Intricate 3D architecture of a DNA mimic of GFP.

Numerous studies have shown how RNA molecules can adopt elaborate three-dimensional (3D) architectures1-3. By contrast, whether DNA can self-assemble into complex 3D folds capable of sophisticated biochemistry, independent of protein or RNA partners, has remained mysterious. Lettuce is an in vitro-evolved DNA molecule that binds and activates4 conditional fluorophores derived from GFP. To extend previous structural studies5,6 of fluorogenic RNAs, GFP and other fluorescent proteins7 to DNA, we characterize Lettuce-fluorophore complexes by X-ray crystallography and cryogenic electron microscopy. The results reveal that the 53-nucleotide DNA adopts a four-way junction (4WJ) fold. Instead of the canonical L-shaped or H-shaped structures commonly seen8 in 4WJ RNAs, the four stems of Lettuce form two coaxial stacks that pack co-linearly to form a central G-quadruplex in which the fluorophore binds. This fold is stabilized by stacking, extensive nucleobase hydrogen bonding-including through unusual diagonally stacked bases that bridge successive tiers of the main coaxial stacks of the DNA-and coordination of monovalent and divalent cations. Overall, the structure is more compact than many RNAs of comparable size. Lettuce demonstrates how DNA can form elaborate 3D structures without using RNA-like tertiary interactions and suggests that new principles of nucleic acid organization will be forthcoming from the analysis of complex DNAs.

In vivo single-molecule RNA structural profiling.

Cellular RNAs exhibit substantial heterogeneity in structure and function. Recently, Yang et al. developed an in vivo single-molecule RNA structure profiling methodology and revealed that individual isoforms of noncoding transcripts adopt multiple diverse and functionally relevant structural conformations, which change in abundance and structure in response to temperature conditions.

The adaptor protein ECAP, the corepressor LEUNIG, and the transcription factor BEH3 interact and regulate microsporocyte generation in Arabidopsis.

Histospecification and morphogenesis of anthers during development in Arabidopsis (Arabidopsis thaliana) are well understood. However, the regulatory mechanism of microsporocyte generation at the pre-meiotic stage remains unclear, especially how archesporial cells are specified and differentiate into 2 cell lineages with distinct developmental fates. SPOROCYTELESS (SPL) is a key reproductive gene that is activated during early anther development and remains active. In this study, we demonstrated that the EAR motif-containing adaptor protein (ECAP) interacts with the Gro/Tup1 family corepressor LEUNIG (LUG) and the BES1/BZR1 HOMOLOG3 (BEH3) transcription factor to form a transcription activator complex, epigenetically regulating SPL transcription. SPL participates in microsporocyte generation by modulating the specification of archesporial cells and the archesporial cell-derived differentiation of somatic and reproductive cell layers. This study illustrates the regulation of SPL expression by the ECAP-LUG-BEH3 complex, which is essential for the generation of microsporocytes. Moreover, our findings identified ECAP as a key transcription regulator that can combine with different partners to regulate gene expression in distinct ways, thereby facilitating diverse processes in various aspects of plant development.

Centimeter-sized diamond composites with high electrical conductivity and hardness.

Achieving high-performance materials with superior mechanical properties and electrical conductivity, especially in large-sized bulk forms, has always been the goal. However, it remains a grand challenge due to the inherent trade-off between these properties. Herein, by employing nanodiamonds as precursors, centimeter-sized diamond/graphene composites were synthesized under moderate pressure and temperature conditions (12 GPa and 1,300 to 1,500 °C), and the composites consisted of ultrafine diamond grains and few-layer graphene domains interconnected through covalently bonded interfaces. The composites exhibit a remarkable electrical conductivity of 2.0 × 104 S m-1 at room temperature, a Vickers hardness of up to ~55.8 GPa, and a toughness of 10.8 to 19.8 MPa m1/2. Theoretical calculations indicate that the transformation energy barrier for the graphitization of diamond surface is lower than that for diamond growth directly from conventional sp2 carbon materials, allowing the synthesis of such diamond composites under mild conditions. The above results pave the way for realizing large-sized diamond-based materials with ultrahigh electrical conductivity and superior mechanical properties simultaneously under moderate synthesis conditions, which will facilitate their large-scale applications in a variety of fields.

