Impaired cell fate through gain-of-function mutations in a chromatin reader.

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by 'reader' proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatin-reader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.

m6Aexpress-enet: Predicting the regulatory expression m6A sites by an enet-regularization negative binomial regression model.

As the most abundant mRNA modification, m6A controls and influences many aspects of mRNA metabolism including the mRNA stability and degradation. However, the role of specific m6A sites in regulating gene expression still remains unclear. In additional, the multicollinearity problem caused by the correlation of methylation level of multiple m6A sites in each gene could influence the prediction performance. To address the above challenges, we propose an elastic-net regularized negative binomial regression model (called m6Aexpress-enet) to predict which m6A site could potentially regulate its gene expression. Comprehensive evaluations on simulated datasets demonstrate that m6Aexpress-enet could achieve the top prediction performance. Applying m6Aexpress-enet on real MeRIP-seq data from human lymphoblastoid cell lines, we have uncovered the complex regulatory pattern of predicted m6A sites and their unique enrichment pathway of the constructed co-methylation modules. m6Aexpress-enet proves itself as a powerful tool to enable biologists to discover the mechanism of m6A regulatory gene expression. Furthermore, the source code and the step-by-step implementation of m6Aexpress-enet is freely accessed at https://github.com/tengzhangs/m6Aexpress-enet.

Comparative Proteomics Elucidates the Potential Mechanism of Sperm Capacitation of Chinese Mitten Crabs (Eriocheir sinensis).

Sperm capacitation is broadly defined as a suite of biochemical and biophysical changes resulting from the acquisition of fertilization ability. To gain insights into the regulation mechanism of crustacean sperm capacitation, 4D label-free quantitative proteomics was first applied to analyze the changes of sperm in Eriocheir sinensis under three sequential physiological conditions: seminal vesicles (X2), hatched with the seminal receptacle content (X3), and incubated with egg water (X5). In total, 1536 proteins were identified, among which 880 proteins were quantified, with 82 and 224 proteins significantly altered after incubation with the seminal receptacle contents and egg water. Most differentially expressed proteins were attributed to biological processes by Gene Ontology annotation analysis. As the fundamental bioenergetic metabolism of sperm, the oxidative phosphorylation, glycolysis, and the pentose phosphate pathway presented significant changes under the treatment of seminal receptacle contents, indicating intensive regulation for sperm in the seminal receptacle. Additionally, the seminal receptacle contents also significantly increased the oxidation level of sperm, whereas the enhancement of abundance in superoxide dismutase, peroxiredoxin 1, and glutathione S-transferase after incubation with egg water significantly improved the resistance against oxidation. These results provided a new perspective for reproduction studies in crustaceans.

A pattern recognition receptor interleukin-1 receptor is involved in reproductive immunity in Macrobrachium nipponense ovary.

The family of TIR domain-containing receptors includes numerous proteins involved in innate immunity. In this study, a member of this family was characterized from the ovary of the oriental river prawn Macrobrachium nipponense and identified as interleukin-1 receptor (MnIL-1R). Meanwhile, to elucidate the conservation of IL-1R, its orthologous were identified in several crustacean species as well. In addition, the expression pattern of MnIL-1R in various adult tissues and post different pathogen-associated molecular patterns (PAMPs) challenge in ovary was analyzed with qRT-PCR technology. Finally, the roles of MnIL-1R in the ovary were analyzed by RNAi technology. The main results are as follows: (1) MnIL-1R comprises a 1785 bp ORF encoding 594 amino acids and is structurally composed of five domains: a signal peptide, two immunoglobulin (IG) domains, a transmembrane region, and a TIR-2 domain; (2) the TIR domain showed a high conservation among analyzed crustacean species; (3) MnIL-1R is widely detected in all tested tissues including ovary; (4) MnIL-1R showed a positive response to challenges with LPS, PGN, and polyI:C in the ovary; (5) its IG domain showed strong binding ability to LPS and PGN, confirming its role as a pattern recognition receptor; (6) the expression patterns of several members of the Toll signaling pathway (Myd88, TRAF-6, Dorsal, and Relish) was similar to that of MnIL-1R after challenges with LPS, PGN, and polyI:C in the ovary; (7) the silencing of MnIL-1R resulted in down-regulation of theses gene' (Myd88, TRAF-6, Dorsal, and Relish) expression level in the ovary. These results suggest that MnIL-1R can activate the Toll signaling pathway in the ovary by directly recognizing LPS and PGN through its IG domain, thereby contributing to the immune response in the ovary of M. nipponense.

