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The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-Gi complex in the absence of a ligand at 2.58 Å. Structural analysis and comparison revealed that our apo CCR8 structure undergoes some conformational changes and is similar to that in the CCL1-CCR8 complex structure, indicating an active state. In addition, the key residues of CCR8 involved in the recognition of LMD-009, a potent nonpeptide agonist, were investigated by mutating CCR8 and testing the calcium flux induced by LMD-009-CCR8 interaction. Three mutants of CCR8, Y1133.32A, Y1724.64A, and E2867.39A, showed a dramatically decreased ability in mediating calcium mobilization, indicating their key interaction with LMD-009 and key roles in activation. These structural and biochemical analyses enrich molecular insights into the agonism and activation of CCR8 and will facilitate CCR8-targeted therapy.
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Microscopía por Crioelectrón , Receptores CCR8 , Humanos , Receptores CCR8/metabolismo , Receptores CCR8/química , Receptores CCR8/genética , Modelos Moleculares , Conformación Proteica , Calcio/metabolismo , Células HEK293RESUMEN
The synthesis of chiral α-azaheteroaryl oxiranes via enantioselective catalysis is a formidable challenge due to the required complex stereoselectivity and diverse N-heterocyclic structures. These compounds play a crucial role in developing bioactive molecules, where precise chirality significantly influences biological activity. Here we show that using chiral phosphoric acid as a catalyst, our method efficiently addresses these challenges. This technique not only achieves high enantio- and diastereoselectivity but also demonstrates superior chemo- and stereocontrol during the epoxidation of alkenyl aza-heteroarenes. Our approach leverages a synergistic blend of electrostatic and hydrogen-bonding interactions, enabling the effective activation of both substrates and hydrogen peroxide. The resulting chiral oxiranes exhibit enhanced diversity and functionality, aiding the construction of complex chiral azaaryl compounds with contiguous stereocenters. Kinetic and density functional theory studies elucidate the mechanism, highlighting chiral phosphoric acid's pivotal role in this intricate enantioselective process.
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The classification of garbage types is an important issue in today's world, and its proper implementation can contribute to environmental conservation and improved efficiency of recycling processes. Unfortunately, the classification of garbage types is currently predominantly performed through human supervision, which leads to high errors and environmental risks. It is crucial to automate this procedure utilizing machine vision methods as a result. This research proposes a revolutionary deep learning-based strategy for classifying domestic waste. The suggested method uses deep learning methods to extract information from images. The Capuchin Search Algorithm (CapSA) is used to improve the hyperparameters of the convolutional neural network (CNN) used as the feature extraction model. Furthermore, for categorizing the retrieved features from the CNN model, a hybrid learning model based on Error-Correcting Output Codes (ECOC) and Artificial Neural Networks (ANN) is used. The classification accuracy may be successfully increased by using this hybrid model, and the benefit becomes more pronounced as the number of target categories rises. The TrashNet and HGCD databases were used to assess the suggested method's effectiveness, and its results in waste type detection were contrasted with those of earlier techniques. Based on the study findings, the suggested approach can identify trash types with an accuracy of 98.81 % and 99.01 % on the TrashNet and HGCD databases, respectively. This is at least a 1.46 % improvement over earlier approaches. The study's conclusions validate that the suggested strategy may be used in real-world scenarios and show how successful the approaches used in it are.
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Air pollution by sulfur dioxide (SO2) remains a pressing concern for both the environment and human health. Desulfurization enhanced by persulfate based advanced oxidation processes (PS-AOPs) has been proven to be a feasible method. However, the inherent contradiction between the rapid diffusion mass transfer of SO2 in the "gas-liquid-gas" phase and the limited lifespan of reactive oxygen species (ROS) can not be ignored. Excessive investment in PS is required to sustainably generate ROS to achieve continuous desulfurization performance, which may lead to excessive PS consumption. To address this issue, whether PS can achieve the oxidation absorption of SO2 via a non-reactive oxygen species pathway was investigated. Experimental and computational results demonstrated that peroxymonosulfate (PMS) instead of peroxydisulfate (PDS) had a great SO2 removal performance, the utilization of PS could be effectively achieved by maintaining a 1:1 molar ratio of PMS and removed SO2. The presence of HOO bonds in the PMS introduced a partial positive charge to the oxygen atom, making the PMS polar and more susceptible to be attacked by the nucleophile HSO3-. So SO2 underwent a series of processes including dissolution, dissociation, one-oxygen atom transfer, and ionization before ultimately being converted into SO42- ions, effectively achieving its removal from flue gas. This study may presents a novel approach for achieving high-efficiency flue gas desulfurization.
