and to provide a theoretical basis for determining the minimum effective volume of heterotopic ovarian tissue transplantation.
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Ciclo Estral , Ovariectomia , Ovário , Transplante Heterotópico , Animais , Feminino , Ovário/transplante , Ratos , Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/sangue , Estradiol/sangue , Ratos Sprague-Dawley , Tamanho do Órgão , Folículo Ovariano , Reprodução/fisiologiaRESUMO
Characterizing the cross-links responsible for the covalent high-molecular-weight (HMW) species in therapeutic monoclonal antibodies (mAbs) is of great importance as it not only provides a framework for risk assessment but also offers insights for process improvement. However, owing to the complexity and low abundance, identification of novel and unknown cross-links in mAb products can be very challenging. Here, applying a multipronged MS-based approach, we report the discovery of a novel covalent cross-link formed via an imine bond between lysine and serine residues. In particular, this Ser-Lys cross-link was found to be acid-labile and can be easily overlooked by conventional LC-MS techniques operated at low pH. It is worth noting that although imine-based cross-link has been previously reported in collagen protein cross-linking, this is the first time that a Ser-Lys cross-link has been found in a mAb product that contributes to covalent HMW species formation.
Assuntos
Anticorpos Monoclonais , Lisina , Iminas , Espectrometria de Massas , SerinaRESUMO
OBJECTIVES: The study aimed to assess the efficiency of whole-body high-resolution compressed sensing-sensitivity encoding isotropic T1-Weighted Dixon (CSI-T1W-Dixon) scans in evaluating bone metastasis. METHODS: Forty-five high-risk prostate cancer patients with bone metastases were enrolled prospectively and underwent whole-body MRI sequences, which included the following: pre- and post-contrast CSI-T1W-Dixon and conventional multi-planar T1-Weighted Dixon (CMP-T1W-Dixon) (coronal, sagittal, and axial scans), short tau inversion recovery (STIR), and DWI. Comparison between the CMP-T1W-Dixon and CSI-T1W-Dixon images was done for the subjective image quality, the quantitative contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). Furthermore, the diagnostic performance based on per-lesion and per-patient basis utilizing non-contrast T1-weighted (T1)/T1+ contrasted T1-weighted (T1C)/T1 + T1C + STIR + DWI sequences was compared between the CSI-T1W-Dixon and CMP-T1W-Dixon methods using reference standards (combining biopsy data and 6-month imaging follow-up). RESULT: The CSI-T1W-Dixon images produced fewer image artifacts in the axial and coronal planes compared to the CMP-T1W-Dixon images. Also, the CSI-T1W-Dixon images provided better a CNR in fat-only images of all three planes and water-only images of the axial plane (p < 0.05). The CSI-T1W-Dixon showed a higher sensitivity than the CMP-T1W-Dixon techniques in analyzing T1-only images on a per-lesion basis (82.7% vs. 53.8% for sensitivity, p = 0.03). On a per-patient basis, no difference was found in the diagnostic capacity between the CSI-T1W-Dixon and CMP-T1W-Dixon sequences either alone or in combinations (p = 0.57-1). CONCLUSION: High-resolution CSI-T1W-Dixon with higher image quality and diagnostic capacity can replace the CMP-T1W-Dixon method in evaluating bone metastasis in clinical practice. KEY POINTS: ⢠Compressed sensing isotropic acquisition for 3D T1-weighted Dixon images can improve the image quality with fewer artifacts compared to the anisotropic multiplanar acquisition. ⢠Compressed sensing isotropic acquisition can save 67% of scanning time compared to anisotropic multiplanar acquisition. ⢠Compressed sensing isotropic 3D T1-weighted Dixon images can offer better diagnostic performance with higher sensitivity compared to anisotropic multiplanar images.
