Biomarker identification and risk prediction model development for differentiated thyroid carcinoma lung metastasis based on primary lesion proteomics.

PURPOSE: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. EXPERIMENTAL DESIGN: Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and immunohistochemistry, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. RESULTS: This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS and VDAC2- as potential biomarkers for predicting DTC lung metastasis risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC: 0.986) and calibration (Brier score: 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. CONCLUSIONS: As a large sample size study in lung metastatic DTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting DTC lung metastasis and establishing personalised treatment strategies.

Oxidative Dissolution Process of Sphalerite in Fe2(SO4)3-O3 System: Implications for Heavy Metals Removal and Recovery.

Metal sulfides in waste rocks and tailings are susceptible to serious soil and water contamination due to the generation of acid mine drainage (AMD) during stockpiling. The hydrometallurgical process is one of the most essential heavy metal remediation technologies through harmless disposal and resource utilization of the waste sulfides. However, atmospheric hydrometallurgy of sulfides still faces great challenges due to low leaching efficiency and high cost. In this work, we proposed a cooperative leaching system (Fe2(SO4)3-O3) and investigated the oxidative dissolution process of sphalerite (ZnS). Under the optimal conditions, the extracted zinc reached 97.8%. Reactive oxygen species (ROS) (·OH, 1O2 and ·O2-) were identified in the radical quenching experiments. The dissolution of sphalerite did not show passivation due to the ozone's capability to oxidize the sulfur in sphalerite to sulfate. In addition, stirring rate, O3 inlet concentration, and Fe2(SO4)3 concentration had a significant effect on the dissolution of sphalerite. Meanwhile, the apparent activation energy was 24.11 kJ/mol based on kinetic fitting, which indicated that the controlling step of the reaction was mainly a diffusion process. This work demonstrated the cooperative effect of sphalerite leaching in the O3-Fe2(SO4)3 system and provided a theoretical reference for efficient and atmospheric dissolution of sphalerite.

Mechanistic study on the promotion of Ca2+ leaching in steel slag through high-temperature solid waste modification.

Indirect carbonation of steel slag is an effective method for CO2 storage, reducing emissions, and promoting cleaner production in the steel industry. However, challenges remain, such as low Ca2+ leaching rates and slag management complexities arising from variations in mineral compositions. To address this, a high-temperature modification process is proposed to alter the mineral composition and facilitate the synergistic utilization of calcium and iron. This study delves into the effects of various solid waste modifications on the leaching of Ca2+ and the total iron content within steel slag. Results show that high-basicity modified slag forms Ca2(Al, Fe)2O5, reducing calcium leaching. Low-alkalinity modified slag produces calcium-rich aluminum minerals and also reduces the leaching of Ca2+ ions. At a basicity of 2.5, coal gangue, fly ash, and blast slag achieve maximum Ca2+ leaching rates of 88.93%, 89.46%, and 90.17%, respectively, with corresponding total iron contents of 41.46%, 37.72%, and 35.29%. Upgraded coal gangue exhibits a 50.02% increase in calcium leaching and a 15.58% increase in total iron content compared to the original slag. This enhances CO2 fixation and iron resource utilization. Overall, the proposed indirect carbonation and iron enrichment modification offer a novel approach for the resource utilization and environmental stability of steel slag.

OfBFT genes play an essential role in the proliferate flower formation of Osmanthus fragrans.

Floral organ development is one of the most vital events in flowering plants and is closely related to ornamental properties. The proliferate flower (a new branch or flower occurring in the centre of a flower) in plants is an interesting type, while the specific molecular mechanism remains largely unknown. Osmanthus fragrans 'Tianxiang Taige' has two different flower morphologies: normal flower and proliferate flower. Phenotypic observation suggested that a normal flower was composed of calyx, petal, stamen and pistil (reduced to leaf-like carpel). While in proliferate flower, the leaf-like carpel continued to grow and was replaced by a new branch. Paraffin section indicated that the re-growth of leaf carpels might be the main reason for proliferate flower formation. Transcriptome sequencing of normal and proliferate flower was performed, and the expression levels of related genes were analysed. Among the differentially expressed genes, OfBFT-a and OfBFT-b had differential expression during the proliferate flower formation process. The expression patterns revealed that both OfBFT-a and OfBFT-b were highly accumulated in carpels, and were significantly downregulated during the proliferate flower development process. Subcellular localization indicated that OfBFT-a and OfBFT-b proteins were located in the nucleus. Functional studies in 'Tianxiang Taige' and Arabidopsis showed that OfBFT-a and OfBFT-b had important roles in floral organ development, especially the proliferate flower formation process by downregulating the accumulation of AG and SEP3 homologous genes. These results may shed new light on the study of proliferate flower formation and flower morphology breeding in flowering plants.

