Coordinated control for the auricle asymmetric development by ZmIDD14 and ZmIDD15 fine-tune the high-density planting adaption in maize.

Multiple distinct specialized regions shape the architecture of maize leaves. Among them, the fringe-like and wedge-shaped auricles alter the angle between the leaf and stalk, which is a key trait in crop plant architecture. As planting density increased, a small leaf angle (LA) was typically selected to promote crop light capture efficiency and yield. In the present study, we characterized two paralogous INDETERMINATE DOMAIN (IDD) genes, ZmIDD14 and ZmIDD15, which contain the Cys2-His2 zinc finger domain and function redundantly to regulate auricle development and LA in maize. Loss-of-function mutants showed decreased LA by reducing adaxial sclerenchyma thickness and increasing the colourless cell layers. In addition, the idd14;idd15 double mutant exhibited asymmetrically smaller auricles, which might cause by a failed maintenance of symmetric expression of the key auricle size controlling gene, LIGULELESS(LG1). The transcripts of ZmIDD14 and ZmIDD15 enriched in the ligular region, where LG1 was highly expressed, and both proteins physically interacted with ZmILI1 to promote LG1 transcription. Notably, the idd14;idd15 enhanced the grain yield of hybrids under high planting densities by shaping the plant architecture with a smaller LA. These findings demonstrate the functions of ZmIDD14 and ZmIDD15 in controlling the abaxial/adaxial development of sclerenchyma in the midrib and polar development along the medial-lateral axes of auricles and provide an available tool for high-density and high-yield breeding in maize.

KRN5b regulates maize kernel row number through mediating phosphoinositol signalling.

Kernel row number (KRN) is a major yield related trait for maize (Zea mays L.) and is also a major goal of breeders, as it can increase the number of kernels per plant. Thus, identifying new genetic factors involving in KRN formation may accelerate improving yield-related traits genetically. We herein describe a new kernel number-related gene (KRN5b) identified from KRN QTL qKRN5b and encoding an inositol polyphosphate 5-phosphatase (5PTase). KRN5b has phosphatase activity towards PI(4,5)P2, PI(3,4,5)P3, and Ins(1,4,5)P3 in vitro. Knocking out KRN5b caused accumulation of PI(4,5)P2 and Ins(1,4,5)P3, resulting in disordered kernel rows and a decrease in the number of kernels and tassel branches. The introgression of the allele with higher expression abundance into different inbred lines could increase the ear weight of the inbred lines and the corresponding hybrids by 10.1%-12.2% via increasing KRN, with no adverse effects on other agronomic traits. Further analyses showed that KRN5b regulates inflorescence development through affecting the synthesis and distribution of hormones. Together, KRN5b contributes to spikelet pair meristem development through inositol phosphate and phosphatidylinositols, making it a selecting target for yield improvement.

The effect of increasing the gaps between the front teeth on torque and intrusion control of the incisors for anterior retraction with clear aligners: a prospective study.

OBJECTIVE: To investigate the effect of sequential distalization on increasing gaps in the maxillary anterior teeth, focusing on the control of torque and three-dimensional teeth movement during anterior retraction with clear aligners in extraction cases. METHODS: We recruited 24 patients who were undergoing extraction bilateral maxillary first premolars with clear aligners. According to a predetermined increment in the spaces between the maxillary anterior teeth, the patients were divided into three groups: those with no gap (9 cases), a 0.5 mm gap (6 cases) and a 1.0 mm gap (9 cases). In each group, a 2.0 mm en-mass retraction was applied on the anterior teeth. Plaster casts of the upper full dentition were obtained both before and after a 2 mm retraction. The palatal folds were used to overlap each pair of models. The three-dimensional movement of the teeth and the change of torque for the anterior teeth were subsequently analyzed using Geomagic Studio 2014 software. RESULTS: The change in torque in the groups with added gaps was significantly smaller than that in the group with no gaps (P < 0.05). There was no significant difference in this respect when comparing the group with a 0.5 mm gap added to the group with a 1.0 mm gap was added (P > 0.05). In the labial-lingual and vertical directions, the displacements of the central and lateral incisors were smaller in the groups with additional gaps compared to those in the groups without gaps (P < 0.05). However, there was no significant difference observed when comparing the group with a 0.5 mm added gap to the group with a 1.0 mm added gap (P > 0.05). Then, a comparison was made between the displacement of the second premolar to the second molar in the mesial-distal direction across all groups. The study revealed that the anchorage molars in the group without gaps demonstrated significantly smaller displacement compared to those in the group with additional gaps (P < 0.05). CONCLUSION: Advantages were observed in controlling the torque of the anterior teeth and achieving a desired pattern closer to normal bodily movement by sequentially distalizing the maxillary anterior teeth gaps. Increasing the gaps between the maxillary anterior teeth also resulted in improved control of the vertical direction of the anterior teeth. However, this retraction strategy necessitates substantial protection of the anchorage molars.

