2D ferroelectric material has emerged as an attractive building block for high‐density data storage nanodevices. Although monolayer van der Waals ferroelectrics have been theoretically predicted, a ...key experimental breakthrough for such calculations is still not realized. Here, hexagonally stacking α‐In2Se3 nanoflake, a rarely studied van der Waals polymorph, is reported to exhibit out‐of‐plane (OOP) and in‐plane (IP) ferroelectricity at room temperature. Ferroelectric multidomain states in a hexagonal α‐In2Se3 nanoflake with uniform thickness can survive to 6 nm. Most strikingly, the electric‐field‐induced polarization switching and hysteresis loop are, respectively, observed down to the bilayer and monolayer (≈1.2 nm) thicknesses, which designates it as the thinnest layered ferroelectric and verifies the corresponding theoretical calculation. In addition, two types of ferroelectric nanodevices employing the OOP and IP polarizations in 2H α‐In2Se3 are developed, which are applicable for nonvolatile memories and heterostructure‐based nanoelectronics/optoelectronics.
The thinnest layered ferroelectric is demonstrated for the first time at room temperature. The semiconducting hexagonal α‐In2Se3 nanoflakes exhibit out‐of‐plane and in‐plane ferroelectricity that are closely intercorrelated. The polarization switching and hysteresis loops can be realized in the thickness as thin as ≈2.3 nm (bilayer) and ≈1.2 nm (monolayer). Two types of ferroelectric switchable devices are proposed to show the potential application in nonvolatile memories.
The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains ...poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells.
Plant exosome-like nanovesicles, being innately replete with bioactive lipids, proteins, RNA, and other pharmacologically active molecules, offer unique morphological and compositional ...characteristics as natural nanocarriers. Furthermore, their compelling physicochemical traits underpin their modulative role in physiological processes, all of which have fostered the concept that these nanovesicles may be highly proficient in the development of next-generation biotherapeutic and drug delivery nanoplatforms to meet the ever-stringent demands of current clinical challenges. This review systemically deals with various facets of plant exosome-like nanovesicles ranging from their origin and isolation to identification of morphological composition, biological functions, and cargo-loading mechanisms. Efforts are made to encompass their biotherapeutic roles by elucidating their immunological modulating, anti-tumor, regenerative, and anti-inflammatory roles. We also shed light on re-engineering these nanovesicles into robust, innocuous, and non-immunogenic nanovectors for drug delivery through multiple stringent biological hindrances to various targeted organs such as intestine and brain. Finally, recent advances centered around plant exosome-like nanovesicles along with new insights into transdermal, transmembrane and targeting mechanisms of these vesicles are also elucidated. We expect that the continuing development of plant exosome-like nanovesicle-based therapeutic and delivery nanoplatforms will promote their clinical applications.
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Herein, the origin, fabrication, and characterization of plant exosome-like nanovesicles (PELNVs) are reviewed. The unique features, therapeutic effects, and re-engineering of PELNVs into nanoplatforms for delivering functional biomacromolecules, such as nucleic acids, proteins for the treatment of immunological disease, inflammation, and cancer, among others, are also summarized and prospected.
Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer’s disease (AD), little is known about the molecular changes and cellular interactions that ...characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
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•Spatial transcriptomics identifies a plaque-induced gene (PIG) network•Spatial transcriptomics identifies an oligodendrocyte gene (OLIG) response in AD•In situ sequencing in mouse and human confirms these responses at single-cell level•PIG and OLIG responses are conserved over different neurodegenerative diseases
A combination of spatial transcriptomics and in situ sequencing on mouse and human brain demonstrates multicellular gene co-expression networks in Alzheimer’s disease, two of which are induced by accumulating amyloid plaques. A plaque-induced gene (PIG) network mainly involving micro- and astroglia and an oligodendrocyte gene (OLIG) and myelination response are identified.
The pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) remained unclear. We aimed to profile the metabolic alterations in urine of SFTS patients and provide new evidence for its ...pathogenesis.
A case-control study was conducted in the 154th hospital in China. Totally 88 cases and 22 controls aged ≥ 18 years were enrolled. The cases were selected from laboratory-confirmed SFTS patients. The controls were selected among SFTSV-negative population. Those with diabetes, cancer, hepatitis and other sexually transmitted diseases were excluded in both groups. Fatal cases and survival cases were 1:1 matched. Inter-group differential metabolites and pathways were obtained, and the inter-group discrimination ability was evaluated.
Tryptophan metabolism and phenylalanine metabolism were the top one important metabolism pathway in differentiating the control and case groups, and the survival and fatal groups, respectively. The significant increase of differential metabolites in tryptophan metabolism, including 5-hydroxyindoleacetate (5-HIAA), L-kynurenine (KYN), 5-hydroxy-L-tryptophan (5-HTP), 3-hydroxyanthranilic acid (3-HAA), and the increase of phenylpyruvic acid and decrease of hippuric acid in phenylalanine metabolism indicated the potential metabolic alterations in SFTSV infection. The increase of 5-HIAA, KYN, 5-HTP, phenylpyruvic acid and hippuric acid were involved in the fatal progress of SFTS patients.
Tryptophan metabolism and phenylalanine metabolism might be involved in the pathogenesis of SFTSV infection. These findings provided new evidence for the pathogenesis and treatment of SFTS.
The combination of transition‐metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with ...chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α‐aminonitriles and α‐aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α‐functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
The first enantioselective reductive cyanation and phosphonylation of secondary amides have been achieved by the combination of iridium with chiral thiourea catalysis. The protocol is highly efficient and enantioselective, providing a novel route for the synthesis of optically active α‐aminonitriles and α‐aminophosphonates from bench‐stable feedstocks.