Near-field coupling of interlayer excitons in MoSe2/WSe2 heterobilayers to surface plasmon polaritons.

Two-dimensional (2D) transition metal dichalcogenides have emerged as promising quantum functional blocks benefitting from their unique combination of spin, valley, and layer degrees of freedom, particularly for the tremendous flexibility of moiré superlattices formed by van der Waals stacking. These degrees of freedom coupled with the enhanced Coulomb interaction in 2D structures allow excitons to serve as on-chip information carriers. However, excitons are spatially circumscribed due to their low mobility and limited lifetime. One way to overcome these limitations is through the coupling of excitons with surface plasmon polaritons (SPPs), which facilitates an interaction between remote quantum states. Here, we showcase the successful coupling of SPPs with interlayer excitons in molybdenum diselenide/tungsten diselenide heterobilayers. Our results indicate that the valley polarization can be efficiently transferred to SPPs, enabling preservation of polarization information even after propagating tens of micrometers.

In-Plane Electric-Field-Induced Orbital Hybridization of Excitonic States in Monolayer WSe_{2}.

The giant exciton binding energy and the richness of degrees of freedom make monolayer transition metal dichalcogenide an unprecedented playground for exploring exciton physics in 2D systems. Thanks to the well-energetically separated excitonic states, the response of the discrete excitonic states to the electric field could be precisely examined. Here we utilize the photocurrent spectroscopy to probe excitonic states under a static in-plane electric field. We demonstrate that the in-plane electric field leads to a significant orbital hybridization of Rydberg excitonic states with different angular momentum (especially orbital hybridization of 2s and 2p) and, consequently, optically actives 2p-state exciton. Besides, the electric-field controlled mixing of the high lying exciton state and continuum band enhances the oscillator strength of the discrete excited exciton states. This electric field modulation of the excitonic states in monolayer TMDs provides a paradigm of the manipulation of 2D excitons for potential applications of the electro-optical modulation in 2D semiconductors.

Characterization of the LysP2110-HolP2110 Lysis System in Ralstonia solanacearum Phage P2110.

Ralstonia solanacearum, a pathogen causing widespread bacterial wilt disease in numerous crops, currently lacks an optimal control agent. Given the limitations of traditional chemical control methods, including the risk of engendering drug-resistant strains and environmental harm, there is a dire need for sustainable alternatives. One alternative is lysin proteins that selectively lyse bacteria without contributing to resistance development. This work explored the biocontrol potential of the LysP2110-HolP2110 system of Ralstonia solanacearum phage P2110. Bioinformatics analyses pinpointed this system as the primary phage-mediated host cell lysis mechanism. Our data suggest that LysP2110, a member of the Muraidase superfamily, requires HolP2110 for efficient bacterial lysis, presumably via translocation across the bacterial membrane. LysP2110 also exhibits broad-spectrum antibacterial activity in the presence of the outer membrane permeabilizer EDTA. Additionally, we identified HolP2110 as a distinct holin structure unique to the Ralstonia phages, underscoring its crucial role in controlling bacterial lysis through its effect on bacterial ATP levels. These findings provide valuable insights into the function of the LysP2110-HolP2110 lysis system and establish LysP2110 as a promising antimicrobial agent for biocontrol applications. This study underpins the potential of these findings in developing effective and environment-friendly biocontrol strategies against bacterial wilt and other crop diseases.

