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1.
Nature ; 608(7922): 330-335, 2022 08.
Article in English | MEDLINE | ID: mdl-35948713

ABSTRACT

Earth is the only planet known to have continents, although how they formed and evolved is unclear. Here using the oxygen isotope compositions of dated magmatic zircon, we show that the Pilbara Craton in Western Australia, Earth's best-preserved Archaean (4.0-2.5 billion years ago (Ga)) continental remnant, was built in three stages. Stage 1 zircons (3.6-3.4 Ga) form two age clusters with one-third recording submantle δ18O, indicating crystallization from evolved magmas derived from hydrothermally altered basaltic crust like that in modern-day Iceland1,2. Shallow melting is consistent with giant impacts that typified the first billion years of Earth history3-5. Giant impacts provide a mechanism for fracturing the crust and establishing prolonged hydrothermal alteration by interaction with the globally extensive ocean6-8. A giant impact at around 3.6 Ga, coeval with the oldest low-δ18O zircon, would have triggered massive mantle melting to produce a thick mafic-ultramafic nucleus9,10. A second low-δ18O zircon cluster at around 3.4 Ga is contemporaneous with spherule beds that provide the oldest material evidence for giant impacts on Earth11. Stage 2 (3.4-3.0 Ga) zircons mostly have mantle-like δ18O and crystallized from parental magmas formed near the base of the evolving continental nucleus12. Stage 3 (<3.0 Ga) zircons have above-mantle δ18O, indicating efficient recycling of supracrustal rocks. That the oldest felsic rocks formed at 3.9-3.5 Ga (ref. 13), towards the end of the so-called late heavy bombardment4, is not a coincidence.

2.
Nature ; 592(7852): 70-75, 2021 04.
Article in English | MEDLINE | ID: mdl-33790444

ABSTRACT

Much of the current volume of Earth's continental crust had formed by the end of the Archaean eon1 (2.5 billion years ago), through melting of hydrated basaltic rocks at depths of approximately 25-50 kilometres, forming sodic granites of the tonalite-trondhjemite-granodiorite (TTG) suite2-6. However, the geodynamic setting and processes involved are debated, with fundamental questions arising, such as how and from where the required water was added to deep-crustal TTG source regions7,8. In addition, there have been no reports of voluminous, homogeneous, basaltic sequences in preserved Archaean crust that are enriched enough in incompatible trace elements to be viable TTG sources5,9. Here we use variations in the oxygen isotope composition of zircon, coupled with whole-rock geochemistry, to identify two distinct groups of TTG. Strongly sodic TTGs represent the most-primitive magmas and contain zircon with oxygen isotope compositions that reflect source rocks that had been hydrated by primordial mantle-derived water. These primitive TTGs do not require a source highly enriched in incompatible trace elements, as 'average' TTG does. By contrast, less sodic 'evolved' TTGs require a source that is enriched in both water derived from the hydrosphere and also incompatible trace elements, which are linked to the introduction of hydrated magmas (sanukitoids) formed by melting of metasomatized mantle lithosphere. By concentrating on data from the Palaeoarchaean crust of the Pilbara Craton, we can discount a subduction setting6,10-13, and instead propose that hydrated and enriched near-surface basaltic rocks were introduced into the mantle through density-driven convective overturn of the crust. These results remove many of the paradoxical impediments to understanding early continental crust formation. Our work suggests that sufficient primordial water was already present in Earth's early mafic crust to produce the primitive nuclei of the continents, with additional hydrated sources created through dynamic processes that are unique to the early Earth.

3.
Proc Natl Acad Sci U S A ; 121(20): e2306776121, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38709933

ABSTRACT

A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.


Subject(s)
Breast Neoplasms , Cell Differentiation , Diet, High-Fat , Disease Progression , Gastrointestinal Microbiome , Leucine , Myeloid-Derived Suppressor Cells , Animals , Diet, High-Fat/adverse effects , Leucine/metabolism , Female , Humans , Mice , Myeloid-Derived Suppressor Cells/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/microbiology , Breast Neoplasms/metabolism , Obesity/microbiology , Obesity/metabolism , Obesity/pathology , Cell Line, Tumor
4.
Phys Chem Chem Phys ; 26(11): 8784-8793, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38420852

