KMT2D-mediated H3K4me1 recruits YBX1 to facilitate triple-negative breast cancer progression through epigenetic activation of c-Myc.

BACKGROUND: Lysine methyltransferase 2D (KMT2D) mediates mono-methylation of histone H3 lysine 4 (H3K4me1) in mammals. H3K4me1 mark is involved in establishing an active chromatin structure to promote gene transcription. However, the precise molecular mechanism underlying the KMT2D-mediated H3K4me1 mark modulates gene expression in triple-negative breast cancer (TNBC) progression is unresolved. METHODS AND RESULTS: We recognized Y-box-binding protein 1 (YBX1) as a "reader" of the H3K4me1 mark, and a point mutation of YBX1 (E121A) disrupted this interaction. We found that KMT2D and YBX1 cooperatively promoted cell growth and metastasis of TNBC cells in vitro and in vivo. The expression levels of KMT2D and YBX1 were both upregulated in tumour tissues and correlated with poor prognosis for breast cancer patients. Combined analyses of ChIP-seq and RNA-seq data indicated that YBX1 was co-localized with KMT2D-mediated H3K4me1 in the promoter regions of c-Myc and SENP1, thereby activating their expressions in TNBC cells. Moreover, we demonstrated that YBX1 activated the expressions of c-Myc and SENP1 in a KMT2D-dependent manner. CONCLUSION: Our results suggest that KMT2D-mediated H3K4me1 recruits YBX1 to facilitate TNBC progression through epigenetic activation of c-Myc and SENP1. These results together unveil a crucial interplay between histone mark and gene regulation in TNBC progression, thus providing novel insights into targeting the KMT2D-H3K4me1-YBX1 axis for TNBC treatment. HIGHLIGHTS: YBX1 is a KMT2D-mediated H3K4me1-binding effector protein and mutation of YBX1 (E121A) disrupts its binding to H3K4me1. KMT2D and YBX1 cooperatively promote TNBC proliferation and metastasis by activating c-Myc and SENP1 expression in vitro and in vivo. YBX1 is colocalized with H3K4me1 in the c-Myc and SENP1 promoter regions in TNBC cells and increased YBX1 expression predicts a poor prognosis in breast cancer patients.

MDNNSyn: A Multi-Modal Deep Learning Framework for Drug Synergy Prediction.

Synergistic drug combination prediction tasks based on the computational models have been widely studied and applied in the cancer field. However, most of models only consider the interactions between drug pairs and specific cell lines, without taking into account the multiple biological relationships of drug-drug and cell line-cell line that also largely affect synergistic mechanisms. To this end, here we propose a multi-modal deep learning framework, termed MDNNSyn, which adequately applies multi-source information and trains multi-modal features to infer potential synergistic drug combinations. MDNNSyn extracts topology modality features by implementing the multi-layer hypergraph neural network on drug synergy hypergraph and constructs semantic modality features through similarity strategy. A multi-modal fusion network layer with gated neural network is then employed for synergy score prediction. MDNNSyn is compared to five classic and state-of-the-art prediction methods on DrugCombDB and Oncology-Screen datasets. The model achieves area under the curve (AUC) scores of 0.8682 and 0.9013 on two datasets, an improvement of 3.70% and 2.71% over the second-best model. Case study indicates that MDNNSyn is capable of detecting potential synergistic drug combinations.

Resveratrol for inflammatory bowel disease in preclinical studies: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid polyphenolic organic compound derived from various plants, has a potential effect on IBD. The current research was set out to investigate the therapeutic effects of resveratrol on animal models of IBD. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Chinese databases was performed. The literature search process was completed independently by two people and reviewed by a third person. The risk of bias in the included literature was assessed using the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-point quality checklist. The meta-analysis utilized Review Manager 5.4 software to evaluate the efficacy of resveratrol, with histopathological index as the primary outcome measure. Subgroup analysis was conducted based on this indicator. Additionally, meta-analyses were carried out on different outcomes reported in the literature, including final disease activity index, final body weight change, colon length, splenic index, and inflammatory factors. Results: After conducting a thorough literature search and selection process, a total of 28 studies were ultimately included in the analysis. It was found that over half of the selected studies had more than five items with low risk of bias in the bias risk assessment. Relevant datas from included literature indicated that the histopathological index of the resveratrol group was significantly lower than that of the control group (WMD = -2.58 [-3.29, -1.87]). Subgroup analysis revealed that higher doses of resveratrol (>80 mg/kg) had a better efficacy (WMD = -3.47 [-4.97, -1.98]). Furthermore, The data summary and quantitative analysis results of SI and colon length also showed that resveratrol was effective in alleviating intestinal mucosal pathological injury of IBD. In terms of biochemical indicators, the summary analysis revealed that resveratrol affected interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), interferon-γ (IFN-γ), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) significantly. These effects may be attributed to the mechanism of resveratrol in regulating immune response and inhibiting oxidative stress. Conclusion: This review suggests that resveratrol demonstrated a notable therapeutic impact in preclinical models of IBD, particularly at doses exceeding 80 mg/kg. This efficacy is attributed to the protective mechanisms targeting the intestinal mucosa involved in the pathogenesis of IBD through various pathways. As a result, resveratrol holds promising prospects for potential clinical use in the future.

