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Ovarian fibrosis is a reproduction obstacle leading to female infertility in vertebrates, but the cause underlying the cellular events is unclear. Here, we found that the small adaptor protein SH3‐domain‐binding glutamate‐rich protein like (Sh3bgrl) plays an important role in female reproduction in zebrafish. Two sh3bgrl mutant alleles that result in sh3bgrl depletion contribute to female spawning inability. Comparative transcriptome analysis revealed that sh3bgrl knockout mechanistically causes the upregulation of genes associated with extracellular matrix (ECM) and fiber generation in the zebrafish ovary. Consequently, extra ECM or fibers accumulate and are deposited in the ovary, resulting in eventual spawning inability. Our findings thus provide insights into understanding the underlying mechanism of infertility by ovarian fibrosis and provide a novel and valuable model to study female reproduction abnormality. [ABSTRACT FROM AUTHOR]

N-Glycosylation plays an important role in the structure and function of membrane and secreted proteins. Viral proteins used in cell entry are often extensively glycosylated to assist in protein folding, provide stability, and shield the virus from immune recognition by its host (described as a "glycan shield"). The SARS-CoV-2 spike protein (S) is a prime example, having 22 potential sites of N-glycosylation per protein protomer, as predicted from the primary sequence. In this report, we conducted mass spectrometric analysis of the N-glycosylation profiles of recombinant spike proteins derived from four common SARS-CoV-2 variants classified as Variant of Concern, including Alpha, Beta, Gamma, and Delta along with D614G variant spike as a control. Our data reveal that the amino acid substitutions and deletions between variants impact the abundance and type of glycans on glycosylation sites of the spike protein. Some of the N-glycosylation sequons in S show differences between SARS-CoV-2 variants in the distribution of glycan forms. In comparison with our previously reported site-specific glycan analysis on the S-D614G and its ancestral protein, glycan types on later variants showed high similarity on the site-specific glycan content to S-D614G. Additionally, we applied multiple digestion methods on each sample, and confirmed the results for individual glycosylation sites from different experiment conditions to improve the identification and quantification of glycopeptides. Detailed site-specific glycan analysis of a wide variety of SARS-CoV-2 variants provides useful information toward the understanding of the role of protein glycosylation on viral protein structure and function and development of effective vaccines and therapeutics. [ABSTRACT FROM AUTHOR]

The outcome of cardiac arrest is worse when there is fever after spontaneous circulation is restored (ROSC). The purpose of this study was to investigate the mechanism of post-ROSC cardiac dysfunction after hyperthermia treatment and the effects of temperature control. Twenty-four male Bama minipigs were randomized into 3 groups (8 per group): CPR + controlled normothermia (CN), CPR + hyperthermia (HT), and CPR + therapeutic mild hypothermia (TMH). Defibrillation was given to pigs with ventricular fibrillation after 8 min of untreated fibrillation. Subsequently, these animals received the post-ROSC treatments of hyperthermia (38 °C), controlled normothermia (37 °C) or hypothermia (33 °C) according to the groups. Hemodynamic parameters, left ventricular ejection fraction, blood samples and myocardial tissues were assessed. At 24 h after the post-ROSC treatments, the pigs treated with hyperthermia showed increments in heart rate and plasma cardiac troponin I, and decreases in mean arterial pressure, cardiac index, and left ventricular ejection fraction, compared to those with the controlled normothermia pigs. However, the deterioration of the above parameters can be attenuated by TMH. The pigs in the TMH group also had a reduced percentage of apoptotic cardiomyocytes, an increased anti-apoptotic Bcl-2/Bax ratio and a decreased caspase-3 activity in myocardium, as compared with both controlled normothermia and hyperthermia pigs. In conclusion, hyperthermia is associated with a worse myocardial dysfunction. TMH improves hyperthermia-induced myocardial dysfunction by attenuating apoptosis in a porcine model of cardiac arrest. [ABSTRACT FROM AUTHOR]

The inter-satellite link is an important technology to improve the accuracy of clock offset measurement and prediction for BeiDou Navigation Satellite System (BDS). At present, BDS measures clock offsets of invisible satellite mainly through the "one-hop" reduction mode based on the satellite-ground clock offset of the node visible satellite and the inter-satellite clock offset between the two satellites. However, there exists a systematic deviation caused by the node satellite reduction, and there is still a large room for improvement in clock offset measurement and prediction. Therefore, this paper firstly proposes a method of whole-network adjustment for clock offset based on the satellite-ground and inter-satellite two-way data. The least square method is used to realize the whole-network adjustment of clock offset based on the observations of two sources, and to obtain optimal estimates of different clock offset reduction. Secondly, the evaluation method combining internal and external symbols are proposed by the fitting residual, prediction error and clock offset closure error. Finally, experimental verification is completed based on BDS measured data. In comparison with the "one-hop" reduction method, the fitting residual and prediction error of the whole-network adjustment method reduces about 45.06% and 52.15%, respectively. In addition, inter-satellite station closure error and three-satellite closure error are reduced from 0.69 ns and 0.23 ns to about 0 ns. It can be seen that the accuracy of BDS time synchronization is significantly improved. [ABSTRACT FROM AUTHOR]