ABSTRACT

The homogeneous condensation of water vapor at ambient temperature is studied using molecular dynamics simulation. We reveal that there is a droplet size at the nanoscale where water droplets can be stabilized in the condensation process. Our simulations show that the growth of water droplets is dominated by collision and coagulation between small water droplets after nucleation. This process is found to be accompanied by exceptionally fast evaporation such that droplet growth is balanced by evaporation when water droplets grow to a critical size, approximately 12.5 Å in radius, reaching a stable size distribution. The extremely high evaporation rate is attributed to the curvature dependence of surface tension. Surface tension shows a significant decrease with decreasing droplet size below 20 Å, which causes the total free energy of nanoscaled water droplets to rise after collision and coagulation. Consequently, water droplets have to shrink via fast evaporation. The curvature dependence of surface tension is related to the dielectric ordering of water molecules near the surface of water droplets. Owing to fast evaporation, secondary condensation occurs, and many small water clusters form, ultimately exhibiting a bimodal distribution of water-droplet size.

5.
Appl Microbiol Biotechnol ; 108(1): 7, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38170311

ABSTRACT

Carotenoids are natural lipophilic pigments, which have been proven to provide significant health benefits to humans, relying on their capacity to efficiently scavenge singlet oxygen and peroxyl radicals as antioxidants. Strains belonging to the genus Rhodosporidium represent a heterogeneous group known for a number of phenotypic traits including accumulation of carotenoids and lipids and tolerance to heavy metals and oxidative stress. As a representative of these yeasts, Rhodosporidium toruloides naturally produces carotenoids with high antioxidant activity and grows on a wide variety of carbon sources. As a result, R. toruloides is a promising host for the efficient production of more value-added lipophilic compound carotenoids, e.g., torulene and torularhodin. This review provides a comprehensive summary of the research progress on carotenoid biosynthesis in R. toruloides, focusing on the understanding of biosynthetic pathways and the regulation of key enzymes and genes involved in the process. Moreover, the relationship between the accumulation of carotenoids and lipid biosynthesis, as well as the stress from diverse abiotic factors, has also been discussed for the first time. Finally, several feasible strategies have been proposed to promote carotenoid production by R. toruloides. It is possible that R. toruloides may become a critical strain in the production of carotenoids or high-value terpenoids by genetic technologies and optimal fermentation processes. KEY POINTS: • Biosynthetic pathway and its regulation of carotenoids in Rhodosporidium toruloides were concluded • Stimulation of abiotic factors for carotenoid biosynthesis in R. toruloides was summarized • Feasible strategies for increasing carotenoid production by R. toruloides were proposed.


Subject(s)
Carotenoids , Rhodotorula , Humans , Carotenoids/metabolism , Rhodotorula/genetics , Yeasts/metabolism , Biosynthetic Pathways
6.
Mol Cell Proteomics ; 21(5): 100233, 2022 05.
Article in English | MEDLINE | ID: mdl-35427813

ABSTRACT

Legionella pneumophila, an environmental bacterium that parasitizes protozoa, causes Legionnaires' disease in humans that is characterized by severe pneumonia. This bacterium adopts a distinct biphasic life cycle consisting of a nonvirulent replicative phase and a virulent transmissive phase in response to different environmental conditions. Hence, the timely and fine-tuned expression of growth and virulence factors in a life cycle-dependent manner is crucial for survival and replication. Here, we report that the completion of the biphasic life cycle and bacterial pathogenesis is greatly dependent on the protein homeostasis regulated by caseinolytic protease P (ClpP)-dependent proteolysis. We characterized the ClpP-dependent dynamic profiles of the regulatory and substrate proteins during the biphasic life cycle of L. pneumophila using proteomic approaches and discovered that ClpP-dependent proteolysis specifically and conditionally degraded the substrate proteins, thereby directly playing a regulatory role or indirectly controlling cellular events via the regulatory proteins. We further observed that ClpP-dependent proteolysis is required to monitor the abundance of fatty acid biosynthesis-related protein Lpg0102/Lpg0361/Lpg0362 and SpoT for the normal regulation of L. pneumophila differentiation. We also found that the control of the biphasic life cycle and bacterial virulence is independent. Furthermore, the ClpP-dependent proteolysis of Dot/Icm (defect in organelle trafficking/intracellular multiplication) type IVB secretion system and effector proteins at a specific phase of the life cycle is essential for bacterial pathogenesis. Therefore, our findings provide novel insights on ClpP-dependent proteolysis, which spans a broad physiological spectrum involving key metabolic pathways that regulate the transition of the biphasic life cycle and bacterial virulence of L. pneumophila, facilitating adaptation to aquatic and intracellular niches.


