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SUMMARY Licorice is one of the most extensively studied medicinal plants in the world, whose roots and rhizomes have long been used as both a sweetener and an essential component in numerous herbal preparations. However, the genus Glycyrrhiza has a complex composition, and the interspecies chromosomal relationships, origin, and evolution are still largely unclear. Here, we develop a set of whole‐chromosome painting probes that allowed identification of all eight chromosomes of licorice on same metaphase chromosomes. Comparative chromosome painting analyses in seven different Glycyrrhiza species revealed that the genus Glycyrrhiza maintained extraordinarily conserved chromosomal synteny after about 3–12 million years of divergence. No cytologically visible inter‐chromosomal rearrangements were identified in any species. By comparative chromosomal karyotype analyses, we revealed interspecific chromosome evolutionary relationships and dramatic variable chromosomal karyotype after independent divergence and demonstrated that G. prostrate was the most closely related to the ancestral type among the seven Glycyrrhiza species. Furthermore, we also discovered a G. glandulosa seed with distinct triploid‐genome for the first time in China, suggesting the existence of a polyploid evolutionary pathway in the genus Glycyrrhiza, which challenges the previous notion that only diploids of licorice existed in nature. This study expands our knowledge of the chromosome evolution of licorice and will lay an important foundation for the genome origin and evolution studies in the genus Glycyrrhiza. [ABSTRACT FROM AUTHOR]

The recent period has witnessed automated crawlers designed to automatically crack passwords, which greatly risks various aspects of our lives. To prevent passwords from being cracked, image verification codes have been implemented to accomplish the human–machine verification. It is important to note, however, that the most widely‐used image verification codes, especially the visual reasoning Completely Automated Public Turing tests to tell Computers and Humans Apart (CAPTCHAs), are still susceptible to attacks by artificial intelligence. Taking the visual reasoning CAPTCHAs representing the image verification codes, this study introduces an enhanced approach for generating image verification codes and proposes an improved Convolutional Neural Network (CNN)‐based recognition system. After we add a fully connected layer and briefly solve the edge of stability issue, the accuracy of the improved CNN model can smoothly approach 98.40% within 50 epochs on the image verification codes with four digits using a large initial learning rate of 0.01. Compared with the baseline model, it is approximately 37.82% better in accuracy without obvious curve oscillation. The improved CNN model can also smoothly reach the accuracy of 99.00% within 7500 epochs on the image verification codes with six characters, including digits, upper‐case alphabets, lower‐case alphabets, and symbols. A detailed comparison between our proposed approach and the baseline one is presented. The relationship between the time consumption and the length of the seeds is compared theoretically. Subsequently, we figure out the threat assignments on the visual reasoning CAPTCHAs with different lengths based on four machine learning models. Based on the threat assignments, the Kaplan‐Meier (KM) curves are computed. [ABSTRACT FROM AUTHOR]

Background: With the rapid increase of chest computed tomography (CT) images, the workload faced by radiologists has increased dramatically. It is undeniable that the use of artificial intelligence (AI) image‐assisted diagnosis system in clinical treatment is a major trend in medical development. Therefore, in order to explore the value and diagnostic accuracy of the current AI system in clinical application, we aim to compare the detection and differentiation of benign and malignant pulmonary nodules between AI system and physicians, so as to provide a theoretical basis for clinical application. Methods: Our study encompassed a cohort of 23 336 patients who underwent chest low‐dose spiral CT screening for lung cancer at the Health Management Center of West China Hospital. We conducted a comparative analysis between AI‐assisted reading and manual interpretation, focusing on the detection and differentiation of benign and malignant pulmonary nodules. Results: The AI‐assisted reading exhibited a significantly higher screening positive rate and probability of diagnosing malignant pulmonary nodules compared with manual interpretation (p < 0.001). Moreover, AI scanning demonstrated a markedly superior detection rate of malignant pulmonary nodules compared with manual scanning (97.2% vs. 86.4%, p < 0.001). Additionally, the lung cancer detection rate was substantially higher in the AI reading group compared with the manual reading group (98.9% vs. 90.3%, p < 0.001). Conclusions: Our findings underscore the superior screening positive rate and lung cancer detection rate achieved through AI‐assisted reading compared with manual interpretation. Thus, AI exhibits considerable potential as an adjunctive tool in lung cancer screening within clinical practice settings. [ABSTRACT FROM AUTHOR]

Apoptosis is a genetically programmed form of cell death that is substantially conserved across the evolutionary tree. Apoptotic cell elimination includes recognition, phagocytosis, and degradation. Failure to clear apoptotic cells can ultimately cause a series of human diseases, such as systemic lupus erythematosus, Alzheimer's disease, atherosclerosis, and cancer. Consequently, the timely and effective removal of apoptotic cells is crucial to maintaining the body's homeostasis. GPCRs belong to the largest membrane receptor family. Its intracellular domain exerts an effect on the trimer G protein. By combining with a variety of ligands, the extracellular domain of G protein initiates the dissociation of G protein trimers and progressively transmits signals downstream. Presently, numerous G protein‐coupled receptors (GPCRs) have been identified as participants in the apoptosis signal transduction pathway and the apoptotic cell clearance pathway. Therefore, studies on the mechanism of GPCRs in the clearance of apoptotic cells is important for the development of GPCRs therapeutics. [ABSTRACT FROM AUTHOR]

Objectives: Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low‐dose computed tomography (LDCT) screening for the high‐risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real‐world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick‐slice LDCT scanning. Methods: A total of 29 296 subjects who underwent low‐dose thick‐slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low‐dose thin‐slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups. Results: The positive rate of LDCT screening in the thin‐slice scanning group was significantly higher than that in the thick‐slice scanning group (20.1% vs. 14.4%, p < 0.001). In addition, the lung cancer detection rate in the thin‐slice LDCT screening positive group was significantly higher than that in the thick‐slice scanning group (78.0% vs. 52.9%, p < 0.001). Conclusions: The screening positive rate of low‐dose thin‐slice CT scanning is higher and more early‐stage lung cancer (IA1 stage) can be detected in the screen‐positive group. [ABSTRACT FROM AUTHOR]

Efficient water dissociation to atomic hydrogen (H*) with restrained recombination of H* is crucial for improving the H* utilization for electrochemical dechlorination, but is currently limited by the lack of feasible electrodes. Herein, we developed a monolithic single‐atom electrode with Co single atoms anchored on the inherent oxide layer of titanium foam (Co1−TiOx/Ti), which can efficiently dissociate water into H* and simultaneously inhibit the recombination of H*, by taking advantage of the single‐atom reverse hydrogen spillover effect. Experimental and theoretical calculations demonstrated that H* could be rapidly generated on the oxide layer of titanium foam, and then overflowed to the adjacent Co single atom for the reductive dechlorination. Using chloramphenicol as a proof‐of‐concept verification, the resulting Co1−TiOx/Ti monolithic electrode exhibited an unprecedented performance with almost 100 % dechlorination at −1.0 V, far superior to that of traditional indirect reduction‐driven commercial Pd/C (52 %) and direct reduction‐driven Co1−N−C (44 %). Moreover, its dechlorination rate constant of 1.64 h−1 was 4.3 and 8.6 times more active than those of Pd/C (0.38 h−1) and Co1−N−C (0.19 h−1), respectively. Our research sheds light on the rational design of hydrogen spillover‐related electrocatalysts to simultaneously improve the H* generation, transfer, and utilization for environmental and energy applications. [ABSTRACT FROM AUTHOR]

