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Inspired by the porous structures of photosynthetic organelles, we report here a new type of photoelectrode based on a standalone macroporous conjugated polymer network (MCN) that converts sunlight into high-energy electrons for CO2 reduction to CH3OH. The MCN provides supramolecular cavities with sufficient functional groups that control the structures of photocatalytic assemblies, which circumvents the geometric limitations of traditional inorganic counterparts. Stabilized interfacial contact between MCN and photocatalysts is achieved by strong chemical linkages throughout the network. Solar irradiation of MCN with a cobalt-based catalyst generates highly reducing electrons for the reduction of CO2 to CH3OH at a conversion efficiency of 70%. Production of CH3OH sustains for at least 100 h, with a small decrease in yield rates. Scaling up the photoelectrode from 1 to 100 cm2 results in photocurrent generation stabilized at 0.25 A and continuous CH3OH production at a conversion efficiency of 85%, demonstrating the scalability and high performances.
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(1) Currently, the survival prognosis for patients with relapsed and refractory acute myeloid leukemia (R/R AML) is extremely poor. Therefore, the exploration of novel drugs is imperative to enhance the prognosis of patients with R/R AML. The therapeutic efficacy and mechanism of Chidamide, a novel epigenetic regulatory drug, in the treatment of R/R AML remain unclear. METHODS: The mechanism of action of Chidamide has been explored in various AML cell lines through various methods such as cell apoptosis, cell cycle analysis, high-throughput transcriptome sequencing, gene silencing, and xenograft models. RESULTS: Here, we have discovered that chidamide potently induces apoptosis, G0/G1 phase arrest, and mitochondrial membrane potential depolarization in R/R AML cells, encompassing both primary cells and cell lines. Through RNA-seq analysis, we further revealed that chidamide epigenetically regulates the upregulation of differentiation-related pathways while suppressing those associated with cell replication and cell cycle progression. Notably, our screening identified NR4A3 as a key suppressor gene whose upregulation by chidamide leads to P21-dependent cell cycle arrest in the G0/G1 phase. CONCLUSIONS: We have discovered a novel epigenetic regulatory mechanism of chidamide in the treatment of relapsed and refractory acute myeloid leukemia (R/R AML).
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Parkinson's disease (PD) is currently the second most incurable central neurodegenerative disease resulting from various pathogenesis. As the "energy factory" of cells, mitochondria play an extremely important role in supporting neuronal signal transmission and other physiological activities. Mitochondrial dysfunction can cause and accelerate the occurrence and progression of PD. How to effectively prevent and suppress mitochondrial disorders is a key strategy for the treatment of PD from the root. Therefore, the emerging mitochondria-targeted therapy has attracted considerable interest. Herein, the relationship between mitochondrial dysfunction and PD, the causes and results of mitochondrial dysfunction, and major strategies for ameliorating mitochondrial dysfunction to treat PD are systematically reviewed. The study also prospects the main challenges for the treatment of PD.
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Mitocôndrias , Doença de Parkinson , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , AnimaisRESUMO
The industrialization of lithium-sulfur (Li-S) batteries faces challenges due to the shuttling effect of lithium polysulfides (LiPSs) and the growth of lithium dendrites. To address these issues, a simple and scalable method is proposed to synthesize 2D membranes comprising a single layer of cubic graphitic cages encased with few-layer, curved MoS2. The distinctive 2D architecture is achieved by confining the epitaxial growth of MoS2 within the open cages of a 2D-ordered mesoporous graphitic framework (MGF), resulting in MoS2@MGF heterostructures with abundant sulfur vacancies. The experimental and theoretical studies establish that these MoS2@MGF membranes can act as a multifunctional interlayer in Li-S batteries to boost their comprehensive performance. The inclusion of the MoS2@MGF interlayer facilitates the trapping and conversion kinetics of LiPSs, preventing their shuttling effect, while simultaneously promoting uniform lithium deposition to inhibit dendrite growth. As a result, Li-S batteries with the MoS2@MGF interlayer exhibit high electrochemical performance even under high sulfur loading and lean electrolyte conditions. This work highlights the potential of designing advanced MoS2-encased heterostructures as interlayers, offering a viable solution to the current limitations plaguing Li-S batteries.
