Information-incorporated gene network construction with FDR control.

MOTIVATION: Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial correlation-based networks are preferred over marginal correlations. However, FDR control for partial correlation-based network construction is not well-studied. In addition, currently available partial correlation-based methods cannot take existing biological knowledge to help network construction while controlling FDR. RESULTS: In this paper, we propose a method called Partial Correlation Graph with Information Incorporation (PCGII). PCGII estimates partial correlations between each pair of genes by regularized node-wise regression that can incorporate prior knowledge while controlling the effects of all other genes. It handles high-dimensional data where the number of genes can be much larger than the sample size and controls FDR at the same time. We compare PCGII with several existing approaches through extensive simulation studies and demonstrate that PCGII has better FDR control and higher power. We apply PCGII to a plant gene expression dataset where it recovers confirmed regulatory relationships and a hub node, as well as several direct associations that shed light on potential functional relationships in the system. We also introduce a method to supplement observed data with a pseudogene to apply PCGII when no prior information is available, which also allows checking FDR control and power for real data analysis. AVAILABILITY AND IMPLEMENTATION: R package is freely available for download at https://cran.r-project.org/package=PCGII.

CYP4B1 polymorphisms and the risk of breast cancer in Chinese women: a case-control study.

BACKGROUND: Breast cancer (BC) is one of the malignant diseases threatening the life and health of women worldwide. The CYP4B1 gene was abnormally expressed in BC and was associated with the prognosis of BC patients. This study aimed to explore the relationship between CYP4B1 single nucleotide polymorphisms (SNPs) and BC risk in Chinese women. METHODS: A case-control study of 1,143 women (571 patients and 572 healthy individuals) was conducted. Rs2297813 G/T, rs12142787 G/A, and rs3766197 C/T in CYP4B1 were selected and genotyped by MassARRAY system. The relationships between these SNPs and the risk of BC were assessed by logistic regression analysis. In addition, multi-factor dimensionality reduction (MDR) was used to analyze SNP-SNP interactions. RESULTS: CYP4B1 rs2297813 had a risk-increasing effect on BC in women with body mass index (BMI) ≤ 24 kg/m2 (OR = 1.72, p = 0.026). CYP4B1 rs12142787 was associated with an increased BC risk in smokers (AA: OR = 1.32, p = 0.045). Among non-drinkers, rs2297813 (OR = 1.69, p = 0.009) and rs12142787 (OR = 1.51, p = 0.020) were related to an increased incidence of BC. CYP4B1 rs3766197 (OR = 1.61p = 0.031) was associated with a higher risk of advanced stages (III/IV stage) of BC. Besides, the contributions of CYP4B1 rs2297813 (OR = 1.55, p = 0.021) and rs12142787 (OR = 1.53, p = 0.033) to BC risk might be associated with more than one birth in patients with BC. The three-locus model consisting of rs2297813, rs12142787, and rs3766197 was regarded as the best predictive model for BC risk. CONCLUSION: CYP4B1 SNPs were associated with BC risk in Chinese women, especially in patients with BMI ≤ 24 kg/m2, smokers, non-drinkers, patients in advanced stages (III/IV stage), and patients who reproduced once. These findings shed light on the relationship between CYP4B1 SNPs and BC risk in Chinese women.

Imaging signs and the qualitative diagnosis of solitary rib lesions using 99mtechnetium-methylene diphosphonate whole-body bone imaging in patients with a malignant tumor.

