ABSTRACT
The survival and suppressive function of regulatory T (Treg) cells rely on various intracellular metabolic and physiological processes. Our study demonstrates that Vps34 plays a critical role in maintaining Treg cell homeostasis and function by regulating cellular metabolic activities. Disruption of Vps34 in Treg cells leads to spontaneous fatal systemic autoimmune disorder and multi-tissue inflammatory damage, accompanied by a reduction in the number of Treg cells, particularly eTreg cells with highly immunosuppressive activity. Mechanistically, the poor survival of Vps34-deficient Treg cells is attributed to impaired endocytosis, intracellular vesicular trafficking and autophagosome formation, which further results in enhanced mitochondrial respiration and excessive ROS production. Removal of excessive ROS can effectively rescue the death of Vps34-deficient Treg cells. Functionally, acute deletion of Vps34 within established Treg cells enhances anti-tumor immunity in a malignant melanoma model by boosting T-cell-mediated anti-tumor activity. Overall, our results underscore the pivotal role played by Vps34 in orchestrating Treg cell homeostasis and function towards establishing immune homeostasis and tolerance.
ABSTRACT
Raising attentions have focused on how to alleviate greenhouse gas (GHG) emissions from orchard system while simultaneously increase fruit production. Microalgae-based biofertilizer represents a promising resource for improving soil fertility and higher productivity. However, the effects of microalgae application more especially live microalgae on GHG emissions are understudied. In this study, fruit yield and quality, GHG emissions, as well as soil organic carbon and nitrogen fractions were examined in a hawthorn orchard, under the effects of live microalgae-based biofertilizer applied at three doses and two modes. Compared with conventional fertilization, microalgae improved hawthorn yield by 15.7%-29.6% with a maximal increment at medium dose by root application, and significantly increased soluble and reducing sugars contents at high dose. While microalgae did not increase GHG emissions except for nitrous oxide at high dose by root application, instead it significantly increased methane uptake by 1.5-2.3 times in root application. In addition, microalgae showed an increasing trend in soil organic carbon content, and significantly increased the contents of soil dissolved organic carbon and microbial biomass carbon, as well as soil ammonium nitrogen and dissolved organic nitrogen at medium dose with root application. Overall, the results indicated that the live microalgae could be used as a green biofertilizer for improving fruit yield without increasing GHG emissions intensity and the comprehensive greenhouse effect, in particular at medium dose with root application. We presume that if lowering chemical fertilizer rates, application of the live microalgae-based biofertilizer may help to reduce nitrous oxide emissions without compromising fruit yield and quality.
Subject(s)
Crataegus , Fertilizers , Fruit , Greenhouse Gases , Microalgae , Nitrogen , Soil , Fertilizers/analysis , Greenhouse Gases/analysis , Fruit/growth & development , Fruit/metabolism , Microalgae/growth & development , Microalgae/metabolism , Soil/chemistry , Nitrogen/analysis , Nitrogen/metabolism , Crataegus/growth & development , Carbon/analysis , Carbon/metabolism , Biomass , Methane/analysis , Methane/metabolism , Nitrous Oxide/analysis , Nitrous Oxide/metabolismABSTRACT
Magnolia bark is a traditional Chinese medicine used for hypoglycaemia. With the widespread use of Magnolia bark, its resources are facing a serious shortage. To address this issue, a strategy based on high-coverage mass spectrometry (HCMS) and multidimensional chemical-biological analysis (MCBA) was proposed for the comprehensive exploration of Magnolia officinalis which is the main source of Magnolia bark. The strategy is divided into three main steps. In the first step, the stem bark, stem xylem, root bark, root xylem, leaf and rootlet of Magnolia officinalis were comprehensively analyzed using high-coverage mass spectrometry. In the second step, multivariate statistical analysis was used to explore the heterogeneity of the six parts and detect differential chemical components. In the third step, a combination of experimental screening and molecular docking was used to explore α-glucosidase inhibitors from Magnolia officinalis. Multidimensional chemical-biological analysis (MCBA) of Magnolia officinalis was achieved by combining the last two steps. Finally, a total of 103 compounds were identified from the whole plant of Magnolia officinalis. Differential components of stem bark, stem xylem, leaf, root bark, root xylem and rootlet were systematically revealed. A pair of positional isomers, namely magnolol and honokiol, were found to be α-glucosidase inhibitors. The activity of their combination is superior to that of each single compound, indicating that magnolol and honokiol are in a synergistic relationship. This strategy contributes to comprehensive exploitation of functional plants and effective alleviation of resource shortage. This study also provides a research paradigm for other similar traditional Chinese medicinal plants.
