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The latest Ordovician to earliest Silurian graptolite Avitograptus avitus is important in the biostratigraphy of the Ordovician–Silurian boundary interval. Two additional species of Avitograptus are described from the sponge-dominated Anji Biota of the Upper Ordovician Wenchang Formation (Metabolograptus persculptus Biozone) of Zhejiang Province, South China. One species, Avitograptus akidomorphus new species, is new; the other, Avitograptus acanthocystus new combination, which was previously placed in Climacograptus, is herein assigned to Avitograptus. The former species may represent the ancestral akidograptid because it is identical in thecal form to Akidograptus, but differs in the development of the proximal end. The evolutionary changes from Avitograptus avitus to Akidograptus and Parakidograptus involved distal movement of the origins of th11 and th12, thecal elongation, and greater outward inclination of the thecal walls.UUID: http://zoobank.org/81c433a0-9069-48d2-ae72-1267400cbf77.

In this study, a coupling model is developed to include the aero ball bearing dynamic performance in the mixed thermal elastohydrodynamic lubrication analysis, and the low-speed and heavy-load conditions during start-up and shut-down are involved. Based on the bearing quasi-dynamics, the inside motion state of the main loading surface is obtained, and the mixed thermal elastohydrodynamic lubrication is conducted to get bearing lubrication state and properties. The numerical lubrication model under low-speed and heavy-load conditions is validated against published tested data, which reveal well consistency in central film thickness. The lubrication properties between a single ball and inner race during start-up have been studied, which indicate the lubrication film transforms from boundary lubrication to unsafe mixed thermal elastohydrodynamic lubrication, and then goes into safe lubrication. The lubrication properties of the balls at different azimuths have been investigated during shut-down and compared with those in start-up, which have a similar opposite changing trend, but not a simple invertible process. The time in boundary lubrication region during shut-down is shorter, and the ball number in boundary lubrication region gets less, which means the lubrication properties are relatively better. At last, the parametric study on mixed thermal elastohydrodynamic lubrication properties during shut-down has been carried out. It is found that the small bearing curve coefficient and increasing ball number can reduce the boundary lubrication time and improve the bearing lubrication.

Changes in water quality from source water to finished water and tap water at two conventional drinking water treatment plants (DWTPs) were monitored. Beside the routine water quality testing, Caenorhabditis elegans-based toxicity assays and the fluorescence excitation-emission matrices technique were also applied. Both DWTPs supplied drinking water that met government standards. Under current test conditions, both the investigated finished water and tap water samples exhibited stronger lethal, genotoxic and reprotoxic potential than the relative source water sample, and the tap water sample was more lethal but tended to be less genotoxic than the corresponding finished water sample. Meanwhile, the nearly complete removal of tryptophan-like substances and newly generated tyrosine-like substances were observed after the treatment of drinking water, and humic-like substances were identified in the tap water. Based on these findings, toxic pollutants, including genotoxic/reproductive toxicants, are produced in the drinking water treatment and/or distribution processes. Moreover, further studies are needed to clarify the potentially important roles of tyrosine-like and humic-like substances in mediating drinking water toxicity and to identify the potential sources of these contaminants. Additionally, tryptophan-like fluorescence may be adopted as a useful parameter to monitor the treatment performance of DWTPs. Our observations provided insights into the importance of utilizing biotoxicity assays and fluorescence spectroscopy as tools to complement the routine evaluation of drinking water.

In Convolutional Neural Network (ConvNet) based age estimation algorithms, softmax loss is usually chosen as the loss function directly, and the problems of Cost Sensitivity (CS), such as class imbalance and misclassification cost difference between different classes, are not considered. Focus on these problems, this paper constructs a rectified softmax loss function with all-sided CS, and proposes a novel cost-sensitive ConvNet based age estimation algorithm. Firstly, a loss function is established for each age category to solve the imbalance of the number of training samples. Then, a cost matrix is defined to reflect the cost difference caused by misclassification between different classes, thus constructing a new cost-sensitive error function. Finally, the above methods are merged to construct a rectified softmax loss function for ConvNet model, and a corresponding Back Propagation (BP) training scheme is designed to enable ConvNet network to learn robust face representation for age estimation during the training phase. Simultaneously, the rectified softmax loss is theoretically proved that it satisfies the general conditions of the loss function used for classification. The effectiveness of the proposed method is verified by experiments on face image datasets of different races.

