Hemolysis-driven IFNα production impairs erythropoiesis by negatively regulating EPO signaling in sickle cell disease.

ABSTRACT: Disordered erythropoiesis is a feature of many hematologic diseases, including sickle cell disease (SCD). However, very little is known about erythropoiesis in SCD. Here, we show that although bone marrow (BM) erythroid progenitors and erythroblasts in Hbbth3/+ thalassemia mice were increased more than twofold, they were expanded by only ∼40% in Townes sickle mice (SS). We further show that the colony-forming ability of SS erythroid progenitors was decreased and erythropoietin (EPO)/EPO receptor (EPOR) signaling was impaired in SS erythroid cells. Furthermore, SS mice exhibited reduced responses to EPO. Injection of mice with red cell lysates or hemin, mimicking hemolysis in SCD, led to suppression of erythropoiesis and reduced EPO/EPOR signaling, indicating hemolysis, a hallmark of SCD, and could contribute to the impaired erythropoiesis in SCD. In vitro hemin treatment did not affect Stat5 phosphorylation, suggesting that hemin-induced erythropoiesis suppression in vivo is via an indirect mechanism. Treatment with interferon α (IFNα), which is upregulated by hemolysis and elevated in SCD, led to suppression of mouse BM erythropoiesis in vivo and human erythropoiesis in vitro, along with inhibition of Stat5 phosphorylation. Notably, in sickle erythroid cells, IFN-1 signaling was activated and the expression of cytokine inducible SH2-containing protein (CISH), a negative regulator of EPO/EPOR signaling, was increased. CISH deletion in human erythroblasts partially rescued IFNα-mediated impairment of cell growth and EPOR signaling. Knocking out Ifnar1 in SS mice rescued the defective BM erythropoiesis and improved EPO/EPOR signaling. Our findings identify an unexpected role of hemolysis on the impaired erythropoiesis in SCD through inhibition of EPO/EPOR signaling via a heme-IFNα-CISH axis.

Trunk distortion weakens the tree productivity revealed by half-sib progeny determination of Pinus yunnanensis.

Twisted trunks are not uncommon in trees, but their effects on tree growth are still unclear. Among coniferous tree species, the phenomenon of trunk distortion is more prominent in Pinus yunnanensis. To expand the germplasm of genetic resources, we selected families with excellent phenotypic traits to provide material for advanced generation breeding. The progeny test containing 93 superior families (3240 trees) was used as the research material. Phenotypic measurements and estimated genetic parameters (family heritability, realistic gain and genetic gain) were performed at 9, 15, and 18 years of age, respectively. The genetic evaluation yielded the following results (1) The intra-family variance component of plant height (PH) was greater than that of the inter-family, while the inter-family variance components of other traits (diameter at breast height (DBH), crown diameter (CD), height under branches (HUB), degree of stem-straightness (DS)) were greater than that of the intra-family, indicating that there was abundant variation among families and potential for selection. (2) At half rotation period (18 years old), there was a significant correlation among the traits. The proportion of trees with twisted trunks (level 1-3 straightness) reached 48%. The DS significantly affected growth traits, among which PH and DBH were the most affected. The volume loss rate caused by twisted trunk was 18.06-56.75%, implying that trunk distortion could not be completely eliminated after an artificial selection. (3) The influence of tree shape, crown width, and trunk on volume increased, and the early-late correlation between PH, DBH and volume was extremely significant. The range of phenotypic coefficient of variation, genetic variation coefficient and family heritability of growth traits (PH, DBH, and volume) were 44.29-127.13%, 22.88-60.87%, and 0.79-0.83, respectively. (4) A total of 21 superior families were selected by the method of membership function combined with independent selection. Compared with the mid-term selection (18 years old), the accuracy of early selection (9 years old) reached 77.5%. The selected families' genetic gain and realistic gain range were 5.79-19.82% and 7.12-24.27%, respectively. This study can provide some useful reference for the breeding of coniferous species.

