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G-quadruplex (G4) structures are found in eukaryotic cell replication origins, but their role in origin function remains unclear. In this study G4 motifs are found in the lytic DNA replication origin (oriLyt) of human cytomegalovirus (HCMV) and recombinant viruses show that a G4 motif in oriLyt essential region I (ER-I) is necessary for viral growth. Replication assays of oriLyt-containing plasmids and biochemical/biophysical analyses show that G4 formation in ER-I is crucial for viral DNA replication. G4 pull-down analysis identifies viral DNA replication factors, such as IE2, UL84, and UL44, as G4-binding proteins. In enzyme-linked immunosorbent assays, specific G4-binding ligands inhibit G4 binding by the viral proteins. The Epstein-Barr virus oriLyt core element also forms a stable G4 that could substitute for the oriLyt ER-I G4 in HCMV. These results demonstrate that viral G4s in replication origins represent an essential structural element in recruiting replication factors and might be a therapeutic target against viral infections.
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Citomegalovirus , Replicación del ADN , ADN Viral , G-Cuádruplex , Proteínas Inmediatas-Precoces , Origen de Réplica , Proteínas Virales , Replicación Viral , Citomegalovirus/genética , Citomegalovirus/fisiología , Humanos , Replicación Viral/genética , Origen de Réplica/genética , Proteínas Virales/metabolismo , Proteínas Virales/genética , Proteínas Inmediatas-Precoces/metabolismo , Proteínas Inmediatas-Precoces/genética , ADN Viral/genética , ADN Viral/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiología , Unión ProteicaRESUMEN
Introduction: Upper limb rehabilitation assessment plays a pivotal role in the recovery process of stroke patients. The current clinical assessment tools often rely on subjective judgments of healthcare professionals. Some existing research studies have utilized physiological signals for quantitative assessments. However, most studies used single index to assess the motor functions of upper limb. The fusion of surface electromyography (sEMG) and functional near-infrared spectroscopy (fNIRS) presents an innovative approach, offering simultaneous insights into the central and peripheral nervous systems. Methods: We concurrently collected sEMG signals and brain hemodynamic signals during bilateral elbow flexion in 15 stroke patients with subacute and chronic stages and 15 healthy control subjects. The sEMG signals were analyzed to obtain muscle synergy based indexes including synergy stability index (SSI), closeness of individual vector (CV) and closeness of time profile (CT). The fNIRS signals were calculated to extract laterality index (LI). Results: The primary findings were that CV, SSI and LI in posterior motor cortex (PMC) and primary motor cortex (M1) on the affected hemisphere of stroke patients were significantly lower than those in the control group (p < 0.05). Moreover, CV, SSI and LI in PMC were also significantly different between affected and unaffected upper limb movements (p < 0.05). Furthermore, a linear regression model was used to predict the value of the Fugl-Meyer score of upper limb (FMul) (R2 = 0.860, p < 0.001). Discussion: This study established a linear regression model using force, CV, and LI features to predict FMul scale values, which suggests that the combination of force, sEMG and fNIRS hold promise as a novel method for assessing stroke rehabilitation.
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Mildew poses a significant threat to tobacco production; however, there is limited information on the structure of the abundant and rare microbial subcommunities in moldy tobacco leaves. In this study, we employed high-throughput sequencing technology to discern the disparities in the composition, diversity, and co-occurrence patterns of abundant and rare fungal and bacterial subcommunities between moldy and normal tobacco leaves collected from Guizhou, Shanghai, and Jilin provinces, China. Furthermore, we explored the correlation between microorganisms and metabolites by integrating the metabolic profiles of moldy and normal tobacco leaves. The results showed that the fungi are more sensitive to mildew than bacteria, and that the fungal abundant taxa exhibit greater resistance and environmental adaptability than the rare taxa. The loss of rare taxa results in irreversible changes in the diversity, richness, and composition of the fungal community. Moreover, rare fungal taxa and abundant bacterial taxa played crucial roles in maintaining the stability and functionality of the tobacco microecosystem. In moldy tobacco, however, the disappearance of rare taxa as key nodes resulted in reduced connectivity and stability within the fungal network. In addition, metabolomic analysis showed that the contents of indoles, pyridines, polyketones, phenols, and peptides were significantly enriched in the moldy tobacco leaves, while the contents of amino acids, carbohydrates, lipids, and other compounds were significantly reduced in these leaves. Most metabolites showed negative correlations with Dothideomycetes, Alphaproteobacteria, and Gammaproteobacteria, but showed positive correlations with Eurotiales and Bacilli. This study has demonstrated that abundant fungal taxa are the predominant biological agents responsible for tobacco mildew, while bacteria may indirectly contribute to this process through the production and degradation of metabolites. KEY POINTS: ⢠Fungi exhibited greater sensitivity to mildew of tobacco leaf compared to bacteria ⢠Rare fungal taxa underwent significant damage during the mildew process ⢠Mildew may damage the defense system of the tobacco leaf microecosystem.
