Theoretical study of the saturation and nature of the hydrogen bonds to gold.

Traditional hydrogen bonds are well-known to exhibit directionality and saturation. By contrast, gold involved hydrogen bonds (GHBs) have been extensively studied but remain lack of in-depth understanding towards the intrinsic nature and saturation property. This work exemplifies three series of complexes: [L-Au-L]-⋯(HF)n (L = H, CH3, (CH3)3; n = 1-8) containing GHBs to dig into the intrinsic nature with the aid of multiple theoretical analysis methods, finding that the formation of GHB is highly subject to orbital interactions along with steric hindrance. Moreover, the saturation level of GHBs largely depends on the ligand attached to the gold center, since different ligands typically possess varying electron-giving ability and steric volume. This work confirms the coexistence of as many as 6 GHBs for one Au atom and thoroughly studies the saturation level of GHBs, which will provide new insights into GHBs and facilitate future synthesis of more complicated gold complexes.

Spatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding.

Spatially resolved transcriptomics provides the opportunity to investigate the gene expression profiles and the spatial context of cells in naive state, but at low transcript detection sensitivity or with limited gene throughput. Comprehensive annotating of cell types in spatially resolved transcriptomics to understand biological processes at the single cell level remains challenging. Here we propose Spatial-ID, a supervision-based cell typing method, that combines the existing knowledge of reference single-cell RNA-seq data and the spatial information of spatially resolved transcriptomics data. We present a series of benchmarking analyses on publicly available spatially resolved transcriptomics datasets, that demonstrate the superiority of Spatial-ID compared with state-of-the-art methods. Besides, we apply Spatial-ID on a self-collected mouse brain hemisphere dataset measured by Stereo-seq, that shows the scalability of Spatial-ID to three-dimensional large field tissues with subcellular spatial resolution.

Sodium Cationization Enables Exotic Deprotonation Sites on Gaseous Mononucleotides.

We report observation and photoelectron spectroscopic characterization of sodium cationization on four doubly deprotonated mononucleotide dianions Na+·[dNMP-2H]2- (N = A, G, C, or T) in the gas phase. Multiple tautomers with distinct deprotonated sites are identified, in which Na+ enables novel double deprotonation patterns and folds the resultant mononucleotide dianions. The most stable isomer for the whole family is derived from detaching one proton from the phosphate and the other from the nucleobase (amino group for N = A, G, and C, but nitrogen atom for T), whereas high-lying isomers with protons detached separately from the phosphate and the hydroxy group of sugar coexist. Particularly, an exotic deprotomer with both protons deprived from guanosine is populated as well. This work thus displays a remarkably diverse binding landscape enabled by sodium cationization, a potentially critical element in developing a general formulism to better model metal cation and nucleotide interactions.

Identification of spatially variable genes with graph cuts.

Single-cell gene expression data with positional information is critical to dissect mechanisms and architectures of multicellular organisms, but the potential is limited by the scalability of current data analysis strategies. Here, we present scGCO, a method based on fast optimization of hidden Markov Random Fields with graph cuts to identify spatially variable genes. Comparing to existing methods, scGCO delivers a superior performance with lower false positive rate and improved specificity, while demonstrates a more robust performance in the presence of noises. Critically, scGCO scales near linearly with inputs and demonstrates orders of magnitude better running time and memory requirement than existing methods, and could represent a valuable solution when spatial transcriptomics data grows into millions of data points and beyond.

Theoretical study on L-H+-L with identical donors: Short strong hydrogen bond or not?

Short strong hydrogen bonds (SSHBs) play a crucial role in many chemical processes. Recently, as the representative of SSHBs, [F-H-F]- was experimentally observed. [F-H-F]- has a symmetric structure, which can be described as a H+ acid shared by two terminal F- donors (F--H+-F-). To explore whether two identical donors are bound to result in SSHBs, we performed theoretical studies on a series of compounds (L-H+-L) with two identical electron donors (L corresponds to donors containing group 14, 15, 16, and 17 elements). The results show that identical donors do not definitely lead to SSHBs. Instead, typical hydrogen bonds also exist. Both electronegativity and basicity contribute to the patterns of hydrogen bonds, where more electronegative and weaker donors benefit to SSHBs. In addition, it was found that zero-point energies also respond to the hydrogen bonding systems. This systemic work is expected to provide more insights into SSHBs.

Revisiting the covalent nature of halogen bonding: a polarized three-center four-electron bond.

As an important intermolecular interaction, halogen bonding has been studied extensively, but its nature still suffers from controversy without one uniform essence. Electrostatics, charge transfer, polarization and dispersion are emphasized, but the covalent nature is usually overlooked except for the strong halogen bonding species I3 -, which is widely accepted as a result of a three-center four-electron (3c-4e) interaction. In our study, the potential energy surface of I3 - has been evaluated to explore the dissociation from I3 - to I2⋯I-. We found that different from an equivalent 3c-4e bond in I3 -, I2⋯I- can be rationalized by a polarized one. In addition, when the orbitals are polarized, it is exactly what traditional charge transfer or the popular σ-hole picture describes. I3 - can be described by the Lewis theory model with the middle I+ cation serving as the Lewis acid and two terminal I- anions acting as Lewis base. Therefore, we further extended this model to a series of I-containing species with chemical composition of L-I+-L, F--I+-L and H3P-I+-L (L = OH-, F-, Cl-, Br-, I-, PH3, NH3, H2S, HI, H2O, HBr and HCl) to explore the nature of halogen bonding. When the forces of two bases around I+ are the same, it corresponds to an equivalent 3c-4e bond, such as I3 -. Otherwise, it is a polarized multicenter bond, such as I2⋯I-. This work gives a new insight into the nature of halogen bonding compounds: besides the well-known I3 -, the nature of the other species is also a multicenter bond, existing as equivalent and polarized 3c-4e bonds, respectively.