Survival outcomes and prognostic factors of advanced gastrointestinal stromal tumors: in the era of multiple tyrosine kinase inhibitors.

Background: Tyrosine kinase inhibitors (TKIs) have shown great efficacy in the treatment of advanced gastrointestinal stromal tumors (GISTs), significantly prolonging the survival of patients. In the era of imatinib, a few studies reported some prognostic factors for patients with advanced GISTs, such as age, sex, performance status, diameter of the largest lesions, KIT exon mutations, and some hematological examination results. However, with the advent of more TKIs, the prognostic factors for patients with advanced GISTs have not been fully understood in the era of multiple TKIs. In this study, we aimed to identify independent prognostic factors associated with the survival of patients diagnosed with advanced GISTs. Methods: Data on clinicopathologic characteristics, treatment approaches, and survival were retrospectively collected for patients with primary unresectable or recurrent GISTs treated from January 2010 to July 2023 at the First Affiliated Hospital of Chongqing Medical University, China. Univariable and multivariable Cox proportional hazards regression models were used to identify independent prognostic factors of survival. Results: A total of 194 patients were included in the analysis. The median follow-up duration was 59.9 months (range, 2.7-141.7 months). The median overall survival (mOS) in this cohort was 76.5 months (95% confidence interval, 63.4 to 89.6 months). All patients received TKI therapy during the follow-up period, and 56.2% received two or more types of TKIs. In multivariable Cox analysis, younger age, a single lesion at enrollment, no previous use of TKIs, smaller tumor burden, good Eastern Cooperative Oncology Group performance status (ECOG PS ≤1), and lesions limited to the liver were independent prognostic factors for better survival. Conclusions: We found that a single lesion at enrollment, no previous use of TKIs, a smaller tumor burden, and lesions limited to the liver were associated with better survival. Drug resistance is a severe challenge for advanced GISTs, and several factors mentioned above may be correlated with the development of drug resistance, leading to the poor survival of patients.

An end-to-end geometry-based pipeline for automatic preoperative surgical planning of pelvic fracture reduction and fixation.

Computer-assisted preoperative planning of pelvic fracture reduction surgery has the potential to increase the accuracy of the surgery and to reduce complications. However, the diversity of the pelvic fractures and the disturbance of small fracture fragments present a great challenge to perform reliable automatic preoperative planning. In this paper, we present a comprehensive and automatic preoperative planning pipeline for pelvic fracture surgery. It includes pelvic fracture labeling, reduction planning of the fracture, and customized screw implantation. First, automatic bone fracture labeling is performed based on the separation of the fracture sections. Then, fracture reduction planning is performed based on automatic extraction and pairing of the fracture surfaces. Finally, screw implantation is planned using the adjoint fracture surfaces. The proposed pipeline was tested on different types of pelvic fracture in 14 clinical cases. Our method achieved a translational and rotational accuracy of 2.56 mm and 3.31° in reduction planning. For fixation planning, a clinical acceptance rate of 86.7% was achieved. The results demonstrate the feasibility of the clinical application of our method. Our method has shown accuracy and reliability for complex multi-body bone fractures, which may provide effective clinical preoperative guidance and may improve the accuracy of pelvic fracture reduction surgery.

Evolutional heterochromatin condensation delineates chromocenter formation and retrotransposon silencing in plants.

