The H3K4 demethylase JMJ1 is required for proper timing of flowering in Brachypodium distachyon.

Flowering is a key developmental transition in the plant life cycle. In temperate climates, flowering often occurs in response to the perception of seasonal cues such as changes in day-length and temperature. However, the mechanisms that have evolved to control the timing of flowering in temperate grasses are not fully understood. We identified a Brachypodium distachyon mutant whose flowering is delayed under inductive long-day conditions due to a mutation in the JMJ1 gene, which encodes a Jumonji domain-containing protein. JMJ1 is a histone demethylase that mainly demethylates H3K4me2 and H3K4me3 in vitro and in vivo. Analysis of the genome-wide distribution of H3K4me1, H3K4me2, and H3K4me3 in wild-type plants by chromatin immunoprecipitation and sequencing combined with RNA sequencing revealed that H3K4m1 and H3K4me3 are positively associated with gene transcript levels, whereas H3K4me2 is negatively correlated with transcript levels. Furthermore, JMJ1 directly binds to the chromatin of the flowering regulator genes VRN1 and ID1 and affects their transcription by modifying their H3K4me2 and H3K4me3 levels. Genetic analyses indicated that JMJ1 promotes flowering by activating VRN1 expression. Our study reveals a role for JMJ1-mediated chromatin modification in the proper timing of flowering in B. distachyon.

Dominance complementation of parental heading date alleles of Hd1, Ghd7, DTH8, and PRR37 confers transgressive late maturation in hybrid rice.

Rice (Oryza sativa L.) is a short-day plant whose heading date is largely determined by photoperiod sensitivity (PS). Many parental lines used in hybrid rice breeding have weak PS, but their F1 progenies have strong PS and exhibit an undesirable transgressive late-maturing phenotype. However, the genetic basis for this phenomenon is unclear. Therefore, effective methods are needed for selecting parents to create F1 hybrid varieties with the desired PS. In this study, we used bulked segregant analysis with F1 Ningyou 1179 (strong PS) and its F2 population, and through analyzing both parental haplotypes and PS data for 918 hybrid rice varieties, to identify the genetic basis of transgressive late maturation which is dependent on dominance complementation effects of Hd1, Ghd7, DTH8, and PRR37 from both parents rather than from a single parental genotype. We designed a molecular marker-assisted selection system to identify the genotypes of Hd1, Ghd7, DTH8, and PRR37 in parental lines to predict PS in F1 plants prior to crossing. Furthermore, we used CRISPR/Cas9 technique to knock out Hd1 in Ning A (sterile line) and Ning B (maintainer line) and obtained an hd1-NY material with weak PS while retaining the elite agronomic traits of NY. Our findings clarified the genetic basis of transgressive late maturation in hybrid rice and developed effective methods for parental selection and gene editing to facilitate the breeding of hybrid varieties with the desired PS for improving their adaptability.

Effects of the core heading date genes Hd1, Ghd7, DTH8, and PRR37 on yield-related traits in rice.

KEY MESSAGE: We clarify the influence of the genotypes of the heading date genes Hd1, Ghd7, DTH8, and PRR37 and their combinations on yield-related traits and the functional differences between different haplotypes. Heading date is a key agronomic trait in rice (Oryza sativa L.) that determines yield and adaptability to different latitudes. Heading date 1 (Hd1), Grain number, plant height, and heading date 7 (Ghd7), Days to heading on chromosome 8 (DTH8), and PSEUDO-RESPONSE REGULATOR 37 (PRR37) are core rice genes controlling photoperiod sensitivity, and these genes have many haplotypes in rice cultivars. However, the effects of different haplotypes at these genes on yield-related traits in diverse rice materials remain poorly characterized. In this study, we knocked out Hd1, Ghd7, DTH8, or PRR37, alone or together, in indica and japonica varieties and systematically investigated the agronomic traits of each knockout line. Ghd7 and PRR37 increased the number of spikelets and improved yield, and this effect was enhanced with the Ghd7 DTH8 or Ghd7 PRR37 combination, but Hd1 negatively affected yield. We also identified a new weak functional Ghd7 allele containing a mutation that interferes with splicing. Furthermore, we determined that the promotion or inhibition of heading date by different PRR37 haplotypes is related to PRR37 expression levels, day length, and the genetic background. For rice breeding, a combination of functional alleles of Ghd7 and DTH8 or Ghd7 and PRR37 in the hd1 background can be used to increase yield. Our study clarifies the effects of heading date genes on yield-related traits and the functional differences among their different haplotypes, providing valuable information to identify and exploit elite haplotypes for heading date genes to breed high-yielding rice varieties.

