Reciprocal conversion between annual and polycarpic perennial flowering behavior in the Brassicaceae.

The development of perennial crops holds great promise for sustainable agriculture and food security. However, the evolution of the transition between perenniality and annuality is poorly understood. Here, using two Brassicaceae species, Crucihimalaya himalaica and Erysimum nevadense, as polycarpic perennial models, we reveal that the transition from polycarpic perennial to biennial and annual flowering behavior is a continuum determined by the dosage of three closely related MADS-box genes. Diversification of the expression patterns, functional strengths, and combinations of these genes endows species with the potential to adopt various life-history strategies. Remarkably, we find that a single gene among these three is sufficient to convert winter-annual or annual Brassicaceae plants into polycarpic perennial flowering plants. Our work delineates a genetic basis for the evolution of diverse life-history strategies in plants and lays the groundwork for the generation of diverse perennial Brassicaceae crops in the future.

Biolinguistic graph fusion model for circRNA-miRNA association prediction.

Emerging clinical evidence suggests that sophisticated associations with circular ribonucleic acids (RNAs) (circRNAs) and microRNAs (miRNAs) are a critical regulatory factor of various pathological processes and play a critical role in most intricate human diseases. Nonetheless, the above correlations via wet experiments are error-prone and labor-intensive, and the underlying novel circRNA-miRNA association (CMA) has been validated by numerous existing computational methods that rely only on single correlation data. Considering the inadequacy of existing machine learning models, we propose a new model named BGF-CMAP, which combines the gradient boosting decision tree with natural language processing and graph embedding methods to infer associations between circRNAs and miRNAs. Specifically, BGF-CMAP extracts sequence attribute features and interaction behavior features by Word2vec and two homogeneous graph embedding algorithms, large-scale information network embedding and graph factorization, respectively. Multitudinous comprehensive experimental analysis revealed that BGF-CMAP successfully predicted the complex relationship between circRNAs and miRNAs with an accuracy of 82.90% and an area under receiver operating characteristic of 0.9075. Furthermore, 23 of the top 30 miRNA-associated circRNAs of the studies on data were confirmed in relevant experiences, showing that the BGF-CMAP model is superior to others. BGF-CMAP can serve as a helpful model to provide a scientific theoretical basis for the study of CMA prediction.

Likelihood-based feature representation learning combined with neighborhood information for predicting circRNA-miRNA associations.

Connections between circular RNAs (circRNAs) and microRNAs (miRNAs) assume a pivotal position in the onset, evolution, diagnosis and treatment of diseases and tumors. Selecting the most potential circRNA-related miRNAs and taking advantage of them as the biological markers or drug targets could be conducive to dealing with complex human diseases through preventive strategies, diagnostic procedures and therapeutic approaches. Compared to traditional biological experiments, leveraging computational models to integrate diverse biological data in order to infer potential associations proves to be a more efficient and cost-effective approach. This paper developed a model of Convolutional Autoencoder for CircRNA-MiRNA Associations (CA-CMA) prediction. Initially, this model merged the natural language characteristics of the circRNA and miRNA sequence with the features of circRNA-miRNA interactions. Subsequently, it utilized all circRNA-miRNA pairs to construct a molecular association network, which was then fine-tuned by labeled samples to optimize the network parameters. Finally, the prediction outcome is obtained by utilizing the deep neural networks classifier. This model innovatively combines the likelihood objective that preserves the neighborhood through optimization, to learn the continuous feature representation of words and preserve the spatial information of two-dimensional signals. During the process of 5-fold cross-validation, CA-CMA exhibited exceptional performance compared to numerous prior computational approaches, as evidenced by its mean area under the receiver operating characteristic curve of 0.9138 and a minimal SD of 0.0024. Furthermore, recent literature has confirmed the accuracy of 25 out of the top 30 circRNA-miRNA pairs identified with the highest CA-CMA scores during case studies. The results of these experiments highlight the robustness and versatility of our model.

Kaposi's sarcoma herpesvirus latency-associated nuclear antigen broadly regulates viral gene expression and is essential for lytic infection.