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Imageamento por Ressonância Magnética , Neoplasias da Próstata , Masculino , Humanos , Estudos de Viabilidade , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento Tridimensional/métodos , Razão Sinal-RuídoRESUMO
Polysorbates are nonionic surfactants that have been widely used in biotherapeutic formulations to prevent protein aggregation and denaturation. However, polysorbates are subject to degradation after prolonged storage if certain lipases are present in the biotherapeutic product. Because the degradation of polysorbates compromises the shelf life of biotherapeutics and leads to the formation of undesirable products such as protein aggregates and subvisible particles, it is important to identify the active enzymes that catalyze polysorbate hydrolysis. In this study, we developed a novel fluorophosphonate activity-based protein profiling (ABPP) probe (termed the REGN probe), which mimics the structure of polysorbate and targets lipases catalyzing polysorbate degradation. We demonstrated that the REGN probe could enrich certain lipases from Chinese hamster ovary (CHO) cell lysate by more than 100-fold compared with direct tryptic digestion. Furthermore, we found that the REGN probe had higher lipase enrichment efficiency than commercially available ABPP probes including fluorophosphonate-biotin (FP-biotin) and FP-desthiobiotin. Remarkably, the REGN probe can enrich several lipases that cannot be labeled by commercial probes, such as lysosomal acid lipase and cytosolic phospholipase A2. Additionally, we showed that lipases with abundances as low as 0.08 ppm in drug substances were detected by the REGN probe enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Collectively, we have developed a novel ABPP probe with higher enrichment efficiency and broader coverage for lipases compared with commercial probes, and this probe can be used to detect the trace level of lipases in biotherapeutic products and to facilitate their development and manufacturing.
Assuntos
Polissorbatos , Espectrometria de Massas em Tandem , Animais , Células CHO , Cromatografia Líquida , Cricetinae , Cricetulus , Lipase , Polissorbatos/química , Tensoativos/químicaRESUMO
Aiming at the intrusion detection problem of the wireless sensor network (WSN), considering the combined characteristics of the wireless sensor network, we consider setting up a corresponding intrusion detection system on the edge side through edge computing. An intrusion detection system (IDS), as a proactive network security protection technology, provides an effective defense system for the WSN. In this paper, we propose a WSN intelligent intrusion detection model, through the introduction of the k-Nearest Neighbor algorithm (kNN) in machine learning and the introduction of the arithmetic optimization algorithm (AOA) in evolutionary calculation, to form an edge intelligence framework that specifically performs the intrusion detection when the WSN encounters a DoS attack. In order to enhance the accuracy of the model, we use a parallel strategy to enhance the communication between the populations and use the Lévy flight strategy to adjust the optimization. The proposed PL-AOA algorithm performs well in the benchmark function test and effectively guarantees the improvement of the kNN classifier. We use Matlab2018b to conduct simulation experiments based on the WSN-DS data set and our model achieves 99% ACC, with a nearly 10% improvement compared with the original kNN when performing DoS intrusion detection. The experimental results show that the proposed intrusion detection model has good effects and practical application significance.
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Recently, eicosanoid-lysophospholipids were identified as novel metabolites generated from the direct cyclooxygenase- or lipoxygenase-catalyzed oxidation of 2-arachidonoyl-lysophospholipids produced from either phospholipase A1-mediated hydrolysis of diacyl arachidonoyl-phospholipids or through the cytochrome c-catalyzed oxidative hydrolysis of the vinyl ether linkage of arachidonoyl-plasmalogens. Although the metabolic pathways generating eicosanoid-lysophospholipids have been increasingly appreciated, the signaling functions of eicosanoid-lysophospholipids remain largely unknown. Herein, we demonstrate that 2-12(S)-HETE-lysophospholipids as well as nonesterified 12(S)-HETE are potent lipid mediators that activate THP-1 human monocytic cells to generate tumor necrosis factor α (TNFα) and interleukin 8 (IL8). Remarkably, low nanomolar concentrations of 12(S)-HETE-lysophospholipids, but not other oxidized signaling lipids examined activated THP-1 cells resulting in the production of large amounts of TNFα. Moreover, TNFα release induced by 12(S)-HETE-lysophospholipids was inhibited by the TNFα converting enzyme inhibitor TAPI-0 indicating normal processing of TNFα in THP-1 cells stimulated with these agonists. Western blotting analyses revealed that 12(S)-HETE-lysophospholipids activated the phosphorylation of NFκB p65, suggesting activation of the canonical NFκB signaling pathway. Importantly, activation of THP-1 cells to release TNFα was stereoselective with 12(S)-HETE favored over 12(R)-HETE. Furthermore, the EC50 of 2-12(S)-HETE-lysophosphatidylcholine in activating THP-1 cells was 2.1 nm, whereas the EC50 of free 12(S)-HETE was 23 nm Additionally, lipid extracts of activated platelets were separated by RP-HPLC demonstrating the coelution of 12(S)-HETE with fractions initiating TNFα release. Collectively, these results demonstrate the potent signaling properties of 2-12(S)-HETE-lysophospholipids and 12(S)-HETE by their ability to release TNFα and activate NFκB signaling thereby revealing a previously unknown role of 2-12(S)-HETE-lysophospholipids in mediating inflammatory responses.