Photocatalytic activation of persulfate is considered to be a promising purification technology. In this study, a novel nanospherical composite material is synthesized by loading MoS2 Quantum Dots on Bi4O5I2. MoS2 Quantum Dots enhance the activity of the composite material and separation efficiency of electrons and holes. Meanwhile the composite material demonstrates a strong photocurrent response by optoelectronic analysis. In addition, the light absorption range is further expanded. Based on the improvement of photoelectric properties and light absorption performance, the BM0.5%/PS/Vis system exhibits the most excellent performance with a degradation rate of 69.7% for tetracycline within 60 min. The degradation mechanism is verified through free radical capture experiments, the radicals involve in degradation are ·OH, ·SO4−, ·O2− and 1O2. The possible degradation pathway of tetracycline is proposed by liquid chromatography‐mass spectrometry (LC‐MS). This work is expected to provide a research direction for the application of modified bismuth halide in PS activation. [ABSTRACT FROM AUTHOR]

Background: The value of SyMRI‐derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R‐ISS) in participants with multiple myeloma (MM) is unknown. Methods: We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re‐epithelialization through mesenchymal‐epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal‐epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal‐derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal‐epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal‐epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal‐epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by β‐catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re‐epithelialization in future. [ABSTRACT FROM AUTHOR]

Introduction: Esthetic procedures are currently among the most effective options for consumers seeking to correct aging signs such as fine lines, wrinkles, and skin tone unevenness. Currently, there is a scientific need for an adjunct active to be paired with esthetic procedures to encourage wound recovery and address postprocedure pigmentation concerns. Objective: Toward that goal, this study assessed the efficacy of a peptide created from a multi‐component reaction (multi‐component peptide, MCP) as a model active for postprocedure care and evaluated its ability to promote skin healing in an ablative laser‐induced wound model on the forearm. Methods: The mechanism of action of MCP was investigated using tubo assays, 2D melanocyte, and fibroblast cultures, reconstructed skin equivalents, and ex vivo skin explants. The MCP formula and the clinical benchmark formula of Aquaphor were assessed head‐to‐head by applying the products topically in an ablative laser‐induced wound model (n = 20 subjects). The promotion of wound healing was evaluated by the investigator assessment of epithelial confluence, crusting or scabbing, general wound appearance, erythema, and edema. Results: MCP was determined to be beneficial to postprocedure skin recovery and healing by four main mechanisms of action: barrier repair as determined in an ex vivo tape‐stripping model, reduction of inflammation and postinflammatory hyperpigmentation, reduction of elastase activity, and stimulation of fibroblast through the mTOR pathway. The formula containing 10% MCP enhanced the kinetics of epithelial confluence and improvement of the crusting or scabbing appearance of the laser‐generated wounds in a laser‐induced mini‐zone wound healing study on the forearm. Conclusion: This study demonstrates the use of MCP as a proof of concept regenerative active that when incorporated into an optimized postprocedure skincare formula can improve skin healing and enhance the appearance of skin after injury with relevance to ablative aesthetic procedures. [ABSTRACT FROM AUTHOR]

Considering the cooperative willingness of multiple heterogeneous energy sources to participate in the alliance, the stability of the cooperative operation of each entity (hereinafter referred to as stability) and the supporting mechanism of its optimal combination to realize the high proportion of new energy generation are studied. Through simulating load peak‐cutting and valley‐filling in the power system, the difference between the load value and the base load in the 24 h of the daily load curve is used as the calculation condition for the supply balance of the alliance. Based on the source‐load power balance model, the feasibility of power data normalization is derived and demonstrated. Simultaneously, taking into account the time‐of‐use price cost of each entity, a multiscale operation cost allocation and stability evolution analysis model for the alliance is constructed using the Shapley value and the largest consistent set method. By comparing the willingness of each entity to engage in the alliance, as well as the multiscale operation stability and economic change rule of different alliances, the results demonstrate that: (1) Alliance 1 has the advantage of economic operation. (2) The common stability period of different alliances is influenced by the participation preferences of each entity (wind power, photovoltaic, and thermal power tend to participate in Alliance 1, while hydropower tends to participate in Alliance 2). (3) Alliance internal restructuring can be carried out by utilizing spatial and temporal difference characteristics of different entities' participation in alliance preferences, thereby achieving alliance stability and efficient operation. This study provides a theoretical basis for making decisions regarding the optimized stable operation of the alliance. [ABSTRACT FROM AUTHOR]

Objective: Our previous research have found that mesenchymal β‐catenin may be involved in palatal shelf (PS) elevation by regulating F‐actin. Here, we further investigated the exact mechanism of β‐catenin/F‐actin in the PS mesenchyme to regulate palatal reorientation. Materials and Methods: (1) Firstly, Ctnnb1ex3f (β‐catenin) mice were conditionally overexpressed in the palatal mesenchyme by crossing with the Sox9‐creERT2 mice (induced by Tamoxifen injections); (2) Subsequently, histology and immunohistochemistry were used to characterize the variations of PS morphology and expression of key molecules associated with developmental process; (3) Finally, experiments in vivo and ex vivo were employed to identify the critical mechanisms in β‐catenin silenced and overexpressed models. Results: We found that the Sox9CreER; Ctnnb1ex3f mice exhibited failed palatal elevation and visible cleft palate, and overexpression of β‐catenin disturbed the F‐actin responsible for cytoskeletal remodeling in palatal mesenchymal cells. qRT‐PCR results showed mRNA levels of α‐actinin4, a gene involved in F‐actin cross‐linking, were associated with knockdown or overexpression of β‐catenin in ex vivo, respectively. Experiments in vivo revealed that mesenchymal specific inactivation or overexpression of β‐catenin exhibited decreased or increased α‐actinin‐4 expression. Conclusions: Mesenchymal β‐catenin/F‐actin plays an essential role in PS reorientation, which mediate α‐actinin‐4 to regulate F‐actin cytoskeleton reorganization. [ABSTRACT FROM AUTHOR]

Palmitoylation, a critical lipid modification of proteins, is involved in various physiological processes such as altering protein localization, transport, and stability, which perform essential roles in protein function. Palmitoyltransferases are specific enzymes involved in the palmitoylation modification of substrates. S‐palmitoylation, as the only reversible palmitoylation modification, is able to be deacylated by deacyltransferases. As an important mode of programmed cell death, apoptosis functions in the maintenance of organismal homeostasis as well as being associated with inflammatory and immune diseases. Recently, studies have found that palmitoylation and apoptosis have been demonstrated to be related in many human diseases. In this review, we will focus on the role of palmitoylation modifications in apoptosis. [ABSTRACT FROM AUTHOR]

SUMMARY: Two parallel pathways compartmentalized in the chloroplast and the endoplasmic reticulum contribute to thylakoid lipid synthesis in plants, but how these two pathways are coordinated during thylakoid biogenesis and remodeling remains unknown. We report here the molecular characterization of a homologous ADIPOSE TRIGLYCERIDE LIPASE‐LIKE gene, previously referred to as ATGLL. The ATGLL gene is ubiquitously expressed throughout development and rapidly upregulated in response to a wide range of environmental cues. We show that ATGLL is a chloroplast non‐regioselective lipase with a hydrolytic activity preferentially towards 16:0 of diacylglycerol (DAG). Comprehensive lipid profiling and radiotracer labeling studies revealed a negative correlation of ATGLL expression and the relative contribution of the chloroplast lipid pathway to thylakoid lipid biosynthesis. Additionally, we show that genetic manipulation of ATGLL expression resulted in changes in triacylglycerol levels in leaves. We propose that ATGLL, through affecting the level of prokaryotic DAG in the chloroplast, plays important roles in balancing the two glycerolipid pathways and in maintaining lipid homeostasis in plants. Significance Statement: This study reveals that the ADIPOSE TRIGLYCERIDE LIPASE‐LIKE gene encodes a chloroplast diacylglycerol lipase which plays important roles in modulating glycerolipid pathway balance and in maintaining lipid homeostasis in Arabidopsis. [ABSTRACT FROM AUTHOR]

