To understand how infection by
(Mtb) is modulated by host cell phenotype, we characterized those host phagocytes that controlled or supported bacterial growth during early infection, focusing on the ...ontologically distinct alveolar macrophage (AM) and interstitial macrophage (IM) lineages. Using fluorescent Mtb reporter strains, we found that bacilli in AM exhibited lower stress and higher bacterial replication than those in IM. Interestingly, depletion of AM reduced bacterial burden, whereas depletion of IM increased bacterial burden. Transcriptomic analysis revealed that IMs were glycolytically active, whereas AMs were committed to fatty acid oxidation. Intoxication of infected mice with the glycolytic inhibitor, 2-deoxyglucose, decreased the number of IMs yet increased the bacterial burden in the lung. Furthermore, in in vitro macrophage infections, 2-deoxyglucose treatment increased bacterial growth, whereas the fatty acid oxidation inhibitor etomoxir constrained bacterial growth. We hypothesize that different macrophage lineages respond divergently to Mtb infection, with IMs exhibiting nutritional restriction and controlling bacterial growth and AMs representing a more nutritionally permissive environment.
Due to the abundant and promising biological activities of aromatic hydrazones, it is of great significance to study the biological activities of their metal complexes for the research and ...development of metal-based drugs. In this review, we focus on the metal complexes of polycyclic aromatic hydrazones, which still do not receive much attention, and summarize the studies related to their biological activities. Although the large number of metal complexes in phenylhydrazone prevent them all from being summarized, the significant value of polycyclic aromatic hydrocarbons themselves (such as naphthalene and anthracene) as pharmacophores are also considered. Therefore, the bioactivities of the metal complexes of naphthylhydrazone and anthrahydrazone are focused on, and the recent research progress on the metal complexes of anthrahydrazone by the authors is also included. In terms of biological activities, these complexes mainly show antibacterial and anticancer activities, along with less bioactivities. The present review demonstrates that the structural design and bioactivities of these complexes are fundamental, which also indicates a certain structure-activity relationship (SAR) in some substructural areas. However, a systematic and comprehensive conclusion of the SAR is still not available, which suggests that more attention should be paid to the bioactivities of the metal complexes of polycyclic aromatic hydrazones since their potential in structural design and biological activity remains to be explored. We hope that this review will attract more researchers to devote their interest and energy into this promising area.
The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating host-cell functions using hundreds of effector proteins delivered ...by its Dot/Icm secretion system
. Among these, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism that bypasses the canonical ubiquitination machinery
. The activity of SidEs is regulated by another Dot/Icm effector known as SidJ
; however, the mechanism of this regulation is not completely understood
. Here we demonstrate that SidJ inhibits the activity of SidEs by inducing the covalent attachment of glutamate moieties to SdeA-a member of the SidE family-at E860, one of the catalytic residues that is required for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation
. This inhibition by SidJ is spatially restricted in host cells because its activity requires the eukaryote-specific protein calmodulin (CaM). We solved a structure of SidJ-CaM in complex with AMP and found that the ATP used in this reaction is cleaved at the α-phosphate position by SidJ, which-in the absence of glutamate or modifiable SdeA-undergoes self-AMPylation. Our results reveal a mechanism of regulation in bacterial pathogenicity in which a glutamylation reaction that inhibits the activity of virulence factors is activated by host-factor-dependent acyl-adenylation.
