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Lymphocyte receptors independently evolved in both jawed and jawless vertebrates with similar adaptive immune responses. However, the diversity of functional subtypes and molecular architecture in jawless vertebrate lymphocytes, comparable to jawed species, is not well defined. Here, we profile the gills, intestines, and blood of the lamprey, Lampetra morii, with single-cell RNA sequencing, using a full-length transcriptome as a reference. Our findings reveal higher tissue-specific heterogeneity among T-like cells in contrast to B-like cells. Notably, we identify a unique T-like cell subtype expressing a homolog of the nonlymphoid hematopoietic growth factor receptor, MPL-like (MPL-L). These MPL-L+ T-like cells exhibit features distinct from T cells of jawed vertebrates, particularly in their elevated expression of hematopoietic genes. We further discovered that MPL-L+ VLRA+ T-like cells are widely present in the typhlosole, gill, liver, kidney, and skin of lamprey and they proliferate in response to both a T cell mitogen and recombinant human thrombopoietin. These findings provide new insights into the adaptive immune response in jawless vertebrates, shedding new light on the evolution of adaptive immunity. Lymphocyte subsets remain inadequately understood in jawless vertebrates, relative to jawed vertebrates. In this study, the authors combine single-cell RNA and whole-transcriptome sequencing to demonstrate that the lamprey, Lampreta morii, harbours specialised T-like cells that are distinct from those found in jawed vertebrates. [ABSTRACT FROM AUTHOR]

Elucidating cellular architecture and cell-type evolution across species is central to understanding immune system function and susceptibility to disease. Adaptive immunity is a shared trait of the common ancestor of cartilaginous and bony fishes. However, evolutionary features of lymphocytes in these two jawed vertebrates remain unclear. Here, we present a single-cell RNA sequencing atlas of immune cells from cartilaginous (white-spotted bamboo shark) and bony (zebrafish and Chinese tongue sole) fishes. Cross-species comparisons show that the same cell types across different species exhibit similar transcriptional profiles. In the bamboo shark, we identify a phagocytic B cell population expressing several pattern recognition receptors, as well as a T cell sub-cluster co-expressing both T and B cell markers. In contrast to a division by function in the bony fishes, we show close linkage and poor functional specialization among lymphocytes in the cartilaginous fish. Our cross-species single-cell comparison presents a resource for uncovering the origin and evolution of the gnathostome immune system. Both cartilaginous and bony fishes have adaptive immune cells, but the evolutionary features of these diverse cell populations remain understudied. Here the authors report single-cell RNA sequencing atlas of both species to define these features and to find reduced evolutionary diversification of immune cells in cartilaginous fishes. [ABSTRACT FROM AUTHOR]

To describe the transmission dynamics of maize streak virus infection, in the paper, we first formulate a stochastic maize streak virus infection model, in which the stochastic fluctuations are depicted by a logarithmic Ornstein–Uhlenbeck process. This approach is reasonable to simulate the random impacts of main parameters both from the biological significance and the mathematical perspective. Then we investigate the detailed dynamics of the stochastic system, including the existence and uniqueness of the global solution, the existence of a stationary distribution, the exponential extinction of the infected maize and infected leafhopper vector. Especially, by solving the five-dimensional algebraic equations corresponding to the stochastic system, we obtain the specific expression of the probability density function near the quasi-endemic equilibrium of the stochastic system, which provides valuable insights into the stationary distribution. Finally, the model is discretized using the Milstein higher-order numerical method to illustrate our theoretical results numerically. Our findings provide a groundwork for better methods of preventing the spread of this type of virus. [ABSTRACT FROM AUTHOR]

Sarcocystis infection in sheep has caused significant economic losses in the livestock industry, and the genetic similarity among Sarcocystis species highlights the need for precise diagnostic methods in sheep. This study developed a loop-mediated isothermal amplification (LAMP) method targeting COX-1 and 28S rRNA genes to detect Sarcocystis tenella and Sarcocystis gigantea, respectively. The LAMP method exhibited high specificity, selectively amplifying target DNA sequences without cross-reactivity with closely related protozoa, such as Toxoplasma gondii and Neospora caninum. Detection limits were determined as 3 × 105 copies/L for S. tenella and 6 × 104 copies/L for S. gigantea, enabling sensitive identification of low-level infections. Comparative analysis with conventional PCR on sheep cardiac tissues demonstrated a higher LAMP detection rate (80.0% vs 66.7%). In conclusion, the LAMP method offers superior sensitivity to conventional PCR, allows visual confirmation of results, and provides a rapid diagnostic tool for identifying S. tenella and S. gigantea infection in sheep. However, due to the limitation of sample availability, we were unable to assess all Sarcocystis species that use sheep as intermediate hosts, which warrants further research. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) systems surpass certain human intelligence abilities in a statistical sense as a whole, but are not yet the true realization of these human intelligence abilities and behaviors. There are differences, and even contradictions, between the cognition and behavior of AI systems and humans. With the goal of achieving general AI, this study contains a review of the role of cognitive science in inspiring the development of the three mainstream academic branches of AI based on the three-layer framework proposed by David Marr, and the limitations of the current development of AI are explored and analyzed. The differences and inconsistencies between the cognition mechanisms of the human brain and the computation mechanisms of AI systems are analyzed. They are found to be the cause of the differences and contradictions between the cognition and behavior of AI systems and humans. Additionally, eight important research directions and their scientific issues that need to focus on brain-inspired AI research are proposed: highly imitated bionic information processing, a large-scale deep learning model that balances structure and function, multi-granularity joint problem solving bidirectionally driven by data and knowledge, AI models that simulate specific brain structures, a collaborative processing mechanism with the physical separation of perceptual processing and interpretive analysis, embodied intelligence that integrates the brain cognitive mechanism and AI computation mechanisms, intelligence simulation from individual intelligence to group intelligence (social intelligence), and AI-assisted brain cognitive intelligence. [ABSTRACT FROM AUTHOR]

One-shot knowledge graph completion (KGC) aims to infer unseen facts when only one support entity pair is available for a particular relationship. Prior studies learn reference representations from one support pair for matching query pairs. This strategy can be challenging, particularly when dealing with multiple relationships between identical support pairs, resulting in indistinguishable reference representations. To this end, we propose a disentangled representation learning framework for one-shot KGC. Specifically, to learn sufficient representations, we construct an entity encoder with a fine-grained attention mechanism to explicitly model the input and output neighbors. We adopt an orthogonal regularizer to promote the independence of learned factors in entity representation, enabling the matching processor with max pooling to adaptively identify the semantic roles associated with a particular relation. Subsequently, the one-shot KGC is accomplished by seamlessly integrating the aforementioned modules in an end-to-end learning manner. Extensive experiments on real-world datasets demonstrate the outperformance of the proposed framework. [ABSTRACT FROM AUTHOR]

