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Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)-a transcription factor known to regulate expression of actin and actin regulators in other cell types-as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the mechanistic role of SRF in oligodendrocyte lineage cells. Here, we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in oligodendrocyte precursor cells and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Surprisingly, oligodendrocyte-restricted loss of SRF results in upregulation of gene signatures associated with aging and neurodegenerative diseases. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies an essential pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.

A computational investigation of New MEXICO test cases operating under axial flow conditions is reported. Three wind speed cases (10, 15, 24 m/s) corresponding to three different tip speed ratios (10, 6.67, 4.17) when the turbine operates at 425.1 rpm were considered. ANSYS CFX 2021R1 was employed to perform simulations using Single Reference Frame (SRF) and Multiple Reference Frame (MRF) approaches. The flow field is computed by solving unsteady Reynolds Averaged Navier-Stokes (uRANS) equations coupled with SST k - ω turbulence model and Gamma-Theta transition model. Validation involved comparing CFD-predicted integral quantities, static pressure distributions, and loads with corresponding experimental values demonstrating reasonably good agreement at all three wind speeds. Overall, SRF exhibited slightly better wake predictions (hypothetical), while MRF predictions were closer to measurements for integral quantities, static pressure and loads. This study demonstrates the utility of uRANS-based 3D CFD computations in wind turbine aerodynamics studies. [ABSTRACT FROM AUTHOR]

Abstract Background Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-β (TGF-β), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-β remain poorly understood. Methods The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-β-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. Results KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-β-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-β-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-β treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. Conclusion Our results shed light on KAT14 as a key effector of TGF-β–induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis.

Abstract The transcription factor TRPS1 is a context-dependent oncogene in breast cancer. In the mammary gland, TRPS1 activity is restricted to the luminal population and is critical during puberty and pregnancy. Its function in the resting state remains however unclear. To evaluate whether it could be a target for cancer therapy, we investigated TRPS1 function in the healthy adult mammary gland using a conditional ubiquitous depletion mouse model where long-term depletion does not affect fitness. Using transcriptomic approaches, flow cytometry and functional assays, we show that TRPS1 activity is essential to maintain a functional luminal progenitor compartment. This requires the repression of both YAP/TAZ and SRF/MRTF activities. TRPS1 represses SRF/MRTF activity indirectly by modulating RhoA activity. Our work uncovers a hitherto undisclosed function of TRPS1 in luminal progenitors intrinsically linked to mechanotransduction in the mammary gland. It may also provide new insights into the oncogenic functions of TRPS1 as luminal progenitors are likely the cells of origin of many breast cancers.

Background: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-β (TGF-β), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-β remain poorly understood. Methods: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-β-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. Results: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-β-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-β-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-β treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. Conclusion: Our results shed light on KAT14 as a key effector of TGF-β–induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis. [ABSTRACT FROM AUTHOR]

Fifth Generation (5G) Technology, representing the latest advancement in wireless communication networks, has brought attention to the rising concerns regarding Specific Absorption Rate (SAR) due to temperature fluctuations. The negative impacts of SAR, particularly in the context of mobile users' head exposure, have prompted the exploration of effective mitigation strategies. This article introduces a novel approach, employing a Planar Inverted F-Antenna (PIFA) operating at 26 GHz, with the integration of RF shields, specifically a flexible ferrite sheet and a foam absorber, aimed at reducing SAR in the human head. Dosimetry investigations, conducted at frequencies exceeding 26 GHz, reveal that SAR values without shielding materials (1.59 W/kg) approach the safety limit of SAR. The incorporation of ferrite and foam absorber leads to SAR reductions of 1.53 and 1.48 W/kg, respectively. Notably, the proposed antenna demonstrates significant SAR Reduction Factor (SRF) values, particularly at 5G network frequencies (26 GHz). Comparative analysis highlights the superior performance of the foam absorber across various parameters. The prototype of the proposed antenna has been fabricated and subjected to testing, affirming its potential for alleviating SAR in the context of 5G technology. [ABSTRACT FROM AUTHOR]

Background: Serum response factor (SRF) and myocardial‐associated transcription factor‐A (MRTF‐A) had different regulatory effects on the tumorigenesis and development in different cancers. However, the role of MRTF‐A/SRF in oral squamous cell carcinoma (OSCC) remains to be determined. Methods: CCK‐8 assay, cell scratch experiment, and transwell invasion assay were conducted to investigate the effects of MRTF‐A/SRF on biological behavior of OSCC cells. The expression pattern and prognostic value of MRTF‐A/SRF in OSCC were analyzed based on cBioPortal website and TCGA database. Protein–protein interaction network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to investigate related pathways. The effect of MRTF‐A/SRF on epithelial–mesenchymal transformation (EMT) of OSCC cells was explored by western blot assay. Results: Overexpression of MRTF‐A/SRF inhibited the proliferation, migration, and invasion of OSCC cells in vitro. High expression of SRF was related to better prognosis of OSCC patients on hard palate, alveolar ridge, and oral tongue. Besides, overexpression of MRTF‐A/SRF inhibited the EMT of OSCC cells. Conclusion: SRF was closely related to the prognosis of OSCC. High expression of SRF and its co‐activator MRTF‐A inhibited proliferation, migration, and invasion of OSCC cells in vitro, possibly via EMT suppression. [ABSTRACT FROM AUTHOR]

The transcription factor TRPS1 is a context-dependent oncogene in breast cancer. In the mammary gland, TRPS1 activity is restricted to the luminal population and is critical during puberty and pregnancy. Its function in the resting state remains however unclear. To evaluate whether it could be a target for cancer therapy, we investigated TRPS1 function in the healthy adult mammary gland using a conditional ubiquitous depletion mouse model where long-term depletion does not affect fitness. Using transcriptomic approaches, flow cytometry and functional assays, we show that TRPS1 activity is essential to maintain a functional luminal progenitor compartment. This requires the repression of both YAP/TAZ and SRF/MRTF activities. TRPS1 represses SRF/MRTF activity indirectly by modulating RhoA activity. Our work uncovers a hitherto undisclosed function of TRPS1 in luminal progenitors intrinsically linked to mechanotransduction in the mammary gland. It may also provide new insights into the oncogenic functions of TRPS1 as luminal progenitors are likely the cells of origin of many breast cancers. [ABSTRACT FROM AUTHOR]