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Edge detection in images is a vital application of image processing in fields such as object detection and identification of lesion regions in medical images. This problem is more complex in the domain of color images due to the combination of color layer information and the need to achieve a unified edge boundary across these layers, which increases the complexity of the problem. In this paper, a simple and effective method for edge detection in color images is proposed using a combination of support vector machine (SVM) and the social spider optimization (SSO) algorithm. In the proposed method, the input color image is first converted to a grayscale image, and an initial estimation of the image edges is performed based on it. To this end, the proposed method utilizes an SVM with a Radial Basis Function (RBF) kernel, in which the model's hyperparameters are tuned using the SSO algorithm. After the formation of initial image edges, the resulting edges are compared with pairwise combinations of color layers, and an attempt is made to improve the edge localization using the SSO algorithm. In this step, the optimization algorithm's task is to refine the image edges in a way that maximizes the compatibility with pairwise combinations of color layers. This process leads to the formation of prominent image edges and reduces the adverse effects of noise on the final result. The performance of the proposed method in edge detection of various color images has been evaluated and compared with similar previous strategies. According to the obtained results, the proposed method can successfully identify image edges more accurately, as the edges identified by the proposed method have an average accuracy of 93.11% for the BSDS500 database, which is an increase of at least 0.74% compared to other methods.
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Landfills are commonly used for waste disposal in many countries, and pose a significant threat of groundwater contamination. Dissolved organic matter (DOM) plays a crucial role as a carbon and energy source, supporting the growth and activity of microorganisms. However, the changes in the DOM signature and microbial community composition in landfill-affected groundwater and their bidirectional relationships remain inadequately explored. Herein, we showed that DOM originating from more recent landfills mainly comprises microbially produced substances resembling tryptophan and tyrosine. Conversely, DOM originating from older landfills predominantly comprises fulvic-like and humic-like compounds. Leachate leakage increases microbial diversity and richness and facilitates the transfer of foreign bacteria from landfills to groundwater, thereby increasing the vulnerability of the microbial ecosystem in groundwater. Deterministic processes dominated the assembly of the groundwater microbial community, while stochastic processes accounted for an increased proportion of the microbial community in the old landfills. The dominant phyla observed in groundwater were Proteobacteria, Bacteroidota, and Actinobacteriota, and humic-like substances play a crucial role in driving the variation in microbial communities in landfill-affected groundwater. Predictions using PICRUSt2 suggested significant associations between various metabolic pathways and microbial communities, with the Kyoto Encyclopedia of Genes and Genomes pathway "Metabolism" being the most predominant. The findings contribute to advancing our understanding of the transformation of DOM and its interplay with microbial communities and can serve as a scientific reference for decision-making regarding groundwater pollution monitoring and remediation.
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Agua Subterránea , Sustancias Húmicas , Contaminantes Químicos del Agua , Agua Subterránea/microbiología , Agua Subterránea/química , Sustancias Húmicas/análisis , Contaminantes Químicos del Agua/análisis , Instalaciones de Eliminación de Residuos , Microbiota , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificaciónRESUMEN
As an energy-storage substance of microorganisms, polyhydroxybutyrate (PHB) is a promising alternative to petrochemical polymers. Under appropriate fermentation conditions, PHB-producing strains with metabolic diversity can efficiently synthesize PHB using various carbon sources. Carbon-rich wastes may serve as alternatives to pure sugar substrates to reduce the cost of PHB production. Genetic engineering strategies can further improve the efficiency of substrate assimilation and PHB synthesis. In the downstream link, PHB recycling strategies based on green chemistry concepts can replace PHB extraction using chlorinated solvents to enhance the economics of PHB production and reduce the potential risks of environmental pollution and health damage. To avoid carbon loss caused by biodegradation in the traditional sense, various strategies have been developed to degrade PHB waste into monomers. These monomers can serve as platform chemicals to synthesize other functional compounds or as substrates for PHB reproduction. The sustainable potential and cycling value of PHB are thus reflected. This review summarized the recent progress of strains, substrates, and fermentation approaches for microbial PHB production. Analyses of available strategies for sustainable PHB recycling were also included. Furthermore, it discussed feasible pathways for PHB waste valorization. These contents may provide insights for constructing PHB-based comprehensive biorefinery systems.