Strong photoperiod sensitivity is controlled by cooperation and competition among Hd1, Ghd7 and DTH8 in rice heading.

Rice (Oryza sativa) is a short-day (SD) plant originally having strong photoperiod sensitivity (PS), with SDs promoting and long days (LDs) suppressing flowering. Although the evolution of PS in rice has been extensively studied, there are few studies that combine the genetic effects and underlying mechanism of different PS gene combinations with variations in PS. We created a set of isogenic lines among the core PS-flowering genes Hd1, Ghd7 and DTH8 using CRISPR mutagenesis, to systematically dissect their genetic relationships under different day-lengths. We investigated their monogenic, digenic, and trigenic effects on target gene regulation and PS variation. We found that Hd1 and Ghd7 have the primary functions for promoting and repressing flowering, respectively, regardless of day-length. However, under LD conditions, Hd1 promotes Ghd7 expression and is recruited by Ghd7 and/or DTH8 to form repressive complexes that collaboratively suppress the Ehd1-Hd3a/RFT1 pathway to block heading, but under SD conditions Hd1 competes with the complexes to promote Hd3a/RFT1 expression, playing a tradeoff relationship with PS flowering. Natural allelic variations of Hd1, Ghd7 and DTH8 in rice populations have resulted in various PS performances. Our findings reveal that rice PS flowering is controlled by crosstalk of two modules - Hd1-Hd3a/RFT1 in SD conditions and (Hd1/Ghd7/DTH8)-Ehd1-Hd3a/RFT1 in LD conditions - and the divergences of these genes provide the basis for rice adaptation to broad regions.

Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway.

Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy. Here, we report that Thymopentin (TP5), a synthetic immunomodulator pentapeptide (Arg-Lys-Asp-Val-Tyr) with an excellent safety profile in the clinic, protects mice against cecal ligation and puncture (CLP)-induced sepsis, as shown by improved survival rate, decreased level of pro-inflammatory cytokines and reduced ratios of macrophages and neutrophils in spleen and peritoneum. Regarding mechanism, TP5 changed the characteristics of LPS-stimulated macrophages by increasing the production of 15-deoxy-Δ12,14 -prostaglandin J2 (15-d-PGJ2). In addition, the improved effect of TP5 on survival rates was abolished by the peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662. Our results uncover the mechanism of the TP5 protective effects on CLP-induced sepsis and shed light on the development of TP5 as a therapeutic strategy for lethal systemic inflammatory disorders.

Enhancement of the localization and quantitative performance of fluorescence molecular tomography by using linear nBorn method.

The nonlinear normalized Born ratio (nBorn) method normalizes emission data with excitation data nonlinearly, which makes the relative distributions of the normalized measurements different from those of the emission data. When compared with the reconstruction using only emission data, what the nonlinear nBorn method does is equivalent to introducing the noisy excitation data to emission data. In our linear nBorn method, the emission data for each projection is linearly normalized with the average excitation data of all detectors. Phantom and in vivo mice studies indicate that the linear nBorn method provides better localization and quantitative performance than the nonlinear nBorn method.

Sparsity-promoting Bayesian approximation error method for compensating for the mismodeling of optical properties in fluorescence molecular tomography.

In fluorescence molecular tomography, the quality of image reconstruction of fluorophore distribution is heavily reduced by the mismodeling of inaccurately known tissue optical properties. We propose an efficient sparsity-promoting Bayesian approximation error (spBAE) method to compensate for this mismodeling. The spBAE method incorporates sparsity prior into the BAE method by updating the parameters of the Gaussian prior according to its initial solution. In vivo experiments demonstrate that this new method greatly improves the reconstruction quality.

High-dynamic-range fluorescence molecular tomography for imaging of fluorescent targets with large concentration differences.