ABSTRACT
Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).
Subject(s)
Flow Cytometry , High-Throughput Nucleotide Sequencing , Neoplasm, Residual , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Humans , High-Throughput Nucleotide Sequencing/methods , Adult , Male , Female , Flow Cytometry/methods , Middle Aged , Young Adult , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , AdolescentABSTRACT
Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 µM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.
Subject(s)
Acetylcholinesterase , Cholinesterase Inhibitors , Mass Spectrometry , Molecular Docking Simulation , Plant Leaves , Zanthoxylum , Zanthoxylum/chemistry , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Plant Leaves/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Plant Stems/chemistry , Chromatography, High Pressure Liquid , Humans , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacologyABSTRACT
B cell acute lymphoblastic leukemia (ALL) is characterized by the highly heterogeneity of pathogenic genetic background, and there are still approximately 30-40% of patients without clear molecular markers. To identify the dysregulated genes in B cell ALL, we screened 30 newly diagnosed B cell ALL patients and 10 donors by gene expression profiling chip. We found that ECM1 transcription level was abnormally elevated in newly diagnosed B cell ALL and further verified in another 267 cases compared with donors (median, 124.57% vs. 7.14%, P < 0.001). ROC analysis showed that the area under the curve of ECM1 transcription level at diagnosis was 0.89 (P < 0.001). Patients with BCR::ABL1 and IKZF1 deletion show highest transcription level (210.78%) compared with KMT2A rearrangement (39.48%) and TCF3::PBX1 rearrangement ones (30.02%) (all P < 0.05). Also, the transcription level of ECM1 was highly correlated with the clinical course, as 20 consecutive follow-up cases indicated. The 5-year OS of patients (non-KMT2A and non-TCF3::PBX1 rearrangement) with high ECM1 transcription level was significantly worse than the lower ones (18.7% vs. 72.9%, P < 0.001) and high ECM1 transcription level was an independent risk factor for OS (HR = 5.77 [1.75-19.06], P = 0.004). After considering transplantation, high ECM1 transcription level was not an independent risk factor, although OS was still poor (low vs. high, 71.1% vs. 56.8%, P = 0.038). Our findings suggested that ECM1 may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B cell ALL.Trial registration Trial Registration Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTR-OPC-14005546]; http://www.chictr.org.cn .
Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Biomarkers , Risk Factors , Extracellular Matrix Proteins/geneticsABSTRACT
Saikosaponin D (SsD), a natural triterpenoid saponin compound, exhibits notable potential in suppressing tumor growth and inhibiting metastasis, particularly in breast cancer. However, its underlying mechanism of action for SsD remains unclear. In this study, a combination strategy to reveal the metabolism modulation of SsD on breast cancer was performed by integration of histopathological assessments and untargeted metabolomics analysis. Pathological evaluation of the efficacy of SsD from a visual and intuitive perspective. Accordingly, a non-targeted metabolomics study was used to investigate the pharmacological efficacy using a set of serum samples from mice before and after (0-30 days) modulated with SsD based on ultra-high performance liquid chromatography tandem orbitrap mass spectrometry to discover metabolite biomarkers for finding the key metabolic mechanism in a molecular perspective. As a result, 20 metabolites were selected as potential biomarkers for SsD efficacy evaluation with high sensitivity and specificity. These metabolites changes were involved in sphingolipid metabolism, glycerophospholipid metabolism, phenylalanine and tryptophan metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis pathways, suggesting that SsD exerted anti-breast cancer effects through the regulation of the underlying metabolism. In conclusion, we developed a new analysis strategy that effectively discovers tumor-progressing related metabolite biomarkers in serum for pharmacological efficacy evaluation.