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Polihidroxibutiratos , Polímeros , Polímeros/química , Fermentación , Carbohidratos , Carbono/química , Hidroxibutiratos/análisis , Hidroxibutiratos/química , Hidroxibutiratos/metabolismoRESUMEN
Objective. In this study, nonlinearly frequency-modulated (NLFM) ultrasound was applied to magneto-acousto-electrical tomography (MAET) to increase the dynamic range of detection.Approach. Generation of NLFM signals using window function method-based on the principle of stationary phase-and piecewise linear frequency modulation method-based on the genetic algorithm-was discussed. The MAET experiment systems using spike, linearly frequency-modulated (LFM), or NLFM pulse stimulation were constructed, and three groups of MAET experiments on saline agar phantom samples were carried out to verify the performance-respectively the sensitivity, the dynamic range, and the longitudinal resolution of detection-of MAET using NLFM ultrasound in comparison to that using LFM ultrasound. Based on the above experiments, a pork sample was imaged by ultrasound imaging method, spike MAET method, LFM MAET method, and NLFM MAET method, to compare the imaging accuracy.Main results. The experiment results showed that, through sacrificing very little main-lobe width of pulse compression or equivalently the longitudinal resolution, the MAET using NLFM ultrasound achieved higher signal-to-interference ratio (and therefore higher detection sensitivity), lower side-lobe levels of pulse compression (and therefore larger dynamic range of detection), and large anti-interference capability, compared to the MAET using LFM ultrasound.Significance. The applicability of the MAET using NLFM ultrasound was proved in circumferences where sensitivity and dynamic range of detection were mostly important and slightly lower longitudinal resolution of detection was acceptable. The study furthered the scheme of using coded ultrasound excitation toward the clinical application of MAET.
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Electricidad , Tomografía , Tomografía/métodos , Ultrasonografía/métodos , Fantasmas de Imagen , Tomógrafos Computarizados por Rayos XRESUMEN
Motion recognition (MR)-based somatosensory interaction technology, which interprets user movements as input instructions, presents a natural approach for promoting human-computer interaction, a critical element for advancing metaverse applications. Herein, this work introduces a non-intrusive muscle-sensing wearable device, that in conjunction with machine learning, enables motion-control-based somatosensory interaction with metaverse avatars. To facilitate MR, the proposed device simultaneously detects muscle mechanical activities, including dynamic muscle shape changes and vibrational mechanomyogram signals, utilizing a flexible 16-channel pressure sensor array (weighing ≈0.38 g). Leveraging the rich information from multiple channels, a recognition accuracy of ≈96.06% is achieved by classifying ten lower-limb motions executed by ten human subjects. In addition, this work demonstrates the practical application of muscle-sensing-based somatosensory interaction, using the proposed wearable device, for enabling the real-time control of avatars in a virtual space. This study provides an alternative approach to traditional rigid inertial measurement units and electromyography-based methods for achieving accurate human motion capture, which can further broaden the applications of motion-interactive wearable devices for the coming metaverse age.
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Músculo Esquelético , Dispositivos Electrónicos Vestibles , Humanos , Músculo Esquelético/fisiología , Electromiografía/métodos , Electromiografía/instrumentación , Miografía/métodos , Miografía/instrumentación , Adulto , Masculino , Inteligencia Artificial , Diseño de EquipoRESUMEN
Rice blast is one of the most devastating diseases, causing a significant reduction in global rice production. Developing and utilizing resistant varieties has proven to be the most efficient and cost-effective approach to control blasts. However, due to environmental pressure and intense pathogenic selection, resistance has rapidly broken down, and more durable resistance genes are being discovered. In this paper, a novel wall-associated kinase (WAK) gene, Pb4, which confers resistance to rice blast, was identified through a genome-wide association study (GWAS) utilizing 249 rice accessions. Pb4 comprises an N-terminal signal peptide, extracellular GUB domain, EGF domain, EGF-Ca2+ domain, and intracellular Ser/Thr protein kinase domain. The extracellular domain (GUB domain, EGF domain, and EGF-Ca2+ domain) of Pb4 can interact with the extracellular domain of CEBiP. Additionally, its expression is induced by chitin and polygalacturonic acid. Furthermore, transgenic plants overexpressing Pb4 enhance resistance to rice blast. In summary, this study identified a novel rice blast-resistant gene, Pb4, and provides a theoretical basis for understanding the role of WAKs in mediating rice resistance against rice blast disease.