ZmBET5L1 inhibits primary root growth and decreases osmotic stress tolerance by mediating vesicle aggregation and tethering in maize.

Improving osmotic stress tolerance is critical to help crops to thrive and maintain high yields in adverse environments. Here, we characterized a core subunit of the transport protein particle (TRAPP) complex, ZmBET5L1, in maize using knowledge-driven data mining and genome editing. We found that ZmBET5L1 can interact with TRAPP I complex subunits and act as a tethering factor to mediate vesicle aggregation and targeting from the endoplasmic reticulum to the Golgi apparatus. ZmBET5L1 knock-out increased the primary root elongation rate under 20% polyethylene glycol-simulated osmotic stress and the survival rate under drought stress compared to wild-type seedlings. In addition, we found that ZmBET5L1 moderates PIN1 polar localization and auxin flow to maintain normal root growth. ZmBET5L1 knock-out optimized auxin flow to the lateral side of the root and promoted its growth to generate a robust root, which may be related to improved osmotic stress tolerance. Together, these findings demonstrate that ZmBET5L1 inhibits primary root growth and decreases osmotic stress tolerance by regulating vesicle transport and auxin distribution. This study has improved our understanding of the role of tethering factors in response to abiotic stresses and identified desirable variants for breeding osmotic stress tolerance in maize.

Identifying risk factors for chronic kidney disease stage 3 in adults with acquired solitary kidney from unilateral nephrectomy: a retrospective cohort study.

BACKGROUND: We aimed to examine the risk factors for chronic kidney disease (CKD) stage 3 among adults with ASK from unilateral nephrectomy. METHODS: We retrospectively collected data from adult patients with ASK between January, 2009 and January, 2019, identified from a tertiary hospital in China. The clinical data were compared between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up. RESULTS: In total, 172 patients with ASK (110 men; median 58.0 years) were enrolled, with a median follow-up duration of 5.0 years. During follow-up, 91 (52.9%) and 24 (14.0%) patients developed CKD stage 3 and end-stage renal disease, respectively. Multiple regression analyses showed that age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.039-1.115, p < 0.001), diabetes (OR 4.401, 95% CI 1.693-11.44, p = 0.002), hyperuricemia (OR 2.733, 95% CI 1.104-6.764, p = 0.03), a history of cardiovascular disease (CVD) (OR 5.583, 95% CI 1.884-18.068, p = 0.002), and ASK due to renal tuberculosis (OR 8.816, 95% CI 2.92-26.62, p < 0.001) were independent risk factors for developing CKD stage 3 among patients with ASK. CONCLUSIONS: Regular follow-up of renal function is needed among adult patients with ASK. Optimal management of diabetes, hyperuricemia, and CVD may reduce their risk of CKD stage 3, especially among those that undergo unilateral nephrectomy for renal tuberculosis.

High-resolution 1 H-MRSI of the brain using short-TE SPICE.

PURPOSE: To improve signal-to-noise ratio (SNR) for high-resolution spectroscopic imaging using a subspace-based technique known as SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE). METHODS: The proposed method is based on a union-of-subspaces model of MRSI signals, which exploits the partial separability properties of water, lipid, baseline and metabolite signals. Enabled by this model, a special scheme is used for accelerated data acquisition, which includes a double-echo CSI component used to collect a "training" dataset (for determination of the basis functions) and a short-TE EPSI component used to collect a sparse "imaging" dataset (for determination of the overall spatiospectral distributions). A set of signal processing algorithms are developed to remove the water and lipid signals and jointly reconstruct the metabolite and baseline signals. RESULTS: In vivo 1 H-MRSI results show that the proposed method can effectively remove the remaining water and lipid signals from sparse MRSI data acquired at 20 ms TE. Spatiospectral distributions of metabolite signals at 2 mm in-plane resolution with good SNR were obtained in a 15.5 min scan. CONCLUSIONS: The proposed method can effectively remove nuisance signals and reconstruct high-resolution spatiospectral functions from sparse data to make short-TE SPICE possible. The method should prove useful for high-resolution 1 H-MRSI of the brain. Magn Reson Med 77:467-479, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

De novo genome assembly and analyses of 12 founder inbred lines provide insights into maize heterosis.

