Squaraine Dyes Exhibit Spontaneous Fluorescence Blinking That Enables Live-Cell Nanoscopy.

Hampered by their susceptibility to nucleophilic attack and chemical bleaching, electron-deficient squaraine dyes have long been considered unsuitable for biological imaging. This study unveils a surprising twist: in aqueous environments, bleaching is not irreversible but rather a reversible spontaneous quenching process. Leveraging this new discovery, we introduce a novel deep-red squaraine probe tailored for live-cell super-resolution imaging. This probe enables single-molecule localization microscopy (SMLM) under physiological conditions without harmful additives or intense lasers and exhibits spontaneous blinking orchestrated by biological nucleophiles, such as glutathione or hydroxide anion. With a low duty cycle (∼0.1%) and high-emission rate (∼6 × 104 photons/s under 400 W/cm2), the squaraine probe surpasses the benchmark Cy5 dye by 4-fold and Si-rhodamine by a factor of 1.7 times. Live-cell SMLM with the probe reveals intricate structural details of cell membranes, which demonstrates the high potential of squaraine dyes for next-generation super-resolution imaging.

Fusion Genes Landscape of Lung Cancer Patients From Inner Mongolia, China.

Lung cancer is the leading cause of cancer-related deaths globally. Gene fusion, a key driver of tumorigenesis, has led to the identification of numerous driver gene fusions for lung cancer diagnosis and treatment. However, previous studies focused on Western populations, leaving the possibility of unrecognized lung cancer-associated gene fusions specific to Inner Mongolia due to its unique genetic background and dietary habits. To address this, we conducted DNA sequencing analysis on tumor and adjacent nontumor tissues from 1200 individuals with lung cancer in Inner Mongolia. Our analysis established a comprehensive fusion gene landscape specific to lung cancer in Inner Mongolia, shedding light on potential region-specific molecular mechanisms underlying the disease. Compared to Western cohorts, we observed a higher occurrence of ALK and RET fusions in Inner Mongolian patients. Additionally, we discovered eight novel fusion genes in three patients: SLC34A2-EPHB1, CCT6P3-GSTP1, BARHL2-APC, HRAS-MELK, FAM134B-ERBB2, ABCB1-GIPC1, GPR98-ALK, and FAM134B-SALL1. These previously unreported fusion genes suggest potential regional specificity. Furthermore, we characterized the fusion genes' structures based on breakpoints and described their impact on major functional gene domains. Importantly, the identified novel fusion genes exhibited significant clinical and pathological relevance. Notably, patients with SLC34A2-EPHB1, CCT6P3-GSTP1, and BARHL2-APC fusions showed sensitivity to the combination of chemotherapy and immunotherapy. Patients with HRAS-MELK, FAM134B-ERBB2, and ABCB1-GIPC1 fusions showed sensitivity to chemotherapy. In summary, our study provides novel insights into the frequency, distribution, and characteristics of specific fusion genes, offering valuable guidance for the development of effective clinical treatments, particularly in Inner Mongolia.

Identification of shared and disease-specific intratumoral microbiome-host gene associations in gastrointestinal tumors.

Intratumoral microbiota and host genes interact to promote gastrointestinal disorders, but how the two interact to influence host tumorigenesis remains unclear. Here, we utilized a machine learning-based framework to jointly dissect the paired intratumoral microbiome and host transcriptome profiles in patients with colon adenocarcinoma, hepatocellular carcinoma, and gastric cancer. We identified associations between intratumoral microbes and host genes that depict shared as well as cancer type-specific patterns. We found that a common set of host gene and pathways implicated in cell proliferation and energy metabolism are associated with cancer type-specific intratumoral microbes. Additionally, we also found that intratumoral microbes that have been implicated in three gastrointestinal tumors, such as Lachnoclostridium, are correlated with different host pathways in each tumor, indicating that similar microbes can influence host tumorigenesis in a cancer type-specific manner by regulation of different host genes. Our study reveals patterns of association between intratumoral microbiota and host genes in gastrointestinal tumors, providing new insights into the biology of gastrointestinal tumors.