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Lisofosfatidilcolinas/metabolismo , Monócitos/metabolismo , Transdução de Sinais , Animais , Ciclo-Oxigenase 1/metabolismo , Humanos , Camundongos , Monócitos/citologia , Células THP-1 , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
It has been suggested that some cancer cells rely upon fatty acid oxidation (FAO) for energy. Here we show that when FAO was reduced approximately 90% by pharmacological inhibition of carnitine palmitoyltransferase I (CPT1) with low concentrations of etomoxir, the proliferation rate of various cancer cells was unaffected. Efforts to pharmacologically inhibit FAO more than 90% revealed that high concentrations of etomoxir (200 µM) have an off-target effect of inhibiting complex I of the electron transport chain. Surprisingly, however, when FAO was reduced further by genetic knockdown of CPT1, the proliferation rate of these same cells decreased nearly 2-fold and could not be restored by acetate or octanoic acid supplementation. Moreover, CPT1 knockdowns had altered mitochondrial morphology and impaired mitochondrial coupling, whereas cells in which CPT1 had been approximately 90% inhibited by etomoxir did not. Lipidomic profiling of mitochondria isolated from CPT1 knockdowns showed depleted concentrations of complex structural and signaling lipids. Additionally, expression of a catalytically dead CPT1 in CPT1 knockdowns did not restore mitochondrial coupling. Taken together, these results suggest that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO.
Assuntos
Carnitina O-Palmitoiltransferase/fisiologia , Proliferação de Células/fisiologia , Inibidores Enzimáticos/farmacologia , Compostos de Epóxi/farmacologia , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral , Transporte de Elétrons/efeitos dos fármacos , Ácidos Graxos/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio , Interferência de RNARESUMO
PURPOSE: To investigate the ability of magnetic resonance (MR) subtraction to evaluate neurovascular conflict (NVC) and to compare it with conventional MR protocols. METHODS: This prospective study included 82 patients with trigeminal neuralgia who underwent microvascular decompression for NVC. All patients had a pre-operative examination using 3T MRI. The MRI protocols used comprised 3D balanced (B)-fast field echo (FFE), 3D steady-state magnetic resonance angiography (MRA), and 3D T1-FFE sequences. MR subtraction images were obtained by subtracting native images from B-FFE and steady-state MRA. NVC evaluation was performed using subtraction images (MR subtraction) and combination images (conventional MR protocols using B-FFE and T1-FFE in combination). Clinical assessment of the degree of compression, the type of compressing vessel, and the location of conflict were undertaken by two independent observers. The two methods were then compared using surgical criteria. RESULTS: MR subtraction exhibited greater accuracy than the conventional method in terms of the estimated severity of conflict (87.80% vs. 57.32%, p < 0.05), and demonstrated better consistency with surgical findings (k = 0.794 vs. k = 0.365, p < 0.05). For the type of compressing vessel and the location of conflict, both methods were highly accurate and agreed to a similar extent with surgical findings (p = 0.987, compressing vessel; p = 0.665, location of conflict). CONCLUSION: MR subtraction proved reliable in NVC pre-operative evaluation, with increased accuracy when estimating severity. This result strongly supports the wider use of MR subtraction as the preferred choice in clinical application.
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Neuralgia do Trigêmeo , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Estudos Prospectivos , Nervo Trigêmeo , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/cirurgiaRESUMO
With the new coronavirus raging around the world, home isolation has become an effective way to interrupt the spread of the virus. Effective monitoring of people in home isolation has also become a pressing issue. However, the large number of isolated people and the privatized isolated spaces pose challenges for traditional sensing techniques. Ubiquitous Wi-Fi offers new ideas for sensing people indoors. Advantages such as low cost, wide deployment, and high privacy make indoor human activity sensing technology based on Wi-Fi signals increasingly used. Therefore, this paper proposes a contactless indoor person continuous activity sensing method based on Wi-Fi signal Wi-CAS. The method allows for the sensing of continuous movements of home isolated persons. Wi-CAS designs an ensemble classification method based on Hierarchical Clustering (HEC) for the classification of different actions, which effectively improves the action classification accuracy while reducing the processing time. We have conducted extensive experimental evaluations in real home environments. By recording the activities of different people throughout the day, Wi-CAS is very sensitive to unusual activities of people and also has a combined activity recognition rate of 94.3%. The experimental results show that our proposed method provides a low-cost and highly robust solution for supervising the activities of home isolates.