Key message: The genetic diversity and loci underlying agronomic traits were analyzed by the reads coverage and genome-wide association study based genotyping-by-sequencing in a diverse population consisting of 199 accessions. Triticale (× Triticosecale Wittmack) is an economically important grain forage and energy crop planted worldwide for its high biomass. Little is known about the genetic diversity and loci underlying agronomic traits in triticale. We performed genotyping-by-sequencing of 199 cultivars and mapped reads to the A, B, D, and R genomes for karyotype analysis. These cultivars could mostly be grouped into five types. Some chromosome abnormalities occurred with high frequency, such as 2D (2R) substitution, deletion of the long arm of chromosome 2D or the short arm of 5R, and translocation of the long arms of 7D/7A, the short arms of 6D/6A, or the long arms of 1D/1A. We chose only widely planted hexaploid triticale cultivars (153) for genome-wide association study. These cultivars could be divided into nine distinct groups, and the linkage disequilibrium decay was 25.4 kb in this population. We identified 253 significant marker-trait associations (MTAs) on 20 chromosomes, except 7R. Twenty-one reliable MTAs were identified repeatedly over two environments. We predicted 16 putative candidate genes involved in plant growth and development using the genome sequences of wheat and rye. These results provide a basis for understanding the genetic mechanisms of agronomic traits and will benefit the breeding of improved hexaploid triticale. [ABSTRACT FROM AUTHOR]

N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins. [ABSTRACT FROM AUTHOR]

The distributed alternating direction method of multipliers (ADMM) is one of the most widely used algorithms to solve large-scale optimization problems. Since the memory consumption, communication cost and convergence of the distributed ADMM are affected by the number of workers, how to improve the scalability of the distributed ADMM is one of the main challenges. To address this challenge, this paper proposes an asynchronous distributed ADMM based on the hybrid parallel model (HPAD-ADMM), which uses OpenMP for parallelization inside the node and MPI for message passing between nodes in the distributed system. Each worker solves sub-problem in parallel by multithreading, which reduces the system time at each iteration without affecting the convergence of the system or increasing the communication cost and memory consumption. Furthermore, this paper designs efficient parallelized algorithms to solve sub-problems for different applications. For the L1-regularized logistic regression problem, the sub-problem is solved by parallel trust region newton method and system time is reduced by adjusting the accuracy of the sub-problem. For the lasso problem, parallel matrix inversion algorithms are selected dynamically to reduce the system time according to the size of the data set. Finally, large-scale data sets are used to test the performance of the HPAD-ADMM. Experimental results show that compared with the state-of-the-art distributed ADMM, the HPAD-ADMM has higher scalability without losing accuracy. [ABSTRACT FROM AUTHOR]

The distributed alternating direction method of multipliers (ADMM) is an effective algorithm for solving large-scale optimization problems. However, its high communication cost limits its scalability. An asynchronous lazy ADMM algorithm based on hierarchical sparse allreduce communication mode (HSAC-ALADMM) is proposed to reduce the communication cost of the distributed ADMM: firstly, this paper proposes a lazily aggregate parameters strategy to filter the transmission parameters of the distributed ADMM, which reduces the payload of the node per iteration. Secondly, a hierarchical sparse allreduce communication mode is tailored for sparse data to aggregate the filtered transmission parameters effectively. Finally, a Calculator-Communicator-Manager framework is designed to implement the proposed algorithm, which combines the asynchronous communication protocol and the allreduce communication mode effectively. It separates the calculation and communication by multithreading, thus improving the efficiency of system calculation and communication. Experimental results for the L1-regularized logistic regression problem with public datasets show that the HSAC-ALADMM algorithm is faster than existing asynchronous ADMM algorithms. Compared with existing sparse allreduce algorithms, the hierarchical sparse allreduce algorithm proposed in this paper makes better use of the characteristics of sparse data to reduce system time in multi-core cluster. [ABSTRACT FROM AUTHOR]

The awnless trait is the favorite trait for wheat breeding in Qinghai, China, but the major gene underlying the trait is unknown. This study aimed to analyze a recombinant inbred line (RIL) population containing 112 lines by crossing common wheat varieties GY448 (awnless) and GY115 (awned) using genotyping-by-sequencing analysis. A total of 56.62 Gb of clean sequence data were generated. A major gene was identified for the awnless trait based on 101,275 single-nucleotide polymorphisms by quantitative trait locus (QTL)-seq analysis. The region from 685.50 to 709.77 Mb on chromosome 5AL contained 334 genes and 394 transcripts, including B1, the major gene controlling the awnless trait. A 25-bp indel located in the B1 promoter region has a diagnostic value for the awnless/awned genotypes in the RIL population. A total of 42 spring wheat cultivars in Qinghai, China, were analyzed. Further, 23 awnless cultivars had the alleles of the GY448 parent, while 19 awned cultivars had the alleles of the GY115 parent. B1 is crucial in the awnless trait in wheat cultivars in Qinghai, China. The findings of this study might guide the breeding of new wheat cultivars in this region. [ABSTRACT FROM AUTHOR]

