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Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and the leading monogenic cause of autism. The condition stems from loss of fragile X mental retardation protein (FMRP), which regulates a wide range of ion channels via translational control, protein–protein interactions and second messenger pathways. Rapidly increasing evidence demonstrates that loss of FMRP leads to numerous ion channel dysfunctions (that is, channelopathies), which in turn contribute significantly to FXS pathophysiology. Consistent with this, pharmacological or genetic interventions that target dysregulated ion channels effectively restore neuronal excitability, synaptic function and behavioural phenotypes in FXS animal models. Recent studies further support a role for direct and rapid FMRP–channel interactions in regulating ion channel function. This Review lays out the current state of knowledge in the field regarding channelopathies and the pathogenesis of FXS, including promising therapeutic implications.Ion channel dysfunctions contribute significantly to fragile X pathophysiology. In this Review, Deng and Klyachko discuss the mechanisms underlying the effects of these channelopathies in fragile X syndrome, and the therapeutic potential of pharmacological interventions that target ion channels.

Genetic and genomic studies have advanced our knowledge of inherited Parkinson’s disease (PD), however, the etiology and pathophysiology of idiopathic PD remain unclear. Herein, we perform a meta-analysis of 8 PD postmortem brain transcriptome studies by employing a multiscale network biology approach to delineate the gene-gene regulatory structures in the substantia nigra and determine key regulators of the PD transcriptomic networks. We identify STMN2 , which encodes a stathmin family protein and is down-regulated in PD brains, as a key regulator functionally connected to known PD risk genes. Our network analysis predicts a function of human STMN2 in synaptic trafficking, which is validated in Stmn2 -knockdown mouse dopaminergic neurons. Stmn2 reduction in the mouse midbrain causes dopaminergic neuron degeneration, phosphorylated α-synuclein elevation, and locomotor deficits. Our integrative analysis not only begins to elucidate the global landscape of PD transcriptomic networks but also pinpoints potential key regulators of PD pathogenic pathways. Parkinson’s disease (PD) is characterized by neurodegeneration associated with loss of dopaminergic (DA) neurons and deposition of Lewy bodies. Here, Wang et al. use co-expression network analysis to pinpoint disease pathways and propose reduced expression of STMN2 as a cause of presynaptic function loss in PD.

Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute to nerve regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC are distinct from Schwann cells and share similarities with astrocytes. Nerve injury elicits changes in the expression of genes related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of fatty acid synthase ( Fasn ) in SGC impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC. These results indicate that PPARα activity downstream of FASN in SGC contributes to promote axon regeneration in adult peripheral nerves and highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair. The contribution of satellite glia to peripheral nerve regeneration is unclear. Here, the authors show that satellite glia are transcriptionally distinct from Schwann cells, share similarities with astrocytes, and, upon injury, they contribute to axon regeneration via Fasn-PPARα signalling pathway.

Institutions have an important impact on corporate outward foreign direct investment, while differences in environmental regulations play a significant role in international capital flows based on the pollution haven hypothesis (PHH). This study examines the effect of green insurance, an institutional innovation tool designed to diversify and transfer environmental risks, on the decisions of firms regarding their overseas investment. Using a quasi-natural experiment of green insurance in 2007, this paper investigates the relationship between green insurance and corporate outward foreign direct investment and then further examines the effects of marketization and the Belt and Road Initiative (BRI) on this relationship. The results show that green insurance significantly reduces corporate outward foreign direct investment. Furthermore, the effect of green insurance on corporate outward foreign direct investment is stronger in regions with higher marketization and is weaker when investing in BRI countries. These findings suggest that green insurance is playing a gradually important role in influencing corporate overseas investment decisions. This study contributes to the research on the effects of institutions on corporate outward foreign direct investment while also broadening the research perspective of the PHH.

Overexpressed Aurora-A kinase promotes tumor growth through various pathways, but whether Aurora-A is also involved in metabolic reprogramming-mediated cancer progression remains unknown. Here, we report that Aurora-A directly interacts with and phosphorylates lactate dehydrogenase B (LDHB), a subunit of the tetrameric enzyme LDH that catalyzes the interconversion between pyruvate and lactate. Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD + regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates. Mechanistically, LDHB serine 162 phosphorylation relieves its substrate inhibition effect by pyruvate, resulting in remarkable elevation in the conversions of pyruvate and NADH to lactate and NAD + . Blocking S162 phosphorylation by expression of a LDHB-S162A mutant inhibited glycolysis and tumor growth in cancer cells and xenograft models. This study uncovers a function of Aurora-A in glycolytic modulation and a mechanism through which LDHB directly contributes to the Warburg effect. Aurora-A kinase is frequently over-expressed in tumours. Here, the authors show that it modulates the activity of lactate dehydrogenase B, resulting in enhanced glycolysis, bio-synthesis and tumour growth.