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Atividades Humanas , Ambiente Domiciliar , HumanosRESUMO
Recently, oxidized phospholipid species have emerged as important signaling lipids in activated immune cells and platelets. The canonical pathway for the synthesis of oxidized phospholipids is through the release of arachidonic acid by cytosolic phospholipase A2α (cPLA2α) followed by its enzymatic oxidation, activation of the carboxylate anion by acyl-CoA synthetase(s), and re-esterification to the sn-2 position by sn-2 acyltransferase activity (i.e. the Lands cycle). However, recent studies have demonstrated the unanticipated significance of sn-1 hydrolysis of arachidonoyl-containing choline and ethanolamine glycerophospholipids by other phospholipases to generate the corresponding 2-arachidonoyl-lysolipids. Herein, we identified a pathway for oxidized phospholipid synthesis comprising sequential sn-1 hydrolysis by a phospholipase A1 (e.g. by patatin-like phospholipase domain-containing 8 (PNPLA8)), direct enzymatic oxidation of the resultant 2-arachidonoyl-lysophospholipids, and the esterification of oxidized 2-arachidonoyl-lysophospholipids by acyl-CoA-dependent sn-1 acyltransferase(s). To circumvent ambiguities associated with acyl migration or hydrolysis, we developed a synthesis for optically active (d- and l-enantiomers) nonhydrolyzable analogs of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC). sn-1 acyltransferase activity in murine liver microsomes stereospecifically and preferentially utilized the naturally occurring l-enantiomer of the ether analog of lysophosphatidylcholine. Next, we demonstrated the high selectivity of the sn-1 acyltransferase activity for saturated acyl-CoA species. Importantly, we established that 2-15-hydroxyeicosatetraenoic acid (HETE) ether-LPC sn-1 esterification is markedly activated by thrombin treatment of murine platelets to generate oxidized PC. Collectively, these findings demonstrate the enantiomeric specificity and saturated acyl-CoA selectivity of microsomal sn-1 acyltransferase(s) and reveal its participation in a previously uncharacterized pathway for the synthesis of oxidized phospholipids with cell-signaling properties.
Assuntos
Aciltransferases/metabolismo , Ácidos Hidroxieicosatetraenoicos/metabolismo , Lisofosfolipídeos/metabolismo , Fosfolipases/metabolismo , Fosfolipídeos/metabolismo , Acilação , Aciltransferases/genética , Animais , Plaquetas/metabolismo , Ácidos Hidroxieicosatetraenoicos/química , Lisofosfolipídeos/química , Camundongos , Microssomos Hepáticos/metabolismo , Oxirredução , Fosfolipídeos/química , Especificidade por SubstratoRESUMO
Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position. However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive. Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes. Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction. Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue. Furthermore, incorporation of 18O from 18O2 was predominantly located at the α-carbon. In contrast, reactions with H218O yielded 18O linked to the aldehyde carbon. Importantly, no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2 was present. Intriguingly, phosphatidylinositol phosphates (PIP2 and PIP3) effectively substituted for cardiolipin. Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
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Citocromos c/metabolismo , Hidrolases/metabolismo , Mitocôndrias Cardíacas/metabolismo , Estresse Oxidativo , Plasmalogênios/metabolismo , Compostos de Vinila/química , Animais , Citocromos c/química , Cavalos , Humanos , Hidrólise , Lipídeos/análise , Masculino , Oxirredução , Coelhos , Compostos de Vinila/metabolismoRESUMO
Cardiolipin (CL) is a dimeric phospholipid with critical roles in mitochondrial bioenergetics and signaling. Recently, inhibition of the release of oxidized fatty acyl chains from CL by the calcium-independent phospholipase A2γ (iPLA2γ)-selective inhibitor (R)-BEL suggested that iPLA2γ is responsible for the hydrolysis of oxidized CL and subsequent signaling mediated by the released oxidized fatty acids. However, chemical inhibition by BEL is subject to off-target pharmacologic effects. Accordingly, to unambiguously determine the role of iPLA2γ in the hydrolysis of oxidized CL, we compared alterations in oxidized CLs and the release of oxidized aliphatic chains from CL in experiments with purified recombinant iPLA2γ, germ-line iPLA2γ-/- mice, cardiac