Hybrid maize displays superior heterosis and contributes over 30% of total worldwide cereal production. However, the molecular mechanisms of heterosis remain obscure. Here we show that structural variants (SVs) between the parental lines have a predominant role underpinning maize heterosis. De novo assembly and analyses of 12 maize founder inbred lines (FILs) reveal abundant genetic variations among these FILs and, through expression quantitative trait loci and association analyses, we identify several SVs contributing to genomic and phenotypic differentiations of various heterotic groups. Using a set of 91 diallel-cross F1 hybrids, we found strong positive correlations between better-parent heterosis of the F1 hybrids and the numbers of SVs between the parental lines, providing concrete genomic support for a prevalent role of genetic complementation underlying heterosis. Further, we document evidence that SVs in both ZAR1 and ZmACO2 contribute to yield heterosis in an overdominance fashion. Our results should promote genomics-based breeding of hybrid maize.

A NAC-EXPANSIN module enhances maize kernel size by controlling nucellus elimination.

Maize early endosperm development is initiated in coordination with elimination of maternal nucellar tissues. However, the underlying mechanisms are largely unknown. Here, we characterize a major quantitative trait locus for maize kernel size and weight that encodes an EXPANSIN gene, ZmEXPB15. The encoded ß-expansin protein is expressed specifically in nucellus, and positively controls kernel size and weight by promoting nucellus elimination. We further show that two nucellus-enriched transcription factors (TFs), ZmNAC11 and ZmNAC29, activate ZmEXPB15 expression. Accordingly, these two TFs also promote kernel size and weight through nucellus elimination regulation, and genetic analyses support their interaction with ZmEXPB15. Importantly, hybrids derived from a ZmEXPB15 overexpression line have increased kernel weight, demonstrates its potential value in breeding. Together, we reveal a pathway modulating the cellular processes of maternal nucellus elimination and early endosperm development, and an approach to improve kernel weight.

The Coordinated KNR6-AGAP-ARF1 Complex Modulates Vegetative and Reproductive Traits by Participating in Vesicle Trafficking in Maize.

The KERNEL NUMBER PER ROW6 (KNR6)-mediated phosphorylation of an adenosine diphosphate ribosylation factor (Arf) GTPase-activating protein (AGAP) forms a key regulatory module for the numbers of spikelets and kernels in the ear inflorescences of maize (Zea mays L.). However, the action mechanism of the KNR6-AGAP module remains poorly understood. Here, we characterized the AGAP-recruited complex and its roles in maize cellular physiology and agronomically important traits. AGAP and its two interacting Arf GTPase1 (ARF1) members preferentially localized to the Golgi apparatus. The loss-of-function AGAP mutant produced by CRISPR/Cas9 resulted in defective Golgi apparatus with thin and compact cisternae, together with delayed internalization and repressed vesicle agglomeration, leading to defective inflorescences and roots, and dwarfed plants with small leaves. The weak agap mutant was phenotypically similar to knr6, showing short ears with fewer kernels. AGAP interacted with KNR6, and a double mutant produced shorter inflorescence meristems and mature ears than the single agap and knr6 mutants. We hypothesized that the coordinated KNR6-AGAP-ARF1 complex modulates vegetative and reproductive traits by participating in vesicle trafficking in maize. Our findings provide a novel mechanistic insight into the regulation of inflorescence development, and ear length and kernel number, in maize.

An ethylene biosynthesis enzyme controls quantitative variation in maize ear length and kernel yield.

Maize ear size and kernel number differ among lines, however, little is known about the molecular basis of ear length and its impact on kernel number. Here, we characterize a quantitative trait locus, qEL7, to identify a maize gene controlling ear length, flower number and fertility. qEL7 encodes 1-aminocyclopropane-1- carboxylate oxidase2 (ACO2), a gene that functions in the final step of ethylene biosynthesis and is expressed in specific domains in developing inflorescences. Confirmation of qEL7 by gene editing of ZmACO2 leads to a reduction in ethylene production in developing ears, and promotes meristem and flower development, resulting in a ~13.4% increase in grain yield per ear in hybrids lines. Our findings suggest that ethylene serves as a key signal in inflorescence development, affecting spikelet number, floral fertility, ear length and kernel number, and also provide a tool to improve grain productivity by optimizing ethylene levels in maize or in other cereals.

Calcineurin promotes proliferation, migration, and invasion of small cell lung cancer.