Antioxidant Peptides Derived from Millet Bran Promote Longevity and Stress Resistance in Caenorhabditis elegans.

Millet bran as a by-product of millet grain processing remains a reservoir of active substances. In this study, functional millet bran peptides (MBPE) were obtained from bran proteins after alcalase hydrolysis and ultrafiltration. The activity of MBPE was assessed in vitro and in the model organism Caenorhabditis elegans (C. elegans). In vitro, compared to unhydrolyzed proteins, MBPE significantly enhanced the 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate (ABTS) and hydroxyl radicals scavenging activity, and the scavenging rate of MBPE with 15,000 U/g alcalase reached 42.79 ± 0.31%, 61.38 ± 0.41 and 45.69 ± 0.84%, respectively. In C. elegans, MBPE at 12.5 µg/mL significantly prolonged the lifespan by reducing lipid oxidation, oxidative stress, and lipofuscin levels. Furthermore, MBPE increased the activities of the antioxidant enzymes. Genetic analyses showed that MBPE-mediated longevity was due to a significant increase in the expression of daf-16 and skn-1, which are also involved in xenobiotic and oxidative stress responses. In conclusion, this study found that MBPE had antioxidant and life-prolonging effects, which are important for the development and utilization of millet bran proteins as resources of active ingredients.

Controlled Self-assembly of Gold(I) Complexes by Multiple Kinetic Aggregation States with Nonlinear Optical and Waveguide Properties.

Introduction of multiple kinetic aggregation states (Aggs) into the self-assembly pathway could bring complexity and flexibility to the self-assemblies, which is difficult to realize due to the delicate equilibria established among different Aggs bonded by weak noncovalent interactions. Here, we describe a series of chiral and achiral d10 AuI bis(N-heterocyclic carbene, NHC) complexes, and the achiral complex could undergo self-assembly with multiple kinetic Aggs. Generation of multiple kinetic Aggs was realized by applying chiral or achiral seeds exhibiting large differences in elongation temperatures for their respective cooperative self-assembly processes. We further showed that the chiral AuI self-assemblies having non-centrosymmetric packing forms exhibit nonlinear optical response of second harmonic generation (SHG), while the SHG signal is absent in the achiral analogue. The crystalline achiral AuI self-assemblies could function as optical waveguides with strong emission polarization.

First report of bacterial leaf spot disease on Pueraria montana var. thomsonii caused by Robbsia andropogonis in China.