Subject(s)
Legionella pneumophila , Legionnaires' Disease , Animals , Bacterial Proteins/metabolism , Endopeptidase Clp/metabolism , Humans , Legionnaires' Disease/microbiology , Life Cycle Stages , Proteolysis , Proteomics , Virulence
7.
J Stroke Cerebrovasc Dis ; 32(3): 106938, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36621119

ABSTRACT

OBJECTIVES: Mutations in the MYH11 gene result in smooth muscle cell dysfunction and are associated with familial thoracic aortic aneurysms and dissection. We describe a pediatric patient with a stroke and a pathogenic MYH11 IVS32G>A mutation, and a phenotype similar to ACTA2. METHODS: A proband girl with an acute ischemic stroke underwent genetic analysis and 7T high-resolution MRI. RESULTS: A 12-year-old girl presented with a right middle cerebral artery occlusion. She received thrombolysis and underwent mechanical thrombectomy. An extensive stroke work-up was negative. A three-generation pedigree showed a splice site mutation of MYH11 IVS32G>A of the proband and three more family members. A 7T-MRI showed "broomstick-like" straightening of distal arterial segments, a V-shaped anterior corpus callosum and a post-stroke cystic area of encephalomalacia. This vascular appearance and parenchymal abnormalities typically present in patients with an ACTA2 phenotype. 7T-MRI also demonstrated thickening of the right middle cerebral arterial wall. DISCUSSION: This case suggests that MYH11 patients may have a similar angiographic and brain parenchymal phenotype to patients with ACTA2 mutations. This is the first report of arterial wall thickening in a MYH11 stroke patient using 7T-MRI. Patients with MYH11 mutations may display a focal cerebral steno-occlusive arteriopathy that may lead to stroke.


Subject(s)
Cerebral Arterial Diseases , Cerebrovascular Disorders , Ischemic Stroke , Stroke , Female , Humans , Stroke/etiology , Stroke/genetics , Magnetic Resonance Imaging , Myosin Heavy Chains/genetics
8.
Bioorg Med Chem ; 73: 117006, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36150342

ABSTRACT

Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) is an important virulence factor that blocks the host immune response and facilitates M. tuberculosis growth in host cells. MptpB inhibitors are potential components of tuberculosis combination treatment. Herein, we present the development of new biphenyls MptpB inhibitors with greatly improved MptpB inhibition based on our reported thiobarbiturate lead 6 by rational design with the structure-based strategy. The eight biphenyls bearing thiobarbiturate fragment target compounds showed more potent MptpB inhibition (IC50: 1.18-14.13 µM) than the lead compound 6. Further molecular docking studies showed that compounds 13, 26, 27 and 28 had multiple interactions with active sites. Among them, compound 13 exhibited dose-dependent increased antituberculosis activity in mouse macrophages. The results displayed that the strategy of modification utilizing biphenyl scaffold was efficient. Our study identifies biphenyls bearing thiobarbiturate fragment as new MptpB inhibitors and verifies the therapeutic potential of antimycobacterial agent targeting MptpB.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Antitubercular Agents/chemistry , Bacterial Proteins/metabolism , Biphenyl Compounds , Enzyme Inhibitors/chemistry , Mice , Molecular Docking Simulation , Mycobacterium tuberculosis/metabolism , Protein Tyrosine Phosphatases , Thiobarbiturates , Tuberculosis/microbiology , Virulence Factors
9.
J Chem Phys ; 157(21): 214703, 2022 Dec 07.
Article in English | MEDLINE | ID: mdl-36511537

ABSTRACT

The rotational dynamics of water near the ice/water interface and its relation with the crystal growth of ice are investigated by using molecular dynamics simulations. We find that the dipole-moment profiles of water adjacent to interfaces display an oscillation behavior, which is in contrast to the monotonic decay near the free surface for water films. This dielectric oscillation phenomenon is associated with the strong response to hard solid/water interface. It significantly suppresses the dielectric relaxation and slows down the rotational diffusion near the interface compared to bulk water. We propose that the rotational diffusion determines the active degree of growth sites on interfaces, and its slowdown due to the interfacial dielectric oscillation contributes to reducing the growth rate of ice. With this idea, we predict the crystal growth rate of ice based on the modified Wilson-Frenkel model involving rotational dynamics. The theoretical result agrees well with the simulation.