During the progression of pleural fibrosis, pleural mesothelial cells (PMCs) undergo a phenotype switching process known as mesothelial–mesenchymal transition (MesoMT). During MesoMT, transformed PMCs become myofibroblasts that produce increased extracellular matrix (ECM) proteins, including collagen and fibronectin (FN1) that is critical to develop fibrosis. Here, we studied the mechanism that regulates FN1 expression in myofibroblasts derived from human pleural mesothelial cells (HPMCs). We found that myocardin (Myocd), a transcriptional coactivator of serum response factor (SRF) and a master regulator of smooth muscle and cardiac muscle differentiation, strongly controls FN1 gene expression. Myocd gene silencing markedly inhibited FN1 expression. FN1 promoter analysis revealed that deletion of the Smad3-binding element diminished FN1 promoter activity, whereas deletion of the putative SRF-binding element increased FN1 promoter activity. Smad3 gene silencing decreased FN1 expression, whereas SRF gene silencing increased FN1 expression. Moreover, SRF competes with Smad3 for binding to Myocd. These results indicate that Myocd activates FN1 expression through Smad3, whereas SRF inhibits FN1 expression in HPMCs. In HPMCs, TGF-β induced Smad3 nuclear localization, and the proximity ligation signal between Myocd and Smad3 was markedly increased after TGF-β stimulation at nucleus, suggesting that TGF-β facilitates nuclear translocation of Smad3 and interaction between Smad3 and Myocd. Moreover, Myocd and Smad3 were coimmunoprecipitated and isolated Myocd and Smad3 proteins directly bound each other. Chromatin immunoprecipitation assays revealed that Myocd interacts with the FN1 promoter at the Smad3-binding consensus sequence. The results indicate that Myocd regulates FN1 gene activation through interaction and activation of the Smad3 transcription factor. NEW & NOTEWORTHY: During phenotype switching from mesothelial to mesenchymal, pleural mesothelial cells (PMCs) produce extracellular matrix (ECM) proteins, including collagen and fibronectin (FN1), critical components in the development of fibrosis. Here, we found that myocardin, a transcriptional coactivator of serum response factor (SRF), strongly activates FN1 expression through Smad3, whereas SRF inhibits FN1 expression. This study provides insights about the regulation of FN1 that could lead to the development of novel interventional approaches to prevent pleural fibrosis. [ABSTRACT FROM AUTHOR]

Silicon carbide (SiC) based inverters are widely used due to their fast switching and ability to withstand high temperatures and Voltage. This helps to increase efficiency and reduces switching losses compared to the silicon-based inverter. However, this fast-switching device causes an increase in the Voltage at the junction of the cable and motor due to the reflected wave. The main causes of overvoltage are cable/motor impedance mismatch, fast-switching inverter devices (IGBT), and inverter-motor separation. To extend the induction motor lifespan, overvoltage reduction is necessary. Passive and active filters solve the problem, but passive filters are bulky and have high power loss. This paper presents a shunt active filter approach for an inverter-fed induction motor to reduce overvoltage. To show the effectiveness of the proposed approach, the findings were compared to the topology of the clamp-type active filter already in use. The shunt active filter used Proportional Integral (PI) and fuzzy controllers to generate reference current according to the Synchronous Reference Frame (SRF) theory. Harmonics in the power system were removed using the SRF theory. The unique aspect of this work is how the reference current is produced in the shunt active filter using the SRF theory. The proposed shunt active filter with a fuzzy controller was added to the hardware implementation to achieve better results than previous active filters. [ABSTRACT FROM AUTHOR]

Fifth Generation (5G) Technology, representing the latest advancement in wireless communication networks, has brought attention to the rising concerns regarding Specific Absorption Rate (SAR) due to temperature fluctuations. The negative impacts of SAR, particularly in the context of mobile users' head exposure, have prompted the exploration of effective mitigation strategies. This article introduces a novel approach, employing a Planar Inverted F-Antenna (PIFA) operating at 26 GHz, with the integration of RF shields, specifically a flexible ferrite sheet and a foam absorber, aimed at reducing SAR in the human head. Dosimetry investigations, conducted at frequencies exceeding 26 GHz, reveal that SAR values without shielding materials (1.59 W/kg) approach the safety limit of SAR. The incorporation of ferrite and foam absorber leads to SAR reductions of 1.53 and 1.48 W/kg, respectively. Notably, the proposed antenna demonstrates significant SAR Reduction Factor (SRF) values, particularly at 5G network frequencies (26 GHz). Comparative analysis highlights the superior performance of the foam absorber across various parameters. The prototype of the proposed antenna has been fabricated and subjected to testing, affirming its potential for alleviating SAR in the context of 5G technology.

Artificial intelligence (AI)- and deep learning (DL)-based systems have shown significant progress in the field of macular disorders, demonstrating high performance in detecting retinal fluid and assessing anatomical changes during disease progression. This study aimed to validate an AI algorithm for identifying and quantifying prognostic factors in visual recovery after macular hole (MH) surgery by analyzing major optical coherence tomography (OCT) biomarkers. This study included 20 patients who underwent vitrectomy for a full-thickness macular hole (FTMH). The mean diameter of the FTMH was measured at 285.36 ± 97.4 μm. The preoperative best-corrected visual acuity (BCVA) was 0.76 ± 0.06 logMAR, improving to 0.38 ± 0.16 postoperatively, with a statistically significant difference (p = 0.001). AI software was utilized to assess biomarkers, such as intraretinal fluid (IRF) and subretinal fluid (SRF) volume, external limiting membrane (ELM) and ellipsoid zone (EZ) integrity, and retinal hyperreflective foci (HRF). The AI analysis showed a significant decrease in IRF volume, from 0.08 ± 0.12 mm3 preoperatively to 0.01 ± 0.01 mm3 postoperatively. ELM interruption improved from 79% ± 18% to 34% ± 37% after surgery (p = 0.006), whereas EZ interruption improved from 80% ± 22% to 40% ± 36% (p = 0.007) postoperatively. Additionally, the study revealed a negative correlation between preoperative IRF volume and postoperative BCVA recovery, suggesting that greater preoperative fluid volumes may hinder visual improvement. The integrity of the ELM and EZ was found to be essential for postoperative visual acuity improvement, with their disruption negatively impacting visual recovery. The study highlights the potential of AI in quantifying OCT biomarkers for managing MHs and improving patient care. [ABSTRACT FROM AUTHOR]