Transcriptome-wide analysis of the differences between MCF7 cells cultured in DMEM or αMEM.

MCF7 cells have been used as an experimental model for breast cancer for decades. Typically, a culture medium is designed to supply cells with the nutrients essential for their continuous proliferation. Each medium has a specific nutritional composition. Therefore, cells cultured in different media may exhibit differences in their metabolism. However, only a few studies have investigated the effects of media on cells. In this study, we compared the effects of Dulbecco's modified Eagle medium (DMEM) and minimum essential medium alpha modification (αMEM) on MCF7 cells. The two media differentially affected the morphology, cell cycle, and proliferation of MCF7 cells, but had no effect on cell death. Replacement of DMEM with αMEM led to a decrease in ATP production and an increase in reactive oxygen species production, but did not affect the cell viability. RNA-sequencing and bioinformatic analyses revealed 721 significantly upregulated and 1247 downregulated genes in cells cultured in αMEM for 48 h compared with that in cells cultured in DMEM. The enriched gene ontology terms were related to mitosis and cell proliferation. Kyoto encyclopedia of genes and genomes analysis revealed cell cycle and DNA replication as the top two significant pathways. MCF7 cells were hypoxic when cultured in αMEM. These results show that the culture medium considerably affects cultured cells. Thus, the stability of the culture system in a study is very important to obtain reliable results.

Substrate specificity mapping of fungal CAZy AA3_2 oxidoreductases.

BACKGROUND: Oxidative enzymes targeting lignocellulosic substrates are presently classified into various auxiliary activity (AA) families within the carbohydrate-active enzyme (CAZy) database. Among these, the fungal AA3 glucose-methanol-choline (GMC) oxidoreductases with varying auxiliary activities are attractive sustainable biocatalysts and important for biological function. CAZy AA3 enzymes are further subdivided into four subfamilies, with the large AA3_2 subfamily displaying diverse substrate specificities. However, limited numbers of enzymes in the AA3_2 subfamily are currently biochemically characterized, which limits the homology-based mining of new AA3_2 oxidoreductases. Importantly, novel enzyme activities may be discovered from the uncharacterized parts of this large subfamily. RESULTS: In this study, phylogenetic analyses employing a sequence similarity network (SSN) and maximum likelihood trees were used to cluster AA3_2 sequences. A total of 27 AA3_2 proteins representing different clusters were selected for recombinant production. Among them, seven new AA3_2 oxidoreductases were successfully produced, purified, and characterized. These enzymes included two glucose dehydrogenases (TaGdhA and McGdhA), one glucose oxidase (ApGoxA), one aryl alcohol oxidase (PsAaoA), two aryl alcohol dehydrogenases (AsAadhA and AsAadhB), and one novel oligosaccharide (gentiobiose) dehydrogenase (KiOdhA). Notably, two dehydrogenases (TaGdhA and KiOdhA) were found with the ability to utilize phenoxy radicals as an electron acceptor. Interestingly, phenoxy radicals were found to compete with molecular oxygen in aerobic environments when serving as an electron acceptor for two oxidases (ApGoxA and PsAaoA), which sheds light on their versatility. Furthermore, the molecular determinants governing their diverse enzymatic functions were discussed based on the homology model generated by AlphaFold. CONCLUSIONS: The phylogenetic analyses and biochemical characterization of AA3_2s provide valuable guidance for future investigation of AA3_2 sequences and proteins. A clear correlation between enzymatic function and SSN clustering was observed. The discovery and biochemical characterization of these new AA3_2 oxidoreductases brings exciting prospects for biotechnological applications and broadens our understanding of their biological functions.

DNA methylome analysis reveals novel insights into active hypomethylated regulatory mechanisms of temperature-dependent flower opening in Osmanthus fragrans.