In deep coal mining, the high temperature and humidity environment are one of the main disasters threatening workers and equipment. To predict the temperature and humidity of airflow in the airway accurately, this study establishes a numerical calculation model of the surrounding rock temperature, airflow temperature, and humidity under the conditions of considering the moisture evaporation and heat absorption of the airway wall, the condensation and heat release of supersaturated water vapor in the airflow, and the influence of air compression or expansion. Combined with the two‐dimensional (2D) heat conduction model (considering the influence of the axial surrounding rock heat conduction of the airway), the axial strip partial moisture calculation model of the airway is proposed, and then the uniform moist wall model and the axial strip partial moist wall model are established. The influence of different parameters on the temperature and humidity of airflow is discussed by analyzing the results of numerical simulation of the uniform wet surface model (UWSM) and partly wet surface model (PWSM) of the airway wall. The results show that the surrounding rock temperature, especially the temperature distribution of the airway wall, calculated by using the 2D heat conduction model under the local humid airway conditions, is more realistic. The increment of airflow temperature decreases with the increase of wet area ratio, airflow temperature at the entrance and airway radius, and increases with relative humidity at the entrance. The calculation accuracy of temperature and humidity prediction for large ventilation networks can be further improved by using the equivalent humidity of the UWSM to replace the correction coefficient of the wet area ratio of the PWSM. [ABSTRACT FROM AUTHOR]

Purpose: Simulation course serves as an efficient supplement to the experiential learning inside the operation room in surgical residency programs. Furlow double‐opposing Z‐plasty (DOZ) remains an important and challenging surgical technique in cleft palate repair, but the simulation is currently limited. This study aims to develop a blended learning module with low‐cost and easy‐to‐promote DOZ simulation. Methods: Comparison among the common rodent experimental animals and the readily available porcine tongue was made to select the ideal animal for surgical simulation, with which a DOZ learning module was developed. Oral surgery residents were enrolled to attend the blended learning module. An after‐session questionnaire and a quiz were distributed to the participants to collect their feedback of the course perceptions and to assess their learning outcomes. Results: The porcine tongue had more advantages in simulating the human soft palate over the common experimental animals. The surgical procedure of DOZ could be well designed and simulated on the porcine tongue. The vast majority of the participant liked the learning module regarded it as beneficial for the comprehension if DOZ principles and procedures. With the help of the porcine tongue simulator, the blended learning module helped the participants grasp the designing principles of DOZ procedure and promote their associative learning. Conclusions: The blended learning module incorporating the porcine tongue simulator can help oral surgery residents master the principles and procedures of DOZ palatoplasty. [ABSTRACT FROM AUTHOR]

Background: Observational epidemiological studies suggest that lung cancer risk may be raised by gastroesophageal reflux disease (GERD); however, the causal relationship between them remains unknown. Our study performed the two‐sample Mendelian randomization (MR) approach to examine the causal relationship between GERD and lung cancer. Methods: Instrument variables were found to be independent single nucleotide polymorphisms (SNPs) that were highly linked with GERD (n = 129,080). Summary data from genome‐wide association studies (GWAS) data were used to determine outcomes for lung cancer (n = 11,348), squamous cell lung cancer (LUSC), and lung adenocarcinoma (LUAD). In this study, three MR statistical techniques (inverse variance weighted (IVW), MR‐Egger, and weighted median) were used to examine the potential causative relationship between GERD and the risk of lung cancer. Cochran's Q test, MR‐Egger intercept test, leave‐one‐out analysis, and the funnel plot were all used in sensitivity analyses. Results: The main IVW method revealed that GERD substantially increased the risk of lung cancer [odds ratio (OR) = 1.37; 95% CI 1.16–1.63, p = 0. 0003], which was also supported by weighted median and MR‐Egger analyses. Using IVW estimate, similar causal relationships were also observed between GERD and LUSC (OR = 1.56; 95% CI 1.26–1.93, p = 5.35 × 10−5) and LUAD (OR = 1.45; 95% CI 1.09–1.93, p = 0.01). Although potential heterogeneity was observed in some studies, random effect IVW was not violated by the heterogeneity, indicating that the causal effect was robust. Conclusion: GERD was positively associated with the risk of lung cancer, for LUSC and LUAD. This study shed light on a new direction for prevent strategy of lung cancer and therapeutic perspectives in patients with GERD. [ABSTRACT FROM AUTHOR]

Let Ln8,4 represent a linear octagonal‐quadrilateral network, consisting of n eight‐member rings and n four‐member rings. Such a graph contains a unique pair of opposite edges. The Möbius graph Qn(8, 4) is constructed by reverse identifying these opposite edges, whereas the cylinder graph Qn′(8, 4) identifies the opposite edges in the natural manner. In this paper, the explicit formulas for the Kirchhoff index and complexity of Qn(8, 4) and Qn′(8, 4) are deduced from Laplacian characteristic polynomials using to decomposition theorem and Vieta's theorem. A consequence is the surprising fact that the Kirchhoff index of Qn(8, 4) (resp. Qn′(8, 4)) is approximately a third (resp. half) of its Wiener index as n→∞. [ABSTRACT FROM AUTHOR]

BACKGROUND: Auricularia auricula (A. auricula) is one of the most abundant sources of plant protein in edible fungi. Problems of low protein yield exist in traditional methods of protein extraction such as alkali extraction and ultrasonic-assisted alkali after pretreatment with enzymes. Thus, the protein extraction process was investigated and optimized using a definitive screening design from A. auricula to improve the protein yield under practical operating conditions of temperature, the concentration of NaCl, meal/water ratio, extraction time and pH. RESULTS: The yield of protein isolates of the isoelectric-ammonium sulfate precipitation (9.34% w/w) was obtained almost three times and the protein content (55.23% w/w) was approximately 1.6 times that of the traditional extraction method of isoelectric precipitation. Next, the optimized method was successfully applied to the analysis of the functional properties of the protein. A. auricula protein isolate (AAPI) had better solubility, emulsification and foaming capacity than soy protein isolate (SPI) and pea protein isolate (PPI), and the oil holding capacity of AAPI exhibited extremely well, which was approximately five times that of SPI and six times that of PPI. The texture properties of AAPI gel were similar to those of PPI gels. CONCLUSION: AAPI extracted by the optimized method had a satisfactory yield and had the potential to substitute plant-originated proteins in food processing. [ABSTRACT FROM AUTHOR]

The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDPF is significantly increased in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and recurrence of PDAC patients. Overexpression of PPDPF promotes PDAC cell growth in vitro and in vivo, while PPDPF knockout exerts opposite effects. Pancreatic‐specific deletion of PPDPF profoundly inhibits tumor development in KRASG12D‐driven genetic mouse models of PDAC. PPDPF can bind GTP and transfer GTP to SOS1. Mutations of the GTP‐binding sites severely impair the tumor‐promoting effect of PPDPF. Consistently, mutations of the critical amino acids mediating SOS1–PPDPF interaction significantly impair the GEF activity of SOS1. Therefore, this study demonstrates a novel model of KRAS activation via PPDPF‐SOS1 axis, and provides a promising therapeutic target for PDAC. [ABSTRACT FROM AUTHOR]