Suppressor of cancer cell invasion (SCAI) acts as a transcriptional repressor of serum response factor (SRF)‐mediated gene expression by binding to megakaryoblastic leukemia (MKL)/myocardin‐related transcription factor (MRTF), which is an SRF transcriptional coactivator. Growing evidence suggests that SCAI is a negative regulator of neuronal morphology, whereas MKL2/MRTFB is a positive regulator. The mRNA expression of SCAI is downregulated during brain development, suggesting that a reduction in SCAI contributes to the reduced suppression of SRF‐mediated gene induction, thus increasing dendritic complexity and developing neuronal circuits. In the present study, we hypothesized that brain‐derived neurotrophic factor (BDNF), which is important for neuronal plasticity and development, might alter SCAI mRNA levels. We therefore investigated the effects of BDNF on SCAI mRNA levels in primary cultured cortical neurons. Furthermore, because alternative splicing generates several SCAI variants in the brain, we measured SCAI variant mRNA after BDNF stimulation. Both SCAI variant 1 and total SCAI mRNA expression levels were downregulated by BDNF. Moreover, the extracellular signal‐regulated protein kinase/mitogen‐activated protein kinase (ERK/MAPK) pathway was involved in the BDNF‐mediated decrease in SCAI mRNA expression. Our findings provide insights into the molecular mechanism underlying a neurotrophic factor switch for the repressive transcriptional complex that includes SCAI. [ABSTRACT FROM AUTHOR]

Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, a highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral in orchestrating various vascular pathologies by modulating the phenotypic dynamics of VSMCs. The influence of CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk RNA sequencing, has uncovered a significant suppression of CARMN in AAA specimens, which correlates strongly with the contractile function of VSMCs. This reduced expression of CARMN was consistent in both 7- and 14-day porcine pancreatic elastase (PPE)-induced mouse models of AAA and in human clinical cases. Functional analyses disclosed that the diminution of CARMN exacerbated PPE-precipitated AAA formation, whereas its augmentation conferred protection against such formation. Mechanistically, we found CARMN's capacity to bind with SRF, thereby amplifying its role in driving the transcription of VSMC marker genes. In addition, our findings indicate an enhancement in CAMRN transcription, facilitated by the binding of NRF2 to its promoter region. Our study indicated that CARMN plays a protective role in preventing AAA formation and restrains the phenotypic transformation of VSMC through its interaction with SRF. Additionally, we observed that the expression of CARMN is augmented by NRF2 binding to its promoter region. These findings suggest the potential of CARMN as a viable therapeutic target in the treatment of AAA. [ABSTRACT FROM AUTHOR]

Background: Vascular smooth muscle cell (VSMC) proliferation is the leading cause of vascular stenosis or restenosis. Therefore, investigating the molecular mechanisms and pivotal regulators of the proliferative VSMC phenotype is imperative for precisely preventing neointimal hyperplasia in vascular disease. Methods: Wire-induced vascular injury and aortic culture models were used to detect the expression of staphylococcal nuclease domain-containing protein 1 (SND1). SMC-specific Snd1 knockout mice were used to assess the potential roles of SND1 after vascular injury. Primary VSMCs were cultured to evaluate SND1 function on VSMC phenotype switching, as well as to investigate the mechanism by which SND1 regulates the VSMC proliferative phenotype. Results: Phenotype-switched proliferative VSMCs exhibited higher SND1 protein expression compared to the differentiated VSMCs. This result was replicated in primary VSMCs treated with platelet-derived growth factor (PDGF). In the injury model, specific knockout of Snd1 in mouse VSMCs reduced neointimal hyperplasia. We then revealed that ETS transcription factor ELK1 (ELK1) exhibited upregulation and activation in proliferative VSMCs, and acted as a novel transcription factor to induce the gene transcriptional activation of Snd1. Subsequently, the upregulated SND1 is associated with serum response factor (SRF) by competing with myocardin (MYOCD). As a co-activator of SRF, SND1 recruited the lysine acetyltransferase 2B (KAT2B) to the promoter regions leading to the histone acetylation, consequently promoted SRF to recognize the specific CArG motif, and enhanced the proliferation- and migration-related gene transcriptional activation. Conclusions: The present study identifies ELK1/SND1/SRF as a novel pathway in promoting the proliferative VSMC phenotype and neointimal hyperplasia in vascular injury, predisposing the vessels to pathological remodeling. This provides a potential therapeutic target for vascular stenosis. [ABSTRACT FROM AUTHOR]

Skeletal myogenesis is an intricate process involving the differentiation of progenitor cells into myofibers, which is regulated by actin cytoskeletal dynamics and myogenic transcription factors. Although recent studies have demonstrated the pivotal roles of actin-binding proteins (ABPs) as mechanosensors and signal transducers, the biological significance of WAVE2 (Wiskott–Aldrich syndrome protein family member 2), an ABP essential for actin polymerization, in myogenic differentiation of progenitor cells has not been investigated. Our study provides important insights into the regulatory roles played by WAVE2 in the myocardin-related transcription factor A (MRTFA)–serum response factor (SRF) signaling axis and differentiation of myoblasts. We demonstrate that WAVE2 expression is induced during myogenic differentiation and plays a pivotal role in actin cytoskeletal remodeling in C2C12 myoblasts. Knockdown of WAVE2 in C2C12 cells reduced filamentous actin levels, increased globular actin accumulation, and impaired the nuclear translocation of MRTFA. Furthermore, WAVE2 depletion in myoblasts inhibited the expression and transcriptional activity of SRF and suppressed cell proliferation in myoblasts. Consequently, WAVE2 knockdown suppressed myogenic regulatory factors (i.e., MyoD, MyoG, and SMYD1) expressions, thereby hindering the differentiation of myoblasts. Thus, this study suggests that WAVE2 is essential for myogenic differentiation of progenitor cells by modulating the mechanosensitive MRTFA–SRF axis. [ABSTRACT FROM AUTHOR]