Background: The aim of this study was to summarize the valuable information for qualitative diagnosis by investigating the imaging signs from the whole-body bone imaging of solitary rib lesions. Methods: A retrospective analysis was conducted of the data from 313 patients with malignant tumors and solitary rib lesions identified using whole-body bone imaging in Department of Nuclear Medicine of Central South University Xiangya School Affiliated Haikou Hospital between January 2015 and December 2017. Based on the final comprehensive diagnosis of the rib lesions, the patients were divided into a bone metastasis group, fracture group, other benign lesions group, and an uncertain group, and the characteristic imaging changes in rib lesions in each group were explored. Results: (I) Significant differences were identified among the 4 groups (P<0.001) in the distribution of lesions in the anterior, posterior, and lateral ribs and proximal costal cartilage. The fracture group had the highest proportion of lesions in the anterior ribs (99/121, 81.8%) and proximal costal cartilage (74.4%, 90/121). (II) Significant differences were detected in morphology, concentration, boundaries, and radioactivity distribution among the 4 groups of patients (P<0.001). The bone metastasis group had the highest proportion of lesions appearing as stripes (35/67, 52.2%), and the fracture group had the highest proportion of lesions appearing as spots (94.2%, 114/121) and the lowest proportion appearing as stripes (3/121, 2.5%). (III) Significant differences were found in the longitudinal diameter, transverse diameter, aspect ratio, and tumor-to-normal tissue ratio between the 4 groups (P<0.001). The longitudinal diameter (27.8±16.0 mm) and aspect ratio (1.9±1.0) of the bone metastasis group were the highest, whereas the longitudinal diameter (15.2±3.9 mm) and aspect ratio (1.0±0.2) of the fracture group were the smallest. Conclusions: This study revealed that different types of solitary rib lesions had relatively characteristic imaging signs in whole-body bone imaging.

Brassinosteroid gene regulatory networks at cellular resolution in the Arabidopsis root.

Brassinosteroids are plant steroid hormones that regulate diverse processes, such as cell division and cell elongation, through gene regulatory networks that vary in space and time. By using time series single-cell RNA sequencing to profile brassinosteroid-responsive gene expression specific to different cell types and developmental stages of the Arabidopsis root, we identified the elongating cortex as a site where brassinosteroids trigger a shift from proliferation to elongation associated with increased expression of cell wall-related genes. Our analysis revealed HOMEOBOX FROM ARABIDOPSIS THALIANA 7 (HAT7) and GT-2-LIKE 1 (GTL1) as brassinosteroid-responsive transcription factors that regulate cortex cell elongation. These results establish the cortex as a site of brassinosteroid-mediated growth and unveil a brassinosteroid signaling network regulating the transition from proliferation to elongation, which illuminates aspects of spatiotemporal hormone responses.

Brassinosteroids modulate autophagy through phosphorylation of RAPTOR1B by the GSK3-like kinase BIN2 in Arabidopsis.

Macroautophagy/autophagy is a conserved recycling process that maintains cellular homeostasis during environmental stress. Autophagy is negatively regulated by TOR (target of rapamycin), a nutrient-regulated protein kinase that in plants is activated by several phytohormones, leading to increased growth. However, the detailed molecular mechanisms by which TOR integrates autophagy and hormone signaling are poorly understood. Here, we show that TOR modulates brassinosteroid (BR)-regulated plant growth and stress-response pathways. Active TOR was required for full BR-mediated growth in Arabidopsis thaliana. Autophagy was constitutively up-regulated upon blocking BR biosynthesis or signaling, and down-regulated by increasing the activity of the BR pathway. BIN2 (brassinosteroid-insensitive 2) kinase, a GSK3-like kinase functioning as a negative regulator in BR signaling, directly phosphorylated RAPTOR1B (regulatory-associated protein of TOR 1B), a substrate-recruiting subunit in the TOR complex, at a conserved serine residue within a typical BIN2 phosphorylation motif. Mutation of RAPTOR1B serine 916 to alanine, to block phosphorylation by BIN2, repressed autophagy and increased phosphorylation of the TOR substrate ATG13a (autophagy-related protein 13a). By contrast, this mutation had only a limited effect on growth. We present a model in which RAPTOR1B is phosphorylated and inhibited by BIN2 when BRs are absent, activating the autophagy pathway. When BRs signal and inhibit BIN2, RAPTOR1B is thus less inhibited by BIN2 phosphorylation. This leads to increased TOR activity and ATG13a phosphorylation, and decreased autophagy activity. Our studies define a new mechanism by which coordination between BR and TOR signaling pathways helps to maintain the balance between plant growth and stress responses.