CMOS-compatible reconstructive spectrometers with self-referencing integrated Fabry-Perot resonators.

Miniaturized reconstructive spectrometers play a pivotal role in on-chip and portable devices, offering high-resolution spectral measurement through precalibrated spectral responses and AI-driven reconstruction. However, two key challenges persist for practical applications: artificial intervention in algorithm parameters and compatibility with complementary metal-oxide-semiconductor (CMOS) manufacturing. We present a cutting-edge miniaturized reconstructive spectrometer that incorporates a self-adaptive algorithm referenced with Fabry-Perot resonators, delivering precise spectral tests across the visible range. The spectrometers are fabricated with CMOS technology at the wafer scale, achieving a resolution of ~2.5 nm, an average wavelength deviation of ~0.27 nm, and a resolution-to-bandwidth ratio of ~0.46%. Our approach provides a path toward versatile and robust reconstructive miniaturized spectrometers and facilitates their commercialization.

Entanglement of two quantum memories via fibres over dozens of kilometres.

A quantum internet that connects remote quantum processors1,2 should enable a number of revolutionary applications such as distributed quantum computing. Its realization will rely on entanglement of remote quantum memories over long distances. Despite enormous progress3-12, at present the maximal physical separation achieved between two nodes is 1.3 kilometres10, and challenges for longer distances remain. Here we demonstrate entanglement of two atomic ensembles in one laboratory via photon transmission through city-scale optical fibres. The atomic ensembles function as quantum memories that store quantum states. We use cavity enhancement to efficiently create atom-photon entanglement13-15 and we use quantum frequency conversion16 to shift the atomic wavelength to telecommunications wavelengths. We realize entanglement over 22 kilometres of field-deployed fibres via two-photon interference17,18 and entanglement over 50 kilometres of coiled fibres via single-photon interference19. Our experiment could be extended to nodes physically separated by similar distances, which would thus form a functional segment of the atomic quantum network, paving the way towards establishing atomic entanglement over many nodes and over much longer distances.

The lack of negative association between TE load and subgenome dominance in synthesized Brassica allotetraploids.

Polyploidization is important to the evolution of plants. Subgenome dominance is a distinct phenomenon associated with most allopolyploids. A gene on the dominant subgenome tends to express to higher RNA levels in all organs as compared to the expression of its syntenic paralogue (homoeolog). The mechanism that underlies the formation of subgenome dominance remains unknown, but there is evidence for the involvement of transposon/DNA methylation density differences nearby the genes of parents as being causal. The subgenome with lower density of transposon and methylation near genes is positively associated with subgenome dominance. Here, we generated eight generations of allotetraploid progenies from the merging of parental genomes Brassica rapa and Brassica oleracea. We found that transposon/methylation density differ near genes between the parental (rapa:oleracea) existed in the wide hybrid, persisted in the neotetraploids (the synthetic Brassica napus), but these neotetraploids expressed no expected subgenome dominance. This absence of B. rapa vs. B. oleracea subgenome dominance is particularly significant because, while there is no negative relationship between transposon/methylation level and subgenome dominance in the neotetraploids, the more ancient parental subgenomes for all Brassica did show differences in transposon/methylation densities near genes and did express, in the same samples of cells, biased gene expression diagnostic of subgenome dominance. We conclude that subgenome differences in methylated transposon near genes are not sufficient to initiate the biased gene expressions defining subgenome dominance. Our result was unexpected, and we suggest a "nuclear chimera" model to explain our data.

CsPAT1, a GRAS transcription factor, promotes lignin accumulation by antagonistic interacting with CsWRKY13 in tea plants.