Sall1 and Sall4 (Sall1/4), zinc-finger transcription factors, are expressed in the progenitors of the second heart field (SHF) and in cardiomyocytes during the early stages of mouse development. To understand the function of Sall1/4 in heart development, we generated heart-specific Sall1/4 functionally inhibited mice by forced expression of the truncated form of Sall4 (ΔSall4) in the heart. The ΔSall4-overexpression mice exhibited a hypoplastic right ventricle and outflow tract, both of which were derived from the SHF, and a thinner ventricular wall. We found that the numbers of proliferative SHF progenitors and cardiomyocytes were reduced in ΔSall4-overexpression mice. RNA-sequencing data showed that Sall1/4 act upstream of the cyclin-dependent kinase (CDK) and cyclin genes, and of key transcription factor genes for the development of compact cardiomyocytes, including myocardin (Myocd) and serum response factor (Srf). In addition, ChIP-sequencing and co-immunoprecipitation analyses revealed that Sall4 and Myocd form a transcriptional complex with SRF, and directly bind to the upstream regulatory regions of the CDK and cyclin genes (Cdk1 and Ccnbl). These results suggest that Sall1/4 are critical for the proliferation of cardiac cells via regulation of CDK and cyclin genes that interact with Myocd and SRF. [ABSTRACT FROM AUTHOR]

The mercury content is among the parameters that characterise the quality of Solid Recovered Fuels (SRFs), which constitute alternative solid fuels of increasing interest. In this study, a direct mercury analyser was utilised in the analyses of SRF samples originating from Automotive Shredded Residues (ASRs). Two SRFs and one liquid reference material were measured to test the accuracy and sensitivity of the instrument. The mean values of the two SRFs and one liquid reference material (RM) were 0.171, 0.324 mg/kg, and 0.141 mg/L. These values were compared with the reference ones as follows: 0.168, 0.382 mg/kg, and 0.137 mg/L. Mercury content was detected in the analysis samples of four different particle sizes (8 mm, 2 mm, 1 mm, 0.5 mm, and 0.25 mm) for each SRF sample in order to demonstrate the direct mercury analyser operation and to compare it as an alternative to mercury determination via atomic absorption spectrometry. The measurements showed that grinding down to 1 mm was sufficient for most SRF cases while grinding down to 2 mm might be enough for a few cases. As an overall conclusion, the direct mercury analyser can be regarded as an efficient laboratory tool, offering a robust alternative to the atomic absorption spectrometry procedure, especially in terms of accuracy, speed, safety, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

This work offers a comprehensive examination of ICP-MS as a higher-level analytical method compared to atomic absorption spectrometry (AAS) and X-ray fluorescence (XRF). Comparisons between the ICP-MS average mean difference and AAS were made with the determination of the concentration of trace elements in the same solid alternative fuel samples, while comparisons between ICP-MS and XRF were made by the determination of the concentration of major elements in the same solid alternative fuel samples, resulting in the superiority of the method. The results of the relative mean differences (RDMs) between ICP-MS (7.56%) and XRF (9.42%) regarding the concentration of major elements compared with the reference values in solid biofuel samples, while the RDMs for the solid recovered fuel samples were 8.9% for ICP-MS and 12.27% for XRF. The same procedure was followed for the determination of the concentration of trace elements with ICP-MS and AAS, thus obtaining the results for solid biofuel samples (average %RMDICP-MS = 12.77 and RMDAAS = 13.9) and SRF samples (average %RMDICP-MS = 10.02 and RDMAAS = 11.10) in relation to the reference values. While acknowledging that the initial cost and complexity of operation may deter some from adopting ICP-MS, the study asserts that the advantages of enhanced precision, sensitivity and speed of analysis validate the investment. Hence, ICP-MS is an extremely important laboratory tool used in modern physics and chemistry and has a wide range of applications: biological materials, high purity reagents and metals, atomic nuclear materials, geological samples and food. [ABSTRACT FROM AUTHOR]

Abstract: The forming limit diagram (FLD) of high-purity niobium sheets used for the manufacturing of superconducting radiofrequency (SRF) cavities is presented. The Marciniak (in-plane) test was used with niobium blanks with a thickness of 1 mm and blank carriers of annealed oxygen-free electronic (OFE) copper. A high formability was measured, with an approximate true major strain at necking for plane strain of 0.44. The high formability of high-purity niobium is likely caused by its high strain rate sensitivity of 0.112. Plastic strain anisotropies (r-values) of 1.66, 1.00, and 2.30 were measured in the 0 deg, 45 deg, and 90 deg directions. However, stress–strain curves at a nominal strain rate of ∼10−3 s−1 showed similar mechanical properties in the three directions. Theoretical calculations of the forming limit curves (FLCs) were conducted using an analytical two-zone model. The obtained results indicate that the anisotropy and strain rate sensitivity of niobium affect its formability. The model was used to investigate the influence of strain rate on strains at necking. The obtained results suggest that the use of high-speed sheet forming should further increase the formability of niobium.

PurposeTo assess the early real-world clinical outcomes regarding safety and efficacy after ranizurel administration.MethodsA retrospective, consecutive, interventional, uncontrolled, multi-centre study was conducted incorporating data from four centres in India. 22 eyes with variable indications were included and all patients were treated with at least one intravitreal injection of ranizurel 0.5 mg between January 2021 and April 2021. Each patient underwent best-corrected visual acuity (BCVA) measurement with a Snellen chart (converted to LogMAR for analysis), central subfield thickness (CST) analysis with spectral-domain optical coherence tomography (SD-OCT) and intraocular pressure (IOP) measurement along with complete ophthalmic examination at baseline and the last follow-up for evaluation of adverse events after ranizurel injection.Results- None of the sites reported any signs of inflammation, vasculitis or any other ocular or systemic adverse effects in any of the cases. Mean BCVA at baseline was 0.48 ± 0.26 LogMAR (20/63) which improved significantly 0.26 ± 0.28 (20/40) at the last follow-up. (p = 0.001) Mean CST at baseline was 448.4 ± 122.9 μm which improved significantly to 328.3 ± 89.9 μm. (p = 0.001).Conclusion- The early real-world data from this limited series indicates that ranizurel is a safe alternative biologic for patients who were treatment-naive and in those who had undergone prior treatment with other anti-VEGF agents.