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Porcine circovirus type 2 (PCV2) infection cause multi-systemic inflammation in pigs. Platycodon grandiflorus polysaccharide (PGPSt) has been reported to have the effects of immune regulation and disease resistance. Nevertheless, the role and mechanism of PGPSt in the inflammatory response of 3D4/21 cells induced by PCV2 infection remain unclear. The present study aims to investigate effects of PGPSt on inflammatory response and its possible underlying mechanisms in vitro models. Cells were treated with PCV2 for 36 h to construct a cell inflammation model. The 3D4/21 cell lines were pretreated with or without PGPSt, and the changes of inflammation-related markers and the signaling pathway were detected by CCK-8, ELISA, qPCR and Western blot. The results showed that PGPSt was non-toxic to cells and protected PCV2-infected cells from inflammatory damage. PGPSt could significantly inhibit the high acetylation of histone H3 (AcH3) and histone H4 (AcH4), down-regulate HAT and up-regulate HDAC activity, and reduce the expression of pro-inflammatory enzymes iNOS and COX-2 proteins levels. Then the levels of IL-1ß, IL-6 and TNF-α were significantly inhibited, and the level of IL-10 was promoted. We also observed that PGPSt inhibited the phosphorylation of p65, p38 and Erk1/2, which subsequently inhibited nuclear translocation of NF-κB p65 to express pro-inflammatory factors. In conclusion, PGPSt can reduce the inflammatory response by regulating histone acetylation, reducing the release of inflammatory factors, reducing the expression of pro-inflammatory enzymes, and inhibiting the activation of NF-κB and MAPKs signaling pathways. This suggests that PGPSt had an anti-inflammatory effect on the inflammatory response caused by PCV2 infection, which provided theoretical data support for the research.
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Circovirus , Platycodon , Animais , Suínos , NF-kappa B/metabolismo , Platycodon/metabolismo , Circovirus/fisiologia , Inflamação , Histonas/metabolismo , Polissacarídeos/farmacologiaRESUMO
Enzyme-mediated systems have been widely employed for the biotransformation of environmental contaminants. However, the catalytic performance of free enzymes is restricted by the rapid loss of their catalytic activity, stability, and reusability. In this work, we developed an enzyme immobilization platform by elaborately anchoring fungal laccase onto arginine-functionalized boron nitride nanosheets (BNNS-Arg@Lac). BNNS-Arg@Lac showcased â¼75% immobilization yield and enhanced stability against fluctuating pH values and temperatures, along with remarkable reusability across six consecutive cycles, outperforming free natural laccase (nlaccase). A model pollutant, atrazine, was selected for a proof-of-concept demonstration, given the substantial environmental and public health concerns in agriculture runoff. BNNS-Arg@Lac-catalyzed atrazine degradation rate was nearly twice that of nlaccase. Moreover, BNNS-Arg@Lac consistently demonstrated superior atrazine degradation in synthetic agricultural wastewater and various mediator systems compared to nlaccase. Comprehensive product analysis unraveled distinct degradation pathways for BNNS-Arg@Lac and nlaccase. Overall, this research provides a foundation for the future development of enzyme-nanomaterial hybrids for degrading environmental chemicals and may unlock new potential for green and efficient resource recovery and waste management strategies.
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BACKGROUND: Septic shock is a lethal disease, and identifying high-risk patients through noninvasive and widely available biomarkers can help improve global outcomes. While the clinical impact of chloride levels on critically ill patients remains unclear, this study aims to investigate the association between hypochloremia and mortality following ICU admission among septic shock patients. METHODS: This is an analysis of data stored in the databases of Medical Information Mart for Intensive Care IV (MIMIC-IV). The initial chloride levels were classified ashypochloremia, normal chloraemia, and hyperchloraemia. A multivariate logistic regression model was applied, adjusting for age, lactate, pH, PO2, urine volume, RDW, creatinine, and liver disease, to assess the association between the three categories of chloride levels and mortality. RESULTS: Of 3726 patients included in the study, 470 patients (12.6%) had hypochloremia on ICU admission. During the follow-up period, 1120 (33.5%) patients died. Hypochloremia was significantly associated with increased mortality and the incidence of AKI after adjusting for several variables. CONCLUSIONS: Hypochloremia is independently associated with higher hospital mortality, AKI incidence among septic shock patients. However, further high-quality research is necessary to establish the precise relationship between hypochloremia and septic shock prognosis.