In multimodal data processing of image captioning, data from different modalities usually exhibit distinct feature distributions. The gap in unimodal representation makes capturing cross-modal mappings in multimodal learning challenging. Current image captioning models transform images into captions directly. However, this approach results in large data requirements and limited performance on small quantities of multimodal data. In this paper, we introduce a novel self-supervised modal optimization transformer (SMOT) for image captioning. Specifically, we leverage self-supervised learning to propose a cross-modal feature optimizer. This optimizer aims to optimize the distribution of semantic information in images by leveraging raw images and their corresponding paired captions, ultimately approaching the semantic object of the caption. The optimized image features inherit information from both modalities, reducing the disparity in feature distribution between modalities and decreasing reliance on extensive training data. Furthermore, we fuse the features with image grid features and text features, using their complementary information to bridge the differences between features, providing more comprehensive semantic guidance for image captioning. Experimental results demonstrate that our proposed SMOT outperforms state-of-the-art models when trained on limited data, showing efficient learning and good generalization capabilities on small training datasets. Additionally, it also exhibits competitive performance on the MSCOCO dataset, further highlighting its efficacy and potential in the field of image captioning. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is a complex multifactorial clinical syndrome leading to abnormal cardiac structure and function. The severe form of this ailment is characterized by high disability, high mortality, and morbidity. Worldwide, 2–17% of patients die at first admission, of which 17–45% die within 1 year of admission and >50% within 5 years. Yangshen Maidong Decoction (YSMDD) is frequently used to treat the deficiency and pain of the heart. The specific mechanism of action of YSMDD in treating CHF, however, remains unclear. Therefore, a network pharmacology-based strategy combined with molecular docking and molecular dynamics simulations was employed to investigate the potential molecular mechanism of YSMDD against CHF. The effective components and their targets of YSMDD and related targets of CHF were predicted and screened based on the public database. The network pharmacology was used to explore the potential targets and possible pathways that involved in YSMDD treated CHF. Molecular docking and molecular dynamics simulations were performed to elucidate the binding affinity between the YSMDD and CHF targets. Screen results, 10 main active ingredients, and 6 key targets were acquired through network pharmacology analysis. Pathway enrichment analysis showed that intersectional targets associated pathways were enriched in the Prostate cancer pathway, Hepatitis B pathway, and C-type lectin receptor signaling pathways. Molecular docking and molecular dynamics simulations analysis suggested 5 critical active ingredients have high binding affinity to the 5 key targets. This research shows the multiple active components and molecular mechanisms of YSMDD in the treatment of CHF and offers resources and suggestions for future studies. [ABSTRACT FROM AUTHOR]

Multi-generational asexual reproduction of Gastrodia elata Bl. will cause seedling species degeneration. Sexual reproduction of Gastrodia elata Bl. seed is an effective method to solve the problem of degeneration. The development of Gastrodia elata Bl. seeds cannot be separated from the germination fungus. However, there are few strains of germination fungus in production, and there is also the problem of species degradation in application for many years. It is very important for the sexual reproduction of Gastrodia elata Bl. to isolate more new strains of excellent germination fungus from the origin. This study used the Gastrodia elata Bl. f. glauca S. chow seeds germination vegetative propagation corms capture method to isolate its symbiotic germination fungus, and comprehensively identified the species of germination fungus by colony morphology, ITS, sporocarps regeneration and germination function, and compared the growth characteristics and germination ability with other germination fungus (Mycena purpureofusca, Mycena dendrobii and Mycena osmundicola). The germination fungus was isolated from the vegetative propagation corms of Gastrodia elata Bl. f. glauca S. chow seeds and named GYGL-1. After comprehensive identification, GYGL-1 was Mycetinis scorodonius. Compared with other germination fungus, GYGL-1 has fast germination speed, vigorous growth, and high germination ability for Gastrodia elata Bl. f. glauca S. chow seeds. Innovated the isolation method of Gastrodia elata Bl. seeds germination fungus, obtained the regenerated sporocarps of the germination fungus, and discovered that Mycetinis scorodonius has a new function of germinating Gastrodia elata Bl. f. glauca S. chow seeds, enriching the resource library of Gastrodia elata Bl. germination fungus. [ABSTRACT FROM AUTHOR]

In this paper, assuming the certain variable satisfies the Ornstein–Uhlenbeck process, we formulate a stochastic within-host dengue model with immune response to obtain further understanding of the transmission dynamics of dengue fever. Then we analyze the dynamical properties of the stochastic system in detail, including the existence and uniqueness of the global solution, the existence of a stationary distribution, and the extinction of infected monocytes and free viruses. In particular, it is worth revealing that we get the specific form of covariance matrix in its probability density around the quasi-endemic equilibrium of the stochastic system. Finally, numerical illustrative examples are depicted to confirm our theoretical findings. [ABSTRACT FROM AUTHOR]

Primary Sjögren’s Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage. [ABSTRACT FROM AUTHOR]

The flow of calcium ions (Ca2+) is involved in numerous vital activities of Toxoplasma gondii. Calreticulin is a type of Ca2+-binding protein in the endoplasmic reticulum (ER) that is involved in Ca2+ signaling pathway regulation, Ca2+ storage, and protein folding. In this work, the calreticulin (CALR), a protein predicted to possess a conserved domain of calreticulin in T. gondii, was characterized. The CALR localized in the ER. Using reverse genetics, we discovered that CALR is not necessary for the lytic cycle, including invasion and replication. However, depletion of CALR affected microneme secretion triggered by A23187, which is a Ca2+ ionophore used to increase cytoplasmic Ca2+ concentration. Furthermore, we discovered that CALR influences Ca2+ release. Transcriptomic comparison between Δcalr and Δku80 parasites showed that 226 genes in the Δcalr parasites were significantly downregulated (p < 0.05). The cellular biological functions of the downregulated genes were mainly involved in calmodulin-dependent protein kinase pathways. Furthermore, in the absence of CALR, tachyzoites were still able to cause acute infection in mice. These results imply that by influencing ER Ca2+ release content, CALR may further impair the ionophore-induced secretion of the parasite. However, this protein is not required for the completion of the parasite’s lytic cycle or for the acute virulence of the parasite. [ABSTRACT FROM AUTHOR]