Heterochromatic condensates (chromocenters) are critical for maintaining the silencing of heterochromatin. It is therefore puzzling that the presence of chromocenters is variable across plant species. Here we reveal that variations in the plant heterochromatin protein ADCP1 confer a diversity in chromocenter formation via phase separation. ADCP1 physically interacts with the high mobility group protein HMGA to form a complex and mediates heterochromatin condensation by multivalent interactions. The loss of intrinsically disordered regions (IDRs) in ADCP1 homologues during evolution has led to the absence of prominent chromocenter formation in various plant species, and introduction of IDR-containing ADCP1 with HMGA promotes heterochromatin condensation and retrotransposon silencing. Moreover, plants in the Cucurbitaceae group have evolved an IDR-containing chimaera of ADCP1 and HMGA, which remarkably enables formation of chromocenters. Together, our work uncovers a coevolved mechanism of phase separation in packing heterochromatin and silencing retrotransposons.

A novel NIR fluorescent probe for visualizing hydrogen sulfide in Alzheimer's disease.

Alzheimer's disease (AD) represents a devastating form of neurodegeneration, hallmarked by a relentless erosion of memory and cognitive faculties. One key player in this complex pathology is hydrogen sulfide (H2S), a gaseous neurotransmitter that is highly concentrated in the brain. Its fluctuating levels have been compellingly linked to the onset and progression of AD. Despite the availability of numerous fluorescent probes for detecting H2S, targeted imaging of this neurotransmitter within AD models remains underexplored. To bridge this gap, we have engineered an innovative near-infrared (NIR) "turn-on" fluorescent probe, designated as probe 1. Crafted around a dicyanoisophorone scaffold, the probe incorporates a strategic methoxy modification to facilitate a bathochromic spectral shift. Impressively, upon binding with H2S, probe 1 exhibited a robust 46-fold enhancement in fluorescence at a wavelength of 680 nm. We successfully deployed this probe to visualize both exogenous and endogenous H2S in living cells and zebrafish. Further, our pathogenic investigations have corroborated that diminished H2S levels are intricately linked to an escalation in amyloid plaque formation. Most crucially, we employed probe 1 to capture real-time images of H2S concentrations within the hippocampal tissue of AD mouse models. This revealed a significant depletion in H2S levels, thereby underscoring the probe's immense potential as an effective tool for the diagnosis and prevention of Alzheimer's disease.

Proteomic profiling of laser capture microdissection kidneys from diabetic nephropathy patients.

Diabetic nephropathy (DN) remains the primary cause of end-stage renal disease (ESRD), warranting equal attention and separate analysis of glomerular, tubular, and interstitial lesions in its diagnosis and intervention. This study aims to identify the specific proteomics characteristics of DN, and assess changes in the biological processes associated with DN. 5 patients with DN and 5 healthy kidney transplant donor control individuals were selected for analysis. The proteomic characteristics of glomeruli, renal tubules, and renal interstitial tissue obtained through laser capture microscopy (LCM) were studied using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Significantly, the expression of multiple heat shock proteins (HSPs), tubulins, and heterogeneous nuclear ribonucleoproteins (hnRNPs) in glomeruli and tubules was significantly reduced. Differentially expressed proteins (DEPs) in the glomerulus showed significant enrichment in pathways related to cell junctions and cell movement, including the regulation of actin cytoskeleton and tight junction. DEPs in renal tubules were significantly enriched in glucose metabolism-related pathways, such as glucose metabolism, glycolysis/gluconeogenesis, and the citric acid cycle. Moreover, the glycolysis/gluconeogenesis pathway was a co-enrichment pathway in both DN glomeruli and tubules. Notably, ACTB emerged as the most crucial protein in the protein-protein interaction (PPI) analysis of DEPs in both glomeruli and renal tubules. In this study, we delve into the unique proteomic characteristics of each sub-region of renal tissue. This enhances our understanding of the potential pathophysiological changes in DN, particularly the potential involvement of glycolysis metabolic disorder, glomerular cytoskeleton and cell junctions. These insights are crucial for further research into the identification of disease biomarkers and the pathogenesis of DN.

Single-cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape.