When CCD-based free-space fluorescence molecular tomography (FMT) is used for imaging of fluorescent targets with a large concentration difference, the limited dynamic range of the CCD diminishes the localization and quantitative accuracy of FMT. To overcome this, we present a high-dynamic-range FMT (HDR-FMT) method. Under the multiple-exposure scheme, HDR fluorescence projection images are constructed using the recovered CCD response curve. Image reconstruction is implemented using iterative reweighted L1 regularization which can reduce artifacts by using fewer HDR fluorescence projection images. Phantom and in vivo animal studies indicate that localization of fluorescent targets with a large concentration difference is effectively improved with HDR-FMT and with good quantitative accuracy.

Boundary Element Method for Reconstructing Absorption and Diffusion Coefficients of Biological Tissues in DOT/MicroCT Imaging.

The functional information, the absorption and diffusion coefficients, as well as the structural information of biological tissues can be provided by the DOT(Diffuse Optical Tomograph)/MicroCT. In this paper, we use boundary element method to calculate the forward problem of DOT based on the structure prior given by the MicroCT, and then we reconstruct the absorption and diffusion coefficients of different biological tissues by the Levenberg-Marquardt algorithm. The method only needs surface meshing, reducing the complexity of calculation; in addition, it reconstructs a single value within an organ, which reduces the ill-posedness of the inverse problem to make reconstruction results have good noise stability. This indicates that the boundary element method-based reconstruction can serve as an new scheme for getting absorption and diffusion coefficients in DOT/MicroCT multimodality imaging.

Accurate quantification of fluorescent targets within turbid media based on a decoupled fluorescence Monte Carlo model.

We propose a method based on a decoupled fluorescence Monte Carlo model for constructing fluorescence Jacobians to enable accurate quantification of fluorescence targets within turbid media. The effectiveness of the proposed method is validated using two cylindrical phantoms enclosing fluorescent targets within homogeneous and heterogeneous background media. The results demonstrate that our method can recover relative concentrations of the fluorescent targets with higher accuracy than the perturbation fluorescence Monte Carlo method. This suggests that our method is suitable for quantitative fluorescence diffuse optical tomography, especially for in vivo imaging of fluorophore targets for diagnosis of different diseases and abnormalities.

Reweighted L1 regularization for restraining artifacts in FMT reconstruction images with limited measurements.

In fluorescence molecular tomography (FMT), many artifacts exist in the reconstructed images because of the inherently ill-posed nature of the FMT inverse problem, especially with limited measurements. A new method based on iterative reweighted L1 (IRL1) regularization is proposed for reducing artifacts with limited measurements. Phantom experiments demonstrate that the reconstructed images have fewer artifacts even with very limited measurements. This indicates that FMT based on IRL1 can obtain high-quality images and thus has the potential to observe dynamic changes in fluorescence-targeted molecules.

TRIM27 Promotes Endothelial Progenitor Cell Apoptosis in Patients with In-Stent Restenosis by Ubiquitinating TBK1.

Approximately 2-10% in-stent restenosis (ISR) may occur following percutaneous coronary intervention (PCI) despite the use of modern drug-eluting stents (DES); thus, our study aimed to explore the effects of tripartite motif-containing (TRIM) 27 on ISR and the underlying mechanism. For this purpose, a total of 42 patients undergoing coronary angiography who had prior coronary angiography with DES implantation were recruited. Endothelial progenitor cells (EPCs) markers (defined as CD34 and vascular endothelial growth factoreceptor-2 (VEGFR-2)) in peripheral blood were measured to asses the circulating EPC level. The TRIM family-related gene expressions were detected by reverse transcription-quantitative polymerase chain reaction. Results suggested that ISR patients had reduced CD34+VEGFR-2+ and increased apoptosis rate of EPCs, along with upregulated TRIM27 and TRIM37 and downregulated TRIM28. TRIM27 promoted and TBK1 inhibited the apoptosis rate of EPCs. Mechanically, TRIM27 interacted with TBK1 to ubiquitinate TBK1 in in vitro study. In summary, TRIM27 promoted the progression of ISR in patients after PCI by ubiquitinating TBK1, which might provide novel ideas for the clinical treatment of ISR.

Unloading Model of Elastic-Plastic Half-Space Contacted by an Elastic Spherical Indenter.