Plant nutrient uptake and productivity are driven by a multitude of factors that have been modified by human activities, like climate change and the activity of decomposers. However, interactive effects of climate change and key decomposer groups like earthworms have rarely been studied. In a field microcosm experiment, we investigated the effects of a mean future climate scenario with warming (+ 0.50 °C to + 0.62 °C) and altered precipitation (+ 10% in spring and autumn, − 20% in summer) and earthworms (anecic—two Lumbricus terrestris, endogeic—four Allolobophora chlorotica and both together within 10 cm diameter tubes) on plant biomass and stoichiometry in two land-use types (intensively used meadow and conventional farming). We found little evidence for earthworm effects on aboveground biomass. However, future climate increased above- (+40.9%) and belowground biomass (+44.7%) of grass communities, which was mainly driven by production of the dominant Festulolium species during non-summer drought periods, but decreased the aboveground biomass (− 36.9%) of winter wheat. Projected climate change and earthworms interactively affected the N content and C:N ratio of grasses. Earthworms enhanced the N content (+1.2%) thereby decreasing the C:N ratio (− 4.1%) in grasses, but only under ambient climate conditions. The future climate treatment generally decreased the N content of grasses (aboveground: − 1.1%, belowground: − 0.15%) and winter wheat (− 0.14%), resulting in an increase in C:N ratio of grasses (aboveground: + 4.2%, belowground: +6.3%) and wheat (+5.9%). Our results suggest that climate change diminishes the positive effects of earthworms on plant nutrient uptakes due to soil water deficit, especially during summer drought. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a zoonotic parasite that is very common in livestock. Meat products from livestock infected with T. gondii are one of the important transmission routes of toxoplasmosis. Rapid and reliable diagnosis is a prerequisite for the prevention and control of toxoplasmosis. Neospora caninum and T. gondii are similar in morphology and life history, and there are a large number of cross antigens between them, making clinical diagnosis of toxoplasmosis more difficult. In this study, immunoprecipitation-mass spectrometry (IP-MS) was used to screen for T. gondii–specific antigens, and the specific antigen was cloned and expressed in Escherichia coli. The specific antigen was then used to establish an indirect ELISA diagnostic method. A total of 241 specific antigens of T. gondii and 662 cross antigens between T. gondii and N. caninum were screened by IP-MS. Through bioinformatics analysis and homology comparison, seven proteins were selected for gene cloning and prokaryotic expression, and the most suitable antigen, TgGRA54, was selected to establish an indirect ELISA for T. gondii. Compared with the indirect immunofluorescent antibody test (IFAT), the positive coincidence rate of the ELISA based on rTgGRA54 was 100% (72/72) and the negative coincidence rate was 80.95% (17/21). The indirect ELISA method based on TgGRA54 recombinant protein was established to detect T. gondii antibodies in bovine sera, and the recombinant protein reacted well with T. gondii positive sera from sheep, mouse, and swine, indicating that the recombinant protein is a good diagnostic antigen for T. gondii. [ABSTRACT FROM AUTHOR]

At present, image completion models are often used to handle images in public datasets and are not competent for tasks in practical scenarios such as USV scenes. On one hand, the practical missing regions are often located at the boundaries, which presents a challenge for the model to extract image features. On the other hand, real images are often blurred, and filling the content without optimizing the image quality will limit the application of completed images. To address these challenges, a novel image completion model using an attention mechanism and a joint enhancive discriminator, which can effectively fill in the missing and enhance the image quality in various missing situations, has been proposed in this paper. First, an attention mechanism is used as the condition of the generator to extract the related missing information according to different weights. To ensure that the output of the algorithm is semantically consistent with the original image and has a higher quality than the original image, a joint discriminator is introduced to constrain the conditional generator from different aspects. In particular, the cloud model (a cognitive model) in the joint enhancive discriminator can promote the quality and practicability of the generated images. Experimental results show that our model achieves better performance than state-of-the-art models in both qualitative and quantitative measurements on four public datasets and one USV real dataset. Compared with the baselines, our method has an average improvement of 4.90 % and 1.00 % in image completion evaluation and image quality evaluation, respectively. We also verify the performance of our model for practical application in real scenarios. The code is available at https://github.com/wrq-cqupt/IC. [ABSTRACT FROM AUTHOR]

Remote sensing spatiotemporal fusion is currently a popular research field in remote sensing that can cost-effectively generate remote sensing images with high spatiotemporal resolution. The deep neural network-based approach has strong feature extraction capability and has achieved great success in the fields of signal and image processing, but the deep network lacks interpretability. In this paper, a new interpretable deep network-based spatiotemporal fusion (UNSTF) method is proposed. The method proposes a new network model by first establishing a concise a priori formulation using sparse representation, constructing the proposed network by unfolding the proximal gradient algorithm for solving the model, and carefully designing each basic network module in the model to have a reasonable physical meaning, making the whole network interpretable. In addition, the UNSTF network method proposes a new network iteration loss function, where the predicted images of each iteration stage of the network are constrained by the real images, and the final stage and the intermediate network stages conform well to their inherent prior structures, effectively improving the accuracy and reliability of model prediction. Through extensive experiments, it is shown that the proposed method outperforms existing fusion methods in terms of both subjective and objective metrics. [ABSTRACT FROM AUTHOR]

Investigating the impacts of climatic factors and human activities on sedimentary records of heavy metal (HM) contamination in lakes is essential for decision-making in global environmental monitoring and assessment. Spatiotemporal distributions of grain size (GS) and HM (Al, Cr, Mn, Ni, Cu, Zn, As, and Pb) concentrations have been conducted in core sediments that are collected from two adjacent plateau fault-bound lakes in southwest China with contrasting environments, i.e., deep oligotrophic Lake Fuxian (FX) and shallow hypertrophic Lake Xingyun (XY). Results showed that the average value of d50 in FX (4.61 μm) was lower than that in XY (8.35 μm), but the average concentrations of HMs (except Cr and Mn) in XY were higher than those in FX. Heavy metal burial rates (HMBR) were mainly controlled by sediment accumulation rates (SARs) rather than HM concentrations. The correlation coefficients between GS and HM concentrations became strong as the increasing water depths were associated with a stable sedimentary environment. Time-integrated enrichment factors (EF) and source identification of HMs between FX and XY represented that Cr, Ni, and Cu originated from natural sources but Mn, Zn, As, and Pb from anthropogenic sources, respectively. Regardless of FX and XY, the transition times of HMs from natural to anthropogenic sources occurred in the mid-1960s. Comparison of qualification impacts of climatic factors and human-induced factors on increased anthropogenic HMBR by the partial least squares path modeling (PLS-PM) implied that socio-economic activities, such as population density (PD) and gross domestic product (GDP), provided higher contributors to increased anthropogenic HMBR in XY (0.23/0.71) than FX (0.11/0.18). The comparative results of this study provided new insights into environmental monitoring and management of HM contamination for adjacent lakes with contrasting environments. [ABSTRACT FROM AUTHOR]

The six species of lungfish possess both lungs and gills and are the closest extant relatives of tetrapods. Here, we report a single-cell transcriptome atlas of the West African lungfish (Protopterus annectens). This species manifests the most extreme form of terrestrialization, a life history strategy to survive dry periods that can last for years, characterized by dormancy and reversible adaptive changes of the gills and lungs. Our atlas highlights the cell type diversity of the West African lungfish, including gene expression consistent with phenotype changes of terrestrialization. Comparison with terrestrial tetrapods and ray-finned fishes reveals broad homology between the swim bladder and lung cell types as well as shared and idiosyncratic changes of the external gills of the West African lungfish and the internal gills of Atlantic salmon. The single-cell atlas presented here provides a valuable resource for further exploration of the respiratory system evolution in vertebrates and the diversity of lungfish terrestrialization. The water-to-land transition of vertebrates is a landmark event in evolutionary history. This work utilizes single-cell RNA sequencing to explore the adaptations in African lungfish lungs and gills to terrestrialization. [ABSTRACT FROM AUTHOR]