FERONIA functions through Target of Rapamycin (TOR) to negatively regulate autophagy.

FERONIA (FER) receptor kinase plays versatile roles in plant growth and development, biotic and abiotic stress responses, and reproduction. Autophagy is a conserved cellular recycling process that is critical for balancing plant growth and stress responses. Target of Rapamycin (TOR) has been shown to be a master regulator of autophagy. Our previous multi-omics analysis with loss-of-function fer-4 mutant implicated that FER functions in the autophagy pathway. We further demonstrated here that the fer-4 mutant displayed constitutive autophagy, and FER is required for TOR kinase activity measured by S6K1 phosphorylation and by root growth inhibition assay to TOR kinase inhibitor AZD8055. Taken together, our study provides a previously unknown mechanism by which FER functions through TOR to negatively regulate autophagy.

The deubiquitinating enzymes UBP12 and UBP13 positively regulate recovery after carbon starvation by modulating BES1 stability in Arabidopsis thaliana.

BRI1-EMS-SUPPRESSOR1 (BES1), a core transcription factor in the brassinosteroid (BR) signaling pathway, primarily regulates plant growth and development by influencing BR-regulated gene expression. Several E3 ubiquitin (Ub) ligases regulate BES1 stability, but little is known about BES1 deubiquitination, which antagonizes E3 ligase-mediated ubiquitination to maintain BES1 homeostasis. Here, we report that two Arabidopsis thaliana deubiquitinating enzymes, Ub-SPECIFIC PROTEASE (UBP) 12 and UBP13, interact with BES1. UBP12 and UBP13 removed Ub from polyubiquitinated BES1 to stabilize both phosphorylated and dephosphorylated forms of BES1. A double mutant, ubp12-2w ubp13-3, lacking UBP12 and UBP13 function showed both BR-deficient and BR-insensitive phenotypes, whereas transgenic plants overexpressing UBP12 or UBP13 exhibited an increased BR response. Expression of UBP12 and UPB13 was induced during recovery after carbon starvation, which led to BES1 accumulation and quick recovery of stressed plants. Our work thus establishes a mechanism by which UBP12 and UBP13 regulate BES1 protein abundance to enhance BR-regulated growth during recovery after carbon starvation.

Comparison of effectiveness and postoperative complications of different surgical methods in the treatment of benign prostatic hyperplasia: a systematic review and meta-analysis based on randomized controlled trials.

Background: More and more new surgical procedures for the treatment of benign prostate hyperplasia (BPH) are proposed creatively. However, the existing clinical evidence shows that the effectiveness and safety of various procedures exist inconsistent. Methods: The randomized controlled trials comparing the international prostate score, length of hospital stay, maximum urinary flow rate, operation time, and complication rates of prostatic artery embolization (PAE), Greenlight-XPS Laser prostate vaporization procedure (GLL PVP), diode laser enucleation of prostate (DILEP) and plasmakinetic resection of the prostate (PKRP), transurethral resection of the prostate (TURP) in patients with BPH were screened out in databases. The primary outcome was pooled using a restricted maximum likelihood-based random-effect model and inverse variance-based fixed-effect model. Cochrane Q statistics and I2 statistics were computed to quantify between-study heterogeneity. The risk of bias of each included study was assessed using the revised Cochrane risk of bias tool. Results: This meta-analysis ultimately included 14 original research papers, with 1,940 participants enrolled. Eight studies were considered to be at moderate risk of bias, while the others were at mild risk of bias. Although the improvement in functional outcome of the DILEP procedure was equivalent to that of the PKRP procedure, the DILEP procedure group had fewer hospital stays than the PKRP group (P=0.01). In addition, even though the performance of the GLL PVP procedure in the improvement of functional outcome was inferior to the counterpart of TURP (P=0.64), it had a much fewer hospital stays (P=0.01). Moreover, there is still insufficient evidence for the improvement of subjective functional indicators of postoperative patients with PAE compared with TURP [international prostate symptom score (IPSS): P=0.73; IPSS QoL: P=0.91], but achieved less satisfactory objective functional outcomes (Qmax: P=0.06; PVR: P=0.00). Discussion: New surgical procedures such as GLL PVP, PAE, and DILEP were safer than traditional TURP procedures. However, it is not superior to traditional surgery in the improvement of clinical symptoms. In clinical practice, the pros and cons of the new operation and the traditional operation should be carefully weighed, and the operation that is most suitable for the patient's condition should be selected.