AbstractAn investigation of the tensile mechanical properties of electron beam welded OFE copper and high-purity niobium sheets is presented. Specimens were deformed in tension at strain rates ranging from 10−3 to ~ 1600 s−1. The 0.2% yield stress and ultimate tensile strength (UTS) of the welded niobium specimens are similar to those of unwelded specimens at strain rates lower or equal to 20 s−1. At higher strain rates, these mechanical properties are lower for welded niobium specimens. The 0.2% yield stress of welded OFE copper specimens is consistently lower than unwelded specimens over the range of strain rates studied, while the UTS is comparable at all strain rates. The elongation to failure of welded OFE copper specimens remains unchanged at all strain rates while the ductility of niobium specimens reduces at strain rates greater or equal to 20 s−1 and reaches a minimum at ~ 400 s−1. The effects of the weld on a non-standardized short specimen geometry, developed for this study to obtain strain rates in the order of 103 s−1, are more pronounced for niobium due to large grain sizes (up to 1200 μm) in the fusion region. However, comparable strength and ductility trends, with respect to a standard specimen, were measured at low strain rates. The conservation of strength and the relatively high ductility of the welded sheets, especially for OFE copper, suggest that bent and electron beam welded tubes could be used for the fabrication of seamless superconducting radiofrequency (SRF) cavities. These results are promising for the use of high-speed forming techniques, like electro-hydraulic forming, for the manufacturing of parts using welded tubes and sheets.

Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These SrfGFAP-ERCKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains of Srf knockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases, SrfGFAP-ERCKO astrocytes abrogate nigral dopaminergic neuron death and reduce β-amyloid plaques in mouse models of Parkinson’s and Alzheimer’s disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.

The role of serum response factor (Srf), a central mediator of actin dynamics and mechanical signaling, in cell identity regulation is debated to be either a stabilizer or a destabilizer. We investigated the role of Srf in cell fate stability using mouse pluripotent stem cells. Despite the fact that serum-containing cultures yield heterogeneous gene expression, deletion of Srf in mouse pluripotent stem cells leads to further exacerbated cell state heterogeneity. The exaggerated heterogeneity is detectible not only as increased lineage priming but also as the developmentally earlier 2C-like cell state. Thus, pluripotent cells explore more variety of cellular states in both directions of development surrounding naïve pluripotency, a behavior that is constrained by Srf. These results support that Srf functions as a cell state stabilizer, providing rationale for its functional modulation in cell fate intervention and engineering. [ABSTRACT FROM AUTHOR]

The peculiarities of waveforms of the P and S receiver functions, constructed from the records of three closely located broadband seismic stations, are studied. The stations are located in the Avacha Bay area, near the subducting part of the Pacific Plate. This is an inclined slab, which is characterized by higher seismic velocities and can cause complex patterns of seismic waves, thus distorting the waveforms of receiver functions. In order to reveal the degree of such influence, we calculated two pairs of receiver functions. To calculate the first pair, we used the seismic events where seismic waves traveled through the subducting oceanic slab; in the case of the second pair, the waves did not travel through the slab. It is shown that converted and multiple waves formed at the boundaries of the high-velocity layer considerable distort the shapes of P receiver functions beginning approximately 30 seconds after the main arrival. The subducting slab does not show any considerable effect on the records of the S receiver function. This fact empirically supports the applicability of local one-dimensional models for interpreting the receiver functions. The seismic noise, generated by the oceanic slab, limits the maximum depth of these models at around 200 km in the study area. [ABSTRACT FROM AUTHOR]

Natural compounds known as phytochemicals have served as valuable resources for the development of new anti-cancer drugs and treatment of malignancies. Among these phytochemicals, baicalein is an emerging anti-tumor flavonoid obtained from Scutellaria baicaleinsis (Lamiaceae), but its underlying mechanisms of action and molecular targets have not yet been completely elucidated. Here, we identified new mechanisms for the anti-tumor activities of baicalein, providing evidence that hyaluronan-mediated motility receptor (HMMR) and androgen receptor (AR) are new molecular targets of baicalein in human cancer cells. We observed that HMMR, known to be highly associated with poor prognosis in a wide range of human cancers, was substantially downregulated by baicalein at mRNA and protein levels. Reporter assays further revealed that the suppression of HMMR by baicalein might occur through a transcriptional regulatory mechanism with the participation of Egr-1, E2F3α, and serum response factor (SRF). We also found that baicalein significantly inhibits androgenic responses in hormone-responsive prostate cancer cells, indicating that this might be attributed to the downregulation of AR promoter activity by baicalein. Additionally, baicalein markedly induced the expression of tumor suppressive miR-30C, which might be partly involved in baicalein-mediated autophagy and anti-cancer effects. Overall, our study sheds light on new diverse mechanisms of the anti-cancer effects exhibited by baicalein, implying that baicalein could be a potential therapeutic agent against human cancers and function as an inhibitor of HMMR and AR. [ABSTRACT FROM AUTHOR]

Megawatt solar plants are the reality now with nations looking for GW installed capacity. This high power is possible because of increased power levels in photovoltaic (PV) energy conversion systems. The multilevel converter (MLC) is the emerging technology for interfacing medium and higher voltage grids. This paper gives the design and analysis of transformerless grid interfaced single-stage 43-level Cascaded H-bridge (CHB)-based MLC for integrating large-scale solar PV plants with improved Total Harmonic Distortion (THD). Transformerless integration and reduced filter size, due to improved THD, contribute appreciable savings in the Capital Expenditure and Operation and Maintenance cost of the big solar PV plant. This paper also showcases the design-based strategy for deciding the levels used in the MLC, making it both efficient and economical. The control scheme comprises voltage-oriented control (VOC) with synchronous reference frame (SRF) and phase-locked loop (PLL). The low-frequency phase-shifted pulse width modulation (PWM) suitable for the cascaded MLC is used for modulation. The separate incremental conductance (InC) algorithm is used for the extraction of maximum power from each solar PV array. This algorithm takes care of the unforeseen insolation level changes, shading effect, ambient temperature, and other related factors of the multi-string SPV system. The simulation is performed in MATLAB/Simulink and validated on an OPAL RT simulator. Both steady-state and dynamic behaviors at different insolation levels of the considered system are studied. The performance is validated as per the IEEE-519 standard requirement. Decent decrease in THD of grid current is observed with low switching losses. [ABSTRACT FROM AUTHOR]