Short-term ambient low temperature (ALT) stimulation is necessary for Osmanthus fragrans to facilitate continued flower opening after floral bud development reaches maturity. DNA methylation, a vital epigenetic modification, regulates various biological processes in response to temperature fluctuations. However, its role in temperature-driven flower opening remains elusive. In this study, we identified the pivotal timeframe during which O. fragrans promptly detected temperature cues. Using whole-genome bisulfite sequencing, we explored global DNA hypomethylation during this phase, with the most significant changes occurring in CHH sequence contexts. Auxin transport inhibitor (TIBA) application revealed that ALT-induced endogenous auxin accumulation promoted peduncle elongation. In our mRNA-seq analysis, we discovered that the differentially expressed genes (DEGs) with hypo-differentially methylated regions (hypo-DMRs) were mainly enriched in auxin and temperature response, RNA processing, and carbohydrate and lipid metabolism. Transcripts of three DNA demethylase genes (OfROS1a, OfDML3, OfDME) showed upregulation. Furthermore, all DNA methylase genes, except OfCMT2b, also displayed increased expression, specifically with two of them, OfCMT3a and OfCMT1, being associated with hypo-DMRs. Promoter assays showed that OfROS1a, with promoters containing low-temperature- and auxin-responsive elements, were activated by ALT and exogenous IAA at low concentrations but inhibited at high concentrations. Overexpression of OfROS1 reduced endogenous auxin levels but enhanced the expression of genes related to auxin response and spliceosome in petunia. Furthermore, OfROS1 promoted sucrose synthesis in petunia corollas. Our data characterized the rapid response of active DNA hypomethylation to ALT and suggested a possible epiregulation of temperature-dependent flower opening in O. fragrans. This study revealed the pivotal role of DNA hypomethylation in O. fragrans during the ALT-responsive phase before flower opening, involving dynamic DNA demethylation, auxin signaling modulation, and a potential feedback loop between hypomethylation and methylation.

Comprehensive analysis of anoikis-related genes in diagnosis osteoarthritis: based on machine learning and single-cell RNA sequencing data.

Osteoarthritis (OA) is a degenerative disease closely associated with Anoikis. The objective of this work was to discover novel transcriptome-based anoikis-related biomarkers and pathways for OA progression.The microarray datasets GSE114007 and GSE89408 were downloaded using the Gene Expression Omnibus (GEO) database. A collection of genes linked to anoikis has been collected from the GeneCards database. The intersection genes of the differential anoikis-related genes (DEARGs) were identified using a Venn diagram. Infiltration analyses were used to identify and study the differentially expressed genes (DEGs). Anoikis clustering was used to identify the DEGs. By using gene clustering, two OA subgroups were formed using the DEGs. GSE152805 was used to analyse OA cartilage on a single cell level. 10 DEARGs were identified by lasso analysis, and two Anoikis subtypes were constructed. MEgreen module was found in disease WGCNA analysis, and MEturquoise module was most significant in gene clusters WGCNA. The XGB, SVM, RF, and GLM models identified five hub genes (CDH2, SHCBP1, SCG2, C10orf10, P FKFB3), and the diagnostic model built using these five genes performed well in the training and validation cohorts. analysing single-cell RNA sequencing data from GSE152805, including 25,852 cells of 6 OA cartilage.

Biocatalytic cascade to polysaccharide amination.