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Moiré superlattices of twisted van der Waals heterostructures provide a promising and tunable platform for simulating correlated two-dimensional physical models. In twisted bilayer transition-metal dichalcogenides with twist angles close to 0°, the Γ and K valley moiré bands are described by the honeycomb and the triangular effective lattice models, respectively, with distinct physics. Using large-scale first-principles calculations, we show that in-plane biaxial strain and out-of-plane pressure provide effective knobs for switching the moiré lattice models that emerged at the band edges in twisted bilayer WSe2 by shifting the energy positions of the Γ and K valley minibands. The shifting mechanism originates from the differences in the orbital characters of the Γ and K valley states and their responses to strain and pressure. The critical strain and pressure for switching the Γ/K valleys are 2.11% and 2.175 GPa, respectively.
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BACKGROUND: Porcine infection with Porcine circovirus type 2 (PCV2) causes immunosuppression, which is easy to cause concurrent or secondary infection, making the disease complicated and difficult to treat, and causing huge economic losses to the pig industry. Total polysaccharide from the rhizoma of Atractylodes macrocephala Koidz. (PAMK) is outstanding in enhancing non-specific immunity and cellular immunity, and effectively improving the body's disease resistance, indicating its potential role in antiviral immunotherapy. RESULTS: PAMK had the characteristics of compact, polyporous and agglomerated morphology, but does not have triple helix conformation. PCV2 infection led to the increase in LC3-II, degradation of p62 and the increase of viral Cap protein expression and viral copy number. PAMK treatment significantly alleviated PCV2-induced autophagy and inhibited PCV2 replication. Moreover, PAMK treatment significantly attenuated the increase of PINK1 protein expression and the decrease of TOMM20 protein expression caused by PCV2 infection, alleviated Parkin recruitment from cytoplasm to mitochondria and intracellular reactive oxygen species accumulation, restored mitochondrial membrane charge, alleviated viral Cap protein expression. CONCLUSION: PAMK alleviates PCV2-induced mitophagy to suppress PCV2 replication by inhibiting the Pink 1/Parkin pathway. These findings may provide new insights into the prevention and treatment of PCV2. © 2023 Society of Chemical Industry.
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Atractylodes , Circovirus , Animais , Suínos , Atractylodes/química , Circovirus/genética , Circovirus/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Polissacarídeos/química , Replicação ViralRESUMO
Electrochemical nitrate (NO3-) reduction in aqueous media provides a useful approach for ammonia (NH3) synthesis. While efforts are focused on developing catalysts, the local microenvironment surrounding the catalyst centers is of great importance for controlling electrocatalytic performance. Here, we demonstrate that a self-assembled molecular iron catalyst integrated in a free-standing conductive hydrogel is capable of selective production of NH3 from NO3- at efficiencies approaching unity. With the electrocatalytic hydrogel, the NH3 selectivity is consistently high under a range of negative biases, which results from the hydrophobicity increase of the polycarbazole-based electrode substrate. In mildly acidic media, proton reduction is suppressed by electro-dewetting of the hydrogel electrode, enhancing the selectivity of NO3- reduction. The electrocatalytic hydrogel is capable of continuous production of NH3 for at least 100 h with NH3 selectivity of â¼89 to 98% at high current densities. Our results highlight the role of constructing an internal hydrophobic surface for electrocatalysts in controlling selectivity in aqueous media.