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Factor de Crecimiento Epidérmico , Estudio de Asociación del Genoma Completo , Quitina , Leucocitos , Plantas Modificadas Genéticamente/genéticaRESUMEN
Pancreatic cancer is a deadly disease that is largely resistant to immunotherapy, in part because of the accumulation of immunosuppressive cells in the tumor microenvironment (TME). Much evidence suggests that tumor-derived exosomes (TDE) contribute to the immunosuppressive activity mediated by myeloid-derived suppressor cells (MDSC) within the pancreatic cancer TME. However, the underlying mechanisms remain elusive. Herein, we report that macrophage migration inhibitory factor (MIF) in TDEs has a key role in inducing MDSC formation in pancreatic cancer. We identified MIF in both human and murine pancreatic cancer-derived exosomes. Upon specific shRNA-mediated knockdown of MIF, the ability of pancreatic cancer-derived exosomes to promote MDSC differentiation was abrogated. This phenotype was rescued by reexpression of the wild-type form of MIF rather than a tautomerase-null mutant or a thiol-protein oxidoreductase-null mutant, indicating that both MIF enzyme activity sites play a role in exosome-induced MDSC formation in pancreatic cancer. RNA sequencing data indicated that MIF tautomerase regulated the expression of genes required for MDSC differentiation, recruitment, and activation. We therefore developed a MIF tautomerase inhibitor, IPG1576. The inhibitor effectively inhibited exosome-induced MDSC differentiation in vitro and reduced tumor growth in an orthotopic pancreatic cancer model, which was associated with decreased numbers of MDSCs and increased infiltration of CD8+ T cells in the TME. Collectively, our findings highlight a pivotal role for MIF in exosome-induced MDSC differentiation in pancreatic cancer and underscore the potential of MIF tautomerase inhibitors to reverse the immunosuppressive pancreatic cancer microenvironment, thereby augmenting anticancer immune responses.
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Factores Inhibidores de la Migración de Macrófagos , Células Supresoras de Origen Mieloide , Neoplasias Pancreáticas , Animales , Humanos , Ratones , Diferenciación Celular , Línea Celular Tumoral , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Microambiente TumoralRESUMEN
BACKGROUND: Necroptosis induced by receptor-interacting protein kinase 3 (RIPK3) is engaged in intracerebral hemorrhage (ICH) pathology. In this study, we explored the impact of RIPK3 activation on neuronal necroptosis and the mechanism of the death domain-associated protein (DAXX)-mediated nuclear necroptosis pathway after ICH. METHODS: Potential molecules linked to the progression of ICH were discovered using RNA sequencing. The level of DAXX was assessed by quantitative real-time PCR, ELISA, and western blotting. DAXX localization was determined by immunofluorescence and immunoprecipitation assays. The RIPK3 inhibitor GSK872 and DAXX knockdown with shRNA-DAXX were used to examine the nuclear necroptosis pathway associated with ICH. Neurobehavioral deficit assessments were performed. RESULTS: DAXX was increased in patients and mice after ICH. In an ICH mouse model, shRNA-DAXX reduced brain water content and alleviated neurologic impairments. GSK872 administration reduced the expression of DAXX. shRNA-DAXX inhibited the expression of p-MLKL. Immunofluorescence and immunoprecipitation assays showed that RIPK3 and AIF translocated into the nucleus and then bound with nuclear DAXX. CONCLUSIONS: RIPK3 revitalization promoted neuronal necroptosis in ICH mice, partially through the DAXX signaling pathway. RIPK3 and AIF interacted with nuclear DAXX to aggravate ICH injury.
