Steric hindrance of N6-methyl in m6A and its application for specific loci detection.

We found that the N6 methyl group of N6-methyladenine is able to hinder the methylation of N6-methyladenine at the N1 position by DMS. Based on this, we have devised a novel method for detecting N6-methyladenine, which was successfully applied to identify specific m6A loci in 28S rRNA.

"Gear-driven"-type chirality transfer of tetraphenylethene-based supramolecular organic frameworks for peptides in water.

Chirality transfer for natural chiral biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we report the synthesis and characterization of a series of achiral supramolecular organic frameworks (SOF-1, SOF-2, and SOF-3), constructed from cucurbit[8]uril (CB[8]) and tetraphenylethene (TPE) derivatives (1, 2, and 3), respectively, as chirality-sensing platforms to explore their chirality transfer mechanism for peptides in water. Given the right-handed (P) and left-handed (M) rotational conformation of TPE units and the selective binding of CB[8] to aromatic amino acids, these achiral SOFs can be selectively triggered in water by peptides containing N-terminal tryptophan (W) and phenylalanine (F) residues into their P- or M-rotational conformation, exhibiting significantly different circular dichroism (CD) spectra. Although various peptides have the same l-type chiral configuration, they can induce positive CD signals of SOF-1 and negative CD signals of SOF-2 and SOF-3, respectively. Based on the structural analysis of the linkage units between CB[8] and TPE units in these SOFs, a "gear-driven"-type chirality transfer mechanism has been proposed to visually illustrate the multiple-step chirality transfer process from the recognition site in the CB[8]'s cavity to TPE units. Furthermore, by utilizing the characteristic CD signals generated through the "gear-driven"-type chirality transfer, these SOFs can serve as chiroptical sensor arrays to effectively recognize and distinguish various peptides based on their distinctive CD spectra.

Experimental realization of free-space continuous-variable quantum key distribution based on fiber Sagnac interferometer.

The Gaussian-modulated coherent state (GMCS) is a well-known continuous-variable quantum key distribution (CV-QKD) protocol that is robust to incoherent background noise and can effectively suppress ambient light in free space. However, it is difficult to implement this protocol in free space using existing polarization coding schemes. In this Letter, we propose a polarization coding structure based on a self-compensating fiber Sagnac interferometer, which can reduce the required modulation voltage by two orders of magnitude and achieve fast and arbitrary polarization modulation, and experimentally demonstrate polarization coding-based GMCS CV-QKD for, it is believed, the first time. The proposed polarization modulation structure, which uses off-the-shelf fiber components, is compact, simple, and suitable for mobile terminals, such as flying lifts.

Transcriptome-wide profiling of A-to-I RNA editing by Slic-seq.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome and is responsible for various biological processes. In this context, we developed a new method based on the highly selective cleavage activity of Endonuclease V against Inosine and the universal activity of sodium periodate against all RNAs to enrich the inosine-containing RNA and accurately identify the editing sites. We validated the reliability of our method in human brain in both Alu and non-Alu elements. The conserved sites of A-to-I editing in human cells (HEK293T, HeLa, HepG2, K562 and MCF-7) primarily occurs in the 3'UTR of the RNA, which are highly correlated with RNA binding and protein binding. Analysis of the editing sites between the human brain and mouse brain revealed that the editing of exons is more conserved than that in other regions. This method was applied to three neurological diseases (Alzheimer's, epilepsy and ageing) of mouse brain, reflecting that A-to-I editing sites significantly decreased in neuronal activity genes.

Dynamic Epitaxial Growth of Organic Heterostructures for Polarized Exciton Conversion.

Highly spatial and angular precision in epitaxial-growth process is crucial for constructing organic low-dimensional heterostructures (OLDHs) with the desired substructures, which remains significant challenge owing to the unpredicted location of complex heterogeneous nucleation. Herein, a dynamic epitaxial-growth approach is developed along the tailored longitudinal/horizontal directions to create diverse OLDHs with hierarchical architectures. The controlled morphology evolution of seed crystals from kinetic to thermodynamic species is achieved via incrementally increasing the crystallization time from 0 to 600 s. Accordingly, the kinetic and thermodynamic seed crystals respectively present the specific lattice-matching crystal-planes of (100) and (011), which facilitates the longitudinal epitaxial-growth (LG) process for triblock heterostructures, and the horizontal epitaxial-growth (HG) process for axial-branch heterostructures. The dominant core/shell heterostructures are prepared via both LG and HG processes with a crystallization time of ≈30 s. Significantly, these prepared OLDHs realize the rationally polarized exciton conversion for optical logic gate application through the exciton conversion and photon propagation at the heterojunction. This strategy provides an avenue for the precise synthesis of OLDHs with anisotropy optical characters for integrated optoelectronics.