Objective: Genetic variants in ninjurin‐2 (NINJ2; nerve injury‐induced protein 2) confer risk of ischemic strokes and coronary artery disease as well as endothelial activation and inflammation. However, little is known about NINJ2's in vivo functions and underlying mechanisms. Methods: The phenotypes of NINJ2 knockout mice were analyzed, and mechanisms of NINJ2 that regulate body weight, insulin resistance, and glucose homeostasis and lipogenesis were investigated in vivo and in vitro. Results: This study found that mice lacking NINJ2 showed impaired adipogenesis, increased insulin resistance, and abnormal glucose homeostasis, all of which are risk factors for strokes and coronary artery disease. Mechanistically, NINJ2 directly interacts with insulin receptor/insulin‐like growth factor 1 receptor (INSR/IGF1R), and NINJ2 knockdown can block insulin‐induced mitotic clonal expansion during preadipocyte differentiation by inhibiting protein kinase B/extracellular signal‐regulated kinase (AKT/ERK) signaling and by decreasing the expression of key adipocyte transcriptional regulators CCAAT/enhancer‐binding protein β (C/EBP‐β), C/EBP‐α, and peroxisome proliferator‐activated receptor γ (PPAR‐γ). Furthermore, the interaction between NINJ2 and INSR/IGF1R is needed for maintaining insulin sensitivity in adipocytes and muscle via AKT and glucose transporter type 4. Notably, adenovirus‐mediated NINJ2 overexpression can ameliorate diet‐induced insulin resistance in mice. Conclusions: In conclusion, these findings reveal NINJ2 as an important new facilitator of insulin receptors, and the authors propose a unique regulatory mechanism between insulin signaling, adipogenesis, and insulin resistance. [ABSTRACT FROM AUTHOR]

Fabricating single‐atom electrodes via atomic dispersion of active metal atoms into monolithic metal supports is of great significance to advancing the lab‐to‐fab translation of the electrochemical technologies. Here, we report an inherent oxide anchoring strategy to fasten ligand‐free isolated Ru atoms on the amorphous layer of monolithic Ti support by regulating the electronic metal‐support interactions. The prepared Ru single atom electrode exhibited exceptional electrochemical chlorine evolution activity, three orders of magnitude higher mass activity than that of commercial dimensionally stable anode, and also selectively reduced nitrate to ammonia with an unprecedented ammonia yield rate of 22.2 mol g−1 h−1 at −0.3 V. Furthermore, the Ru single atom monolithic electrode can be scaled up from 2×2 cm to 25×15 cm at least, thus demonstrating great potential for industrial electrocatalytic applications. [ABSTRACT FROM AUTHOR]

SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS‐CoV‐2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T‐LNPs. Leading 4N4T‐LNPs exhibit much higher mRNA translation efficiency than the approved SM‐102‐LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full‐length S protein of the SARS‐CoV‐2 variant is synthesized and loaded in 4N4T‐LNPs. The obtained 4N4T‐DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD‐specific IgG titers and neutralizing antibody titers than SM‐102‐based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine‐induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T‐DS mRNA vaccines also induce strong Th1‐skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS‐CoV‐2 variants. [ABSTRACT FROM AUTHOR]

Summary: Known for their regulatory roles in stem cell homeostasis, CLAVATA3/ESR‐RELATED (CLE) peptides also function as mediators of external stimuli such as hormones. De novo shoot regeneration, representing the remarkable plant cellular plasticity, involves reconstitution of stem cells under control of stem‐cell regulators. Yet whether and how stem cell‐regulating CLE peptides are implicated in plant regeneration remains unknown.By CRISPR/Cas9‐induced loss‐of‐function studies, peptide application, precursor overexpression, and expression analyses, the role of CLE1–CLE7 peptides and their receptors in de novo shoot regeneration was studied in Arabidopsis thaliana.CLE1–CLE7 are induced by callus‐induction medium and dynamically expressed in pluripotent callus. Exogenously‐applied CLE1–CLE7 peptides or precursor overexpression effectively leads to shoot regeneration suppression, whereas their simultaneous mutation results in enhanced regenerative capacity, demonstrating that CLE1–CLE7 peptides redundantly function as negative regulators of de novo shoot regeneration. CLE1–CLE7‐mediated shoot regeneration suppression is impaired in loss‐of‐function mutants of callus‐expressed CLAVATA1 (CLV1) and BARELY ANY MERISTEM1 (BAM1) genes, indicating that CLV1/BAM1 are required for CLE1–CLE7‐mediated shoot regeneration signaling. CLE1–CLE7 signaling resulted in transcriptional repression of WUSCHEL (WUS), a stem cell‐promoting transcription factor known as a principal regulator of plant regeneration.Our results indicate that functionally‐redundant CLE1–CLE7 peptides genetically act through CLV1/BAM1 receptors and repress WUS expression to modulate shoot‐regeneration capacity, establishing the mechanistic basis for CLE1–CLE7‐mediated shoot regeneration and a novel role for CLE peptides in hormone‐dependent developmental plasticity. [ABSTRACT FROM AUTHOR]

Introduction: Angelica dahurica(BZ) and Angelica dahurica var. formosana(HBZ) are two plant sources of Angelicae dahuricae Radix. Although BZ and HBZ are commonly used herbal medicines with great medicinal and dietary values, study on their phytochemicals and bioactive compositions is limited. Objective: To compare the chemical compositions of BZ and HBZ and find the chemical makers for discrimination and quality evaluation of the two botanical origins of Angelicae dahuricae Radix. Methodology: A high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry method was established for chemical profiling of BZ and HBZ. Then, a quantitative analysis of multiple components by a single marker method was developed for simultaneous determination of nine bioactive coumarins (xanthotoxol, oxypeucedanin hydrate, byakangelicin, xanthotoxin, bergapten, oxypeucedanin, phellopterin, imperatorin and isoimperatorin). Moreover, chemometrics were performed to compare and discriminate BZ and HBZ samples. Results: A total of 30 coumarins compounds were identified, and the chemical compositions in BZ and HBZ were quite similar. The quantitative analysis showed that there were significant differences in the contents of bioactive coumarins, and the chemometric analysis indicated five coumarins (xanthotoxol, xanthotoxin, bergapten, phellopterin and isoimperatorin) were responsible for the significant differences between BZ and HBZ, which could be used as chemical markers to distinguish the two original plant sources of Angelicae dahuricae Radix. Conclusion: The present work provided useful information for understanding the chemical differences between BZ and HBZ and also provided feasible methods for quality evaluation and discrimination of herbal medicines originating from multiple botanical sources. To comprehensively comparison and quality evaluation of Angelica dahurica (BZ) and Angelica dahurica var. formosana (HBZ), the chemical compositions in these two plant resources of Angelicae dahuricae Radix were characterized by HPLC‐Q/TOF‐MS, QAMS and chemometric methods. A total of 30 coumarins compounds were identified, and five coumarins were selected as chemical markers for responsible for the significant differences between BZ and HBZ, which could be used to distinguish the two original plant sources of Angelicae dahuricae Radix. [ABSTRACT FROM AUTHOR]

A new series of rare‐earth‐cerate high‐entropy ceramics with compositions of (La0.2Nd0.2Sm0.2Gd0.2Dy0.2)2Ce2O7 (HEC1), (La0.2Nd0.2Sm0.2Gd0.2Yb0.2)2Ce2O7 (HEC2), (La0.2Nd0.2Sm0.2Yb0.2Dy0.2)2Ce2O7 (HEC3), (La0.2Nd0.2Yb0.2Gd0.2Dy0.2)2Ce2O7 (HEC4), (La0.2Yb0.2Sm0.2Gd0.2Dy0.2)2Ce2O7 (HEC5) as well as a single component of Nd2Ce2O7 are fabricated via sintering the corresponding sol–gel‐derived powders at 1600°C for 10 h. HEC1–5 samples exhibit a single‐cerate phase with fluorite structure and high configurational entropy. Compared with Nd2Ce2O7, HEC1–5 samples have a lower grain growth rate owing to the sluggish diffusion effect. The chemical compositional uniformity of HEC1–5 as well as Nd2Ce2O7 does not apparently change after annealing at 1500°C for different time intervals (1, 6, 12, and 18 h). Compared with 8YSZ, HEC1–5 samples display the decreased thermal conductivity and increased thermal expansion coefficient. The lattice size disorder parameter of HEC1–5 is negatively related to the thermal conductivity in 26–450°C. Furthermore, HEC1–5 and Nd2Ce2O7 exhibit lower oxygen‐ion conductivity, meaning an increased resistance to oxygen diffusion. [ABSTRACT FROM AUTHOR]