The disposal of laundry wastewater into the septic tank and the condition of the septic tank in the IPLT Balai PIALAM service area which does not meet the quality standards caused the fecal sludge product from the IPLT Balai PIALAM difficult to dry because of the high water content and it still emits pungent smell. IPLT Balai PIALAM has carried out the process of increasing the operating unit and dewatering process unit but has not yet obtained optimum dewatering results. Therefore, it is necessary to optimize the chemical conditioning process to increase dewatering efficiency. Chemical agent used in the process are alum, lime, and a combination of alum and lime. The purpose of this study is to analyze the effect of increasing the dose of chemical agent that can increase the efficiency of sludge dewatering in IPLT Balai PIALAM as well as assess the type and optimum dosage of chemical agent that used in the chemical conditioning process. The parameters used in this study are water content, TSS, TS, SRF, and CST in faecal sludge. The result of chemical conditioning optimization based on the study is the type of the most optimum chemical agent which is the combination of alum and lime ratio of 1:2 with an optimum dose of 14 g/L that can reduce the water content in the sludge from 90,14% to 64,68%, TSS from 73.000 to 6.915, TS from 102.950 to 13.620, CST from 90,29 to 22,4 seconds, and SRF value from 6,69 x 1010 to 1,23 x 1010 m/kg. [ABSTRACT FROM AUTHOR]

Abstract Breast cancer (BC)‐related mortality primarily results from metastatic colonization of disseminated cells. Actin polymerization plays an important role in driving post‐extravasation metastatic outgrowth of tumor cells. This study examines the role of myocardin‐related transcription factor (MRTF)/serum‐response (SRF), a transcription system well known for regulation of cytoskeletal genes, in metastatic colonization of BC cells. We demonstrated that co‐depletion of MRTF isoforms (MRTF‐A and MRTF‐B) dramatically impairs single‐cell outgrowth ability of BC cells as well as retards growth progression of pre‐established BC cell colonies in three‐dimensional (3D) cultures. Conversely, overexpression of MRTF‐A promotes initiation and progression of tumor‐cell outgrowth in vitro, primary tumor formation, and metastatic outgrowth of seeded BC cells in vivo, and these changes can be dramatically blocked by molecular disruption of MRTF‐A's interaction with SRF. Correlated with the outgrowth phenotypes, we further demonstrate MRTF's ability to augment the intrinsic cellular ability to polymerize actin and formation of F‐actin‐based protrusive structures requiring SRF's interaction. Pharmacological proof‐of‐concept studies show that small molecules capable of interfering with MRTF/SRF signaling robustly suppresses single‐cell outgrowth and progression of pre‐established outgrowth of BC cells in vitro as well as experimental metastatic burden of BC cells in vivo. Based on these data, we conclude that MRTF activity potentiates metastatic colonization of BC cells and therefore, targeting MRTF may be a promising strategy to diminish metastatic burden in BC.

Background: Congenital heart disease (CHD) is one of the most important birth defects caused by more than one mutated gene. Mutations in the genes could cause different types of congenital heart defects including atrial septal defect (ASD), tetralogy of Fallot (TOF), and ventricular septal defect (VSD). Objectives: Cardiac transcription factors are key players for heart development and are actively involved in controlling stress regulation of the heart. Transcription factors are sequence-specific DNA binding proteins that control the process of transcription and work in a synergistic manner. We aim to characterize core cardiac transcription factors including NKX2–5, TBX, SRF, GATA4, and MEF2, which encode homeobox and MADS domain and play a crucial role in heart development. Methods: In this study, we have explored the important transcription factors involved in cardiac development and genes controlling the expression and regulation process by using the bioinformatics approach. Results: We have predicted the orthologs and homologs based on their evolutionary history, conserved protein domains, functional sites, and 3D structures for better understanding and presentation of factors responsible for causing CHD. Results showed the importance of these transcription factors for normal heart functioning and development. Conclusion: Understanding the molecular pathways and genetic basis of CHD will help to open a new door for the treatment of patients with cardiac defects. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) is an abnormal intraocular scarring process that can complicate cases of rhegmatogenous retinal detachment (RRD). Although previous studies have examined the relevance of microRNAs (miRNAs) in ophthalmic diseases, only a few studies have evaluated the expression profiles of microRNAs in subretinal fluid. We hypothesized that the expression profiles of specific miRNAs may change in response to RRD, in the subretinal fluid that is directly in contact with photoreceptors and the retinal pigment epithelium (RPE). We looked for a potential correlation between the expression of specific miRNAs in eyes with RRD and known clinical risk factors of PVR. A total of 24 patients (59 ± 11 years) who underwent scleral buckling procedure were enrolled in this prospective study. Twenty-four undiluted subretinal fluid samples were collected, RNA was isolated and qRT-PCR was performed to analyze the expression of 12 miRNAs. We found the existence of a positive association between the expression of miR-21 (p = 0.017, r = 0.515) and miR-34 (p = 0.030, r = 0.624) and the duration of symptoms related to retinal detachment. Moreover, the expression of miR-146a tended to decrease in patients who developed PVR. Subretinal fluid constitutes an intriguing biological matrix to evaluate the role of miRNAs leading to the development of PVR. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI)- and deep learning (DL)-based systems have shown significant progress in the field of macular disorders, demonstrating high performance in detecting retinal fluid and assessing anatomical changes during disease progression. This study aimed to validate an AI algorithm for identifying and quantifying prognostic factors in visual recovery after macular hole (MH) surgery by analyzing major optical coherence tomography (OCT) biomarkers. This study included 20 patients who underwent vitrectomy for a full-thickness macular hole (FTMH). The mean diameter of the FTMH was measured at 285.36 ± 97.4 μm. The preoperative best-corrected visual acuity (BCVA) was 0.76 ± 0.06 logMAR, improving to 0.38 ± 0.16 postoperatively, with a statistically significant difference (p = 0.001). AI software was utilized to assess biomarkers, such as intraretinal fluid (IRF) and subretinal fluid (SRF) volume, external limiting membrane (ELM) and ellipsoid zone (EZ) integrity, and retinal hyperreflective foci (HRF). The AI analysis showed a significant decrease in IRF volume, from 0.08 ± 0.12 mm3 preoperatively to 0.01 ± 0.01 mm3 postoperatively. ELM interruption improved from 79% ± 18% to 34% ± 37% after surgery (p = 0.006), whereas EZ interruption improved from 80% ± 22% to 40% ± 36% (p = 0.007) postoperatively. Additionally, the study revealed a negative correlation between preoperative IRF volume and postoperative BCVA recovery, suggesting that greater preoperative fluid volumes may hinder visual improvement. The integrity of the ELM and EZ was found to be essential for postoperative visual acuity improvement, with their disruption negatively impacting visual recovery. The study highlights the potential of AI in quantifying OCT biomarkers for managing MHs and improving patient care.