Pueraria montana var. thomsonii (Hereinafter referred to as Pmt) belongs to the Leguminosae and is widely distributed in China, Laos, Thailand, Myanmar, Bhutan and other Asian countries. The plant is called "Fenge" in China, and its root is widely used in medicine and food. In recent years, an unknown leaf spot disease of Pmt has occurred in Gaoming, Zhaoqing and Yunfu districts of Guangdong Province in China, where 1,600 hectares of Pmt plants were affected. The incidence rate of plants were more than 80% and led to 10-15% death of Pmt plants in Gaoming district. . In the early stage of the disease, radiating and water-soaking lesions appeared between the main veins and side veins of Pmt leaves. After the spread of the lesions, they formed brown and short strips with yellow haloes around them, which led to leaf shedding, plant death and decline of production. To isolate bacteria, diseased leaves were surface sterilized with 0.6% sodium hypochlorite solution for 30 s, followed by three consecutive rinses in distilled water. The leaves were aseptically macerated, and the macerate streaked on PDA medium. Whitish to dull white, mucoid, raised, round, and translucent colonies were obtained. All isolates were gram-negative and had a single, polar, sheathed flagellum. Sequences (approx. 1,458 bp each) of the 16S rRNA gene amplified from five isolates (FG2, FG3, FG9, FG12 and FG17) using primer pair 27F/1492R (Lane et al,1991) (GenBank Accession Nos. OL677034, OL677351, OL677352, OL677353 and OL677354 respectively) shared 99.93% sequence identity with that of Robbsia andropogonis (Synonyms: Burkholderia andropogonis) (Lopes-Santos et al,2017) type strain LMG2129 (NR104960.1). The specific 410-bp and 704-bp target fragments were also amplified from isolates using R. andropogonis-specific primers Pf/Pr (Bagsic et al,1995) and LJ23f/LJ24R (Duan et al,2009). The four housekeeping genes atpD, lepA, gyrB and rpoD were partially sequenced for FG9 isolates using primers atpD-F3/atpD-R3, lepA-F2/lepA-R, LJ23f/LJ24R and LJ25f/LJ26r (Duan et al,2009; Estrada-De et al,2013) respectively. Multilocus sequence analyses confirmed the isolates from Pmt as R. andropogonis. Physiological and biochemical tests revealed the isolates are negative for oxidase, arginine dihydrolase, saccharose and betaine, and positive for sorbitol, lactose and galactose (Gillis et al,1995; Lopes-Santos et al,2017). In addition, all isolates caused a hypersensitive reaction on leaves of Nicotiana benthamiana and were pathogenic to some crops, including maize (Zea mays), sorghum (Sorghum bicolor), carnation (Dianthus caryophilus), common bean (Phaseolus vulgaris), tomato. Five isolates (FG2, FG3, FG9, FG12 and FG17) pathogenicity were tested twice with a total of three replications per isolate. Two young leaves each of 3-month-old Pmt plants grow in greenhouse were sprayed a bacterial suspension at 108 CFU/ml, then covered the inoculated leaves individually with plastic bags for 24 h, and incubated at 100% relative humidity with 16 h of daylight at 30°C and 8 h of darkness at 22°C in a greenhouse. Radiating and water-soaked lesions with yellow haloes were observed between the main veins and side veins of Pmt leaves 5 days after inoculation and were similar to those caused by R. andropogonis in the field. Koch's postulates were fulfilled by reisolating bacteria from typical lesions on inoculated plants. And the reisolated bacteria were identical to the inoculated ones. To our knowledge, this is the first report of R. andropogonis on Pueraria montana var. thomsonii in China.

Promotion of Interface Fusion of Solid Polymer Electrolyte and Cathode by Ultrasonic Vibration.

All-solid-state polymer lithium batteries have good safety, stability, and high energy densities and are employed in wireless sensors. However, the solid contact between the polymer electrolyte and the cathode leads to high interface resistance, limiting the broad application of solid-state lithium batteries. This paper proposes an ultrasonic fusion method to reduce the interface resistance between the polymer electrolyte and the cathode. The method applied a high-frequency ultrasonic vibration technique to impact the polymer electrolyte/cathode structure, melting the electrolyte at the interface and thus generating good contact at the interface. The experimental results showed that the ultrasonic fusion method decreased the interface resistance between the polymer electrolyte and the cathode by 96.2%. During the ultrasonic fusion process, high-frequency ultrasonic vibrations generated high temperatures at the interface, and the polymer electrolyte became molten, improving the contact between the electrolyte and the cathode. The ultrasonic fusion method eliminated the gaps at the interface, and the interface became more compact. Furthermore, ultrasonic vibrations made the molten electrolyte fill the holes in the cathode, and the contact area was enhanced, providing more Li+ ions transmission paths.

Protective Effects of Flavonoids against Alzheimer's Disease: Pathological Hypothesis, Potential Targets, and Structure-Activity Relationship.