Objective: We conducted a survey‐based discrete‐choice experiment (DCE) to understand the test features that drive women's preferences for prenatal genomic testing, and explore variation across countries. Methods: Five test attributes were identified as being important for decision‐making through a literature review, qualitative interviews and quantitative scoring exercise. Twelve scenarios were constructed in which respondents choose between two invasive tests or no test. Women from eight countries who delivered a baby in the previous 24 months completed a DCE presenting these scenarios. Choices were modeled using conditional logit regression analysis. Results: Surveys from 1239 women (Australia: n = 178; China: n = 179; Denmark: n = 88; Netherlands: n = 177; Singapore: n = 90; Sweden: n = 178; UK: n = 174; USA: n = 175) were analyzed. The key attribute affecting preferences was a test with the highest diagnostic yield (p < 0.01). Women preferred tests with short turnaround times (p < 0.01), and tests reporting variants of uncertain significance (VUS; p < 0.01) and secondary findings (SFs; p < 0.01). Several country‐specific differences were identified, including time to get a result, who explains the result, and the return of VUS and SFs. Conclusion: Most women want maximum information from prenatal genomic tests, but our findings highlight country‐based differences. Global consensus on how to return uncertain results is not necessarily realistic or desirable. Key points: What's already known about this topic?Prenatal genome‐wide sequencing approaches increase diagnostic yield but also the chance of identifying uncertain findings.It is unclear which test features drive women's preferences for prenatal genomic testing. What does this study add?The findings add to our understanding of whether and how attitudes differ across countries with varying cultures and healthcare services.This work highlights the importance of guidelines tailored to individual countries as well as pre‐test counseling that identifies the personal values and preferences of patients. [ABSTRACT FROM AUTHOR]

The aim of latent variable selection in multidimensional item response theory (MIRT) models is to identify latent traits probed by test items of a multidimensional test. In this paper the expectation model selection (EMS) algorithm proposed by Jiang et al. (2015) is applied to minimize the Bayesian information criterion (BIC) for latent variable selection in MIRT models with a known number of latent traits. Under mild assumptions, we prove the numerical convergence of the EMS algorithm for model selection by minimizing the BIC of observed data in the presence of missing data. For the identification of MIRT models, we assume that the variances of all latent traits are unity and each latent trait has an item that is only related to it. Under this identifiability assumption, the convergence of the EMS algorithm for latent variable selection in the multidimensional two‐parameter logistic (M2PL) models can be verified. We give an efficient implementation of the EMS for the M2PL models. Simulation studies show that the EMS outperforms the EM‐based L1 regularization in terms of correctly selected latent variables and computation time. The EMS algorithm is applied to a real data set related to the Eysenck Personality Questionnaire. [ABSTRACT FROM AUTHOR]

Corner is an important local feature of image which has been widely applied on various computer vision and image processing tasks. Here, a contour‐based corner detector is developed by using the ratio of parallelogram diagonals (RPD) to estimate the curve curvature. The main advantage of RPD detector is that only once square root operation is required to calculate the curvature value at each point on a contour while maintaining good noise robustness. The contributions of this paper include the following three aspects: First, the motivation of the proposed RPD curvature is illustrated by means of parallelogram theory; second, a complete corner detector is proposed based on RPD curvature; third, comprehensive experiments are carried out and the experimental results show superior performances of the proposed method against another five strong baselines. In these experiments, RPD runs 100% faster than the prior works. Moreover, a mean accuracy of 83.87% is reported on GCM dataset which is an improvement of about 0.9% and a mean accuracy of 74.21% is reported on CPDA dataset which is an improvement of about 0.2%. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) has come into the spotlight due to its potential for addressing a staggering number of diseases, while the lack of effective and safe carriers for in vivo delivery significantly limits its clinical application. Herein, the potential of lipid‐like nanoparticles (LLNs) containing three new cholesterol derivatives to achieve the liver targeting delivery of mRNA is investigated. The central composite design (CCD) is used to tailor the formulation of LLNs through in vivo optimization of the molar ratios of these cholesterol derivatives required for liver targeting. The optimized LLNs (O‐LLNs) are able to systemically deliver mRNA to the liver of mice with a synergistic action of prolonged systemic circulation, increased liver targeting, and enhanced hepatocyte uptake. The O‐LLNs outperformed DLin‐MC3‐DMA (MC3) in functional delivery of Cre‐recombinase (Cre) and human erythropoietin (hEPO) mRNA. Successful delivery of cytidine base editor mRNA (CBE mRNA) and sgRNA by O‐LLNs achieved more than 8% correction rates in a liver‐related metabolism disorder, phenylketonuria (PKU). In conclusion, the general method above can accelerate in vivo screening and optimization of multicomponent nanoparticle formulations, and the optimized ones demonstrate great potential as delivery vehicles for targeted gene therapy in specific tissues. [ABSTRACT FROM AUTHOR]

A second phase of Y2O3‐stabilized Bi2O3 (Bi0.75Y0.25O1.5,YSB) is introduced into Y2O3‐doped CeO2 (Ce0.8Y0.2O1.9,YDC) as a sintering additive and the composite ceramics of YDC‐xYSB (x = 0, 5, 10, 20, 30, 40 wt%) are prepared through sintering at 1100°C for 6 h in air atmosphere. The YDC‐xYSB ceramics are composed of both YDC and YSB with cubic fluorite structure, and no other impurity phases are detected in XRD patterns. The relative density of YDC‐xYSB rises firstly for x ≤5 wt%, and then it declines with YSB addition from 5 to 40 wt%. The average grain size of YDC decreases from 270 nm to 85.7 nm with YSB addition from 0 to 40 wt%. The YSB phase segregates at the grain boundaries of YDC based on the TEM analysis result. The ionic conductivity of YDC‐xYSB (x ≥5 wt%) is lower than that of YDC in the test temperature of 200°C–500°C, while it gradually exceeds that of YDC in 500°C–750°C. At 750°C, the conductivity of YDC‐30%YSB (6.22 × 10−2 S/cm) is 1.35 times higher than that of YDC (4.6 × 10−2 S/cm). The YSB addition can improve the ionic conductivity of YDC in 500°C–750°C and decrease its sintering temperature. [ABSTRACT FROM AUTHOR]

Aims: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease to cause end‐stage kidney disease. This study investigated the difference in urinary exosomal circular RNA (circRNA) expression profiles between patients with IgAN and healthy controls (HCs), for better understanding of gene regulation in exosomes of IgAN patients. Methods: A pairwise comparison of urinary circRNA expression profiles between IgAN patients and HCs was performed using methods, including high‐throughput sequencing and quantitative polymerase chain reaction. Moreover, the potential functions of differentially expressed circRNAs (DECs) in IgAN were investigated by gene ontology (GO) enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; and the circRNA‐miRNA‐mRNA network. Results: We identified 450 upregulated and 26 downregulated circRNAs in the IgAN patients. GO analysis showed that these enriched circRNAs might regulate primary miRNA processing, the ability of angiotensin receptor binding, and stress fibre function. KEGG analysis suggested these DECs may be closely associated with the phosphoinositide‐3‐kinase‐protein kinase B/Akt (PI3K‐Akt) signalling pathways. Network analysis revealed the relationship between circRNAs and their target genes. Conclusion: The identified DECs may be useful for both researches on molecular aetiology of IgAN and development of potentially novel non‐invasive biomarkers of IgAN. SUMMARY AT A GLANCE: An RNA‐sequence analysis of RNAs in urinary exosomes identified a number of differentially expressed circular RNAs in immunoglobulin A nephropathy (IgAN) patients as compared to healthy controls. These circRNAs are associated with the regulation of pathways relevant to IgAN and may provide useful non‐invasive biomarkers for this condition. [ABSTRACT FROM AUTHOR]