This work offers a comprehensive examination of ICP-MS as a higher-level analytical method compared to atomic absorption spectrometry (AAS) and X-ray fluorescence (XRF). Comparisons between the ICP-MS average mean difference and AAS were made with the determination of the concentration of trace elements in the same solid alternative fuel samples, while comparisons between ICP-MS and XRF were made by the determination of the concentration of major elements in the same solid alternative fuel samples, resulting in the superiority of the method. The results of the relative mean differences (RDMs) between ICP-MS (7.56%) and XRF (9.42%) regarding the concentration of major elements compared with the reference values in solid biofuel samples, while the RDMs for the solid recovered fuel samples were 8.9% for ICP-MS and 12.27% for XRF. The same procedure was followed for the determination of the concentration of trace elements with ICP-MS and AAS, thus obtaining the results for solid biofuel samples (average %RMDICP-MS = 12.77 and RMDAAS = 13.9) and SRF samples (average %RMDICP-MS = 10.02 and RDMAAS = 11.10) in relation to the reference values. While acknowledging that the initial cost and complexity of operation may deter some from adopting ICP-MS, the study asserts that the advantages of enhanced precision, sensitivity and speed of analysis validate the investment. Hence, ICP-MS is an extremely important laboratory tool used in modern physics and chemistry and has a wide range of applications: biological materials, high purity reagents and metals, atomic nuclear materials, geological samples and food.

Skeletal myogenesis is an intricate process involving the differentiation of progenitor cells into myofibers, which is regulated by actin cytoskeletal dynamics and myogenic transcription factors. Although recent studies have demonstrated the pivotal roles of actin-binding proteins (ABPs) as mechanosensors and signal transducers, the biological significance of WAVE2 (Wiskott–Aldrich syndrome protein family member 2), an ABP essential for actin polymerization, in myogenic differentiation of progenitor cells has not been investigated. Our study provides important insights into the regulatory roles played by WAVE2 in the myocardin-related transcription factor A (MRTFA)–serum response factor (SRF) signaling axis and differentiation of myoblasts. We demonstrate that WAVE2 expression is induced during myogenic differentiation and plays a pivotal role in actin cytoskeletal remodeling in C2C12 myoblasts. Knockdown of WAVE2 in C2C12 cells reduced filamentous actin levels, increased globular actin accumulation, and impaired the nuclear translocation of MRTFA. Furthermore, WAVE2 depletion in myoblasts inhibited the expression and transcriptional activity of SRF and suppressed cell proliferation in myoblasts. Consequently, WAVE2 knockdown suppressed myogenic regulatory factors (i.e., MyoD, MyoG, and SMYD1) expressions, thereby hindering the differentiation of myoblasts. Thus, this study suggests that WAVE2 is essential for myogenic differentiation of progenitor cells by modulating the mechanosensitive MRTFA–SRF axis.

The lncRNA PVT1 reportedly functions as a competing endogenous RNA (ceRNA) of miR-186 and miR-26b in different tissue types. In this study, we investigated the possible involvement of the miR-186/ Srf / Ctgf and miR-26b/ Ctgf signaling pathways in the pathogenesis of hypoxia-induced PAH. Expression of PVT1, miR-186, miR-26b, and Srf and Ctgf mRNAs were evaluated by real-time polymerase chain reaction. Protein expression of SRF, CTGF, LC3B-I, LC3B-II, and Beclin-I was evaluated using western blotting. The regulatory relationship between the lncRNA, miRNAs, and target mRNAs was explored using luciferase assays. Immunohistochemistry was used to evaluate the expression of SRF and CTGF in situ. MTT assay was performed to assess the proliferation of PASMCs. Exposure to hypoxia markedly altered the expression of PVT1, Srf, Ctgf , miR-186, and miR-26b in a rat model. MiR-186 binding sites in the sequences of Srf mRNA and PVT1 were confirmed by luciferase assays, indicating that miR-186 may interact with both PVT1 and Srf mRNA. Additionally, miR-26b binding sites were identified in the sequences of Ctgf mRNA and PVT1, suggesting that miR-26b may interact with both PVT1 and Ctgf mRNA. In line with this, we found that overexpression of PVT1 reduced expression of miR-26b and miR-186 but activated expression of Srf , Ctgf , LC3B-II, and Beclin-I. Upregulation of PVT1 by exposure to hypoxia promoted the expression of CTGF, leading to deregulation of autophagy and abnormal proliferation of PASMCs. Dysregulation of the miR-186/ Srf / Ctgf and miR-26b/ Ctgf signaling pathways may be involved in the pathogenesis of hypoxia-induced PASMCs. [Display omitted] • PVT1 could promote the progression of hypoxic pulmonary hypertension. • MiR-186 and miR-26b were dysregulated in the hypoxia-induced PASMCs and participated in the progression of HPH. • PVT1/miR-186/ Srf / Ctgf and PVT1/ miR -26b / Ctgf regulatory networks ultimately affected the proliferation of PASMCs through CTGF in the HPH model. [ABSTRACT FROM AUTHOR]