Alzheimer's disease (AD) is a neurodegenerative disease with high morbidity and mortality, for which there is no available cure. Currently, it is generally believed that AD is a disease caused by multiple factors, such as amyloid-beta accumulation, tau protein hyperphosphorylation, oxidative stress, and inflammation. Multitarget prevention and treatment strategies for AD are recommended. Interestingly, naturally occurring dietary flavonoids, a class of polyphenols, have been reported to have multiple biological activities and anti-AD effects in several AD models owing to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties. In this review, we summarize and discuss the existing multiple pathogenic factors of AD. Moreover, we further elaborate on the biological activities of natural flavonoids and their potential mode of action and targets in managing AD by presenting a wide range of experimental evidence. The gathered data indicate that flavonoids can be regarded as prophylactics to slow the advancement of AD or avert its onset. Different flavonoids have different activities and varying levels of activity. Further, this review summarizes the structure-activity relationship of flavonoids based on the existing literature and can provide guidance on the design and selection of flavonoids as anti-AD drugs.

Efficient Long-Range Triplet Exciton Transport by Metal-Metal Interaction at Room Temperature.

Efficient and long-range exciton transport is critical for photosynthesis and opto-electronic devices, and for triplet-harvesting materials, triplet exciton diffusion length ( L D ) and coefficient ( D ) are key parameters in determining their performances. Herein, we observed that PtII and PdII organometallic nanowires exhibit long-range anisotropic triplet exciton LD of 5-7 µm along the M-M direction using direct photoluminescence (PL) imaging technique by low-power continuous wave (CW) laser excitation. At room temperature, via a combined triplet-triplet annihilation (TTA) analysis and spatial PL imaging, an efficient triplet exciton diffusion was observed for the PtII and PdII nanowires with extended close M-M contact, while is absent in nanowires without close M-M contact. Two-dimensional electronic spectroscopy (2DES) and calculations revealed a significant contribution of the delocalized 1/3 [dσ*(M-M)→π*] excited state during the exciton diffusion modulated by the M-M distance.

Slight up-regulation of Kir2.1 channel promotes endothelial progenitor cells to transdifferentiate into a pericyte phenotype by Akt/mTOR/Snail pathway.

It was shown that endothelial progenitor cells (EPCs) have bidirectional differentiation potential and thus perform different biological functions. The purpose of this study was to investigate the effects of slight up-regulation of the Kir2.1 channel on EPC transdifferentiation and the potential mechanism on cell function and transformed cell type. First, we found that the slight up-regulation of Kir2.1 expression promoted the expression of the stem cell stemness factors ZFX and NS and inhibited the expression of senescence-associated ß-galactosidase. Further studies showed the slightly increased expression of Kir2.1 could also improve the expression of pericyte molecular markers NG2, PDGFRß and Desmin. Moreover, adenovirus-mediated Kir2.1 overexpression had an enhanced contractile response to norepinephrine of EPCs. These results suggest that the up-regulated expression of the Kir2.1 channel promotes EPC transdifferentiation into a pericyte phenotype. Furthermore, the mechanism of EPC transdifferentiation to mesenchymal cells (pericytes) was found to be closely related to the channel functional activity of Kir2.1 and revealed that this channel could promote EPC EndoMT by activating the Akt/mTOR/Snail signalling pathway. Overall, this study suggested that in the early stage of inflammatory response, regulating the Kir2.1 channel expression affects the biological function of EPCs, thereby determining the maturation and stability of neovascularization.

Oscillating shear stress mediates mesenchymal transdifferentiation of EPCs by the Kir2.1 channel.