EpoR-tdTomato-Cre mice enable identification of EpoR expression in subsets of tissue macrophages and hematopoietic cells.

The erythropoietin receptor (EpoR) has traditionally been thought of as an erythroid-specific gene. Notably, accumulating evidence suggests that EpoR is expressed well beyond erythroid cells. However, the expression of EpoR in non-erythroid cells has been controversial. In this study, we generated EpoR-tdTomato-Cre mice and used them to examine the expression of EpoR in tissue macrophages and hematopoietic cells. We show that in marked contrast to the previously available EpoR-eGFPcre mice, in which a very weak eGFP signal was detected in erythroid cells, tdTomato was readily detectable in both fetal liver (FL) and bone marrow (BM) erythroid cells at all developmental stages and exhibited dynamic changes during erythropoiesis. Consistent with our recent finding that erythroblastic island (EBI) macrophages are characterized by the expression of EpoR, tdTomato was readily detected in both FL and BM EBI macrophages. Moreover, tdTomato was also detected in subsets of hematopoietic stem cells, progenitors, megakaryocytes, and B cells in BM as well as in spleen red pulp macrophages and liver Kupffer cells. The expression of EpoR was further shown by the EpoR-tdTomato-Cre-mediated excision of the floxed STOP sequence. Importantly, EPO injection selectively promoted proliferation of the EpoR-expressing cells and induced erythroid lineage bias during hematopoiesis. Our findings imply broad roles for EPO/EpoR in hematopoiesis that warrant further investigation. The EpoR-tdTomato-Cre mouse line provides a powerful tool to facilitate future studies on EpoR expression and regulation in various non-hematopoietic cells and to conditionally manipulate gene expression in EpoR-expressing cells for functional studies.

Analyses of erythropoiesis from embryonic stem cell-CD34+ and cord blood-CD34+ cells reveal mechanisms for defective expansion and enucleation of embryomic stem cell-erythroid cells.

Red blood cells (RBCs) generated ex vivo have the potential to be used for transfusion. Human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) possess unlimited self-renewal capacity and are the preferred cell sources to be used for ex vivo RBC generation. However, their applications are hindered by the facts that the expansion of ES/iPS-derived erythroid cells is limited and the enucleation of ES/iPS-derived erythroblasts is low compared to that derived from cord blood (CB) or peripheral blood (PB). To address this, we sought to investigate the underlying mechanisms by comparing the in vitro erythropoiesis profiles of CB CD34+ and ES CD34+ cells. We found that the limited expansion of ES CD34+ cell-derived erythroid cells was associated with defective cell cycle of erythroid progenitors. In exploring the cellular and molecular mechanisms for the impaired enucleation of ES CD34+ cell-derived orthochromatic erythroblasts (ES-ortho), we found the chromatin of ES-ortho was less condensed than that of CB CD34+ cell-derived orthochromatic erythroblasts (CB-ortho). At the molecular level, both RNA-seq and ATAC-seq analyses revealed that pathways involved in chromatin modification were down-regulated in ES-ortho. Additionally, the expression levels of molecules known to play important role in chromatin condensation or/and enucleation were significantly lower in ES-ortho compared to that in CB-ortho. Together, our findings have uncovered mechanisms for the limited expansion and impaired enucleation of ES CD34+ cell-derived erythroid cells and may help to improve ex vivo RBC production from stem cells.

Strain parameters for predicting the prognosis of non-ischemic dilated cardiomyopathy using cardiovascular magnetic resonance tissue feature tracking.

