Molecular mechanism of specific DNA sequence recognition by NRF1.

Nuclear respiratory factor 1 (NRF1) regulates the expression of genes that are vital for mitochondrial biogenesis, respiration, and various other cellular processes. While NRF1 has been reported to bind specifically to GC-rich promoters as a homodimer, the precise molecular mechanism governing its recognition of target gene promoters has remained elusive. To unravel the recognition mechanism, we have determined the crystal structure of the NRF1 homodimer bound to an ATGCGCATGCGCAT dsDNA. In this complex, NRF1 utilizes a flexible linker to connect its dimerization domain (DD) and DNA binding domain (DBD). This configuration allows one NRF1 monomer to adopt a U-turn conformation, facilitating the homodimer to specifically bind to the two TGCGC motifs in the GCGCATGCGC consensus sequence from opposite directions. Strikingly, while the NRF1 DBD alone could also bind to the half-site (TGCGC) DNA of the consensus sequence, the cooperativity between DD and DBD is essential for the binding of the intact GCGCATGCGC sequence and the transcriptional activity of NRF1. Taken together, our results elucidate the molecular mechanism by which NRF1 recognizes specific DNA sequences in the promoters to regulate gene expression.

Structural basis for specific DNA sequence motif recognition by the TFAP2 transcription factors.

The TFAP2 family regulates gene expression during differentiation, development, and organogenesis, and includes five homologs in humans. They all possess a highly conserved DNA binding domain (DBD) followed by a helix-span-helix (HSH) domain. The DBD-HSH tandem domain specifically binds to a GCC(N3)GGC consensus sequence, but the precise recognition mechanisms remain unclear. Here, we found that TFAP2 preferred binding to the GCC(N3)GGC sequence, and the pseudo-palindromic GCC and GGC motifs and the length of the central spacer between the two motifs determined their binding specificity. Structural studies revealed that the two flat amphipathic α-helical HSH domains of TFAP2A stacked with each other to form a dimer via hydrophobic interactions, while the stabilized loops from both DBD domains inserted into two neighboring major grooves of the DNA duplex to form base-specific interactions. This specific DNA binding mechanism controlled the length of the central spacer and determined the DNA sequence specificity of TFAP2. Mutations of the TFAP2 proteins are implicated in various diseases. We illustrated that reduction or disruption of the DNA binding ability of the TFAP2 proteins is the primary cause of TFAP2 mutation-associated diseases. Thus, our findings also offer valuable insights into the pathogenesis of disease-associated mutations in TFAP2 proteins.

Spontaneous Particle Ordering, Sorting, and Assembly on Soap Films.

Soap bubbles exhibit abundant fascinating phenomena throughout the entire life of evolution with different fundamental physics governing them. Nevertheless, the complicated dynamics of small objects in soap films are still unrevealed. Here, we report the first observation of spontaneous particle ordering in a complicated galaxy of soap films without any external energy. The balance of interfacial tension at two liquid-gas interfaces is theoretically predicted to govern belted wetted particles (BWPs) traveling along a specified path spontaneously. Such spontaneous particle path-finding is found to depend on the particle size and hydrophilic properties. Spontaneous particle sorting is directly realized via these discrete and distinctive paths for different particles. The deformation of the soap membrane facilitates 1D/2D particle organization along the path. This observation represents the discovery of a new spontaneous order phenomenon in soap film systems and provides a new energy-free approach for particle separation and soft colloidal crystal assembly.

Structural insights into DNA recognition by the BEN domain of the transcription factor BANP.

The BEN domain-containing transcription factors regulate transcription by recruiting chromatin-modifying factors to specific chromatin regions via their DNA-binding BEN domains. The BEN domain of BANP has been shown to bind to a CGCG DNA sequence or an AAA-containing matrix attachment regions DNA sequence. Consistent with these in vivo observations, we identified an optimal DNA-binding sequence of AAATCTCG by protein binding microarray, which was also confirmed by our isothermal titration calorimetry and mutagenesis results. We then determined crystal structures of the BANP BEN domain in apo form and in complex with a CGCG-containing DNA, respectively, which revealed that the BANP BEN domain mainly used the electrostatic interactions to bind DNA with some base-specific interactions with the TC motifs. Our isothermal titration calorimetry results also showed that BANP bound to unmethylated and methylated DNAs with comparable binding affinities. Our complex structure of BANP-mCGCG revealed that the BANP BEN domain bound to the unmethylated and methylated DNAs in a similar mode and cytosine methylation did not get involved in binding, which is also consistent with our observations from the complex structures of the BEND6 BEN domain with the CGCG or CGmCG DNAs. Taken together, our results further elucidate the elements important for DNA recognition and transcriptional regulation by the BANP BEN domain-containing transcription factor.

