Search

Abstract In mammals, global passive demethylation contributes to epigenetic reprogramming during early embryonic development. At this stage, the majority of DNA-methyltransferase 1 (DNMT1) protein is excluded from nucleus, which is considered the primary cause. However, whether the remaining nuclear activity of DNMT1 is regulated by additional mechanisms is unclear. Here, we report that nuclear DNMT1 abundance is finetuned through proteasomal degradation in mouse zygotes. We identify a maternal factor, Pramel15, which targets DNMT1 for degradation via Cullin-RING E3 ligases. Loss of Pramel15 elevates DNMT1 levels in the zygote pronuclei, impairs zygotic DNA demethylation, and causes a stochastic gain of DNA methylation in early embryos. Thus, Pramel15 can modulate the residual level of DNMT1 in the nucleus during zygotic DNA replication, thereby ensuring efficient DNA methylation reprogramming in early embryos.

IntroductionIntra-speciic variation is the main source of functional trait diversity and has similar ecological effects as inter-speciic variation.MethodsWe studied 79 species and 3546 individuals from 50 ixed monitoring plots in subtropical evergreen broad - leaved secondary forests in Zhejiang Province, China. Using trait gradient analysis, we examined nine traits (speciic leaf area, leaf dry matter content, wood density, leaf area, chlorophyll content, leaf nitrogen content, leaf phosphorus content, leaf potassium content, and nitrogen-phosphorus ratio) by decomposing species functional traits into alpha (within-community) and beta (among-communities) measure the impact of environmental gradients and the presence of other species on the variation of traits.ResultAll nine functional traits showed some degree of differentiation in the forest communities, with a greater range of variation in alpha values than in beta values . Correlations were signiicantly different between the trait differences in the communities. The alpha values of each trait showed a higher correlation with other components than the beta values. The factors affecting intra-speciic trait variation were relatively complex. The alpha component had a more signiicant and stronger effect on intra-speciic trait variation compared to the beta component. Abiotic factors, such as soil nutrient content, soil nitrogen-phosphorus content, directly affected the beta component. In contrast, biotic factors, such as tree height variation, had a direct and stronger effect on the alpha component.DiscussionOur results demonstrate that alpha and beta components, as independent differentiation axes among coexisting species, have different sensitivities to different environmental factors and traits in different ecological strategies and spatial scales. Trait gradient analysis can more clearly reveal the variation patterns of species traits in communities, which will help to understand the scale effects and potential mechanisms of trait relationships.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

The Nantong Ancient Ship refers to an ancient Chinese wooden ship of the late Ming Dynasty excavated in Nantong city in December 2022. This paper identifies the wood and discusses its related analysis. Wood samples extracted from the Nantong Ancient Ship were studied from the viewpoints of anatomy, physics, and chemistry. Microscopic identification results concluded that willow and Chinese fir were the main wood species used to make this ship. The content of holocellulose in the ancient wood was only 37.9 to 38.9%, while the content of lignin was 55.2 to 56.4%. The cellulose crystallinity of ancient wood was 39 to 42% lower than that of healthy recent wood. Fourier transform infrared (FTIR) spectra revealed that the deterioration of ancient wood caused cellulose and hemicellulose degradation, but no apparent lignin alteration. The results could provide a basis for drawing up a conservation plan for the Nantong Ancient Ship. They could also provide a reference for the research and conservation of other archaeological shipwrecks in China.

Abstract Janus particles with anisotropic surfaces possess considerable potential for biological functionalization. However, little is known about the effect of surface anisotropy of Janus particles on the shelf life of perishable food. Herein, plant protein–based nanogels prepared by acylated rapeseed protein isolate (ARPI) are exploited as novel building blocks to decorate the surface of latex particles for Janus particle synthesis. The surface anisotropy of patchy latex particles can be facilely tailored via the suspension polymerization of the Pickering emulsion using ARPI nanogels as stabilizers. The surface distribution of ARPI nanogel on latex particles can be controlled by varying the aqueous phase conditions, and thus, the tunable hydrophilic–lipophilic balance (viz., Janus balance) varied from 0.78 to 1.76 for resulting patchy latex particles. Patchy latex particles with varied Janus balance were further investigated for the effects of their anti‐perishable coatings on perishable fruit preservation. The anisotropic patchy latex particles can act as a novel type of antibacterial agent to inhibit Ascomycota microorganisms’ growth on the surface of fruits and reduce the dehydration and respiration of fruits, all of which devote to a lengthened shelf life while being safe. Furthermore, it is found that the patchy latex particle with a spatial pattern of a hydrophobic area on its surface occupying 51.3% (Janus balance = 0.95) extends the shelf life of perishable food more effectively than that of other spatial arrangements. Overall, the exploration of anisotropic Janus particles offers an alternative strategy to preserve perishable food without using antimicrobial agents.