Quinoa (Chenopodium quinoa Willd.) cultivars that produce black grains are thought to be more nutritious and contain powerful antioxidant properties, but little is known about the chemical foundation and the genetic mechanism behind this trait. In this research, widely-targeted metabolome and transcriptome analyses were employed to unveil the chemical and genetic differences between black and white quinoa cultivars. A total of 157 differentially expressed metabolites were found in the black and white quinoa cultivars. The tannins and flavonoids were present at high levels in the black quinoa grains. The tannins comprised 13 proanthocyanins, all of which could barely be detected in white grains. Proanthocyanidins are suggested to cause the black grain trait in Arabidopsis thaliana and Brassica species and are thought to produce the black grain trait, while contributing to antioxidant activity, in black grain quinoa. A total of 4620 differentially expressed unigenes were identified in the black and white quinoa grains. Structural genes associated with proanthocyanin biosynthesis, particularly DFR, LAR, LDOX and ANR, were more highly expressed in black than white grains. Genes involved in the betalain biosynthetic pathway, which competes with anthocyanin biosynthesis, showed relatively lower levels of expression in black grains. Two MYB and one MYC transcription factor related to the phenylpropane metabolic pathway displayed higher expression levels in black grains, while BvMYB1, associated with betalain biosynthesis, was not detected. This study suggested that the accumulation of proanthocyanins produces the black grain trait in quinoa, and the activation of transcription factors triggers the proanthocyanidin biosynthesis pathway. [ABSTRACT FROM AUTHOR]

Red-fleshed pummelo (Citrus grandis), a mutant of 'Guanxi', is an important economic plant rich in carotenoids. The transcriptome of 'Guanxi' pummelo was compared with red-fleshed pummelo, with the aim of identifying the key genes responsible for red flesh through RNA sequencing. In total, 44.11 and 47.71 Gb clean reads were respectively obtained after filtering in red and white flesh. Altogether 46,425 unigenes, with an average length of 1208 bp, were assembled. Compared with that of white flesh, 3722 genes were up-regulated, whereas 1421 genes appeared down-regulated in the red-fleshed pummelo. A GO analysis assigned 11,983 differentially expressed genes to 53 subcategories, and 3582, 4722 and 3679 differentially expressed genes were involved in biological processes, cellular components and molecular functions, respectively. The mevalonate pathway involved in terpenoid backbone biosynthesis was significantly different between 'Guanxi' pummelo and its red-fleshed mutant, and the differences were closely associated with carotenoid biosynthesis. The expression levels of the carotenoid biosynthetic pathway genes were different between 'Guanxi' pummelo and its red-fleshed mutant, with the upstream genes having higher expression levels in red-fleshed pummelo than in 'Guanxi' pummelo, whereas the downstream gene β-CHX was downregulated. Two bHLH transcription factors (CL4778.Contig1 and CL4778.Contig2) were of the same branch as CubHLH1, regulating carotenoid biosynthesis in Citrus unshiu Marc., and Unigene CL4778.Contig2 had expression differences in two kinds of pummelo, which suggested CL4778.Contig2 should be a candidate gene controlling carotenoid accumulation in red pummelo. The study would be beneficial to identify the major gene regulating the red flesh trait. [ABSTRACT FROM AUTHOR]

Potato tuberization is a complicated biological process regulated by multiple phytohormones, in particular cytokinins (CKs). The information available on the molecular mechanisms regulating tuber development by CKs remains largely unclear. Physiological results initially indicated that low 6‐benzylaminopurine (BAP) concentration (3 mg l−1) advanced the tuberization beginning time and promoted tuber formation. A comparative proteomics approach was applied to investigate the proteome change of tuber development by two‐dimensional gel electrophoresis in vitro, subjected to exogenous BAP treatments (0, 3, 6 and 13 mg l−1). Quantitative image analysis showed a total of 83 protein spots with significantly altered abundance (>2.5‐fold, P < 0.05), and 55 differentially abundant proteins were identified by MALDI‐TOF/TOF MS. Among these proteins, 22 proteins exhibited up‐regulation with the increase of exogenous BAP concentration, and 31 proteins were upregulated at 3 mg l−1 BAP whereas being downregulated at higher BAP concentrations. These proteins were involved in metabolism and bioenergy, storage, redox homeostasis, cell defense and rescue, transcription and translation, chaperones, signaling and transport. The favorable effects of low BAP concentrations on tuber development were found in various cellular processes, mainly including the stimulation of starch and storage protein accumulation, the enhancement of the glycolysis pathway and ATP synthesis, the cellular homeostasis maintenance, the activation of pathogen defense, the higher efficiency of transcription and translation, as well as the enhanced metabolite transport. However, higher BAP concentration, especially 13 mg l−1, showed disadvantageous effects. The proposed hypothetical model would explain the interaction of these proteins associated with CK‐induced tuber development in vitro. [ABSTRACT FROM AUTHOR]