BACKGROUND: A considerable number of non-ischemic dilated cardiomyopathy (NDCM) patients had been found to have normalized left ventricular (LV) size and systolic function with tailored medical treatments. Accordingly, we aimed to evaluate if strain parameters assessed by cardiovascular magnetic resonance (CMR) feature tracking (FT) analysis could predict the NDCM recovery. METHODS: 79 newly diagnosed NDCM patients who underwent baseline and follow-up CMR scans were enrolled. Recovery was defined as a current normalized LV size and systolic function evaluated by CMR. RESULTS: Among 79 patients, 21 (27%) were confirmed recovered at a median follow-up of 36 months. Recovered patients presented with faster heart rates (HR) and larger body surface area (BSA) at baseline (P < 0.05). Compared to unrecovered patients, recovered pateints had a higher LV apical radial strain divided by basal radial strain (RSapi/bas) and a lower standard deviation of time to peak radial strain in 16 segments of the LV (SD16-TTPRS). According to a multivariate logistic regression model, RSapi/bas (P = 0.035) and SD16-TTPRS (P = 0.012) resulted as significant predictors for differentiation of recovered from unrecovered patients. The sensitivity and specificity of RSapi/bas and SD16-TTPRS for predicting recovered conditions were 76%, 67%, and 91%, 59%, with the area under the curve of 0.75 and 0.76, respectively. Further, Kaplan Meier survival analysis showed that patients with RSapi/bas ≥ 0.95% and SD16-FTPRS ≤ 111 ms had the highest recovery rate (65%, P = 0.027). CONCLUSIONS: RSapi/bas and CMR SD16-TTPRS may be used as non-invasive parameters for predicting LV recovery in NDCM. This finding may be beneficial for subsequent treatments and prognosis of NDCM patients. Registration number: ChiCTR-POC-17012586.

Serological Assays Estimate Highly Variable SARS-CoV-2 Neutralizing Antibody Activity in Recovered COVID-19 Patients.

The development of neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following infection or vaccination is likely to be critical for the development of sufficient population immunity to drive cessation of the coronavirus disease of 2019 (COVID-19) pandemic. A large number of serologic tests, platforms, and methodologies are being employed to determine seroprevalence in populations to select convalescent plasma samples for therapeutic trials and to guide policies about reopening. However, the tests have substantial variations in sensitivity and specificity, and their ability to quantitatively predict levels of NAbs is unknown. We collected 370 unique donors enrolled in the New York Blood Center Convalescent Plasma Program between April and May of 2020. We measured levels of antibodies in convalescent plasma samples using commercially available SARS-CoV-2 detection tests and in-house enzyme-linked immunosorbent assays (ELISAs) and correlated serological measurements with NAb activity measured using pseudotyped virus particles, which offer the most informative assessment of antiviral activity of patient sera against viral infection. Our data show that a large proportion of convalescent plasma samples have modest antibody levels and that commercially available tests have various degrees of accuracy in predicting NAb activity. We found that the Ortho anti-SARS-CoV-2 total Ig and IgG high-throughput serological assays (HTSAs) and the Abbott SARS-CoV-2 IgG assay quantify levels of antibodies that strongly correlate with the results of NAb assays and are consistent with gold standard ELISA results. These findings provide immediate clinical relevance to serology results that can be equated to NAb activity and could serve as a valuable roadmap to guide the choice and interpretation of serological tests for SARS-CoV-2.

Evaluation of elevated left ventricular end diastolic pressure in patients with preserved ejection fraction using cardiac magnetic resonance.