myocyte-specific iPLA2γ transgenic mice, and wild-type mice. Using charge-switch high mass accuracy LC-MS/MS with selected reaction monitoring and product ion accurate masses, we demonstrated that iPLA2γ is the major enzyme responsible for the release of oxidized aliphatic chains from CL. Our results also indicated that iPLA2γ selectively hydrolyzes 9-hydroxy-octadecenoic acid in comparison to 13-hydroxy-octadecenoic acid from oxidized CLs. Moreover, oxidative stress (ADP, NADPH, and Fe3+) resulted in the robust production of oxidized CLs in intact mitochondria from iPLA2γ-/- mice. In sharp contrast, oxidized CLs were readily hydrolyzed in mitochondria from wild-type mice during oxidative stress. Finally, we demonstrated that CL activates the iPLA2γ-mediated hydrolysis of arachidonic acid from phosphatidylcholine, thereby integrating the production of lipid messengers from different lipid classes in mitochondria. Collectively, these results demonstrate the integrated roles of CL and iPLA2γ in lipid second-messenger production and mitochondrial bioenergetics during oxidative stress.
Assuntos
Cardiolipinas/metabolismo , Metabolismo Energético , Fosfolipases A2 do Grupo VI/metabolismo , Mitocôndrias Cardíacas/enzimologia , Estresse Oxidativo , Transdução de Sinais , Animais , Cardiolipinas/genética , Fosfolipases A2 do Grupo VI/genética , Camundongos , Camundongos Knockout , Mitocôndrias Cardíacas/genética , OxirreduçãoRESUMO
Inspired by the protein folding and DNA packing, we have systematically studied the thermodynamic and kinetic behaviors of single semiflexible homopolymers by Langevin dynamics simulations. In line with experiments, a rich variety of folding products, such as rod-like bundles, hairpins, toroids, and a mixture of them, are observed in the complete diagram of states. Moreover, knotted structures with a significant population are found in a certain range of bending stiffness in thermal equilibrium. As the solvent quality becomes poorer, the population of the intermediate occurring in the folding process increases, which leads to a severe chevron rollover for the folding arm. However, the population of the intermediates in the unfolding process is very low, insufficient to induce unfolding arm rollover. The total types of folding pathways from the coil state to the toroidal state for a semiflexible polymer chain remain unchanged by varying the solvent quality or temperature, whereas the kinetic partitioning into different folding events can be tuned significantly. In the process of knotting, three types of mechanisms, namely, plugging, slipknotting, and sliding, are discovered. Along the folding evolution, a semiflexible homopolymer chain can knot at any stage of folding upon leaving the extended coil state, and the probability to find a knot increases with chain compactness. In addition, we find rich types of knotted topologies during the folding of a semiflexible homopolymer chain. This study should be helpful in gaining insight into the general principles of biopolymer folding.
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To overcome challenges in assessing the impact of environmental factors on heavy metal accumulation in soil due to limited comprehensive data, our study in Yangxin County, Hubei Province, China, analyzed 577 soil samples in combination with extensive big data. We used machine learning techniques, the potential ecological risk index, and the bivariate local Moran's index (BLMI) to predict Cr, Pb, Cd, As, and Hg concentrations in cultivated soil to assess ecological risks and identify pollution sources. The random forest model was selected for its superior performance among various machine learning models, and results indicated that heavy metal accumulation was substantially influenced by environmental factors such as climate, elevation, industrial activities, soil properties, railways, and population. Our ecological risk assessment highlighted areas of concern, where Cd and Hg were identified as the primary threats. BLMI was used to analyze spatial clustering and autocorrelation patterns between ecological risk and environmental factors, pinpointing areas that require targeted interventions. Additionally, redundancy analysis revealed the dynamics of heavy metal transfer to crops. This detailed approach mapped the spatial distribution of heavy metals, highlighted the ecological risks, identified their sources, and provided essential data for effective land management and pollution mitigation.