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Bacillus , Micobioma , China , Bacterias/genética , Hongos/genética , NicotianaRESUMEN
Colorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. Circular RNAs may play important roles in the progression of CRC. In this study, we investigated the roles and mechanisms of action of circ-MALAT1 in CRC. Gene expression and protein abundance were determined using qRT-PCR and western blot, respectively. Cell proliferation and migration were assessed by MTT, clone formation, and wound-healing assays. The interactions among the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (circ-MALAT1), miR-506-3p, and lysine acetyltransferase 6B (KAT6B) were predicted using the StarBase software and confirmed by the luciferase activity assay. Circ-MALAT1 and KAT6B were upregulated, while miR-506-3p was downregulated in CRC cells. We validated that knocking down of circ-MALAT1 suppressed proliferation, migration, and epithelial-mesenchymal transition (EMT) of CRC cells, and these effects were abolished by miR-506-3p downregulation or KAT6B sufficiency. Our study suggests that circ-MALAT1 could sponge miR-506-3p to regulate the expression of KAT6B. Moreover, KAT6B sufficiency could neutralize miR-506-3p-dependent growth arrest, migration, and EMT. Circ-MALAT1 promotes cell proliferation, migration, and EMT of CRC cells via the miR-506-3p/KAT6B axis, thereby acting as a novel potential therapeutic target for the treatment of colorectal cancer.
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Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Transición Epitelial-Mesenquimal/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Proliferación Celular/genética , Movimiento Celular/genética , Histona AcetiltransferasasRESUMEN
Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in ß-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD.
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Varicella-Zoster virus (VZV) causes varicella in primary infection of children and zoster during reactivation in adults. Type I interferon (IFN) signaling suppresses VZV growth, and stimulator of interferon genes (STING) plays an important role in anti-VZV responses by regulating type I IFN signaling. VZV-encoded proteins are shown to inhibit STING-mediated activation of the IFN-ß promoter. However, the mechanisms by which VZV regulates STING-mediated signaling pathways are largely unknown. In this study, we demonstrate that the transmembrane protein encoded by VZV open reading frame (ORF) 39 suppresses STING-mediated IFN-ß production by interacting with STING. In IFN-ß promoter reporter assays, ORF39 protein (ORF39p) inhibited STING-mediated activation of the IFN-ß promoter. ORF39p interacted with STING in co-transfection assays, and this interaction was comparable to that of STING dimerization. The cytoplasmic N-terminal 73 amino acids region of ORF39P was not necessary for ORF39 binding and suppression of STING-mediated IFN-ß activation. ORF39p also formed a complex containing both STING and TBK1. A recombinant VZV expressing HA-tagged ORF39 was produced using bacmid mutagenesis and showed similar growth to its parent virus. During HA-ORF39 virus infection, the expression level of STING was markedly reduced, and HA-ORF39 interacted with STING. Moreover, HA-ORF39 also colocalized with glycoprotein K (encoded by ORF5) and STING at the Golgi during virus infection. Our results demonstrate that the transmembrane protein ORF39p of VZV plays a role in evading the type I IFN responses by suppressing STING-mediated activation of the IFN-ß promoter.