Although endothelial progenitor cells (EPCs) are considered to be an essential source of vascular endothelial repair, their bidirectional differentiation determines that they play a double-edged role in the restoration of endothelial injury. In this research, we investigated the effect of Kir2.1 ion channel on the transdifferentiation of endothelial progenitor cells (EPCs) under the oscillating shear stress (OSS) and the molecular mechanisms underlying the pathological vascular remodeling. EPCs were treated with OSS (± 3.5 dynes/cm2, 1 Hz) simulated with the parallel flow chamber system. The results have shown that OSS promoted the expression of α-SMA and SM22, markers of mesenchymal cells on EPCs. Moreover, OSS also increased expression of Kir2.1 in EPCs. The down-regulation of Kir2.1 reduced OSS-induced EPC mesenchymal transdifferentiation. The overexpression of Kir2.1 suppressed the angiogenic abilities of EPCs in vitro. In parallel, the overexpression of Kir2.1 on EPCs thickened the carotid tunica intima in rat carotid artery balloon injured model in vivo. Taken together, those data indicated that the OSS could facilitate the transdifferentiation of EPCs by increasing Kir2.1 expression. This study provides a novel insight into the pathogenesis of cardiovascular diseases and gives evidence for Kir2.1 as a potential therapeutic target.

Preparation, characterization, and evaluation of antioxidant activity and bioavailability of a self-nanoemulsifying drug delivery system (SNEDDS) for buckwheat flavonoids.

The self-nanoemulsifying drug delivery system has shown many advantages in drug delivery. In this study, a self-nanoemulsifying drug delivery system of buckwheat flavonoids was prepared for enhancing its antioxidant activity and oral bioavailability. A nanoemulsion of buckwheat flavonoids was developed and characterized, and its antioxidant, in vitro release, and in vivo bioavailability were determined. The nanoemulsion was optimized by the central composite design response surface experiment, and its particle size, polymer dispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and stability were evaluated. The antioxidant activity was tested by measuring its 2,2-diphenyl-1-picrylhydrazyl scavenging activity, hydroxyl radical scavenging activity, and superoxide anion scavenging ability. In vitro release of buckwheat flavonoids nanoemulsion showed a higher cumulative release than the suspension, and the release fitting model followed the Ritger-Peppas and Weibull models. The effective concentration of the nanoemulsion was evaluated in vivo using a Wistar rat model, and the area under the plasma concentration-time curve of the buckwheat flavonoids nanoemulsion was 2.2-fold higher than that of the buckwheat flavonoid suspension. The Cmax of the nanoemulsion was 2.6-fold greater than that of the suspension. These results indicate that the nanoemulsion is a promising oral drug delivery system that can improve the oral bioavailability to satisfy the clinical requirements.

Inhibition of Kir2.1 channel-induced depolarization promotes cell biological activity and differentiation by modulating autophagy in late endothelial progenitor cells.

AIMS: Endothelial progenitor cells (EPCs) play a crucial role in postnatal angiogenesis and neovascularization. Inward rectifier potassium channel 2.1 (Kir2.1) have been identified in EPCs. However, the effect of Kir2.1 on EPC function is not known. Here, we try to establish the role of Kir2.1 channels in EPC function and to provide first insights into the mechanisms. METHODS AND RESULTS: We first observed that the expression of Kir2.1 gradually decreased with the differentiation of EPCs into ECs in gene and protein levels. Treatment with the Kir2.1-selective inhibitor ML133 or knockdown of Kir2.1 by shRNA triggered EPC depolarization and promoted EPC biological functions, such as migration, adhesion, angiogenesis and differentiation into ECs in vitro. Transplantation of ML133-treated or Kir2.1 knockdown EPCs facilitated re-endothelialization in the rat injured arterial segment and inhibited neointima formation in vivo. In parallel, ML133 significantly enhanced autophagy and autophagic flux. After suppression of autophagy by 3-methyladenine (3-MA), the effects of ML133 on in vitro function and in vivo endothelialization capacity of EPCs were significantly inhibited. Mechanistically, ML133-induced autophagy was mediated at least partly by increased the activity of reactive oxygen species (ROS) that likely through intracellular calcium. CONCLUSION: Our study indicates that blocking or knockdown Kir2.1 results in a moderate depolarization of EPCs, which directly participated in enhancing EPC functions both in vitro and in vivo. In the mean time, autophagy signaling pathway is, at least in part, involved in this process. It may provide a potential target for the treatment or prevention of vascular injury and disease.