Cooperative Membrane Damage as a Mechanism for Pentamidine-Antibiotic Mutual Sensitization.

Most Gram-positive-selective antibiotics have low activity against Gram-negative bacteria due to the presence of an outer membrane barrier. There is, therefore, interest in developing combination therapies that can penetrate the outer membrane (OM) with known antibiotics coupled with membrane-active sensitizing adjuvants. However, two unanswered questions hinder the development of such combination therapies: the sensitization spectrum of the sensitizer and the mechanism of antibiotic-sensitizer mutual potentiation. Here, with pentamidine as an example, we screened a library of 170 FDA-approved antibiotics in combination with pentamidine, a compound known to disturb the OM of Gram-negative bacteria. We found that four antibiotics, minocycline, linezolid, valnemulin, and nadifloxacin, displaced enhanced activity in combination with pentamidine against several multidrug-resistant Gram-negative bacteria. Through a descriptor-based structural-activity analysis and multiple cell-based biochemical assays, we found that hydrophobicity, partial charge, rigidity, and surface rugosity were key factors that affected sensitization via a cooperative membrane damage mechanism in which lipopolysaccharides and phospholipids were identified as sites of synergy. Finally, in vitro experiments showed that the linezolid-pentamidine combination slowed the generation of drug resistance, and there was also potent activity in in vivo experiments. Overall, our results highlight the importance of the physicochemical properties of antibiotics and cooperative membrane damage for synergistic pentamidine-antibiotic drug combinations.

Formation Mechanism of Microbial Diversity in Artificial Intelligence Devices due to Intermediate Disturbance by Low-Dose UV Radiation for Complementary Medicine.

The development of artificial intelligence devices in the complementary medicine field is rapid and the surface microbial diversity pollution was found with periodic low-dose ultraviolet radiation (LDUVR). Since artificial intelligence devices do not have enough different types of substrates for microbial communities, it is unclear how the great microbial diversity can emerge and persist, as this clearly defies the competitive exclusion principle of ecology. In this study, the 5 most common genera in the artificial intelligence devices, Escherichia, Pseudomonas, Streptococcus, Staphylococcus and Aeromonas have been sampled without and with periodic LDUVR, respectively. A new hypothesis was put up to clarify the construction and maintenance process of high microbiological diversity in artificial intelligence devices by comparing and evaluating the variations between the dynamic response characteristics of their relative abundances in the two scenarios as follows: the periodic LDUVR can be regarded as an adverse factor with intermediate disturbance, causing stronger microbial stochastic growth responses (SGR) which would inevitably give rise to stronger random variation of the other important processes tightly correlated with SGR, such as intra- and interspecific competition process, and substrates production and consumption process, which could effectively diminish the auto- and cross-correlation of stochastic processes of microbial populations, alleviating the intra- and inter-specific competitions. In artificial intelligence devices with LDUVR, these crucial succession processes can propel the microbial communities to generate and sustain a high species diversity. Finally, thorough Monte Carlo simulations were used to thoroughly confirm the idea. This research can build the theoretical groundwork, offer fresh viewpoints, and suggest potential microbial prevention strategies for the succession of microbial communities in LDUVR.

Organic Charge-Transfer Cocrystals toward Large-Area Nanofiber Membrane for Photothermal Conversion and Imaging.

Organic photothermal materials integrating a high-efficiency light-heat conversion effect and high flexibility have generated immense interest in fundamental research and practical applications. Nevertheless, their practical applications still remain a challenge, owing to the complicated design, tedious synthesis, and limited programmable substrates. Herein, an organic charge-transfer cocrystal with a narrow energy gap of 0.33 eV and a high photothermal conversion efficiency (PCE) of 69.3% was rationally designed and synthesized via a facile self-assembly process, which was introduced into polyurethane for forming a large-area photothermal nanofiber membrane via electrospinning technology. Femtosecond transient absorption spectroscopy elucidates that the excellent PCE is attributed to the nonradiation transition process, including internal conversion and charge dissociation processes. Furthermore, the temperature of the as-prepared photothermal nanofiber membrane could quickly rise to 52 °C under laser irradiation with a power density of 0.183 W/cm2, suggesting a high PCE of 53.7%. This work successfully achieves the fabrication of a large-area photothermal membrane and the development of photothermal imaging.