Characterization of TBP and TAFs in Mungbean (Vigna radiata L.) and Their Potential Involvement in Abiotic Stress Response.

The TATA-box binding protein (TBP) and TBP-associated factors (TAFs) constitute the transcription factor IID (TFIID), a crucial component of RNA polymerase II, essential for transcription initiation and regulation. Several TFIID subunits are shared with the Spt-Ada-Gcn5-acetyltransferase (SAGA) coactivator complex. Recent research has revealed the roles of TBP and TAFs in organogenesis and stress adaptation. In this study, we identified 1 TBP and 21 putative TAFs in the mungbean genome, among which VrTAF5, VrTAF6, VrTAF8, VrTAF9, VrTAF14, and VrTAF15 have paralogous genes. Their potential involvement in abiotic stress responses was also investigated here, including high salinity, water deficit, heat, and cold. The findings indicated that distinct genes exerted predominant influences in the response to different abiotic stresses through potentially unique mechanisms. Specifically, under salt stress, VrTBP, VrTAF2, and VrTAF15-1 were strongly induced, while VrTAF10, VrTAF11, and VrTAF13 acted as negative regulators. In the case of water-deficit stress, it was likely that VrTAF1, VrTAF2, VrTAF5-2, VrTAF9, and VrTAF15-1 were primarily involved. Additionally, in response to changes in ambient temperature, it was possible that genes such as VrTAF5-1, VrTAF6-1, VrTAF9-2, VrTAF10, VrTAF13, VrTAF14b-2, and VrTAF15-1 might play a dominant role. This comprehensive exploration of VrTBP and VrTAFs can offer a new perspective on understanding plant stress responses and provide valuable insights into breeding improvement.

[Research Progress of Helicobacter pylori-Associated Extragastric Diseases].

Helicobacter pylori (Hp) is a common Gram-negative bacillus causing gastrointestinal infections.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter Candida to release toxins continuously and play a role in escaping the recognition of the host immune system and the bactericidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other diseases by Hp.

Thiolation for Enhancing Photostability of Fluorophores at the Single-Molecule Level.

Fluorescent probes are essential for single-molecule imaging. However, their application in biological systems is often limited by the short photobleaching lifetime. To overcome this, we developed a novel thiolation strategy for squaraine dyes. By introducing thiolation of the central cyclobutene of squaraine (thio-squaraine), we observed a ≈5-fold increase in photobleaching lifetime. Our single-molecule data analysis attributes this improvement to improved photostability resulting from thiolation. Interestingly, bulk measurements show rapid oxidation of thio-squaraine to its oxo-analogue under irradiation, giving the perception of inferior photostability. This discrepancy between bulk and single-molecule environments can be ascribed to the factors in the latter, including larger intermolecular distances and restricted mobility, which reduce the interactions between a fluorophore and reactive oxygen species produced by other fluorophores, ultimately impacting photobleaching and photoconversion rate. We demonstrate the remarkable performance of thio-squaraine probes in various imaging buffers, such as glucose oxidase with catalase (GLOX) and GLOX+trolox. We successfully employed these photostable probes for single-molecule tracking of CD56 membrane protein and monitoring mitochondria movements in live neurons. CD56 tracking revealed distinct motion states and the corresponding protein fractions. This investigation is expected to propel the development of single-molecule imaging probes, particularly in scenarios where bulk measurements show suboptimal performance.

Predicting colorectal cancer tumor mutational burden from histopathological images and clinical information using multi-modal deep learning.