Effect of Co-Adsorbed Guest Adsorbates on the Separation of Ethylene/Ethane Mixtures on Metal-Organic Frameworks with Open Metal Sites.

Direct determination of the equilibrium adsorption and spectroscopic observation of adsorbent-adsorbate interaction is crucial to evaluate the olefin/paraffin separation performance of porous adsorbents. However, the experimental characterization of competitive adsorption of various adsorbates at atomic-molecular level in the purification of multicomponent gas mixtures is challenging and rarely conducted. Herein, solid-state NMR spectroscopy is employed to examine the effect of co-adsorbed guest adsorbates on the separation of ethylene/ethane mixtures on Mg-MOF-74, Zn-MOF-74 and UTSA-74. 1H MAS NMR facilitates the determination of equilibrium uptake and adsorption selectivity of ethylene/ethane in ternary mixtures. The co-adsorption of H2O and CO2 significantly leads to the degradation of ethylene uptake and ethylene/ethane selectivity. The detailed host-guest and guest-guest interactions are unraveled by 2D 1H-1H spin diffusion homo-nuclear correlation and static 25Mg NMR experiments. The experimental results verify H2O coordinated on open metal sites can supply a new adsorption site for ethylene and ethane. The effects of guest adsorbates on the adsorption capacity and adsorption selectivity of ethylene/ethane mixtures are in the following order: H2O>CO2>O2. This work provides a direct approach for exploring the equilibrium adsorption and detailed separation mechanism of multicomponent gas mixtures using MOFs adsorbents.

Taming Chiral Quaternary Stereocenters via Remote H-Bonding Stereoinduction in Palladium-Catalyzed (3+2) Cycloadditions.

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

Self-Assembly of Mechanoluminochromic Ladder-Shaped Gold(I) Clusters Promoted Using Cooperative Aurophilicity.

The self-assembly of mechanoluminochromic polynuclear gold(I) complexes has attracted more and more attention in the field of supramolecular gold(I) chemistry. In this work, we adopted a stepwise self-assembly strategy to precisely synthesize two polynuclear gold(I) supramolecular clusters. Through cooperative AuI···AuI and Au-N interactions, the gold(I) clusters 1+•BF4- and 24+•4BF4- with Au4 and Au16 cores, respectively, were successfully constructed. In these supramolecular clusters, (dppm)Au2Cl2 coordination motifs and trithiocyanuric linkers were stepwise assembled via sequential thiolate-chloride/phosphine coordination substitution and Au-S/Au-N coordination bond rearrangement. Two well-defined gold(I) supramolecular clusters displayed intense emission both in the solid state and in solution. Furthermore, the ladder-shaped cluster 24+•4BF4- exhibited reversible mechanochromic luminescence behavior in the solid state as well as aggregation-caused redshifted emission in solution. Upon mechanical grinding, the emission of the cluster 24+•4BF4- changed from yellow at 582 nm to red at 612 nm. The initial emission could be fully recovered by treatment with acetonitrile.

Preferential adsorption sites for propane/propylene separation on ZIF-8 as revealed by solid-state NMR spectroscopy.