Clostridium botulinum produces botulinum neurotoxins (BoNTs) that are one of the most poisonous substances. In order to respond to public health emergencies, there is a need to develop sensitive and specific methods for detecting botulinum toxin in various clinical matrices. Our laboratory has developed a mass spectrometry-based Endopep-MS assay that is able to rapidly detect and differentiate BoNT serotypes A–G by immunoaffinity capture of toxins and detection of unique cleavage products of peptide substrates. To improve the sensitivity of the Endopep-MS assay for the detection of BoNT serotype G, we report here the optimization of synthetic peptide substrates through systematic substitution, deletion, and incorporation of unnatural amino acids. Our data show that the resulting optimized peptides produced a significant improvement (two orders of magnitude) in assay sensitivity and allowed the detection of 0.01 mouseLD50 toxin present in buffer solution. [ABSTRACT FROM AUTHOR]

Abstract Atomic clocks are the core equipment aboard navigation satellites, and their performances and predictions directly determine PNT accuracy. In this paper, the on-orbit performances and prediction accuracies of atomic clocks used in new generation navigation satellites are evaluated using two-way time synchronization data. First, using clock error data preprocessed based on combined MAD gross error detection, the method used to evaluate satellite clock performance is studied. The results illustrate that gross error can be eliminated effectively and that the performances of the new generation of satellites are improved in comparison with those of regional satellites. The frequency accuracy has been enhanced from 6.91 × 10−12 to 3.29 × 10−12, and daily stability has been enhanced from 4.036 × 10−14 to 2.339 × 10−14. Second, a weighted combined clock error prediction model was designed that synthesizes polynomial and gray models using the classical weighted method. The results using the combined models show that the prediction accuracies of the new generation satellites are improved by a factor of two when compared with those for regional satellites, and the mean prediction was enhanced was from 0.77 ns to 0.38 ns. Moreover, from the research findings, it was found that prediction accuracy is significantly correlated with daily stability and frequency accuracy and has a micro-correlation with daily drift rate. Finally, in order to study the prediction accuracies of the new generation of satellites, we studied ISL and concluded that it has greatly increased the measured arc of the MEO satellites and can improve re-entry prediction accuracies from 3–4 ns to 1 ns. [ABSTRACT FROM AUTHOR]

Abstract Radio Determination Satellite Service (RDSS) is the advantage and particular characteristics of Beidou, which is different from other satellite navigation systems. According to the rare existing researches of its timing service, this article evaluates timing performance of one-way and two-way using the time series analysis method. Moreover, this paper systematically studies the one-way timing and two-way timing principle and introduces Beidou measured data and analysis method. By analyzing the clock error total curve, the mean value segment, noise situation and timing accuracy, we have the conclusions: (1) one-way timing accuracy is less than 30 ns, and its Root Mean Square (RMS) is less than 6.81 ns; (2) two-way timing accuracy is less than 20 ns, and its Root Mean Square (RMS) is less than 3.60 ns; (3) there exist period switching phenomenon of timing data of one-way and two-way in each beam, and stratification of one-way timing data. These conclusions can be used for the difference compensation of Radio Determination Satellite Service (RDSS), which can provide reference for the clock error consistency of Beidou system, and then improve the system service precision. Highlights • RDSS one-way timing and two-way timing are evaluated using the time series analysis method. • RDSS timing service performance are analysed by Beidou measured data. • RDSS one-way timing accuracy is less than 30 ns, RMS is less than 6.81 ns. • RDSS two-way timing accuracy is less than 20 ns, RMS is less than 3.60 ns. • These conclusions are benefit for the clock error consistency of Beidou system. [ABSTRACT FROM AUTHOR]

Auxin (IAA) is one of the important factors regulating potato tuberization among the multiple environmental signals and hormonal factors. To understand the molecular mechanism of potato tuberization regulated by IAA, a comparative proteomic approach was applied to analyze proteome change of tubers in vitro subjected to exogenous IAA treatments (0, 2 and 4 mg L−1) using two-dimensional gel electrophoresis (2-DE). Quantitative image analysis showed a total of 76 protein spots with abundance significantly altered (P < 0.05) more than 1.2-fold. Mass spectrometry analysis allowed the identification of 49 differential abundance proteins, mainly involved in metabolism and bioenergy, storage, redox homeostasis, transcription and translation, defense and rescue, chaperone and unknown. The promotion effects of low IAA concentration treatment (2 mg L−1) on tuberization were found in various cellular processes, which mainly included changes in the metabolism of carbohydrates and amino acids, the accumulation of storage proteins, the activation of more antioxidation and defense systems as well as the higher efficiency of transcription and translation for protein synthesis. The corresponding inhibition effects were shown at higher concentration (4 mg L−1). This study provides some new insights into the underlying molecular mechanism of potato tuberization regulated by IAA. [ABSTRACT FROM AUTHOR]