MOTIVATION: Tumor mutational burden (TMB) is an indicator of the efficacy and prognosis of immune checkpoint therapy in colorectal cancer (CRC). In general, patients with higher TMB values are more likely to benefit from immunotherapy. Though whole-exome sequencing is considered the gold standard for determining TMB, it is difficult to be applied in clinical practice due to its high cost. There are also a few DNA panel-based methods to estimate TMB; however, their detection cost is also high, and the associated wet-lab experiments usually take days, which emphasize the need for faster and cheaper alternatives. RESULTS: In this study, we propose a multi-modal deep learning model based on a residual network (ResNet) and multi-modal compact bilinear pooling to predict TMB status (i.e. TMB high (TMB_H) or TMB low(TMB_L)) directly from histopathological images and clinical data. We applied the model to CRC data from The Cancer Genome Atlas and compared it with four other popular methods, namely, ResNet18, ResNet50, VGG19 and AlexNet. We tested different TMB thresholds, namely, percentiles of 10%, 14.3%, 15%, 16.3%, 20%, 30% and 50%, to differentiate TMB_H and TMB_L.For the percentile of 14.3% (i.e. TMB value 20) and ResNet18, our model achieved an area under the receiver operating characteristic curve of 0.817 after 5-fold cross-validation, which was better than that of other compared models. In addition, we also found that TMB values were significantly associated with the tumor stage and N and M stages. Our study shows that deep learning models can predict TMB status from histopathological images and clinical information only, which is worth clinical application.

Enhancing long-term frequency stability of a single-mode optoelectronic oscillator based on phase conjugation.

We propose and experimentally demonstrate what we believe to be a novel single-mode optoelectronic oscillator (OEO) with low frequency drift based on phase conjugation. The long-term frequency stabilization of the OEO is achieved by using photonic microwave phase-conjugate passive compensation. Besides, since there happens to be a nonlinear coupled double loop structure in the OEO, single-mode oscillation can be achieved. The experimental results show that the side mode suppression ratio (SMSR) of the radio frequency (RF) signal from the OEO at 9.93 GHz is enhanced from 5 dB to 68 dB after side mode suppression, and the maximum frequency drift within 600 s reduced from 1.51 ppm to 0.04 ppm, optimized by a factor of about 40. The OEO has a simple structure, no external injection, and the phase noise is not limited by the injected signal.

Identification of the Immune Subtypes for the Prediction of Metastasis in Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Most patients with pancreatic neuroendocrine tumors (pNETs) present with unresectable or metastatic disease. Increasing evidence shows that the immune cell infiltration patterns play a pivotal role in tumor progression in pNETs. Nonetheless, there has been no comprehensive analysis of the effect of immune infiltration patterns on metastasis. METHODS: The gene expression profiling dataset and clinical data were obtained from the Gene Expression Omnibus database. Estimation of Stromal and Immune Cells in Malignant Tumors using the Expression Data and single-sample Gene Set Enrichment Analysis were used to uncover the landscape of the tumor immune microenvironment. Subtypes based on the immune infiltration patterns were identified by the unsupervised clustering algorithm. Differentially expressed genes were identified using the limma packages of R. Functional enrichment analyses of these genes were carried out using STRING, Kyoto Encyclopedia of Genes and Genomes, and Reactome. RESULTS: The landscape of immune cells in pNET samples was constructed, and three immune cell infiltration subtypes (Immunity-H, Immunity-M, and Immunity-L) were identified. Immune cell infiltration degrees and metastasis were positively correlated. A protein-protein interaction network containing 80 genes was constructed, and functional enrichment revealed that these genes were mainly enriched in immune-related pathways. Eleven metastasis-related genes were differentially expressed among three subtypes, including MMP14, MMP2, MMP12, MMP7, SPARC, MMP19, ITGAV, MMP23B, MMP1, MMP25, and MMP9. There is a certain consistency of immune infiltration pattern between the primary tumor and metastatic tumor samples. CONCLUSION: Our findings may deepen the understanding of the immune-mediated regulatory mechanisms underlying pNETs and may provide some promising targets for immunotherapy.