Solid-state NMR spectroscopy in conjunction with theoretical calculation was employed to investigate the adsorbent-adsorbate host-guest interactions during propane/propylene separation on ZIF-8. 1H NMR chemical shifts of free gaseous and adsorbed propane/propylene are unambiguously assigned with the assistance of two-dimensional (2D) 1H-1H correlation spectroscopy (COSY) MAS NMR spectra. Meanwhile, the adsorption selectivity for propane/propylene mixtures on ZIF-8 at a pressure in range of 1.9-9.6 bar is quantitatively determined using 1H MAS NMR experiments, which agreed well with the ideal adsorbed solution theory (IAST) predictions. The preferential adsorption of propane compared with propylene on ZIF-8 is directly visualized from the 2D 1H-1H spin diffusion homo-nuclear correlation (HOMCOR) MAS NMR spectroscopy. Moreover, the preferential adsorption sites for propane and propylene are deduced from the 1H-1H spin diffusion buildup curves, which is further confirmed by DFT theoretical calculations. This work provides insights to understand the structure-property relationship during the propane/propylene separation on ZIF-8 as adsorbent.

Application of solid-state NMR techniques for structural characterization of metal-organic frameworks.

Solid-state NMR can afford the structural information about the chemical composition, local environment, and spatial coordination at the atomic level, which has been extensively applied to characterize the detailed structure and host-guest interactions in metal-organic frameworks (MOFs). In this review, recent advances for the structural characterizations of MOFs using versatile solid-state NMR techniques were briefly introduced. High-field sensitivity-enhanced solid-state NMR method enabled the direct observation of metal centers in MOFs containing low-γ nuclei. Two-dimensional (2D) homo- and hetero-nuclear correlation MAS NMR experiments provided the spatial proximity among linkers, metal clusters and the introduced guest molecules. Moreover, quantitative measurement of inter-nuclear distances using solid-state NMR provided valuable structural information about the connectivity geometry as well as the host-guest interactions within MOFs. Furthermore, solid-state NMR has exhibited great potential for unraveling the structure property of MOFs containing paramagnetic metal centers.

[Virtual screening of active ingredients of traditional Chinese medicine in treating COVID-19 based on molecular docking and molecular dynamic simulation].

We aim to screen out the active components that may have therapeutic effect on coronavirus disease 2019 (COVID-19) from the severe and critical cases' prescriptions in the "Coronavirus Disease 2019 Diagnosis and Treatment Plan (Trial Ninth Edition)" issued by the National Health Commission of the People's Republic of China and explain its mechanism through the interactions with proteins. The ETCM database and SwissADME database were used to screen the active components contained in 25 traditional Chinese medicines in 3 prescriptions, and the PDB database was used to obtain the crystal structures of 4 proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular docking was performed using Autodock Vina and molecular dynamics simulations were performed using GROMACS. Binding energy results showed that 44 active ingredients including xambioona, gancaonin L, cynaroside, and baicalin showed good binding affinity with multiple targets of SARS-CoV-2, while molecular dynamics simulations analysis showed that xambioona bound more tightly to the nucleocapsid protein of SARS-CoV-2 and exerted a potent inhibitory effect. Modern technical methods are used to study the active components of traditional Chinese medicine and show that xambioona is an effective inhibitor of SARS-CoV-2 nucleocapsid protein, which provides a theoretical basis for the development of new anti-SARS-CoV-2 drugs and their treatment methods.

Digging metagenomic data of pangolins revealed SARS-CoV-2 related viruses and other significant viruses.

Pangolin metagenomic data obtained from public databases were used to assemble partial or complete viral genomes showing genetic relationship to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Sendai virus, flavivirus, picornavirus, parvovirus, and genomovirus, respectively. Most of these virus genomes showed genomic recombination signals. Phylogeny based on the SARS-CoV-2-related virus sequences assembled in this study and those recently published indicated that pangolin SARS-CoV-2-related viruses were clustered into two sub-lineages according to geographic sampling sites. These findings suggest the need for further pangolin samples, from different countries, to be collected and analyzed for coronavirus to elucidate whether pangolins are intermittent hosts for SARS-CoV-2.

Host-Guest Interaction in Ethylene and Ethane Separation on Zeolitic Imidazolate Frameworks as Revealed by Solid-State NMR Spectroscopy.

