Phthalate alternatives and their monoesters in indoor dust from several regions, China and implications for human exposure.

Household products, in response to regulations, increasingly incorporate phthalate (PAE) alternatives instead of traditional PAEs. However, limited information exists regarding the fate and exposure risk of these PAE alternatives and their monoesters in indoor environments. The contamination levels of PAE alternatives and their monoesters in indoor dust might vary across regions due to climate, population density, industrial activities, and interior decoration practices. By analyzing indoor dust samples from six geographical regions across China, this study aims to shed light on concentrations, profiles, and human exposure to 12 PAE alternatives and 9 their monoesters. Bis(2-ethylhexyl) benzene-1,4-dicarboxylate (DEHTP), tributyl 2-acetyloxypropane-1,2,3-tricarboxylate (ATBC), and tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (TOTM) were the main PAE alternatives in dust across all regions. The total concentrations of 12 PAE alternatives ranged from 0.125 to 4160 µg/g in indoor dust. High molecular weight PAE alternatives had significantly correlated concentrations (p < 0.05) based on Spearman analysis, suggesting their co-use in heat-resistant plastic products. A collective of nine monoesters were identified in most samples, with total concentrations ranging from 0.048 to 29.6 µg/g. The median concentrations of PAE alternatives were highest in North China (66.8 µg/g), while those of monoesters were highest in Southwest China (6.93 µg/g). A significant correlation (p < 0.05) between the concentrations of DEHTP and its monoester suggested that degradation could be a potential source of monoesters. Although hazard quotients (HQs) have been calculated to suggest that the current exposure is unlikely to pose a significant health risk, the lack of toxicity threshold data and the existence of additional exposure pathways necessitate a further confirmation.

Automatic detection of adenoid hypertrophy on cone-beam computed tomography based on deep learning.

INTRODUCTION: This study proposed an automatic diagnosis method based on deep learning for adenoid hypertrophy detection on cone-beam computed tomography. METHODS: The hierarchical masks self-attention U-net (HMSAU-Net) for segmentation of the upper airway and the 3-dimensional (3D)-ResNet for diagnosing adenoid hypertrophy were constructed on the basis of 87 cone-beam computed tomography samples. A self-attention encoder module was added to the SAU-Net to optimize upper airway segmentation precision. The hierarchical masks were introduced to ensure that the HMSAU-Net captured sufficient local semantic information. RESULTS: We used Dice to evaluate the performance of HMSAU-Net and used diagnostic method indicators to test the performance of 3D-ResNet. The average Dice value of our proposed model was 0.960, which was superior to the 3DU-Net and SAU-Net models. In the diagnostic models, 3D-ResNet10 had an excellent ability to diagnose adenoid hypertrophy automatically with a mean accuracy of 0.912, a mean sensitivity of 0.976, a mean specificity of 0.867, a mean positive predictive value of 0.837, a mean negative predictive value of 0.981, and a F1 score of 0.901. CONCLUSIONS: The value of this diagnostic system lies in that it provides a new method for the rapid and accurate early clinical diagnosis of adenoid hypertrophy in children, allows us to look at the upper airway obstruction in three-dimensional space and relieves the work pressure of imaging doctors.

The CSRP2BP histone acetyltransferase drives smooth muscle gene expression.

The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression.

Serum response factor micromanaging cardiogenesis.

Serum response factor (SRF), a cardiac-enriched transcription factor, is required for the appearance of beating sarcomeres in the heart. SRF may also direct the expression of microRNAs (miRs) that inhibit the expression of cardiac regulatory factors. The recent knockout of miR-1-2, an SRF gene target, showed defective heart development, caused in part by the induction of GATA6, Irx4/5, and Hand2, that may alter cardiac morphogenesis, channel activity, and cell cycling. SRF and cofactors play an obligatory role in cardiogenesis, as major determinants of myocyte differentiation not only by regulating the biogenesis of muscle contractile proteins but also by driving the expression of silencer miRNA.

Effect of Co-doping on the electrochromic performance of hexagonal phase WO3 nanorods.

In this study, cobalt-doped hexagonal phase WO3 nanorods were prepared by a template-free hydrothermal method. The effects of varying the cobalt doping concentration on the microscopic morphology and electrochromic properties of hexagonal phase WO3 films were investigated. Films synthesized with the optimal cobalt element doping concentration demonstrate a notable improvement in their electrochromic properties compared to the pure hexagonal phase WO3 films. The film doped with 1.5% Co exhibited excellent cycling stability, retaining 98.55% of its original value after 500 cycles. The introduction of cobalt results in the formation of a nanorod structure with a high specific surface area within the film. This structure provides additional reaction sites for the electrochromic reaction process, thereby enhancing the optical modulation and coloration efficiency of WO3. The resulting films with excellent electrochromic properties provide a convenient and effective means for ion-doped modification of WO3-based electrochromic films.

Intercalation Electrode and Grain Reconstruction Induce Significant Sensitivity Enhancement for Perovskite X-ray Detectors.