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Herpes Zóster , Interferón beta , Proteínas de la Membrana , Humanos , Herpesvirus Humano 3/genética , Interferón beta/genética , Interferón beta/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Regiones Promotoras Genéticas , Transducción de SeñalRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PADA) represents a devastating type of pancreatic cancer with high mortality. Defining a prognostic gene signature that can stratify patients with different risk will benefit cancer treatment strategies. METHODS: Gene expression profiles of PADA patients were acquired from the Cancer Genome Atlas and Gene Expression Omnibus, including GSE62452 and GSE28735. Differential expression analysis was carried out using the package edgeR in R. Intro-tumor immune infiltrates were quantified by six different computational algorithms XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT. Biological processes were investigated based on R package "clusterProfiler". RESULTS: 13 genes (ARNTL2, BHLHE40, FBXL17, FBXL8, PPP1CB, RBM4B, ADRB1, CCAR2, CDK1, CSNK1D, KLF10, PSPC1, SIAH2) were eligible for the development of a prognostic gene signature. Performance of the prognostic gene signature was assessed in the discovery set (n = 210), validation set (n = 52), and two external data set (GSE62452, n = 65, and GSE28735, n = 84). Area under the curve (AUC) for predicting 3-year overall survival was 0.727, 0.732, 0.700, and 0.658 in the training set, the validation set, and the two test sets, respectively. KM curve revealed that the low-risk group had an improved prognosis than the high-risk group in all four datasets. PCA analysis demonstrated that the low-risk group was apparently separated from the high-risk group. CD8 T cell and B cell were significantly reduced in the high-risk group than in the low-risk group, while neutrophils were significantly augmented in the high-risk group than in the low-risk group. BMS-536924, Foretinib, Linsitinib, and Sabutoclax were more sensitive in the low-risk group, whereas Erlotinib was more effective in the high-risk group. CONCLUSIONS: We successfully established and verified a novel circadian clock-related gene signature, which could stratify patients with different risk and be reflective of the therapeutic effect of molecular targeted therapy. Our findings could incorporate the pharmacological modulation of circadian clock into future therapeutic strategies.
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Carcinoma Ductal Pancreático , Relojes Circadianos , Neoplasias Pancreáticas , Humanos , Pronóstico , Terapia Molecular Dirigida , Relojes Circadianos/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Inmunidad , Proteínas de Unión al ARN , Proteínas Adaptadoras Transductoras de Señales , Neoplasias PancreáticasRESUMEN
Objective: To study the chemical constituents from the leaves and twigs of Callicarpa cathayana. Methods: The chemical constituents were isolated and purified by column chromatography on silica gel, MCI gel CHP 20P/P120, Sephadex LH-20, and HPLC. The structures of the compounds were determined by HR-ESI-MS, 1D and 2D NMR data. Results: A total of 24 compounds were isolated from the 85% methanol extract of leaves and twigs of C. cathayana. They were identified as cathayanalactone G (1), a new diterpene, and 23 known compounds as patagonic acid (2), (-)-16-hydroxycledroda-3,13-dien-16,15-olide-18-oic acid (3), 15-methoxypatagonic acid (4), oleanolic acid (5), ursolic acid (6), siaresinolic acid (7), pomolic acid (8), α-amyrin (9), tormentic acid (10), lupeol (11), 5,7-dihydroxy-3,4'-dimethoxyflavone (12), 5,4'-dihydroxy-3,7,3'-dimethoxyfla-vone (13), 5-hydroxy-3,6,7,4'- tetramethoxyflavone (14), salvigenin (15), kaemferol (16), astragalin (17), pinoresinol 4-O-ß-D-glucopyranoside (18), paulownin (19), ß-sitosterol (20), ß-sitosterol ß-D-glucopyranoside (21), 5-hydroxy-coumarin (22), isocopoletin (23), and 4-hydroxycinnamic acid (24). Conclusion: Compound 1 is a new labdane diterpene. Compounds 10, 13, 16 and 17 are isolated from the genus Callicarpa for the first time. Compounds 7, 8, 9, 12, 14, 23 and 24 are reported from C. cathayana for the first time.