10.
Biotechnol Lett ; 44(5-6): 777-786, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35416565

ABSTRACT

Legionella pneumophila is the major causative agent of Legionnaires' disease and Pontiac fever, which pose major public health problems. Rapid detection of L. pneumophila is important for global control of these diseases. Aptamers, short oligonucleotides that bind to targets with high affinity and specificity, have great potential for use in pathogenic bacterium detection, diagnostics, and therapy. Here, we used a whole-cell SELEX (systematic evolution of ligands by exponential enrichment) method to isolate and characterize single-stranded DNA (ssDNA) aptamers against L. pneumophila. A total of 60 ssDNA sequences were identified after 17 rounds of selection. Other bacterial species (Escherichia coli, Bacillus subtilis, Pseudomonas syringae, Staphylococcus aureus, Legionella quateirensis, and Legionella adelaidensis) were used for counterselection to enhance the specificity of ssDNA aptamers against L. pneumophila. Four ssDNA aptamers showed strong affinity and high selectivity for L. pneumophila, with Kd values in the nanomolar range. Bioinformatic analysis of the most specific aptamers revealed predicted conserved secondary structures that might bind to L. pneumophila cell walls. In addition, the binding of these four fluorescently labeled aptamers to the surface of L. pneumophila was observed directly by fluorescence microscopy. These aptamers identified in this study could be used in the future to develop medical diagnostic tools and public environmental detection assays for L. pneumophila.


Subject(s)
Aptamers, Nucleotide , Legionella pneumophila , Aptamers, Nucleotide/chemistry , DNA, Single-Stranded/genetics , Escherichia coli/genetics , Legionella pneumophila/genetics , Legionella pneumophila/metabolism , SELEX Aptamer Technique
11.
Stroke ; 52(4): 1465-1468, 2021 04.
Article in English | MEDLINE | ID: mdl-33563021

ABSTRACT

BACKGROUND AND PURPOSE: Atherosclerotic remodeling of the aneurysm wall, which could be detected as aneurysm wall enhancement (AWE) by magnetic resonance-vessel wall imaging, is a part of degenerative change of unruptured intracranial aneurysms (UIAs). The purpose of this study was to determine whether the luminal concentrations of atherosclerotic proteins in the aneurysm sac were associated with increased wall enhancement of UIAs in vessel wall imaging. METHODS: We performed a prospective study of subjects undergoing endovascular treatments for UIAs. All subjects underwent evaluation using 3T-magnetic resonance imaging, including pre/postcontrast vessel wall imaging of the UIAs. Blood samples were collected from the aneurysm sac and the parent artery during endovascular procedures. Presence/absence of AWE was correlated with the delta difference in concentration for each atherosclerotic protein between the lumen of UIA and in the parent artery. RESULTS: A total of consecutive 17 patients with 19 UIAs were enrolled. The delta difference of lipoprotein(a) was significantly higher in UIAs with AWE compared with those without AWE (-6.9±16.0 versus -45.4±44.9 µg/mL, P=0.03). CONCLUSIONS: Higher luminal concentrations of lipoprotein(a) in the aneurysm sac were significantly associated with increased wall enhancement of UIAs. A larger study is needed to confirm these findings.


Subject(s)
Intracranial Aneurysm/pathology , Lipoprotein(a)/analysis , Aged , Atherosclerosis/diagnostic imaging , Atherosclerosis/pathology , Female , Humans , Intracranial Aneurysm/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged
12.
Langmuir ; 37(44): 13059-13066, 2021 Nov 09.
Article in English | MEDLINE | ID: mdl-34709837