Lignin is an important component of plant cell walls and plays crucial roles in the essential agronomic traits of tea quality and tenderness. However, the molecular mechanisms underlying the regulation of lignin biosynthesis in tea plants remain unclear. CsWRKY13 acts as a negative regulator of lignin biosynthesis in tea plants. In this study, we identified a GRAS transcription factor, phytochrome A signal transduction 1 (CsPAT1), that interacts with CsWRKY13. Silencing CsPAT1 expression in tea plants and heterologous overexpression in Arabidopsis demonstrated that CsPAT1 positively regulates lignin accumulation. Further investigation revealed that CsWRKY13 directly binds to the promoters of CsPAL and CsC4H and suppresses transcription of CsPAL and CsC4H. CsPAT1 indirectly affects the promoter activities of CsPAL and CsC4H by interacting with CsWRKY13, thereby facilitating lignin biosynthesis in tea plants. Compared with the expression of CsWRKY13 alone, the co-expression of CsPAT1 and CsWRKY13 in Oryza sativa significantly increased lignin biosynthesis. Conversely, compared with the expression of CsPAT1 alone, the co-expression of CsPAT1 and CsWRKY13 in O. sativa significantly reduced lignin accumulation. These results demonstrated the antagonistic regulation of the lignin biosynthesis pathway by CsPAT1 and CsWRKY13. These findings improve our understanding of lignin biosynthesis mechanisms in tea plants and provide insights into the role of the GRAS transcription factor family in lignin accumulation.

Deep learning can predict subgenome dominance in ancient but not in neo/synthetic polyploidized genomes.

Deep learning offers new approaches to investigate the mechanisms underlying complex biological phenomena, such as subgenome dominance. Subgenome dominance refers to the dominant expression and/or biased fractionation of genes in one subgenome of allopolyploids, which has shaped the evolution of a large group of plants. However, the underlying cause of subgenome dominance remains elusive. Here, we adopt deep learning to construct two convolutional neural network (CNN) models, binary expression model (BEM) and homoeolog contrast model (HCM), to investigate the mechanism underlying subgenome dominance using DNA sequence and methylation sites. We apply these CNN models to analyze three representative polyploidization systems, Brassica, Gossypium, and Cucurbitaceae, each with available ancient and neo/synthetic polyploidized genomes. The BEM shows that DNA sequence of the promoter region can accurately predict whether a gene is expressed or not. More importantly, the HCM shows that the DNA sequence of the promoter region predicts dominant expression status between homoeologous gene pairs retained from ancient polyploidizations, thus predicting subgenome dominance associated with these events. However, HCM fails to predict gene expression dominance between new homoeologous gene pairs arising from the neo/synthetic polyploidizations. These results are consistent across the three plant polyploidization systems, indicating broad applicability of our models. Furthermore, the two models based on methylation sites produce similar results. These results show that subgenome dominance is associated with long-term sequence differentiation between the promoters of homoeologs, suggesting that subgenome expression dominance precedes and is the driving force or even the determining factor for sequence divergence between subgenomes following polyploidization.

Self-assembled soft alloy with Frank-Kasper phases beyond metals.

Soft building blocks, such as micelles, cells or soap bubbles, tend to adopt near-spherical geometry when densely packed together. As a result, their packing structures do not extend beyond those discovered in metallic glasses, quasicrystals and crystals. Here we report the emergence of two Frank-Kasper phases from the self-assembly of five-fold symmetric molecular pentagons. The µ phase, an important intermediate in superalloys, is indexed in soft matter, whereas the ϕ phase exhibits a structure distinct from known Frank-Kasper phases in metallic systems. We find a broad size and shape distribution of self-assembled mesoatoms formed by molecular pentagons while approaching equilibrium that contribute to the unique packing structures. This work provides insight into the manipulation of soft building blocks that deviate from the typical spherical geometry and opens avenues for the fabrication of 'soft alloy' structures that were previously unattainable in metal alloys.

TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

Targeting ENPP1 depletion may be a promising therapeutic strategy for treating oral squamous cell carcinoma via cytotoxic autophagy-related apoptosis.

ENPP1 depletion closely related with modulation immunotherapy of several types of cancer. However, the role of ENPP1 correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, effects of ENPP1 on OSCC cells in vitro were examined by cell proliferation assay, transwell chamber assay, flow cytometry analysis and shRNA technique. Cellular key proteins related to cell autophagy and apoptosis were evaluated by Western blot and immunofluorescent staining. Moreover, functions of ENPP1 on OSCC process were observed in nude mouse model. We reported that overexpression of ENPP1 promote the growth of OSCC cell xenografts in nude mouse model. In contrast, ENPP1 downregulation significantly inhibits OSCC cancer growth and induces apoptosis both in vitro and in vivo, which are preceded by cytotoxic autophagy. ENPP1downregulation induces a robust accumulation of autophagosomes, increases LC3B-II and decreases SQSTM1/p62 in ENPP1-shRNA-treated cells and xenografts. Mechanistic studies show that ENPP1 downregulation increases PRKAA1 phosphorylation leading to ULK1 activation. AMPK-inhibition abrogates ENPP1 downregulation-induced ULK1-activation, LC3B-turnover and SQSTM1/p62-degradation while AMPK-activation potentiates it's effects. Collectively, these data uncover that ENPP1 downregulation induces autophagic cell death in OSCC cancer, which may provide a potential therapeutic target for the treatment of OSCC.

Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia.

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

Genetically encoded RNA-based sensors with Pepper fluorogenic aptamer.

Sensors to measure the abundance and signaling of intracellular molecules are crucial for understanding their physiological functions. Although conventional fluorescent protein-based sensors have been designed, RNA-based sensors are promising imaging tools. Numerous RNA-based sensors have been developed. These sensors typically contain RNA G-quadruplex (RG4) motifs and thus may be suboptimal in living cells. Here we describe RNA-based sensors based on Pepper, a fluorogenic RNA without an RG4 motif. With Pepper, we engineered various sensors for metabolites, synthetic compounds, proteins and metal ions in vitro and in living cells. In addition, these sensors show high activation and selectivity, demonstrating their universality and robustness. In the case of sensors responding to S-adenosylmethionine (SAM), a metabolite produced by methionine adenosyltransferase (MATase), we showed that our sensors exhibited positively correlated fluorescence responding to different SAM levels. Importantly, we revealed the SAM biosynthesis pathway and monitored MATase activity and gene expression spatiotemporally in living individual human cells. Additionally, we constructed a ratiometric SAM sensor to determine the inhibition efficacy of a MATase inhibitor in living cells. Together, these sensors comprising Pepper provide a useful platform for imaging diverse cellular targets and their signaling pathway.

OCTOPUS regulates BIN2 to control leaf curvature in Chinese cabbage.

Heading is one of the most important agronomic traits for Chinese cabbage crops. During the heading stage, leaf axial growth is an essential process. In the past, most genes predicted to be involved in the heading process have been based on leaf development studies in Arabidopsis. No genes that control leaf axial growth have been mapped and cloned via forward genetics in Chinese cabbage. In this study, we characterize the inward curling mutant ic1 in Brassica rapa ssp. pekinensis and identify a mutation in the OCTOPUS (BrOPS) gene by map-based cloning. OPS is involved in phloem differentiation in Arabidopsis, a functionalization of regulating leaf curvature that is differentiated in Chinese cabbage. In the presence of brassinosteroid (BR) at the early heading stage in ic1, the mutation of BrOPS fails to sequester brassinosteroid insensitive 2 (BrBIN2) from the nucleus, allowing BrBIN2 to phosphorylate and inactivate BrBES1, which in turn relieves the repression of BrAS1 and results in leaf inward curving. Taken together, the results of our findings indicate that BrOPS positively regulates BR signaling by antagonizing BrBIN2 to promote leaf epinastic growth at the early heading stage in Chinese cabbage.