Organic-inorganic hybrid perovskites have been recognized as potential candidates in direct X-ray detectors and have triggered tremendous interest in the past years. The blade coating method meets the requirements of large area and low cost for perovskite X-ray detectors, while the low compactness resulting from solvent evaporation limits the charge collection efficiency (CCE) and device sensitivity. Most of the reports are focused on the melioration of perovskite films to increase device sensitivity; there are still problems of low CCE. Herein, we introduce an intercalation-electrode device structure and achieve a ∼20-fold sensitivity enhancement. Carrier distribution throughout the thick films is simulated, and the electrode intercalating site can be optimized according to the mobility-lifetime factor to achieve the highest CCE. A methylamine thiocyanate (MASCN) additive-assisted coating strategy is developed, and pinhole free thick films with regrown particles are obtained without frequently used hot/soft pressing. A sensitivity level of ∼105 µC Gyair-1 cm-2 as well as a detection limit of 77 nGyair s-1 is achieved under low bias, which is among the best performance for polycrystalline perovskite direct X-ray detectors. This work provides a universal device structure design to overcome carrier loss through a long transport distance and enhances the CCE for ultrahigh sensitivity.

Ginsenoside Rg5 alleviates Ang II-induced cardiac inflammation and remodeling by inhibiting the JNK/AP-1 pathway.

Increased level of Angiotensin II (Ang II) contributes to hypertensive heart failure via -hemodynamic and non-hemodynamic actions. Ginsenoside Rg5 (Rg5) occurs naturally in ginseng, which has shown various benefits for cardiovascular diseases. This study evaluated Rg5's effects on Ang II-caused cardiac remodeling and heart failure. C57BL/6 mice developed hypertensive cardiac failure after four weeks of Ang II infusion. The mice were administered Rg5 via oral gavage for the last two weeks to investigate the potential mechanism of Rg5. RNA sequencing of heart tissues was performed for mechanistic studies. It was discovered that Rg5 inhibited cardiac inflammation, myocardial fibrosis, and hypertrophy, and prevented cardiac malfunction in mice challenged with Ang II, without altering blood pressure. RNA sequencing showed that Rg5's cardioprotective effect involves the JNK/AP-1 signaling pathway. Rg5 diminished inflammation in mice hearts and cultured cardiomyocytes by blocking Ang II-activated JNK/AP-1 pathway. In the absence of JNK or AP-1 in cardiomyocytes, the anti-inflammatory effects of Rg5 were nullified. The study found that Rg5 preserved the hearts of Ang II-induced mice by reducing JNK-mediated inflammatory responses, suggesting that Rg5 is an effective therapy for hypertensive heart failure.

The molecular recognition of cordycepin arabinoside and analysis of changes on cordycepin and its arabinoside in fruiting body and pupa of Cordyceps militaris.

Cordyceps militaris is an edible fungus that is widely used as a functional food in many countries. In order to objectively evaluate its nutritional value, free and glycosidic cordycepins need to be analyzed. The cordycepin arabinoside molecule was recognized by the MS2 fragmentation rule, and both cordycepin and its arabinoside were quantitatively analyzed in the fruiting body and pupa of Cordyceps militaris by high-performance liquid chromatography with tandem mass spectrometric (HPLC-MS/MS). The method had good linear regression (R2 = 0.9999), with a detection limit of 0.021 ng/mL. The recovery range was 94.32-103.09% in the fruiting body and pupa. The content of cordycepin and its arabinoside showed an upward trend with growth, and the total contents reached the highest level at the mature stage (60-70th day) without mildew. This study provides a useful reference for the evaluation and application of Cordyceps militaris as a functional food resource.

Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts.

Myocardin, a serum response factor (SRF)-dependent cofactor, is a potent activator of smooth muscle gene activity but a poor activator of cardiogenic genes in pluripotent 10T1/2 fibroblasts. Posttranslational modification of GATA4, another myocardin cofactor, by sumoylation strongly activated cardiogenic gene activity. Here, we found that myocardin's activity was strongly enhanced by SUMO-1 via modification of a lysine residue primarily located at position 445 and that the conversion of this residue to arginine (K445R) impaired myocardin transactivation. PIAS1 was involved in governing myocardin activity via its E3 ligase activity that stimulated myocardin sumoylation on an atypical sumoylation site(s) and by its physical association with myocardin. Myocardin initiated the expression of cardiac muscle-specified genes, such as those encoding cardiac alpha-actin and alpha-myosin heavy chain, in an SRF-dependent manner in 10T1/2 fibroblasts, but only in the presence of coexpressed SUMO-1/PIAS1. Thus, SUMO modification acted as a molecular switch to promote myocardin's role in cardiogenic gene expression.

Quercetin liposomes ameliorate streptozotocin-induced diabetic nephropathy in diabetic rats.

