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Visible-light-driven organic transformations are of great interest in synthesizing valuable fine chemicals under mild conditions. The merger of heterogeneous photocatalysts and transition metal catalysts has recently drawn much attention due to its versatility for organic transformations. However, these semi-heterogenous systems suffered several drawbacks, such as transition metal agglomeration on the heterogeneous surface, hindering further applications. Here, we introduce heterogeneous single Ni atoms supported on carbon nitride (NiSAC/CN) for visible-light-driven C-N functionalization with a broad substrate scope. Compared to a semi-heterogeneous system, high activity and stability were observed due to metal-support interactions. Furthermore, through systematic experimental mechanistic studies, we demonstrate that the stabilized single Ni atoms on CN effectively change their redox states, leading to a complete photoredox cycle for C-N coupling.

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site. In this study, an integrated approach combining quantitative phosphoproteomics and cell-based functional screening using phosphorylation competition peptides was developed. A pathological cardiac hypertrophy model, junctate-1 transgenic mice and control mice, were analyzed using label-free quantitative phosphoproteomics to identify differentially phosphorylated proteins and sites. A cell-based functional assay system measuring hypertrophic cell growth of neonatal rat ventricle cardiomyocytes (NRVMs) following phenylephrine treatment was applied, and changes in phosphorylation of individual differentially phosphorylated sites were induced by incorporation of phosphorylation competition peptides conjugated with cell-penetrating peptides. Cell-based functional screening against 18 selected phosphorylation sites identified three phosphorylation sites (Ser-98, Ser-179 of Ldb3, and Ser-1146 of palladin) displaying near-complete inhibition of cardiac hypertrophic growth of NRVMs. Changes in phosphorylation levels of Ser-98 and Ser-179 in Ldb3 were further confirmed in NRVMs and other pathological/physiological hypertrophy models, including transverse aortic constriction and swimming models, using site-specific phospho-antibodies. Our integrated approach can be used to identify functionally important phosphorylation sites among differentially phosphorylated sites, and unlike conventional approaches, it is easily applicable for large-scale and/or high-throughput analyses.

Construction of extracellular matrix-mimetic nanofilms has considerable potential in biomedical and nanomedicinal fields. In this work, we fabricated neurocompatible layer-by-layer (LbL) films based on ulvan (ULV), a highly sulfated polysaccharide having compositional similarity to glycosaminoglycans that play important functional roles in the brain. ULV was durably assembled as a film with chitosan, another marine-derived polysaccharide, and the film enabled the stable adhesion of primary hippocampal neurons with high viability, comparable to the conventional poly-d-lysine surface. Notably, the ULV-based LbL films accelerated neurite outgrowth and selectively suppressed the adhesion of astrocytes, highlighting its potential as an advanced platform for neural implants and devices.

Environmental chemical and physical cues dynamically interact with migrating neurons and sprouting axons, and in particular, the gradients of environmental cues are regarded as one of the factors intimately involved in the neuronal movement. Since a growth cone was first described by Cajal, more than one century ago, chemical gradients have been suggested as one of the mechanisms by which the neurons determine proper paths and destinations. However, the gradients of physical cues, such as stiffness and topography, which also interact constantly with the neurons and their axons as a component of the extracellular environments, have rarely been noted regarding the guidance of neurons, despite their gradually increasingly reported influences in the case of nonneuronal-cell migration. In this review, we discuss chemical (i.e., chemo- and hapto-) and physical (i.e., duro-) taxis phenomena on the movement of neurons including axonal elongation. In addition, we suggest topotaxis, the most recently proposed physical-taxis phenomenon, as another potential mechanism in the neuronal movement, based on the reports of neuronal recognition of and responses to nanotopography.

This study evaluated the accuracy of tangential axial radiography of the patellofemoral joints using an auxiliary device, which we named patellofemoral joint radiography (PJR). To compare the PJR and conventional radiography methods such as the Laurin, Merchant, and Settegast, the images taken by three methods were evaluated using a whole body phantom (PBU-31). Settegast was the radiographic method that had the smallest inclination of the patella and showed the best half lateral image of the patella, with a difference of 5.76% when compared with PJR (p = 0.001). PJR was the method that had the largest distance between the patellar and femoral joint spaces, with a difference of 14.54% when compared with the Merchant method (p = 0.001). PJR was the method in which the two bones were well overlapped (i.e., measured by the distance between the femoral trochlear groove and the tibial tuberosity), with a difference of 109.41% when compared with the Merchant method (p = 0.001). The Settegast method has the image with the smallest inclination of the patella, but the PJR has the image that best describes the patellofemoral joint and the least distortion of the image. when using PJR, bending the knee by 40° degree and setting a 140° angle between the long axis of the femur and the long axis of the lower leg were considered to be the most beneficial conditions. We propose the use of PJR for tangential axial radiography of the patellar and patellofemoral joints.