A linear regression model is constructed to predict the April–May precipitation in central China (PCC) with a lead time of 1–2 months. This model not only reproduces the historical April–May PCC from 1985 to 2006 but also demonstrates strong robustness and reliability during the independent test period of 2007–16. Two preceding factors are selected to build the model, the February–March Arctic stratospheric ozone (ASO) and Indian Ocean sea surface temperature (IOSST), indicating a synergistic impact of Arctic and tropical signals on the midlatitude climate. A possible mechanism of ASO changes affecting Chinese precipitation is that the stratospheric circulation anomalies related to ASO changes may downward influence circulation over North Pacific, and then extend westward to influence East Asia, leading to changes in Chinese precipitation. Anomalies of the other predictor, IOSST, are associated with a baroclinic structure over central China. For example, warm IOSST causes anomalous convection over central China and affects the warm and humid airstream flowing from the Pacific to China. These processes related to the two predictors result in the April–May PCC anomalies. Sensitivity experiments and a transient experiment covering a longer period than the observations/reanalysis support the results from our statistical analysis based on observations. It implies that this statistical model could be applied to the output of seasonal forecasts from observations and improve the forecasting ability of April–May PCC in the future.

The pedestrian block, famous for its entertainment and commercial vitality, plays an important role in our daily life. The use of this space is determined by the outdoor thermal comfort which can directly affect human's thermal sensation and commercial value. A field questionnaire survey is carried out simultaneously with collecting the microclimatic data in this area. The thermal acceptability and the thermal comfort sensation votes are assessed based on the PET, in addition, a three-dimensional microclimatic modelling tool Envi-met 4.0 is used to evaluate the outdoor thermal comfort and validate the accuracy of the software through comparing the measured data with the simulated data. After putting forward some suggestion for redesigning this area, the result shows that there is as strong improvement in broadening the cooling time, early morning (8:00 a.m. to 11:00 a.m.) and after 18:00 p.m. are the most comfortable time for visiting.

Psoriasis is a common chronic inflammatory skin disease with multifactor etiology, characterized by abnormal proliferation and differentiation of keratinocytes. Huang-Lian Jie-Du decoction (HLJDD) is a traditional Chinese medicine prescription with good clinical curative effect on psoriasis. However, its therapeutic mechanisms are still unclear.The psoriasis model of SKH-1 nude mice was established by imiquimod-induced and HLJDD gavage was given. Hematoxylin and eosin staining were used to evaluate pathological morphologies, and immunohistochemistry was used to detect the expressions of Wnt1,In this study, HLJDD reduced skin erythema and lesions, decreased the thickness of epidermal and downregulated the expressions of Wnt1,HLJDD can effectively treat psoriasis and inhibit the Wnt/

Glufosinate-ammonium (GLA) is a widely used herbicide with emerging concern over its male reproductive toxicity. Abnormalities in sperm histone modification induced by GLA exposure observed in our previous study aroused our interest in whether such alterations could further affect embryonic gene expression. Here we administered adult male mice with 0.2 mg/kg⋅day of GLA for 5 weeks to collect their sperm or 4-cell embryos after copulation. Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing showed alterations of sperm H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac), which are active histone modification marks involved in embryo development, while RNA sequencing identified differentially expressed genes in 4-cell embryos. Differentially H3K4me3 and H3K27ac occupied regions were mainly distributed at the gene promoters and putative enhancers, and were enriched in pathways related to the immune system and nervous system. Integrative analysis of these sequencing data showed that genes such as Mgl2 with increased H3K4me3 and H3K27ac in sperm were up-regulated in embryos, and vice versa for genes such as Dcn. Additionally, differentially occupied H3K4me3 and H3K27ac in sperm were linked to gene expression changes in both paternal and maternal alleles of 4-cell embryos. In conclusion, GLA-induced changes in sperm H3K4me3 and H3K27ac are concordant with gene expression in preimplantation embryos, which might further affect embryo development and offspring health.