A model beyond protein corona: thermodynamics and binding stoichiometries of the interactions between ultrasmall gold nanoclusters and proteins.

Nanoparticles (NPs) will inevitably interact with proteins and form protein coronas once they are exposed to biological fluids. This conventional model for nano-bio interactions has been used for over twenty years. Growing numbers of new nanomaterials are emerging every year. Among them, noble metal nanoclusters (NMNCs) are new types of fluorescent nanomaterials with considerable advantages in biomedical applications. Compared with NPs (typically >10 nm) like Au NPs, carbon nanotubes, etc., NMNCs have ultrasmall sizes (∼2 nm), so when NMNCs are exposed to biological milieu, will they form protein coronas like NPs? Due to a lack of characterization techniques for ultrasmall nanoparticles (USNPs), to date, studies on the binding stoichiometries of USNPs to proteins have been heavily hampered. To address this challenge, we combined the characteristics of various methods and selected human serum albumin (HSA) and transferrin (Trf) as model proteins to study their interactions with dihydrolipoic acid (DHLA) protected gold nanoclusters (DHLA-AuNCs). Steady-state fluorescence, transient fluorescence spectroscopy and isothermal titration calorimetry (ITC) were used to study the thermodynamic parameters (K, ΔH, ΔS, ΔG) and interaction mechanisms. The results showed that the intrinsic fluorescence of both proteins was quenched by DHLA-AuNCs, and the quenching process of HSA was an endothermic dynamic process. In contrast, the quenching process of Trf was an exothermic static process. The combination of ITC, agarose gel electrophoresis (AGE) and zeta potential showed that one HSA could bind 8 ± 1 DHLA-AuNCs and one Trf could bind 7 ± 2 DHLA-AuNCs, which was quite different from the conventional model of protein coronas. Based on these findings, the "protein complex" was termed for proteins upon binding with USNPs. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) showed that DHLA-AuNCs could induce the agglomeration of proteins. Circular dichroism (CD) and synchronous fluorescence spectroscopy showed that DHLA-AuNCs had a very minor effect on the secondary structures of HSA and Trf, which demonstrated the good biocompatibility of DHLA-AuNCs at the molecular scale. This work has shed light on a new interaction model beyond the protein corona, indicating a possible biological identity of USNPs.

Hydrazine-solvothermal methods to synthesize polymeric thioarsenates from one-dimensional chains to a three-dimensional framework.

A series of polymeric Mn(ii)-thioarsenates [Mn(en)3] n [(N2H4)2Mn6(µ6-S)(µ-N2H4)2(µ3-AsS3)4] n (1), [N2H5] n [{Mn(µ-N2H4)2(µ-AsS4)}·0.5en] n (2), [Mn(µ-trien){Mn(µ-N2H4)(µ-AsS3)}2] n (3), [{Mn(N2H4)}2(µ-N2H4)2{Mn(µ-N2H4)2(µ-AsS3)2}] n (4), [Mn3(µ-N2H4)6(µ3-AsS4)(µ2-AsS4)] n (5), and [Mn(NH3)6] n [{Mn(NH3)(µ-AsS4)}2] n (6) were synthesized using a hydrazine-solvothermal method. The thioarsenate units AsS3 and AsS4 coordinate to Mn(ii) ions with variable coordination modes, forming a Mn-As-S ternary cluster (1), chains (2, 4-6), and layers (3), respectively. The hydrazine molecules act as inter-cluster, intra-chain and intra-layer bridging ligands to join the Mn(ii) ions, resulting in hydrazine hybrid 1-D, 2-D, and 3-D Mn(ii)-thioarsenate moieties in 1-5. Compounds 1-6 exhibit tunable semiconducting band gaps varying in the range of 2.19-2.47 eV. Compound 1 displays stronger antiferromagnetic coupling interactions than that of compound 2.

Cloning and Characterization of the Acetylcholinesterase1 Gene of Tetranychus cinnabarinus (Acari: Tetranychidae).