BACKGROUND: Chitin, the main form of aminated polysaccharide in nature, is a biocompatible, polycationic, and antimicrobial biopolymer used extensively in industrial processes. Despite the abundance of chitin, applications thereof are hampered by difficulties in feedstock harvesting and limited structural versatility. To address these problems, we proposed a two-step cascade employing carbohydrate oxidoreductases and amine transaminases for plant polysaccharide aminations via one-pot reactions. Using a galactose oxidase from Fusarium graminearum for oxidation, this study compared the performance of CvATA (from Chromobacterium violaceum) and SpATA (from Silicibacter pomeroyi) on a range of oxidized carbohydrates with various structures and sizes. Using a rational enzyme engineering approach, four point mutations were introduced on the SpATA surface, and their effects on enzyme activity were evaluated. RESULTS: Herein, a quantitative colorimetric assay was developed to enable simple and accurate time-course measurement of the yield of transamination reactions. With higher operational stability, SpATA produced higher product yields in 36 h reactions despite its lower initial activity. Successful amination of oxidized galactomannan by SpATA was confirmed using a deuterium labeling method; higher aminated carbohydrate yields achieved with SpATA compared to CvATA were verified using HPLC and XPS. By balancing the oxidase and transaminase loadings, improved operating conditions were identified where the side product formation was largely suppressed without negatively impacting the product yield. SpATA mutants with multiple alanine substitutions besides E407A showed improved product yield. The E407A mutation reduced SpATA activity substantially, supporting its predicted role in maintaining the dimeric enzyme structure. CONCLUSIONS: Using oxidase-amine transaminase cascades, the study demonstrated a fully enzymatic route to polysaccharide amination. Although the activity of SpATA may be further improved via enzyme engineering, the low operational stability of characterized amine transaminases, as a result of low retention of PMP cofactors, was identified as a key factor limiting the yield of the designed cascade. To increase the process feasibility, future efforts to engineer improved SpATA variants should focus on improving the cofactor affinity, and thus the operational stability of the enzyme.

Effect of Phanerochaete chrysosporium induced phosphate precipitation on bacterial diversity during the soil remediation process.

Biomineralization by phosphate minerals and phosphate solubilizing fungi (PSF) has attracted great interest as a novel remediation method for heavy metal(loid) co-contaminated soil. It was very essential to investigate the microenvironment response with the application of amendments. In this study, three grain sizes of hydroxyapatites (HAP) and Phanerochaete chrysosporium (P. chrysosporium) were used to investigate the change in heavy metal(loid) fractions, soil physicochemical properties, and bacterial community during the remediation of Mangchang and Dabaoshan acidic mine soils. The results showed that the residual fractions in the two soils increased significantly after 35 days of remediation, especially that of As and Zn in Dabaoshan soils were presented at over 87%. In addition, soil pH, organic matter (OM), and available phosphorous (AP) were almost improved. 16S rRNA sequencing analysis indicated that the introduction of culture medium and P. chrysosporium alone changed bacterial abundance, but the addition of HAP changed the bacterial diversity and community composition by altering environmental conditions. The amendments in the research showed good performance on immobilizing heavy metal(loid)s and reducing their bioavailability. Moreover, the research suggested that environmental factors and soil inherent properties could influence the microbial community structure and composition.

A cross-scale framework for evaluating flexibility values of battery and fuel cell electric vehicles.

Flexibility has become increasingly important considering the intermittency of variable renewable energy in low-carbon energy systems. Electrified transportation exhibits great potential to provide flexibility. This article analyzed and compared the flexibility values of battery electric vehicles and fuel cell electric vehicles for planning and operating interdependent electricity and hydrogen supply chains while considering battery degradation costs. A cross-scale framework involving both macro-level and micro-level models was proposed to compute the profits of flexible EV refueling/charging with battery degradation considered. Here we show that the flexibility reduction after considering battery degradation is quantified by at least 4.7% of the minimum system cost and enlarged under fast charging and low-temperature scenarios. Our findings imply that energy policies and relevant management technologies are crucial to shaping the comparative flexibility advantage of the two transportation electrification pathways. The proposed cross-scale methodology has broad implications for the assessment of emerging energy technologies with complex dynamics.

Beyond Constant Current: Origin of Pulse-Induced Activation in Phase-Transforming Battery Electrodes.

Mechanistic understanding of phase transformation dynamics during battery charging and discharging is crucial toward rationally improving intercalation electrodes. Most studies focus on constant-current conditions. However, in real battery operation, such as in electric vehicles during discharge, the current is rarely constant. In this work we study current pulsing in LiXFePO4 (LFP), a model and technologically important phase-transforming electrode. A current-pulse activation effect has been observed in LFP, which decreases the overpotential by up to ∼70% after a short, high-rate pulse. This effect persists for hours or even days. Using scanning transmission X-ray microscopy and operando X-ray diffraction, we link this long-lived activation effect to a pulse-induced electrode homogenization on both the intra- and interparticle length scales, i.e., within and between particles. Many-particle phase-field simulations explain how such pulse-induced homogeneity contributes to the decreased electrode overpotential. Specifically, we correlate the extent and duration of this activation to lithium surface diffusivity and the magnitude of the current pulse. This work directly links the transient electrode-level electrochemistry to the underlying phase transformation and explains the critical effect of current pulses on phase separation, with significant implication on both battery round-trip efficiency and cycle life. More broadly, the mechanisms revealed here likely extend to other phase-separating electrodes, such as graphite.