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Atomically dispersed iron on nitrogen doped carbon displays high intrinsic activity toward oxygen reduction reaction, and has been identified as an attractive candidate to precious platinum catalysts. However, the loading of atomic iron sites is generally limited to below 4 wt% due to the undesired formation of iron-related particles at higher contents. Herein, this work overcomes this limit by a double riveting and steric hindrance strategy to achieve monodispersed iron with a high-loading of 12.8 wt%. Systematic study reveals that chemical riveting of atomic iron in ZIF-8 framework, chelation of Fe ions with interconfined 1,4-phenylenebisboronic, and physical hindrance are essential to obtain high-loading monodispersed Fe moieties. Resultantly, designed Fe-N-C-PDBA exhibits superior catalytic activity and excellent stability over commercial platinum catalysts toward oxygen reduction reaction in both half-cells and zinc-air fuel cells (ZAFCs). This provides an avenue for developing high-loading single-atom catalysts (SACs) for energy devices.
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The intestinal barrier is essential in early life to prevent infection, inflammation, and food allergies. It consists of microbiota, a mucus layer, an epithelial layer, and the immune system. Microbial metabolites, the mucus, antimicrobial peptides, and secretory immunoglobulin A (sIgA) protect the intestinal mucosa against infection. The complex interplay between these functionalities of the intestinal barrier is crucial in early life by supporting homeostasis, development of the intestinal immune system, and long-term gut health. Exclusive breastfeeding is highly recommended during the first 6 months. When breastfeeding is not possible, milk-based infant formulas are a safe alternative. Breast milk contains many bioactive components that help to establish the intestinal microbiota and influence the development of the intestinal epithelium and the immune system. Importantly, breastfeeding lowers the risk for intestinal and respiratory tract infections. Here we review all aspects of intestinal barrier function and the nutritional components that impact its functionality in early life, such asmicronutrients, bioactive milk proteins, milk lipids, and human milk oligosaccharides. These components are present in breast milk and can be added to milk-based infant formulas to support gut health and immunity.
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Microbioma Gastrointestinal , Leite Humano , Aleitamento Materno , Feminino , Trato Gastrointestinal , Humanos , Lactente , Mucosa Intestinal/metabolismoRESUMO
Many diseases are related to changes in the biomechanical properties of cells; their study can provide a theoretical basis for drug screening and can explain the internal working of living cells. In this study, the biomechanical properties of nephrocytes (VERO cells), hepatocytes (HL-7702 cells), and hepatoma cells (SMCC-7721 cells) in culture were detected by atomic force microscopy (AFM) to analyse the side effects of colchicine at different concentrations (0.1 µg/mL (A) and 0.2 µg/mL (B)) at the nanoscale for 2, 4 and 6 h. Compared with the corresponding control cells, the damage to the treated cells increased in a dose-dependent manner. Among normal cells, the injury of nephrocytes (VERO cells) was markedly worse than that of hepatocytes (HL-7702 cells) in both colchicine solutions A and B. Based on the analyses of biomechanical properties, the colchicine solution reduced the rate of division and inhibited metastasis of SMCC-7721 cells. By comparing these two concentrations, we found that the anticancer effect of colchicine solution A was greater than that of solution B. Studying the mechanical properties of biological cells can help understand the mechanism of drug action at the molecular level and provide a theoretical basis for preventing the emergence and diagnosis of diseases at the nanoscale.
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Colchicina , Hepatócitos , Animais , Chlorocebus aethiops , Colchicina/toxicidade , Fenômenos Biomecânicos , Células Vero , Microscopia de Força AtômicaRESUMO
Achieving organized assembly structures with high complexity and adjustable functionalities is a central quest in supramolecular chemistry. In this report, we study what happens when a discotic benzene-1,3,5-tricarboxamide (BTA) ligand containing three dipicolinic acid (DPA) groups is allowed to coordinate with lanthanide (Ln) ions. A multi-BTA coordination cluster forms, which behaves as a type of "supramolecular monomer", stacking into fibers via hydrogen bonds enabled by multiple BTA cores. The fibrous morphology and size, as well as the packing unit and the process by which it grows, were investigated by light scattering measurements, luminescence spectra, TEM images and molecular simulation data. More notably, by selecting the kind of lanthanide or mixture of lanthanides that is incorporated, tunable luminescence and magnetic relaxation properties without compromising the fibrous structure can be realized. This case of hierarchical self-assembly is made possible by the special structure of our BTA-like building block, which makes non-covalent bond types that are different along the radial (coordination bonds) and axial (H-bonds) directions, respectively, each with just the right strength. Moreover, the use of lanthanide coordination leads to materials with metal-derived optical and magnetic properties. Therefore, the established approach demonstrates a novel strategy for designing and fabrication of multi-functional supramolecular materials.