OBJECTIVES: This study aims to validate the reliability of cardiac magnetic resonance (CMR) parameters for estimating left ventricular end diastolic pressure (LVEDP) in heart failure patients with preserved ejection fraction (HFpEF) and compare their accuracy to conventional echocardiographic ones, with reference to left heart catheterisation. METHODS: Sixty patients with exertional dyspnoea (New York Heart Association function class II to III) were consecutively enrolled. CMR-derived time-volume curve and deformation parameters, conventional echocardiographic diastolic indices as well as LVEDP evaluated by left heart catheterisation were collected and analysed. RESULTS: Fifty-one patients, who accomplished all three examinations, were divided into HFpEF group and non-HFpEF group based on LVEDP measurements. Compared to the non-HFpEF group, CMR-derived time-volume curve showed lower peak filling rate adjusted for end diastolic volume (PFR/EDV, p = 0.027), longer time to peak filling rate (T-PFR, p < 0.001), and increased T-PFR in one cardiac cycle (%T-PFR, p < 0.001) in HFpEF group. In multivariable linear regression analysis, %T-PFR (ß = 0.372, p = 0.024), left ventricular global peak longitudinal diastolic strain rate (LDSR, ß = -0.471, p = 0.006), and E/e' (ß = 0.547, p = 0.001) were independently associated with invasively measured LVEDP. The sensitivity and specificity of E/e' and LDSR for predicting the elevated LVEDP were 76%, 92% and 76%, 89%, respectively. CONCLUSIONS: These findings suggest that CMR-derived time-volume curve and strain indices could predict HFpEF patients. Not only E/e' assessed by echocardiography but also the CMR-derived %T-PFR and LDSR correlated well with LVEDP. These non-invasive parameters were validated to evaluate the left ventricular diastolic function. KEY POINTS: • The abnormal time-volume curve revealed insufficient early diastole in HFpEF patients. • Non-invasive parameters including E/e', %T-PFR, and LDSR correlated well with LVEDP.

Poly r(C) binding protein 1-mediated regulation of microRNA expression underlies post-sevoflurane amelioration of acute lung injury in rats.

Acute lung injury (ALI) presents a pervasive health burden due to the high morbidity and mortality associated with it. Volatile anesthetics like sevoflurane has been previously shown to have organ-protective effect, both in the context of normal physiological function in liver, and during LPS-induced ALI. Sevoflurane was shown to exert lung protective effect during LPS-induced ALI by modulating expression level of microRNAs (miRNAs), specifically miR-155. The objective of the current study was to define the underlying mechanism by which sevoflurane alters miRNA expression levels. Lung injury caused by LPS and its amelioration post sevoflurane administration was first confirmed. Expression levels of different miRNA and messenger RNAs (mRNAs) encoding inflammatory cytokines were measured in a rat model of lipopolysaccharide (LPS)-induced ALI, which were subsequently treated with either sevoflurane or vehicle control. Host of miRNAs and messenger RNAs encoding pro-inflammatory cytokines are overexpressed during LPS-induced ALI, which are reversed following sevoflurane administration. Mass spectrometry analysis revealed that the RNA-binding protein, poly r(C) binding protein 1 (PCBP1) expression is induced in ALI and is repressed following sevoflurane treatment. RNA immunoprecipitation experiments revealed that PCBP1 expression dictates the altered miRNA expression and sevoflurane altered miRNA expression by suppressing PCBP1 expression. Our study thus elucidates a unique mechanism of lung protective effect of sevoflurane mediated by suppression of expression of a RNA-binding protein that potentiates expression of pro-inflammatory miRNAs.

Strain Values of Left Ventricular Segments Reduce Non-homogeneously in Dilated Cardiomyopathy with Moderately and Severely Deteriorated Heart Function Assessed by MRI Tissue Tracking Imaging.

Changes of global and segmental ventricular strain at different deterioration levels of cardiac function in patients with dilated cardiomyopathy (DCM) using cardiac magnetic resonance (CMR) have not yet been explored. In total, 101 patients diagnosed with DCM consecutively underwent CMR. They were categorized according to the reduction in left ventricular ejection fraction (LVEF) into the following groups: moderately reduced (n = 43) and severely reduced group (n = 58). LV global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), and segmental strain values were assessed using tissue tracking technique. LV segmental circumferential strain (CS) and radial strain (RS) in healthy volunteers increased from base to apex stepwisely. The LV base-to-apex increasing pattern disappeared in the moderate DCM group (RS: 26.61% ± 20.63% versus 21.97% ± 4.85% versus 29.05% ± 9.90%, P > 0.05; CS: -13.16% ± 6.40% versus -12.96%± 2.45% versus -15.32% ± 3.89%, P > 0.05). While in the severe group, CS and RS of base segment had the highest values, there was no significant difference between mid and apex segments. GLSLV, GRSLV, and GCSLV were significantly reduced in moderate and severe groups in steps, similar to the three parameters of RV. During a 17-month median follow-up, 25 patients had an index composite outcome event. GLSLV > -11.62%, GCSLV > -9.35%, and GRSLV≤ 12.42% were significantly associated with the occurrence of cardiac events in DCM patients. LV segmental values reduce non-homogeneously in DCM patients with moderately and severely deteriorated heart function.