Multi- elemental and -dimensional data are more and more important during the development of data-driven research, as is the case in modern palaeontology, in which visual examination, by experts or someday the artificial intelligence, to every fossil specimen acts a crucial and fundamental role. We here release an integrated image dataset of 113 Ordovician to Silurian graptolite species or subspecies that are significant in global stratigraphy and shale gas exploration. The dataset contains 1550 high-resolution graptolite specimen images and scientific information related to the specimen, e.g., every specimen's taxonomic, geologic, geographic, and related references. We develop a tool, FSIDvis (Fossil Specimen Image Dataset Visualiser), to facilitate the human-interactive exploration of the rich-attribution image dataset. A nonlinear dimension reduction technique, t-SNE (t-Distributed Stochastic Neighbor Embedding), is employed to project the images into the two-dimensional space to visualise and explore the similarities. Our dataset potentially contributes to the analysis of the global biostratigraphic correlations and improves the shale gas exploration efficiency by developing an image-based automated classification model. All images are available from https://doi.org/10.5281/zenodo.5205216 (Xu, 2021).

When it comes to association rule mining, all frequent itemsets are first found, and then the confidence level of association rules is calculated through the support degree of frequent itemsets. As all non-empty subsets in frequent itemsets are still frequent itemsets, all frequent itemsets can be acquired only by finding all maximal frequent itemsets (MFIs), whose supersets are not frequent itemsets. In this study, an algorithm, named right-hand side expanding (RHSE), which can accurately find all MFIs, was proposed. First, an Expanding Operation was designed, which, starting from any given frequent itemset, could add items using certain rules and form some supersets of given frequent itemsets. In addition, these supersets were all MFIs. Next, this operator was used to add items by taking all frequent 1-itemsets as the starting point alternately, and all MFIs were found in the end. Due to the special design of the Expanding Operation, each MFI could be found. Moreover, the path found was unique, which avoided the algorithm redundancy in temporal and spatial complexity. This algorithm, which has a high operating rate, is applicable to the big data of high-dimensional mass transactions as it is capable of avoiding the computing redundancy and finding all MFIs. In the end, a detailed experimental report on 10 open standard transaction sets was given in this study, including the big data calculation results of million-class transactions.

Background Soil salinization is causing ecosystem degradation and crop yield reduction worldwide, and elucidation of the mechanism of salt-tolerant plants to improve crop yield is highly significant. Podocarpus macrophyllus is an ancient gymnosperm species with a unique environmental adaptation strategy that may be attributed to its lengthy evolutionary process. The present study investigated the physiological and molecular responses of P. macrophyllus plants to salt stress by analyzing its photosynthetic system and antioxidant enzyme activity. We also analyzed the differentially expressed genes (DEGs) in P. macrophyllus under salt stress using RNA sequencing and de novo transcriptome assembly. Results Salt treatment significantly affected the photosynthetic system in P. macrophyllus seedlings, which decreased chlorophyll content, altered chloroplast ultrastructure, and reduced photosynthesis. The activities of antioxidant enzymes increased significantly following salt stress treatment. Transcriptome analysis showed that salt stress induced a large number of genes involved in multiple metabolic and biological regulation processes. The transcription levels of genes that mediate phytohormone transport or signaling were altered. K+ and Ca2+ transporter-encoding genes and the MYB transcription factor were upregulated under salt stress. However, the genes involved in cell wall biosynthesis and secondary metabolism were downregulated. Conclusion Our research identified some important pathways and putative genes involved in salt tolerance in P. macrophyllus and provided clues for elucidating the mechanism of salt tolerance and the utilization of the salt tolerance genes of P. macrophyllus for crop improvement.

