Conspectus Silica-based nanoparticles (SNPs) are a classic type of material employed in biomedical applications because of their excellent biocompatibility and tailorable physiochemical properties. ...Typically, SNPs are designed as nanocarriers for therapeutics delivery, which can address a number of intrinsic drawbacks of therapeutics, including limited bioavailability, short circulation lifetime, and unfavorable biodistribution. To improve the delivery efficiency and spatiotemporal precision, tremendous efforts have been devoted to engineering the physiochemical properties of SNPs, including particle size, morphology, and mesostructure, as well as conjugating targeting ligands and/or “gatekeepers” to endow improved cell selectivity and on demand release profiles. Despite significant progress, the biologically inert nature of the bare silica framework has largely restricted the functionalities of SNPs, rendering conventional SNPs mainly as nanocarriers for targeted delivery and controlled release. To meet the requirements of next generation nanomedicines with improved efficacy and precision, new insights on the relationship between the physiochemical properties of SNPs and their biological behavior are highly valuable. Meanwhile, a conceptual shift from a simple spatiotemporal control mechanism to a more sophisticated biochemistry and signaling pathway modulation would be of great importance. In this Account, an overview of our recent contribution to the field is presented, wherein SNPs with rationally designed nanostructures and nanochemistry are applied as nanocarriers (defined as “nanomaterials being used as a transport module for another substance” according to Wikipedia) and/or biomodulators (defined as “any material that modifies a biological response” according to Wiktionary). This Account encompasses two main sections. In the first section, we focus on the conventional nanocarriers concept with new insights on the design principles of the nanostructures. We present examples to demonstrate the engineering of pore geometry, surface topology, and asymmetry of nanoparticles to achieve enhanced drug, gene, and protein delivery efficiency. The contribution of surface roughness of SNPs on improving the cellular uptake efficiency, adhesion property, and DNA transfection capacity is particularly highlighted. In the second section, we discuss novel SNPs designed as biomodulators to regulate intracellular microenvironment and cell signaling, such as the oxidative stress and glutathione levels for improving the anticancer efficacy of therapeutics and mRNA transfection in specific cell lines. The interplay between the nanoparticles, biological system, and drugs is discussed. We further discuss how to engineer the composition of SNPs to modulate metal hemostasis to realize inherent anticancer activity. Two typical examples, including modulating copper signaling for tumor vasculature targeted therapy and controlling iron signaling for macrophage polarization based immunotherapy, are presented to highlight the unique advantages of SNPs as nanosized therapeutics in comparison to molecular drugs. Moreover, utilizing these two examples, we showcase the possibility of designing SNPs with intrinsic pharmaceutical activity to indirectly control tumor growth without inducing significant cytotoxicity, thus alleviating the biosafety concerns of nanomedicines. At the end of this Account, we discuss our personal perspectives on the promises, opportunities, and issues in engineered SNPs as nanocarriers as well as their transition toward biomodulators. With a major focus on the latter scenario, the current status and possible future directions are outlined.
The unconformity-related uranium (URU) deposits in the Proterozoic Athabasca Basin (Canada) represent the richest, and one of the most important, uranium endowments in the world. Most of the URU ...deposits are associated with pre-existing graphitic basement faults that were reactivated after the formation of the basin. These graphite-rich structures have been widely used as a vector for exploration, but the nature of the association of the URU deposits with graphitic basement faults has been debated for over four decades. Proposed roles of graphite include: (1) as a direct reducing agent to reduce U6+ to U4+ and precipitate uraninite; (2) as a precursor of hydrocarbons (mainly CH4) produced in situ or nearby and then used as a reducing agent for uraninite precipitation; (3) as a precursor of hydrocarbons produced at depth that were remobilized to the site of mineralization and acted as a reducing agent for uraninite precipitation; and (4) as a lubricant facilitating faulting and fluid flow that led to uranium mineralization. This paper uses the Phoenix uranium deposit in the southeastern Athabasca Basin as a case study to address these uncertainties. Petrographic studies indicate that there is no direct contact between graphite and uraninite at microscopic scales, and the content of graphite in the graphitic metapelite along the ore-controlling WS Shear Zone does not show a systematic change with the distance from the unconformity surface. Raman spectroscopic studies of graphite suggest that the degree of structural disorder of graphite, expressed by various parameters related to the D bands and G band ratios, does not change systematically with the distance from the unconformity surface either. The minor irregularities in these parameters near the unconformity are better explained by paleo-weathering related to the unconformity and/or diagenetic processes than by hydrothermal activity related to uranium mineralization. Based on these observations and interpretations, the role of graphite as an in situ reducing agent, either directly or as a provider of hydrocarbons, is discounted. It is proposed that hydrocarbons derived from graphite at depth, tapped by episodic reactivation or seismicity of the basement faults that was facilitated by graphite as a lubricant, were responsible for URU mineralization.