Abstract Protein nanowires are critical electroactive components for electron transfer of Geobacter sulfurreducens biofilm. To determine the applicability of the nanowire proteins in improving bioelectricity production, their genes including pilA, omcZ, omcS and omcT were overexpressed in G. sulfurreducens. The voltage outputs of the constructed strains were higher than that of the control strain with the empty vector (0.470–0.578 vs. 0.355 V) in microbial fuel cells (MFCs). As a result, the power density of the constructed strains (i.e. 1.39–1.58 W m−2) also increased by 2.62‐ to 2.97‐fold as compared to that of the control strain. Overexpression of nanowire proteins also improved biofilm formation on electrodes with increased protein amount and thickness of biofilms. The normalized power outputs of the constructed strains were 0.18–0.20 W g−1 that increased by 74% to 93% from that of the control strain. Bioelectrochemical analyses further revealed that the biofilms and MFCs with the constructed strains had stronger electroactivity and smaller internal resistance, respectively. Collectively, these results demonstrate for the first time that overexpression of nanowire proteins increases the biomass and electroactivity of anode‐attached microbial biofilms. Moreover, this study provides a new way for enhancing the electrical outputs of MFCs.

For stochastic loss reserving, we propose an individual information model (IIM) which accommodates not only individual/micro data consisting of incurring times, reporting developments, settlement developments as well as payments of individual claims but also heterogeneity among policies. We give over-dispersed Poisson assumption about the moments of reporting developments and payments of every individual claims. Model estimation is conducted under quasi-likelihood theory. Analytic expressions are derived for the expectation and variance of outstanding liabilities, given historical observations. We utilise conditional mean square error of prediction (MSEP) to measure the accuracy of loss reserving and also theoretically prove that when risk portfolio size is large enough, IIM shows a higher prediction accuracy than individual/micro data model (IDM) in predicting the outstanding liabilities, if the heterogeneity indeed influences claims developments and otherwise IIM is asymptotically equivalent to IDM. Some simulations are conducted to investigate the conditional MSEPs for IIM and IDM. A real data analysis is performed basing on real observations in health insurance.

The crucial roles of soil carbon (C) and nutrients and their stoichiometric characteristics in indicating the soil interior nutrient cycling and plant nutrient supply of forest ecosystems have been widely verified, whereas it has been less explored when considering the influencing factors regionally, especially for the widely cultivated plantation tree species. In the current study, the patterns of soil organic C (SOC), total nitrogen (TN), and total phosphorus (TP) stoichiometry in Chinese fir [Cunninghamia lanceolata (Lamb.) Hook] plantations across subtropical China were analyzed, and their influencing factors were also investigated. The results showed that the range of SOC: TN (C:N), SOC: TP (C:P), and TN: TP (N:P) ratios were 7.32–18.27, 20.15–230.48, and 2.11–15.05 with a mean value of 13.22, 83.50, and 6.05, respectively. Well-constrained correlations were found in SOC and TN, as well as in TN and TP. Soil TN and TP contents increased with increasing altitude, whereas soil C:N, C:P, and N:P ratios decreased. Soil TP content decreased, and the C:P ratio increased with increasing mean annual temperature (MAT) and annual total solar radiation (ATSR). Soil C:N, C:P, and N:P ratios increased with increased mean annual precipitation (MAP) and mean annual evaporation (MAE). Overall, our findings suggested that the soil nutrient supply is relatively adequate in Chinese fir plantations across subtropical China. Meanwhile, soil C, N, and P stoichiometric characteristics were affected by geographical and climatic variables to different degrees.