A novel role for calcineurin (Cn) has been reported recently regarding the oncogenic potential in pancreatic and colorectal cancer. The aim of this study was to investigate the putative causal role calcineurin could play in the development of lung cancer with bone metastases. We found that CnAalpha, an isoform of calcineurin, was significantly overexpressed in lung cancer tissues with bone metastasis as compared to tumors with non-bone metastases as investigated by RT-PCR. Strong nuclear staining of tumor cells was observed in small cell lung cancer tissues with bone metastasis. Conversely, cytoplasmic staining of tumor cells was observed in small cell lung cancer tissues with non-bone metastasis. Western blots of nuclear proteins from lung cancer tissues indicated that CnAalpha was highly expressed in lung cancer tissues with bone metastases, but not in those with non-bone metastases. In vitro, it was demonstrated that the CnAalpha gene obviously promoted cell proliferation and inhibited cell apotosis. The CnAalpha gene affected the cell cycle and promoted G1[Symbol: see text]S transition in SBC-3 cells. Transfection with the CnAalpha gene promoted cell migration and invasion. These results indicated that CnAalpha may affect the biological behavior of the human small cell lung cancer cell line SBC-3 in vitro and may be a candidate tumor promotor gene for developing bone metastases.

Modeling Hierarchical Brain Networks via Volumetric Sparse Deep Belief Network.

It has been recently shown that deep learning models such as convolutional neural networks (CNN), deep belief networks (DBN) and recurrent neural networks (RNN), exhibited remarkable ability in modeling and representing fMRI data for the understanding of functional activities and networks because of their superior data representation capability and wide availability of effective deep learning tools. For example, spatial and/or temporal patterns of functional brain activities embedded in fMRI data can be effectively characterized and modeled by a variety of CNN/DBN/RNN deep learning models as shown in recent studies. However, it has been rarely investigated whether it is possible to directly infer hierarchical brain networks from volumetric fMRI data using deep learning models such as DBN. The perceived difficulties of such studies include very large number of input variables, very large number of training parameters, the lack of effective software tools, the challenge of results interpretation, and etc. To bridge these technical gaps, we designed a novel volumetric sparse deep belief network (VS-DBN) model and implemented it through the popular TensorFlow open source platform to reconstruct hierarchical brain networks from volumetric fMRI data based on the Human Connectome Project (HCP) 900 subjects release. Our experimental results showed that a large number of interpretable and meaningful brain networks can be robustly reconstructed from HCP 900 subjects in a hierarchical fashion, and importantly, these brain networks exhibit reasonably good consistency and correspondence across multiple HCP task-based fMRI datasets. Our work contributed a new general deep learning framework for inferring multiscale volumetric brain networks and offered novel insights into the hierarchical organization of functional brain architecture.

A serine/threonine protein kinase encoding gene KERNEL NUMBER PER ROW6 regulates maize grain yield.

Increasing grain yield of maize (Zea mays L.) is required to meet the rapidly expanding demands for maize-derived food, feed, and fuel. Breeders have enhanced grain productivity of maize hybrids by pyramiding desirable characteristics for larger ears. However, loci selected for improving grain productivity remain largely unclear. Here, we show that a serine/threonine protein kinase encoding gene KERNEL NUMBER PER ROW6 (KNR6) determines pistillate floret number and ear length. Overexpression of KNR6 or introgression of alleles lacking the insertions of two transposable elements in the regulatory region of KNR6 can significantly enhance grain yield. Further in vitro evidences indicate that KNR6 can interact with an Arf GTPase-activating protein (AGAP) and its phosphorylation by KNR6 may affect ear length and kernel number. This finding provides knowledge basis to enhance maize hybrids grain yield.

Regulation of miR-155 affects the invasion and migration of gastric carcinoma cells by modulating the STAT3 signaling pathway.

Studies investigating the effects of microRNA (miR)-155 on the behavior of tumor cells have concentrated primarily on proliferation and apoptosis. The aim of the present study was to investigate the effect of miR-155 inhibitor on the metastatic and invasive ability of gastric carcinoma cells and whether this effect is mediated via the signal transduction and activators of transcription 3 (STAT3) signaling pathway. The miR-155 inhibitor and miR-155 negative control (NC) were transfected into the AGs and MKN-45 cell lines. The migratory and invasive abilities of the cells were analyzed. The level of phosphorylated (p-)STAT3 and the expression levels of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF) and suppressor of cytokine signaling 1 (SOCS1) were also detected. For the AGS cell line, the cell counts (mean ± standard deviation) for the Transwell migration assay were 98.99±9.13 in the miR-155 NC group and 45.32±4.32 in the miR-155 inhibitor group (P<0.01). For the MKN-45 cell line, the cell counts for the migration assay were 129.99±10.12 and 50.36±5.2 in the miR-155 NC and miR-155 inhibitor groups, respectively (P<0.01). The cell counts of the AGS cell line for the invasion assay were 70.25±7.94 in the miR-155 NC group and 40.68±4.73 in the miR-155 inhibitor group (P<0.05). For the MKN-45 cell line, the cell counts for the invasion assay were 84.63±8.12 and 40.35±4.29 in the miR-155 NC and miR-155 inhibitor groups, respectively (P<0.05). Transfection with the miR-155 inhibitor was able to significantly decrease the level of p-STAT3 in the AGS and MKN-45 cell lines compared with the negative control group (all P<0.05). The levels of MMP2 and MMP9 expression were decreased following transfection with miR-155 in AGS and MKN-45 cells (both P<0.05). Notably, transfection with the miR-155 inhibitor was able to decrease the level of VEGF expression, whilst increasing the SOCS1 expression level compared with the negative control group (both P<0.05). Additionally, the downregulation of miR-155 expression in gastric carcinoma cell lines was able to significantly decrease the expression of VEGF, MMP2 and MMP9, thereby inhibiting the invasion and metastasis of gastric carcinoma cells.