Kaposi's sarcoma herpesvirus (KSHV) is a leading cause of malignancy in AIDS and current therapies are limited. Like all herpesviruses, KSHV infection can be latent or lytic. KSHV latency-associated nuclear antigen (LANA) is essential for viral genome persistence during latent infection. LANA also maintains latency by antagonizing expression and function of the KSHV lytic switch protein, RTA. Here, we find LANA null KSHV is not capable of lytic replication, indicating a requirement for LANA. While LANA promoted both lytic and latent gene expression in cells partially permissive for lytic infection, it repressed expression in non-permissive cells. Importantly, forced RTA expression in non-permissive cells led to induction of lytic infection and LANA switched to promote, rather than repress, most lytic viral gene expression. When basal viral gene expression levels were high, LANA promoted expression, but repressed expression at low basal levels unless RTA expression was forcibly induced. LANA's effects were broad, but virus gene specific, extending to an engineered, recombinant viral GFP under control of host EF1α promoter, but not to host EF1α. Together, these results demonstrate that, in addition to its essential role in genome maintenance, LANA broadly regulates viral gene expression, and is required for high levels of lytic gene expression during lytic infection. Strategies that target LANA are expected to abolish KSHV infection.

CHIP suppresses the proliferation and migration of A549 cells by mediating the ubiquitination of eIF2α and upregulation of tumor suppressor RBM5.

The protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor 2 subunit α (eIF2α) pathway plays an essential role in endoplasmic reticulum (ER) stress. When the PERK-eIF2α pathway is activated, PERK phosphorylates eIF2α (p-eIF2α) at Ser51 and quenches global protein synthesis. In this study, we verified eIF2α as a bona fide substrate of the E3 ubiquitin ligase carboxyl terminus of the HSC70-interaction protein (CHIP) both in vitro and in cells. CHIP mediated the ubiquitination and degradation of nonphosphorylated eIF2α in a chaperone-independent manner and promoted the upregulation of the cyclic AMP-dependent transcription factor under endoplasmic reticulum stress conditions. Cyclic AMP-dependent transcription factor induced the transcriptional enhancement of the tumor suppressor genes PTEN and RBM5. Although transcription was enhanced, the PTEN protein was subsequently degraded by CHIP, but the expression of the RBM5 protein was upregulated, thereby suppressing the proliferation and migration of A549 cells. Overall, our study established a new mechanism that deepened the understanding of the PERK-eIF2α pathway through the ubiquitination and degradation of eIF2α. The crosstalk between the phosphorylation and ubiquitination of eIF2α shed light on a new perspective for tumor progression.

An Epigenomic fingerprint of human cancers by landscape interrogation of super enhancers at the constituent level.

Super enhancers (SE), large genomic elements that activate transcription and drive cell identity, have been found with cancer-specific gene regulation in human cancers. Recent studies reported the importance of understanding the cooperation and function of SE internal components, i.e., the constituent enhancers (CE). However, there are no pan-cancer studies to identify cancer-specific SE signatures at the constituent level. Here, by revisiting pan-cancer SE activities with H3K27Ac ChIP-seq datasets, we report fingerprint SE signatures for 28 cancer types in the NCI-60 cell panel. We implement a mixture model to discriminate active CEs from inactive CEs by taking into consideration ChIP-seq variabilities between cancer samples and across CEs. We demonstrate that the model-based estimation of CE states provides improved functional interpretation of SE-associated regulation. We identify cancer-specific CEs by balancing their active prevalence with their capability of encoding cancer type identities. We further demonstrate that cancer-specific CEs have the strongest per-base enhancer activities in independent enhancer sequencing assays, suggesting their importance in understanding critical SE signatures. We summarize fingerprint SEs based on the cancer-specific statuses of their component CEs and build an easy-to-use R package to facilitate the query, exploration, and visualization of fingerprint SEs across cancers.

Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome.

BACKGROUND: There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. RESULTS: In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. CONCLUSIONS: This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.

Randomly Layered Superstructure of In2O3 Truncated Nano-Octahedra and Its High-Pressure Behavior.

This study outlines the preparation and characterization of a unique superlattice composed of indium oxide (In2O3) vertex-truncated nano-octahedra, along with an exploration of its response to high-pressure conditions. Transmission electron microscopy and scanning transmission electron microscopy were employed to determine the average circumradius (15.2 nm) of these vertex-truncated building blocks and their planar superstructure. The resilience and response of the superlattice to pressure variations, peaking at 18.01 GPa, were examined using synchrotron-based wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS) techniques. The WAXS data revealed no phase transitions, reinforcing the stability of the 2D superlattice composed of random layers in alignment with a p31m planar symmetry as discerned by SAXS. Notably, the SAXS data also unveiled a pressure-induced, irreversible translation of octahedra and ligand interaction occurring within the random layer. Through our examination of these pressure-sensitive behaviors, we identified a distinctive translation model inherent to octahedra and observed modulation of the superlattice cell parameter induced by pressure. This research signifies a noteworthy advancement in deciphering the intricate behaviors of 2D superlattices under a high pressure.

Membrane-Free Electrosynthesis of Epichlorohydrins Mediated by Bromine Radicals over Nanotips.