In this work, we calculate the magnetic moments of the
P
ψ
N
0
states and
P
ψ
Δ
0
states with valence quark content
c
¯
c
u
d
d
in molecular model, diquark–diquark–antiquark model and ...diquark–triquark model, as well as the transition magnetic moments in the molecular model. At the same time, we also calculate magnetic moments and transition magnetic moments of
P
ψ
Δ
+
+
states and
P
ψ
Δ
-
states in the molecular model as additional products. Our results show that in the diquark–diquark–antiquark model, the magnetic moments of
λ
excitation state are usually larger than the magnetic moments of
ρ
excitation state. We find some interesting proportional relationships between the expressions of transition magnetic moments. The results provide important insights for future experimental observation of hidden-charm pentaquark states and help to distinguish their inner structures. With these efforts, our understanding of the properties for the hidden-charm pentaquark states will become more abundant.
Oxide graphene (GO) nanosheets were prepared by modified Hummers and Offeman methods. The products were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier ...transform infrared spectrometry (FTIR), and thermogravimetric analysis (TGA). The tribological properties of GO nanosheets as water-base lubricant additive were investigated using a UMT-2 ball-plate tribotester. By the addition of GO nanosheets in pure water, the antiwear ability was improved and the friction coefficient was decreased. The water with GO nanosheets showed better tribological properties than the water with oxide multiwall carbon nanotubes (CNTs-COOH). It is concluded that the formation of a thin physical tribofilms on the substrate can explain the good friction and wear properties of GO nanosheets.
Electroactive microorganisms (EAMs) are ubiquitous in nature and have attracted considerable attention as they can be used for energy recovery and environmental remediation via their extracellular ...electron transfer (EET) capabilities. Although the EET mechanisms of Shewanella and Geobacter have been rigorously investigated and are well characterized, much less is known about the EET mechanisms of other microorganisms. For EAMs, efficient EET is crucial for the sustainable economic development of bioelectrochemical systems (BESs). Currently, the low efficiency of EET remains a key factor in limiting the development of BESs. In this review, we focus on the EET mechanisms of different microorganisms, (i.e., bacteria, fungi, and archaea). In addition, we describe in detail three engineering strategies for improving the EET ability of EAMs: (1) enhancing transmembrane electron transport via cytochrome protein channels; (2) accelerating electron transport via electron shuttle synthesis and transmission; and (3) promoting the microbe-electrode interface reaction via regulating biofilm formation. At the end of this review, we look to the future, with an emphasis on the cross-disciplinary integration of systems biology and synthetic biology to build high-performance EAM systems.
•Extracellular electron transfer mechanisms are summarized.•Extracellular electron transport pathways of microorganisms are summarized.•Engineering strategies for improving EET capabilities are reviewed.•New insights on further EET research are presented.