ABSTRACT

The slab-confined water at the nanoscale exhibits anomalous dielectric properties compared to bulk water, for example, significantly low dielectric constant. In this work, we study the dielectric properties of nanoscale water droplets at room temperature using molecular dynamics simulations. We find that the nanoscale water droplets feature weakly anisotropic dielectric constant: the radial component of dielectric constants is distinctly smaller than the tangential component although they both decrease with reducing droplet size in a similar way. Such dielectric behavior is closely related to the orientational preference of water molecules near the convex surface. The molecular dipole prefers to slightly orientate toward the interior of droplets in contrast to the out-of-plane preference for free-standing water films and slab-confined water, which suppresses the fluctuation of dipole moments in the radial direction. Meanwhile, it facilitates the formation of the open hydrogen-bond network in the surface layer and ultimately leads to the relatively weak suppression of tangential fluctuations. The differential suppression is responsible for the anisotropic dielectric constant of water droplets. This anisotropic characteristic is also found in dielectric relaxation: both the radial and the tangential relaxation are consistently slowed down upon approaching surface but the latter is universally slower.

13.
Phys Chem Chem Phys ; 23(6): 3942-3948, 2021 Feb 19.
Article in English | MEDLINE | ID: mdl-33543736

ABSTRACT

We investigate the melting process of polycrystalline copper doped with hydrogen atoms by using the newly developed Cu/H ReaxFF force field. Hydrogen atoms are found to effectively promote the melting of copper, and even make it happen at temperatures below the equilibrium melting temperature of copper during rapid heating. The enhanced melting is closely relevant to the interaction of hydrogen atoms with the grain boundary. We find that host Cu atoms perform cooperative vibration around the grain boundaries as the precursor of premelting. The doping of hydrogen atoms is shown to drive the vibration more violent so that the grain boundary becomes broader and the premelting is prematurely triggered. Meanwhile, hydrogen atoms segregated in grain boundaries massively diffuse into the bulk region with increasing temperature, resulting in intensification of lattice distortion of the bulk phase. This facilitates the rapid advancement of the liquid-solid interface during melting in contrast to the slow and discontinuous interface advancement in hydrogen-free polycrystalline copper. Our results suggest that even a small amount of hydrogen atoms is expected to significantly affect the thermodynamic properties of metals with the existence of structural defects.

14.
Bioorg Chem ; 106: 104495, 2021 01.
Article in English | MEDLINE | ID: mdl-33293055

ABSTRACT

The secreted Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (MptpB) is an essential virulence factor required for the intracellular survival of Mtb within host macrophages. MptpB has become a promising target for the development of novel anti-tuberculosis (TB) drugs. In this study, two new fusarielins, fusarielins M (1) and N (2), and a biogenetically related known compound, fusarielin G (3) were isolated from the marine-derived fungus Fusarium graminearum SYSU-MS5127. Their inhibitory effects on MptpB were evaluated. Among these compounds, fusarielin M substantially inhibited MptpB with a half-maximal inhibitory concentration (IC50) of 1.05 ± 0.08 µM, and an inhibition constant (Ki) of 1.03 ± 0.39 µM. Surface plasmon resonance analysis was used to characterize the interaction between fusarielin M and MptpB in vitro. Fusarielin M also exhibited cellular activity in blocking MptpB-mediated Erk1/2 and p38 inactivation in macrophages. Importantly, fusarielin M (20 µM) substantially reduced intracellular mycobacterial growth within macrophages, causing a 62% reduction in the bacterial burden. The binding mode of fusarielin M was further explored via molecular docking which suggested that fusarielin M binds to the active site of MptpB, forming a hydrogen bond with the side chain of Asp165; this is unique in the P-loop of MptpB compared to conventional human PTPs. The contact between fusarielin M and Asp165 in the catalytic loop provides a potential basis for inhibitor selectivity. Therefore, fusarielin M shows great potential as an anti-TB drug candidate.


Subject(s)
Antitubercular Agents/pharmacology , Enzyme Inhibitors/pharmacology , Mycobacterium tuberculosis/drug effects , Protein Tyrosine Phosphatases/antagonists & inhibitors , Animals , Antitubercular Agents/chemistry , Antitubercular Agents/isolation & purification , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Fusarium/chemistry , Humans , Mice , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/enzymology , Mycobacterium tuberculosis/growth & development , Protein Tyrosine Phosphatases/metabolism , Structure-Activity Relationship
15.
Bioorg Chem ; 115: 105156, 2021 10.
Article in English | MEDLINE | ID: mdl-34314917

