The environmental impacts of plastic pollution have recently attracted universal attention, especially in the aquatic environment. However, research has mostly been focused on marine ecosystems, even ...though freshwater ecosystems are equally if not more polluted by plastics. In addition, the mechanism and extent to which plastic pollution affects aquatic biota and the rates of transfer to organisms through food webs eventually reaching humans are poorly understood, especially considering leaching hazardous chemicals. Several studies have demonstrated extreme toxicity in freshwater organisms such Daphnia. When such keystone species are affected by ambient pollution, entire food webs are destabilized and biodiversity is threatened. The unremitting increase in plastic contaminants in freshwater environments would cause impairments in ecosystem functions and structure, leading to various kinds of negative ecological consequences. As various studies have reported the effects on daphnids, a consolidation of this literature is critical to discuss the limitations and knowledge gaps and to evaluate the risk posed to the aquatic environment. This review was undertaken due to the evident need to evaluate this threat. The aims were to provide a meaningful overview of the literature relevant to the potential impact of plastic pollution and associated contaminants on freshwater daphnids as primary consumers. A critical evaluation of research gaps and perspectives is conducted to provide a comprehensive risk assessment of microplastic as a hazard to aquatic environments. We outlined the challenges and limitations to microplastic research in hampering better‐focused investigations that could support the development of new plastic materials and/or establishment of new regulations.
LSD1 (lysine specific demethylase; also known as KDM1A), the first histone demethylase discovered, regulates cell-fate determination and is overexpressed in multiple cancers. LSD1 demethylates ...histone H3 Lys4, an epigenetic mark for active genes, but requires the CoREST repressor to act on nucleosome substrates. To understand how an accessory subunit (CoREST) enables a chromatin enzyme (LSD1) to function on a nucleosome and not just histones, we have determined the crystal structure of the LSD1/CoREST complex bound to a 191-bp nucleosome. We find that the LSD1 catalytic domain binds extranucleosomal DNA and is unexpectedly positioned 100 Å away from the nucleosome core. CoREST makes critical contacts with both histone and DNA components of the nucleosome, explaining its essential function in demethylating nucleosome substrates. Our studies also show that the LSD1(K661A) frequently used as a catalytically inactive mutant in vivo (based on in vitro peptide studies) actually retains substantial H3K4 demethylase activity on nucleosome substrates.
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•The structure explains why CoREST is necessary for LSD1 to demethylate nucleosomes•LSD1 unexpectedly binds to extranucleosomal/linker DNA away from the nucleosome core•The LSD1(K661A) putative catalytically inactive mutant is active on nucleosomes•LSD1 can bind to two distinct sites on the nucleosome
This crystal structure shows how the LSD1/CoREST histone demethylase binds to its nucleosome substrate to remove the transcriptionally active histone H3 Lys4 methyl mark. This study describes the mechanistic basis for how a non-catalytic accessory subunit (CoREST) enables a catalytic subunit (LSD1) to function on a nucleosome substrate.
Polymeric semiconductors have demonstrated great potential in the mass production of low‐cost, lightweight, flexible, and stretchable electronic devices, making them very attractive for commercial ...applications. Over the past three decades, remarkable progress has been made in donor–acceptor (D–A) polymer‐based field‐effect transistors, with their charge‐carrier mobility exceeding 10 cm2 V−1 s−1. Numerous molecular designs of D–A polymers have emerged and evolved along with progress in understanding the charge transport physics behind their high mobility. In this review, the current understanding of charge transport in polymeric semiconductors is covered along with significant features observed in high‐mobility D–A polymers, with a particular focus on polymeric microstructures. Subsequently, emerging molecular designs with further prospective improvements in charge‐carrier mobility are described. Moreover, the current issues and outlook for future generations of polymeric semiconductors are discussed.
An improved understanding of charge transport physics has enabled high‐performance organic field‐effect transistors through microstructure and electronic structure control by altering various donor and acceptor units. This report discusses in detail the relationship between donor–acceptor‐conjugated polymer structure and charge transport and summarizes the key features of the molecular design strategies.
We report a highly effective interface engineering strategy for thermally stable perovskite solar cells (PSCs) by employing a zwitterion-modified SnO 2 electron transport layer (ETL) and a ...dopant-free hole transport layer (HTL). A zwitterionic compound, 3-(1-pyridinio)-1-propanesulfonate, is used to modify the SnO 2 ETL. The zwitterion, which forms interfacial dipoles, plays a few important roles: (1) it causes shifts in the work function of SnO 2 resulting in more efficient charge extraction and an increase in the built-in potential. (2) It pulls electrons from perovskite layers to the ETL/perovskite interface, enhancing the electron transport ability. (3) Interfacial dipoles prevent back transfer of electrons from the ETL to the perovskite and suppress charge recombination. (4) Positively charged atoms in the zwitterion passivate Pb–I antisite defects, improving the stability of devices. With these desirable properties, the PSC with doped Spiro-OMeTAD obtained a power conversion efficiency of 21.43%. In addition, the PSC with the dopant-free HTL exhibited a record high efficiency of 20.5% among dopant-free polymeric HTLs using green solvents. The resulting PSCs without encapsulation showed excellent thermal stability. Accordingly, this work suggests that the use of a modified ETL and a dopant-free HTL is a promising strategy to overcome the thermal instability of planar-PSCs (P-PSCs).