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With the rapid increase in its incidence in the last decade, colorectal cancer (CRC) is becoming one of the most life-threatening cancers. Circular RNA PTK2 (circPTK2) has multiple functions in oncogenesis, including in CRC. However, it remains elusive if circPTK2 also plays an important role in CRC malignancy. The levels of circPTK2, miR-506-3p, and AKT serine/threonine kinase 2 (AKT2) were measured by qPCR. The protein level of AKT2 was evaluated by western blotting assay. The proliferation, migration, and invasion of CRC cancer cells were evaluated by MTT, colony formation, wound-healing, and transwell assays. The interaction between circPTK2 and miR-506-3p and between miR-506-3p and AKT2 mRNA were verified by dual-luciferase reporter assay. The expressions of circPTK2 and AKT2 were elevated in CRC cells, with a concomitant reduction of miR-506-3p. The knockdown of circPTK2 suppressed the proliferation, migration, and invasion of CRC cells. CircPTK2 targeted miR-506-3p and negatively regulated its expression. Furthermore, miR-506-3p overexpression suppressed the CRC progression by downregulating the AKT2 expression. AKT2 overexpression or miR-506-3p inhibition restored the suppression of growth and invasiveness of CRC cancer cells caused by circPTK2 silencing. The circPTK2/miR-506-3p/AKT2 axis plays a novel and essential role in promoting CRC progression, providing potential targets for CRC therapeutic modality.
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Neoplasias Colorrectales , MicroARNs , Proteínas Proto-Oncogénicas c-akt , ARN Circular , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Circular/genéticaRESUMEN
Illumination-integrated nonuniformity (IINU) is a key factor in determining resolution and critical dimension uniformity, which are important performance parameters in advanced lithography systems. To further reduce the IINU, a uniformity correction technology was adopted. In this paper, a low-cost and simple-structure approach for uniformity correction with higher flexibility and better correction capability is proposed. The method is composed of two dynamic gray filters with a specific transmittance distribution, which can form different correction curves by controlling the displacement of the gray filters. The frequency limitation of the defocus uniformity correction system is analyzed. A uniformity correction system design method based on the particle swarm optimization algorithm is introduced. Based on the proposed method, a dynamic gray filter uniformity correction system is applied to an illumination optical system. The experimental results show that the value of the corrected IINU reaches less than 0.7%, which satisfies the IINU requirements of advanced lithography systems. This verifies the higher flexibility and better correction capability of the proposed method.
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The appearance of drug-resistant mutations in UL54 DNA polymerase and UL97 kinase genes is problematic for the treatment of human cytomegalovirus (HCMV) diseases. During treatment of HCMV infection in a pediatric hematopoietic cell transplant recipient, H600L and T700A mutations and E576G mutation were independently found in the UL54 gene. Foscarnet (FOS; phosphonoformic acid) resistance by T700A mutation is reported. Here, we investigated the role of novel mutations in drug resistance by producing recombinant viruses and a model polymerase structure. The H600L mutant virus showed an increase in resistance to ganciclovir (GCV) by 11-fold and to FOS and cidofovir (CDV) by 5-fold, compared to the wild type, while the E756G mutant virus showed an increase in resistance to FOS by 9-fold and modestly to CDV by 2-fold. With the FOS-resistant T700A mutation, only H600L produced increased FOS resistance up to 37-fold, indicating an additive effect of these mutations on FOS resistance. To gain insight into drug resistance mechanisms, a model structure for UL54 polymerase was constructed using the yeast DNA polymerase as a template. In this model, HCMV DNA polymerase contains a long palm loop domain of which H600 and T700 are located on each end and T700 interacts with the FOS binding pocket. Our results demonstrate that H600L and E756G mutations in UL54 polymerase are novel drug-resistant mutations and that the acquisition of both H600L and T700A mutations in the DNA-binding loop confers increased resistance to FOS treatment, providing novel insights for the mechanism acquiring foscarnet resistance.
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Targeted protein degradation using small molecules is an intriguing strategy for drug development. The marine sesterterpene compound MHO7 had been reported to be a potential ERα degradation agent. In order to further improve its biological activity, two series of novel MHO7 derivatives with long side chains were designed and identified as novel selective estrogen receptor down-regulators (SERDs). The growth inhibition activity of the novel SERD compounds were significantly affected by the type and length of the side chain. Most of the derivatives were significantly more potent than MHO7 against both drug-sensitive and drug-resistant breast cancer cells. Among them, compound 16a, with IC50 values of 0.41 µM against MCF-7 cell lines and 9.6-fold stronger than MHO7, was the most potential molecule. A whole-genome transcriptomic analysis of MCF-7 cells revealed that the mechanism of 16a against MCF-7 cell was similar with that of MHO7. The estrogen signaling pathway was the most affected among the disturbed genes, but the ERα degradation activity of 16a was observed higher than that of MHO7. Other effects of 16a were confirmed similar with MHO7, which means that the basic mechanisms of the derivatives are the same with the ophiobolin backbone, i.e. the degradation of ERα is mediated via proteasome-mediated process, the induction of apoptosis and the cell cycle arrest at the G1 phase. Meanwhile, a decrease of mitochondrial membrane potential and an increase of cellular ROS were also detected. Based on these results, as a novel modified ophiobolin derived compound, 16a may warrant further exploitation as a promising SERD candidate agent for the treatment of breast cancer.