Subject(s)
Antineoplastic Agents , Neoplasms , Oleanolic Acid/analogs & derivatives , Saponins , Mice , Animals , Tryptophan , Metabolomics/methods , Saponins/pharmacology , Biomarkers , Chromatography, High Pressure Liquid/methods , PhenylalanineABSTRACT
BACKGROUND: Adolescence is a period characterized by a high vulnerability to emotional disorders, which are modulated by biological, psychological, and social factors. However, the underlying mechanisms remain poorly understood. METHODS: Combining physical or emotional social defeat stress (PS and ES) and pair or isolation rearing conditions, we investigated the effects of stress type and social support on emotional behavior and central immune molecules in adolescent mice, including anxiety, social fear, and social interaction strategies, as well as changes in microglia-specific molecules (ionized calcium-binding adaptor molecule 1 (Iba1) and a cluster of differentiation molecule 11b (CD11b)) in the medial prefrontal cortex (mPFC), hippocampus (HIP), amygdala (AMY), and nucleus accumbens (NAc). RESULTS: Mice exposed to both physical stress and isolated rearing condition exhibited the highest levels of anxiety, social fear, and microglial CD11b expression in the NAc. In terms of social support, pair-housing with siblings ameliorated social fear and NAc molecular changes in ES mice, but not in PS mice. The reason for the differential benefit from social support was attributed to the fact that ES mice exhibited more active and less passive social strategies in social environment compared to PS mice. Further, the levels of stress-induced social fear were positively associated with the expression of microglial CD11b in the NAc. CONCLUSION: These findings offer extensive evidence regarding the intricate effects of multiple social factors on social anxiety and immune alteration in the NAc of adolescent mice. Additionally, they suggest potential behavioral and immune intervention strategies for anxiety-related disorders in adolescents.
Subject(s)
Microglia , Nucleus Accumbens , Mice , Male , Animals , Nucleus Accumbens/metabolism , Microglia/metabolism , Social Interaction , Social Factors , Anxiety , Stress, Psychological/psychology , Mice, Inbred C57BLABSTRACT
BACKGROUND: Driven by the accelerated aging of the population of China, the number of older adults has increased rapidly in the country. Meanwhile, following children, migrant older adults (MOA) have emerged as a vulnerable group in the process of fast urbanization. Existed studies have illustrated the association between social support and loneliness and the relationship between sleep disturbance and loneliness; however, the underlying mechanisms and the migrant-local difference in the association between social support, sleep disturbance, and loneliness have not been identified. OBJECTIVE: This study aimed to clarify the migrant-local difference in the relationship between social support, sleep disturbance, and loneliness in older adults in China. METHODS: Multistage cluster random sampling was used to select participants: 1205 older adults (n=613, 50.9%, MOA and n=592, 49.1%, local older adults [LOA]) were selected in Weifang City, China, in August 2021. Loneliness was assessed with the 6-item short-form University of California, Los Angeles Loneliness Scale, social support was evaluated with the Social Support Rating Scale, and sleep disturbance was measured with the Pittsburgh Sleep Quality Index. The chi-square test, t test, and structural equation modeling (SEM) were adopted to explore the migrant-local difference between social support, sleep disturbance, and loneliness among the MOA and LOA. RESULTS: The mean score of loneliness was 8.58 (SD 3.03) for the MOA and 8.00 (SD 2.79) for the LOA. SEM analysis showed that social support exerts a direct negative effect on both sleep disturbance (standardized coefficient=-0.24 in the MOA and -0.20 in the LOA) and loneliness (standardized coefficient=-0.44 in the MOA and -0.40 in the LOA), while sleep disturbance generates a direct positive effect on loneliness (standardized coefficient=0.13 in the MOA and 0.22 in the LOA). CONCLUSIONS: Both MOA and LOA have a low level of loneliness, but the MOA show higher loneliness than the LOA. There is a negative correlation between social support and loneliness as well as between social support and sleep disturbance among the MOA and LOA (MOA>LOA), while loneliness is positively associated with sleep disturbance in both populations (MOASubject(s)