Rapid degradation of Fe3+-tannic acid films is achieved under mild conditions via ascorbic acid-mediated Fe3+ reduction, which overcomes the problems in the disassembly of a metal–organic complex including slow reaction rates and reaction incompatibility with living cells. The strategy of reductive disassembly is applied to degradable single-cell nanoencapsulation, providing an advanced tool for tightly controlling and manipulating the cell–material interface.

Poly(methyl methacrylate) (PMMA) is widely used as a transparent material for optical applications, owing to its high light transmittance. However, it exhibits poor heat resistance and high moisture absorption, leading to distortion and deformation upon exposure to elevated temperatures and/or moisture. These structural changes decrease the transparency of PMMA, critically limiting its applicability. In this study, we synthesized poly(methyl methacrylate-co-styrene-co-acrylamide) (PMSAm) as a reference polymer and introduced one of four different comonomers [N-phenylmaleimide (PMI), N-cyclohexylmaleimide (CHMI), allyltrimethylsilane (ATMS), or 2,2,2-trifluoroethyl methacrylate (TF)] as a means to improve heat resistance and reduce moisture absorption. Four series of PMMA-based random copolymers (PMSAm-PMI, PMSAm-CHMI, PMSAm-ATMS, and PMSAm-TF) were synthesized by conventional thermal radical polymerization. All of the polymers synthesized exhibited improved heat resistance, with PMSAm-CHMI exhibiting the highest glass transition temperature (Tg = 122.54 °C) and 5% weight loss thermal decomposition temperature (T5d = 343.40 °C) as well as the lowest thermal expansion coefficient (90.3 μm m-1 °C-1). The highest hydrophobicity was exhibited by PMSAm-TF, with a water contact angle of 78.9°, indicating higher hydrophobicity compared to that of pure PMMA (69.4°). More importantly, high transparency (∼90%) was exhibited by all of the synthesized polymers. Thus, our copolymerization strategy successfully addresses the limitations, i.e., low heat resistance and high moisture absorption, of conventional PMMA-based materials.

Patients with neuromuscular disorders suffer from a lack of treatment options for skeletal muscle weakness and disease comorbidities. Here, we introduce as a potential therapeutic agent a heterodimeric ligand-trapping fusion protein, ActRIIB:ALK4-Fc, which comprises extracellular domains of activin-like kinase 4 (ALK4) and activin receptor type IIB (ActRIIB), a naturally occurring pair of type I and II receptors belonging to the TGF-β superfamily. By surface plasmon resonance (SPR), ActRIIB:ALK4-Fc exhibited a ligand binding profile distinctly different from that of its homodimeric variant ActRIIB-Fc, sequestering ActRIIB ligands known to inhibit muscle growth but not trapping the vascular regulatory ligand bone morphogenetic protein 9 (BMP9). ActRIIB:ALK4-Fc and ActRIIB-Fc administered to mice exerted differential effects — concordant with SPR results — on vessel outgrowth in a retinal explant assay. ActRIIB:ALK4-Fc induced a systemic increase in muscle mass and function in wild-type mice and in murine models of Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS), and disuse atrophy. Importantly, ActRIIB:ALK4-Fc improved neuromuscular junction abnormalities in murine models of DMD and presymptomatic ALS and alleviated acute muscle fibrosis in a DMD model. Furthermore, in combination therapy ActRIIB:ALK4-Fc increased the efficacy of antisense oligonucleotide M12-PMO on dystrophin expression and skeletal muscle endurance in an aged DMD model. ActRIIB:ALK4-Fc shows promise as a therapeutic agent, alone or in combination with dystrophin rescue therapy, to alleviate muscle weakness and comorbidities of neuromuscular disorders.