Genome-Wide Identification, Expression Analysis, and Potential Roles under Abiotic Stress of the YUCCA Gene Family in Mungbean (Vigna radiata L.).

YUCCA, belonging to the class B flavin-dependent monooxygenases, catalyzes the rate-limiting step for endogenous auxin synthesis and is implicated in plant-growth regulation and stress response. Systematic analysis of the YUCCA gene family and its stress response benefits the dissection of regulation mechanisms and breeding applications. In this study, 12 YUCCA genes were identified from the mungbean (Vigna radiata L.) genome and were named based on their similarity to AtYUCCAs. Phylogenetic analysis revealed that the 12 VrYUCCAs could be divided into 4 subfamilies. The evidence from enzymatic assays in vitro and transgenetic Arabidopsis in vivo indicated that all the isolated VrYUCCAs had biological activity in response to IAA synthesis. Expression pattern analysis showed that functional redundancy and divergence existed in the VrYUCCA gene family. Four VrYUCCAs were expressed in most tissues, and five VrYUCCAs were specifically highly expressed in the floral organs. The response toward five stresses, namely, auxin (indole-3-acetic acid, IAA), salinity, drought, high temperatures, and cold, was also investigated here. Five VrYUCCAs responded to IAA in the root, while only VrYUCCA8a was induced in the leaf. VrYUCCA2a, VrYUCCA6a, VrYUCCA8a, VrYUCCA8b, and VrYUCCA10 seemed to dominate under abiotic stresses, due to their sensitivity to the other four treatments. However, the response modes of the VrYUCCAs varied, indicating that they may regulate different stresses in distinct ways to finely adjust IAA content. The comprehensive analysis of the VrYUCCAs in this study lays a solid foundation for further investigation of VrYUCCA genes' mechanisms and applications in breeding.

Antitumor Activity of s-Triazine Derivatives: A Systematic Review.

1,3,5-triazine derivatives, also called s-triazines, are a series of containing-nitrogen heterocyclic compounds that play an important role in anticancer drug design and development. To date, three s-triazine derivatives, including altretamine, gedatolisib, and enasidenib, have already been approved for refractory ovarian cancer, metastatic breast cancer, and leukemia therapy, respectively, demonstrating that the s-triazine core is a useful scaffold for the discovery of novel anticancer drugs. In this review, we mainly focus on s-triazines targeting topoisomerases, tyrosine kinases, phosphoinositide 3-kinases, NADP+-dependent isocitrate dehydrogenases, and cyclin-dependent kinases in diverse signaling pathways, which have been extensively studied. The medicinal chemistry of s-triazine derivatives as anticancer agents was summarized, including discovery, structure optimization, and biological applications. This review will provide a reference to inspire new and original discoveries.

Critical size effect for the surface heat capacities of nano-CdS: theoretical and experimental studies.

The unique physical and chemical properties of nanomaterials are closely related to their surface thermodynamic functions, which mainly depend on their sizes. In this study, the thermodynamic properties of nano-cadmium sulphide (nano-CdS) were investigated by solubility technology. The nano-CdS powders with different particle sizes were prepared via a traditional solvothermal method, and the electrical conductivities of nano-CdS aqueous solutions at different temperatures were measured. The standard dissolution equilibrium constants of nano-CdS at different temperatures were calculated using the theory of dissolution thermodynamics. The standard molar dissolution thermodynamic functions, the molar surface thermodynamic functions and the specific surface thermodynamic functions of nano-CdS with different particle sizes were calculated by combining the thermodynamic functions of bulk-CdS, the principle of the thermodynamic cycle and the principle of electrochemical equilibrium. The experimental results show that the critical size values for the molar surface heat capacity and the specific surface heat capacity for approximately spherical nanoparticles are 9.3 nm and 8.7 nm, respectively. Within an acceptable range of error, the thermodynamic functions have linear and curved relationships with particle sizes and temperatures. Based on these results, it is disclosed that the critical size effect on surface heat capacities of nano-CdS is valuable to understand the energy storage processes of nanomaterials.