ABSTRACT

Under guidance of 1H NMR, ten new polypropionate derivatives, decempyrones A-J (1-10) along with two known analogues (11 and 12), were isolated from the marine-derived fungusFusarium decemcellulare SYSU-MS6716. The planar structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, and HR-ESIMS). The absolute configuration of the chiral centers in the side chain is a major obstacle for the structure identification of natural polypropionate derivatives. Herein, the J-based configurational analysis (JBCA), chemical degradation, geminal proton rule, and the modified Mosher's method were adopted to fix their absolute configurations in the side chain. Compounds 3 and 10 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC50values 22.4 ± 1.8 and 21.7 ± 1.1 µM. In addition, compounds 3 and 10 displayed MptpA inhibitory activity with an IC50 value of 19.2 ± 0.9 and 33.1 ± 2.9 µM. Structure-activity relationships of the polypropionate derivatives were discussed.


Subject(s)
Anti-Inflammatory Agents/chemistry , Propionates/chemistry , Protein Tyrosine Phosphatases/antagonists & inhibitors , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/metabolism , Fusarium/chemistry , Fusarium/metabolism , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Magnetic Resonance Spectroscopy , Mice , Molecular Conformation , Nitric Oxide/metabolism , Propionates/isolation & purification , Propionates/pharmacology , Protein Tyrosine Phosphatases/metabolism , RAW 264.7 Cells
16.
J Comput Chem ; 41(10): 1026-1033, 2020 Apr 15.
Article in English | MEDLINE | ID: mdl-31970817

ABSTRACT

Metal azides have attracted increasing attention as precursors for synthesizing polymeric nitrogen. In this article, we report the amorphous polymerization of nitrogen by compressing cupric azide. The ab initio molecular dynamics simulations show that crystalline cupric azide transforms into a disordered network composed of singly bonded nitrogen at a hydrostatic pressure of 40 GPa and room temperature. The transformation manifests the formation of a π delocalization along the disordered Cu-N network, thus resulting in a semiconductor-metal transition. The estimated heat of formation of the amorphous polymeric nitrogen system is comparable to conventional high-energy-density materials. The amorphization provides an alternative route to the polymerization of nitrogen under moderate conditions.

17.
Cell Microbiol ; 21(6): e13014, 2019 06.
Article in English | MEDLINE | ID: mdl-30702192

ABSTRACT

The major virulence determinant of Legionella pneumophila is the type IVB secretion system (T4BSS), which delivers approximately 330 effector proteins into the host cell to modulate various cellular processes. However, the functions of most effector proteins remain unclear. WipA, an effector, was the first phosphotyrosine phosphatase of Legionella with unknown function. In this study, we found that WipA induced relatively strong growth defects in yeast in a phosphatase activity-dependent manner. Phosphoproteomics data showed that WipA was likely involved into endocytosis, FcγR-mediated phagocytosis, tight junction, and regulation of actin cytoskeleton pathways. Western blotting further confirmed WipA dephosphorylates several proteins associated with actin polymerisation, such as p-N-WASP, p-ARP3, p-ACK1, and p-NCK1. Thus, we hypothesised that WipA targets N-WASP/ARP2/3 complex signalling pathway, leading to disturbance of actin polymerisation. Indeed, we demonstrated that WipA inhibits host F-actin polymerisation by reducing the G-actin to F-actin transition during L. penumophila infection. Furthermore, the intracellular proliferation of wipA/legK2 double mutant was significantly impaired at the late stage of infection, although the absence of WipA does not confer any further effect on actin polymerisation to the legK2 mutant. Collectively, this study provides unique insights into the WipA-mediated regulation of host actin polymerisation and assists us to elucidate the pathogenic mechanisms of L. pnuemophila infection.


Subject(s)
Actin Cytoskeleton/metabolism , Actins/metabolism , Legionella pneumophila/enzymology , Macrophages/metabolism , Phosphotyrosine/metabolism , Protein Tyrosine Phosphatases/metabolism , Virulence Factors/metabolism , Actin Cytoskeleton/microbiology , Actin-Related Protein 2-3 Complex/metabolism , Actins/chemistry , Animals , Chromatography, Liquid , HEK293 Cells , HeLa Cells , Host-Pathogen Interactions , Humans , Legionella pneumophila/metabolism , Legionella pneumophila/pathogenicity , Legionnaires' Disease/metabolism , Macrophages/microbiology , Mice , Phagocytosis/genetics , Protein Tyrosine Phosphatases/genetics , Protein Tyrosine Phosphatases/toxicity , Proteomics , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae/metabolism , Signal Transduction/genetics , Tandem Mass Spectrometry , Tight Junctions/metabolism
18.
Phys Chem Chem Phys ; 22(8): 4815-4822, 2020 Feb 26.
Article in English | MEDLINE | ID: mdl-32068220