Urchin-like α-Fe 2 O 3 /MnO 2 hierarchical hollow composite microspheres have been synthesized by using carbon as sacrificial templates. By combining the advantages of Fe 2 O 3 with high electrical conductivity and MnO 2 with high theoretical capacity, the urchin-like α-Fe 2 O 3 /MnO 2 composites present better electrochemical performances as a lithium ion battery anode compared with α-Fe 2 O 3 hollow spheres and MnO 2 hollow spheres. The α-Fe 2 O 3 /MnO 2 composites exhibit high initial discharge capacity of 1531 mAhg −1 and excellent reversible capacity of 860 mAhg −1 after 150 cycles at 0.1Ag −1 . Furthermore, the composites retain a discharge capacity of 494 mAhg −1 after 500 cycles at 0.5 Ag −1 . The excellent performances may originate from reinforced structural stability, large surface area and good electrical conductivity. The urchin-like α-Fe 2 O 3 /MnO 2 composite material may serve as a potential anode material for lithium-ion battery. [ABSTRACT FROM AUTHOR]

Abstract: Metal oxides/MnO2 hierarchical hollow hybrid nanostructures have attracted significant attention because of their wide potential applications. However, the exploration of a general synthetic approach for fabricating hierarchical hollow hybrid nanostructures is still a great challenge. Herein, a “penetration‐carbonization and reduction‐coating–annealing” route is presented for the generalized synthesis of metal oxides/MnO2 hierarchical hollow hybrid spheres, including NiO/MnO2, Co3O4/MnO2, and CuO/MnO2. Because of the unique hierarchical hollow hybrid nanostructures, NiO/MnO2 nanomaterials possess a desirable capacity (1520 mA h g−1) and outstanding cyclic stability (909 mA h g−1 at the 200th cycle) as Li‐ion battery anode materials. The work reported herein can not only pave the way for the generalized synthetic strategy of metal oxides/MnO2 hierarchical hollow hybrid nanostructures, but also provide a promising application of NiO/MnO2 nanomaterials for Li‐ion battery anode. [ABSTRACT FROM AUTHOR]

Rapid and sensitive detection of botulinum neurotoxins (BoNTs), which cause botulism, is essential in a public health emergency or bioterrorism event. We have previously developed a mass spectrometry (MS)-based functional method, Endopep-MS assay, for the fast detection and differentiation of all BoNT serotypes by affinity enriching the toxin and detecting the serotype-specific cleavage products of peptide substrates derived from the in vivo targets. To improve the performance of the Endopep-MS assay, we report here the further optimization of the peptide substrate for the detection of serotype A botulinum neurotoxins. An increased substrate cleavage was achieved by extending the original peptide N-terminus with optimized amino acid sequence, increasing the detection sensitivity of the method. In addition, the resistance of the substrate to nonspecific hydrolysis was dramatically improved by selectively substituting amino acids at the scissile bond and various other positions of the extended peptide. Moreover, incorporating the N-terminal hydrophobic residues dramatically improved the relative intensity of the cleavage products in the mass spectra. This allowed easy detection of the cleavage products, further enhancing the performance of the assay. The limit of detection for spiked serum sample was enhanced from 0.5 to 0.1 mouseLD and from 0.5 to 0.2 mouseLD for spiked stool. [ABSTRACT FROM AUTHOR]

The intestine of zebrafish consists of mucosa, muscularis and serosa. Intestinal epithelial cells (IECs) act as a physical and biochemical barrier to protect against invasion by external commensal bacteria. Cell junction is one of the crucial basis of the barrier function. When cell junctions were disrupted, intestinal permeability would be naturally impeded. Extracellular signal-regulated kinase 5 (ERK5), belonging to the Mitogen-activated protein kinase (MAPK) family, is involved in the normal physiological development of the cardiovascular system and nervous system. But the role of erk5 in intestinal morphogenesis and intestinal function is yet to know. Here, we showed that knockout of the erk5 in zebrafish larvae resulted in intestinal wall hypoplasia, including the thinned intestinal wall, reduced intestinal folds, and disrupted cell junctions. In addition, the intestinal permeability assay demonstrated that knockout of erk5 resulted in increased intestinal permeability. All of these showed that erk5 plays an essential role in the maintenance of intestinal barrier function. Thus, our data indicate that erk5 is a critical effector in intestinal morphogenesis and intestinal function, and dysfunction of erk5 would lead to intestinal diseases. [ABSTRACT FROM AUTHOR]

It's no secret that polymers have been employed extensively in a variety of industries. Polymers, on the other hand, have faced difficulties in their development because of their complicated chemical composition and structure. Data-driven approaches in polymer science and technology have resulted in new directions in research leading to the implementation of deep learning models and vast data assets. In the growing area of polymer informatics, deep learning methods based on factual data are being used to speed up the performance assessment and process improvement of new polymers. Using a deep neural network (DNN), we can now forecast the surface metallization properties of polymer materials, which we describe in this research. First, we collect a raw dataset of polymer materials' characteristics. The raw data are filtered and normalized using the min–max normalization approach. To convert normalized data into numerical characteristics, principal component analysis (PCA) is employed. Polymer surface metallization characteristics can then be predicted using a suggested DNN technique. The proposed and conventional approaches are also compared so that our research can be done to its full potential. [ABSTRACT FROM AUTHOR]

