BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility.

The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.

Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation.

BACKGROUND: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. METHODS: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. RESULTS: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1ß levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte-endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. CONCLUSIONS: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.

C(NH2)3Cd(C2O4)Cl(H2O)·H2O and BaCd(C2O4)1.5Cl(H2O)2: Two Oxalate Chlorides Obtained by Chemical Scissors Strategy Exhibiting Low-Dimensional Structural Networks and Balanced Overall Optical Properties.

Low-dimensional crystalline materials have attracted much attention due to their special physical and chemical properties. Herein, two new oxalate chlorides, C(NH2)3Cd(C2O4)Cl(H2O)·H2O and BaCd(C2O4)1.5Cl(H2O)2, were synthesized. C(NH2)3Cd(C2O4)Cl(H2O)·H2O presents the unique {[Cd(C2O4)Cl(H2O)]-}∞ zigzag chain, while BaCd(C2O4)1.5Cl(H2O)2 shows a novel {[Cd(C2O4)1.5Cl]2-}∞ layer. They showed large measured band gaps, which were 3.76 and 4.53 eV, respectively, and the latter was the largest band gap in the A-M-C2O4-X (A = Monovalent cationic or alkaline earth metals, X = F, Cl, Br, I) family. They exhibit a large calculated birefringence of 0.075 and 0.096 at 1064 nm, respectively. This study promotes the exploration of synthesizing low-dimensional crystalline materials with balanced overall optical performances by a chemical scissors strategy.

Factors influencing passage of time judgment in individuals' daily lives: evidence from the experience sampling and diary methods.

People often express feeling that time passes quickly or slowly in their daily lives, which is termed passage of time judgment (PoTJ). Past studies have shown that PoTJ is affected by emotional valence and arousal; however, few studies have verified the effects of alertness, attention to time, and time expectation on PoTJ and whether the effects are stable over different time periods. Using the experience sampling method (ESM) and diary method, the present study collected data from 105 participants and examined for the first time whether alertness, attention to time, and time expectation affect PoTJ based on daily life data, as well as whether above factors, emotional valence, and arousal are stable over different time periods. All participants answered a questionnaire five times a day on their in-the-day PoTJ and related factors regarding the last 30 min, and answered the same questionnaire once a day at 23:00 regarding the of-the-day PoTJ. The results showed that alertness and time expectation, as well as emotional valence and arousal, predicted an individual's in-the-day PoTJ over a shorter period (i.e., the last 30 min); in contrast, only time expectation and emotional arousal predicted of-the-day PoTJ over a longer period (i.e., the past day). These results suggest that, alertness and time expectation are important factors influencing PoTJ, in addition to emotional state. Of-the-day PoTJ correlates most strongly with the mean and latest in-the-day PoTJ, implying that overall perception of time passage is influenced by both cumulative temporal experience and recent temporal experience.

Evaluating the Use of Vibrational Spectroscopy to Detect the Level of Adulteration of Cricket Powder in Plant Flours: The Effect of the Matrix.

Edible insects have been recognised as an alternative food or feed ingredient due to their protein value for both humans and domestic animals. The objective of this study was to evaluate the ability of both near- (NIR) and mid-infrared (MIR) spectroscopy to identify and quantify the level of adulteration of cricket powder added into two plant proteins: chickpea and flaxseed meal flour. Cricket flour (CKF) was added to either commercial chickpea (CPF) or flaxseed meal flour (FxMF) at different ratios of 95:5% w/w, 90:10% w/w, 85:15% w/w, 80:20% w/w, 75:25% w/w, 70:30% w/w, 65:35% w/w, 60:40% w/w, or 50:50% w/w. The mixture samples were analysed using an attenuated total reflectance (ATR) MIR instrument and a Fourier transform (FT) NIR instrument. The partial least squares (PLS) cross-validation statistics based on the MIR spectra showed that the coefficient of determination (R2CV) and the standard error in cross-validation (SECV) were 0.94 and 6.68%, 0.91 and 8.04%, and 0.92 and 4.33% for the ALL, CPF vs. CKF, and FxMF vs. CKF mixtures, respectively. The results based on NIR showed that the cross-validation statistics R2CV and SECV were 0.95 and 3.16%, 0.98 and 1.74%, and 0.94 and 3.27% using all the samples analyzed together (ALL), the CPF vs. CKF mixture, and the FxMF vs. CKF mixture, respectively. The results of this study showed the effect of the matrix (type of flour) on the PLS-DA data in both the classification results and the PLS loadings used by the models. The different combination of flours (mixtures) showed differences in the absorbance values at specific wavenumbers in the NIR range that can be used to classify the presence of CKF. Research in this field is valuable in advancing the application of vibrational spectroscopy as routine tools in food analysis and quality control.