ABSTRACT

Crystallization in highly supercooled Cu50Zr50 films close to the glass transition is studied by using molecular dynamics simulations. Spontaneous nucleation is observed at the simulation timescale in contrast to the bulk counterpart. We find that nucleation occurs at free surfaces owing to the partial wetting of the nucleus by melt. The anomalous wetting phenomenon is closely related to strong density layering arising from the surface: the high density associated with surface layering increases surface energy of supercooled melts, resulting in that one facet of the crystalline embryo is preferentially formed on the film surface. The surface-based embryo is then developed into a stable nucleus by bridging two surfaces of thin films. The kinetics and thermodynamics analyses based on the mean first-passage time method show that the nucleation process still follows the description of the classical nucleation theory despite extremely high supercoolings. In nucleating, the slow interface dynamics becomes dominant and induces a low nucleation rate although the nucleation barrier is very low. The subsequent crystal growth is found to proceed in a quasi-two-dimensional manner with a ramified interface morphology, which is analogous to percolative crystals predicted in glass-forming liquids.

19.
Mult Scler ; 25(9): 1316-1325, 2019 08.
Article in English | MEDLINE | ID: mdl-30113252

ABSTRACT

BACKGROUND: Intestinal microbiota is an important environmental factor in the initiation and progression of autoimmune diseases. However, investigations on the gut microbiome in neuromyelitis optica spectrum disorders (NMOSD) are relatively insufficient, especially for that of the Asia population. OBJECTIVES: To evaluate whether or not the intestinal microbiota of NMOSD patients had specific microbial signatures. METHODS: Next-generation sequencing and gas chromatography were employed to compare the fecal microbial composition and short-chain fatty acids (SCFAs) spectrum between patients with NMOSD (n = 84) and healthy controls (n = 54). RESULTS: The gut microbial composition of NMOSD distinguished from healthy individuals. Streptococcus, significantly increased in NMOSD, is positively correlated with disease severities (p < 0.05). The use of immunosuppressants results in a decrease of Streptococcus, suggesting that Streptococcus might play a significant role in the pathogenesis of NMOSD. A striking depletion of fecal SCFAs was observed in NMOSD patients (p < 0.0001), with acetate and butyrate showing significantly negative correlation with disease severities (p < 0.05). CONCLUSION: The fecal organismal structures and SCFAs level of patients with NMOSD were distinctive from healthy individuals. These findings not only could be critical events driving the aberrant immune response responsible for the pathogenesis of these disorders but could also provide suggestions for disease therapy.


Subject(s)
Dysbiosis/microbiology , Fatty Acids, Volatile , Feces , Gastrointestinal Microbiome , Neuromyelitis Optica/microbiology , Streptococcus , Adult , China , Feces/microbiology , Female , Humans , Male , Middle Aged , Severity of Illness Index
20.
Langmuir ; 35(15): 5162-5167, 2019 Apr 16.
Article in English | MEDLINE | ID: mdl-30907599

ABSTRACT

The dendritic growth of ice in supercooled water droplets is studied theoretically and experimentally. The measured dendritic growth velocity of ice shows a good agreement with the prediction of the Langer and Müller-Krumbhaar (LM-K) growth model at supercoolings less than 7 K, whereas an increasing overestimation in the latter is observed as the droplets are further supercooled. Therefore, the LM-K dendritic growth model is modified by considering the influence of interface kinetics. In the modified model, a dendrite grows in the limit of marginal stability coupled with diffusion at the liquid-solid interface, and the interface kinetics supercooling is introduced to predict the dendritic growth velocity. The interface kinetics factor is determined by fitting the experimental dendritic growth velocity within the framework of the modified model. This modification to the LM-K model well describes the dendritic growth of ice in water supercooled up to 25 K. It provides a solution to the dendritic growth of ice in the high-supercooling regime and can serve as a reliable input for studies on icing problems in engineering fields.

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