It is essential to have a simple, quick and sensitive method for the detection and quantification of botulinum neurotoxins, the most toxic substances and the causative agents of botulism. Type C botulinum neurotoxin (BoNT/C) represents one of the seven members of distinctive BoNT serotypes (A to G) that cause botulism in animals and avians. Here we report the development of optimized peptide substrates for improving the detection of BoNT/C and /CD mosaic toxins using an Endopep-MS assay, a mass spectrometry-based method that is able to rapidly and sensitively detect and differentiate all types of BoNTs by extracting the toxin with specific antibodies and detecting the unique cleavage products of peptide substrates. Based on the sequence of a short SNAP-25 peptide, we conducted optimization through a comprehensive process including length determination, terminal modification, single and multiple amino acid residue substitution, and incorporation of unnatural amino acid residues. Our data demonstrate that an optimal peptide provides a more than 200-fold improvement over the substrate currently used in the Endopep-MS assay for the detection of BoNT/C1 and /CD mosaic. Using the new substrate in a four-hour cleavage reaction, the limit of detection for the BoNT/C1 complex spiked in buffer, serum and milk samples was determined to be 0.5, 0.5 and 1 mouseLD 50 /mL, respectively, representing a similar or higher sensitivity than that obtained by traditional mouse bioassay. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are the most poisonous substances known to humankind. It is essential to have a simple, quick, and sensitive method for the detection and quantification of botulinum toxin in various media, including complex biological matrices. Our laboratory has developed a mass spectrometry-based Endopep–MS assay that is able to rapidly detect and differentiate all types of BoNTs by extracting the toxin with specific antibodies and detecting the unique cleavage products of peptide substrates. Botulinum neurotoxin type E (BoNT/E) is a member of a family of seven distinctive BoNT serotypes (A–G) and is the causative agent of botulism in both humans and animals. To improve the sensitivity of the Endopep–MS assay, we report here the development of novel peptide substrates for the detection of BoNT/E activity through systematic and comprehensive approaches. Our data demonstrate that several optimal peptides could accomplish 500-fold improvement in sensitivity compared with the current substrate for the detection of both not-trypsin-activated and trypsin-activated BoNT/E toxin complexes. A limit of detection of 0.1 mouse LD 50 /ml was achieved using the novel peptide substrate in the assay to detect not-trypsin-activated BoNT/E complex spiked in serum, stool, and food samples. [ABSTRACT FROM AUTHOR]

Abstract: Clostridium botulinum neurotoxins (BoNTs) cause the life-threatening disease botulism through the inhibition of neurotransmitter release by cleaving essential SNARE proteins. There are seven serologically distinctive types of BoNTs and many subtypes within a serotype have been identified. BoNT/A5 is a recently discovered subtype of type A botulinum neurotoxin which possesses a very high degree of sequence similarity and identity to the well-studied A1 subtype. In the present study, we examined the endopeptidase activity of these two BoNT/A subtypes and our results revealed significant differences in substrate binding and cleavage efficiency between subtype A5 and A1. Distinctive hydrolysis efficiency was observed between the two toxins during cleavage of the native substrate SNAP-25 versus a shortened peptide mimic. N-terminal truncation studies demonstrated that a key region of the SNAP-25, including the amino acid residues at 151 through 154 located in the remote binding region of the substrate, contributed to the differential catalytic properties between A1 and A5. Elevated binding affinity of the peptide substrate resulted from including these important residues and enhanced BoNT/A5's hydrolysis efficiency. In addition, mutations of these amino acid residues affect the proteolytic performance of the two toxins in different ways. This study provides a better understanding of the biological activity of these toxins, their performance characteristics in the Endopep-MS assay to detect BoNT in clinical samples and foods, and is useful for the development of peptide substrates. [Copyright &y& Elsevier]

Radio determination satellite service (RDSS) is one of the characteristic services of Beidou navigation satellite system (BDS), and also distinguishes with other GNSS systems. BDS-3 RDSS adopts new signals, which is compatible with BDS-2 RDSS signals in order to guarantee the services of old users. Moreover, the new signals also separate civil signals and military signals which are modulated on different carriers to improve their isolation and RDSS service performance. Timing is an important part of RDSS service, which has been widely used in the field of the power, transportation, marine and others. Therefore, the timing accuracy, availability and continuity is an important guarantee for RDSS service. This paper summarizes the principle of one-way and two-way timing, and provides the evaluation method of RDSS timing accuracy, availability and continuity. Based on BDS-3 RDSS signal measurements of system, the performance of one-way timing and two-way timing is analyzed and evaluated for the first time. The results show that: (1) the accuracy of one-way timing and two-way timing is better than 30 ns and 8 ns respectively, which are better than the official claimed accuracy; (2) the RMS of one-way timing accuracy is 5.45 ns, which is 20% smaller than BDS-2, and the availability and continuity are 100%; (3) the RMS of two-way timing accuracy is 3.59 ns, which is 34% smaller than one-way timing, and both of the availability and continuity are 100%; (4) the orbit maneuver of GEO satellite make the one-way timing has 7.68 h recovery, but has no affection on the two-way timing. [ABSTRACT FROM AUTHOR]