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Antineoplásicos/síntesis química , Productos Biológicos/química , Neoplasias de la Mama/tratamiento farmacológico , Receptor alfa de Estrógeno/metabolismo , Sesterterpenos/síntesis química , Anastrozol/química , Anastrozol/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Productos Biológicos/farmacología , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Humanos , Letrozol/química , Letrozol/farmacología , Células MCF-7 , Simulación del Acoplamiento Molecular , Unión Proteica , Proteolisis , Clorhidrato de Raloxifeno/química , Clorhidrato de Raloxifeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sesterterpenos/farmacología , Transducción de Señal , Relación Estructura-Actividad , Tamoxifeno/química , Tamoxifeno/farmacologíaRESUMEN
In this study, the deposition angle parameter was introduced into the traditional deposition model to eliminate the coating thickness errors caused by large deposition angles and differences in the microstructures of coatings from the expected values. Based on the different thickness distributions of MgF2 and LaF3 coatings, a method that involves switching shadowing masks and a stepwise numerical optimization algorithm were proposed to control each coating thickness distribution accurately. When designing shadowing masks for a multilayer antireflective (AR) coating with a wide incident angle range, the correlation between the thickness distributions of the MgF2 and LaF3 layers was added to the merit function to ensure consistency in the two distributions. Two-layer deep-ultraviolet (DUV) AR fluoride coatings and a six-layer DUV low-polarization antireflection fluoride coating at 193 nm were fabricated on spherical substrate holders using thermal evaporation. In the experiment, when the ratio of the clear aperture to the radius of curvature was increased from -1.68 to 1.63, the thickness uniformities of the MgF2 and LaF3 layers of the two-layer DUV AR coatings on the fused silica substrates increased to a minimum of 98.49%. Owing to the transmission spectra and the incidence angle-resolved transmission, uniform optical performance and low-variation polarization transmittance were also achieved for the 193 nm AR coating deposited on the fused silica substrates.
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Viral deubiquitinases (DUBs) regulate cellular innate immunity to benefit viral replication. In human cytomegalovirus (HCMV), the UL48-encoded DUB regulates innate immune responses, including NF-κB signaling. Although UL48 DUB is known to regulate its stability via auto-deubiquitination, its impact on other viral proteins is not well understood. In this study, we investigated the role of UL48 DUB in regulating the ubiquitination of viral proteins by comparing the levels of ubiquitinated viral peptides in cells infected with wild-type virus and DUB active-site mutants using mass spectrometry. We found that ubiquitinated peptides were increased in DUB mutant virus infection for 90% of viral proteins, with the innermost tegument proteins pp150 (encoded by UL32) and pUL48 itself being most significantly affected. The highly deubiquitinated lysine residues of pUL48 were mapped within its N-terminal DUB domain and the nuclear localization signal. Among them, the arginine substitution of lysine 2 (K2R) increased pUL48 stability and enhanced viral growth at low multiplicity of infection, indicating that K2 auto-deubiquitination has a role in regulating pUL48 stability. pUL48 also interacted with pp150 and increased pp150 expression by downregulating its ubiquitination. Furthermore, we found that, unlike the wild-type virus, mutant viruses expressing the UL48 protein with the DUB domain deleted or DUB active site mutated contain higher levels of ubiquitin conjugates, including the ubiquitinated forms of pp150, in their virions. Collectively, our results demonstrate that UL48 DUB mainly acts on the innermost tegument proteins pp150 and pUL48 itself during HCMV infection and may play a role in protecting virions from the inclusion of ubiquitin conjugates. IMPORTANCE Herpesviruses encode highly conserved tegument proteins that contain deubiquitinase (DUB) activity. Although the role of viral DUBs in the regulation of host innate immune responses has been established, their roles in the stability and function of viral proteins are not well understood. In this study, we performed a comparative analysis of the levels of ubiquitinated viral peptides between wild-type and DUB-inactive HCMV infections and demonstrated that the innermost tegument proteins pp150 and pUL48 (DUB itself) are major targets of viral DUB. We also show that ubiquitinated viral proteins are effectively incorporated into the virions of DUB mutant viruses but not the wild-type virus. Our study demonstrates that viral DUBs may play important roles in promoting the stability of viral proteins and inhibiting the inclusion of ubiquitin conjugates into virions.