Whole-Genome Survey Analyses of Five Goby Species Provide Insights into Their Genetic Evolution and Invasion-Related Genes.

As one of the most abundant groups in marine fish families, Gobiidae fish are important fishery resources in China, and some are also invasive species in certain regions worldwide. However, the phylogenetic relationships of Gobiidae fish remain ambiguous, and the study of their invasion-related genes is still scarce. This study used high-throughput sequencing technology to conduct a whole-genome survey of five Gobiidae fish species: Acanthogobius flavimanus, Acanthogobius stigmothonus, Favonigobius gymnauchen, Ctenotrypauchen microcephalus, and Tridentiger barbatus. De novo assembly of five fish genomes was performed, and genomic traits were compared through K-mer analysis. Among the five Gobiidae fish genomes, F. gymnauchen had the largest genome size (1601.98 Mb) and the highest heterozygosity (1.56%) and repeat rates (59.83%). Phylogenetic studies showed that A. flavimanus was most closely linked to A. stigmothonus, while Apogonidae and Gobiidae were closely related families. PSMC analysis revealed that C. microcephalus experienced a notable population expansion than the other four fish species in the Early Holocene. By using the KOG, GO, and KEGG databases to annotate single-copy genes, the annotated genes of the five fish were mainly classified as "signal transduction mechanisms", "cellular process", "cellular anatomical entity", and "translation". Acanthogobius flavimanus, A. stigmothonus, and T. barbatus had more genes classified as "response to stimulus" and "localization", which may have played an important role in their invasive processes. Our study also provides valuable material about Gobiidae fish genomics and genetic evolution.

Biodiversity conservation and management of lake wetlands based on the spatiotemporal evolution patterns of crane habitats.

The typical lake wetlands in the middle and lower reaches of the Yangtze River are important wintering sites of cranes in China. The spatiotemporal evolution of crane populations and their habitats has great value in clarifying the pivotal role of regional lake wetlands in biodiversity conservation. Therefore, 2562 data points of four crane species were selected in this study. The data reflected the distributional position of the cranes over the period 2000-2020. Twelve surrounding environmental factors were selected to investigate the spatiotemporal evolution in the study area by using the MaxEnt model. The Jackknife method was used to identify the main environmental factors affecting the choice of crane habitats. The results indicated that: (1) Developed land in the study area increased by 42,795.81 hm2. The crane populations were mainly distributed in the farmland and mudflat, and their number decreased yearly. (2) From 2000 to 2020, the area of suitable crane habitat experienced an overall decrease. Specifically, the mid-suitable area dwindled by 6234.23 hm2, marking a substantial reduction of 52.05 %. Similarly, the most suitable area saw a decline of 786.41 hm2, representing a noteworthy decrease of 71.09 %. (3) The findings from the analysis of influencing factors revealed a dynamic pattern over the years. Habitat type, water density, and distance to water were the main influencing factors in the study area from 2000 to 2020. This study provides a new perspective on the conservation and structural habitat restoration of crane populations in the middle and lower reaches of the Yangtze River.

Electronic Modulation Induced by Ni-VN Heterojunction Reinforces Electrolytic Hydrogen Evolution Coupled with Biomass Upgrade.