Myricetin ameliorates scopolamine-induced memory impairment in mice via inhibiting acetylcholinesterase and down-regulating brain iron.

The aim of our study was to investigate to investigate the effect of myricetin on Alzheimer's disease (AD) and its underlying mechanisms. In our study, Myricetin effectively attenuated Fe2+-induced cell death in SH-SY5Y cells in vitro. In a mouse model of AD, myricetin treatment significantly reversed scopolamine-induced cognitive deficits deriving from a novel action of inhibiting acetylcholinesterase (AChE) and down-regulating brain iron. Furthermore, Myricetin treatment reduced oxidative damage and increased antioxidant enzymes activity in mice. Interestingly, the effect of myricetin was largely abolished by high iron diet. Therefore we suggested that treatment with myricetin attenuated cognitive deficits in mice via inhibiting AChE and brain iron regulation. In addition, myricetin reduce iron contents may via inhibiting transferrin receptor 1 (TrR1) expression. In conclusion, accumulated data demonstrates that myricetin is a potential multifunctional drug for AD.

3-aminopropyltriethoxysilane modified MXene on three-dimensional nonwoven fiber substrates for low-cost, stable, and efficient solar-driven interfacial evaporation desalination.

Recently, the solar-driven interfacial evaporation desalination has attracted more and more attentions due to the advantages of low cost, zero energy consumption, and high water purification rate, etc. One of the bottlenecks of this emerging technique lies in a lack of simple and low-cost ways to construct three-dimensional (3D) hierarchical microstructures for photothermal membranes. To this end, a two-step strategy is carried out by combining surface functionalization with substrate engineering. Firstly, a silane coupling agent 3-aminopropyltriethoxysilane (APTES) is grafted onto an ideal photothermal material of Ti3C2Tx MXene, to improve the nanochannel sizes and hydrophilicity, which are attributed to enlarged interspaces of MXene and introduced hydrophilic group e.g., -NH2 and -OH, respectively. Secondly, a low-cost and robust nonwoven fiber (NWF) substrate, which has a 3D micron-sized mesh structure with interlaced fiber stacks, is employed as the skeleton to load enough APTES-grafted MXene by a simple soaking method. Benefited from above design, the Ti3C2Tx-APTES/NWF composite membrane with a 3D hierarchical structure shows enhanced light scattering and utilization, water transport and vapor escape. A remarkable evaporation rate of 1.457 kg m-2 h-1 and an evaporation efficiency of 91.48 % are attained for a large-area (5 × 5 cm2) evaporator, and the evaporation rate is further increased to 1.672 kg m-2 h-1 for a small-area (2 × 2 cm2) device. The rejection rates of salt ions and heavy metal ions are higher than 99 % and 99.99 %, respectively, and the removal rates of organic dye molecules are nearly to 100 %. Besides, the composite photothermal membrane exhibits great stabilities in harsh conditions such as high salinities, long cycling, large light intensities, strong acid/alkali environments, and mechanical bending. Most importantly, the photothermal membrane shows a considerable cost-effectiveness of 89.4 g h-1/$. Hence, this study might promote the commercialization of solar-driven interfacial evaporation desalination by collaboratively considering surface modification and substrate engineering for MXene.