Abstract: Based on the nonlinear controllability theory, this paper analyzes the attitude controllability for an underactuated spacecraft using two or one thrusters in sequence. In order to provide a preconditional guide on designing the control law for the underactuated attitude control system in the actual case, the underactuated spacecraft with respect to the orbit frame is investigated in the presence of periodical oscillation disturbance. First, attitude dynamic model was established for an underactuated spacecraft actuated by three thrusters, one or two of which has failed separately, and the special orthogonal group (SO(3)) is deployed to describe the attitude motions. Second, Liouville theorem and Poincaré’s recurrence theorem were used to confirm that the drift field is Weakly Positively Poisson Stable (WPPS). Furthermore, the sufficient and necessary condition of controllability was obtained on the basis of Lie Algebra Rank Condition (LARC). Finally, according to the case of two available thrusters, angular velocity stabilization and three-axis attitude stabilization control laws are designed, and proved by Lyapunov stability theory and LaSalle invariant theorem. The analysis and simulation results illustrate the feasibility of the proposed control law. [Copyright &y& Elsevier]

Abstract: Botulinum neurotoxins (BoNTs) are a family of seven toxin serotypes that are the most toxic substances known to humans. Intoxication with BoNT causes flaccid paralysis and can lead to death if untreated with serotype-specific antibodies. Supportive care, including ventilation, may be necessary. Rapid and sensitive detection of BoNT is necessary for timely clinical confirmation of clinical botulism. Previously, our laboratory developed a fast and sensitive mass spectrometry (MS) method termed the Endopep–MS assay. The BoNT serotypes are rapidly detected and differentiated by extracting the toxin with serotype-specific antibodies and detecting the unique and serotype-specific cleavage products of peptide substrates that mimic the sequence of the BoNT native targets. To further improve the sensitivity of the Endopep–MS assay, we report here the optimization of the substrate peptide for the detection of BoNT/A. Modifications on the terminal groups of the original peptide substrate with acetylation and amidation significantly improved the detection of BoNT/A cleavage products. The replacement of some internal amino acid residues with single or multiple substitutions led to further improvement. An optimized peptide increased assay sensitivity 5-fold with toxin spiked into buffer solution or different biological matrices. [Copyright &y& Elsevier]

Abstract: Botulinum neurotoxins (BoNTs) are the most toxic substances known to humankind. Rapid and sensitive detection of BoNTs is necessary for timely clinical confirmation of the disease state in botulism. BoNTs cleave proteins and peptide mimics at specific sites. A mass spectrometry (MS)-based method, Endopep–MS, can detect these cleavages and has detection limits of 0.05–0.5 mouse LD50 (U) in serum, depending on the BoNT serotypes. In this method, the products generated from cleavage of peptide substrates using antibody affinity-purified toxins are detected by MS. Nonspecific bound endogenous proteases or peptidases in stool can coextract with the toxin, cleaving the peptide substrates and reducing the sensitivity of the method. Here we report a method to reduce nonspecific substrate cleavage by reducing stool protease coextraction in the Endopep–MS assay. [Copyright &y& Elsevier]

N-terminal derivatization of peptides with Edman's reagent, phenyl isothiocyanate (PITC), promotes gas-phase Edman cleavage that yields abundant complementary b1 and Yn-1 ion pairs by tandem mass spectrometry (MS/ MS). The fonnation of b1 ions can be utilized as a mass tag to enhance the interpretation of MS/MS spectra and increase the confidence of peptide identification during mass spectrometry analysis. Derivatization of tryptic peptides with another isothiocyanate analogue, 4-sulfophenyl isothiocyanate, also produces signature ions resulting from Edman cleavage and facilitates peptide sequencing on linear or branched peptides. The limitation of these derivatizations, however, is reduced MS signal intensities of modified peptides, due presumably to the tags themselves. Here we have demonstrated that several other isothiocyanate analogues bearing basic moieties can derivatize peptides and significantly improve the MS sensitivity of tagged analytes, while promoting Edman fragmentation and maintaining other sequence fragments as well. [ABSTRACT FROM AUTHOR]

Protein ubiquitination plays an important role in the degradation and other functional regulation of cellular proteins in organisms ranging from yeasts to mammals. Trypsin digestion of ubiquitin conjugated proteins produces diglycine branched peptides in which the C-terminal Gly-Gly fragment of ubiquitin is attached to the &epsiv;-amino group of a modified lysine residue within the peptide. This provides a platform for mapping ubiquitination sites using mass spectrometry. Here we report the development of a novel strategy for determining posttraslational protein ubiquitination based on the N-terminal sulfonation of diglycine branched peptides. In contrast to conventional tandem MS spectra of native tryptic peptides, MALDI MS/MS analysis of a sulfonated tryptic peptide containing a diglycine branch generates a unique spectrum composed of a signature portion and a sequence portion. The signature portion of the spectrum consists of several intense ions resulting from the elimination of the tags, the N-terminal residues at the peptide and the branch, and their combination. This unique ion distribution pattern can distinguish ubiquitination modificatons from others and can identify the first N-terminal residues of the peptides as well. The sequence portion consists of an exclusive series of y-type ions and y' ions (differing by the loss of one glycine residue from the sulfonated diglycine branch) that can directly reveal the amino acid sequence of the peptide and the precise location of the ubiquitination site. The technique is demonstrated for a series of synthetic peptides and is validated by a model protein, tetraubiquitin. Our results show that the MALDI MS/MS analysis of sulfonated tryptic peptides can provide a highly effective method for the determination of ubiquitination substrates, ubiquitination sites on protein targets, and modification sites on ubiquitins themselves. [ABSTRACT FROM AUTHOR]