Nine new highly oxygenated 3,5-dimethylorsellinic acid-derived meroterpenoids, talaromynoids A-I (

Background: Combination of fasting with chemotherapy has been drawn an increasing attention because of the encouraging efficacy. SLC7A11 is frequently over-expressed in most of cancer cells, and elevated expression of SLC7A11 renders cancer cells more susceptible to glucose starvation owing to SLC7A11-mediated redox collapse. Selenite is a representative inorganic form of selenium, and is preferentially accumulated in tumors. This selenophilic peculiarity of cancer cells is closely associated with the elevated expression of SLC7A11. Given the established the link among glucose deprivation, SLC7A11, oxidative stress and selenite, we hypothesized that glucose starvation could specifically sensitize cancer cells to selenite-mediated cytotoxic effect. Methods: The cytotoxic effect of combining selenite with glucose starvation on cancer cell was assessed by crystal violet staining and Annexin V/PI staining. Flow cytometry were employed to assess intracellular ROS levels, labile iron pool and lipid peroxidation. Xenograft models were used to test its in vivo antitumor activity. Commercial assay kit, LC-MS, RNA interference and western blot were applied to investigate the mechanism underlying synergistic effect.Results: It showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to accumulation of cystine, depletion of NADPH, and inhibition of cystine to cysteine conversion, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. Conclusion: The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite, and imply that combination of selenite with fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer.

(+)- and (-)-talaromyoxaones A and B (

The solution space of a frequent itemset generally presents exponential explosive growth because of the high-dimensional attributes of big data. However, the premise of the big data association rule analysis is to mine the frequent itemset in high-dimensional transaction sets. Traditional and classical algorithms such as the Apriori and FP-Growth algorithms, as well as their derivative algorithms, are unacceptable in practical big data analysis in an explosive solution space because of their huge consumption of storage space and running time. A multi-objective optimization algorithm was proposed to mine the frequent itemset of high-dimensional data. First, all frequent 2-itemsets were generated by scanning transaction sets based on which new items were added in as the objects of population evolution. Algorithms aim to search for the maximal frequent itemset to gather more non-void subsets because non-void subsets of frequent itemsets are all properties of frequent itemsets. During the operation of algorithms, lethal gene fragments in individuals were recorded and eliminated so that individuals may resurge. Finally, the set of the Pareto optimal solution of the frequent itemset was gained. All non-void subsets of these solutions were frequent itemsets, and all supersets are non-frequent itemsets. Finally, the practicability and validity of the proposed algorithm in big data were proven by experiments.

Diabetic nephropathy (DN) is one of the most serious and major renal complications of diabetes. Previously, Six-transmembrane Protein of Prostate 2 (STAMP2) was reported to contribute to nutritional stress. The purpose of this study is to investigate whether overexpression of STAMP2 attenuates diabetic renal injuries in DN rats. We induced the DN rat model by high-fat diet and low-dose streptozotocin and evaluated the metabolite and urine albumin/creatinine. Recombinant adeno-associated virus vectors were injected for overexpression of STAMP2. Pathophysiologic and ultrastructure features of DN by histochemical stain and transmission electron microscope, autophagy-related proteins and signaling pathway by western blotting were assessed. We found the expression of STAMP2 was decreased and autophagy was blunted in DN rat kidneys. Overexpressing STAMP2 significantly ameliorated metabolic disturbance, insulin resistance, and specifically restoring diabetic renal injury. Furthermore, overexpressing STAMP2 improved the autophagy deficiency in DN rats, as revealed by changes in the expressions of Beclin1, p62, and LC3. Furthermore, STAMP2 overexpressing promoted autophagy by inhibiting the mTOR and activating the AMPK/SIRT1 signaling pathway. Our results suggested that STAMP2 overexpression attenuated renal injuries via upregulating autophagy in DN rats. STAMP2 overexpressing promoted autophagy may been involved with inhibition of the mTOR/ULK1 and activation of the AMPK/SIRT1 signaling pathway.

