PIF7-mediated epigenetic reprogramming promotes the transcriptional response to shade in Arabidopsis.

For shade-intolerant plants, changes in light quality through competition from neighbors trigger shade avoidance syndrome (SAS): a series of morphological and physiological adaptations that are ultimately detrimental to plant health and crop yield. Phytochrome-interacting factor 7 (PIF7) is a major transcriptional regulator of SAS in Arabidopsis; however, how it regulates gene expression is not fully understood. Here, we show that PIF7 directly interacts with the histone chaperone anti-silencing factor 1 (ASF1). The ASF1-deprived asf1ab mutant showed defective shade-induced hypocotyl elongation. Histone regulator homolog A (HIRA), which mediates deposition of the H3.3 variant into chromatin, is also involved in SAS. RNA/ChIP-sequencing analyses identified the role of ASF1 in the direct regulation of a subset of PIF7 target genes. Furthermore, shade-elicited gene activation is accompanied by H3.3 enrichment, which is mediated by the PIF7-ASF1-HIRA regulatory module. Collectively, our data reveal that PIF7 recruits ASF1-HIRA to increase H3.3 incorporation into chromatin to promote gene transcription, thus enabling plants to effectively respond to environmental shade.

Spt4 is selectively required for transcription of extended trinucleotide repeats.

Lengthy trinucleotide repeats encoding polyglutamine (polyQ) stretches characterize the variant proteins of Huntington's disease and certain other inherited neurological disorders. Using a phenotypic screen to identify events that restore functionality to polyQ proteins in S. cerevisiae, we discovered that transcription elongation factor Spt4 is required to transcribe long trinucleotide repeats located either in ORFs or nonprotein-coding regions of DNA templates. Mutation of SPT4 selectively decreased synthesis of and restored enzymatic activity to expanded polyQ protein without affecting protein lacking long-polyQ stretches. RNA-seq analysis revealed limited effects of Spt4 on overall gene expression. Inhibition of Supt4h, the mammalian ortholog of Spt4, reduced mutant huntingtin protein in neuronal cells and decreased its aggregation and toxicity while not altering overall cellular mRNA synthesis. Our findings identify a cellular mechanism for transcription through repeated trinucleotides and a potential target for countermeasures against neurological disorders attributable to expanded trinucleotide regions.

Arabidopsis CHROMATIN REMODELING 19 acts as a transcriptional repressor and contributes to plant pathogen resistance.

Chromatin remodelers act in an ATP-dependent manner to modulate chromatin structure and thus genome function. Here, we report that the Arabidopsis (Arabidopsis thaliana) remodeler CHROMATIN REMODELING19 (CHR19) is enriched in gene body regions, and its depletion causes massive changes in nucleosome position and occupancy in the genome. Consistent with these changes, an in vitro assay verified that CHR19 can utilize ATP to slide nucleosomes. A variety of inducible genes, including several important genes in the salicylic acid (SA) and jasmonic acid (JA) pathways, were transcriptionally upregulated in the chr19 mutant under normal growth conditions, indicative of a role of CHR19 in transcriptional repression. In addition, the chr19 mutation triggered higher susceptibility to the JA pathway-defended necrotrophic fungal pathogen Botrytis cinerea, but did not affect the growth of the SA pathway-defended hemibiotrophic bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Expression of CHR19 was tissue-specific and inhibited specifically by SA treatment. Such inhibition significantly decreased the local chromatin enrichment of CHR19 at the associated SA pathway genes, which resulted in their full activation upon SA treatment. Overall, our findings clarify CHR19 to be a novel regulator acting at the chromatin level to impact the transcription of genes underlying plant resistance to different pathogens.

AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations.

Transcription factors (TFs) are proteins that interact with specific DNA sequences to regulate gene expression and play crucial roles in all kinds of biological processes. To keep up with new data and provide a more comprehensive resource for TF research, we updated the Animal Transcription Factor Database (AnimalTFDB) to version 4.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB4/) with up-to-date data and functions. We refined the TF family rules and prediction pipeline to predict TFs in genome-wide protein sequences from Ensembl. As a result, we predicted 274 633 TF genes and 150 726 transcription cofactor genes in AnimalTFDB 4.0 in 183 animal genomes, which are 86 more species than AnimalTFDB 3.0. Besides double data volume, we also added the following new annotations and functions to the database: (i) variations (including mutations) on TF genes in various human cancers and other diseases; (ii) predicted post-translational modification sites (including phosphorylation, acetylation, methylation and ubiquitination sites) on TFs in 8 species; (iii) TF regulation in autophagy; (iv) comprehensive TF expression annotation for 38 species; (v) exact and batch search functions allow users to search AnimalTFDB flexibly. AnimalTFDB 4.0 is a useful resource for studying TF and transcription regulation, which contains comprehensive annotation and classification of TFs and transcription cofactors.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Evaluation of Kidney Injury Using Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI: An Experimental Study in Rats With Carbon Tetrachloride-Induced Liver Cirrhosis.