The effects of quercetin liposomes (Q-PEGL) on streptozotocin (STZ)-induced diabetic nephropathy (DN) was investigated in rats. Male Sprague Dawley rats were used to establish a STZ induced DN model. DN rats randomly received one of the following treatments for 8 weeks: blank treatment (DN), free quercetin (Que), pegylated liposomes (PEGL) and pegylated quercetin liposomes (Q-PEGL). A group of healthy rats served as the normal control. The fasting blood glucose (FBG), body weights (BWs), renal hypertrophy index (rHI), serum and urine biochemistry, renal histopathology, oxidative stress and immunohistochemical measurements of AGEs were analyzed to compare the effect of different treatments. Que and Q-PEGL significantly improved DN biochemistry and pathological changes, although the treated rats still had some symptoms of DN. The therapeutic effect of Q-PEGL surpassed that of Que. Pegylated quercetin liposomes allow maintaining higher quercetin concentrations in plasma than non-encapsulated quercetin. In conclusion the use of quercetin liposomes allows to reduce disease symptoms in a rat model of DN.

Targeted expression of receptor-associated late transducer inhibits maladaptive hypertrophy via blocking epidermal growth factor receptor signaling.

Receptor-associated late transducer (RALT) is a feedback inhibitor of epidermal growth factor receptor signaling. RALT has been shown previously to be induced in the ischemic heart and to promote cardiomyocyte apoptosis in vitro. However, the role of RALT in cardiac hypertrophy remains unclear. We hypothesized that forced expression of RALT in the murine heart would protect the heart against cardiac hypertrophy in vivo. We investigated the effect of cardiac overexpression of rat RALT on cardiac hypertrophy induced by angiotensin II and isoproterenol in RALT transgenic mice and wild-type littermates. The extent of cardiac hypertrophy was assessed by 2D and M-mode echocardiography as well as by molecular and pathological analyses of cardiac samples. Constitutive expression of rat RALT in cardiac myocytes of murine heart attenuated both hypertrophic and inflammatory responses and preserved cardiac function. These beneficial effects were associated with the attenuation of the epidermal growth factor receptor-dependent cascade that was triggered by angiotensin II and isoproterenol stimulation. Additional evidence demonstrated that RALT expression blocked fibrosis in vivo and collagen synthesis in vitro. Therefore, cardiac overexpression of RALT improves cardiac function and inhibits maladaptive hypertrophy, inflammation, and fibrosis through attenuating epidermal growth factor receptor-dependent signaling.

Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.

MicroRNAs (miRNAs) are genomically encoded small RNAs used by organisms to regulate the expression of proteins generated from messenger RNA transcripts. The in vivo requirement of specific miRNAs in mammals through targeted deletion remains unknown, and reliable prediction of mRNA targets is still problematic. Here, we show that miRNA biogenesis in the mouse heart is essential for cardiogenesis. Furthermore, targeted deletion of the muscle-specific miRNA, miR-1-2, revealed numerous functions in the heart, including regulation of cardiac morphogenesis, electrical conduction, and cell-cycle control. Analyses of miR-1 complementary sequences in mRNAs upregulated upon miR-1-2 deletion revealed an enrichment of miR-1 "seed matches" and a strong tendency for potential miR-1 binding sites to be located in physically accessible regions. These findings indicate that subtle alteration of miRNA dosage can have profound consequences in mammals and demonstrate the utility of mammalian loss-of-function models in revealing physiologic miRNA targets.

Receptor-ligand interaction between vitellogenin receptor (VtgR) and vitellogenin (Vtg), implications on low density lipoprotein receptor and apolipoprotein B/E. The first three ligand-binding repeats of VtgR interact with the amino-terminal region of Vtg.

The vitellogenin receptor (VtgR) belongs to the low density lipoprotein receptor (LDLR) gene family. It mediates the uptake of vitellogenin (Vtg) in oocyte development of oviparous animals. In this study, we cloned and characterized two forms of Oreochromis aureus VtgR. Northern analysis showed that VtgR was specifically expressed in ovarian tissues. However, reverse transcription-PCR indicates that either there are trace levels of expression of VtgR or a homolog of LDLR exists in nonovarian tissues. The VtgR is highly homologous to the very low density lipoprotein receptor. To better understand the mechanism by which similar structural modules in the ligand-binding domain bind different ligands, we used the yeast two-hybrid system to screen for the minimal interaction motifs in Vtg and VtgR. The amino-terminal region of the lipovitellin I domain of Vtg interacts with the ligand-binding domain of VtgR. The first three ligand-binding repeats of the receptor were found to be essential for ligand binding. Computational analysis of the binding sequence indicates that Vtg has a similar receptor-binding region to apolipoprotein (apo) E and apoB. Site-directed mutagenesis of this region indicates electrostatic interaction between Vtg and its receptor. Sequence analysis suggests the coevolution of receptor-ligand pairs for the LDLR/apo superfamily and suggests that the mode of binding of LDLR/very low density lipoprotein receptor to apoB and apoE is inherited from the electrostatic attraction of VtgR and Vtg.