SET domain group (SDG) proteins have been identified to be involved in histone modification and participate in diverse biological processes. Rice contains 41 SDG genes, however, most of which have not been functionally characterized. Here, we report the identification and functional investigation of rice SDG712 gene. Phylogenic analysis revealed that SDG712 belongs to the H3K9-specific SDG subclade. SDG712 is highly expressed in leaves during reproductive growth stage with obvious circadian rhythmic pattern. Mutation of SDG712 promotes rice flowering, while overexpression of SDG712 delays rice flowering. Gene expression analysis suggested that SDG712 acts downstream of Hd1, while acts upstream of Ehd1, Hd3a and RFT1. Subcellular localization assay demonstrated that SDG712 is localized in the nucleus. Chromatin immunoprecipitation (ChIP) assay showed that the H3K9me2 levels at Hd3a and RFT1 loci were increased in SDG712 overexpression transgenic plants, indicating that SDG712 may mediate the H3K9 di-methylation on these loci to repress rice flowering. Taken together, our findings demonstrated that SDG712 is a negative flowering regulatory gene in rice, and it delays flowering through repressing key flowering regulator gene Ehd1 and the florigen genes Hd3a and RFT1.

Cell death-inducing DFF45-like effector C (CIDEC) is involved in diet-induced adipose inflammation. Whether CIDEC plays a role in diabetic vascular inflammation remains unclear. A type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated its characteristics by metabolic tests, Western blot analysis of CIDEC and C1q/tumor necrosis factor-related protein-3 (CTRP3) expression, and histopathological analysis of aortic tissues. The diabetic group exhibited elevated CIDEC expression, aortic inflammation, and remodeling. To further investigate the role of CIDEC in the pathogenesis of aortic inflammation, gene silencing was used. With CIDEC gene silencing, CTRP3 expression was restored, accompanied with amelioration of insulin resistance, aortic inflammation, and remodeling in diabetic rats. Thus, the silencing of CIDEC is potent in mediating the reversal of aortic inflammation and remodeling, indicating that CIDEC may be a potential therapeutic target for vascular complications in diabetes.

This paper analyses the synchronization problem of switched cellular neural networks. The admissible edge-dependent average dwell time method is used to design switching signals. By virtue of the multiple Lyapunov function technology and Newton-Leibniz formula, a sufficient condition is established to guarantee the exponential synchronization of switched cellular neural networks. Finally, a numerical example is employed to verify the effectiveness of proposed methods.

In this paper, a unified virtual cloud storage method for federated data based on the middle layer is proposed, which aims at solving the problems of the heterogeneous data sources of remote sensing data in the shared platform among the federated remote sensing data management application under loose coupling mode. A federated remote sensing image data management model is developed based on NASA's Unified Metadata Model (UMM). This platform implements services such as unified access to multi-source heterogeneous image data which effectively solves the problem of heterogeneous data sources in the loosely coupled federated system, and provides better access methods for upper-level applications.

Nucleic acid‐based hydrogels that integrate intrinsic biological properties of nucleic acids and mechanical behavior of their advanced assemblies are appealing bioanalysis and biomedical studies for the development of new‐generation smart biomaterials. It is inseparable from development and incorporation of novel structural and functional units. This review highlights different functional units of nucleic acids, polymers, and novel nanomaterials in the order of structures, properties, and functions, and their assembly strategies for the fabrication of nucleic acid‐based hydrogels. Also, recent advances in the design of multifunctional and stimuli‐responsive nucleic acid‐based hydrogels in bioanalysis and biomedical science are discussed, focusing on the applications of customized hydrogels for emerging directions, including 3D cell cultivation and 3D bioprinting. Finally, the key challenge and future perspectives are outlined., Nucleic acid‐based hydrogels present the trend of interdisciplinary development from the diversified construction building blocks to the extensive application fields, mainly including biosensing, drug delivery, 3D cell cultivation, 3D bioprinting, bioimaging, and treatment and analysis of environmental pollutants.