Integration of multi-omics data reveals interplay between brassinosteroid and Target of Rapamycin Complex signaling in Arabidopsis.

Brassinosteroids (BRs) and Target of Rapamycin Complex (TORC) are two major actors coordinating plant growth and stress responses. Brassinosteroids function through a signaling pathway to extensively regulate gene expression and TORC is known to regulate translation and autophagy. Recent studies have revealed connections between these two pathways, but a system-wide view of their interplay is still missing. We quantified the level of 23 975 transcripts, 11 183 proteins, and 27 887 phosphorylation sites in wild-type Arabidopsis thaliana and in mutants with altered levels of either BRASSINOSTEROID INSENSITIVE 2 (BIN2) or REGULATORY ASSOCIATED PROTEIN OF TOR 1B (RAPTOR1B), two key players in BR and TORC signaling, respectively. We found that perturbation of BIN2 or RAPTOR1B levels affects a common set of gene-products involved in growth and stress responses. Furthermore, we used the multi-omic data to reconstruct an integrated signaling network. We screened 41 candidate genes identified from the reconstructed network and found that loss of function mutants of many of these proteins led to an altered BR response and/or modulated autophagy activity. Altogether, these results establish a predictive network that defines different layers of molecular interactions between BR- or TORC-regulated growth and autophagy.

Interactions between autophagy and phytohormone signaling pathways in plants.

Autophagy is a conserved recycling process with important functions in plant growth, development, and stress responses. Phytohormones also play key roles in the regulation of some of the same processes. Increasing evidence indicates that a close relationship exists between autophagy and phytohormone signaling pathways, and the mechanisms of interaction between these pathways have begun to be revealed. Here, we review recent advances in our understanding of how autophagy regulates hormone signaling and, conversely, how hormones regulate the activity of autophagy, both in plant growth and development and in environmental stress responses. We highlight in particular recent mechanistic insights into the coordination between autophagy and signaling events controlled by the stress hormone abscisic acid and by the growth hormones brassinosteroid and cytokinin and briefly discuss potential connections between autophagy and other phytohormones.

Integrated omics reveal novel functions and underlying mechanisms of the receptor kinase FERONIA in Arabidopsis thaliana.

The receptor kinase FERONIA (FER) is a versatile regulator of plant growth and development, biotic and abiotic stress responses, and reproduction. To gain new insights into the molecular interplay of these processes and to identify new FER functions, we carried out quantitative transcriptome, proteome, and phosphoproteome profiling of Arabidopsis (Arabidopsis thaliana) wild-type and fer-4 loss-of-function mutant plants. Gene ontology terms for phytohormone signaling, abiotic stress, and biotic stress were significantly enriched among differentially expressed transcripts, differentially abundant proteins, and/or misphosphorylated proteins, in agreement with the known roles for FER in these processes. Analysis of multiomics data and subsequent experimental evidence revealed previously unknown functions for FER in endoplasmic reticulum (ER) body formation and glucosinolate biosynthesis. FER functions through the transcription factor NAI1 to mediate ER body formation. FER also negatively regulates indole glucosinolate biosynthesis, partially through NAI1. Furthermore, we found that a group of abscisic acid (ABA)-induced transcription factors is hypophosphorylated in the fer-4 mutant and demonstrated that FER acts through the transcription factor ABA INSENSITIVE5 (ABI5) to negatively regulate the ABA response during cotyledon greening. Our integrated omics study, therefore, reveals novel functions for FER and provides new insights into the underlying mechanisms of FER function.