A new unloading contact model of an elastic-perfectly plastic half-space indented by an elastic spherical indenter is presented analytically. The recovered deformation of the elastic indenter and the indented half-space has been found to be dependent on the elastic modulus ratio after fully unloading. The recovered deformation of the indented half-space can be calculated based on the deformation of the purely elastic indenter. The unloading process is assumed to be entirely elastic, and then the relationship of contact force and indentation can be determined based on the solved recovered deformation and conforms to Hertzian-type. The model can accurately predict the residual indentation and residual curvature radius after fully unloading. Numerical simulations are performed to demonstrate the assumptions and the unloading model. The proposed unloading model can cover a wide range of indentations and material properties and is compared with existing unloading models. The cyclic behavior including loading and unloading can be predicted by combining the proposed unloading law with the existing contact loading model. The combined model can be employed for low-velocity impact and nanoindentation tests and the comparison results are in good agreement.

Histone methylation readers MRG1/2 interact with PIF4 to promote thermomorphogenesis in Arabidopsis.

Warm ambient conditions induce thermomorphogenesis and affect plant growth and development. However, the chromatin regulatory mechanisms involved in thermomorphogenesis remain largely obscure. In this study, we show that the histone methylation readers MORF-related gene 1 and 2 (MRG1/2) are required to promote hypocotyl elongation in response to warm ambient conditions. A transcriptome sequencing analysis indicates that MRG1/2 and phytochrome interacting factor 4 (PIF4) coactivate a number of thermoresponsive genes, including YUCCA8, which encodes a rate-limiting enzyme in the auxin biosynthesis pathway. Additionally, MRG2 physically interacts with PIF4 to bind to thermoresponsive genes and enhances the H4K5 acetylation of the chromatin of target genes in a PIF4-dependent manner. Furthermore, MRG2 competes with phyB for binding to PIF4 and stabilizes PIF4 in planta. Our study indicates that MRG1/2 activate thermoresponsive genes by inducing histone acetylation and stabilizing PIF4 in Arabidopsis.

New Quasi-Solid-State Li-SPAN Battery Enhanced by In Situ Thermally Polymerized Gel Polymer Electrolytes.

A lithium-sulfur (Li-S) battery is a promising candidate for an electrochemical energy-storage system. However, for a long time, it suffered from the "shuttle effect" of the intermediate products of soluble polysulfides and safety issues concerning the combustible liquid electrolyte and lithium anode. In this work, sulfide polyacrylonitrile (SPAN) is employed as a solid cycled cathode to resolve the "shuttle effect" fundamentally, a gel polymer electrolyte (GPE) based on poly(ethylene glycol) diacrylate (PEGDA) is matched to the SPAN cathode to minimize the safety concerns, and finally, a quasi-solid-state Li-SPAN battery is combined by an in situ thermal polymerization strategy to improve its adaptability to the existing battery assembly processes. The PEGDA-based GPE achieved at 60 °C for 40 min ensures little damage to the in situ battery, a good electrode-electrolyte interface, a high ionic conductivity of 6.87 × 10-3 S cm-1 at 30 °C, and a wide electrochemical window of 4.53 V. Ultimately, the as-prepared SPAN composite exerts a specific capacity of 1217.3 mAh g-1 after 250 cycles at 0.2 C with a high capacity retention rate of 89.9%. The combination of the SPAN cathode and in situ thermally polymerized PEGDA-based GPE provides a new inspiration for the design of Li-SPAN batteries with both high specific energy and high safety.

Hydrophilic Modification of Dialysis Membranes Sustains Middle Molecule Removal and Filtration Characteristics.