BACKGROUND The fruiting body of Pleurotus tuoliensis deteriorates rapidly after harvest, causing a decline in its commercial value and a great reduction in its shelf life. According to the present research, carbohydrate‐active enzymes (CAZymes) may cause the softening, liquefaction and autolysis of mature mushrooms after harvest. To further understand the in vivo molecular mechanism of CAZymes affecting the postharvest quality of P. tuoliensis fruiting bodies, a tandem mass tags labelling combined liquid chromatography–tandem mass spectrometry (TMT‐MS/MS) proteomic analysis was performed on P. tuoliensis fruiting bodies during storage at 25 °C. RESULTS: A total of 4737 proteins were identified, which had at least one unique peptide and had a confidence level above 95%. Consequently, 1307 differentially expressed proteins (DEPs) were recruited using the criteria of abundance fold change (FC) >1.5 or < 0.67 and P < 0.05. The identified proteins were annotated by dbCAN2, a meta server for automated CAZymes annotation. Subsequently, 222 CAZymes were obtained. Several CAZymes participating in the cell wall degradation process, including β‐glucosidase, glucan 1,3‐β‐glucosidase, endo‐1,3(4)‐β‐glucanase and chitinases, were significantly upregulated during storage. The protein expression level of CAZymes, such as xylanase, amylase and glucoamylase, were upregulated significantly, which may participate in the P. tuoliensis polysaccharide degradation. CONCLUSIONS: The identified CAZymes degraded the polysaccharides and lignin, destroying the cell wall structure, preventing cell wall remodeling, causing a loss of nutrients and the browning phenomenon, accelerating the deterioration of P. tuoliensis fruiting body. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

mascRNA is a small cytoplasmic RNA derived from the lncRNAMALAT1. After being processed by the tRNA processing enzymes RNase P and RNase Z, mascRNA undergoes CCA addition like tRNAs and folds into a tRNA‐like cloverleaf structure. While MALAT1 functions in multiple cellular processes, the role of mascRNA was largely unknown. Here, we show that mascRNA binds directly to the multi‐tRNA synthetase complex (MSC) component glutaminyl‐tRNA synthetase (QARS). mascRNA promotes global protein translation and cell proliferation by positively regulating QARS protein levels. Our results uncover a role of mascRNA that is independent of MALAT1, but could be part of the molecular mechanism of MALAT1's function in cancer, and provide a paradigm for understanding tRNA‐like structures in mammalian cells. Synopsis: tRNA‐like noncoding RNA mascRNA increases the cytosolic protein levels of multi‐tRNA synthetase complex (MSC) component glutaminyl‐tRNA synthetase (QARS) by interacting with it and promoting its stability, thereby upregulating global protein translation. mascRNA interacts specifically with QARS in the cytosol.Binding of mascRNA increases QARS stability and protein levels.Increasing QARS protein levels by mascRNA results in an upregulation of global protein translation. [ABSTRACT FROM AUTHOR]

Due to complex root–soil interactions, the responses of carbon (C) dynamics in the rhizosphere to elevated nitrogen (N) deposition may be different from those in bulk soil. However, the potentially different response of C dynamics in the rhizosphere and bulk soils and their contributions to soil C sequestration under N deposition is still not elucidated.We conducted an N addition experiment in an alpine shrubland dominated by Sibiraea angustata located on the eastern Qinghai‐Tibet Plateau (QTP). We measured the soil organic C (SOC) contents and density fractions in the rhizosphere and bulk soils in the top 15 cm of mineral soil and then employed a numerical model based on the rhizosphere extent to evaluate how the rhizosphere modulates soil C sequestration under N addition. We also measured the microbial gene abundance and C‐acquisition enzyme activities to assess microbial community responses to N addition.The results showed that nitrogen addition had opposite effects on the rhizosphere and bulk‐soil C stocks. Specifically, N addition decreased the rhizosphere SOC content by increasing bacterial abundance, β‐glucosidase activity, and thus accelerating the loss of free light fraction C (FLF‐C). However, N addition increased the bulk‐soil C content, which was corresponding with the reduced oxidase activities and the accelerated accumulation of heavy fraction C (HF‐C) under N addition. Numerical model analysis showed that the decrease induced by N addition in rhizosphere SOC stock ranged from 0.11 to 3.01 kg C/m2 as root exudation diffusion distance extended from 0.5 to 2 mm, while the corresponding increase in the bulk‐soil C stock ranged from 1.91 to 4.08 kg C/m2. By synthesizing the dynamics of the SOC stocks in these two soil compartments under N addition, the SOC stock at the ecosystem level exhibited an increase in range of 0.73–2.44 kg C/m2.Synthesis. Our results suggest that alpine shrublands on the eastern QTP have great potential for soil C sequestration under N deposition, and the magnitude of the sequestration would depend closely on the responses of rhizosphere microbial C processes and the rhizosphere extent. Our results highlight the importance of integrating rhizosphere processes into land surface models to accurately predict ecosystem functions in the background of elevated N deposition. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real‐time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan–Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC‐M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p <.05). The diagnostic value of PLCE1 was validated with the datasets (all p <.01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse‐free survival (both p <.05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤.05). The oncogene PLCE1 was differentially expressed in HCC and non‐HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability. [ABSTRACT FROM AUTHOR]

Summary: Awns, bristle‐like structures extending from grass lemmas, provide protection against predators, contribute to photosynthesis and aid in grain dispersal. In wheat, selection of awns with minimal extension, termed awnletted, has occurred during domestication by way of loci that dominantly inhibit awn development, such as Tipped1 (B1), Tipped2 (B2), and Hooded (Hd). Here we identify and characterize the B1 gene.B1 was identified using bulked segregant RNA‐sequencing of an F2 durum wheat population and through deletion mapping of awned bread wheat mutants. Functional characterization was accomplished by gene overexpression while haplotype analyses assessed B1 polymorphisms and genetic variation.Located on chromosome 5A, B1 is a C2H2 zinc finger encoding gene with ethylene‐responsive element binding factor‐associated amphiphilic repression (EAR) motifs. Constitutive overexpression of B1 in awned wheat produced an awnletted phenotype with pleiotropic effects on plant height and fertility. Transcriptome analysis of B1 overexpression plants suggests a role as transcriptional repressor, putatively targeting pathways involved in cell proliferation. Haplotype analysis revealed a conserved B1 coding region with proximal polymorphisms and supported the contention that B1 is mainly responsible for awnletted wheats globally.B1, predominantly responsible for awn inhibition in wheat, encodes a C2H2 zinc finger protein with EAR motifs which putatively functions as a transcriptional repressor. [ABSTRACT FROM AUTHOR]

With continued increasing construction of both electrified facilities and buried high‐strength pipelines in China, stray current corrosion defects have become an nonignorable threat for these pipelines. A comprehensive investigation on a new failure pressure prediction model for high‐strength pipes with stray current corrosion defects was conducted in this study. The mechanism of stray current corrosion in steel pipes was firstly elaborated in brief. After that, a parameterized finite element model for stress analysis of pipes with external corrosion defects was programmed by APDL code developed by general software ANSYS. By comparing numerical results with full‐scale experimental results, both the numerical model and the failure criteria for pipe burst were proven to be reasonable. Based on the finite element model, parametric analysis was performed using a calculation matrix set by orthogonal testing method to investigate the effects of three main dimensionless factors, that is, ratio of pipe diameter to wall thickness, nondimensional corrosion defect length, and nondimensional corrosion defect depth on pipe's failure pressure. Utilizing the parametric analysis results as database, a multilayer feed‐forward artificial neural network (ANN) was developed for failure pressure prediction. By comparison with experimental burst test results and results of previous failure pressure estimation model, the ANN model results were proven to have both high accuracy and efficiency, which could be referenced in residual strength or safety assessment of high‐strength pipes with corrosion defects. [ABSTRACT FROM AUTHOR]