The carmine spider mite, Tetranychus cinnabarinus (Boisduval), is a major agriculture pest. It can be found worldwide, has an extensive host plant range, and has shown resistance to pesticides. Organophosphate and carbamate insecticides account for more than one-third of all insecticide sales. Insecticide resistance and the toxicity of organophosphate and carbamate insecticides to mammals have become a growing concern. Acetylcholinesterase (AChE) is the major targeted enzyme of organophosphate and carbamate insecticides. In this study, we fully cloned, sequenced and characterized the ace1 gene of T. cinnabarinus, and identified the differences between T. cinnabarinus AChE1, Tetranychus urticae Koch AChE1, and human AChE1. Resistance-associated target-site mutations were displayed by comparing the AChE amino acid sequences and their AChE three-dimensional (3D) structures of the insecticide-susceptible strains of T. cinnabarinus and T. urticae to that of a T. urticae-resistant strain. We identified variation in the active-site gorge and the sites interacting with gorge residues by comparing AChE1 3D structures of T. cinnabarinus, T. urticae, and humans, though their 3D structures were similar. Furthermore, the expression profile of T. cinnabarinus AChE, at the different developmental stages, was determined by quantitative real-time polymerase chain reaction; the transcript levels of AChE were higher in the larvae stage than in other stages. The changes in AChE expression between different developmental stages may be related to their growth habits and metabolism characteristics. This study may offer new insights into the problems of insecticide resistance and insecticide toxicity of nontarget species.

Transcriptome Analysis of the Carmine Spider Mite, Tetranychus cinnabarinus (Boisduval, 1867) (Acari: Tetranychidae), and Its Response to ß-Sitosterol.

Tetranychus cinnabarinus (Acari: Tetranychidae) is a worldwide polyphagous agricultural pest that has the title of resistance champion among arthropods. We reported previously the identification of the acaricidal compound ß-sitosterol from Mentha piperita and Inula japonica. However, the acaricidal mechanism of ß-sitosterol is unclear. Due to the limited genetic research carried out, we de novo assembled the transcriptome of T. cinnabarinus using Illumina sequencing and conducted a differential expression analysis of control and ß-sitosterol-treated mites. In total, we obtained >5.4 G high-quality bases for each sample with unprecedented sequencing depth and assembled them into 22,941 unigenes. We identified 617 xenobiotic metabolism-related genes involved in detoxification, binding, and transporting of xenobiotics. A highly expanded xenobiotic metabolic system was found in mites. T. cinnabarinus detoxification genes-including carboxyl/cholinesterase and ABC transporter class C-were upregulated after ß-sitosterol treatment. Defense-related proteins, such as Toll-like receptor, legumain, and serine proteases, were also activated. Furthermore, other important genes-such as the chloride channel protein, cytochrome b, carboxypeptidase, peritrophic membrane chitin binding protein, and calphostin-may also play important roles in mites' response to ß-sitosterol. Our results demonstrate that high-throughput-omics tool facilitates identification of xenobiotic metabolism-related genes and illustration of the acaricidal mechanisms of ß-sitosterol.

Climate oscillation during the Quaternary associated with landscape heterogeneity promoted allopatric lineage divergence of a temperate tree Kalopanax septemlobus (Araliaceae) in East Asia.

We investigated the biogeographic history of Kalopanax septemlobus, one of the most widespread temperate tree species in East Asia, using a combined phylogeographic and palaeodistribution modelling approach. Range-wide genetic differentiation at nuclear microsatellites (G'(ST) = 0.709; 2205 samples genotyped at five loci) and chloroplast DNA (G(ST) = 0.697; 576 samples sequenced for 2055 bp at three fragments) was high. A major phylogeographic break in Central China corresponded with those of other temperate species and the spatial delineation of the two temperate forest subkingdoms of East Asia, consistent with the forests having been isolated within both East and West China for multiple glacial-interglacial cycles. Evidence for multiple glacial refugia was found in most of its current range in China, South Japan and the southernmost part of the Korean Peninsula. In contrast, lineage admixture and absence of private alleles and haplotypes in Hokkaido and the northern Korean Peninsula support a postglacial origin of northernmost populations. Although palaeodistribution modelling predicted suitable climate across a land-bridge extending from South Japan to East China during the Last Glacial Maximum, the genetic differentiation of regional populations indicated a limited role of the exposed sea floor as a dispersal corridor at that time. Overall, this study provides evidence that differential impacts of Quaternary climate oscillation associated with landscape heterogeneity have shaped the genetic structure of a wide-ranging temperate tree in East Asia.