Author Correction: Competitive endogenous RNA is an intrinsic component of EMT regulatory circuits and modulates EMT.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Competitive endogenous RNA is an intrinsic component of EMT regulatory circuits and modulates EMT.

The competitive endogenous RNA (ceRNA) hypothesis suggests an intrinsic mechanism to regulate biological processes. However, whether the dynamic changes of ceRNAs can modulate miRNA activities remains controversial. Here, we examine the dynamics of ceRNAs during TGF-ß-induced epithelial-to-mesenchymal transition (EMT). We observe that TGFBI, a transcript highly induced during EMT in A549 cells, acts as the ceRNA for miR-21 to modulate EMT. We further identify FN1 as the ceRNA for miR-200c in the canonical SNAIL-ZEB-miR200 circuit in MCF10A cells. Experimental assays and computational simulations demonstrate that the dynamically induced ceRNAs are directly coupled with the canonical double negative feedback loops and are critical to the induction of EMT. These results help to establish the relevance of ceRNA in cancer EMT and suggest that ceRNA is an intrinsic component of the EMT regulatory circuit and may represent a potential target to disrupt EMT during tumorigenesis.

CRISPR/dCas9-mediated transcriptional improvement of the biosynthetic gene cluster for the epothilone production in Myxococcus xanthus.

BACKGROUND: The CRISPR/dCas9 system is a powerful tool to activate the transcription of target genes in eukaryotic or prokaryotic cells, but lacks assays in complex conditions, such as the biosynthesis of secondary metabolites. RESULTS: In this study, to improve the transcription of the heterologously expressed biosynthetic genes for the production of epothilones, we established the CRISPR/dCas9-mediated activation technique in Myxococcus xanthus and analyzed some key factors involving in the CRISPR/dCas9 activation. We firstly optimized the cas9 codon to fit the M. xanthus cells, mutated the gene to inactivate the nuclease activity, and constructed the dCas9-activator system in an epothilone producer. We compared the improvement efficiency of different sgRNAs on the production of epothilones and the expression of the biosynthetic genes. We also compared the improvement effects of different activator proteins, the ω and α subunits of RNA polymerase, and the sigma factors σ54 and CarQ. By using a copper-inducible promoter, we determined that higher expressions of dCas9-activator improved the activation effects. CONCLUSIONS: Our results showed that the CRISPR/dCas-mediated transcription activation is a simple and broadly applicable technique to improve the transcriptional efficiency for the production of secondary metabolites in microorganisms. This is the first time to construct the CRISPR/dCas9 activation system in myxobacteria and the first time to assay the CRISPR/dCas9 activations for the biosynthesis of microbial secondary metabolites.

Error-prone DnaE2 Balances the Genome Mutation Rates in Myxococcus xanthus DK1622.

dnaE is an alpha subunit of the tripartite protein complex of DNA polymerase III that is responsible for the replication of bacterial genome. The dnaE gene is often duplicated in many bacteria, and the duplicated dnaE gene was reported dispensable for cell survivals and error-prone in DNA replication in a mystery. In this study, we found that all sequenced myxobacterial genomes possessed two dnaE genes. The duplicate dnaE genes were both highly conserved but evolved divergently, suggesting their importance in myxobacteria. Using Myxococcus xanthus DK1622 as a model, we confirmed that dnaE1 (MXAN_5844) was essential for cell survival, while dnaE2 (MXAN_3982) was dispensable and encoded an error-prone enzyme for replication. The deletion of dnaE2 had small effects on cellular growth and social motility, but significantly decreased the development and sporulation abilities, which could be recovered by the complementation of dnaE2. The expression of dnaE1 was always greatly higher than that of dnaE2 in either the growth or developmental stage. However, overexpression of dnaE2 could not make dnaE1 deletable, probably due to their protein structural and functional divergences. The dnaE2 overexpression not only improved the growth, development and sporulation abilities, but also raised the genome mutation rate of M. xanthus. We argued that the low-expressed error-prone DnaE2 played as a balancer for the genome mutation rates, ensuring low mutation rates for cell adaptation in new environments but avoiding damages from high mutation rates to cells.

[Spatial variation of soil properties and quality evaluation for arable Ustic Cambosols in central Henan Province].

A GIS-based 500 m x 500 m soil sampling point arrangement was set on 248 points at Wenshu Town of Yuzhou County in central Henan Province, where the typical Ustic Cambosols locates. By using soil digital data, the spatial database was established, from which, all the needed latitude and longitude data of the sampling points were produced for the field GPS guide. Soil samples (0-20 cm) were collected from 202 points, of which, bulk density measurement were conducted for randomly selected 34 points, and the ten soil property items used as the factors for soil quality assessment, including organic matter, available K, available P, pH, total N, total P, soil texture, cation exchange capacity (CEC), slowly available K, and bulk density, were analyzed for the other points. The soil property items were checked by statistic tools, and then, classified with standard criteria at home and abroad. The factor weight was given by analytic hierarchy process (AHP) method, and the spatial variation of the major 10 soil properties as well as the soil quality classes and their occupied areas were worked out by Kriging interpolation maps. The results showed that the arable Ustic Cambosols in study area was of good quality soil, over 95% of which ranked in good and medium classes and only less than 5% were in poor class.