BACKGROUND: Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified. PURPOSE: To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease. STUDY TYPE: Prospective. ANIMAL MODEL: Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7). FIELD STRENGTH/SEQUENCE: 3-T, ASL, BOLD, and T2W. ASSESSMENT: Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested. STATISTICAL TESTS: Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant. RESULTS: Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964). DATA CONCLUSION: Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease.

COVID-19 has caused severe consequences in terms of public health and economy worldwide since its outbreak in December 2019. SARS-CoV-2 3C-like protease (3CLpro), crucial for the viral replications, is an attractive target for the development of antiviral drugs. In this study, several kinds of Michael acceptor warheads were utilized to hunt for potent covalent inhibitors against 3CLpro. Meanwhile, novel 3CLpro inhibitors with the P3-3,5-dichloro-4-(2-(dimethylamino)ethoxy)phenyl moiety were designed and synthesized which may form salt bridge with residue Glu166. Among them, two compounds 12b and 12c exhibited high inhibitory activities against SARS-CoV-2 3CLpro. Further investigations suggested that 12b with an acrylate warhead displayed potent activity against HCoV-OC43 (EC50 = 97 nM) and SARS-CoV-2 replicon (EC50 = 45 nM) and low cytotoxicity (CC50 > 10 µM) in Huh7 cells. Taken together, this study devised two series of 3CLpro inhibitors and provided the potent SARS-CoV-2 3CLpro inhibitor (12b) which may be used for treating coronavirus infections.

An MRI-based radiomics nomogram to predict progression-free survival in patients with endometrial cancer.

Aim: This study aimed to explore the importance of an MRI-based radiomics nomogram in predicting the progression-free survival (PFS) of endometrial cancer.Methods: Based on clinicopathological and radiomic characteristics, we established three models (clinical, radiomics and combined model) and developed a nomogram for the combined model. The Kaplan-Meier method was utilized to evaluate the association between nomogram-based risk scores and PFS.Results: The nomogram had a strong predictive ability in calculating PFS with areas under the curve (ROC) of 0.905 and 0.901 at 1 and 3 years, respectively. The high-risk groups identified by the nomogram-based scores had shorter PFS compared with the low-risk groups.Conclusion: The radiomics nomogram has the potential to serve as a noninvasive imaging biomarker for predicting individual PFS of endometrial cancer.

[Box: see text].

Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

Diagnostic value of LGE and T1 mapping in multiple myeloma patients'heart.

BACKGROUND: Unidentified heart failure occurs in patients with multiple myeloma when their heart was involved. CMR with late gadolinium enhancement (LGE) and T1 mapping can identify myocardial amyloid infiltrations. PURPOSE: To explore the role of CMR with late gadolinium enhancement (LGE) and T1 mapping for detection of multiple myeloma patients'heart. MATERIAL AND METHODS: A total of 16 MM patients with above underwent CMR (3.0-T) with T1 mapping (pre-contrast and post-contrast) and LGE imaging. In addition, 26 patients with non-obstructive hypertrophic cardiomyopathy and 26 healthy volunteers were compared to age- and sex-matched healthy controls without a history of cardiac disease, diabetes mellitus, or normal in CMR. All statistical analyses were performed using the statistical software GraphPad Prism. The measurement data were represented by median (X) and single sample T test was adopted. Enumeration data were represented by examples and Chi-tested was adopted. All tests were two-sided, and P values < 0.05 were considered statistically significant. RESULTS: In MM group, LVEF was lower than healthy controls and higher than that of non-obstructive hypertrophic cardiomyopathy group, but without statistically significant difference (%: 49.1 ± 17.5 vs. 55.6 ± 10.3, 40.4 ± 15.6, all P > 0.05). Pre-contrast T1 values of MM group were obviously higher than those of healthy controls and non-obstructive hypertrophic cardiomyopathy group (ms:1462.0 ± 71.3vs. 1269.3 ± 42.3, 1324.0 ± 45.1, all P < 0.05). 16 cases (100%) in MM group all had LGE. CONCLUSION: LGE joint T1 mapping wider clinical use techniques and follow-up the patients'disease severity.