Sleep Wake Disorders
, Transients and Migrants
, Child
, Humans
, Aged
, Cross-Sectional Studies
, Loneliness
, China/epidemiology
, Sleep Wake Disorders/epidemiology
, Social Support
, Sleep
ABSTRACT
While single-shot late gadolinium enhancement (LGE) is useful for imaging patients with arrhythmia and/or dyspnea, it produces low spatial resolution. One approach to improve spatial resolution is to accelerate data acquisition using compressed sensing (CS). Our previous work described a single-shot, multi-inversion time (TI) LGE pulse sequence using radial k-space sampling and CS, but over-regularization resulted in significant image blurring that muted the benefits of data acceleration. The purpose of the present study was to improve the spatial resolution of the single-shot, multi-TI LGE pulse sequence by incorporating view sharing (VS) and k-space weighted contrast (KWIC) filtering into a GRASP-Pro reconstruction. In 24 patients (mean age = 61 ± 16 years; 9/15 females/males), we compared the performance of our improved multi-TI LGE and standard multi-TI LGE, where clinical standard LGE was used as a reference. Two clinical raters independently graded multi-TI images and clinical LGE images visually on a five-point Likert scale (1, nondiagnostic; 3, clinically acceptable; 5, best) for three categories: the conspicuity of myocardium or scar, artifact, and noise. The summed visual score (SVS) was defined as the sum of the three scores. Myocardial scar volume was quantified using the full-width at half-maximum method. The SVS was not significantly different between clinical breath-holding LGE (median 13.5, IQR 1.3) and multi-TI LGE (median 12.5, IQR 1.6) (P = 0.068). The myocardial scar volumes measured from clinical standard LGE and multi-TI LGE were strongly correlated (coefficient of determination, R2 = 0.99) and in good agreement (mean difference = 0.11%, lower limit of the agreement = -2.13%, upper limit of the agreement = 2.34%). The inter-rater agreement in myocardial scar volume quantification was strong (intraclass correlation coefficient = 0.79). The incorporation of VS and KWIC into GRASP-Pro improved spatial resolution. Our improved 25-fold accelerated, single-shot LGE sequence produces clinically acceptable image quality, multi-TI reconstruction, and accurate myocardial scar volume quantification.
Subject(s)
Contrast Media , Gadolinium , Male , Female , Humans , Middle Aged , Aged , Cicatrix/pathology , Magnetic Resonance Imaging/methods , Myocardium/pathologyABSTRACT
The plant hormone salicylic acid (SA) plays critical roles in plant innate immunity. Several SA derivatives and associated modification are identified, whereas the range and modes of action of SA-related metabolites remain elusive. Here, the study discovered 2,4-dihydroxybenzoic acid (2,4-DHBA) and its glycosylated form as native SA derivatives in plants whose accumulation is largely induced by SA application and Ps. camelliae-sinensis (Pcs) infection. CsSH1, a 4/5-hydroxylase, catalyzes the hydroxylation of SA to 2,4-DHBA, and UDP-glucosyltransferase UGT95B17 catalyzes the formation of 2,4-DHBA glucoside. Down-regulation reduced the accumulation of 2,4-DHBA glucosides and enhanced the sensitivity of tea plants to Pcs. Conversely, overexpression of UGT95B17 increased plant disease resistance. The exogenous application of 2,4-DHBA and 2,5-DHBA, as well as the accumulation of DHBA and plant resistance comparison, indicate that 2,4-DHBA functions as a potentially bioactive molecule and is stored mainly as a glucose conjugate in tea plants, differs from the mechanism described in Arabidopsis. When 2,4-DHBA is applied exogenously, UGT95B17-silenced tea plants accumulated more 2,4-DHBA than SA and showed induced resistance to Pcs infection. These results indicate that 2,4-DHBA glucosylation positively regulates disease resistance and highlight the role of 2,4-DHBA as potentially bioactive molecule in the establishment of basal resistance in tea plants.
Subject(s)
Arabidopsis , Camellia sinensis , Catechols , Hydroxybenzoates , Salicylic Acid/metabolism , Salicylic Acid/pharmacology , Camellia sinensis/metabolism , Disease Resistance , Arabidopsis/metabolism , Tea/metabolismABSTRACT
OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1). METHODS: A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected. RESULTS: After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05). CONCLUSIONS: Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.