Correction: Critical size effect for the surface heat capacities of nano-CdS: theoretical and experimental studies.

Correction for 'Critical size effect for the surface heat capacities of nano-CdS: theoretical and experimental studies' by Shengjiang Zhang et al., Phys. Chem. Chem. Phys., 2022, 24, 6193-6207, https://doi.org/10.1039/D1CP04619E.

Treatment of ankylosing spondylitis complicated with a thoracolumbar Andersson lesion by posterior closed osteotomy, debridement and fusion through the fracture line.

BACKGROUND: An Andersson lesion (AL) is a fatigue fracture occurring across three columns in ankylosing spondylitis (AS), resulting in spinal pseudarthrosis (SP) formation, most commonly in the thoracolumbar segment. However, there is still great controversy and few reports on the best surgical method for the treatment of AS combined with thoracolumbar AL. The purpose of this study was to investigate the efficacy of posterior closed osteotomy, debridement and fusion through the fracture line for the treatment of this disease. METHODS: The clinical data of 13 patients (male 8, female 5, mean age 50.6 years) with AS combined with thoracolumbar AL treated with posterior closed osteotomy, debridement and fusion through the fracture line were retrospectively analysed. The following parameters of the full-length lateral spine radiographs were measured preoperatively and at the last follow-up: cervical 7 tilt (C7T), global kyphosis (GK), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), local kyphosis (LK), angle of the fusion levels (AFL), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and sagittal vertical axis (SVA). The visual analog scale (VAS), Oswestry disability index (ODI) and Scoliosis Research Society-22 (SRS-22) scores were recorded preoperatively and at the last follow-up. RESULTS: The mean operation time was 345 min, the mean blood loss was 673 mL, and the mean follow-up time was 21.9 months. Compared with the preoperative values, the C7T, GK, TK, TLK, LK, AFL, PT, SS and SVA values of all patients were significantly improved at the last follow-up (P < 0.05); GK improved from 81.62 ± 16.11 to 50.15 ± 8.55, with an average of 31° of correction (F = 75.945, P<0.001). The VAS, ODI and SRS-22 scores also significantly improved (P < 0.05). At the last follow-up, bone fusion was found in all fracture ends. One patient developed numbness in the lower limbs after surgery and recovered after 3 months of rehabilitation; none of the remaining patients experienced postoperative complications. CONCLUSIONS: Posterior closed osteotomy, debridement and fusion through the fracture line completely removes the necrotic tissue around the SP, relieves symptoms, and corrects kyphosis simultaneously. It reduces the tension behind the fracture line or changes the tension into compressive stress, enabling stable repair of the fracture and avoiding anterior surgery. It is a safe and effective operation.

A Universal Photoactivatable Tag Attached to Fluorophores Enables Their Use for Single-Molecule Imaging.

Single molecule localization microscopy based on photoactivation is a powerful tool for investigating the ultrastructure of cells. We developed a general strategy for photoactivatable fluorophores, using 2,3-dihydro-1,4-oxathiine group (SO) as a tag to attach to various skeletal structures, including coumarin, BODIPY, rhodamine, and cyanine. The conjugation of SO resulted in a significant loss of fluorescence due to photoinduced electron transfer (PeT). Under the irradiation of excitation light, singlet oxygen generated by the fluorophores converted the SO moiety into its ester derivative, terminated the PeT process, and restored the fluorescence. Single molecule localization imaging was achieved using a dual functional illuminating beam in the visible, acting as both the activating and the exciting source. We successfully applied these photoactivatable probes for time-lapse super-resolution tracking in living cells and super-resolution imaging of microtubule structures in neurons.

Three-dimensional genetic networks among seed oil-related traits, metabolites and genes reveal the genetic foundations of oil synthesis in soybean.