The separation of ethane/ethylene mixture by using metal-organic frameworks (MOFs) as adsorbents is strongly associated with the pore size-sieving effect and the adsorbent-adsorbate interaction. Herein, solid-state NMR spectroscopy is utilized to explore the host-guest interaction and ethane/ethylene separation mechanism on zeolitic imidazolate frameworks (ZIFs). Preferential access to the ZIF-8 and ZIF-8-90 frameworks by ethane compared to ethylene is directly visualized from two-dimensional 1 H-1 H spin diffusion MAS NMR spectroscopy and further verified by computational density distributions. The 1 H MAS NMR spectroscopy provides an alternative for straightforwardly extracting the adsorption selectivity of ethane/ethylene mixture at 1.1∼9.6 bar in ZIFs, which is consistent with the IAST predictions.

A novel anellovirus from hospitalized neonates.

Here, using viral metagenomics combined with conventional PCR, the complete genome sequence of a novel anellovirus (named anel-ch-zj and GenBank no. MT157223) from nasopharynx secretion specimens from hospitalized neonates was determined, and the deduced amino acid sequence of its ODF1 protein was found to be only 33.19%-39.33% identical to those of related anelloviruses with sequences available in the GenBank database, suggesting that it represents a putative new genus within the family Anelloviridae. PCR screening of 135 samples (including 45 nasopharynx secretion, 45 blood, and 45 fecal specimens collected from 45 individual hospitalized neonates) indicated that two nasopharynx secretion, two blood, and four fecal samples were positive for anel-ch-zj. Further PCR screening of 50 blood samples, 115 fecal samples, and 396 nasopharynx secretions collected from hospitalized children 1-5 years old did not yield any positive results. Whether this novel anellovirus detected in neonates is associated with specific diseases needs future investigation.

Viral metagenomics revealed diverse CRESS-DNA virus genomes in faeces of forest musk deer.

BACKGROUND: Musk deer can produce musk which has high medicinal value and is closely related to human health. Viruses in forest musk deer both threaten the health of forest musk deer and human beings. METHODS: Using viral metagenomics we investigated the virome in 85 faeces samples collected from forest musk deer. RESULTS: In this article, eight novel CRESS-DNA viruses were characterized, whole genomes were 2148 nt-3852 nt in length. Phylogenetic analysis indicated that some viral genomes were part of four different groups of CRESS-DNA virus belonging in the unclassified CRESS-DNA virus, Smacoviridae, pCPa-like virus and pPAPh2-like virus. UJSL001 (MN621482), UJSL003 (MN621469) and UJSL017 (MN621476) fall into the branch of unclassified CRESS-DNA virus (CRESSV1-2), UJSL002 (MN621468), UJSL004 (MN621481) and UJSL007 (MN621470) belong to the cluster of Smacoviridae, UJSL005 (MN604398) showing close relationship with pCPa-like (pCRESS4-8) clusters and UJSL006 (MN621480) clustered into the branch of pPAPh2-like (pCRESS9) virus, respectively. CONCLUSION: The virome in faeces samples of forest musk deer from Chengdu, Sichuan province, China was revealed, which further characterized the diversity of viruses in forest musk deer intestinal tract.

Fecal, oral, blood and skin virome of laboratory rabbits.

Here, we investigated the fecal, oral, blood, and skin virome of 10 laboratory rabbits using a viral metagenomic method. In the oral samples, we detected a novel polyomavirus (RabPyV), and phylogenetic analysis based on the large T antigen, VP1 and VP2 regions indicated that the novel strain might have undergone a recombination event. Recombination analysis based on related genomes confirmed that RabPyV is a multiple recombinant between rodent-like and avian-like polyomaviruses. In fecal samples, three partial or complete genome sequences of viruses belonging to the families Picobirnaviridae, Parvoviridae, Microviridae and Coronaviridae were characterized, and phylogenetic trees were constructed based on the predicted amino acid sequences of viral proteins. This study increases the amount of genetic information on viruses present in laboratory rabbits.

Solid-state NMR studies of the acidity of functionalized metal-organic framework UiO-66 materials.