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

Evaluation of pelvic structural abnormalities in primiparous women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the morphological characteristics of pelvic floor structure specific to de novo stress urinary incontinence (SUI) in primiparous women using three-dimensional (3D) reconstruction fusion technology based on static MRI combined with dynamic MRI. METHODS: Eighty-one primiparous women after the first vaginal delivery were studied, 40 with SUI and 41 without SUI. 3D reconstruction models based on static MRI were used to describe the anatomical abnormalities of pelvic floor tissues. Dynamic MRI was used to describe segmental activities of the urethra and vagina. The relationship between the morphometry and postpartum SUI was evaluated by logistic regression analysis and receiver operator characteristic curve. RESULTS: The differences in the distance from the bladder neck to the pubic symphysis (BSD), the angle between the posterior wall of the urethra and the anterior wall of the vagina, the width of the distal region of the vagina, urethral length, urethral compression muscle volume (CUV), and pubovisceral muscle volume, puborectal muscle volume, were measured, and except for the extremity of the anterior urethral wall, the total displacements (TDs) of the other sites between the two groups were statistically significant (p < 0.05). Logistic regression analysis showed that the BSD decreased, the CUV decreased, the TDs of the first site and the eighth site increment correlated significantly with postpartum SUI occurrence (p < 0.05). CONCLUSIONS: 3D reconstruction fusion technology provides an important support for a precise assessment of the pelvic floor dysfunction. The BSD, CUV, and iliococcygeus muscle volume have certain values in predicting de novo SUI after first vaginal birth.

Multi-parametric MRI-based machine learning model for prediction of pathological grade of renal injury in a rat kidney cold ischemia-reperfusion injury model.

BACKGROUND: Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. OBJECTIVE: To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. METHODS: Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. RESULTS: All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). CONCLUSION: The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

Annexin A1 may contribute to the morphological changes in podocytes by mediating endocytic vesicle fusion and transport via promotion of SNARE assembly in idiopathic membranous nephropathy.

BACKGROUND: Annexin A1 is a membrane-associated calcium-binding protein that participates in the progression of many diseases by facilitating vesicle aggregation. It has been documented that reducing vesicle formation alleviates podocyte injury and albuminuria in idiopathic membranous nephropathy (IMN). However, the role of Annexin A1 (ANXA1) in IMN is unknown. METHODS: Electron microscopy was used to observe the numbers of vesicles in podocytes. The expression of ANXA1 in IMN was investigated by bioinformatics analysis. We validated the hub genes with the Nephroseq V5 online tool and microarray data from the GEO. Immunohistochemical staining and qPCR were performed to measure gene and protein expression. RESULTS: The numbers of vesicles in IMN podocytes were significantly increased. Bioinformatics analysis showed that ANXA1, one of the differentially expressed genes, was upregulated in glomeruli from IMN patients. In the validation database and dataset, we confirmed that ANXA1 expression was upregulated in the glomeruli of IMN patients. We revealed that the increased expression of ANXA1 was negatively correlated with the glomerular filtration rate (GFR) and proteinuria. Moreover, ANXA1 was enriched in the biological process of vesicle fusion, in which the expression of SNAREs and the SNARE complex was increased. Finally, the expression of ANXA1 and genes related to SNAREs and the SNARE complex was upregulated in glomeruli from IMN patients according to immunohistochemical staining and qPCR. CONCLUSION: We conclude that ANXA1 may mediate endocytic vesicle fusion and transport by promoting SNARE assembly, contributing to the morphological changes in podocytes and massive proteinuria in IMN.

Association of spinal-pelvic parameters with recurrence of lumbar disc herniation after endoscopic surgery: a retrospective case-control study.

PURPOSE: This study aimed to investigate the relationship between spinal-pelvic parameters and recurrence of lumbar disc herniation (rLDH) after percutaneous endoscopic lumbar discectomy (PELD) through a retrospective case-control study. METHODS: Patients who underwent PELD for single-segment LDH at our hospital were included in this study. The relationship between sagittal balance parameters of the spine and recurrence was analysed through correlation analysis, and ROC curves were plotted. The baseline characteristics, sagittal balance parameters of the spine and radiological parameters of the case and control groups were compared, and the relationship between sagittal balance parameters of the spine and recurrence of rLDH after PELD was determined through univariate and multivariate logistic regression analysis. RESULTS: Correlation analysis showed that PI and ∆PI-LL were negatively correlated with grouping (r = -0.090 and -0.120, respectively, P = 0.001 and 0.038). ROC curve analysis showed that the area under the curve (ROC-AUC) for predicting rLDH based on PI was 0.65 (CI95% = 0.598, 0.720), with a cut-off of 50.26°. The ROC-AUC for predicting rLDH based on ∆PI-LL was 0.56 (CI95% = 0.503, 0.634), with a cut-off of 28.21°. Multivariate logistic regression analysis showed that smoking status (OR = 2.667, P = 0.008), PI ≤ 50.26 (OR = 2.161, P = 0.009), ∆PI-LL ≤ 28.21 (OR = 3.185, P = 0.001) and presence of Modic changes (OR = 4.218, P = 0.001) were independent risk factors, while high DH (OR = 0.788, P = 0.001) was a protective factor. CONCLUSION: PI < 50.26 and ∆PI-LL < 28.21 were risk factors for recurrence of lumbar disc herniation after spinal endoscopic surgery and had some predictive value for post-operative recurrence.