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Necroptosis , Proteínas Quinasas , Animales , Humanos , Ratones , Encéfalo/metabolismo , Hemorragia Cerebral , Proteínas Co-Represoras/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas Quinasas/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
GPR183 is required for humoral immune responses, and its polymorphisms have been associated with inflammatory autoimmune diseases. Despite increasing attention to GPR183 as a potential therapeutic target for autoimmune diseases, relatively few antagonists have been reported, and none of them have progressed to the clinical stage. In this study, we discovered a highly potent GPR183 antagonist, compound 32, with good aqueous solubility, excellent selectivity, and pharmacokinetic properties. Meanwhile, compound 32 showed exceptional efficacy for rheumatoid arthritis (RA) disease in a mouse collagen-induced arthritis (CIA) model, with an efficacious dose of 0.1 mg/kg. Functionally, compound 32 significantly reduced the swelling of paws and joints, the gene expression of proinflammatory cytokines, MCP-1, MMPs, and VEGF, inflammatory cell infiltration, cartilage damage, pannus formation, and bone erosion in the joints of CIA mice in a dose-dependent manner. Hence, these findings suggest compound 32 as a valuable molecule for further development.
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Artritis Experimental , Artritis Reumatoide , Ratones , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Modelos Animales de Enfermedad , Citocinas/metabolismoRESUMEN
Ginger (Zingiber officinale) is an important commercial crop that has been widely cultivated in China for more than 2500 years. One variety, Tongling white ginger, has been grown in the Yi'an District of Tongling city, Anhui province (30°45 N, 117°43 E), China. In August 2022, symptoms of yellowing and wilting were observed on ginger plants, with a disease incidence rate exceeding 20% in the field. The stem base of the diseased plants became soft, brown and water-soaked. Additionally, the rhizomes displayed symptoms of browning and water-soaked rot, resembling those caused by Ralstonia solanacearum and Enterobacter cloacae (Yu et al. 2003; Nishijima et al. 2004; Liu et al. 2021). Consequently, ginger bacterial wilt disease may potentially emerge from a combination of infections by diverse pathogenic bacteria. To identify novel pathogens causing the wilt disease, stem tissues of the diseased plants from different locations were sterilized with 1% sodium hypochlorite (NaOCl) for 10 min, followed by at least three time rinses with sterile water. The sterilized samples were then ground with 0.9% saline solution and left at room temperature for 30 min. A 20 µL aliquot of the suspension was serially diluted and cultured on Luria-Bertani (LB) medium at 28°C. A total of 217 isolates was picked and purified for taxonomic identification by 16S rRNA gene analyses with the primer 27F/1492R (Weisburg et al. 1991). Among these isolates, 23 single colony isolates were identified as A. xylosoxidans through NCBI BLASTn analyses. Furthermore, three single isolates from different locations were randomly selected for further experiments. The growing colonies appeared opaque white and round. Microscopic evaluation revealed that cells were rod-shaped with an average length of 1.95 µm and average width of 0.46 µm. The three isolates shared identical 16S rRNA sequences, displayed 99.72% identity with the sequence from A. xylosoxidans strain SeqID2 (GenBank accession NO. MH266081.1). The glutamate synthase (gltB), GTP-binding membrane protein (lepA), NADH:ubiquinone oxidoreductase subunit L (nuoL), RNA polymerase beta-subunit (rpoB), and the enolase (eno) genes of the three isolates were amplified by PCR using primer pairs gltB-F/gltB-R, lepA-F/lepA-R, nuoL-F/nuoL-R, rpoB-F/rpoB-R and eno-F/eno-R, respectively (Spilker et al. 2012; Vandamme et al. 2016). The gene sequences of 16S rRNA (OQ711945, OQ740153 and OR230037), gltB (OR242732, OQ737692 and OR262112), lepA (OR233727, OQ737693 and OR262113), nuoL (OR233726, OQ737694 and OR262114), ropB (OR233725, OQ737695 and OR262115) and eno (OR242733, OQ737696 and OR262116) for the isolates ZOR02, ZOR05 and ZOR12 were deposited in GenBank database. The gltB, lepA, nuoL, rpoB and eno sequences of the isolates ZOR02, ZOR05 and ZOR12 showed 98.66-99.16%, 98.9-100%, 96.28%-97.34%, 98.47-99.44% and 99.27-99.82% similarity to A. xylosoxidans strain AX27, respectively. Phylogenetic trees were constructed based on the 16S rRNA and gltB-lepA-nuoL-rpoB-eno multilocus using the Neighbor-Joining (NJ) method with 1000 bootstrap replicates in MEGA11.0 software (Álvarez et al. 2018). For pathogenicity tests, bacterial suspensions were initially prepared in sterile water at a final concentration of 108 CFU mL-1. Subsequently, 10 µL of bacterial suspensions was injected into the stem base of two-month-old ginger plants, while sterile water was used as a control (Wang et al. 2022). These plants were then incubated at 28°C and 70% relative humidity. There were three replicates for each treatment, and each replicate contained five plants. After six days of inoculation, the ginger plants injected with bacterial suspensions alone exhibited severe wilting symptoms similar to those observed in the field. However, water-soaked symptoms were not observed on rhizome tissues from the pathogen-infected plants. Bacterial pathogens were re-isolated from the diseased plants and identified using the morphological and molecular methods to meet Koch's hypothetical tests. To our knowledge, this is the first report of A. xylosoxidans causing wilt disease of ginger in China. In 2022, the average yield loss due to wilt disease in the Yi'an District of Tongling exceeded 20%, posing a major threat to local ginger cultivation. Effective disease management strategies are needed to develop for the control and prevention of the disease.