Anti-dementia medications are widely prescribed to patients with Alzheimer's dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with ...AD using a standardized data format-the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009-2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-D-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.
Abstract
Calcium flux regulating intracellular calcium levels is essential and modulated for efficient efferocytosis. However, the molecular mechanism by which calcium flux is modulated during ...efferocytosis remains elusive. Here, we report that Orai1, a Crbn substrate, is upregulated via its attenuated interaction with Crbn during efferocytosis, which increases calcium influx into phagocytes and thereby promotes efferocytosis. We found that Crbn deficiency promoted phagocytosis of apoptotic cells, which resulted from facilitated phagocytic cup closure and was nullified by a CRAC channel inhibitor. In addition, Orai1 associated with Crbn, resulting in ubiquitination and proteasomal degradation of Orai1 and alteration of SOCE-mediated calcium influx. The association of Orai1 with Crbn was attenuated during efferocytosis, leading to reduced ubiquitination of Orai1 and consequently upregulation of Orai1 and calcium influx. Collectively, our study reveals a regulatory mechanism by which calcium influx is modulated by a Crbn-Orai1 axis to facilitate efferocytosis.
This paper aimed to review the literature on the factors associated with parenting stress and resilience among parents of children with autism spectrum disorder (ASD) in the South East Asia (SEA) ...region.
An extensive search of articles in multiple online databases (PsycNET, ProQuest, PudMed, EMBASE, CINAHL, Web of Science, and Google Scholar) resulted in 28 papers that met the inclusion criteria (i.e., conducted in the SEA region, specific to ASD only, published in a peer-reviewed journal, full text in English). Studies found were conducted in the following countries: Brunei,
= 1; Indonesia,
= 2; Malaysia,
= 12; Philippines,
= 5; Singapore,
= 5, Thailand,
= 2; and Vietnam,
= 1, but none from Cambodia, East Timor, Laos, and Myanmar were identified.
Across the studies, six main factors were found to be associated with parenting stress: social support, severity of autism symptoms, financial difficulty, parents' perception and understanding toward ASD, parents' anxiety and worries about their child's future, and religious beliefs. These six factors could also be categorized as either a source of parenting stress or a coping strategy/resilience mechanism that may attenuate parenting stress.
The findings suggest that greater support services in Western countries may underlie the cultural differences observed in the SEA region. Limitations in the current review were identified. The limited number of studies yielded from the search suggests a need for expanded research on ASD and parenting stress, coping, and resilience in the SEA region especially in Cambodia, East Timor, Laos, and Myanmar. The identified stress and resilience factors may serve as sociocultural markers for clinicians, psychologists, and other professionals to consider when supporting parents of children with ASD.
The receptor-interacting serine/threonine-protein kinases RIPK1 and RIPK3 play important roles in necroptosis that are closely linked to the inflammatory response. Although the activation of ...necroptosis is well characterized, the mechanism that tunes down necroptosis is largely unknown. Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson's disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. Parkin prevents the formation of the RIPK1-RIPK3 complex by promoting polyubiquitination of RIPK3. Parkin is phosphorylated and activated by the cellular energy sensor AMP-activated protein kinase (AMPK). Parkin deficiency potentiates the RIPK1-RIPK3 interaction, RIPK3 phosphorylation and necroptosis. Parkin deficiency enhances inflammation and inflammation-associated tumorigenesis. These findings demonstrate that the AMPK-Parkin axis negatively regulates necroptosis by inhibiting RIPK1-RIPK3 complex formation; this regulation may serve as an important mechanism to fine-tune necroptosis and inflammation.
Because thermal interface materials are composites with high-filler-loading, they are rigid, while also having large thermal conductivity. Their use has consequently been limited to fabricating rigid ...electronics. To address this shortcoming, stretchable thermally conductive films in which graphite composite patterns are embedded in a highly stretchable polymer matrix were fabricated in this study. Because the modulus of the graphite composite was 200-fold greater than that of the polymer matrix, the fabricated films consisted of the alternating rigid segments and soft segments. Accordingly, they stretched via elongation of soft segments with the rigid segments undergoing little change. The rigid-segment-to-soft-segment ratio of the films was adjusted by varying either the size of the graphite composite patterns or the gap between the patterns, and the effect of this ratio on the stretchability and creep resistance was investigated. Based on the results, g-hs-PUA (55/1.0), in which 5 mm × 5 mm graphite composite patterns with the gap of 1.0 mm were embedded in highly stretchable polyurethane acrylate (hs-PUA), featured the highest creep resistance and its in-plane thermal conductivity was 1.03 (± 0.10) W m
−1
K
−1
. The thermal conductivity was decreased by 12% after 1000 stretching cycles at 50% strain.
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