Context: Since 1991 when Grätzel et al. improved the conversion efficiency of dye-sensitized solar cells to 7.1% by applying nano technology as the first time, the researches on dye-sensitized solar cells have received widely attentions. The organic dye without precious metals has a lower cost, which is easily to get synthesized and its structure is easily decorated, owing a higher photoelectric conversion efficiency at the same time. Therefore, in recent years, the organic dye has attracted people's attentions more and more. In order to better understand the relationship between structure and properties of dye molecules, with ZL003 as a prototype, molecular modifications are then made and a scheme, with rigid fused π-bridge comprising electron-rich and deficient segments. The calculated results indicate that the π-bridge containing dithienopyrrolobenzothiadiazole and dipyrrolo-dithienobenzothiadiazole as π-bridge has been demonstrated to be successful to significantly redshift the absorption maximum wavelength, extend the lifetime of the first excited state, and decrease the energy gap between the highest occupied molecule orbital (HOMO) and the lowest unoccupied molecule orbital (LUMO). It is hoped that the calculation result of this paper would provide theoretical basis for the experimental synthesis of more efficient dye molecules. Method: All calculations were performed in Gaussian 09 program package. The ground state geometries (S0) and the first excited state (S1) were optimized using density function theory (DFT) with the hybrid function B3LYP functional, coupled with the 6-31G(d, p) basis set for optimization of molecule ground state conformations. TD-DFT calculations of excited state energies and absorption spectra were performed using MPWPW91 functional combined with the 6–31 + G (d) basis set. [ABSTRACT FROM AUTHOR]

Zinc is an essential micronutrient that supports all living organisms through regulating numerous biological processes. However, the mechanism of uptake regulation by intracellular Zn2+ status remains unclear. Here we report a cryo-electron microscopy structure of a ZIP-family transporter from Bordetella bronchiseptica at 3.05 Å resolution in an inward-facing, inhibited conformation. The transporter forms a homodimer, each protomer containing nine transmembrane helices and three metal ions. Two metal ions form a binuclear pore structure, and the third ion is located at an egress site facing the cytoplasm. The egress site is covered by a loop, and two histidine residues on the loop interact with the egress-site ion and regulate its release. Cell-based Zn2+ uptake and cell growth viability assays reveal a negative regulation of Zn2+ uptake through sensing intracellular Zn2+ status using a built-in sensor. These structural and biochemical analyses provide mechanistic insight into the autoregulation of zinc uptake across membranes. Zinc uptake and regulation are vital in all life forms. Here, authors describe a dimer of a ZIP-family zinc transporter in an inward-facing, inhibited conformation. A built-in zinc sensor is proposed to sense the intracellular zinc content to autoregulate zinc uptake across membranes. [ABSTRACT FROM AUTHOR]

Female-to-male sex reversals (pseudomales) are common in lower vertebrates and have been found in natural populations, which is a concern under rapid changes in environmental conditions. Pseudomales can exhibit altered spermatogenesis. However, the regulatory mechanisms underlying pseudomale spermatogenesis remain unclear. Here, we characterized spermatogenesis in Chinese tongue sole (Cynoglossus semilaevis), a species with genetic and environmental sex determination, based on a high-resolution single-cell RNA-seq atlas of cells derived from the testes of genotypic males and pseudomales. We identified five germ cell types and six somatic cell types and obtained a single-cell atlas of dynamic changes in gene expression during spermatogenesis in Chinese tongue sole, including alterations in pseudomales. We detected decreased levels of Ca2+ signaling pathway-related genes in spermatogonia, insufficient meiotic initiation in spermatocytes, and a malfunction of somatic niche cells in pseudomales. However, a cluster of CaSR genes and MAPK signaling factors were upregulated in undifferentiated spermatogonia of pseudomales. Additionally, we revealed that Z chromosome-specific genes, such as piwil2, dhx37, and ehmt1, were important for spermatogenesis. These results improve our understanding of reproduction after female-to-male sex-reversal and provide new insights into the adaptability of reproductive strategies in lower vertebrates. [ABSTRACT FROM AUTHOR]

Lanthanide ion-doped fluorescent materials have always been a hot topic in the field of electronic materials. Eu3+ ion-doped gadolinium borosilicate glass was prepared by high temperature melting method. The luminescence properties of Eu3+ codoped gadolinium borosilicate glass were investigated by X-ray diffraction (XRD), Fourier transform near infrared spectroscopy, excitation spectrum, emission spectrum, fluorescence lifetime and chromaticity analysis. XRD results show that the sample has typical non-crystalline. The fluorescence lifetime of the sample changes regularly with the concentration of Eu3+ ions. The results show that the luminescence intensity increases with the increase of Eu3+ ion concentration, which proves that the change of Eu3+ ion concentration has a great regulation effect on the luminescence properties of gadolinium borosilicate glass. The structural reason of this phenomenon is analyzed by Fourier transform near infrared spectroscopy. The luminescence properties of glass can be improved by regulating Eu3+ ion concentration. [ABSTRACT FROM AUTHOR]

In this paper, we propose a stochastic differential equation model which is used to explore how the environmental noise affects the spread of hepatitis B virus. Firstly, we show that there exists a unique global positive solution of the stochastic system with any positive initial value. Then, we adopt a stochastic Lyapunov function method to establish sufficient conditions for the existence and uniqueness of an ergodic stationary distribution of the proposed stochastic model. Especially, under the same conditions as the existence of a stationary distribution, it is worth noting that we obtain the specific form of probability density around the quasi-infected steady state of the stochastic system. Thirdly, we obtain sufficient criteria for extinction of the infected hepatocytes. Finally, numerical simulations are introduced to validate the theoretical findings. [ABSTRACT FROM AUTHOR]

Apicomplexan parasite growth and replication relies on nutrient acquisition from host cells, in which intracellular multiplication occurs, yet the mechanisms that underlie the nutrient salvage remain elusive. Numerous ultrastructural studies have documented a plasma membrane invagination with a dense neck, termed the micropore, on the surface of intracellular parasites. However, the function of this structure remains unknown. Here we validate the micropore as an essential organelle for endocytosis of nutrients from the host cell cytosol and Golgi in the model apicomplexan Toxoplasma gondii. Detailed analyses demonstrated that Kelch13 is localized at the dense neck of the organelle and functions as a protein hub at the micropore for endocytic uptake. Intriguingly, maximal activity of the micropore requires the ceramide de novo synthesis pathway in the parasite. Thus, this study provides insights into the machinery underlying acquisition of host cell-derived nutrients by apicomplexan parasites that are otherwise sequestered from host cell compartments.Toxoplasma gondii acquires host cytosolic materials, yet the mechanism remains unknown. Wan et al. reveal the micropore as an essential organelle at the plasma membrane for endocytosis of host cytosolic proteins and biotin, and Golgi ceramide. [ABSTRACT FROM AUTHOR]

The gray model is very useful for small sample prediction. Compared with the homogeneous gray model, the nonhomogeneous gray model (NGM) improves the prediction differential equation; thus, the NGM is able to effectively predict a nonhomogeneous exponential sequence. However, the NGM cannot be applied to nonlinear samples because of the linear whitening equation. Inspired by multikernel learning, the central alignment multikernel learning method is integrated into the NGM, and a centered alignment multikernel NGM (CAMKNGM) is presented in this paper. In our model, the kernel trick and kernel function are used to overcome the difficulties in solving the nonlinear mapping problems of the NGM. Additionally, more than one kernel function is utilized to generate responding kernel matrices by mapping the nonlinear features to different kernel spaces. Centered alignment multikernel learning optimization can be carried out according to the obtained kernel matrices to form a more sufficient feature space so that the combined kernel matrix can be used to greatly capture the nonlinear factors of the time series. Through multikernel learning optimization, the proposed model with unknown nonlinear transformation can be solved easily. In the experiment, we assess the performance of our model on three samples and compare the CAMKNGM with the single-kernel NGM (KRNGM) and other state-of-the-art models. The results show that the CAMKNGM model is obviously better than the support vector regression, NGM, optimized NGM and KRNGM. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects. Methods: Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 β, TGF- β 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively. Results: After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 β, IGF-1, TGF-β 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 β, IGF-1, TGF-β 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01). Conclusion: EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 β/IGF-1-TGF- β 1-MMP9 pathway. [ABSTRACT FROM AUTHOR]