Pyruvate kinase M2 (PKM2), playing a central role in regulating aerobic glycolysis, was considered as a promising target for cancer therapy. However, its role in cancer metastasis is rarely known. Here, we found a tight relationship between PKM2 and breast cancer metastasis, demonstrated by the findings that beta‐elemene (β‐elemene), an approved drug for complementary cancer therapy, exerted distinct anti‐metastatic activity dependent on PKM2. The results indicated that β‐elemene inhibited breast cancer cell migration, invasion in vitro as well as metastases in vivo. β‐Elemene further inhibited the process of aerobic glycolysis and decreased the utilization of glucose and the production of pyruvate and lactate through suppressing pyruvate kinase activity by modulating the transformation of dimeric and tetrameric forms of PKM2. Further analysis revealed that β‐elemene suppressed aerobic glycolysis by blocking PKM2 nuclear translocation and the expression of EGFR, GLUT1 and LDHA by influencing the expression of importin α5. Furthermore, the effect of β‐elemene on migration, invasion, PKM2 transformation, and nuclear translocation could be reversed in part by fructose‐1,6‐bisphosphate (FBP) and L‐cysteine. Taken together, tetrameric transformation and nuclear translocation of PKM2 are essential for cancer metastasis, and β‐elemene inhibited breast cancer metastasis via blocking aerobic glycolysis mediated by dimeric PKM2 transformation and nuclear translocation, being a promising anti‐metastatic agent from natural compounds. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N2O) is one of the major human‐induced greenhouse gases. It has a large potential for global warming, a long lifetime and can deplete ozone. In China, nitrogenous fertilizer is an important source of N2O in agricultural soils, especially in vegetable production, where large amounts of nitrogen fertilizers are commonly used. Isotopomer ratios of N2O, oxygen and bulk nitrogen isotope values (δ18O and δ15Nbulk) and intramolecular 15N site preferences (SP) have recently been used to identify the sources of N2O. In this study, vegetable farm soil was incubated with manure (M), compound fertilizers (CF) and no fertilizers (NF). The acetylene inhibition method and a 15N isotopic technique were used to reveal the most likely microbial processes leading to N2O emissions. The results showed that the M treatment produced smaller N2O emissions than the CF treatment of the soil. Nitrifier denitrification or denitrifier denitrification made the greatest contribution to N2O production in the M treatment, accounting for approximately 60–89% of N2O production, whereas it was 25–55% and 37–66% in the CF and NF treatments under non‐acetylene conditions, respectively. Under non‐acetylene conditions, N2O reduction to N2 was largest for treatment M (32–90%), intermediate for NF (42–77%) and smallest for CF (20–51%). The results also showed that nitrifier nitrification and N2O reduction were partly inhibited under acetylene conditions, with a relative contribution of 9–20% and 0–83% for M, 39–48% and 0–46% for CF, and 25–35% and 0–56% for NF, respectively. Our results suggest that analysing isotopomer ratios of N2O with SP would be a practical approach for determining the contributions of microbial processes to N2O emissions from different pools in soil. The results revealed that manure produced smaller N2O emissions and promoted relatively larger rates of denitrification and N2O reduction than compound fertilizers with the same amount of N, which indicated that complementing chemical with manure fertilizers might help to reduce N2O emissions on vegetable‐producing land. Highlights: We investigated emissions and sources of N2O with different types of fertilizers.For the same amount of N, manure produced less N2O than compound fertilizer.Stable isotope analysis revealed that denitrification was the dominant process in the manure treatment.The acetylene inhibition method can supplement δ15Nbulk compared with the SP model to assess N2O reduction in soil. [ABSTRACT FROM AUTHOR]

Background: The number of red blood cell units transfused per capita in China is lower than in western countries and the reason(s) for the difference is unknown.Study Design and Methods: We randomly chose 5050 transfused patients from five Chinese hospitals. We compared transfused cases to nontransfused controls matched for the same underlying diagnosis. We assessed the pretransfusion hemoglobin (Hb) trigger and other clinical characteristics associated with transfusion. After stratifying by underlying disease, we compared pretransfusion Hb level in Chinese hospitals to 12 US hospitals.Results: In 5050 patients who received transfusion, the pretransfusion Hb levels were lower in medical (6.3 g/dL) compared to surgical patients receiving transfusion postoperatively (8.1 g/dL). In patients with nonsurgical diagnoses, the pretransfusion Hb was much lower than that in the United States; the difference in mean Hb level varied by underlying diagnosis from 0.4 to 1.8 g/dL. In case-control analysis of cases (n = 1356) compared to controls (n = 1201), the pretransfusion Hb showed the strongest association with transfusion. Compared to 10 g/dL, the odds ratio (95% confidence interval) for pretransfusion Hb of 7 to 7.9 g/dL was 37.7 (24.8-57.4).Conclusion: Transfusion triggers in five Chinese hospitals appear comparable to those in the United States for surgical patients; however, medical patients have lower pretransfusion Hb levels (approx. 6 g/dL). Of the factors assessed, the pretransfusion Hb was most strongly associated with transfusion. The clinical impact of lower transfusion thresholds used in China is unknown. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to develop an effective one‐step decoloration and deproteinisation method using macroporous resin for Cordyceps militaris polysaccharide (CMP) extraction. Performances of different resins were compared, and the structures and bioactivities of CMP recovered using this one‐step method were evaluated and compared with traditional methods. The results showed that NKA‐9 resin exhibited the highest adsorption capacity for pigment and free protein than other tested resins. Under the optimised condition, NKA‐9 resin adsorption exhibited high decoloration ratio (80.69%), deproteinisation ratio (62.51%) and polysaccharide recovery ratio (78.08%). Furthermore spectroscopic analysis revealed that the structure of CMP remained unchanged after adsorption, but some reagent residues can be detected using traditional methods. Compared with traditional methods, the antioxidant activity of CMP extracted using a one‐step method was significantly higher, without negative impact on cell viability. Thus, this novel technique is a promising alternative method for CMP separation and purification. [ABSTRACT FROM AUTHOR]

Flower blooming is a beautiful phenomenon in nature as flowers open in an intricate and complex manner whereas petals bend, stretch and twist under various deformations. Flower petals are typically thin structures arranged in tight configurations with heavy self-occlusions. Thus, capturing and reconstructing spatially and temporally coherent sequences of blooming flowers is highly challenging. Early in the process only exterior petals are visible and thus interior parts will be completely missing in the captured data. Utilizing commercially available 3D scanners, we capture the visible parts of blooming flowers into a sequence of 3D point clouds. We reconstruct the flower geometry and deformation over time using a template-based dynamic tracking algorithm. To track and model interior petals hidden in early stages of the blooming process, we employ an adaptively constrained optimization. Flower characteristics are exploited to track petals both forward and backward in time. Our methods allow us to faithfully reconstruct the flower blooming process of different species. In addition, we provide comparisons with state-of-the-art physical simulation-based approaches and evaluate our approach by using photos of captured real flowers. [ABSTRACT FROM AUTHOR]