Neural tube defects (NTDs) constitute the second most common congenital malformation of the central nervous system. The pathogenesis of NTDs is not entirely clear. In recent years, microRNAs (miRNAs) have become a hot spot in genetic and developmental biology research. The present study aimed to explore the potential role of miRNA-26a in NTDs and the underlying pathogenesis thereof. First, we found significantly increased miRNA-26a expression in fetuses with NTDs (p < 0.0001), which significantly downregulated EphA2 and ERK1 mRNA and protein expression levels in fetuses with NTDs compared to normal controls (p < 0.01). In addition, a dual-luciferase reporter assay showed that miR-26a negatively regulated EphA2 by directly binding with the 3′-untranslated region of EphA2. Second, the upregulation of miRNA-26a expression increased caspase 3 and 9 protein expression levels (p < 0.01) and decreased EphA2 mRNA and protein expression levels (p < 0.01), as well as ERK1 and SRF protein expression levels (p < 0.01) in mouse neural stem cells (NE-4C) and human astroblastoma cells (U87MG). Furthermore, the upregulation of miRNA-26a inhibited cell proliferation and enhanced apoptosis of NE-4C and U87MG cells (p < 0.05). Similar results were observed with the MAPK inhibitor PD98059 (p < 0.01). These results suggest that miR-26a targets EphA2, modulates phosphorylation of the MAPK/ERK (MEK) pathway, regulates SRF, and participates in regulating nervous cell proliferation and apoptosis. Dysregulation of the aforementioned mechanism may be involved in the pathogenesis of NTDs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Early Nb 3 Sn growth mechanisms were compared on various Nb substrates. • Nb surface determined the distribution and morphology of nucleated Sn and Nb 3 Sn. • Pre-deposition Nb oxidation determines the NbO surface sites present during growth. • NbO atomic structure contributes to poor Nb 3 Sn growth. • Nb grain boundaries do not preferentially nucleate Nb 3 Sn but prevent Sn loss. The enhanced accelerating performance of Nb 3 Sn-coated Nb superconducting radio frequency (SRF) cavities is severely limited by quenching sites at material defects formed during the Nb 3 Sn film growth procedure. In this work, we aimed to understand the complex surface-mediated interactions that drive initial Nb 3 Sn formation during the Sn vapor deposition procedure used to fabricate Nb 3 Sn coated SRF cavities. Nb substrates were modified, coated with Sn, and then characterized using an ultra-high vacuum (UHV) chamber equipped with metal deposition and in situ surface analysis capabilities. The atomic structure of the Nb oxide surface was modified to assess how the Nb surface defect density and crystallographic orientation impact the size of nucleated Sn islands and relative Nb 3 Sn growth rates. Formed Nb 3 Sn/Nb surfaces were visualized using ex situ scanning electron microscopy (SEM) and post-deposition annealing revealed Sn desorption and Nb 3 Sn degradation pathways. Finally, we showed that the Sn deposition conditions can be modified to overcome the growth barriers that are imposed by the Nb morphology. This study provides a unique bridge between fundamental growth studies in pristine conditions with observed phenomena of Nb 3 Sn grown on realistic cavity surfaces. [ABSTRACT FROM AUTHOR]

The mercury content is among the parameters that characterise the quality of Solid Recovered Fuels (SRFs), which constitute alternative solid fuels of increasing interest. In this study, a direct mercury analyser was utilised in the analyses of SRF samples originating from Automotive Shredded Residues (ASRs). Two SRFs and one liquid reference material were measured to test the accuracy and sensitivity of the instrument. The mean values of the two SRFs and one liquid reference material (RM) were 0.171, 0.324 mg/kg, and 0.141 mg/L. These values were compared with the reference ones as follows: 0.168, 0.382 mg/kg, and 0.137 mg/L. Mercury content was detected in the analysis samples of four different particle sizes (8 mm, 2 mm, 1 mm, 0.5 mm, and 0.25 mm) for each SRF sample in order to demonstrate the direct mercury analyser operation and to compare it as an alternative to mercury determination via atomic absorption spectrometry. The measurements showed that grinding down to 1 mm was sufficient for most SRF cases while grinding down to 2 mm might be enough for a few cases. As an overall conclusion, the direct mercury analyser can be regarded as an efficient laboratory tool, offering a robust alternative to the atomic absorption spectrometry procedure, especially in terms of accuracy, speed, safety, and cost-effectiveness.

Background & aimsAging gastric mucosa has increased susceptibility to injury and delayed healing owing to impaired angiogenesis, but the mechanisms are not fully known. We examined whether impairment of angiogenesis in aging gastric mucosa is caused by deficiency of nerve growth factor (NGF) in gastric endothelial cells (ECs), and whether NGF therapy could reverse this impairment.MethodsIn gastric mucosal ECs (GECs) isolated from young and aging rats we examined the following: (1) in vitro angiogenesis, (2) NGF expression, and (3) the effect of NGF treatment on angiogenesis, GEC proliferation and migration, and dependence on serum response factor. In in vivo studies in young and aging rats, we examined NGF expression in gastric mucosa and the effect of NGF treatment on angiogenesis and gastric ulcer healing. To determine human relevance, we examined NGF expression in gastric mucosal biopsy specimens of aging (≥70 y) and young (≤40 y) individuals.ResultsIn cultured aging GECs, NGF expression and angiogenesis were reduced significantly by 3.0-fold and 4.1-fold vs young GECs. NGF therapy reversed impairment of angiogenesis in aging GECs, and serum response factor silencing completely abolished this response. In gastric mucosa of aging rats, NGF expression in GECs was reduced significantly vs young rats. In aging rats, local NGF treatment significantly increased angiogenesis and accelerated gastric ulcer healing. In aging human subjects, NGF expression in ECs of gastric mucosal vessels was 5.5-fold reduced vs young individuals.ConclusionsNGF deficiency in ECs is a key mechanism underlying impaired angiogenesis and delayed ulcer healing in aging gastric mucosa. Local NGF therapy can reverse these impairments.

Background: The underlying mechanisms of the potential tumor-suppressive effects of ginsenoside Rh2 are complex. N6-methyladenosine (m6A) RNA methylation is usually dysregulated in cancer. This study explored the regulatory effect of ginsenoside Rh2 on m6A RNA methylation in cancer.Methods: m6A RNA quantification and gene-specific m6A RIP-qPCR assays were applied to assess total and gene-specific m6A RNA levels. Co-immunoprecipitation, fractionation western blotting, and immunofluorescence staining were performed to detect protein interactions and distribution. QRT-PCR, dual-luciferase, and ChIP-qPCR assays were conducted to check the transcriptional regulation. Results: Ginsenoside Rh2 reduces m6A RNA methylation and KIF26B expression in a dose-dependent manner in some cancers. KIF26B interacts with ZC3H13 and CBLL1 in the cytoplasm of cancer cells and enhances their nuclear distribution. KIF26B inhibition reduces m6A RNA methylation level in cancer cells. SRF bound to the KIF26B promoter and activated its transcription. SRF mRNA m6A abundance significantly decreased upon KIF26B silencing. SRF knockdown suppressed cancer cell proliferation and growth both in vitro and in vivo, the effect of which was partly rescued by KIF26B overexpression.Conclusion: ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.