While efficient removal of uremic toxins and accumulated water is pivotal for the well-being of dialysis patients, protein adsorption to the dialyzer membrane reduces the performance of a dialyzer. Hydrophilic membrane modification with polyvinylpyrrolidone (PVP) has been shown to reduce protein adsorption and to stabilize membrane permeability. In this study we compared middle molecule clearance and filtration performance of nine polysulfone-, polyethersulfone-, and cellulose-based dialyzers over time. Protein adsorption was simulated in recirculation experiments, while ß2-microglobulin clearance as well as transmembrane pressure (TMP) and filtrate flow were determined over time. The results of this study showed that ß2-microglobulin clearance (-7.2 mL/min/m2) and filtrate flow (-54.4 mL/min) decreased strongly during the first 30 min and slowly afterwards (-0.7 mL/min/m2 and -6.8 mL/min, respectively, for the next 30 min); the TMP increase (+37.2 mmHg and +8.6 mmHg, respectively) showed comparable kinetics. Across all tested dialyzers, the dialyzer with a hydrophilic modified membrane (FX CorAL) had the highest ß2-microglobulin clearance after protein fouling and the most stable filtration characteristics. In conclusion, hydrophilic membrane modification with PVP stabilizes the removal capacity of middle molecules and filtration performance over time. Such dialyzers may have benefits during hemodiafiltration treatments which aim to achieve high exchange volumes.

Prurigo nodularis and dialyzer membrane.

Prurigo nodularis is a skin disease with unknown origin which is frequent in patients on maintenance renal replacement therapy. Here, we report a patient who was dialyzed for more than 10 years with different dialyzers using different dialyzer membranes. Each time when the patient was switched to a polymethylmethacrylate membrane (Filtryzer BK-1.6P), itching and skin lesions disappeared completely. This effect could be verified three times.

Construction and validation of a prognostic model for predicting overall survival of primary adrenal malignant tumor patients: A population-based study with 1,080 patients.

Objective: Primary adrenal malignant tumor is rare. The factors affecting the prognosis remain poorly defined. This study targeted to construct and corroborate a model for predicting the overall survival of adrenal malignant tumor patients. Methods: We investigated the SEER database for patients with primary adrenal malignant tumor. 1,080 patients were divided into a construction cohort (n = 756) and a validation cohort (n = 324), randomly. The prognostic factors for overall survival were evaluated using univariate and multivariate Cox analyses. The nomogram was constructed and then validated with C-index, calibration curve, time-dependent ROC curve, and decision curve analysis in both cohorts. Then we divided the patients into 3 different risk groups according to the total points of the nomogram and analyzed their survival status by Kaplan-Meier curve with log-rank test. Results: The baseline characteristics of these two cohorts were not statistically different (P > 0.05). Using univariate and multivariate Cox analyses, 5 variables, including age, tumor size, histological type, tumor stage, and surgery of primary site, were distinguished as prognostic factors (P < 0.05). Based on these variables, we constructed a nomogram to predict the 3- year, 5- year, and 10-year overall survival. The C-indexes were 0.780 (0.760-0.800) in the construction cohort and 0.780 (0.751-0.809) in the validation cohort. In both cohorts, the AUC reached a fairly high level at all time points. The internal and external calibration curves and ROC analysis showed outstanding accuracy and discrimination. The decision curves indicated excellent clinical usefulness. The best cut-off values for the total points of the nomogram were 165.4 and 243.1, and the prognosis was significantly different for the three different risk groups (P < 0.001). Conclusion: We successfully constructed a model to predict the overall survival of primary adrenal malignant tumor patients. This model was validated to perform brilliantly internally and externally, which can assist us in individualized clinical management.

Study on Influencing Factors of Phase Transition Hysteresis in the Phase Change Energy Storage.

Phase change energy storage is a new type of energy storage technology that can improve energy utilization and achieve high efficiency and energy savings. Phase change hysteresis affects the utilization effect of phase change energy storage, and the influencing factors are unknown. In this paper, a low-temperature eutectic phase change material, CaCl2·6H2O-MgCl2·6H2O, was selected as the research object, combined with the mechanism of phase change hysteresis characteristics, using a temperature acquisition instrument to draw the step cooling curve. A differential scanning calorimeter was used to measure the DSC (differential scanning calorimetry) curve, and the hysteresis characteristics of phase transformation were studied by factors, such as heat storage temperature, cooling temperature, and cooling rate. The experimental results show that when heating temperature increases by 30 °C, phase transition hysteresis decreases by about 3 °C. The cooling temperature decreased by 10 °C, and the phase transition hysteresis increased by 2.69 °C. This paper provides a new idea for optimizing the properties of phase change energy storage materials and provides a possibility for realizing the parametric control of phase change hysteresis factors.