How disruptions to normal cell differentiation link to tumorigenesis remains incompletely understood. Wilms tumor, an embryonal tumor associated with disrupted organogenesis, often harbors mutations in epigenetic regulators, but their role in kidney development remains unexplored. Here, we show at single-cell resolution that a Wilms tumor-associated mutation in the histone acetylation reader ENL disrupts kidney differentiation in mice by rewiring the gene regulatory landscape. Mutant ENL promotes nephron progenitor commitment while restricting their differentiation by dysregulating transcription factors such as Hox clusters. It also induces abnormal progenitors that lose kidney-associated chromatin identity. Furthermore, mutant ENL alters the transcriptome and chromatin accessibility of stromal progenitors, resulting in hyperactivation of Wnt signaling. The impacts of mutant ENL on both nephron and stroma lineages lead to profound kidney developmental defects and postnatal mortality in mice. Notably, a small molecule inhibiting mutant ENL's histone acetylation binding activity largely reverses these defects. This study provides insights into how mutations in epigenetic regulators disrupt kidney development and suggests a potential therapeutic approach.

Determining M2 macrophages content for the anti-tumor effects of metal-organic framework-encapsulated pazopanib nanoparticles in breast cancer.

Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment.

Visualization of cysteine in AD mouse with a high-quantum yield NIR fluorescent probe.

Alzheimer's disease (AD) has gradually received enthusiastic attention with the aging process, and studying its biological relevance is expected. Excitingly, fluorescence probes were considered to be powerful tools for exploring biological correlations. Therefore, a highly selective near-infrared (NIR) fluorescent probe (DCM-Cl-Acr) for imaging cysteine (Cys) in AD was designed and synthesized. Through structural optimization, the probe exhibited high fluorescence quantum yield and low detection limit (20 nM) towards Cys. Meanwhile, based on the high selectivity and high sensitivity response exhibited by the probe to Cys, it was successfully applied to visualize endogenous and exogenous Cys in living cells and zebrafish, and showed good discrimination from homocysteine (Hcy) and glutathione (GSH). Further, the correlation between AD and Cys concentration was clarified by imaging studies in hippocampus tissue of AD mouse, and the abnormal accumulation of Cys in the hippocampus of AD brain was demonstrated.

Shear-strained Pd Single-atom Electrocatalysts for Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction method (NitRR) is a low-carbon, environmentally friendly, and efficient method for synthesizing ammonia, which has received widespread attention in recent years. Copper-based catalysts have a leading edge in nitrate reduction due to their good adsorption of *NO3. However, the formation of active hydrogen (*H) on Cu surfaces is difficult and insufficient, resulting in a large amount of the by-product NO2-. In this work, Pd single atoms suspended on the interlayer unsaturated bonds of CuO atoms formed due to dislocations (Pd-CuO) were prepared by low temperature treatment, and the Pd single atoms located on the dislocations were subjected to shear stress and the dynamic effect of support formation to promote the conversion of nitrate into ammonia. The catalysis had an ammonia yield of 4.2 mol.gcat-1. h-1, and a Faraday efficiency of 90% for ammonia production at -0.5 V vs. RHE. Electrochemical in-situ characterization and theoretical calculations indicate that the dynamic effects of Pd single atoms and carriers under shear stress obviously promote the production of active hydrogen, reduce the reaction energy barrier of the decision-making step for nitrate conversion to ammonia, further promote ammonia generation.

A Combination of Exercise and Yogurt Intake Protects Mice against Obesity by Synergistic Promotion of Adipose Browning.

Exercise exerts many beneficial effects on obesity, but the mechanism remains elusive. Here, we report a previously unidentified role of the lactate receptor GPR81 in exercise. We observed that GPR81 was significantly up-regulated in white adipose tissues (WAT) upon exercise training in both lean and obese mice. Exercise could induce thermogenesis and beige adipocyte development, whereas such an effect was markedly impaired by the deficiency of GPR81. Furthermore, the activation of GPR81 by exercise and lactate supplementation (250 or 500 mg/kg) yielded a synergistic enhancement of WAT browning and thermogenesis. Yogurt is a dairy product enriched with lactate. A combination of exercise and yogurt intake (20 g/kg) synergistically protected mice against high-fat-diet-induced obesity, as evidenced by decreased body weight, ameliorative dyslipidemia, improved glucose tolerance, and reduced hepatic steatosis. Mechanistically, lactate-GPR81 axis might aid in the norepinephrine-stimulated beige adipocyte biogenesis cascade via the Ca2+/CaMK pathway. Together, these findings reveal the critical role of lactate-GPR81 signaling in exercise-induced WAT browning and provide a new strategy for personalized diet and lifestyle interventions for obesity management.