Seasonal variations of microbial community structure, assembly processes, and influencing factors in karst river.

The physicochemical properties and microbial communities have significant annual and seasonal changes in karst aquifers. To explore the changes of microbial community and their relationships with environmental factors, water samples were collected from a typical karst river. Microbial communities in winter (Jan-2017 and Jan-2019) were stable with high similarity in spite of the 2 years sampling interval, but the microbial communities in Aug-2017 was different from that in Aug-2018. In four sampling times, there were 275 shared genera, whose average relative abundance ranging from 89.04 to 96.27%. The winter and summer specific genera were mainly from the recharge of tributary site K6 and discharge of waste water treatment plant (K2 and K3), respectively. The deterministic processes had a more significant effect on the microbial community assembly in winter than that in summer, which was affected by environmental pressure from pollution. Furthermore, antibiotics and inorganic nitrogen pollution affected element cycles of nitrogen and sulfur indirectly through microbial ecological modules in karst river, and the denitrification and desulfurization processes were potentially inhibited. These findings contributed to understand the changes and its assembly mechanism of microbial community, as well as the feedback to environment in polluted karst river.

Effects of geo-climate factors on phenotypic variation in cone and seed traits of Pinus yunnanensis.

Evaluating variations in reproductive traits and the response of the variations to geo-climate conditions are essential for understanding the persistence, evolution, and range dynamics of plant populations. However, there are insufficient studies to attempt to analyze the importance of geo-climate factors in explaining within- or among-population variation in reproductive traits. We examined 14 traits for 2671 cones of Pinus yunnanensis collected from nine populations in the mountains of Southwest China to characterize the patterns of phenotypic variation of traits and estimate environmental effects on these trait performances and trait variation. We found the contribution of intrapopulation variation to the overall variation was greater than the interpopulation variation and the larger coefficients of variation for the populations lying at the edge of northern and southern regions. Climatic variables are more important than geographical and tree size variables in their relationships to cone and seed traits. Populations in more humid and warmer climate expressed greater cone and seed weight and seed number but lower seed abortion rate, while the larger coefficients of variation in seed weight and number were detected in northern and southern marginal regions with drier or colder climate. Our study illustrates that intraspecific trait variation should be considered when examining plant species response to changing climate and suggests that the high variability rather than high quality of seed traits in the marginal regions with drier or colder climate might foster plant-population persistence in stressful conditions.

An entire recycling of spent Al-bearing cathode powder as giniite sphere and lithiophophate plate with leaching-hydrothermal-precipitation process.

Spent lithium battery is a polymetallic waste, and valuable to be recovered as Li-bearing chemical with the barriers of impurities separation, especially Fe and Al. Here in, Li-rich cathode powder was manually disassembled from spent battery, and then recovered as lithiophosphate plate in consideration of effective separation of impure Fe/Al. The powder comprised of 23.2% Fe, 3.2% Al, 5.5% Li and 19.6% P, and then dissolved by azotic acid as Li-rich solution. When the solution was heated to 190°C for 10 h with the supplementary of saccharose, more than 99.9% Fe and 98.9% Al were removed as spherical giniite particles, in accordance with the rest of Fe/Al at the concentrations of 2.1 and 14 mg/L, whilst the loss of Li was less than 1.5%. But without saccharose, the Fe/Al removals only achieved by 99.2% and 52.1%. It is also found that the Fe/Al/Li removal achieved by 99.6%, 96% and 25.3% after adjusting the solution to pH 2.7 by NaOH. After hydrothermal treatment, the rest Li can be recycled as lithiophosphate plate by pH adjustment, in contrast to the recovery efficiency of 98.5% Li. Such method raised a facile route to effectively separate impure Fe/Al from Li-rich cathode powder, and showed promising application in the industrial recovery of spent battery.

Comprehensive Characterization and Global Transcriptome Analysis of Human Fetal Liver Terminal Erythropoiesis.