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Citomegalovirus/fisiología , Enzimas Desubicuitinizantes/metabolismo , Ubiquitina/metabolismo , Virión/metabolismo , Citomegalovirus/genética , Infecciones por Citomegalovirus/inmunología , Enzimas Desubicuitinizantes/genética , Genes Virales , Células HEK293 , Humanos , Inmunidad Innata , FN-kappa B/metabolismo , Señales de Localización Nuclear/metabolismo , Proteínas Virales/metabolismo , Replicación ViralRESUMEN
Bacillus amyloliquefaciens strain EA19 is an endophyte isolated from Erigeron annuus with antifungal activity against Blumeria graminis f. sp. tritici, Magnaporthe oryzae, and Fusarium graminearum. The genome sequence of this strain is 3.96 Mb and contains 3,421 coding sequences, which will facilitate an understanding of the mechanisms of biocontrol.
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To investigate the influence of bedding structure and different loading rates on the dynamic fracture characteristics and energy dissipation of Datong coal, a split Hopkinson bar was used to obtain the fracture characteristics of coal samples with different bedding angles. The process of crack initiation and propagation in Datong coal was recorded by the high-speed camera. The formula for the model I fracture toughness of the transversely isotropic material is obtained on the basis of the finite element method (FEM) together with the J-integral. By comparing the incident energy, absorbed energy, fracture energy and residual kinetic energy of Datong coal samples under various impact speeds, the energy dissipation characteristics during the dynamic fracture process of coal considering the bedding structure is acquired. The experimental results indicate that the fracture pattern of notched semi-circular bending (NSCB) Datong coal is tensile failure. After splitting into two parts, the coal sample rotates approximately uniformly around the contact point between the sample and the incident rod. The dynamic fracture toughness is 3.52~8.64 times of the quasi-static fracture toughness for Datong coal. Dynamic fracture toughness increases with increasing impact velocity, and the effect of bedding angle on fracture toughness then decreases. In addition, the residual kinetic energy of coal samples with the same bedding angle increases with the increase of impact speed. The energy utilization rate decreases continuously, and the overall dispersion of statistical data decreases gradually. In rock fragmentation engineering, the optimum loading condition is low-speed loading regardless of energy utilization efficiency or fracture toughness. These conclusions may have significant implications for the optimization of hydraulic fracturing process in coal mass and the further understanding of crack propagation mechanisms in coalbed methane extraction (CME). The anisotropic effect of coal should be fully considered in both these cases.
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Minas de Carbón/normas , Carbón Mineral/análisis , Metabolismo Energético , Fracking Hidráulico/normas , Metano/química , Estrés Mecánico , AnisotropíaRESUMEN
A three-dimensional (3D) binodal 3,5-connected net, {[Cu(MTP)(H2O)](NO3)}n (1) with the Schläfli symbol of {3·72}{32·75·83} can be transformed into a two-dimensional (2D) kagóme network with the Schlafli symbol of {32·62·72} in an irreversible single crystal-single crystal (SC-SC) guest-assisted linker exchange process. The product of this SC-SC represents the first luminescent probe for S2- based on triazole ligand.