Although the biochemical and genetic basis of lipid metabolism is clear in Arabidopsis, there is limited information concerning the relevant genes in Glycine max (soybean). To address this issue, we constructed three-dimensional genetic networks using six seed oil-related traits, 52 lipid metabolism-related metabolites and 54 294 SNPs in 286 soybean accessions in total. As a result, 284 and 279 candidate genes were found to be significantly associated with seed oil-related traits and metabolites by phenotypic and metabolic genome-wide association studies and multi-omics analyses, respectively. Using minimax concave penalty (MCP) and smoothly clipped absolute deviation (SCAD) analyses, six seed oil-related traits were found to be significantly related to 31 metabolites. Among the above candidate genes, 36 genes were found to be associated with oil synthesis (27 genes), amino acid synthesis (four genes) and the tricarboxylic acid (TCA) cycle (five genes), and four genes (GmFATB1a, GmPDAT, GmPLDα1 and GmDAGAT1) are already known to be related to oil synthesis. Using this information, 133 three-dimensional genetic networks were constructed, 24 of which are known, e.g. pyruvate-GmPDAT-GmFATA2-oil content. Using these networks, GmPDAT, GmAGT and GmACP4 reveal the genetic relationships between pyruvate and the three major nutrients, and GmPDAT, GmZF351 and GmPgs1 reveal the genetic relationships between amino acids and seed oil content. In addition, GmCds1, along with average temperature in July and the rainfall from June to September, influence seed oil content across years. This study provides a new approach for the construction of three-dimensional genetic networks and reveals new information for soybean seed oil improvement and the identification of gene function.

Nontargeted Metabolomic Analysis of Plasma Metabolite Changes in Patients with Adolescent Idiopathic Scoliosis.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a relatively common spinal rotation deformity, and the pathogenesis of AIS is accompanied by metabolic dysfunction and changes in biochemical factors. In this study, plasma metabolite changes in AIS patients were analyzed based on nontargeted metabolomics to provide new insights for clarifying functional metabolic abnormalities in AIS patients. METHODS: Clinical indexes and blood samples were collected from 12 healthy subjects and 16 AIS patients. Metabolomics was used to analyze the changes in metabolites in plasma samples. The correlation between plasma metabolites and clinical indexes was analyzed by the Spearman rank correlation coefficient. RESULTS: Analysis of clinical data showed that the body weight, body mass index (BMI), and bone mineral density (BMD) index of the AIS group significantly decreased, while the blood phosphorus and Cobb angles increased significantly. Metabolomic analysis showed significant changes in 72 differential metabolites in the plasma of the AIS group, mainly including organooxygen compounds, carboxylic acids and derivatives, fatty acyls, steroids and steroid derivatives, and keto acids and derivatives. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that arginine biosynthesis, D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and citrate cycle (TCA cycle) were significantly enriched in the AIS and healthy groups. Spearman rank correlation coefficient analysis showed that the plasma metabolites C00026 (oxoglutarate), C00062 (L-arginine, arginine), C01042 (N-acetylaspartate), and C00158 (citrate) were significantly correlated with clinical indexes in AIS patients. In the healthy group, the plasma metabolites C00122 (fumarate), C00025 (glutamate and L-glutamic acid) and C00149 (malate, L-malic acid) were significantly correlated with clinical indexes, while C00624 (N-acetylglutamate) was not significantly correlated with the clinical indexes. CONCLUSION: The occurrence of AIS led to changes in clinical indexes and plasma metabolites. Plasma biomarkers and functional metabolic pathways were correlated with clinical indexes, which might provide new insights for the diagnosis and treatment of AIS.

Impact of Annulus-Sparing on Surgical Adequacy of Pulmonary Valve in Complete Repair of Tetralogy of Fallot with Right Ventricular Outflow Tract Incision.