This paper is devoted to the initial boundary value problem of the Vlasov–Poisson–Fokker–Planck system in a bounded domain. The global existence of a unique strong solution and its exponential convergence rate to the equilibrium state are proved under the specular reflection boundary condition. The proof is based on an elementary energy method and the [Formula: see text] theory developed by Guo et al. [Arch. Ration. Mech. Anal. 236(3), 1389–1454 (2020)] for kinetic models.

Purpose: The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is used to determine disease severity and predict outcomes in critically ill patients. However, there is no dynamic APACHE II score for predicting outcomes among ICU patients.The aim of this study is to explore the optimal timing to predict the outcomes of ICU patients by dynamically evaluating APACHE II score.Methods: Study data of demographics and comorbidities from the first 24 h after ICU admission were retrospectively extracted from MIMIC-III, a multiparameter intensive care database. The primary outcome was hospital mortality. 90-day mortality was a secondary outcome. APACHE II scores on days 1, 2, 3, 5, 7, 14 and 28 were compared using area under the receiver operating characteristic (AUROC) analysis. Hospital survival was visualised using Kaplan-Meier Curves.Results:A total of 6374 eligible subjects were extracted from the MIMIC-III. Mean APACHE II score on day 1 were 18.4±6.3, hospital and 90-day mortality was 19.1% and 25.8%, respectively.The optimal timing where predicted hospital mortality was on day 3 with an area under the cure of 0.666 (0.607-0.726)(P＜0.0001). The best tradeoff for preciction was found at 17 score, more than 17 score predicted mortality of non-survivors with a sensitivity of 92.8% and PPV of 23.1%. Hosmer-lemeshow goodness of fit test showed that APACHE II 3 has a good predictive calibration ability (X2 =6.198, P=0.625) and consistency of predicted death and actual death was 79.4%. The calibration of APACHE II 1 was poor (X2=294.898, PConclusions: APACHE II on 3 dayis the optimal prognostic marker and 17 score provided the best dignostic accuracy to predict outcomes for ICU patients. These finding will help medical make clinical judgment.

Physical fatigue during exercise can be defined as an impairment of physical performance. Multiple factors have been found contributing to physical fatigue, including neurotransmitter-mediated defense action, insufficient energy supply, and induction of oxidative stress. These mechanistic findings provide a sound theoretical rationale for nutritional intervention since most of these factors can be modulated by nutrient supplementation. In this review, we summarize the current evidence regarding the functional role of nutrients supplementation in managing physical performance and propose the issues that need to be addressed for better utilization of nutritional supplementation approach to improve physical performance.

Background With dramatically increasing prevalence, diabetes mellitus has imposed a tremendous toll on individual well-being. Humans are exposed to various environmental chemicals, which have been postulated as underappreciated but potentially modifiable diabetes risk factors. Objectives To determine the utility of environmental chemical exposure in predicting diabetes mellitus. Methods A total of 8501 eligible participants from NHANES 2005–2016 were randomly assigned to a discovery (N = 5953) set and a validation (N = 2548) set. We applied random forest (RF) and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation in the discovery set to select features, and built an optimal model to predict diabetes mellitus, blood insulin, fasting plasma glucose (FPG) and 2-h plasma glucose after oral glucose tolerance test (2-h PG after OGTT). Results The machine learning model using LASSO regression predicted diabetes with an area under the receiver operating characteristics (AUROC) of 0.80 and 0.78 in the discovery set and validation set, respectively. The linear model predicted blood insulin level with an R2 of 0.42 and 0.40 in the discovery set and validation set, respectively. For FPG, the discovery set and validation set yielded an R2 of 0.16 and 0.15, respectively. For 2-h PG after OGTT, the discovery set and validation set yielded an R2 of 0.18 and 0.17, respectively. Conclusion We used environmental chemical exposure, constructed machine learning models and achieved relatively accurate prediction for diabetes, emphasizing the predictive value of widespread environmental chemicals for complicated diseases.