Rapid degradation of Fe

This paper examines the value relevance of corporate environmental performance (CEP) using individual environmental performance indicators and multidimensional constructs derived from Trumpp et al. (2015). Accounting information can be described as &lsquo, value-relevant&rsquo, when the information in financial statements has the ability to explain firm value. In recent years, stakeholders such as governments, public institutions, firms, customers, and local communities have recognized the importance of corporate environmental performance. Thus, one of the main research questions is whether corporate environmental performance is value relevant. The empirical results in this paper indicate that only a few individual environmental performance indicator variables are value relevant, while most environmental performance constructs have a significant impact on firm value. Our findings suggest that firm value significantly increases with improved environmental management or operational performance. In addition, environmental performance indicators and environmental performance constructs have a significant impact on firms in environmentally sensitive industries, confirming the notion of higher value relevance of environmental information for firms in these industries. This study contributes to prior literature by carrying out a comprehensive analysis on the multidimensional nature of corporate environmental performance and its impact on value relevance. This paper also reconciles extant literature on the construct validity of environmental performance indicators and environmental performance constructs by formulating standardized composite measures of CEP following Larker et al. (2007).

As an effort to overcome the physical limitation of scaling down the size of transistors and to implement ultra-low-power consumption in integrated circuits, the use of negative quantum capacitance has attracted significant attention, because it can simply enhance the gate capacitance in field-effect transistors. Among various two-dimensional materials, topological insulators (TI) have immense potential to achieve the effect of negative quantum capacitance, because they can be included in the gate stack of conventional metal oxide semiconductor (MOS) field-effect transistors. In order to verify their advantages for various gate capacitance values, we have fabricated a MOS capacitor with a TI. At room temperature, the capacitance enhancement (i.e., total gate capacitance higher than the theoretically estimated geometric capacitance) of the capacitor was experimentally observed near the depletion region. The effect of negative quantum capacitance, which is caused by the electron system on the surface of TI, demonstrates that the gate capacitance can increase in the range of frequency, i.e., 50–100 kHz.

Proteinopathy in neurodegenerative diseases is typically characterized by deteriorating activity of specific protein aggregates. In tauopathies, including Alzheimer’s disease (AD), tau protein abnormally accumulates and induces dysfunction of the affected neurons. Despite active identification of tau modifications responsible for tau aggregation, a critical modulator inducing tau proteinopathy by affecting its protein degradation flux is not known. Here, we report that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, is crucial for the tau-mediated AD pathology. ALK caused abnormal accumulation of highly phosphorylated tau in the somatodendritic region of neurons through its tyrosine kinase activity. ALK-induced LC3-positive axon swelling and loss of spine density, leading to tau-dependent neuronal degeneration. Notably, ALK activation in neurons impaired Stx17-dependent autophagosome maturation and this defect was reversed by a dominant-negative Grb2. In a Drosophila melanogaster model, transgenic flies neuronally expressing active Drosophila Alk exhibited the aggravated tau rough eye phenotype with retinal degeneration and shortened lifespan. In contrast, expression of kinase-dead Alk blocked these phenotypes. Consistent with the previous RNAseq analysis showing upregulation of ALK expression in AD [1], ALK levels were significantly elevated in the brains of AD patients showing autophagosomal defects. Injection of an ALK.Fc-lentivirus exacerbated memory impairment in 3xTg-AD mice. Conversely, pharmacologic inhibition of ALK activity with inhibitors reversed the memory impairment and tau accumulation in both 3xTg-AD and tauC3 (caspase-cleaved tau) transgenic mice. Together, we propose that aberrantly activated ALK is a bona fide mediator of tau proteinopathy that disrupts autophagosome maturation and causes tau accumulation and aggregation, leading to neuronal dysfunction in AD.

With lots of interest in negative capacitance field-effect transistors for ultralow-power complementary metal–oxide–semiconductor technology, negative capacitance thin-film transistors (NCTFTs) have also received much attention. Although previous studies on NCTFTs were done, the NC effect in organic-based TFTs was not studied yet. In this paper, P(VDF-TrFE) ferroelectric-gated P3HT semiconductor channel TFTs are experimentally demonstrated with solution-based fabrication process. Especially, this paper shed light on the NC effect in the organic-based TFTs. The step-up current-voltage characteristics are repeatedly and reliably observed in diverse TFTs, and then, with the results, transconductance ( $g_{m}$ ) amplification implemented by the negative capacitance was delved. Moreover, with the aid of ferroelectric polarization switching, super steep-switching characteristic of the organic-based TFT was experimentally confirmed. These experimental results and discussion would be helpful in understanding NC effects in TFTs.