Today, strategy of repair remains controversial and rare analyses on annular integrity associated with outcomes in complete repair by RVOT incision were performed in a large TOF cohort in China. This is a retrospective cohort study involving patients with TOF who had undergone complete repair by RVOT incision between January 2012 and December 2017 in Fuwai hospital. The primary outcome was a composite of reintervention, significant pulmonary regurgitation (PR) and significant annular peak gradient (APG). Multivariate Cox proportional-hazards model analyses were used to assess the relationships between annular integrity and outcomes. In total, 1673 survival patients with the median age of 318 days were included, and 1002 were male. During a median follow-up of 49 months, 538 participants developed the primary outcome (27 reinterventions). Multivariate Cox analyses showed that compared with AS, TAP was associated with an increased risk of primary outcome (adjusted HR, 1.94 [95% CI 1.60-2.37]) and the results remained unchanged even in most subgroups defined. In secondary outcomes analyses, TAP is associated with a higher risk of reintervention (adjusted HR, 3.32 [95% CI 1.25-8.79]) and significant PR (adjusted HR, 2.51 [95% CI 2.00-3.16]). However, TAP is not associated with a decreased risk of significant APG (adjusted HR, 1.33 [95% CI 0.94-1.88]). PVA integrity preservation is important in complete repair of TOF with RVOT incision. TAP is associated with a higher risk of reintervention and significant PR, and with a similar risk of significant APG. Significant APG in AS patients at discharge has a downtrend over time.

An evolutionary population structure model reveals pleiotropic effects of GmPDAT for traits related to seed size and oil content in soybean.

Seed oil traits in soybean that are of benefit to human nutrition and health have been selected for during crop domestication. However, these domesticated traits have significant differences across various evolutionary types. In this study, we found that the integration of evolutionary population structure (evolutionary types) with genome-wide association studies increased the power of gene detection, and it identified one locus for traits related to seed size and oil content on chromosome 13. This domestication locus, together with another one in a 200-kb region, was confirmed by the GEMMA and EMMAX software. The candidate gene, GmPDAT, had higher expressional levels in high-oil and large-seed accessions than in low-oil and small-seed accessions. Overexpression lines had increased seed size and oil content, whereas RNAi lines had decreased seed size and oil content. The molecular mechanism of GmPDAT was deduced based on results from linkage analysis for triacylglycerols and on histocytological comparisons of transgenic soybean seeds. Our results illustrate a new approach for identifying domestication genes with pleiotropic effects.

LncRNA ZFAS1 promotes pancreatic adenocarcinoma metastasis via the RHOA/ROCK2 pathway by sponging miR-3924.

BACKGROUND: The mortality and morbidity rates of pancreatic adenocarcinoma have been increasing over the past two decades, and an understanding of the mechanisms underlying pancreatic adenocarcinoma progression is urgently needed. The long non-coding RNA ZFAS1 has been demonstrated to be an oncogene in some cancers, but its function and mechanism in pancreatic adenocarcinoma remain unclear. METHODS: The ZFAS1 expression level in pancreatic adenocarcinoma was predicted by bioinformatic analysis, and the expression level of ZFAS1 in pancreatic adenocarcinoma tissue samples and cell lines was further detected by quantitative real-time PCR and in situ hybridization. The functions of ZFAS1 in pancreatic adenocarcinoma in vitro and in vivo were investigated by further bioinformatic analysis. Dual-luciferase reporter assays were used to confirm the binding of ZFAS1/miR-3924 and miR-3924/ROCK2, and rescue assays were performed to further investigate the underlying mechanism. RESULTS: ZFAS1 overexpression in pancreatic adenocarcinoma was predicted and experimentally verified. ZFAS1 silencing inhibited pancreatic adenocarcinoma metastasis in vitro and in vivo. The competing endogenous RNA mechanism of ZFAS1 was also identified. CONCLUSIONS: Our results demonstrated the promotive effect of ZFAS1 on pancreatic adenocarcinoma metastasis and suggested its potential role as a novel regulator of ROCK2.