The fetal liver (FL) is the key erythropoietic organ during fetal development, but knowledge on human FL erythropoiesis is very limited. In this study, we sorted primary erythroblasts from FL cells and performed RNA sequencing (RNA-seq) analyses. We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis. Notably, the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts (OrthoEs), suggesting the involvement of these pathways in enucleation. We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+ cells. Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences, indicating impacts of the culture system on gene expression. Notably, the expression of lipid metabolism-related genes was increased in cultured erythroblasts. We further immortalized erythroid cell lines from FL and cord blood (CB) CD34+ cells (FL-iEry and CB-iEry, respectively). FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs, but their enucleation ability was very low. Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity, indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate. Additionally, the expression of HBE1, HBZ, and HBG2 was up-regulated in FL-iEry compared with CB-iEry, and this up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1. Our study provides new insights into human FL erythropoiesis and rich resources for future studies.

Overexpression of DsEXLA2 gene from Dendrocalamus sinicus accelerates the plant growth rate of Arabidopsis.

Expansins play crucial roles in cell wall loosening and a range of life activities involving cell wall modification. Nevertheless, the biological functions of expansin genes during fast growth of bamboo remain unclear. In this study, Dendrocalamus sinicus, the largest and fastest growing bamboo species in the world, was used as the research material, and the full length of DsEXLA2 was cloned. Bioinformatics analysis revealed that DsEXLA2 contained expansin family typical domains (DPBB_1 and Pollen_allerg_1, CDRC motif) and amino acid sequence was highly conserved among different species. The expression level of DsEXLA2 increased from top section to basal section in different internodes. Subcellular localization verified that DsEXLA2 protein was located in the cell wall. Further genetic transformation studies in Arabidopsis indicated that compared with the wild type, DsEXLA2 overexpressed transgenic plants exhibited higher plant height, thicker stem, larger leaf, and less epidermal hair number and smaller stomatal aperture in the prophase and metaphase of growth. In addition, the cellulose content in the stem of transgenic plants was increased, and cell wall was thickened significantly. Moreover, a total of 1656 differentially expressed genes (DEGs) were identified by RNA-seq. The upregulated genes were predominantly enriched in the plant-pathogen interaction, MAPK signaling pathway-plant, plant hormone signal transduction, lipid metabolism and amino acid metabolism, while the downregulated genes were mainly enriched in energy metabolism, carbohydrate metabolism, plant hormone signal transduction and ribosome. These data implied that overexpression of DsEXLA2 gene accelerates the plant growth rate of Arabidopsis. This study is helpful to reveal the molecular mechanism of DsEXLA2 in culm growth and development of D. sinicus, and to understand the rapid growth of bamboos.

Regulatory mechanism of fibrosis-related genes in patients with heart failure.

Background: Heart failure (HF) is a complex clinical syndrome characterized by the inability to match cardiac output with metabolic needs. Research on regulatory mechanism of fibrosis-related genes in patients with HF is very limited. In order to understand the mechanism of fibrosis in the development and progression of HF, fibrosis -related hub genes in HF are screened and verified. Methods: RNA sequencing data was obtained from the Gene Expression Omnibus (GEO) cohorts to identify differentially expressed genes (DEGs). Thereafter, fibrosis-related genes were obtained from the GSEA database and that associated with HF were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis was carried out to analyze the biological function of fibrosis-related DEGs. The protein-protein interaction (PPI) network of hub genes was constructed via the STRING database. Moreover, the diagnostic value of hub genes for HF was confirmed using ROC curves and expression analysis. Finally, quantitative real time PCR was used to detect the expression levels of mRNAs. Results: A total of 3, 469 DEGs were identified closely related to HF, and 1, 187 fibrosis-related DEGs were obtained and analyzed for GO and KEGG enrichment. The enrichment results of fibrosis-related DEGs were consistent with that of DEGs. A total of 10 hub genes (PPARG, KRAS, JUN, IL10, TLR4, STAT3, CXCL8, CCL2, IL6, IL1ß) were selected via the PPI network. Receiver operating characteristic curve analysis was estimated in the test cohort, and 6 genes (PPARG, KRAS, JUN, IL10, TLR4, STAT3) with AUC more than 0.7 were identified as diagnosis genes. Moreover, miRNA-mRNA and TF-mRNA regulatory networks were constructed. Finally, quantitative real time PCR revealed these 6 genes may be used as the potential diagnostic biomarkers of HF. Conclusion: In this study, 10 fibrosis-related hub genes in the HF were identified and 6 of them were demonstrated as potential diagnostic biomarkers for HF.