The industrial manufacture of epichlorohydrin (ECH) often suffers from excessive corrosive chlorine and multistep processes. Here, we report a one-pot membrane-free Br radical-mediated ECH electrosynthesis. Bromine radicals electro-oxidized from Br- ions initiate the reaction and then eliminate HBr from bromohydrin to give ECH and release Br- ions for reuse. A high energy barrier for *OH oxidation and isolated Br adsorption sites enables NiCo2O4 to suppress the competitive oxygen and bromine evolution reactions. The high-curvature nanotips with an increased electric field concentrate Br- and OH- ions to accelerate ECH electrosynthesis. This strategy delivers ECH with a Faradaic efficiency of 47% and a reaction rate of 1.4 mol h-1 gcat-1 at a high current density of 100 mA cm-2, exceeding the profitable target from the techno-economic analysis. Economically profitable electrosynthesis, methodological universality, and the extended synthesis of epoxide-drug blocks highlight their promising potential.

Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria.

Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe Mito-Rh-S which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. Mito-Rh-S has an ultrafast response rate (2 s) and large emission shift (115 nm). Mito-Rh-S was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of Mito-Rh-S demonstrated that Fe2+- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe2+ and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, Mito-Rh-S can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.

Bioinspired Nanolayered Structure Tuned by Extensional Stress: A Scalable Way to High-Performance Biodegradable Polyesters.

The nacre-inspired multi-nanolayer structure offers a unique combination of advanced mechanical properties, such as strength and crack tolerance, making them highly versatile for various applications. Nevertheless, a significant challenge lies in the current fabrication methods, which is difficult to create a scalable manufacturing process with precise control of hierarchical structure. In this work, a novel strategy is presented to regulate nacre-like multi-nanolayer films with the balance mechanical properties of stiffness and toughness. By utilizing a co-continuous phase structure and an extensional stress field, the hierarchical nanolayers is successfully constructed with tunable sizes using a scalable processing technique. This strategic modification allows the robust phase to function as nacre-like platelets, while the soft phase acts as a ductile connection layer, resulting in exceptional comprehensive properties. The nanolayer-structured films demonstrate excellent isotropic properties, including a tensile strength of 113.5 MPa in the machine direction and 106.3 MPa in a transverse direction. More interestingly, these films unprecedentedly exhibit a remarkable puncture resistance at the same time, up to 324.8 N mm-1, surpassing the performance of other biodegradable films. The scalable fabrication strategy holds significant promise in designing advanced bioinspired materials for diverse applications.

Chromosome-level reference genome and resequencing of 322 accessions reveal evolution, genomic imprint and key agronomic traits in adzuki bean.

Adzuki bean (Vigna angularis) is an important legume crop cultivated in over 30 countries worldwide. We developed a high-quality chromosome-level reference genome of adzuki bean cultivar Jingnong6 by combining PacBio Sequel long-read sequencing with short-read and Hi-C technologies. The assembled genome covers 97.8% of the adzuki bean genome with a contig N50 of approximately 16 Mb and a total of 32 738 protein-coding genes. We also generated a comprehensive genome variation map of adzuki bean by whole-genome resequencing (WGRS) of 322 diverse adzuki beans accessions including both wild and cultivated. Furthermore, we have conducted comparative genomics and a genome-wide association study (GWAS) on key agricultural traits to investigate the evolution and domestication. GWAS identified several candidate genes, including VaCycA3;1, VaHB15, VaANR1 and VaBm, that exhibited significant associations with domestication traits. Furthermore, we conducted functional analyses on the roles of VaANR1 and VaBm in regulating seed coat colour. We provided evidence for the highest genetic diversity of wild adzuki (Vigna angularis var. nipponensis) in China with the presence of the most original wild adzuki bean, and the occurrence of domestication process facilitating transition from wild to cultigen. The present study elucidates the genetic basis of adzuki bean domestication traits and provides crucial genomic resources to support future breeding efforts in adzuki bean.

The AP2/ERF transcription factor MdDREB2A regulates nitrogen utilisation and sucrose transport under drought stress.

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress.

Multilayer track-etched membrane-based electroosmotic pump for drug delivery.

Herein, we report an electroosmotic pump (EOP) based on a multilayer track-etched polycarbonate (PC) membrane. A remarkable increase of maximum backpressure (198.2-2400 mmH2 O) of a fundamental pump unit was obtained at 0.8 mA, when the number of PC membranes was increased from 1 to 10. Meanwhile, the corresponding flow rate was increased from 80.3 to 111.7 µL/min. Furthermore, multiple pump units were assembled in series to obtain a multistage EOP. For a three-stage EOP (EOP-3), the operating voltage and power can be decreased significantly by 52%-72% under different driving currents, with a minimum power of 26.7 µW. Thus, EOP-3 can run stably over 35 h at a pulse current of 0.1 mA without the generation of gas bubbles. The pump was further integrated into a miniature device, which was successfully used to decrease the blood glucose level of diabetic rats by subcutaneous delivery of fast-acting insulin. This work brings a facile and efficient strategy to enhance the backpressure and lower the operating voltage and power of EOPs, which may find promising applications in drug delivery.