A cryptic inhibitor of cytokinin phosphorelay controls rice grain size.

Plant hormone cytokinin signals through histidine-aspartic acid (H-D) phosphorelay to regulate plant growth and development. While it is well known that the phosphorelay involves histidine kinases, histidine phosphotransfer proteins (HPs), and response regulators (RRs), how this process is regulated by external components remains unknown. Here we demonstrate that protein phosphatase with kelch-like domains (PPKL1), known as a signaling component of steroid hormone brassinosteroid, is actually a cryptic inhibitor of cytokinin phosphorelay in rice (Oryza sativa). Mutation at a specific amino acid D364 of PPKL1 activates cytokinin response and thus enlarges grain size in a semi-dominant mutant named s48. Overexpression of PPKL1 containing D364, either with the deletion of the phosphatase domain or not, rescues the s48 mutant phenotype. PPKL1 interacts with OsAHP2, one of authentic HPs, and D364 resides in a region resembling the receiver domain of RRs. Accordingly, PPKL1 can utilize D364 to suppress OsAHP2-to-RR phosphorelay, whereas mutation of D364 abolishes the effect. This function of PPKL1 is independent of the phosphatase domain that is required for brassinosteroid signaling. Importantly, editing of the D364-residential region produces a diversity of semi-dominant mutations associated with variously increased grain sizes. Further screening of the edited plants enables the identification of two genotypes that confer significantly improved grain yield. Collectively, our study uncovers a noncanonical cytokinin signaling suppressor and provides a robust tool for seed rational design.

Integrated omics networks reveal the temporal signaling events of brassinosteroid response in Arabidopsis.

Brassinosteroids (BRs) are plant steroid hormones that regulate cell division and stress response. Here we use a systems biology approach to integrate multi-omic datasets and unravel the molecular signaling events of BR response in Arabidopsis. We profile the levels of 26,669 transcripts, 9,533 protein groups, and 26,617 phosphorylation sites from Arabidopsis seedlings treated with brassinolide (BL) for six different lengths of time. We then construct a network inference pipeline called Spatiotemporal Clustering and Inference of Omics Networks (SC-ION) to integrate these data. We use our network predictions to identify putative phosphorylation sites on BES1 and experimentally validate their importance. Additionally, we identify BRONTOSAURUS (BRON) as a transcription factor that regulates cell division, and we show that BRON expression is modulated by BR-responsive kinases and transcription factors. This work demonstrates the power of integrative network analysis applied to multi-omic data and provides fundamental insights into the molecular signaling events occurring during BR response.

SlBES1 promotes tomato fruit softening through transcriptional inhibition of PMEU1.

Fruit softening indicated by firmness determines the texture, transportability, and shelf life of tomato products. However, the regulatory mechanism underlying firmness formation in tomato fruit is poorly understood. Here, we report the regulatory role of SlBES1, an essential component of brassinosteroid hormone signaling, in tomato fruit softening. We found that SlBES1 promotes fruit softening during tomato fruit ripening and postharvest storage. RNA-seq analysis suggested that PMEU1, which encodes a pectin methylesterase, might participate in SlBES1-mediated softening. Biochemical and immunofluorescence assays indicated that SlBES1 inhibited PMEU1-related pectin de-methylesterification. Further molecular and genetic evidence verified that SlBES1 directly binds to the E-box of PMEU1 to repress its expression, leading to fruits softening. Loss-of-function SlBES1 mutant generated by CRISPR-Cas9 showed firmer fruits and longer shelf life during postharvest storage without other quality alteration. Collectively, our results indicated the potential of manipulating SlBES1 to regulate firmness without negative consequence on visual and nutrition quality.

The F-box E3 ubiquitin ligase BAF1 mediates the degradation of the brassinosteroid-activated transcription factor BES1 through selective autophagy in Arabidopsis.