Aluminium (Al) is an environmental neurotoxin that humans are widely exposed to, but the molecular mechanism of its toxic effects is not fully understood. Many studies have shown that exposure to Al can cause abnormal phosphorylation of the tau protein that is believed as one of pathological features of Alzheimer's disease. Increasing evidence indicates that microRNAs (miRNAs) may be involved in the pathological processes of neurodegenerative diseases and are potential regulatory factors for related target genes. Phosphorylation at Ser-133 of cAMP response element-binding protein (CREB) is one of the major pathways of CREB activation, and phosphorylation at this site is controlled by protein kinase A (PKA). The catalytic subunit of PKA, cAMP-dependent protein kinase catalytic subunit beta (PRKACB), phosphorylates CREB. The target gene prediction software TargetScan showed that PRKACB was one of the target mRNAs of miR-200a-3p. The purpose of this study was to investigate whether miR-200a-3p regulates the PKA/CREB pathway by targeting PRKACB and leads to abnormal phosphorylation of the tau protein in nerve cells. The results showed that Al exposure increased the expression level of miR-200a-3p, and miR-200a-3p increased the expression of targeted downregulated PRKACB, and then decreased the PKA/CREB signalling pathway activity, leading to abnormal hyperphosphorylation of tau. [ABSTRACT FROM AUTHOR]

Mentha species are planted worldwide for extraction of their metabolites, including essential oils and phenolic acid compounds, which have therapeutic and commercial value. Mentha piperita L. and Mentha canadensis L. both belong to the menthol chemotype. M. piperita is widely used in North America, and M. canadensis is one of the most important mint species in Asia. Here, an improved Agrobacterium-mediated transformation method using internode segments instead of leaves as explants of M. piperita was reported. Histological examination showed that adventitious buds formed from cortical cells of internode. An efficient method for regeneration of M. canadensis was also established. Internode pieces were excised and cultured on a regeneration medium containing Murashige and Skoog (MS) salts plus vitamin B5, 5.0 mg L−1 TDZ, 0.2 mg L−1 IAA, and 25% coconut water. Explants were then moved to the basal MS medium without plant growth regulator after initiation of shoots and regeneration rates achieved 100%. According to different selection markers used in individual transformation experiments, 3 mg L−1 hygromycin B (antibiotic) or bialaphos (herbicide) was appropriate the concentration for the regeneration selection stage, while 5 mg L−1 hygromycin B or bialaphos could be used during the shoot elongation selection stage. An Agrobacterium-mediated genetic transformation protocol for M. canadensis was produced within 4 mo. Positive transgenic lines with gusA gene were verified by polymerase chain reaction (PCR) and β-glucuronidase histochemical staining. Using 500 to 600 internode pieces as explants could obtain 3 to 4 transgenic lines of M. canadensis. Our methods established here will facilitate the basic gene function research as well as genetic breeding and trait improvement of this important mint species. [ABSTRACT FROM AUTHOR]

Aiming to reveal the potential relationships between users, link prediction has been considered as a fundamental research issue in signed social networks. The key of the link prediction is to measure the similarity between users. Many existing researches use connections between users and their common neighbors to measure the similarities, and these methods rely too much on the structure of social networks. Most of them use the deep neural network to enhance the prediction accuracy. However, the complete structure of the huge social network cannot be captured easily, and the models learnt by the deep neural network are unexplainable and uncontrolled. As an explainable model, functional network is a recent replacement for standard neural network. Therefore, we revise the traditional strategy of functional network and propose a novel functional network framework. Firstly, the attributes are preprocessed through the cloud model to define their importance before inputting them into the functional network. Then the association algorithm is used to do aggregate computation in computing neurons for defining the connections between neurons well. Finally, we use three-way decisions to process the samples in the boundary to optimize the performance of model. Experiments executed on six real datasets show that our method has significantly higher link prediction precision than the state-of-the-art works. From our discussions, the improved functional network can be a valid replacement for neural networks in some fields. [ABSTRACT FROM AUTHOR]