Nonreciprocal strong mechanical squeezing based on the Sagnac effect and two-tone driving.

We propose a scheme for generating nonreciprocal strong mechanical squeezing by using two-tone lasers to drive a spinning optomechanical system. For given driving frequencies, strong mechanical squeezing of the breathing mode in the spinning resonator can be achieved in a chosen driving direction but not in the other. The nonreciprocity originates from the Sagnac effect caused by the resonator's spinning. We also find the classical nonreciprocity and the quantum nonreciprocity can be switched by simply changing the angular velocity of the spinning resonator. We show that the scheme is robust to the system's dissipations and the mechanical thermal noise. This work may be meaningful for the study of nonreciprocal device and quantum precision measurement.

Observation of Photoassociation Resonances in Ultracold Atom-Molecule Collisions.

We report on the observation of photoassociation resonances in ultracold collisions between ^{23}Na^{40}K molecules and ^{40}K atoms. We perform photoassociation in a long-wavelength optical dipole trap to form deeply bound triatomic molecules in electronically excited states. The atom-molecule Feshbach resonance is used to enhance the free-bound Franck-Condon overlap. The photoassociation into well-defined quantum states of excited triatomic molecules is identified by observing resonantly enhanced loss features. These loss features depend on the polarization of the photoassociation lasers, allowing us to assign rotational quantum numbers. The observation of ultracold atom-molecule photoassociation resonances paves the way toward preparing ground-state triatomic molecules, provides a new high-resolution spectroscopy technique for polyatomic molecules, and is also important to atom-molecule Feshbach resonances.

Hollow UiO-66-NH2 Encapsulated Pd Catalysts for Highly Selective Hydrogenation of Furfural to Furfuryl Alcohol.

The selective hydrogenation of furfural (FFA) to furfuryl alcohol (FA) is regarded as attractive transformation to achieve the sustainable synthesis of value-added chemicals from biomass resources. However, the conventional supported catalysts are significantly restricted by their narrow pore size, ununiform dispersion and easy leaching or aggregation of catalytic sites. Herein, we designed hollow UiO-66-NH2 as the support to encapsulate Pd nanoparticles (Pd@H-UiO-66-NH2) to achieve the highly active and selective conversion of FFA to FA. Benefiting from the void-confinement effect and substrate enrichment of hollow structure, as well as the surface wrinkles, the as-prepared catalyst Pd@H-UiO-66-NH2 exhibited 96.8 % conversion of FFA with satisfactory selectivity reaching up to 92.4 % at 80 °C, 0.5 MPa H2 in isopropanol solvent within 6 h. More importantly, as-prepared Pd@H-UiO-66-NH2 catalyst exhibited excellent long-term stability, as well as good universality toward a series of hydrogenation of unsaturated hydrocarbons.

BF3 Complexing Phosphate/Phosphonate Ionic Liquids: Synthesis, Characterization and Thermophysical Properties.

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X=dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid-liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] should be considered as fragile liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (-95.33~-98.46 °C) without melting, considerably low viscosities (33.876~58.117 mPa ⋅ s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).

Synergetic Responses of Multiple Functions Induced by Phase Transition in Molecular Materials.

Materials that integrate magnetism, electricity and luminescence can not only improve the operational efficiency of devices, but also potentially generate new functions through their coupling. Therefore, multifunctional synergistic effects have broad application prospects in fields such as optoelectronic devices, information storage and processing, and quantum computing. However, in the research field of molecular materials, there are few reports on the synergistic multifunctional properties. The main reason is that there is insufficient awareness of how to obtain such material. In this brief review, we summarized the molecular materials with this characteristic. The structural phase transition of substances will cause changes in their physical properties, as the electronic configurations of the active unit in different structural phases are different. Therefore, we will classify and describe the multifunctional synergistic complexes based on the structural factors that cause the first-order phase transition of the complexes. This enables us to quickly screen complexes with synergistic responses to these properties through structural phase transitions, providing ideas for studying the synergistic response of physical properties in molecular materials.

Enzyme-Triggered Polyelectrolyte Complex for Responsive Delivery of α-Helical Polypeptides to Optimize Antibacterial Therapy.

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 µg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed ß-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.