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Introduction: G-protein coupled receptor 30 (GPR30) is associated with cell metastasis and drug resistance in many different cancer cells. The present study aimed to reveal the sensitivity of GPR30 to gefitinib in non-small cell lung cancer (NSCLC) cells.Methods: Cell viability and proliferation were detected using cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays, respectively. Western blotting and quantitative real-time reverse transcription PCR were used to detect GPR30 or epithelial-mesenchyme transition (EMT)-related mRNA and protein expression.Results: The results showed that GPR30 expression is associated with gefitinib sensitivity. G15, as a GPR30 antagonist, reduced GPR30 expression. We chose the maximum concentration of G15 with minimal cytotoxicity to detect cell viability after combined treatment with gefitinib in NSCLC cells, which indicated that G15 could increase sensitivity to gefitinib. However, the effect of G15 on gefitinib sensitivity disappeared after treatment with a small interfering RNA targeting GPR30. Further research showed that G15 or GPR30 siRNA treatment could upregulate E-cadherin and downregulate vimentin levels.Conclusion: Taken together, these data suggested that G15 could enhance NSCLC sensitivity to gefitinib by inhibition of GPR30 and EMT.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Gefitinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Transición Epitelial-Mesenquimal , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , ARN Interferente Pequeño , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/uso terapéutico , Proliferación CelularRESUMEN
This study was designed to investigate the effect on wheat yield of applying organic fertilizers (OF) with five different selenium (Se) concentrations. The mineral nutrients, cadmium (Cd) content, and the distribution of Se in wheat plants were also measured. The results showed that wheat yields reached a maximum of 9979.78 kg ha-1 in Mengcheng (MC) County and 8868.97 kg ha-1 in Dingyuan (DY) County, Anhui Province, China when the application amount of selenium-containing organic fertilizer (SOF) was up to 600 kg ha-1. Among the six mineral nutrients measured, only the calcium (Ca) content of the grains significantly increased with an increase in the application amount of SOF in the two regions under study. Cd content showed antagonistic effects with the Se content of wheat grains, and when the SOF was applied at 1200 kg ha-1, the Cd content of the grains was significantly reduced by 30.1% in MC and 67.3% in DY, compared with under the Se0 treatment. After application of SOF, the Se content of different parts of the wheat plant ranked root > grain > spike-stalk > glume > leaf > stem. In summary, SOF application at a suitable concentration could increase wheat yields and significantly promote the Ca content of the grains. Meanwhile, the addition of Se effectively inhibited the level of toxic Cd in the wheat grains.