The renewable electricity-driven hydrogen evolution reaction (HER) coupled with biomass oxidation is a powerful avenue to maximize the energy efficiency and economic feedback, but challenging. Herein, porous Ni-VN heterojunction nanosheets on nickel foam (Ni-VN/NF) are constructed as a robust electrocatalyst to simultaneously catalyze HER and 5-hydroxymethylfurfural electrooxidation reaction (HMF EOR). Benefiting from the surface reconstruction of Ni-VN heterojunction during the oxidation process, the derived NiOOH-VN/NF energetically catalyzes HMF into 2,5-furandicarboxylic acid (FDCA), yielding the high HMF conversion (>99%), FDCA yield (99%), and Faradaic efficiency (>98%) at the lower oxidation potential along with the superior cycling stability. Ni-VN/NF is also surperactive for HER, exhibiting an onset potential of ≈0 mV and Tafel slope of 45 mV dec-1 . The integrated Ni-VN/NF||Ni-VN/NF configuration delivers a compelling cell voltage of 1.426 V at 10 mA cm-2 for the H2 O-HMF paired electrolysis, about 100 mV lower than that for water splitting. Theoretically, for Ni-VN/NF, the superiority in HMF EOR and HER is mainly dominated by the local electronic distribution at the heterogenous interface, which accelerates the charge transfer and optimize the adsorption of reactants/intermediates by modulating the d-band center, therefore being an advisable thermodynamic and kinetic process.

Altered brain structure in preschool-aged children with tetralogy of Fallot.

BACKGROUND: Neurodevelopmental abnormalities are prevalent in children with tetralogy of Fallot. Our aim was to investigate the structural brain alterations of preschool-aged children with tetralogy of Fallot and its correlation with neurodevelopmental outcome. METHODS: T1-weighted structural images were obtained from 25 children with tetralogy of Fallot who had undergone cardiopulmonary bypass surgery and from 24 normal controls. Cortical morphological indices including gray matter volume, cortical thickness, sulcal depth, gyrification, and cortical surface complexity were compared between the two groups. Neurodevelopmental assessments of the children with tetralogy of Fallot were performed with the Wechsler Preschool and Primary Scale of Intelligence. RESULTS: Cortical morphological differences between groups were distributed throughout the right caudal middle frontal gyrus, right fusiform gyrus, right lateral occipital gyrus, right precuneus, and left inferior parietal lobule. Among children with tetralogy of Fallot, altered cortical structures were correlated with the visual spatial index, working memory index, and perioperative variables. CONCLUSION: Our results suggested that abnormal cortical structure in preschool-aged children with tetralogy of Fallot may be the persistent consequence of delayed cortical development in fetuses and cortical morphology can be used as an early potential biomarker to capture regional brain abnormalities that are relevant to neurodevelopmental outcomes. IMPACT: Altered cortical structures in preschool-aged children with ToF were correlated with both neurodevelopmental outcomes and clinical risk factors. Cortical morphology can be used as an effective tool to evaluate neuroanatomical changes and detect underlying neural mechanisms in ToF patients. Abnormal cortical structure may be the continuous consequence of delayed fetal brain development in children with ToF.

The Impact of Broader Value Elements on Cost-Effectiveness Analysis: Two Case Studies.

OBJECTIVES: This study aimed to explore the impact of including broader value elements in cost-effectiveness analyses by presenting 2 case studies, one on human papillomavirus (HPV) infection and one on early-stage Hodgkin's lymphoma (ESHL). METHODS: We identified broader value elements (eg, patient and caregiver time, spillover health effects, productivity) from the Second Panel's Impact Inventory and the ISPOR Special Task Force's value flower. We then evaluated the cost-effectiveness of HPV vaccination versus no vaccination (case 1) and combined modality therapy (CMT) versus chemotherapy alone for treatment of adult ESHL (case 2) using published simulation models. For each case study, we compared incremental cost-effectiveness ratios considering health sector impacts only (the "base-case" scenario) with incremental cost-effectiveness ratios incorporating broader value elements. RESULTS: For vaccination of US girls against HPV before sexual debut versus no vaccination, the base-case result was $38 334 per disability-adjusted life-year averted. Including each broader value element made cost-effectiveness progressively more favorable, with HPV vaccination becoming cost-saving (ie, reducing costs and averting more disability-adjusted life-years) when the analysis incorporated productivity costs. For CMT versus chemotherapy alone in patients with ESHL, the base-case result indicated that CMT was cost-saving. Including all elements made this treatment's net monetary benefits (the sum of its averted resource costs and the net value of its health impacts) less favorable, even as the contribution from CMT's near-term health benefits grew. CONCLUSIONS: Including broader value elements can substantially influence cost-effectiveness ratios, although the direction and the magnitude of their impact can differ across interventions and disease context.