RIPK1 regulates inflammation and cell death and is inhibited by phosphorylation on numerous residues. Here, the authors use a CRISPR whole genome screen to identify that protein phosphatase 1 regulatory subunit 3G regulates RIPK1 apoptotic and necroptotic activity as well as inflammation.

This paper aims to explore the effect and mechanism of water-soluble astaxanthin succinate diester (Asta-SD) on ulcerative colitis (UC) induced by dextran sodium sulfate in zebrafish and C57BL/6J mice. Asta-SD was synthesized with hydrophilic fatty acid succinic anhydride and the hydroxyl groups at the ends of F-Asta were synthesized by esterifying. Through the construction of a zebrafish intestinal inflammation model, it was found that Asta-SD could effectively reduce the levels of ROS and increase the number of healthy intestinal lysosomes in zebrafish. After continuous gavage of Asta-SD for seven days, the body weight, disease activity index, colonic length, colonic histopathology, expression of inflammatory factors, and intestinal flora of the mice were measured. The results showed that Asta-SD could significantly alleviate weight loss and colonic shrinkage, as well as reducing pro-inflammatory cytokines and recess injury in UC mice. The 16S rRNA gene sequencing showed that Asta-SD significantly increased the beneficial bacteria (Lactobacillus, Anaerotruncus) and decreased the relative abundance of pathogenic bacteria, effectively maintaining intestinal microbiota homeostasis in mice. Based on Pearson analysis, Bacteroides, Parabacteroides, and Butyrimionas were expected to be associated with the significant difference in the expression of inflammatory factors between the UC and the corresponding host. Thus, Asta-SD significantly improves UC and maintains intestinal microbiota homeostasis.

Mitochondria are a hub that can direct cellular outcomes in response to stress. Here, the authors show that mitochondrial phosphatase PGAM5 has a role in mitochondrial turnover and regulation of cellular senescence by altering organellar dynamics via fission regulator Drp1.

Background Open pit antimony (Sb) mining causes serious soil pollution, and phytoremediation is a low-cost approach to remediate heavy metal contaminated soil. Rhizosphere bacteria play an important role in ecological restoration in mining areas. There is a knowledge gap on how to find suitable rhizosphere microorganisms to improve the phytoremediation effect. Understanding the differences of rhizosphere bacterial diversity in different restoration stages is helpful to find suitable bacteria for ecological restoration. Methods A method of the substitution of “space” for “time” was used to study the effect of natural restoration on rhizosphere bacterial community. According to the dominant vegetation types (herb, shrub, and tree) in the natural restoration area of Sb mining, the early restoration (ER), middle restoration (MR), and later restoration (LR) from the largest Sb mine (Xikuangshan mine) in the world were selected to evaluate the differences in the composition and diversity of rhizosphere bacteria during three natural restoration stages. Each restoration stage had five samples. To determine the relationship between restoration stages and bacterial diversity in the rhizosphere, high throughput sequencing of PCR amplified were used. Results Alpha diversity, as assessed by Chao indices, appeared lowest in ER but this trend was not seen with other diversity metrics, including the Simpson and Shannon. Beta diversity analysis suggested there were differences in rhizobacterial community structure associate with restoration stage. At the phylum level, natural restoration led to a significant increase in the relative abundance of Actinobacteria in the MR, and a significant decrease in the relative abundance of Patescibacteria in the LR. Additionally, Calditrichaeota, Deferribacteres and Epsilonbacteraeota were only found in ER. At the genus level, the relative abundance of RB41 and Haliangium were highest in LR plots, while that of Bacillus and Gaiella were highest in ER plots. Additionally, the Azorhizobium genus was only detected in the ER phase. Overall, our findings suggested that several rhizosphere microbial communities had significant differences among three natural restoration stages (ER, MR, and LR) and the rhizosphere bacterial communities mainly appeared in the early restoration stage can be preferred for remediation of pollution soil in Xikuangshan.