Glufosinate-ammonium (GLA) is a widely used herbicide with emerging concern over its neural and reproductive toxicity. To uncover potential effects of GLA on male reproductive health in mammals, adult male C57BL/6J mice were administered 0.2 mg/kg·d GLA for 5 weeks. After examination on fertility, testis histology and semen quality in the GLA group, we performed deep sequencing to identify repressive epigenetic marks including DNA methylation and histone modifications (H3K27me3 and H3K9me3), together with mRNA transcript levels in sperm. Then, we integrated multi-omics sequencing data to comprehensively explore GLA-induced epigenetic and transcriptomic alterations. We found no significant difference either on fertility, testis histology or semen quality-related indicators. As for epigenome, the protein level of H3K27me3 was significantly increased in GLA sperm. Next generation sequencing showed alterations of these epigenetic marks and extensive transcription inhibition in sperm. These differential repressive marks were mainly distributed at intergenic regions and introns. According to results by Gene Ontology enrichment analysis, both differentially methylated and expressed genes were mainly enriched in pathways related to synapse organization. Subtle differences in genomic imprinting were also observed between the two groups. These results suggested that GLA predominantly impaired sperm epigenome and transcriptome in mice, with little effect on fertility, testis histology or semen quality. Further studies on human sperm using similar strategies need to be conducted for a better understanding of the male reproductive toxicity of GLA.

Background In plants, microRNAs (miRNAs) are pivotal regulators of plant development and stress responses. Different computational tools and web servers have been developed for plant miRNA target prediction; however, in silico prediction normally contains false positive results. In addition, many plant miRNA target prediction servers lack information for miRNA-triggered phased small interfering RNAs (phasiRNAs). Creating a comprehensive and relatively high-confidence plant miRNA target database is much needed. Results Here, we report TarDB, an online database that collects three categories of relatively high-confidence plant miRNA targets: (i) cross-species conserved miRNA targets; (ii) degradome/PARE (Parallel Analysis of RNA Ends) sequencing supported miRNA targets; (iii) miRNA-triggered phasiRNA loci. TarDB provides a user-friendly interface that enables users to easily search, browse and retrieve miRNA targets and miRNA initiated phasiRNAs in a broad variety of plants. TarDB has a comprehensive collection of reliable plant miRNA targets containing previously unreported miRNA targets and miRNA-triggered phasiRNAs even in the well-studied model species. Most of these novel miRNA targets are relevant to lineage-specific or species-specific miRNAs. TarDB data is freely available at http://www.biosequencing.cn/TarDB. Conclusions In summary, TarDB serves as a useful web resource for exploring relatively high-confidence miRNA targets and miRNA-triggered phasiRNAs in plants.

Most sensorimotor studies investigating the covariation of populations of neurons in primary motor cortex (M1) have considered only a few trained movements made under highly constrained conditions. However, motor behaviors in daily living happen in a far more complex and varied contexts. It is unclear whether M1 neurons would have different population responses in a more naturalistic, unconstrained setting, including requirements to accommodate multiple limbs and body posture, and more extensive proprioceptive inputs. Here, we recorded M1 spiking signals while a monkey performed hand grasp movements in two different contexts: one in the typical constrained lab setting, and the other while moving freely in a large plastic cage. We compared the covariance patterns of the neural activity during movements across the two contexts. We found that the neural covariation patterns accompanying two different hand grasps in the unconstrained context were largely preserved, while they differed across contexts, even for the same type of grasp. We also found that the M1 population activity was confined to context-dependent neural manifolds, but these manifolds were not completely independent, as some dimensions appeared to be shared across the contexts. These results suggest that the coordinated activity of M1 neurons is strongly dependent on behavioral context, in ways that were not entirely anticipated.