Abstract
Monolayer transition metal dichalcogenides, such as MoS
2
and WSe
2
, have been known as direct gap semiconductors and emerged as new optically active materials for novel device ...applications. Here we reexamine their direct gap properties by investigating the strain effects on the photoluminescence of monolayer MoS
2
and WSe
2
. Instead of applying stress, we investigate the strain effects by imaging the direct exciton populations in monolayer WSe
2
–MoS
2
and MoSe
2
–WSe
2
lateral heterojunctions with inherent strain inhomogeneity. We find that unstrained monolayer WSe
2
is actually an indirect gap material, as manifested in the observed photoluminescence intensity–energy correlation, from which the difference between the direct and indirect optical gaps can be extracted by analyzing the exciton thermal populations. Our findings combined with the estimated exciton binding energy further indicate that monolayer WSe
2
exhibits an indirect quasiparticle gap, which has to be reconsidered in further studies for its fundamental properties and device applications.
Background and Aim
Chromoendoscopy with the use of indigo carmine (IC) dye is a crucial endoscopic technique to identify gastrointestinal neoplasms. However, its performance is limited by the ...endoscopist's skill, and no standards are available for lesion identification. Thus, we developed an artificial intelligence (AI) model to replace chromoendoscopy.
Methods
This pilot study assessed the feasibility of our novel AI model in the conversion of white‐light images (WLI) into virtual IC‐dyed images based on a generative adversarial network. The predictions of our AI model were evaluated against the assessments of five endoscopic experts who were blinded to the purpose of this study with a staining quality rating from 1 (unacceptable) to 4 (excellent).
Results
The AI model successfully transformed the WLI of polyps with different morphologies and different types of lesions in the gastrointestinal tract into virtual IC‐dyed images. The quality ratings of the real IC‐dyed and AI images did not significantly differ concerning surface structure (AI vs IC: 3.08 vs 3.00), lesion border (3.04 vs 2.98), and overall contrast (3.14 vs 3.02) from 10 sets of images (10 AI images and 10 real IC‐dyed images). Although the score depended significantly on the evaluator, the staining methods (AI or real IC) and evaluators had no significant interaction (P > 0.05) with each other.
Conclusion
Our results demonstrated the feasibility of employing AI model's virtual IC staining, increasing the possibility of being employed in daily practice. This novel technology may facilitate gastrointestinal lesion identification in the future.
Abstract
Van der Waals heterobilayers of transition metal dichalcogenides with spin–valley coupling of carriers in different layers have emerged as a new platform for exploring spin/valleytronic ...applications. The interlayer coupling was predicted to exhibit subtle changes with the interlayer atomic registry. Manually stacked heterobilayers, however, are incommensurate with the inevitable interlayer twist and/or lattice mismatch, where the properties associated with atomic registry are difficult to access by optical means. Here, we unveil the distinct polarization properties of valley-specific interlayer excitons using epitaxially grown, commensurate WSe
2
/MoSe
2
heterobilayers with well-defined (AA and AB) atomic registry. We observe circularly polarized photoluminescence from interlayer excitons, but with a helicity opposite to the optical excitation. The negative circular polarization arises from the quantum interference imposed by interlayer atomic registry, giving rise to distinct polarization selection rules for interlayer excitons. Using selective excitation schemes, we demonstrate the optical addressability for interlayer excitons with different valley configurations and polarization helicities.
Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals of any age who have been inactive for a prolonged period or immobilization. Additionally, acute diseases such as ...COVID-19 can cause frequent sequelae and exacerbate muscle wasting, leading to additional fatigue symptoms. It is necessary to investigate potent functional nutrients for muscle reinforcement in both disuse atrophy and fatigue to ensure better physical performance.
The effects of Sanghuangporus sanghuang SS-MN4 mycelia were tested on two groups of 6-week-old male mice-one with disuse atrophy and the other with fatigue. The disuse atrophy group was divided into three sub-groups: a control group, a group that underwent hind limb casting for 7 days and then recovered for 7 days and a group that was administered with SS-MN4 orally for 14 days, underwent hind limb casting for 7 days and then recovered for 7 days. The fatigue group was divided into two sub-groups: a control group that received no SS-MN4 intervention and an experimental group that was administered with SS-MN4 orally for 39 days and tested for exhaustive swimming and running on Day 31 and Day 33, respectively. RNA sequencing (RNA-seq) and western blot analysis were conducted on C2C12 cell lines to identify the therapeutic effects of SS-MN4 treatment.
In a disuse atrophy model induced by hind limb casting, supplementing with 250 mg/kg of SS-MN4 for 14 days led to 111.2% gastrocnemius muscle mass recovery and an 89.1% improvement in motor function on a treadmill (P < 0.05). In a fatigue animal model, equivalent SS-MN4 dosage improved swimming (178.7%) and running (162.4%) activities (P < 0.05) and reduced blood urea nitrogen levels by 18% (P < 0.05). SS-MN4 treatment also increased liver and muscle glycogen storage by 34.36% and 55.6%, respectively, suggesting a higher energy reserve for exercise. RNA-seq and western blot studies from the C2C12 myotube showed that SS-MN4 extract upregulates Myh4 and helps sustain myotube integrity against dexamethasone damage.
Supplementation of SS-MN4 (250-mg/kg body weight) with hispidin as active compound revealed a potential usage as a muscle nutritional supplement enhancing muscle recovery, fast-twitch fibre regrowth and fatigue resistance.
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