Wireless capsule endoscopy (WCE) offers a non-invasive evaluation of the digestive system, eliminating the need for sedation and the risks associated with conventional endoscopic procedures. Its significance lies in diagnosing gastrointestinal tissue irregularities, especially in the small intestine. However, existing commercial WCE devices face limitations, such as the absence of autonomous lesion detection and treatment capabilities. Recent advancements in micro-electromechanical fabrication and computational methods have led to extensive research in sophisticated technology integration into commercial capsule endoscopes, intending to supersede wired endoscopes. This Review discusses the future requirements for intelligent capsule robots, providing a comparative evaluation of various methods’ merits and disadvantages, and highlighting recent developments in six technologies relevant to WCE. These include near-field wireless power transmission, magnetic field active drive, ultra-wideband/intrabody communication, hybrid localization, AI-based autonomous lesion detection, and magnetic-controlled diagnosis and treatment. Moreover, we explore the feasibility for future “capsule surgeons”. future requirements for intelligent wireless capsule endoscopy, providing a comparative evaluation of various methods’ merits and disadvantages, and highlighting recent developments in six technologies.

The lignin-carbohydrate complex (LCC) was isolated from milled wood lignin of 2- and 24-month-old crude bamboo (Neosinocalamus affinis) culms using acetic acid (AcOH) and then characterized. The results have shown that the LCC preparation from 2-month-old bamboo (L2) exhibited a slightly lower molecular weight than the LCC preparation from the 24-month-old bamboo (L24). Further studies using Fourier transform infrared spectroscopy (FT-IR) and heteronuclear single quantum coherence (2D-HSQC) NMR spectra analyses indicate that the LCC preparations included glucuronoarabinoxylan and G-S-H lignin-type with G>S>>H. The content of the S lignin units of LCC in the mature bamboo was always higher than in the young bamboo. Combined with sugar composition analysis, the contents of phenyl glycoside and ether linkages in the L24 preparation were higher than in the L2 preparation; however, there was a reverse relationship of ester LCC bonds in L2 and L24. Lignin–xylan was the main type of LCC linkage in bamboo LCCs. Lignin–lignin linkages in the LCC preparations included β-β, β-5 and β-1 carbon-to-carbon, as well as β-O-4 ether linkages, but β-1 linkages were not present in L2.

To discuss the coupling coordination relationship among tourism carbon emissions, economic development and regional innovation it is not only necessary to realize the green development of tourism economy, but also great significance for the tourism industry to take a low-carbon path. Taking the 30 provinces of China for example, this paper calculated the tourism carbon emission efficiency based on the super-efficiency Slacks based measure and Data envelope analyse (SBM-DEA) model from 2007 to 2017, and on this basis, defined a compound system that consists of tourism carbon emissions, tourism economic development and tourism regional innovation. Further, the coupling coordination degree model and dynamic degree model were used to explore its spatiotemporal evolution characteristics of balanced development, and this paper distinguished the core influencing factors by Geodetector model. The results showed that (1) during the study period, the tourism carbon emission efficiency showed a reciprocating trend of first rising and then falling, mainly due to the change of pure technical efficiency. (2) The coupling coordination degree developed towards a good trend, while there were significant differences among provinces, showing a gradient distribution pattern of decreasing from east to west. Additionally, (3) the core driving factors varied over time, however, in general, the influence from high to low were as follows: technological innovation, economic development, urbanization, environmental pollution control, and industrial structure. Finally, some policy recommendations were put forward to further promote the coupling coordination degree.

High crosslinking and low shrinkage stress are difficult to reconcile in the preparation of performance-enhancing photopolymer materials. Here we report the unique mechanism of upconversion particles-assisted NIR polymerization (UCAP) in reducing shrinkage stress and enhancing mechanical properties of cured materials. The excited upconversion particle emit UV-vis light with gradient intensity to the surroundings, forming a domain-limited gradient photopolymerization centered on the particle, and the photopolymer grows within this domain. The curing system remains fluid until the percolated photopolymer network is formed and starts gelation at high functional group conversion, with most of the shrinkage stresses generated by the crosslinking reaction having been released prior to gelation. Longer exposures after gelation contribute to a homogeneous solidification of cured material, and polymer materials cured by UCAP exhibit high gel point conversion, low shrinkage stress and strong mechanical properties than those cured by conventional UV polymerization techniques. High crosslinking and low shrinkage stress are difficult to reconcile in the preparation of performance-enhancing photopolymer materials. Here the authors report the mechanism of upconversion particles-assisted NIR polymerization in reducing shrinkage stress and enhancing mechanical properties of cured materials

. [Display omitted] ► Product review valence and perceived helpfulness have a positive relationship. ► Product review length and perceived helpfulness have a positive relationship. ► All else the same, experiential reviews are less helpful than utilitarian reviews. ► The effects of review valence and length are moderated by product type. ► Reviewer innovativeness has an inverted-U-shaped effect on review helpfulness. Online user-generated product reviews have become an indispensible tool for consumers and thus for retailers who want to attract and retain consumers. Yet, relatively little is known about what causes consumers to find an online peer review helpful to their shopping tasks. Prior research examines mostly the effects of product reviews on consumer product attitude, product choice, and product sales. This paper, however, provides an analysis of the determinants of review helpfulness. In two studies, we examine the effects of review characteristics, product type, and reviewer characteristics on perceived review helpfulness. With data collected from a real online retailer, we provide empirical evidence to support our conceptual predictions. Specifically, both review valence and length have positive effects on review helpfulness, but the product type (i.e., experiential vs. utilitarian product) moderates these effects. Using content analysis of reviews, we develop a measure of expressed reviewer innovativeness (i.e., the predisposition toward new products as revealed in review content). A curvilinear relationship exists between expressed reviewer innovativeness and review helpfulness. These findings lead to pertinent managerial implications.