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This study explored the effect of the long-term partial replacement of chemical fertilizer with organic fertilizer on soil organic carbon composition, enzyme activity, and crop yields in the wheat-maize rotation area of northern Anhui, China. This study also specified the proper amount of organic fertilizer replacement that should be used for chemical fertilizer. Different fertilization modes were used (no fertilization, CK; chemical fertilizer, CF; chemical fertilizer and straw returning, CF + S; chemical fertilizer, straw returning, and straw decomposition agent, CF + S + DA; 70% chemical fertilizer and 50% organic fertilizer, 70% CF + 50% OF; 70% chemical fertilizer, 50% organic fertilizer and straw returning, 70% CF + 50% OF + S; 50% chemical fertilizer and 100% organic fertilizer, 50% CF + 100% OF; and 50% chemical fertilizer, 100% organic fertilizer, and straw returning, 50% CF + 100% OF + S). Variations in the organic carbon composition, enzyme activity, soil pH, and crop yields in the wheat-maize rotation under different fertilization treatments were analyzed. The results showed that the replacement of chemical fertilizer with organic fertilizer results in improved crop yields in wheat-maize rotation. The long-term partial replacement of chemical fertilizer with organic fertilizer can increase the quality of soil humus, alleviate soil acidification, and improve soil enzyme activity. Straw returning and organic fertilizer application can considerably raise the activities of urease, acid phosphatase, and nitrate reductase in soil. The soil pH of the CF treatment was reduced compared to the CK treatment, while organic fertilizer application alleviated soil acidification when compared to CF treatment. Organic fertilization increases the total organic carbon content of the soil, which was 19.6~85.5% higher than in the CK treatment. Applying straw and organic fertilizer significantly increased the ratio of the humic/fulvic acid in the soil. The soil active carbon forms of the soil with the application of organic fertilizer and straw returning were significantly higher than those of the CK and CF treatments. This study suggests that the optimal fertilizer management option in northern Anhui's wheat-maize rotation area is to replace 50% of the chemical fertilizer with organic fertilizer, and to fully return straw to the field. This would include 150 kg N h·m-2, 60 kg P2O5 h·m-2, 50 kg K2O h·m-2, 6000 kg organic fertilizer h·m-2, and full straw return to the field.
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CD38 is a crucial NADase in mammalian tissues that degrades NAD+ and thus regulates cellular NAD+ levels. Abnormal CD38 expression is linked to mitochondrial dysfunction under several pathological conditions. We present a novel CD38 inhibitor, compound 1, with high potency for CD38 (IC50 of 11 nM) and minimal activity against other targets. In a Pus1 knockout (Pus1-/-) mouse model of mitochondrial myopathy, compound 1 treatment rescued the decline in running endurance in a dose-dependent manner, associated with an elevated NAD+ level in muscle tissue, increased expression of Nrf2, which is known to promote mitochondrial biogenesis, and reduced lactate production. RNA sequencing data indicated that compound 1 has a great effect on mitochondrial function, metabolic processes, muscle contraction/development, and actin filament organization via regulating the expression of relevant genes. Compound 1 is a promising candidate for its excellent in vivo efficacy, favorable pharmacokinetics, and attractive safety profile.
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The use of persulfate (PDS) for in-situ chemical oxidation of organic contaminants in soils has garnered significant interest. However, the presence of naturally occurring iron-containing substances and humic acid (HA) in environmental compartments can potentially influence the effectiveness of soil remediation. Thus, this study aimed to investigate the role of key functional groups (adjacent phenolic hydroxyl (Ar-OH) and carboxyl groups (-COOH)) in HA that interact with iron. Modified HAs were used to confirm the significance of these moieties in iron interaction. Additionally, the mechanism by which specific functional groups affect Fe complexation and redox was explored through contaminant degradation experiments, pH-dependent investigations, HA by-products analysis, and theoretical calculations using six specific hydroxybenzoic acids as HA model compounds. The results showed a strong positive correlation between accessible Ar-OH and -COOH groups and Fe3+/Fe2+ redox. This was attributed to HA undergoing a conversion process to a semiquinone-containing radical form, followed by a quinone-containing intermediate, while Fe3+ acted as an electron shuttle between HA and PDS, with Fe3+ leaching facilitated by generated H+ ions. Although the stability of HA-Fe3+ complexes with -COOH as the primary binding sites was slightly higher at neutral/alkaline conditions compared to acidic conditions, the buffering properties of the soil and acidification of the PDS solution played a greater role in determining the Ar-OH groups as the primary binding site in most cases. Therefore, the availability of Ar-OH groups on HA created a trade-off between accelerated Fe3+/Fe2+ redox and quenching reactions. Appropriate HA and iron contents were found to favor PDS activation, while excessive HA could lead to intense competition for reactive oxygen species (ROS), inhibiting pollutant degradation in soil. The findings provide valuable insights into the interaction of HA and Fe-containing substances in persulfate oxidation, offering useful information for the development of in-situ remediation strategies for organic-contaminated soil.