The acid strength of metal-organic frameworks plays a key role in their catalytic performance such as activity and selectivity during catalytic reactions. Solid-state nuclear magnetic resonance in combination with probe molecules including 2-13 C-acetone and pyridine-d5 was employed to characterize the acid strength of UiO-66-X (X = -H, -2COOH, -SO3 H). It was found that after introduction of the functional groups, the acid strength of UiO-66-2COOH and UiO-66-SO3 H is considerably enhanced compared with that of parent UiO-66, with that of the former being similar to that of zeolite H-ZSM-5, and with that of the latter being slightly stronger than that of the former. Even though the acid density can efficiently be modified through changing the relative ratio in multivariate functionalized UiO-66-X, no significant alternation for the acid strength could be discerned in the MTV-UiO-66-X compared with acidic same-link counterpart. Theoretical calculations were employed to further confirm the acid strength of UiO-66-SO3 H and UiO-66-2COOH.

Utilizing Vinylcyclopropane Reactivity: Palladium-Catalyzed Asymmetric [5+2] Dipolar Cycloadditions.

Vinylcyclopropanes (VCPs) are commonly used in transition-metal-catalyzed cycloadditions, and the utilization of their recently realized reactivities to construct new cyclic architectures is of great significance in modern synthetic chemistry. Herein, a palladium-catalyzed, visible-light-driven, asymmetric [5+2] cycloaddition of VCPs with α-diazoketones is accomplished by switching the reactivity of the Pd-containing dipolar intermediate from an all-carbon 1,3-dipole to an oxo-1,5-dipole. Enantioenriched seven-membered lactones were produced with good reaction efficiencies and selectivities (23 examples, 52-92 % yields with up to 99:1 er and 12.5:1 dr). In addition, computational investigations were performed to rationalize the observed high chemo- and periselectivities.

Autofocusing imaging system based on laser ranging and a retina-like sample.

A novel autofocusing method combining active and passive techniques is proposed to improve autofocusing performance. The proposed method is divided into coarse and fine autofocusing stages. First, a laser ranging finder viewed as the active technique is used to obtain a reasonable initial position of the compensating lens group during the coarse autofocusing stage. Second, a retina-like sampling method is used to decrease the volume of processing data during the fine autofocusing stage. We developed a prototype and performed comparative experiments using different targets based on the proposed method and the traditional passive method (TPM). Under optical power of 9×, the TPM consumed 2.5 s, while the proposed method performed at 1.3 s. The comparative experiments also showed that the proposed method exhibited a better anti-interference property than the traditional method.

Fabrication of Efficient Low-Bandgap Perovskite Solar Cells by Combining Formamidinium Tin Iodide with Methylammonium Lead Iodide.

Mixed tin (Sn)-lead (Pb) perovskites with high Sn content exhibit low bandgaps suitable for fabricating the bottom cell of perovskite-based tandem solar cells. In this work, we report on the fabrication of efficient mixed Sn-Pb perovskite solar cells using precursors combining formamidinium tin iodide (FASnI3) and methylammonium lead iodide (MAPbI3). The best-performing cell fabricated using a (FASnI3)0.6(MAPbI3)0.4 absorber with an absorption edge of ∼1.2 eV achieved a power conversion efficiency (PCE) of 15.08 (15.00)% with an open-circuit voltage of 0.795 (0.799) V, a short-circuit current density of 26.86(26.82) mA/cm(2), and a fill factor of 70.6(70.0)% when measured under forward (reverse) voltage scan. The average PCE of 50 cells we have fabricated is 14.39 ± 0.33%, indicating good reproducibility.

Effect of Magnetic Field on Maskless Localized Electrodepositing Three-Dimensional Microstructure of Nano Nickel Crystals.

In the intricate process of maskless localized electrodeposition (MLED) for fabricating three-dimensional microstructures, specifically nickel micro-columns with an aspect ratio of 7:1, magnetic fields of defined strength were employed, oriented both parallel and anti-parallel to the electric field. The aim was to achieve nanocrystalline microstructures and elevated deposition rates. A detailed comparative analysis was conducted to examine the volumetric deposition rate, surface morphology, and grain size of the MLED nickel crystal 3D microstructures, both in the absence and presence of the two magnetic field directions, facilitated by a self-assembled experimental setup. The results indicate that the anti-parallel magnetic field significantly boosts the volumetric deposition rate to a notable 19,050.65 µm3/s and refines the grain size, achieving an average size of 24.82 nm. Conversely, the parallel magnetic field is found to enhance the surface morphology of the MLED nickel crystal 3D microstructure.