Fine particulate matter (PM2.5) has become a significant issue of ecological environment. However, few studies have explored the vertical distribution of PM2.5 in cities. The objectives of this paper are to reveal the vertical distribution regular pattern of PM2.5 over urban underlying surfaces near the ground with a hexacopter-type unmanned aerial vehicle (UAV) in winter. Results showed that the maximum vertical gradient of PM2.5 near the ground was typically the greatest in the morning as the stable atmospheric conditions. Moreover, regression model illustrated that relative humidity had the greatest impact on the vertical profile of PM2.5 compared to air temperature and altitude as hygroscopic of PM2.5 aerosols. Curve model shown that vertical profile of PM2.5 over the surfaces of water and green space first increased slowly and then declined, besides, the highest concentration inflection of PM2.5 above the water body (23.7 m) is higher than the green space (14.3 m). Thus, suggesting residents living vertical of 10–30 m from the ground around large water bodies and green spaces should not open windows for ventilation in the morning. Therefore, this study provides insights into the vertical distributions of PM2.5 over different underlying surfaces and should be of reference value to urban planners for designing urban spaces to optimize atmosphere environment to provide a healthy living environment.

Sensory nerves promote osteogenesis through the release of neuropeptides. However, the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive. The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats. The wound sites were accompanied by extensive nerve innervation and angiogenesis. Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model. Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A (Sema3A) and semaphorin 4D (Sema4D) in the dorsal root ganglion (DRG), as detected by the upregulation of signaling molecules. Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells. These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies. Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model, whereas overexpression of Sema3A promoted the silicon-induced phenomena. Activation of “mechanistic target of rapamycin” (mTOR) pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds. These findings support the role of silicon in inducing Sema3A production by sensory nerves, which, in turn, stimulates osteogenesis and angiogenesis. Taken together, silicon has therapeutic potential in orthopedic rehabilitation., Graphical abstract Image 1, Highlights • Nerve innervation, vascularization and tissue mineralization integrated into a single scaffold. • Silicified collagen scaffolds has therapeutic potential in orthopedic rehabilitation. • Silicified collagen scaffolds promote in-situ bone regeneration via sensory nerve innervation and semaphorin 3A production.

Calcium phosphate cement (CPC) modified with native and pregelatinized normal corn and waxy maize starches was studied. Effects of starch pregelatinization and starch type on the physicochemical properties of CPC were investigated. CPC modified with pregelatinized normal corn starch (CPB-PNC) or pregelatinized waxy maize starch (CPB-PW) was evaluated by two vertebral fracture surgical models in vitro. Both granular and pregelatinized starches significantly improved the setting times and injectability of CPC, but only the pregelatinized starches improved the anti-collapsibility and compressive strength of CPC significantly. CPB-PW, whose micro-structure was compact and uniform, showed the best physicochemical properties. Addition of starch did not inhibit the hydro-reaction of CPC. Unmodified CPC had very poor dispersibility and could not apply in the tests of the surgical models. Pregelatinized starch especially waxy maize starch improved the dispersibility of CPC and showed good dispersion area, volume, improved pull-out force and maximum torque in the Sawbones sponge model. Similarly, in the minimally invasive kyphoplasty model, CPB-PNC and CPB-PW could disperse in the osteoporotic sheep vertebrae and improve the compressive strength of the sheep vertebral body. In conclusion, starch pregelatinization and starch botanical source affect the physicochemical properties of CPC significantly. Bone cements modified by different starches also performed differently in surgical models for osteoporotic vertebral fracture. Pregelatinized waxy maize starch may be a better candidate for CPC modification comparing to the pregelatinized normal corn starch.

The progressive decline of physiological function and the increased risk of age-related diseases challenge healthy aging. Multiple anti-aging manipulations, such as senolytics, have proven beneficial for health; however, the biomarkers that label in vivo senescence at systemic levels are lacking, thus hindering anti-aging applications. In this study, we generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus, which encodes lysosomal β-galactosidase—an enzyme elevated in tissues of old mice. A linear correlation between GAC signal and chronological age is established in a cohort of middle-aged (9 to 13 months) Glb1+/m mice. The high GAC signal is closely associated with cardiac hypertrophy and a shortened lifespan. Moreover, the GAC signal is exponentially increased in pathological senescence induced by bleomycin in the lung. Senolytic dasatinib and quercetin (D + Q) reduce GAC signal in bleomycin treated mice. Thus, the Glb1-2A-mCherry reporter mice monitors systemic aging and function decline, predicts lifespan, and may facilitate the understanding of aging mechanisms and help in the development of anti-aging interventions.