UAV-Assisted Dynamic Monitoring of Wheat Uniformity toward Yield and Biomass Estimation.

Crop uniformity is a comprehensive indicator used to describe crop growth and is important for assessing crop yield and biomass potential. However, there is still a lack of continuous monitoring of uniformity throughout the growing season to explain their effects on yield and biomass. Therefore, this paper proposed a wheat uniformity quantification method based on unmanned aerial vehicle imaging technology to monitor and analyze the dynamic changes in wheat uniformity. The leaf area index (LAI), soil plant analysis development (SPAD), and fractional vegetation cover were estimated from hyperspectral images, while plant height was estimated by a point cloud model from RGB images. Based on these 4 agronomic parameters, a total of 20 uniformity indices covering multiple growing stages were calculated. The changing trends in the uniformity indices were consistent with the results of visual interpretation. The uniformity indices strongly correlated with yield and biomass were selected to construct multiple linear regression models for estimating yield and biomass. The results showed that Pielou's index of LAI had the strongest correlation with yield and biomass, with correlation coefficients of -0.760 and -0.801, respectively. The accuracies of the yield (coefficient of determination [R 2] = 0.616, root mean square error [RMSE] = 1.189 Mg/ha) and biomass estimation model (R 2 = 0.798, RMSE = 1.952 Mg/ha) using uniformity indices were better than those of the models using the mean values of the 4 agronomic parameters. Therefore, the proposed uniformity monitoring method can be used to effectively evaluate the temporal and spatial variations in wheat uniformity and can provide new insights into the prediction of yield and biomass.

Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.

OBJECTIVES: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN: Multicentre, double blind, randomised, placebo controlled trial. SETTING: 244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). CONCLUSIONS: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05439356.

Association of the electrical parameters and photosynthetic characteristics of the tea tree manifests its response to simulated karst drought.

Tea plantations in Karst regions suffer from the serious effects of frequent temporary karst droughts, leading to a decline in tea production and quality in the region. The close relationship between growth and electrical parameters of plants, including physiological capacitance, resistance and impedance, can be used to accurately monitor their plant water status online, quickly, accurately, timely and nondestructively. In this study, three tea tree cultivars of Zhonghuang No.2 (ZH), Wuniuzao (WNZ), and Longjing 43 (LJ) with different levels of drought resistance were selected as experimental materials, and experiments were carried out under controlled conditions according to control (soil water content of 40-45%, D0), (keeping D0 no watering to 5 days, D5), (keeping D0 no watering to 10 days, D10), (the first day after D10 is rehydrated to D0 is regarded as R1) and (the fifth day after D10 rehydration to D0 is regarded as R5), to determine intracellular water metabolism and nutrient translocation characteristics based on intrinsic electrical parameters. The photosynthetic characteristics and chlorophyll fluorescence parameters were also determined to investigate the response of water metabolism to simulated karst drought in the three tea tree cultivars. The results indicated that the water metabolism patterns responded to environmental water changes with a medium water-holding capacity, medium water transport rate, and low water-use efficiency, and the nutrient patterns in those tea tree varieties demonstrated with a high nutrient flux per unit area, low nutrient transfer rate, and high nutrient transport capacity. After rehydration, only the electrical characteristics of WNZ returned to the D0 levels, but the net photosynthetic rate of all varieties returned to or even exceeded the D0 levels. The chlorophyll fluorescence parameters could not be used to characterize the recoverability of metabolism in tea trees. The electrical characteristics quickly reflected the response of the water metabolism in plants to environmental changes, and the fusion of electrical characteristics and photosynthetic characteristics was able to more quickly, accurately, and comprehensively reflect the response of water metabolism to temporary karst drought.

Central Metal-Triggered Structural Transformation of a 2D Layered MOF: Mechanistic Studies and Applications.