Brassinosteroids (BRs) regulate plant growth, development, and stress responses by activating the core transcription factor BRI1-EMS-SUPPRESSOR1 (BES1), whose degradation occurs through the proteasome and autophagy pathways. The E3 ubiquitin ligase(s) that modify BES1 for autophagy-mediated degradation remain to be fully defined. Here, we identified an F-box family E3 ubiquitin ligase named BES1-ASSOCIATED F-BOX1 (BAF1) in Arabidopsis thaliana. BAF1 interacts with BES1 and mediates its ubiquitination and degradation. Our genetic data demonstrated that BAF1 inhibits BR signaling in a BES1-dependent manner. Moreover, BAF1 targets BES1 for autophagic degradation in a selective manner. BAF1-triggered selective autophagy of BES1 depends on the ubiquitin binding receptor DOMINANT SUPPRESSOR OF KAR2 (DSK2). Sucrose starvation-induced selective autophagy of BES1, but not bulk autophagy, was significantly compromised in baf1 mutant and BAF1-ΔF (BAF1 F-box decoy) overexpression plants, but clearly increased by BAF1 overexpression. The baf1 and BAF1-ΔF overexpression plants had increased BR-regulated growth but were sensitive to long-term sucrose starvation, while BAF1 overexpression plants had decreased BR-regulated growth but were highly tolerant of sucrose starvation. Our results not only established BAF1 as an E3 ubiquitin ligase that targets BES1 for degradation through selective autophagy pathway, but also revealed a mechanism for plants to reduce growth during sucrose starvation.

Robotic Assay for Drought (RoAD): an automated phenotyping system for brassinosteroid and drought responses.

Brassinosteroids (BRs) are a group of plant steroid hormones involved in regulating growth, development, and stress responses. Many components of the BR pathway have previously been identified and characterized. However, BR phenotyping experiments are typically performed in a low-throughput manner, such as on Petri plates. Additionally, the BR pathway affects drought responses, but drought experiments are time consuming and difficult to control. To mitigate these issues and increase throughput, we developed the Robotic Assay for Drought (RoAD) system to perform BR and drought response experiments in soil-grown Arabidopsis plants. RoAD is equipped with a robotic arm, a rover, a bench scale, a precisely controlled watering system, an RGB camera, and a laser profilometer. It performs daily weighing, watering, and imaging tasks and is capable of administering BR response assays by watering plants with Propiconazole (PCZ), a BR biosynthesis inhibitor. We developed image processing algorithms for both plant segmentation and phenotypic trait extraction to accurately measure traits including plant area, plant volume, leaf length, and leaf width. We then applied machine learning algorithms that utilize the extracted phenotypic parameters to identify image-derived traits that can distinguish control, drought-treated, and PCZ-treated plants. We carried out PCZ and drought experiments on a set of BR mutants and Arabidopsis accessions with altered BR responses. Finally, we extended the RoAD assays to perform BR response assays using PCZ in Zea mays (maize) plants. This study establishes an automated and non-invasive robotic imaging system as a tool to accurately measure morphological and growth-related traits of Arabidopsis and maize plants in 3D, providing insights into the BR-mediated control of plant growth and stress responses.

The Association Between Lung Fluorodeoxyglucose Metabolism and Smoking History in 347 Healthy Adults.