Purpose: Soil mesofauna-associated biogeochemical cycles could be mediated by nitrogen (N) deposition and plant functional types. However, N addition effects on the contribution of soil mesofauna to litter element release under different plant functional types remain unclear.A litterbag experiment with two mesh sizes (2 and 0.1 mm) examined the soil mesofauna's effect on litter carbon (C), N, and phosphorus (P) release of three functional types (evergreen broadleaf, deciduous broadleaf, and coniferous: 6 tree species for each group). Litterbags were exposed to varying N deposition levels (0, 20, and 40 kg N ha−1 yr−1) in a subtropical forest in southwest China.N addition and soil mesofauna promoted litter C, N, and P loss across three plant functional types. The soil mesofauna's effects on litter N loss were lower in deciduous broadleaf than in evergreen broadleaf and coniferous litter. However, the soil mesofauna's effects on litter P loss were greater in evergreen broadleaf than in deciduous broadleaf and coniferous litter. Further, N addition stimulated the soil mesofauna's effects on litter N release only in evergreen broadleaf. Soil mesofauna's contribution to C and P loss correlated with the initial litter C/P ratio across 18 species. N addition effects were greater under low-N than high-N treatments in 0.1 mm litter bags.The findings suggested N addition and plant functional types independently mediated mesofauna-driven litter element release, highlighting the importance of soil mesofauna and plant functional types for belowground biogeochemical cycles via litter pathways in subtropical regions experiencing pronounced N deposition.Methods: Soil mesofauna-associated biogeochemical cycles could be mediated by nitrogen (N) deposition and plant functional types. However, N addition effects on the contribution of soil mesofauna to litter element release under different plant functional types remain unclear.A litterbag experiment with two mesh sizes (2 and 0.1 mm) examined the soil mesofauna's effect on litter carbon (C), N, and phosphorus (P) release of three functional types (evergreen broadleaf, deciduous broadleaf, and coniferous: 6 tree species for each group). Litterbags were exposed to varying N deposition levels (0, 20, and 40 kg N ha−1 yr−1) in a subtropical forest in southwest China.N addition and soil mesofauna promoted litter C, N, and P loss across three plant functional types. The soil mesofauna's effects on litter N loss were lower in deciduous broadleaf than in evergreen broadleaf and coniferous litter. However, the soil mesofauna's effects on litter P loss were greater in evergreen broadleaf than in deciduous broadleaf and coniferous litter. Further, N addition stimulated the soil mesofauna's effects on litter N release only in evergreen broadleaf. Soil mesofauna's contribution to C and P loss correlated with the initial litter C/P ratio across 18 species. N addition effects were greater under low-N than high-N treatments in 0.1 mm litter bags.The findings suggested N addition and plant functional types independently mediated mesofauna-driven litter element release, highlighting the importance of soil mesofauna and plant functional types for belowground biogeochemical cycles via litter pathways in subtropical regions experiencing pronounced N deposition.Results: Soil mesofauna-associated biogeochemical cycles could be mediated by nitrogen (N) deposition and plant functional types. However, N addition effects on the contribution of soil mesofauna to litter element release under different plant functional types remain unclear.A litterbag experiment with two mesh sizes (2 and 0.1 mm) examined the soil mesofauna's effect on litter carbon (C), N, and phosphorus (P) release of three functional types (evergreen broadleaf, deciduous broadleaf, and coniferous: 6 tree species for each group). Litterbags were exposed to varying N deposition levels (0, 20, and 40 kg N ha−1 yr−1) in a subtropical forest in southwest China.N addition and soil mesofauna promoted litter C, N, and P loss across three plant functional types. The soil mesofauna's effects on litter N loss were lower in deciduous broadleaf than in evergreen broadleaf and coniferous litter. However, the soil mesofauna's effects on litter P loss were greater in evergreen broadleaf than in deciduous broadleaf and coniferous litter. Further, N addition stimulated the soil mesofauna's effects on litter N release only in evergreen broadleaf. Soil mesofauna's contribution to C and P loss correlated with the initial litter C/P ratio across 18 species. N addition effects were greater under low-N than high-N treatments in 0.1 mm litter bags.The findings suggested N addition and plant functional types independently mediated mesofauna-driven litter element release, highlighting the importance of soil mesofauna and plant functional types for belowground biogeochemical cycles via litter pathways in subtropical regions experiencing pronounced N deposition.Conclusion: Soil mesofauna-associated biogeochemical cycles could be mediated by nitrogen (N) deposition and plant functional types. However, N addition effects on the contribution of soil mesofauna to litter element release under different plant functional types remain unclear.A litterbag experiment with two mesh sizes (2 and 0.1 mm) examined the soil mesofauna's effect on litter carbon (C), N, and phosphorus (P) release of three functional types (evergreen broadleaf, deciduous broadleaf, and coniferous: 6 tree species for each group). Litterbags were exposed to varying N deposition levels (0, 20, and 40 kg N ha−1 yr−1) in a subtropical forest in southwest China.N addition and soil mesofauna promoted litter C, N, and P loss across three plant functional types. The soil mesofauna's effects on litter N loss were lower in deciduous broadleaf than in evergreen broadleaf and coniferous litter. However, the soil mesofauna's effects on litter P loss were greater in evergreen broadleaf than in deciduous broadleaf and coniferous litter. Further, N addition stimulated the soil mesofauna's effects on litter N release only in evergreen broadleaf. Soil mesofauna's contribution to C and P loss correlated with the initial litter C/P ratio across 18 species. N addition effects were greater under low-N than high-N treatments in 0.1 mm litter bags.The findings suggested N addition and plant functional types independently mediated mesofauna-driven litter element release, highlighting the importance of soil mesofauna and plant functional types for belowground biogeochemical cycles via litter pathways in subtropical regions experiencing pronounced N deposition. [ABSTRACT FROM AUTHOR]

The control of regioselectivity in Heck-type reaction of unactivated alkenes represents a longstanding challenge due to several detachable hydrogens in β–H elimination step, which generally afford either one specific regioisomer or a mixture. Herein, a copper-catalyzed intermolecular Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides with divergent regioselectivities is reported. The complete switch of regioselectivity mainly depends on the choice of different additives. Employment of alcohol solvent gives access to vinyl products, while the addition of carboxylate leads to the formation of allylic products. In addition, exclusion of these two promoting factors results in β-lactams via a C–N reductive elimination. This protocol shows a broad substrate scope for both alkenes and structurally diverse N-fluoro-sulfonamides, producing the corresponding products with excellent regio- and stereoselectivities. Further control experiments and DFT calculations provide in-depth insights into the reaction mechanism, highlighting the distinct effect of the additives on a bidentate auxiliary-stabilized Cu(III) intermediate. The control of regioselectivity in Heck-type reactions of unactivated alkenes is challenging. Here, the authors realize regiodivergent Heck-type reactions of unactivated alkenes and N-fluoro-sulfonamides. [ABSTRACT FROM AUTHOR]

In addition to apoptosis, it has also been reported that aluminum (Al) causes necroptosis, a new form of programmed necrosis, which has recently been discovered, in nerve cells, but its molecular mechanism is not elucidated. In order to explore the answer, in this study, we apply for this method that after PC12 cells were exposed to maltol aluminum [200 μM Al(mal)3], siRNA were used as interference technique to explore the role of Tumour necrosis factor receptor 1 (TNFR1), receptor interaction proteins 1 (RIP1) and receptor interaction proteins 3 (RIP3) in necroptosis caused by Al(mal)3. After the end of this research, we demonstrated that, initially, Al(mal)3 could trigger apoptosis and necroptosis in PC12 cells and up-regulate both mRNA and protein expressions of TNFR1, RIP1 and RIP3, also, up-regulate the phosphorylated mixed lineage kinase domain-like protein (MLKL) protein expression. Additionally, in PC12 cells treated with Al(mal)3, suppression of TNFR1 was found to enhance apoptosis and attenuate the expression of RIP1/RIP3 and phosphorylated MLKL. At last, deficiency of RIP1/RIP3 reduced the extent of necroptosis. Briefly, our results verify that the TNFR1-RIP1/RIP3 pathway could be involved in Al(mal)3 induced necroptosis. [ABSTRACT FROM AUTHOR]

Ganoderma lucidum is an edible mushroom highly regarded in the traditional Chinese medicine. To better understand the molecular mechanisms underlying fruiting body development in G. lucidum, transcriptome analysis based on RNA sequencing was carried out on different developmental stages: mycelium (G1); primordium (G2); young fruiting body (G3); mature fruiting body (G4); fruiting body in post-sporulation stage (G5). In total, 26,137 unigenes with an average length of 1078 bp were de novo assembled. Functional annotation of transcriptomes matched 72.49% of the unigenes to known proteins available in at least one database. Differentially expressed genes (DEGs) were identified between the evaluated stages: 3135 DEGs in G1 versus G2; 120 in G2 versus G3; 3919 in G3 versus G4; and 1012 in G4 versus G5. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs identified in G1 versus G2 revealed that, in addition to global and overview maps, enriched pathways were related to amino acid metabolism and carbohydrate metabolism. In contrast, DEGs identified in G2 versus G3 were mainly assigned to the category of metabolism of amino acids and their derivatives, comprising mostly upregulated unigenes. In addition, highly expressed unigenes associated with the transition between different developmental stages were identified, including those encoding hydrophobins, cytochrome P450s, extracellular proteases, and several transcription factors. Meanwhile, highly expressed unigenes related to meiosis such as DMC1, MSH4, HOP1, and Mek1 were also analyzed. Our study provides important insights into the molecular mechanisms underlying fruiting body development and sporulation in G. lucidum. [ABSTRACT FROM AUTHOR]