Recombinant Buckwheat Trypsin Inhibitor Improves the Protein and Mitochondria Homeostasis in Caenorhabditis elegans Model of Aging and Age-Related Disease.

BACKGROUND: With the acceleration of aging process in human society, improvements of the physical functionality and life quality in the elderly population are more meaningful than pure longevity. Buckwheat trypsin inhibitor is a low molecular weight polypeptide extracted from buckwheat, which is a beneficial food for improving the health in the elderly. OBJECTIVES: The aim of the current study was to evaluate the potential beneficial effects of recombinant buckwheat trypsin inhibitor (rBTI) on age-dependent function decline and the primary mechanism. METHOD: Day 10 N2 Caenorhabditis elegans and day 6 AM140 C. elegans cultured at 25°C were used as models of aging and age-related disease, respectively. Motor function was as an indicator of age-dependent function. ATP content and damage mitochondrial DNA mass were detected to assess mitochondrial damage and function by ATP Assay Kit and agarose gel electrophoresis, respectively. Soluble protein content was quantified by SDS polyacrylamide gel electrophoresis. Autophagy-related genes transcription levels, autophagy marker proteins lgg-1, and lysosomal content were analyzed to quantify autophagy levels by qRT-PCR, transgenic C. elegans, and lysosomal staining. Autophagy inhibitor chloroquine, daf-16 mutant, and RNA Interference were used to determine the roles of autophagy and DAF-16 in rBTI-mediated effects. RESULTS: In this study, we found that rBTI could decrease the proportions of insoluble protein and impaired mitochondria, finally reduce motility deficits in both models. Further study indicated that rBTI activated the autophagy, and the inhibition of autophagy reduced rBTI-mediated beneficial effects. Genetic analyses showed the transcriptional activity of DAF-16 was increased by rBTI and was required for rBTI-mediated beneficial effects. CONCLUSIONS: These data indicated that rBTI might promote the autophagy to alleviate the age-related functional decline via DAF-16 in C. elegans and suggested a potential role of rBTI as a nutraceutical for the improvement of age-related complications.

Peroxidase from proso millet exhibits endonuclease-like activity.

In this study, the mechanism of DNA cleavage by cationic peroxidase from proso millet (PmPOD) was investigated. PmPOD cleaved supercoiled circular DNA into both nicked circular and linear forms via a cleavage mechanism that resembles those of native endonucleases. Inhibition and ligation studies demonstrated that reactive oxygen species and the ferriprotoporphyrin IX moiety in PmPOD are not involved in PmPOD-mediated DNA cleavage. Similar to other endonucleases, Mg ions considerably enhance the DNA cleavage activity of PmPOD. Further studies suggested that PmPOD can disrupt phosphodiester bonds in DNA and mononucleotides, indicating that it is a phosphatase. The phosphatase activity of PmPOD is higher than that of horseradish peroxidase (HRP), but the peroxidase activity of PmPOD was lower than that of HRP. PmPOD-mediated hydrolytic cleavage of DNA observed in this study is different from those reported for heme proteins. This study provides valuable insights into the distinct mechanisms underlying DNA cleavage by heme proteins.

Manipulating spin-polarized photocurrents in 2D transition metal dichalcogenides.

Manipulating spin polarization of electrons in nonmagnetic semiconductors by means of electric fields or optical fields is an essential theme of the conceptual nonmagnetic semiconductor-based spintronics. Here we experimentally demonstrate an electric method of detecting spin polarization in monolayer transition metal dichalcogenides (TMDs) generated by circularly polarized optical pumping. The spin-polarized photocurrent is achieved through the valley-dependent optical selection rules and the spin-valley locking in monolayer WS2, and electrically detected by a lateral spin-valve structure with ferromagnetic contacts. The demonstrated long spin-valley lifetime, the unique valley-contrasted physics, and the spin-valley locking make monolayer WS2 an unprecedented candidate for semiconductor-based spintronics.