The relationship between biodegraded oil and its source has long been a complex and contentious topic. The Western Halaalate area is located in the Piedmont area on the northwest margin of the ...Junggar Basin. Source rocks of the Fengcheng Formation exist both locally and in the nearby Mahu Depression. In order to determine the source of biodegraded crude oil in this area, the molecular marker characteristics of biodegraded crude oil were analyzed by gas chromatography-mass spectrometry. The results showed that the vitrinite reflectance (Ro) of source rocks of the Permian Fengcheng Formation in the nearby Mahu Depression is greater than 1.3% and has entered a high mature stage of condensate oil and moisture gas; the source rock of Permian Fengcheng Formation in Western Halaalate area is in a mature stage with Ro of 0.79%~1.13%. The ascending configuration of tricyclic terpenes C20-C21-C23 for the crude oil samples found in the Carboniferous strata of the Western Halaalate Area is consistent with the characteristics of the Fengcheng Formation source rocks, which are present in both the Western Halaalate Area and the nearby Mahu Depression. Chromatography spectrometry examination shows that crude oils have undergone a varying degree of biodegradation. The Carboniferous oil was originated from the in situ Fengcheng Formation source rocks based on the application of molecular markers resistant to biodegradation, such as maturity parameters, salinity parameters, the new gammacerane index, and aromatic hydrocarbon parameters, combined with the analysis of hydrocarbon migration pathway. In addition, the oil biodegradation alteration rules in the Western Halaalate area were clarified, which advances regional knowledge of the relationship between biodegraded oil and source rocks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The beetle’s elytra have the characteristics of light weight and high energy absorption (EA). In this paper, based on the internal structure of beetle elytra, two bio-inspired honeycomb column ...thin-walled structures (BHTS) I and II were fabricated by selective laser melting (SLM) technology in additive manufacturing (AM) in order to understand the possible influence of strain rate effect (SRE) on the BHTS under low speed uniaxial compression loading. The influence of three different SREs (0.001 s−1, 0.01 s−1 and 0.1 s−1) on the EA of BHTSs specimens during loading was discussed by means of out-of-plane uniaxial compression tests verified with numerical simulations. The experimental results show that SRE has a significant effect on the EA of BHTSs in low speed out-of-plane uniaxial compression tests: SRE can significantly increase the initial peak crushing force (PCF) and specific energy absorption (SEA) of all types of BHTS specimens. The average increase in PCF/SEA under SRE loading of 0.1 s−1 is 12.70%/9.79% and 17.63 %/11.60%, respectively, compared with 0.001 s−1 and 0.01 s−1. These research methods reduce the use of materials and improve the utilization rate of materials, which can provide important assistance for the design, manufacture and modeling of AM-based materials.
•Design a dc-link voltage oscillation suppression method based on model predictive control for cascaded drive system.•The input impedance of PMSM drive system with voltage stability constraint is ...deduced from the small-signal model of system.•The design criterion of weight factor for voltage stability constraint is given with a tradeoff between the stability margin and velocity sensitivity function.•The influence of the motor parameters on the input impedance is studied, and the robustness of the proposed method to the variation of motor parameters is verified.
The dc-link voltage oscillation caused by the negative impedance characteristic of the constant power load is a significant issue in the series LC branch-permanent magnet synchronous motor (PMSM) cascade system. To this end, this paper proposes a voltage prediction compensation (VPC) strategy to suppress the dc-link voltage oscillation by adding a voltage stability constraint term to the finite control set model predictive current control (FCS-MPCC). First, the linearized q-axis reference voltage is obtained by taking the derivation of the cost function of the VPC, thereby deriving the input impedance of the inverter-permanent magnet motor system. Then, the impedance matching criterion and Nyquist stability criterion are used to theoretically prove that the proposed strategy can effectively improve system stability, and the robustness of the proposed method to changes in motor parameters is analyzed. Finally, experimental verification was conducted on a 1 kW motor platform. The results show that when the motor is running under rated working conditions, after adding the stability constraint, the dc-link voltage fluctuation drops from 40 V to 7 V; the q-axis current pulsation rate also drops to 3.8 %. Theoretical analysis and experimental results show that the VPC strategy can effectively suppress the dc-link voltage oscillation of the cascade drive system.