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Zwitterionic polyelectrolyte nanogels are prospective nanocarriers due to their soft loading pocket and regulated charges. We here report a facile strategy, namely, electrostatic-templated polymerization (ETP) for synthesizing zwitterionic nanogels with controlled size and properties. Specifically, with anionic-neutral diblock polymers as the template, zwitterionic monomers such as carboxybetaine methacrylate (CBMA) or carboxybetaine acrylamide (CBAA) are polymerized together with a cross-linker at pH 2 where the monomers exhibit only positive charge due to the protonation of the carboxyl group. The obtained polyelectrolyte complex micelles dissociate upon introducing a concentrated salt. The subsequent separation yields the released template and zwitterionic nanogels with regulated size and swelling ability, achieved by tuning the salt concentration and cross-linker fraction during polymerization. The obtained PCBMA nanogels exhibit charges depending on the pH, which enables not only the selective loading of different dye molecules, but also encapsulation and intracellular delivery of cytochrome c protein. Our study develops a facile and robust way for fabricating zwitterionic nanogels and validates their potential applications as promising nanocarriers for load and delivery of functional charged cargos.
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Although antibiotics are one of the most significant factors contributing to the propagation of antibiotic resistance genes (ARGs), studies on the dose-response relationship at sub-lethal concentrations of antibiotics remain scarce, despite their importance for assessing the risks of antibiotics in the environment. In this study, we constructed a series of microcosms to investigate the propagation of intracellular (iARGs) and extracellular (eARGs) ARGs in both water and biofilms when exposed to antibiotics at various concentrations (1-100 µg/L) and frequencies. Results showed that eARGs were more abundant than iARGs in water, while iARGs were the dominant ARGs form in biofilms. eARGs showed differentiated dose-response relationships from iARGs. The abundance of iARGs increased with the concentration of antibiotics as enhanced selective pressure overcame the metabolic burden of antibiotic-resistant bacteria carrying ARGs. However, the abundance of eARGs decreased with increasing antibiotic concentrations because less ARGs were secreted from bacterial hosts at higher concentrations (100 µg/L). Furthermore, combined exposure to two antibiotics (tetracycline & imipenem) showed a synergistic effect on the propagation of iARGs, but an antagonistic effect on the propagation of eARGs compared to exposure to a single antibiotic. When exposed to antibiotic at a fixed total dose, one-time dosing (1 time/10 d) favored the propagation of iARGs, while fractional dosing (5 times /10 d) favored the propagation of eARGs. This study sheds light on the propagation of antibiotic resistance in the environment and can help in assessing the risks associated with the use of antibiotics.
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Antibacterianos , Genes Bacterianos , Antibacterianos/farmacologia , Tetraciclina , Resistência Microbiana a Medicamentos/genética , Bactérias , ÁguaRESUMO
Brassica campestris L., a cadmium (Cd) hyperaccumulating herbaceous plant, is considered as a promising candidate for the bioremediation of Cd pollution. However, the molecular mechanisms regulating these processes remain unclear. The present work, using proteome studies combined with a transcriptome analysis, was carried out to reveal the response mechanisms of the hairy roots of Brassica campestris L. under Cd stress. Significant tissue necrosis and cellular damage occurred, and Cd accumulation was observed in the cell walls and vacuoles of the hairy roots. Through quantitative proteomic profiling, a total of 1424 differentially expressed proteins (DEPs) were identified, and are known to be enriched in processes including phenylalanine metabolism, plant hormone signal transduction, cysteine and methionine metabolism, protein export, isoquinoline alkaloid biosynthesis and flavone biosynthesis. Further studies combined with a transcriptome analysis found that 118 differentially expressed genes (DEGs) and their corresponding proteins were simultaneously up- or downregulated. Further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the 118 shared DEGs and DEPs indicated their involvement in calcium, ROS and hormone signaling-mediated response, including regulation of carbohydrate and energy metabolism, biosynthesis of GSH, PCs and phenylpropanoid compounds that play vital roles in the Cd tolerance of Brassica campestris L. Our findings contribute to a better understanding of the regulatory networks of Brassica campestris L. under Cd stress, as well as provide valuable information on candidate genes (e.g., BrPAL, BrTAT, Br4CL, BrCDPK, BrRBOH, BrCALM, BrABCG1/2, BrVIP, BrGCLC, BrilvE, BrGST12/13/25). These results are of particular importance to the subsequent development of promising transgenic plants that will hyperaccumulate heavy metals and efficient phytoremediation processes.