Subject(s)
Electroacupuncture , Peripheral Nerve Injuries , Animals , Female , Male , Rabbits , Muscle, Skeletal , Muscular Atrophy/therapy , NF-kappa B/genetics , Rats, Sprague-Dawley , Sciatic Nerve , RatsABSTRACT
Two-dimensional material-based field-effect transistors (2DM-FETs) are playing a revolutionary role in electronic devices. However, before electronic design automation (EDA) for 2DM-FETs can be achieved, it remains necessary to determine how to incorporate contact transports into model. Reported methods compromise between physical intelligibility and model compactness due to the heterojunction nature. To address this, quasi-Fermi-level phase space theory (QFLPS) is generalized to incorporate contact transports using the Landauer formula. It turns out that the Landauer-QFLPS model effectively overcomes the issue of concern. The proposed new formula can describe 2DM-FETs with Schottky or Ohmic contacts with superior accuracy and efficiency over previous methods, especially when describing non-monotonic drain conductance characteristics. A three-bit threshold inverter quantizer (TIQ) circuit is fabricated using ambipolar black phosphorus and it is demonstrated that the model accurately predicts circuit performance. The model could be very effective and valuable in the development of 2DM-FET-based integrated circuits.
ABSTRACT
Cathepsin D (CTSD) is an aspartic endopeptidase, however, we found that it was also capable of enzymatic digestion of nucleic acids (NAs). The purpose of this study was to investigate the basic properties of CTSD enzymatic activity on NAs, and explore the degradation mechanism. The results showed that NAs were efficiently digested between pH 3.0 and 5.0, and the optimum pH was 3.5. CTSD exhibited optimum activity at the temperature of 50°C. The degradation rate was improved with an increased CTSD concentration, and NAs were digested to an enzyme concentration of 0.001%, at which point, NAs were no longer digested. Ca2+ and Mg2+ at low concentrations of 5 mM promoted the digestion remarkably. As the protein substrate for CTSD, both Hb and BSA had no effect on DNA degradation, even when the molar ratio of protein:DNA was 104:1. Kinetic parameters of Km and kcat/Km value were (42 ± 1) µM and (1.62 ± 0.1) × 10-2 s-1mM-1 respectively, using real-time quantitative PCR (RT-PCR). Specially, pepstatin A which is the specific aspartic protease inhibitor exhibited inhibitory effect on NA digestion by CTSD as well, suggesting that the catalytic active site of CTSD for NAs might be the same as protein. A brief degradation mechanism is discussed. The present study may change the cognition of CTSD specificity for substrate and contribute greatly to enzymology of CTSD.
Subject(s)
Cathepsin D , Nucleic Acids , Aspartic Acid Endopeptidases , Cathepsin D/metabolism , DNA/metabolism , Humans , Animals , CattleABSTRACT
Plants respond to environmental stimuli via the release of volatile organic compounds (VOCs), and neighboring plants constantly monitor and respond to these VOCs with great sensitivity and discrimination. This sensing can trigger increased plant fitness and reduce future plant damage through the priming of their own defenses. The defense mechanism in neighboring plants can either be induced by activation of the regulatory or transcriptional machinery, or it can be delayed by the absorption and storage of VOCs for the generation of an appropriate response later. Despite much research, many key questions remain on the role of VOCs in interplant communication and plant fitness. Here we review recent research on the VOCs induced by biotic (i.e. insects and pathogens) and abiotic (i.e. cold, drought, and salt) stresses, and elucidate the biosynthesis of stress-induced VOCs in tea plants. Our focus is on the role of stress-induced VOCs in complex ecological environments. Particularly, the roles of VOCs under abiotic stress are highlighted. Finally, we discuss pertinent questions and future research directions for advancing our understanding of plant interactions via VOCs.
ABSTRACT
Zero-field-cooling exchange bias (ZFC EB) has always been a research hotspot for researchers, because it can realize the movement of the magnetization hysteresis loop along the field axis without field cooling, which greatly expands the universality and convenience of the application of the exchange bias effect. Achieving ZFC EB at room temperature is an ongoing challenge. To this end, a design strategy from the sublattice level is proposed, and a wide temperature range ZFC EB up to room temperature with a vertical magnetization shift is observed in the strained kagome antiferromagnet Mn3.1Sn0.9. Magnetic analysis and first-principles calculations reveal that the ZFC EB arises from the strong exchange interaction between the non-coplanar antiferromagnetic Mn kagome sublattice occupying normal Mn sites and the collinear ferromagnetic Mn sublattice occupying Sn sites. This discovery is of great significance for the application of ZFC EB in antiferromagnetic spintronic devices.