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OBJECTIVE: To investigate the. METHODS: for locating and selecting the acupoints of "Taixi" (KI3), "Shuiquan" (KI5), "Fuliu" (KI7), "Jiaoxin" (KI8), "Zhubin" (KI9), and "Yingu" (KI10) and the morphological structure of these acupoints in rabbits. MethodsAccording to the WHO and national standards for human acupoints and rabbit X-ray images, acupoint locations were marked using the anatomical landmarks on body surface in 10 New Zealand rabbits. The acupoints were dissected to compare the homologous and analogous tissue between rabbits and human body and thus correct the locations of these acupoints. Potentials were measured for the 10 New Zealand rabbits at the corrected locations of the acupoints and around the acupoints, and the final locations of these acupoints were determined by comparing the anatomical results and the data of potentials. Anatomical observation was performed after marking, and the relationship between acupuncture needle and adjacent structure was observed. RESULTS: "Taixi" was located in the ankle area, at the midpoint between the prominence of the medial malleolus and the calca-neal tendon; "Shuiquan" was located in the calcaneal area below "Taixi" in the depression anterior to the calcaneal tuberosity; "Fuliu" was located at the medial side of the calf, at 2 cun above the prominence of the medial malleolus anterior to the calcaneal tendon; "Jiaoxin" was located at the medial side of the calf, at 2 cun above the prominence of the medial malleolus and in the depression posterior to the medial border of the tibia; "Zhubin" was located at the medial side of the calf, at 5 cun above the medial malleolus on the line between "Taixi" and "Yingu"; "Yingu" was located at the medial side of the knee, at the posterior-inferior border of the semitendinosus tendon on the popliteal crease. The results of skin potentials at the acupoints suggested that "Taixi", "Shuiquan", "Fuliu", and "Zhubin" were high-reliability acupoints, "Jiaoxin" was a medium-reliability acupoint, and "Yingu" was a low-reliability acupoint. CONCLUSION: Comparative anatomy combined with imaging, surface anatomy, and electrophysiological techniques of acupoints can help with the accurate localization and selection of acupoints in experimental animals, improve the reliability of acupoint location, and enrich the comparative anatomical data of acupoints.
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Terapia por Acupuntura , Acupuntura , Puntos de Acupuntura , Anatomía Comparada , Animales , Conejos , Reproducibilidad de los ResultadosRESUMEN
Nine new diterpenoids, Rubellacrns A - I (1-9), including five isopimaranes (1-4, 9), four pimaranes (5-8), together with five known isopimarane analogues (10-14), were isolated from Callicarpa rubella. The structures of these compounds were unambiguously established by HR-ESIMS and NMR spectroscopic data, the absolute configurations of compounds 5 and 9 were determined by ECD. All the isolated compounds were tested for their anti-inflammatory effects and compounds 2 and 11-14 showed NLRP3-inflammasome inhibitory activity with IC50 values ranging from 7.02 to 14.38 µM.
Asunto(s)
Callicarpa/química , Diterpenos/farmacología , Inflamasomas/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Abietanos , Animales , Línea Celular , China , Diterpenos/aislamiento & purificación , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Hojas de la Planta/químicaRESUMEN
Controlling aflatoxigenic Aspergillus flavus and aflatoxins (AFs) in grains and food during storage is a great challenge to humans worldwide. Alcaligenes faecalis N1-4 isolated from tea rhizosphere soil can produce abundant antifungal volatiles, and greatly inhibited the growth of A. flavus in un-contacted face-to-face dual culture testing. Gas chromatography tandem mass spectrometry revealed that dimethyl disulfide (DMDS) and methyl isovalerate (MI) were two abundant compounds in the volatile profiles of N1-4. DMDS was found to have the highest relative abundance (69.90%, to the total peak area) in N1-4, which prevented the conidia germination and mycelial growth of A. flavus at 50 and 100 µL/L, respectively. The effective concentration for MI against A. flavus is 200 µL/L. Additionally, Real-time quantitative PCR analysis proved that the expression of 12 important genes in aflatoxin biosynthesis pathway was reduced by these volatiles, and eight genes were down regulated by 4.39 to 32.25-folds compared to control treatment with significant differences. And the A. flavus infection and AFs contamination in groundnut, maize, rice and soybean of high water activity were completely inhibited by volatiles from N1-4 in storage. Scanning electron microscope further proved that A. flavus conidia inoculated on peanuts surface were severely damaged by volatiles from N1-4. Furthermore, strain N1-4 showed broad and antifungal activity to other six important plant pathogens including Fusarium graminearum, F. equiseti, Alternaria alternata, Botrytis cinerea, Aspergillus niger, and Colletotrichum graminicola. Thus, A. faecalis N1-4 and volatile DMDS and MI may have potential to be used as biocontrol agents to control A. flavus and AFs during storage.