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Brassica , Cádmio , Cádmio/toxicidade , Cádmio/metabolismo , Brassica/metabolismo , Proteoma/metabolismo , Proteômica , Estresse Fisiológico/genética , Perfilação da Expressão Gênica/métodos , Redes e Vias Metabólicas/genética , Transcriptoma , Raízes de Plantas/genética , Raízes de Plantas/metabolismoRESUMO
The intrinsic magnetic topological insulator MnBi2Te4 has attracted significant interest recently as a promising platform for exploring exotic quantum phenomena. Here we report that, when atomically thin MnBi2Te4 is deposited on a substrate such as silicon oxide or gold, there is a very strong mechanical coupling between the atomic layer and the supporting substrate. This is manifested as an intense low-frequency breathing Raman mode that is present even for monolayer MnBi2Te4. Interestingly, this coupling turns out to be stronger than the interlayer coupling between the MnBi2Te4 atomic layers. We further found that these low-energy breathing modes are highly sensitive to sample degradation, and they become drastically weaker upon ambient air exposure. This is in contrast to the higher energy optical phonon modes which are much more robust, suggesting that the low-energy Raman modes found here can be an effective indicator of sample quality.
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Eye tracking technology is increasingly used to understand individuals' non-conscious, moment-to-moment processes during video-based learning. This review evaluated 44 eye tracking studies on video-based learning conducted between 2010 and 2021. Specifically, the review sought to uncover how the utilisation of eye tracking technology has advanced understandings of the mechanisms underlying effective video-based learning and what type of caution should be exercised when interpreting the findings of these studies. Four important findings emerged from the analysis: (1) not all the studies explained the mechanisms underlying effective video-based learning through employing eye tracking technology, and few studies disentangled the complex relationship between eye tracking metrics and cognitive activities these metrics represent; (2) emotional factors potentially serve to explain the processes that facilitate video-based learning, but few studies captured learners' emotional processes or evaluated their affective gains; (3) ecological validity should be improved for eye tracking research on video-based learning through methods such as using eye tracking systems that have high tolerance for head movements, allowing learners to take control of the pacing of the video, and communicating the learning objectives of the video to participants; and (4) boundary conditions, including personal (e.g. age, prior knowledge) and environmental factors (e.g. the topic of videos, type of knowledge), must be considered when interpreting research findings. The findings of this review inspire a number of propositions for designing and interpreting eye tracking research on video-based learning.
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Solar cell is a kind of devices for renewable and environmentally friendly energy conversion. One of the important things for solar cells is conversion efficiency. While much attention has been drawn to improving efficiency, the role of strain engineering in two-dimensional materials is not yet well-understood. Here, we propose aPmc21-As monolayer that can be used as a solar cell absorbing material. The bandgap of single-layerPmc21-As can be tuned from 1.83 to 0 eV by applying tensile strain, while keeping the direct bandgap characteristic. Moreover, it has high light absorption efficiency in the visible and near-infrared regions, which demonstrates a great advantage for improving the conversion efficiency of solar cells. Based on the tunable electronic and optical properties, a novel design strategy for solar cells with a wide absorption range and high absorption efficiency is suggested. Our results not only have direct implication in strain effect on two-dimensional materials, but also give a possible concept for improving the solar cell performance.