With the photovoltaic (PV) penetration increases in dc microgrid, the traditional PV converters with maximum power point tracking (MPPT) control, which are equivalent to current sources, can hardly ...meet the needs of coordinated operation. The PV converter should operate in both MPPT and constant voltage control (CVC) modes. When the operation mode changes, the PV converter needs to switch between current and voltage sources. Inevitably, the bus voltage instability would be caused. This paper presents a novel switching strategy for the smooth and seamless operation of the PV converter between MPPT and CVC modes. The PV converter under these two modes is always controlled as a voltage source, and its control variables are both the output voltage of PV arrays. When its operation mode changes from MPPT to CVC, a small offset signal based on DC bus voltage would be introduced to the reference voltage of inner loop of the PV converter, so as to shift the maximum power point (MPP) voltage. Meanwhile in the voltage inner loop, a double integral sliding mode controller (DISMC) is used to improve the performance and anti-interference ability of the PV converter. This method unifies MPPT and bus voltage adjustment strategy without any communication and changing any hardware structure and control parameters. When mode switching occurs, only the reference value of voltage inner loop would be slightly adjusted near the maximum photovoltaic power point, so the seamless transition for PV converter between the two modes can be ensured. Finally, the effectiveness of the mode seamless switching control strategy is demonstrated by the simulation and experimental tests.
•Double integral sliding mode control is proposed for one-stage PV converter.•Small offset signal based on bus voltage is adopted to adjust PV working voltage.•PV converter under MPPT and CVC modes is always controlled as voltage source.•Parameter setting method of seamless switching controller is analyzed in detail.•Seamless transition for PV converter between MPPT and CVC modes is realized.
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•FOXD2-AS1 was significantly up-regulated in the OS tissue and cell lines.•Transcription factor HIF-1α could bind with the promoter region of FOXD2-AS1 to activate the transcription ...in OS cells.•FOXD2-AS1 inhibited the expression of p21 via interacting with EZH2 to silence p21 gene.
Emerging literature indicates the essential roles of long noncoding RNA (lncRNA) in the osteosarcoma (OS). However, the regulatory function and mechanism of FOXD2-AS1 in the OS is still elusive. In present research, the level of FOXD2-AS1 was significantly up-regulated in the OS tissue and cell lines compared to corresponding controls. The aberrant high-expression of FOXD2-AS1 indicated the poor clinical prognosis of OS patients. Transcription factor HIF-1α could bind with the promoter region of FOXD2-AS1 to activate the transcription in OS cells. Functionally, the knockdown of FOXD2-AS1 could repress the malignant biological properties of OS cells in vitro and vivo, including proliferation, invasion, apoptosis and tumor growth. Mechanistically, FOXD2-AS1 inhibited the expression of p21 via interacting with EZH2 to silence p21 gene expression. Overall, we conclude that FOXD2-AS1, induced by transcription factor HIF-1α, acts as an oncogene in the OS tumorigenesis and FOXD2-AS1 interacts with EZH2 to silence p21 protein. This finding could provide a novel insight and potential therapeutic target for the OS.
Mycobacterium tuberculosis (Mtb) relies on a specialized set of metabolic pathways to support growth in macrophages. By conducting an extensive, unbiased chemical screen to identify small molecules ...that inhibit Mtb metabolism within macrophages, we identified a significant number of novel compounds that limit Mtb growth in macrophages and in medium containing cholesterol as the principle carbon source. Based on this observation, we developed a chemical-rescue strategy to identify compounds that target metabolic enzymes involved in cholesterol metabolism. This approach identified two compounds that inhibit the HsaAB enzyme complex, which is required for complete degradation of the cholesterol A/B rings. The strategy also identified an inhibitor of PrpC, the 2-methylcitrate synthase, which is required for assimilation of cholesterol-derived propionyl-CoA into the TCA cycle. These chemical probes represent new classes of inhibitors with novel modes of action, and target metabolic pathways required to support growth of Mtb in its host cell. The screen also revealed a structurally-diverse set of compounds that target additional stage(s) of cholesterol utilization. Mutants resistant to this class of compounds are defective in the bacterial adenylate cyclase Rv1625/Cya. These data implicate cyclic-AMP (cAMP) in regulating cholesterol utilization in Mtb, and are consistent with published reports indicating that propionate metabolism is regulated by cAMP levels. Intriguingly, reversal of the cholesterol-dependent growth inhibition caused by this subset of compounds could be achieved by supplementing the media with acetate, but not with glucose, indicating that Mtb is subject to a unique form of metabolic constraint induced by the presence of cholesterol.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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