A Targeted Multi-Crystalline Manganese Oxide as a Tumor-Selective Nano-Sized MRI Contrast Agent for Early and Accurate Diagnosis of Tumors.

Introduction: Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy. Methods: Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO). Results: The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells. Conclusion: Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.

Activity-based locomotor training: improving the movement in children with spinal cord injury.

OBJECTIVE: The objective of this study was to investigate the effects of activity-based locomotor training (ABLT) on motor function and walking ability in children with spinal cord injury (SCI). MATERIALS AND METHODS: The Chinese National Knowledge Infrastructure, WanFang, VIP, PubMed, and Web of Science databases were searched for related studies, with two reviewers subsequently evaluating the literature quality using the Cochrane Handbook. RESULTS: A total of 11 studies were eligible, while only one met the ABLT standard program criteria. Overall, ABLT significantly improved the lower limb motor function, increased walking speed and distance, and improved the daily living ability of children with SCI. CONCLUSIONS: The ABLT strategy is of great significance to the motor function and walking ability of children with SCI. At present, there exist few studies on the application of ABLT for pediatric SCI. Further control studies with a larger sample size are required to improve the ABLT program guidelines for children with SCI.

OBJETIVO: Discuta el impacto del entrenamiento ejercicio basado en la actividad en la lesión de la médula espinal en la función de movimiento de los niños y la capacidad de caminar. MATERIALS Y MÉTODOS: Según China Zhiwang, Wanfang, VIP, PubMed, Science Network y otros documentos relacionados como fuente de datos. Dos revisores usan calidad de evaluación manual de Cochrane. RESULTADOS: Un total de 11 estudios cumplen con las condiciones. Solo hay un estudio que cumple con los proyectos estándar de ABLT. General, ABLT mejora significativamente la función de los niños con lesiones de la médula espinal, aumenta la velocidad y la distancia de caminar y mejora la capacidad de la vida diaria. CONCLUSIÓN: La estrategia ABLT es de gran importancia para la función de movimiento de los niños de la médula espinal y la capacidad de caminar. En la actualidad, ABLT tiene menos investigación en lesión pediátrica de la médula espinal. Es necesario mostrar la cantidad de muestra y controlar la investigación para mejorar las pautas del plan ABLT para el daño de la médula espinal a los niños.

Comparative Study of the Mechanical and Fracturing Behaviors of Shale from Different Gas Blocks in the Longmaxi Formation.

With the development of shale gas exploration and exploitation, the mechanical and failure characteristics of shale have become one of the focuses. However, few studies have considered the differences in the mechanical properties of shales in different shale gas blocks. In this study, the effects of bedding orientation on the stress-strain curves, elastic modulus, Poisson's ratio, and fracture morphology of shale samples from the Zhaotong block are analyzed by laboratory experiments, first. Then, a standard deviation method is used to characterize the anisotropy degree of the mechanical and fracturing characteristics of shale. The anisotropy ratio of shale samples between the Zhaotong and Chongqing areas has been comparatively studied. Comparison results show that the shale anisotropy induced by the bedding orientations demonstrates apparent regional characteristics. There are significant differences in the mechanical properties of shale obtained from different shale gas blocks. It indicates that the optimization of engineering practices such as the design of hydraulic fracturing should consider the influences of the bedding orientations and shale gas blocks on the shale anisotropy.

A novel two-dimensional NiCl2O8 lattice with negative Poisson's ratio and magnetic modulation.