The preferred orientation of silver grains was (111) plane, and the nucleation of silver films doped finite glass on ferrite substrates proceeded with a typical non-wetting mode according to X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis. The silver grain growth exponent (n) at high annealing temperatures was 2.7–3.4, which increased as annealing temperatures increased. The activation energy (Q) of grain growth in silver was 33 ± 3 kJ/mol, indicating that the mechanism of grain growth was dominated by surface diffusion mass transport at high annealing temperatures (from 0.85 to 0.94Tm, where Tm is the melting point of silver). SEM analysis showed that the grain boundaries in silver films undergo faceted-defaceted transitions from 820 to 900°C. The annealing temperature had a more pronounced impact on faceted grain boundaries than the holding time. Nickel particles were firstly electrodeposited at the upper corners of the silver film trench at an early stage of the recrystallization process, then grew laterally between the steps and eventually transformed the entire nickel film, which could prevent solder from eroding silver films at high package temperatures. [ABSTRACT FROM AUTHOR]

Bioceramics have been commonly implemented to replace and restore hard tissues such as teeth and bones in recent years. Among different bioceramics, Baghdadite (BAG) has high bioactivity due to its ability to form apatite and stimulate cell proliferation. So, this structure is used widely for medical applications to treat bone-based diseases. Physically, we expect changes in temperature and pressure to affect the Baghdadite-based nanostructure's mechanical behaviour. So, in this computational study, we report the pressure/temperature effect on Baghdadite matrix with nanoscale size by using Molecular Dynamics (MD) approach. To this end, physical values like the total energy, temperature, final strength (FS), stress–strain curve, potential energy, and Young's modulus (YM) are reported. Simulation results indicated the mechanical properties of Baghdadite (BAG) nanostructure weakened by temperature and pressure increase. Numerically, the FS and YM of the defined structure reach 131.40 MPa/159.43 MPa, and 115.15 MPa/139.72 MPa with temperature/pressure increasing. Therefore, the increase in initial pressure and temperature leads to a decrease in the mechanical properties of nanostructures. These results indicate the importance of the initial condition in the Baghdadite-based nanostructures' mechanical behaviour that must be considered in clinical applications. [ABSTRACT FROM AUTHOR]

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8–T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling. [ABSTRACT FROM AUTHOR]

AAA+ proteases regulate numerous physiological and cellular processes through tightly regulated proteolytic cleavage of protein substrates driven by ATP hydrolysis. FtsH is the only known family of membrane-anchored AAA+ proteases essential for membrane protein quality control. Although a spiral staircase rotation mechanism for substrate translocation across the FtsH pore has been proposed, the detailed conformational changes among various states have not been clear due to absence of FtsH structures in these states. We report here the cryo-EM structure for Thermotoga maritima FtsH (TmFtsH) in a fully ADP-bound symmetric state. Comparisons of the ADP-state structure with its apo-state and a substrate-engaged yeast YME1 structure show conformational changes in the ATPase domains, rather than the protease domains. A reconstruction of the full-length TmFtsH provides structural insights for the dynamic transmembrane and the periplasmic domains. Our structural analyses expand the understanding of conformational switches between different nucleotide states in ATP hydrolysis by FtsH. Liu et. al determine the cryo-EM structure of ADP-bound transmembrane AAA+ protease FtsH and provide insights into conformational switches between different nucleotide states important for ATP hydrolysis by FtsH. [ABSTRACT FROM AUTHOR]

Disordered hepatic glucagon response contributes to hyperglycemia in diabetes. The regulators involved in glucagon response are less understood. This work aims to investigate the roles of mitochondrial β-oxidation enzyme HADHA and its downstream ketone bodies in hepatic glucagon response. Here we show that glucagon challenge impairs expression of HADHA. Liver-specific HADHA overexpression reversed hepatic gluconeogenesis in mice, while HADHA knockdown augmented glucagon response. Stable isotope tracing shows that HADHA promotes ketone body production via β-oxidation. The ketone body β-hydroxybutyrate (BHB) but not acetoacetate suppresses gluconeogenesis by selectively inhibiting HDAC7 activity via interaction with Glu543 site to facilitate FOXO1 nuclear exclusion. In HFD-fed mice, HADHA overexpression improved metabolic disorders, and these effects are abrogated by knockdown of BHB-producing enzyme. In conclusion, BHB is responsible for the inhibitory effect of HADHA on hepatic glucagon response, suggesting that HADHA activation or BHB elevation by pharmacological intervention hold promise in treating diabetes. Disordered hepatic glucagon response contributes to hyperglycemia in diabetes via gluconeogenesis. Here the authors report that the mitochondrial β-oxidation enzyme HADHA promotes β-hydroxybutyrate production, which negatively regulates hepatic gluconeogenesis during glucagon challenge by targeting HDAC7 in mice. [ABSTRACT FROM AUTHOR]

In the clades of animals that diverged from the bony fish, a group of Mas-related G-protein-coupled receptors (MRGPRs) evolved that have an active role in itch and allergic signals1,2. As an MRGPR, MRGPRX2 is known to sense basic secretagogues (agents that promote secretion) and is involved in itch signals and eliciting pseudoallergic reactions3–6. MRGPRX2 has been targeted by drug development efforts to prevent the side effects induced by certain drugs or to treat allergic diseases. Here we report a set of cryo-electron microscopy structures of the MRGPRX2–Gi1 trimer in complex with polycationic compound 48/80 or with inflammatory peptides. The structures of the MRGPRX2–Gi1 complex exhibited shallow, solvent-exposed ligand-binding pockets. We identified key common structural features of MRGPRX2 and describe a consensus motif for peptidic allergens. Beneath the ligand-binding pocket, the unusual kink formation at transmembrane domain 6 (TM6) and the replacement of the general toggle switch from Trp6.48 to Gly6.48 (superscript annotations as per Ballesteros–Weinstein nomenclature) suggest a distinct activation process. We characterized the interfaces of MRGPRX2 and the Gi trimer, and mapped the residues associated with key single-nucleotide polymorphisms on both the ligand and G-protein interfaces of MRGPRX2. Collectively, our results provide a structural basis for the sensing of cationic allergens by MRGPRX2, potentially facilitating the rational design of therapies to prevent unwanted pseudoallergic reactions.Cryo-electron microscopy structures of the MRGPRX2–Gi1 trimer in complex with polycationic compound 48/80 or inflammatory peptides provide insights into the sensing of cationic allergens by MRGPRX2, potentially facilitating the design of therapies to prevent unwanted pseudoallergic reactions. [ABSTRACT FROM AUTHOR]

Surplus production models (SPMs) are among the simplest and most widely used fishery stock assessment models. The catch-effort data analysis (CEDA) and a surplus production model incorporating covariates (ASPIC) are softwares for analyzing fishery catch and fishing effort data using nonequilibrium SPMs. In China Fishery Statistical Yearbook, annual fishery production and fishing effort data of the Yellow Sea, Bohai Sea, East China Sea, and South China Sea have been published from 1979 till present. Using its catch and fishing effort data from 1980 to 2018, we apply the CEDA and ASPIC to evaluate fishery resources in Chinese coastal waters. The results show that the total maximum sustainable yield (MSY) estimate of the four China seas is 10.05–10.83 million tons, approximately equal to the marine fishery catch (10.44 million tons) reported in 2018. It can be concluded that China's coastal fishery resources are currently fully exploited and must be protected with a precautionary approach. Both softwares produced similar results; however, the CEDA had a much higher R2 value (above 0.9) than ASPIC (about 0.2), indicating that CEDA can better fit the data and therefore is more suitable for analyzing the fishery resources in the coastal waters of China. [ABSTRACT FROM AUTHOR]