Fatty acid biosynthesis is a primary metabolic pathway that occurs in plastids, whereas the formation of glycerolipid molecules for the majority of cellular membrane systems and the deposition of storage lipid in seeds takes place in the cytosolic compartment. In this report, we present a study of an Arabidopsis mutant, ar21, with a novel seed fatty acid phenotype showing higher contents of eicosanoic acid (20:1) and oleic acid (18:1) and a reduced level of α-linolenic acid (18:3). A combination of map-based cloning and whole-genome sequencing identified the genetic basis underlying the fatty acid phenotype as a lesion in the plant-specific eukaryotic translation initiation factor eIFiso4G1. Transcriptome analysis on developing seeds revealed a reduced level of plastid-encoded genes. Specifically, decreases in both transcript and protein levels of an enzyme involved in fatty acid biosynthesis, the β-subunit of the plastidic heteromeric acetyl-CoA carboxylase (ht ACCase) encoded by accD, were evident in the mutant. Biochemical assays showed that the developing seeds of the mutant possessed a decreased ht ACCase activity in the plastid but an elevated activity of homomeric acetyl-CoA carboxylase (hm ACCase). These results suggested that the increased 20:1 was attributable at least in part to the enhanced cytosolic hm ACCase activity. We also detected a significant repression of FATTY ACID DESATURASE 3 ( FAD3) during seed development, which correlated with a decreased 18:3 level in seed oil. Together, our study on a mutant of eIFiso4G1 uncovered multifaceted interactions between the cytosolic and plastidic compartments in seed lipid biosynthesis that impact major seed oil traits. [ABSTRACT FROM AUTHOR]

CD19 is expressed on normal and neoplastic B cells and is a promising target for immunotherapy. However, there is still an unmet need to further develop novel therapeutic drugs for the treatment of the refractory/relapsing human CD19+ tumors. We have developed a diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19+ tumors. We have constructed three isoforms of the CD19 immunotoxin: monovalent, bivalent, and foldback diabody. In vitro binding affinity and efficacy analysis demonstrated that the bivalent isoform had the highest binding affinity and in vitro efficacy. The in vivo efficacy of the CD19 immunotoxins was assessed using human CD19+ JeKo-1 tumor-bearing NOD/ SCID IL-2 receptor γ−/− ( NSG) mouse model. In these animals, CD19 immunotoxins significantly prolonged the median survival from 31 days in controls to 34, 36, and 40 days in animals receiving the monovalent isoform, foldback diabody isoform, and bivalent isoform, respectively. The bivalent CD19 immunotoxin is a promising therapeutic drug candidate for targeting relapsing/refractory human CD19+ tumors. [ABSTRACT FROM AUTHOR]

Deoxynivalenol ( DON), a trichothecene mycotoxin produced by Fusarium graminearum, is harmful to humans and animals. Because different nitrogen sources are known to have opposite effects on DON production, in this study, we characterized the regulatory mechanisms of the AREA transcription factor in trichothecene biosynthesis. The Δ are A mutant showed significantly reduced vegetative growth and DON production in cultures inoculated with hyphae. Suppression of TRI gene expression and DON production by ammonium were diminished in the Δ are A mutant. The deletion of AREA also affected the stimulatory effects of arginine on DON biosynthesis. The AreA-green fluorescent protein ( GFP) fusion complemented the Δ are A mutant, and its localization to the nucleus was enhanced under nitrogen starvation conditions. Site-directed mutagenesis showed that the conserved predicted protein kinase A ( PKA) phosphorylation site S874 was important for AreA function, indicating that AreA may be a downstream target of the cyclic adenosine monophosphate ( cAMP)- PKA pathway, which is known to regulate DON production. We also showed that AreA interacted with Tri10 in co-immunoprecipitation assays. The interaction of AreA with Tri10 is probably related to its role in the regulation of TRI gene expression. Interestingly, the Δ are A mutant showed significantly reduced PKA activity and expression of all three predicted ammonium permease ( MEP) genes, in particular MEP1, under low ammonium conditions. Taken together, our results show that AREA is involved in the regulation of DON production by ammonium suppression and the cAMP- PKA pathway. The AreA transcription factor may interact with Tri10 and control the expression and up-regulation of MEP genes. [ABSTRACT FROM AUTHOR]

Enhancing the self-symmetry of a shape is of fundamental aesthetic virtue. In this paper, we are interested in recovering the aesthetics of intrinsic reflection symmetries, where an asymmetric shape is symmetrized while keeping its general pose and perceived dynamics. The key challenge to intrinsic symmetrization is that the input shape has only approximate reflection symmetries, possibly far from perfect. The main premise of our work is that curve skeletons provide a concise and effective shape abstraction for analyzing approximate intrinsic symmetries as well as symmetrization. By measuring intrinsic distances over a curve skeleton for symmetry analysis, symmetrizing the skeleton, and then propagating the symmetrization from skeleton to shape, our approach to shape symmetrization is skeleton-intrinsic. Specifically, given an input shape and an extracted curve skeleton, we introduce the notion of a backbone as the path in the skeleton graph about which a self-matching of the input shape is optimal. We define an objective function for the reflective self-matching and develop an algorithm based on genetic programming to solve the global search problem for the backbone. The extracted backbone then guides the symmetrization of the skeleton, which in turn, guides the symmetrization of the whole shape. We show numerous intrinsic symmetrization results of hand drawn sketches and artist-modeled or reconstructed 3D shapes, as well as several applications of skeleton-intrinsic symmetrization of shapes. [ABSTRACT FROM AUTHOR]

Aims This study explored whether surgical stress-induced glucocorticoid receptor ( GR) phosphorylation is related to postoperative cognitive dysfunction ( POCD) in aged individuals. Inhibition of GR activation could be an effective treatment for POCD. Methods A laparotomy was given to C57/BL6 mice in POCD group both 20 and 6 months old. Animals in control group were treated in identical manners except for laparotomy. Cognitive function was evaluated by Morris water maze and elevated plus maze. Western blot and Elisa assay were used to detect related molecules. Mifepristone and roscovitine were treated as inhibitions of GR phosphorylation. Results The cognitive function was impaired, and brain-derived neurotrophic factor ( BDNF) was found reduced in aged POCD group. GR translocation into nucleus and elevated GR phosphorylation were found in prefrontal cortex of aged POCD mice. Cyclin-dependent Kinase 5 ( CDK5), kinase for GR phosphorylation also elevated in aged POCD mice. With GR antagonist and CDK5 inhibitor, reduction of BDNF and cognitive dysfunction in aged mice were both rescued. Conclusion These results presented a mechanism that surgical stress-induced GR phosphorylation contributes to POCD in aged individuals. Inhibition of GR activation and phosphorylation might be a potential treatment target of POCD. [ABSTRACT FROM AUTHOR]

Purpose To develop and validate an automated segmentation method that extracts the interventricular septum (IS) from myocardial black-blood images for the T2* measurement in thalassemia patients. Materials and Methods A total of 144 thalassemia major patients (age range, 11-51 years; 73 males) were scanned with a black-blood multi-echo gradient-echo sequence using a 1.5 Tesla Siemens Sonata system (flip angle 20°, sampling bandwidth 810 Hz/pixel, voxel size 1.56 × 1.56 × 10 mm3 and variable fields of view (20-30) × 40 cm2 depending on patient size). The improved Chan-Vese model with an automated initialization by the circular Hough transformation was implemented to segment the endocardial and epicardial margins of the left ventricle (LV). Consequently, the IS was extracted by analyzing the anatomical relation between the LV and the blood pool of the right ventricle, identified by intensity thresholding. The proposed automated IS segmentation (AISS) method was compared with the conventional manual method by using the Bland-Altman analysis and the coefficient of variation (CoV). Results The T2* measurements using the AISS method were in good agreement with those manually measured by experienced observers with a mean difference of 1.71% and a CoV of 4.15% ( P < 0.001). Conclusion Black-blood myocardial T2* measurement can be fully automated with the proposed AISS method. J. Magn. Reson. Imaging 2015;41:1242-1250. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]