Predictive Value of Cardiac Magnetic Resonance for Left Ventricular Remodeling of Patients with Acute Anterior Myocardial Infarction.

Background: Heart failure is a serious complication resulting from left ventricular remodeling (LVR), especially in patients experiencing acute anterior myocardial infarction (AAMI). It is crucial to explore the predictive parameters for LVR following primary percutaneous coronary intervention (PPCI) in patients with AAMI. Methods: A total of 128 AAMI patients who were reperfused successfully by PPCI were enrolled sequentially from June 2018 to December 2019. Cardiovascular magnetic resonance (CMR) was performed at the early stage (<7 days) and after the 6-month follow-up. The patients were divided into LVR and non-LVR groups according to the increase of left ventricular end diastolic volume (LVEDV) measured by the second cardiac magnetic resonance examination ≥20% from baseline. (3) Results: The left ventricular ejection fraction (LVEF), the global longitudinal strain (GLS), the peak circumferential strain in infarcted segments, and the infarct size (IS) remained significantly different in the multivariate logistic regression analysis (all p < 0.05). The area under the receiver operating characteristic curve of Model 1, wherein the GLS was added to the LVEF, was 0.832 (95% CI 0.758−0.907, p < 0.001). The C-statistics for Model 2, which included the infarct-related regional parameters (IS and the peak circumferential strain in infarcted segments)was 0.917 (95% CI 0.870−0.965, p < 0.001). Model 2 was statistically superior to Model 1 in predicting LVR (IDI: 0.190, p = 0.002). (4) Conclusions: Both the global and regional CMR parameters were valuable in predicting LVR in patients with AAMI following the PPCI. The local parameters of the infarct zones were superior to those of the global ones.

The impacts of flowering phenology on the reproductive success of the narrow endemic Nouelia insignis Franch. (Asteraceae).

Nouelia insignis Franch. (Asteraceae) is a short, narrow endemic and endangered tree, growing with a natural population in the dry and hot valley of the Jinsha River in the southwest area of China. In this work, flowering phenology (time and duration), floral biology, visit frequency and behavior of pollinators, and pollination characteristics were studied based on investigation in the field and analysis in the laboratory with the help of a stereomicroscope, and the relationship between seed setting rate and reproductive traits, as well as the relationship between flowering time and rainfall before flowering, was tested using the method of general linear regression model. The results showed that natural population of N. insignis exhibited high flowering synchrony with relatively stable flowering duration, and the flowering time fluctuated greatly depending on the rainfall 5 months before flowering. The pollination of N. insignis required pollinators, and insect activities played a very important role in the pollination process. However, lack of the pollinators was not a limitation for reproductive fitness in N. insignis, although the number of pollinators was small and the frequency of visits was low. In addition, no pollen limitation was found during pollination. The average seed setting rate of N. insignis in the natural condition was only 1.52%-3.73%, and it was generally affected by changes in flowering phenology between years and had a higher seed set in early flowering year. The annual variation of seed set might be related to the annual variations of stamen and pistil functions, such as changes of pollen viability and stigma receptivity, which were closely related to flowering time. The results of this study are of value for further conservation actions on natural population of this threatened endemic plant.