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Monitoramento Ambiental , Aprendizado de Máquina , Metais Pesados , Poluentes do Solo , Poluentes do Solo/análise , Metais Pesados/análise , Medição de Risco , China , Monitoramento Ambiental/métodos , Solo/químicaRESUMO
Objective: How well cardiovascular risk models perform in selected atherosclerosis patients for predicting outcomes is unknown. We sought to compare the performance of cardiovascular risk models (Framingham, Globorisk, SCORE2 & SCORE2-OP, and an updated new model) in predicting the 4-year outcome of patients with obstructive coronary artery disease (CAD). Methods: Patients with suspected CAD who underwent coronary computed tomography angiography (CCTA) were recruited. Obstructive CAD was defined from CCTA as ≥ 50% stenosis. Computed tomography images, the scores of the cardiovascular risk models, and 4-year composite endpoints were assessed. Whether the patients underwent revascularization within 60 days after CCTA was also recorded. Multivariate regression analysis and receiver operating characteristics (ROC) curve analysis were performed. Results: A total of 95 patients (mean age: 69.5 ± 10.33 years; 69 males) with obstructive CAD were included in this study. After the ROC analysis, the Framingham, Globorisk, SCORE2 & SCORE2-OP risk score showed prediction values with AUC 0.628 (95% CI: 0.532-0.725), 0.647 (95% CI: 0.542-0.742), 0.684 (95% CI: 0.581-0.776), respectively. Multivariate regression analysis showed that, among the three risk models, only SCORE2 & SCORE2-OP risk score was associated with composite endpoints (hazard ratio: 1.050; 95% CI: 1.021-1.079; p = 0.001) after adjusting for confounding factors. The AUC of the new risk model by combing SCORE2 & SCORE2-OP risk score with revascularization and the number of obstructive vessels in predicting composite endpoints reached 0.898 (95% CI: 0.819-0.951). Conclusion: The SCORE2 & SCORE2-OP risk score combined with the number of obstructive vessels and revascularization is predictive for adverse outcomes in patients with obstructive CAD.
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Urease inhibitor (UI) and nitrification inhibitor (NI) can reduce N losses from agricultural soils but effects of inhibitors on N cycle are unclear. A field experiment was conducted with maize to test effects of UI (N-(n-Butyl) thiophosphoric, NBPT) and NI (3,4-dimethylepyrazolephosphate, DMPP) on N uptake and N-cycling soil microbes. Five treatments were imposed: no N fertilizer input (CK), conventional fertilization (CF) and 80% of urea input with NBPT (80%U+UI), with DMPP (80%U+NI) and with half NBPT and half DMPP (80%U+1/2(UI+NI)). There were no significant differences in biomass between 80%U+UI, 80%U+NI and CF but harvest index was increased under 80%U+UI and 80%U+NI. Compared to CF, N use efficiency of grain under 80%U+UI was increased by 7.1%, whereas grain yield and N uptake under 80%U+1/2(UI+NI) were decreased by 8.2% and 9.4%, respectively. The peak soil [Formula: see text] content was at about 15 days after fertilization (DAF) under CF but 30 DAF under the inhibitor treatments. In soils of 80%U+UI, the activities of urease and nitrate reductase were decreased between 15-45 DAF and between 5-30 DAF. The abundance of N-cycling soil microbes was affected: 80%U+UI and 80%U+NI reduced the copies of the amoA AOA and nir genes at about 15 days and reduced the copies of the amoA AOB gene at about 30 days. Correlation analysis indicated that there were significant positive relationships between amoA AOB gene and [Formula: see text], as well as between nirK gene and [Formula: see text]. Overall, urea applied with NBPT has greater potential for improving maize N use efficiency and inhibiting nitrification under reduced fertilizer-N applications.