Spectral Quantification for High-Resolution MR Spectroscopic Imaging With Spatiospectral Constraints.

OBJECTIVE: To obtain reliable spectral estimation from magnetic resonance spectroscopic imaging (MRSI) data. METHODS: The proposed method takes advantage of prior knowledge: 1) along the spectral dimension in the form of spectral bases, and 2) along the spatial dimensions in the form of spatial regularizations (e.g., smoothness or transform sparsity) and jointly estimates parameters from all the voxels. RESULTS: Simulation and in vivo studies have been performed to demonstrate the performance of the proposed method. A Cramér-Rao-bound-based analysis is also provided. CONCLUSION: Incorporation of both spatial and spectral constraints can significantly improve spectral quantification of MRSI data. SIGNIFICANCE: The proposed method is expected to be useful for various quantitative MRSI studies.

QTL Mapping of Kernel Number-Related Traits and Validation of One Major QTL for Ear Length in Maize.

The kernel number is a grain yield component and an important maize breeding goal. Ear length, kernel number per row and ear row number are highly correlated with the kernel number per ear, which eventually determines the ear weight and grain yield. In this study, two sets of F2:3 families developed from two bi-parental crosses sharing one inbred line were used to identify quantitative trait loci (QTL) for four kernel number-related traits: ear length, kernel number per row, ear row number and ear weight. A total of 39 QTLs for the four traits were identified in the two populations. The phenotypic variance explained by a single QTL ranged from 0.4% to 29.5%. Additionally, 14 overlapping QTLs formed 5 QTL clusters on chromosomes 1, 4, 5, 7, and 10. Intriguingly, six QTLs for ear length and kernel number per row overlapped in a region on chromosome 1. This region was designated qEL1.10 and was validated as being simultaneously responsible for ear length, kernel number per row and ear weight in a near isogenic line-derived population, suggesting that qEL1.10 was a pleiotropic QTL with large effects. Furthermore, the performance of hybrids generated by crossing 6 elite inbred lines with two near isogenic lines at qEL1.10 showed the breeding value of qEL1.10 for the improvement of the kernel number and grain yield of maize hybrids. This study provides a basis for further fine mapping, molecular marker-aided breeding and functional studies of kernel number-related traits in maize.

Multi-stable fluorescent silica nanoparticles obtained from in situ doping with aggregation-induced emission molecules.

Microenvironment in biology is diverse and complex which has been a great challenge for in vivo imaging materials, and so materials with environmental tolerance and photostability need to be explored. For aggregation-induced emission (AIE) molecules, the fluorescence is closely related to the restricted structure which is directly affected by the microenvironment. Inorganic silica nanoparticles can provide a rigid microenvironment which can stabilize AIE molecules to obtain fluorescent materials with environmental tolerance. Here, stable fluorescent SiO2 nanoparticles (CWQ-11@SiO2 NPs) have been prepared by doping with typical AIE molecules named CWQ-11. CWQ-11@SiO2 NPs have narrow size distribution and spherical morphology with a size of around 50 nm. The fluorescence intensity of CWQ-11@SiO2 NPs is nearly 45.4 times higher than that of free CWQ-11. CWQ-11@SiO2 NPs maintain excellent fluorescence stabilities under various conditions, such as in solutions with different pH values, different viscosities, or continuous irradiation, and even in simulated gastric fluid (SGF). Cellular imaging research represents efficient imaging ability of CWQ-11@SiO2 NPs in two different tumor cells including MCF-7S and HepG-2. All these results demonstrate that the CWQ-11@SiO2 NPs have been successfully prepared and remain stable under different harsh conditions, and have promising potential in imaging, tracing for drugs or diagnosis in complicated biological systems.