ABSTRACT
Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, few information of BPTF is available in pig, especially in mammalian follicular granulosa cells (GCs). The present study firstly confirmed that BPTF in porcine was relative close to human and mouse. The expression of BPTF could be detected in ovary, testes, lung, kidney, large intestine, and small intestine. And a relative high expression of BPTF was observed in ovarian follicles and GCs. When BPTF was knocked down (BPTF-siRNA), the viability of GCs was affected. And the expression level of CDK1, cyclin B1, CDK4 and CDK2 was higher than the control, which might indicate that the cell cycle of GCs was inhibited from S to G2/M phase. Although the apoptosis level was induced in the BPTF-siRNA GCs, the reduced level of H3K4 methylation was detected with the down regulation of SMYD3, EHMT2 and DPY30. Thereby, results in the present might provide the primary knowledge of BPTF in GCs and the follicular development in pig.
Subject(s)
Chromatin Assembly and Disassembly , Granulosa Cells , Female , Humans , Swine , Animals , Mice , Cell Cycle , Cell Division , Apoptosis , Mammals , Histocompatibility Antigens , Histone-Lysine N-MethyltransferaseABSTRACT
Oxidation of renewable polyol/sugar into formic acid using molecular O2 over heterogeneous catalysts is still challenging due to the insufficient activation of both O2 and organic substrates on coordination-saturated metal oxides. In this study, we develop a defective MnO2 catalyst through a coordination number reduction strategy to enhance the aerobic oxidation of various polyols/sugars to formic acid. Compared to common MnO2, the tri-coordinated Mn in the defective MnO2 catalyst displays the electronic reconstruction of surface oxygen charge state and rich surface oxygen vacancies. These oxygen vacancies create more Mnδ+ Lewis acid site together with nearby oxygen as Lewis base sites. This combined structure behaves much like Frustrated Lewis pairs, serving to facilitate the activation of O2, as well as C-C and C-H bonds. As a result, the defective MnO2 catalyst shows high catalytic activity (turnover frequency: 113.5 h-1) and formic acid yield (>80%) comparable to noble metal catalysts for glycerol oxidation. The catalytic system is further extended to the oxidation of other polyols/sugars to formic acid with excellent catalytic performance.
ABSTRACT
One of the most typical abnormal cleavage patterns during early embryonic development is uneven division, but the first uneven division of pig zygote is common. Uneven division results in different daughter cell sizes and an uneven distribution of organelles such as lipid droplet, mitochondria, but the developmental capacity of daughter cells and proteomic changes of daughter cells are still unclear. Therefore, the developmental ability and proteomic quantification were investigated on blastomeres from even division (ED) or uneven division (UD) embryos at 2-cell stage in the present study. Firstly, the developmental ability was affected by the blastomeric size, when compared with medium blastomeres (MBs), the large blastomeres (LBs) with the higher cleavage rate but the small blastomeres (SBs) with the lower rate was observed. Subsequently, proteomic analysis was performed on blastomeres of LBs, MBs and SBs, a total of 109 DEPs were detected, which were involved in protein metabolism and processing, energy metabolism and ribosome. In particular, DEPs in LBs vs. SBs were focused on RNA binding and actin cytoskeletal tissue. Two protein-dense networks associated with RNA binding and cytoskeleton were revealed by further protein-protein interaction (PPI) analysis of DEPs in LBs vs. SBs, that DDX1 related to RNA binding and ACTB related to cytoskeleton were confirmed in UD embryos. Therefore, a briefly information of DEPs in blastomeres of 2-cell stage pig embryos was described in the present study, and it further confirmed that the formation of uneven division of the first cell cycle of pig embryos might be controlled by the cytoskeleton; the developmental capacity of daughter cells might be affected by the energy metabolism, RNA binding and ribosome, and further account for the developmental potential of the whole embryo.