Food-derived bioactive peptides have received considerable attention as low toxicity nutrient supplements with multiple physiological activities, such as antioxidant, antihypertensive and anti-inflammatory properties. In this study, a RAW 264.7 cell model and spontaneously hypertensive rats model were employed to investigate the antioxidant and anti-inflammatory activities of the angiotensin I-converting enzyme inhibitory peptides Leu-Tyr (LY), Arg-Ala-Leu-Pro (RALP) and Gly-His-Ser (GHS). The results showed that in vitro, LY, RALP and GHS significantly inhibited the secretion of nitric oxide, interleukin-6 and tumor necrosis factor-α in lipopolysaccharide-stimulated RAW 264.7 macrophages. In vivo, LY, RALP and GHS inhibited the release of nitric oxide and the production of lipid peroxides and reactive oxygen species, and improved cell damage caused by oxidative stress in spontaneously hypertensive rats. Furthermore, LY, RALP, and GHS inhibited proinflammatory cytokines including interleukin-6 and tumor necrosis factor-α in plasma. Thus, LY, RALP and GHS can protect the body from oxidative and inflammatory damage.

This paper works on the claims data generated by individual policies which are randomly exposed to a period of continuous time. The main aim is to model the occurrence times of individual claims, as well as their developments given the feature information and exposure periods of individual policies, and thus project the outstanding liabilities. In this paper, we also propose a method to compute the moments of outstanding liabilities in an analytic form. It is significant for a general insurance company to more accurately project outstanding liabilities in risk management. It is well-known that the features of individual policies have effects on the occurrence of claims and their developments and thus the projection of outstanding liabilities. Neglecting the information can unquestionably decrease the prediction accuracy of stochastic reserving, where the accuracy is measured by the mean square error of prediction (MSEP), whose analytic form is computed according to the derived moments of outstanding liabilities. The parameters concerned in the proposed model are estimated based on likelihood and quasi-likelihood and the properties of estimated parameters are further studied. The asymptotic behavior of stochastic reserving is also investigated. The asymptotic distribution of parameter estimators is multivariate normal distribution which is a symmetric distribution and the asymptotic distribution of the deviation of the estimated loss reserving from theoretical loss reserve also follows a normal distribution. The confidence intervals for the parameter estimators and the deviation can be easily obtained through the symmetry of the normal distribution. Some simulations are conducted in order to support the main theoretical results.

In the past, planning to develop an electricity generation capacity supply of consumable load, an acceptable level of reliability, and minimum cost has played significant roles. Due to technological development in energy and the support of energy policymakers to make the most of these clean and cheap resources, a significant amount of research has been conducted to make the most of such energy. Constraints such as low capacity, output power uncertainty, and sustainability problems have made using distributed energy sources costly and complex. Theoretically, capacity development planning in a power system is part of macro-energy planning. It is generally based on specific development policies in each country’s national interest. In addition to being economical, the purpose of this planning was to find the best capacity development plan commensurate with the amount of consumption so that the development plan does not go beyond the permissible limits of reliability, environmental issues, and other constraints. On the other hand, due to the considerable growth of divided production, especially energy sources, it is essential to use microgrids. Accordingly, in this research study, in the process of solving the problem of planning and providing load growth by the distributed generation units to maximize reliability and minimize investment costs, the creation of smaller networks was investigated. To optimize zoning, the weighted graph theory method, in which the weight of the edges is the apparent power passing through the lines, was adopted. In addition, reactive power reliability was included in the calculations to improve the economic aspects. Probabilistic modeling for the presence of renewable resources was employed to bring the model to reality. Since the above problem is very complex, a Seagull-based algorithm and chaos theory were utilized to solve this matter. Finally, the suggested method for the sample system is discussed in different scenarios, indicating an improvement in the system’s performance. According to the numerical results, the NSGA, SPEA, and MOPSO have mean values of 68.3%, 50.2%, and 48.3%, which are covered by the proposed optimization algorithm.

Mixed lineage kinase domain-like protein (MLKL) is the proposed executioner of necroptosis. Our recent findings identify a novel inhibitor necroptosis-blocking compound 1 (NBC1) which specifically conjugates to two cysteines of heat shock protein 70 (HSP70) to block its function. Importantly, HSP70 promotes MLKL polymerization to activate necroptosis.