We consider the bipartite Sherrington–Kirkpatrick model in which the variance of disorders depends only on the species the particles belong to. By using the stochastic calculus method, we obtain the fluctuation result for the partition function in the absence of an external field. When the external field is nonzero, the central limit theorem for the free energy is also derived through a different stochastic calculus approach. It turns out that the corresponding convergence rates are not the same in those two cases. [ABSTRACT FROM AUTHOR]

Versatile methods to organize proteins in space are required to enable complex biomaterials, engineered biomolecular scaffolds, cell-free biology, and hybrid nanoscale systems. Here, we demonstrate how the tailored encapsulation of proteins in DNA-based voxels can be combined with programmable assembly that directs these voxels into biologically functional protein arrays with prescribed and ordered two-dimensional (2D) and three-dimensional (3D) organizations. We apply the presented concept to ferritin, an iron storage protein, and its iron-free analog, apoferritin, in order to form single-layers, double-layers, as well as several types of 3D protein lattices. Our study demonstrates that internal voxel design and inter-voxel encoding can be effectively employed to create protein lattices with designed organization, as confirmed by in situ X-ray scattering and cryo-electron microscopy 3D imaging. The assembled protein arrays maintain structural stability and biological activity in environments relevant for protein functionality. The framework design of the arrays then allows small molecules to access the ferritins and their iron cores and convert them into apoferritin arrays through the release of iron ions. The presented study introduces a platform approach for creating bio-active protein-containing ordered nanomaterials with desired 2D and 3D organizations. Organising proteins in 2D and 3D is needed to develop complex bimolecular materials for a range of applications. Here, the authors report the encapsulation of ferritin and apoferritin in DNA-based voxels with programmed assembly to generate both 2D and 3D protein lattices and demonstrate the retention of protein function. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created global health and economic emergencies. SARS-CoV-2 viruses promote their own spread and virulence by hijacking human proteins, which occurs through viral protein recognition of human targets. To understand the structural basis for SARS-CoV-2 viral-host protein recognition, here we use cryo-electron microscopy (cryo-EM) to determine a complex structure of the human cell junction protein PALS1 and SARS-CoV-2 viral envelope (E) protein. Our reported structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains of PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce E-mediated virulence. SARS-CoV-2 viruses are known to hijack human proteins in order to facilitate their own virulence and replication. In this study, Liu and colleagues present structural analysis of how this phenomenon occurs between SARS-CoV-2 viral envelope protein and human PALS1. The findings provide insights in to viral-host recognition. [ABSTRACT FROM AUTHOR]

Taraxacum antungense Kitag is a wild plant used in traditional medicines, teas, functional foods, and cosmetics. Luteolin is its major secondary metabolite. However, the molecular mechanisms underlying luteolin biosynthesis in T. antungense remain largely unknown. Here, high performance liquid chromatography (HPLC) was employed to measure the luteolin content in the flowers, leaves, and roots during T. antungense flowering. The flowers accumulated significantly more luteolin than the leaves or roots. RNA-seq analysis identified 16 differentially expressed genes (DEGs) including PAL, 4CL, CHS, CHI, and F3′H associated with luteolin biosynthesis and they were significantly upregulated in the flowers. This observation was positively correlated with luteolin accumulation. The extremely high F3′H (GWHGAAAA033111) expression level detected in the flowers was also consistent with high luteolin content. Thus, F3′H might play a vital role in luteolin biosynthesis. We identified 44 TaWRKYs in the T. antungense transcriptome database. Relative to wild type calli, TaWRKY44 was upregulated and the luteolin content was increased in TaWRKY44-transgenic T. antungense calli. Therefore, TaWRKY44 probably regulates luteolin biosynthesis. The results of this study lay a foundation for elucidating the molecular mechanisms and pathways controlling luteolin accumulation in T. antungense. Key message: Developing flowers of Taraxacum antungense Kitag are very rich in the highly useful flavonoid luteolin. Future research may establish ways to enhance luteolin production for multiple industrial purposes. [ABSTRACT FROM AUTHOR]

With SiO2 gel as the main skeleton material, the surface modification with methyl acrylate (MA) and tetraethylenepentamine (TEPA) was carried out by Michael addition and substitution reaction, after CO2 supercritical drying TEPA and MA modified SiO2 aerogel (TEPA–MA–SA aerogel) was obtained. The sample exhibited selectivity and enormous adsorption capacities for Cu2+ (218.57 mg g–1). The removal rate of Cu2+ in ternary-mixed metal solution reached 49.29%, ranking first among the materials we have known. MA and TEPA both contain rich groups such as –NH2 and –NH–, which provide abundant adsorption sites for adsorbing heavy metal ions. BET test showed that the specific surface area, the pore volume, and the pore diameter was 190.2 m2 g−1, 4.426 cm3 g−1 and 9.306 nm respectively. The above properties facilitated capture for Cu (II). The adsorption data were fitted with Langmuir and Freundlich adsorption isotherm models, and both models could describe the adsorption process. However, according to the fitting parameters, Langmuir adsorption isotherm model explicates the adsorption process better. Although the pore structure and specific surface area are beneficial to the physical adsorption, chemical chelation still plays a major role. XPS analysis further proved the possible adsorption mechanism that N and O atoms adsorb Cu (II) ions through chelation. Altogether, TEPA–MA–SA aerogel is suitable as an auxiliary adsorbent to purify contaminated water. Highlights: A novel silica aerogel (TEPA–MA–SA) was prepared by sol–gel technique and surface modification (Michael addition and substitution reaction). Abundant functional groups on the surface of the modified aerogel provide substantial adsorption sites. TEPA–MA–SA aerogel exhibited selectivity and enormous adsorption capacities for Cu2+ (218.57 mg g–1). The removal rate of Cu2+ in ternary-mixed metal solution reached 49.29%, ranking first among the materials we have known. [ABSTRACT FROM AUTHOR]

Approaches to reliably predict the developmental potential of embryos and select suitable embryos for blastocyst culture are needed. The development of time-lapse monitoring (TLM) and artificial intelligence (AI) may help solve this problem. Here, we report deep learning models that can accurately predict blastocyst formation and usable blastocysts using TLM videos of the embryo's first three days. The DenseNet201 network, focal loss, long short-term memory (LSTM) network and gradient boosting classifier were mainly employed, and video preparation algorithms, spatial stream and temporal stream models were developed into ensemble prediction models called STEM and STEM+. STEM exhibited 78.2% accuracy and 0.82 AUC in predicting blastocyst formation, and STEM+ achieved 71.9% accuracy and 0.79 AUC in predicting usable blastocysts. We believe the models are beneficial for blastocyst formation prediction and embryo selection in clinical practice, and our modeling methods will provide valuable information for analyzing medical videos with continuous appearance variation. Liao et al. propose a deep learning model to predict blastocyst formation using TLM videos following the first three days of embryogenesis. The authors develop an ensemble prediction model, STEM and STEM+, which were found to exhibit 78.2% and 71.9% accuracy at predicting blastocyst formation and useable blastocysts respectively. [ABSTRACT FROM AUTHOR]