Two-dimensional (2D) materials with simultaneous magnetic semiconducting properties and a negative Poisson's ratio are crucial for fabricating multifunctional electronic devices. However, progress in this area has been generally constrained. Based on first-principles calculations, we engineered a 2D Ni-based oxyhalide with a honeycomb lattice structure. It was observed that the NiCl2O8 monolayer exhibits both high- and low-buckling states in its geometry, along with intrinsic magnetic semiconductor properties in its electronic structure. Importantly, we demonstrated that the magnetic ordering of the NiCl2O8 lattice is susceptible to applied strain, which resulted in a phase transition from paramagnetic to ferromagnetic under biaxial strain. The Curie temperature was also evaluated using Monte Carlo simulations within the Ising model. Additionally, our research uncovered that the 2D NiCl2O8 lattice chain displays a negative Poisson's ratio (NPR) along the z-direction. The triangular hinge structure in its centrosymmetric configuration was identified as the origin of this unique phenomenon. The coexistence of NPR and magnetic phase transition properties in the NiCl2O8 lattice makes it quite promising for applications in nanoelectronic and spintronic devices.

MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds.

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma.

Accumulating evidence has demonstrated that chromatin regulators (CRs) regulate immune cell infiltration and are correlated with prognoses of patients in some cancers. However, the immunological and prognostic roles of CRs in lung adenocarcinoma (LUAD) are still unclear. Here, we systematically revealed the correlations of CRs with immunological features and the survival in LUAD patients based on a cohort of gene expression datasets from the public TCGA and GEO databases and real RNA-seq data by an integrative analysis using a comprehensive bioinformatics method. Totals of 160 differentially expressed CRs (DECRs) were identified between LUAD and normal lung tissues, and two molecular prognostic subtypes (MPSs) were constructed and evaluated based on 27 prognostic DECRs using five independent datasets (p =0.016, <0.0001, =0.008, =0.00038 and =0.00055, respectively). Six differentially expressed genes (DEGs) (CENPK, ANGPTL4, CCL20, CPS1, GJB3, TPSB2) between two MPSs had the most important prognostic feature and a six-gene prognostic model was established. LUAD patients in the low-risk subgroup showed a higher overall survival (OS) rate than those in the high-risk subgroup in nine independent datasets (p <0.0001, =0.021, =0.016, =0.0099, <0.0001, =0.0045, <0.0001, =0.0038 and =0.00013, respectively). Six-gene prognostic signature had the highest concordance index of 0.673 compared with 19 reported prognostic signatures. The risk score was significantly correlated with immunological features and activities of oncogenic signaling pathways. LUAD patients in the low-risk subgroup benefited more from immunotherapy and were less sensitive to conventional chemotherapy agents. This study provides novel insights into the prognostic and immunological roles of CRs in LUAD.

Temperature-responsive module of OfAP1 and OfLFY regulates floral transition and floral organ identity in Osmanthus fragrans.

The MADS-box transcription factor APETELA1 (AP1) is crucially important for reproductive developmental processes. The function of AP1 and the classic LFY-AP1 interaction in woody plants are not widely known. Here, the OfAP1-a gene from the continuously flowering plant Osmanthus fragrans 'Sijigui' was characterized, and its roles in regulating flowering time, petal number robustness and floral organ identity were determined using overexpression in Arabidopsis thaliana and Nicotiana tabacum. The expression of OfAP1-a was significantly induced by low ambient temperature and was upregulated with the floral transition process. Ectopic expression OfAP1-a revealed its classic function in flowering and flower ABC models. The expression of OfAP1-a is inhibited by LEAFY (OfLFY) through direct promoter binding, as confirmed by yeast one-hybrid and dual luciferase assays. Arabidopsis plants overexpressing OfAP1-a exhibited accelerated flowering and altered floral organ identities. Moreover, OfAP1-a-overexpressing plants displayed variable petal numbers. Likewise, the overexpression of OfLFY in Arabidopsis and Nicotiana altered petal number robustness and inflorescence architecture, partially by regulating native AP1 in transformed plants. Furthermore, we performed RNA-seq analysis of transgenic Nicotiana plants. DEGs were identified by transcriptome analysis, and we found that the expression of several floral homeotic genes was altered in both OfAP1-a and OfLFY-overexpressing transgenic lines. Our results suggest that OfAP1-a may play important roles during floral transition and development in response to ambient temperature. OfAP1-a functions as a petal number modulator and may directly activate a subset of flowers to regulate floral organ formation. OfAP1-a and OfLFY mutually regulate the expression of each other and coregulate genes that might be involved in these phenotypes related to flowering. The results provide valuable data for understanding the function of the LFY-AP1 module in the reproductive process and shaping floral structures in woody plants.