Traditional radar target detection algorithms are mostly based on statistical theory. They have weak generalization capabilities for complex sea clutter environments and diverse target characteristics, and their detection performance would be significantly reduced. In this paper, the range-azimuth-frame information obtained by scanning radar is converted into plain position indicator (PPI) images, and a novel Radar-PPInet is proposed and used for marine target detection. The model includes CSPDarknet53, SPP, PANet, power non-maximum suppression (P-NMS), and multi-frame fusion section. The prediction frame coordinates, target category, and corresponding confidence are directly given through the feature extraction network. The network structure strengthens the receptive field and attention distribution structure, and further improves the efficiency of network training. P-NMS can effectively improve the problem of missed detection of multi-targets. Moreover, the false alarms caused by strong sea clutter are reduced by the multi-frame fusion, which is also a benefit for weak target detection. The verification using the X-band navigation radar PPI image dataset shows that compared with the traditional cell-average constant false alarm rate detector (CA-CFAR) and the two-stage Faster R-CNN algorithm, the proposed method significantly improved the detection probability by 15% and 10% under certain false alarm probability conditions, which is more suitable for various environment and target characteristics. Moreover, the computational burden is discussed showing that the Radar-PPInet detection model is significantly lower than the Faster R-CNN in terms of parameters and calculations.

Drug dosing in clinical practice, which determines optimal efficacy, toxicity or ineffectiveness, is critical to patients’ outcomes. However, many orally administered therapeutic drugs are susceptible to biotransformation by a group of important oxidative enzymes, known as cytochrome P450s (CYPs). In particular, CYP3A4 is a low specificity isoenzyme of the CYPs family, which contributes to the metabolism of approximately 50% of all marketed drugs. Induction or inhibition of CYP3A4 activity results in the varied oral bioavailability and unwanted drug-drug, drug-food, and drug-herb interactions. This review explores the need for addressing intestinal CYP3A4 metabolism and investigates the opportunities to incorporate lipid-based oral drug delivery to enable precise dosing. A variety of lipid- and lipid-polymer hybrid-nanoparticles are highlighted to improve drug bioavailability. These drug carriers are designed to target different intestinal regions, including (1) local saturation or inhibition of CYP3A4 activity at duodenum and proximal jejunum; (2) CYP3A4 bypass via lymphatic absorption; (3) pH-responsive drug release or vitamin-B12 targeted cellular uptake in the distal intestine. Exploitation of lipidic nanosystems not only revives drugs removed from clinical practice due to serious drug-drug interactions, but also provide alternative approaches to reduce pharmacokinetic variability.

Information on the physicochemical variability in rapeseed oil from different varieties during each refining process is lacking. Our purpose was to investigate the physicochemical properties, micronutrients and oxidative stability of the oil extracted from the five varieties of rapeseeds during their different stages of refining process. Increase in the acid value, peroxide value and p-anisidine value were detected in the refining, while content of tocopherols, sterols, β-carotene and phenols, which are regarded as important nutritional compounds diminished. Moreover, the loss rate of total phytosterols of all oils during neutralization (9.23-7.3%) and deodorization (9.97-8.27%) were higher than that of degumming (3.01-0.87%) and bleaching (2.75-1.18%). Deodorization affected total tocopherols contents the most, followed by bleaching, neutralization and degumming. There was a remarkable reduction in total content of phenol, β-carotene and oxygen radical absorbance of all oils during refining. The accumulated information can be used in looking for the optimum condition to meet the basic requirements for oil and minimize micronutrients losses so as to increase their market value.

Forest communities are mosaic systems composed of patches classified into four different developmental patch types: gap patch (G), building patch (B), mature patch (M) and degenerate patch (D). To study the mechanisms maintaining diversity in subalpine coniferous forests, species presence frequency and diversity in the four distinct patch types (G, B, M and D) of Larix chinensis conifer forests at three altitudinal gradients in the Qinling Mountains were analyzed. Our results were as follows: (1) Different species (or functional groups) had distinct presence frequencies in the four different patch types along the altitudinal gradient; (2) Some species or functional groups (species groups sharing similar traits and responses to the environment) only occurred in some specific patches. For seed dispersal, species using wind mainly occurred in G and D, while species using small animals mainly occurred in B and M; (3) Species composition of adjacent patch types was more similar than non-adjacent patch types, based on the lower β diversity index of the former; (4) The maximum numbers of species and two diversity indices (D′ and H′) were found in the middle altitudes. Various gap-forming processes and dispersal limitation may be the two major mechanisms determining species diversity in Larix chinensis coniferous forests at the patch scale.