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Microbiota/efeitos dos fármacos , Nitrogênio/metabolismo , Compostos Organofosforados/administração & dosagem , Ureia/administração & dosagem , Zea mays/efeitos dos fármacos , Zea mays/metabolismo , Agricultura/métodos , Amônia/metabolismo , Biomassa , China , Fertilizantes , Nitrificação/efeitos dos fármacos , Óxido Nitroso/metabolismo , Solo/química , Microbiologia do Solo , Urease/metabolismoRESUMO
The traditional treatment processes for volatile organic compounds (VOCs) removal generally suffered several disadvantages, such as secondary air-pollutants. To overcome these issues, wet scrubber coupled with heterogeneous UV/Fenton was developed for gaseous VOCs (i.e. toluene) removal. ZSM-5 supported iron oxide (Fe/ZSM-5) was prepared as a multifunctional catalyst for activation of H2O2 and enhancement of gas-liquid mass transfer. Toluene was removed efficiently by this coupled process with the removal efficiency of 85% during 120â¯min. Many intermediates were detected in the solution by GC-MS while no intermediates were observed in the outlet gas, suggesting that wet scrubber coupled with heterogeneous UV/Fenton could significantly reduce secondary air pollutants. The possible mechanism of toluene oxidation was proposed including the physical adsorption by Fe/ZSM-5 and OH oxidation. This study provides an environmentally benign and highly efficient chemical scrubbing process for gaseous VOCs removal.
Assuntos
Filtros de Ar , Poluentes Atmosféricos/química , Compostos Orgânicos Voláteis/química , Adsorção , Poluentes Atmosféricos/análise , Catálise , Gases , Peróxido de Hidrogênio/química , Ferro/química , Oxirredução , Tolueno/química , Raios UltravioletaRESUMO
In vitro, kinetically significant non-native interactions have been identified experimentally during the folding of proteins Im7, Im9, and A39V/N53P/V55L Fyn SH3 domain. To understand the role of non-native interactions on the folding of some frustrated proteins in chaperone, we employed native-centric models with and without additional transferable, sequence-dependent non-native hydrophobic interactions to comparatively study the folding behaviors of the three proteins confined in spherical cages. Under purely repulsive confinement, as a decrease of cavity size, the non-native interactions increase, especially in the unfolded state, enhancing the roughness of the folding energy landscape. As a result, the increase in native stability for the three proteins by the model incorporated non-native interactions (db + MJ hÏ model) is much smaller than that by the purely native-centric model (desolvation-barrier (db) model); the acceleration of folding simulated by the db + MJ hÏ model is much slower than that via the db model; in particular, the folding rate of Im7 decreases when reducing the cavity size under zero-denaturant condition. The repulsive confinement can also promote formation of specific non-native contacts in the transition state and favor more folding pathways passing through the misfolded state, leading to a higher population of the misfolded intermediate. In an attractive cage, the attractive interactions could inhibit the formation of intrachain non-native contacts and provide alternate folding pathways to the native state so that the population of the misfolded intermediate decreases when increasing the strength of attractive interaction between the substrate protein and cavity wall. This study should be helpful in general to understand how the chaperonins reshape the folding energy landscape of some frustrated proteins.
Assuntos
Proteínas/química , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Chaperoninas/química , Chaperoninas/metabolismo , Humanos , Modelos Moleculares , Dobramento de Proteína , Proteínas/metabolismo , Termodinâmica , Domínios de Homologia de srcRESUMO
Mulching is critical for increasing water availability and hence winter wheat production in dryland farming systems. A two-year study was conducted to assess the effects of mulches on soil water storage (SWS), temperature, water use efficiency (WUE) and yields of winter wheat on the Loess Plateau. Four treatments were examined: conventional flat planting (CK), straw mulch (FPS), transparent plastic film mulch (FPP) and ridge-furrow with plastic film-mulched ridge and straw-mulched furrow (RFPS). Compared with CK, RFPS greatly increased SWS from 0-60 cm, FPP increased SWS from 0-40 cm, and FPS slightly increased SWS from 0-60 cm; however, FPP significantly (P < 0.05) decreased SWS from 61-100 cm. RFPS and FPP increased soil temperatures in cold seasons relative to CK, especially in RFPS (2.0-2.3 °C). Meanwhile, the rate of soil temperature increase was greater in RFPS and FPP than in CK but was lower in FPS. Mean yields were significantly increased in RFPS (56.78%), FPP (44.72%) and FPS (9.57%), and WUE was significantly increased in RFPS (44.04%) and in FPP (37.50%) compared with CK (P < 0.05). We conclude that ridge-furrow planting with plastic film-mulched ridge and straw-mulched furrow has a good potential for raising winter wheat production on the Loess Plateau.