Identification of hypoxia-related gene signatures based on multi-omics analysis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and one of the malignancies with the highest incidence rate and mortality worldwide. Hypoxia is a typical feature of tumour microenvironment (TME), which affects the progression of LUAD from multiple molecular levels. However, the underlying molecular mechanisms behind LUAD hypoxia are not fully understood. In this study, we estimated the level of hypoxia by calculating a score based on 15 hypoxia genes. The hypoxia scores were relatively high in LUAD patients with poor prognosis and were bound up with tumour node metastasis (TNM) stage, tumour size, lymph node, age and gender. By comparison of high hypoxia score group and low hypoxia score group, 1820 differentially expressed genes were identified, among which up-regulated genes were mainly about cell division and proliferation while down-regulated genes were primarily involved in cilium-related biological processes. Besides, LUAD patients with high hypoxia scores had higher frequencies of gene mutations, among which TP53, TTN and MUC16 had the highest mutation rates. As for DNA methylation, 1015 differentially methylated probes-related genes were found and may play potential roles in tumour-related neurobiological processes and cell signal transduction. Finally, a prognostic model with 25 multi-omics features was constructed and showed good predictive performance. The area under curve (AUC) values of 1-, 3- and 5-year survival reached 0.863, 0.826 and 0.846, respectively. Above all, our findings are helpful in understanding the impact and molecular mechanisms of hypoxia in LUAD.

Myelin debris phagocytosis in demyelinating disease.

Demyelinating diseases are often caused by a variety of triggers, including immune responses, viral infections, malnutrition, hypoxia, or genetic factors, all of which result in the loss of myelin in the nervous system. The accumulation of myelin debris at the lesion site leads to neuroinflammation and inhibits remyelination; therefore, it is crucial to promptly remove the myelin debris. Initially, Fc and complement receptors on cellular surfaces were the primary clearance receptors responsible for removing myelin debris. However, subsequent studies have unveiled the involvement of additional receptors, including Mac-2, TAM receptors, and the low-density lipoprotein receptor-related protein 1, in facilitating the removal process. In addition to microglia and macrophages, which serve as the primary effector cells in the disease phase, a variety of other cell types such as astrocytes, Schwann cells, and vascular endothelial cells have been demonstrated to engage in the phagocytosis of myelin debris. Furthermore, we have concluded that oligodendrocyte precursor cells, as myelination precursor cells, also exhibit this phagocytic capability. Moreover, our research group has innovatively identified the low-density lipoprotein receptor as a potential phagocytic receptor for myelin debris. In this article, we discuss the functional processes of various phagocytes in demyelinating diseases. We also highlight the alterations in signaling pathways triggered by phagocytosis, and provide a comprehensive overview of the various phagocytic receptors involved. Such insights are invaluable for pinpointing potential therapeutic strategies for the treatment of demyelinating diseases by targeting phagocytosis.

Stimulus-Induced Dynamic Behavior Regulation of Flexible Crystals through the Tuning of Module Rigidity.

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

Microbiota-gut-brain axis in perioperative neurocognitive and depressive disorders: Pathogenesis to treatment.

An increasing number of people undergo anesthesia and surgery. Perioperative neurocognitive and depressive disorders are common central nervous system complications with similar pathogeneses. These conditions pose a deleterious threat to human health and a significant societal burden. In recent years, numerous studies have focused on the role of the gut microbiota and its metabolites in the central nervous system via the gut-brain axis. Its involvement in perioperative neurocognitive and depressive disorders has attracted considerable attention. This review aimed to elucidate the role of the gut microbiota and its metabolites in the pathogenesis of perioperative neurocognitive and depressive disorders, as well as the value of targeted interventions and treatments.