Factors of preparedness for loss from cancer among Taiwanese family caregivers.

This cohort study investigated factors associated with 336 Taiwanese family caregivers' emotional and cognitive preparedness for death of a loved one with terminal cancer. Caregivers' death-preparedness states (no-death-preparedness [as reference], cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) were previously identified. Associations of factors with these states were determined by a hierarchical generalized linear model. Financial hardship decreased caregivers' likelihood for the emotional-death-preparedness-only and sufficient-death-preparedness states. Physician prognostic disclosure increased membership in the cognitive-death-preparedness-only and sufficient-death-preparedness states. The better the quality of the patient-caregiver relationship, the higher the odds for the emotional-death-preparedness-only and sufficient-death-preparedness states, whereas the greater the tendency for caregivers to communicate end-of-life issues with their loved one, the lower the odds for emotional-death-preparedness-only state membership. Stronger coping capacity increased membership in the emotional-death-preparedness-only state, but perceived social support was not associated with state membership. Providing effective interventions tailored to at-risk family caregivers' specific needs may facilitate their death preparedness.

[Molecular mechanism of CDO1 regulating common metabolic diseases].

Cysteine dioxygenase type 1 (CDO1) belongs to the cysteine dioxygenase (CDO) family. CDO1 is the key enzyme in cysteine catabolism and taurine synthesis. CDO1 is highly expressed in liver, adipose tissue, pancreas, kidney, lung, brain and small intestine. CDO1 is involved in the pathophysiological regulation of various common metabolic diseases, such as lipid metabolism disorders, insulin resistance, obesity, tumors/cancers, and neurodegenerative diseases. This article summarizes the research progress on the molecular mechanisms of CDO1 regulation of common metabolic diseases in recent years, aiming to provide new theoretical and practical basis for CDO1-targeted therapy for insulin resistance, obesity, tumors/cancers, and neurodegenerative diseases.

The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity.

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: ß = 0.251, P = 0.014; volume: ß = 0.237, P = 0.042; total iron burden: ß = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: ß = 0.325, P = 0.001; Evans's index: ß = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.

Histone chaperones AtChz1A and AtChz1B are required for H2A.Z deposition and interact with the SWR1 chromatin-remodeling complex in Arabidopsis thaliana.

The histone variant H2A.Z plays key functions in transcription and genome stability in all eukaryotes ranging from yeast to human, but the molecular mechanisms by which H2A.Z is incorporated into chromatin remain largely obscure. Here, we characterized the two homologs of yeast Chaperone for H2A.Z-H2B (Chz1) in Arabidopsis thaliana, AtChz1A and AtChz1B. AtChz1A/AtChz1B were verified to bind to H2A.Z-H2B and facilitate nucleosome assembly in vitro. Simultaneous knockdown of AtChz1A and AtChz1B, which exhibit redundant functions, led to a genome-wide reduction in H2A.Z and phenotypes similar to those of the H2A.Z-deficient mutant hta9-1hta11-2, including early flowering and abnormal flower morphologies. Interestingly, AtChz1A was found to physically interact with ACTIN-RELATED PROTEIN 6 (ARP6), an evolutionarily conserved subunit of the SWR1 chromatin-remodeling complex. Genetic interaction analyses showed that atchz1a-1atchz1b-1 was hypostatic to arp6-1. Consistently, genome-wide profiling analyses revealed partially overlapping genes and fewer misregulated genes and H2A.Z-reduced chromatin regions in atchz1a-1atchz1b-1 compared with arp6-1. Together, our results demonstrate that AtChz1A and AtChz1B act as histone chaperones to assist the deposition of H2A.Z into chromatin via interacting with SWR1, thereby playing critical roles in the transcription of genes involved in flowering and many other processes.

Retinal vascular remodeling in photoreceptor degenerative disease.

Abnormal vasculature in the retina, specifically tortuous vessels and capillary degeneration, is common in many of the most prevalent retinal degenerative diseases, currently affecting millions of people across the world. However, the formation and development of abnormal vasculature in the context of retinal degenerative diseases are still poorly understood. The FVB/N (rd1) and rd10 mice are well-studied animal models of retinal degenerative diseases, but how photoreceptor degeneration leads to vascular abnormality in the diseases remains to be elucidated. Here, we used advancements in confocal microscopy, immunohistochemistry, and image analysis software to systematically characterize the pathological vasculature in the FVB/N (rd1) and rd10 mice, known as a chronic, rapid and slower retinal degenerative model, respectively. We demonstrated that there was plexus-specific vascular degeneration in the retinal trilaminar vascular network paralleled to photoreceptor degeneration in the diseased retinas. We also quantitatively analyzed the vascular structural architecture in the wild-type and diseased retinas to provide valuable information on vascular remodeling in retinal degenerative disease.