The structural transformation of metal-organic frameworks (MOFs) has attracted increasing interests, which has not only produced various new structures but also served as a fantastic platform for MOF-based kinetic analysis. Multiple reaction conditions have been documented to cause structural transformation; nevertheless, central metal-induced topological alteration of MOFs is rare. Herein, we reported a structural transformation of a 2D layered Cd-MOF driven by Cd(II) ions. After being submerged in the aqueous solution of cadmium nitrate, the twofold interpenetrated 2D network of [Cd(hsb-2)(bdc)·5H2O]n [HSB-W10; bdc: 1,4-benzenedicarboxylate; hsb-2:1,2-bis(4'-pyridylmethylamino)-ethane] was converted into a novel noninterpenetrated 2D network [Cd1.5(hsb-2)(bdc)1.5(H2O)2·H2O]n (HSB-W16). This partial dissolution-recrystallization process was investigated by integrating controlled experiments, 1H NMR spectra, and photographic tracking analysis. Furthermore, a novel strategy combining in situ multicomponent dye encapsulation and central metal-triggered structural transformation was developed for the fabrication of MOF materials with white-light emission. By adopting this strategy, different dye guest molecules were concurrently introduced into the HSB-W16 host matrix, leading to a range of white-light-emitting MOF composites. This work will enable detailed studies of solid-state transformations and demonstrate a promising application prospect for structural transformation.

Genome-wide analysis of TOPLESS/TOPLESS-RELATED co-repressors and functional characterization of BnaA9.TPL regulating the embryogenesis and leaf morphology in rapeseed.

TOPLESS/TOPLESS-RELATED (TPL/TPR) proteins belong to the Groucho (Gro)/Tup1 family co-repressors and act as broad co-repressors that modulate multiple phytohormone signalling pathways and various developmental processes in plant. However, TPL/TPR co-repressors so far are poorly understood in the rapeseed, one of the world-wide important oilseed crops. In this study, we comprehensively characterized eighteen TPL/TPR genes into five groups in the rapeseed genome. Members of TPL/TPR1/TPR4 and TPR2/TPR3 had close evolutionary relationship, respectively. All TPL/TPRs had similar expression patterns and encode conserved protein domain. In addition, we demonstrated that BnaA9.TPL interacted with all known plant repression domain (RD) sequences, which were distributed in non-redundant 24,238 (22.6 %) genes and significantly enriched in transcription factors in the rapeseed genome. These transcription factors were largely co-expressed with the TPL/TPR genes and involved in diverse pathway, including phytohormone signal transduction, protein kinases and circadian rhythm. Furthermore, BnaA9.TPL was revealed to regulate apical embryonic fate by interaction with Bna.IAA12 and suppression of PLETHORA1/2. BnaA9.TPL was also identified to regulate leaf morphology by interaction with Bna.AS1 (Asymmetric leaves 1) and suppression of KNOTTED-like homeobox genes and YABBY5. These data not only suggest the rapeseed TPL/TPRs play broad roles in different processes, but also provide useful information to uncover more TPL/TPR-mediated control of plant development in rapeseed.

SUPPRESSOR OF FRIGIDA 4 cooperates with the histone methylation reader EBS to positively regulate root development.

Maintenance and homeostasis of the quiescent center (QC) in Arabidopsis (Arabidopsis thaliana) root apical meristems are critical for stem cell organization and root development. Despite great progress in relevant research, the molecular mechanisms that determine the root stem cell fate and QC still need further exploration. In Arabidopsis, SUPPRESSOR OF FRIGIDA 4 (SUF4) encodes a C2H2-type zinc finger protein that represses flowering by transcriptional activation of FLOWERING LOCUS C (FLC) through the FRIGIDA (FRI) pathway, and EARLY BOLTING IN SHORT DAYS (EBS) is a bivalent histone reader that prevents premature flowering. Here, we found that SUF4 directly interacts with EBS in vivo and in vitro. Loss of function of SUF4 and/or EBS resulted in disorganization of the QC, aberrant cell division, and stunted root growth. RNA-seq and reverse transcription quantitative real-time polymerase chain reaction analysis revealed that SUF4 and EBS coregulate many root development-related genes. A series of biochemical analyses demonstrated that SUF4 directly binds to the promoter of SCARECROW (SCR), which encodes a key regulator of root development. Chromatin immunoprecipitation assay indicated that both SUF4 and EBS are recruited to the SCR locus in an interdependent manner to promote H3K4me3 levels and suppress H3K27me3 levels, thereby activating the expression of SCR. These findings improve our understanding of the function of SUF4 and EBS and provide insights into the molecular mechanism that couples a transcription factor and a histone methylation reader to modulate QC specification and root development in Arabidopsis.