Indoline alkaloids constitute a large class of natural products; their diverse and complex structures contribute to potent biological activities in a range of molecules. Designing an appropriate ...strategy for the total synthesis of indoline alkaloids is a difficult task that depends on being able to efficiently assemble the core architectures. The best strategies allow access to a variety of different indoline alkaloid structures in a minimum of steps. The cyclopropanation of simple olefins and the subsequent synthetic transformation of the resulting cyclopropyl intermediates has been intensively studied in recent decades. In contrast, the cyclopropanation of enamines, especially for the construction of complex nitrogen-containing ring systems, remained relatively unexplored. Previous success with the cyclopropanation of simple indoles to form stable indolylcyclopropanocarboxylates encouraged us to explore the assembly of indoline alkaloid skeletons with cyclopropanation as a key reaction. Theoretically, indolylcyclopropanocarboxylates are doubly activated by a vicinally substituted amino group and carboxyl group; that is, they are typical donor−acceptor cyclopropanes. Accordingly, they tend to yield an active iminium intermediate, which can undergo inter- and intramolecular nucleophilic reactions to form the core structure of indoline alkaloids with an expanded ring system. In this Account, we summarize our efforts to develop a cascade or stepwise reaction of cyclopropanation/ring-opening/iminium cyclization (the CRI reaction) on tryptamine derivatives for assembling indoline alkaloid skeletons. With the CRI approach, three types of indoline alkaloid skeletons have been efficiently constructed: (i) hexahydropyrrolo2,3-bindoline (type I), (ii) tetrahydro-9a,4a-iminoethano-9H-carbazole (type II), and (iii) tetrahydroquinolino2,3-bindoline (type III). The effects of substituents on tryptamine derivatives were carefully investigated for inter- and intramolecular CRI reactions during construction of type I and type II skeletons. These results provided a basis for the further design and synthesis of complex natural products containing nitrogen. The usefulness of the CRI reaction is well demonstrated by our total synthesis of structurally intriguing indoline alkaloids such as N-acetylardeemin, minfiensine, vincorine, and communesin F. In addition, we highlight advances by other groups in construction of the three types of skeletons as well as their total syntheses of these indoline alkaloids. Discussion of the total syntheses of these indoline alkaloids focuses on comparing the individual synthetic strategies for forming the ring systems embedded in the final products. We also describe the total synthesis of perophoramidine, which has the same type III skeleton as communesin F. The observation of a retro Diels−Alder reaction during our synthesis of communesin F inspired the hetero Diels−Alder reaction on which our total synthesis of perophoramidine was based.
We have systematically investigated the spin-32 to spin-12 doubly charmed baryon transition magnetic moments to the next-to-next-to-leading order in the heavy baryon chiral perturbation theory ...(HBChPT). Numerical results of transition magnetic moments and decay widths are presented to the next-to-leading order: μΞcc⁎++→Ξcc++=−2.35μN, μΞcc⁎+→Ξcc+=1.55μN, μΩcc⁎+→Ωcc+=1.54μN, ΓΞcc⁎++→Ξcc++=22.0 keV, ΓΞcc⁎+→Ξcc+=9.57 keV, ΓΩcc⁎+→Ωcc+=9.45 keV.
Abstract
Hubei Province is gradually carrying out the preparation of five levels and three types of territorial spatial planning, to scientifically layout construction space, agricultural space and ...ecological space, and strengthen the guiding and constraining role of territorial spatial planning for all planning. At the same time, in order to promote the construction of beautiful countryside and rural revitalization, the preparation of village planning in Hubei Province is also in progress; according to the five levels and three categories of territorial spatial planning, village planning belongs to the township-level detailed planning category, and the conventional village planning can no longer meet the requirements of territorial spatial planning, so the ecological space, agricultural space and construction space in village planning should be adjusted and whitened with the help of GIS technology. Therefore, the GIS technology should be used for landuse adjustment, white space delineation, spatial control and comprehensive improvement of the national land space.
The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale 1, 2. Although bats are regarded as the ...most likely natural hosts for SARS-CoV-2 3, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.
•Metagenomic analysis identified a novel coronavirus, RmYN02, from R. malayanus•RmYN02 was the closest relative of SARS-CoV-2 in most of the virus genome•Two loop deletions in RBD may reduce the binding of RmYN02 with ACE2•RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein
Zhou et al. report a bat-derived coronavirus, RmYN02, which is the closest relative of SARS-CoV-2 in most of the virus genome reported to date. RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein in a similar manner to SARS-CoV-2. This suggests that such insertion events can occur naturally in animal betacoronaviruses.
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