OBJECTIVE: This study aimed to evaluate the relationship between fluorodeoxyglucose metabolism and smoking history in healthy adults by analyzing lung standardized uptake value (SUV). METHODS: The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) studies of 347 patients who did not show signs of having malignant diseases or lung inflammation were retrospectively evaluated. Four circular regions of interest (ROI) were manually drawn on the upper and lower lung regions. The averages of maximum SUV (SUVmax-avr) and mean SUV (SUVmean-avr) were calculated, and the mean values of each parameter for non-smokers, ex-smokers, and current smokers were compared. The correlation between SUVmax-avr and smoking history (tobacco burden and the duration of smoking cessation) was assessed based on present smoking status. The ex-smokers and current smokers were divided into three groups according to their tobacco burden, and the SUVmax-avrs of the two groups were compared. RESULTS: Both the mean values of SUVmax-avr and SUVmean-avr increased based on smoking history, with non-smokers having the lowest values and current smokers the highest. Tobacco burden had a positive correlation with SUVmax-avr in current smokers (r = 0.474, P< 0.001). However, neither tobacco burden (r = 0171, P = 0.162) nor duration of smoking cessation (r = 0.212, P = 0.082) had a significant correlation with SUVmax-avr in ex-smokers. The mean SUVmax-avr of current smokers was significantly higher than that of ex-smokers in patients with a medium or large tobacco burden (P = 0.012, P< 0.001, respectively). Although there was no significant difference between the mean SUVmax-avrs of ex-smokers and current smokers in patients with a small tobacco burden (P = 0.888), the mean SUVmax-avrs of both ex-smokers and current smokers with a small tobacco burden were significantly higher than that of non-smokers (P< 0. 001, P< 0.001, respectively). CONCLUSION: The findings indicate that lung SUV increases in current heavy smokers and partially decreases after the cessation of smoking, which is in line with previous reports studied by analyzingfluorodeoxyglucose (FDG) metabolism of lung specimens.

Effects of in IL-1B/IL-1RN variants on the susceptibility to head and neck cancer in a chinese Han population.

BACKGROUND: The study aimed to evaluate the relationship of IL-1B/IL-1RN polymorphisms to the predisposition of head and neck cancer (HNC) in a Chinese Han population. METHODS: Nine single-nucleotide polymorphisms (SNPs) in IL-1B/IL-1RN were genotyped based on Agena MassARRAY platform. Logistic regression models were used to analyze the genetic association between these SNPs and HNC risk by calculating odds ratios (ORs) and 95% confidence intervals (CI). Haplotype analysis were performed using Haploview program and logistic regression model. RESULTS: The genetic association between rs1143643 in IL-1B and the higher risk of HNC was found (OR = 1.23, 95% CI 1.04-1.46) in the overall. IL-1RN rs17042888 was related to a reduced risk of HNC in the subjects aged > 46 years (OR = 0.70, 95% CI: 0.50-0.98) and in females (OR = 0.71, 95% CI 0.52-0.98), while rs1143643 increased the predisposition of HNC among females (OR = 1.76, 95% CI 1.13-2.74). Furthermore, rs1143643 had an increased susceptibility to thyroid carcinoma (OR = 1.61, 95% CI 1.10-2.34). Moreover, compared with stage I-II, the frequency of IL-1RN rs452204-AG genotype was lower in patients with stage III-IV. CONCLUSIONS: IL-1B (rs1143643) and IL-1RN (rs17042888 and rs452204) polymorphisms might be related to the individual susceptibility of HNC in the Chinese Han population. These results might help to improve the understanding of IL-1B and IL-1RN genes in the occurrence of HNC.

A BIN2-GLK1 Signaling Module Integrates Brassinosteroid and Light Signaling to Repress Chloroplast Development in the Dark.

Arabidopsis GLYCOGEN SYNTHASE KINASE 3 (GSK3)-like kinases play various roles in plant development, including chloroplast development, but the underlying molecular mechanism is not well defined. Here, we demonstrate that transcription factors GLK1 and GLK2 interact with and are phosphorylated by the BRASSINOSTEROID insensitive2 (BIN2). The loss-of-function mutant of BIN2 and its homologs, bin2-3 bil1 bil2, displays abnormal chloroplast development, whereas the gain-of-function mutant, bin2-1, exhibits insensitivity to BR-induced de-greening and reduced numbers of thylakoids per granum, suggesting that BIN2 positively regulates chloroplast development. Furthermore, BIN2 phosphorylates GLK1 at T175, T238, T248, and T256, and mutations of these phosphorylation sites alter GLK1 protein stability and DNA binding and impair plant responses to BRs/darkness. On the other hand, BRs and darkness repress the BIN2-GLK module to enhance BR/dark-mediated de-greening and impair the formation of the photosynthetic apparatus. Our results thus provide a mechanism by which BRs modulate photomorphogenesis and chloroplast development.