The transcriptional coactivator p300 is a histone acetyltransferase (HAT) whose function is critical for regulating gene expression in mammalian cells. However, the molecular events that regulate p300 HAT activity are poorly understood. We evaluated autoacetylation of the p300 HAT protein domain to determine its function. Using expressed protein ligation, the p300 HAT protein domain was generated in hypoacetylated form and found to have reduced catalytic activity. This basal catalytic rate was stimulated by autoacetylation of several key lysine sites within an apparent activation loop motif. This post-translational modification and catalytic regulation of p300 HAT activity is conceptually analogous to the activation of most protein kinases by autophosphorylation. We therefore propose that this autoregulatory loop could influence the impact of p300 on a wide variety of signaling and transcriptional events. [ABSTRACT FROM AUTHOR]

• Effects of lutein against the excessive fat deposition are proposed. • Lutein ameliorates lipid accumulation in adipocyte, both in vivo and in vitro. • Activated SIRT1-mediated pathways accelerate lipolysis and inhibit lipid synthesis. • Lutein administration is a potential strategy for preventing lipid accumulation. Obesity is now a worldwide disease and is mainly attributable to increased body fat deposition. In a growing number of epidemiological studies, lutein has been revealed to have different degrees of anti-obesity properties, but the potential underlying mechanisms that have been reported are limited. Therefore, we aimed to clarify the protective effects of lutein against excessive lipid accumulation, and we explored the role of SIRT1 and SIRT1-mediated pathways both in abdominal adipose tissue and mature 3T3-L1 cells during lutein administration. In our design, male Sprague–Dawley rats were fed either control or high-fat diets with or without 25 mg/kg·bw/day lutein for 5 weeks. Additionally, differentiated 3T3-L1 cells were incubated with 40 μM lutein or 10 μM Ex527 for 24 h. Lutein supplementation decreased the body weight, abdominal fat index ratio, frequency and mean area of larger adipocytes in HE staining induced by the high-fat diet and then activated the expression of SIRT1 and thus upregulated FoxO1, ATGL, and HSL expression and downregulated SREBP-1, FAS, and ACC expression both in abdominal adipose tissue and differentiated 3T3-L1 cells. However, coincubation with Ex527 and lutein suppressed the activation of SIRT1 and reversed the expression of FoxO1, ATGL, HSL, SREBP-1, FAS, and ACC in comparison to those in the Lut group. Overall, we suggest that the effects of lutein on attenuating excessive lipid accumulation are dependent on the SIRT1-mediated pathway in vivo and in vitro, which indicates that lutein administration may be a potential strategy for preventing excessive lipid accumulation and obesity. [ABSTRACT FROM AUTHOR]

Rationale: Hydrogen/deuterium exchange mass spectrometry (HDX‐MS) can provide precise analysis of a protein's conformational dynamics across varied states, such as heat‐denatured versus native protein structures, localizing regions that are specifically affected by such conditional changes. Maximizing protein sequence coverage provides high confidence that regions of interest were located by HDX‐MS, but one challenge for complete sequence coverage is N‐glycosylation sites. The deuteration of peptides post‐translationally modified by asparagine‐bound glycans (glycopeptides) has not always been identified in previous reports of HDX‐MS analyses, causing significant sequence coverage gaps in heavily glycosylated proteins and uncertainty in structural dynamics in many regions throughout a glycoprotein. Methods: We detected deuterated glycopeptides with a Tribrid Orbitrap Eclipse mass spectrometer performing data‐dependent acquisition. An MS scan was used to identify precursor ions; if high‐energy collision‐induced dissociation MS/MS of the precursor indicated oxonium ions diagnostic for complex glycans, then electron transfer low‐energy collision‐induced dissociation MS/MS scans of the precursor identified the modified asparagine residue and the glycan's mass. As in traditional HDX‐MS, the identified glycopeptides were then analyzed at the MS level in samples labeled with D2O. Results: We report HDX‐MS analysis of the SARS‐CoV‐2 spike protein ectodomain in its trimeric prefusion form, which has 22 predicted N‐glycosylation sites per monomer, with and without heat treatment. We identified glycopeptides and calculated their average isotopic mass shifts from deuteration. Inclusion of the deuterated glycopeptides increased sequence coverage of spike ectodomain from 76% to 84%, demonstrated that glycopeptides had been deuterated, and improved confidence in results localizing structural rearrangements. Conclusion: Inclusion of deuterated glycopeptides improves the analysis of the conformational dynamics of glycoproteins such as viral surface antigens and cellular receptors. [ABSTRACT FROM AUTHOR]

Residents' trajectory data denote their instantaneous locations along their movements. Mobility research that applies trajectory mining techniques to identify the transportation modes of these movements can inform urban transportation planning. Herein, we propose a five-step approach with information entropy and a multi-layer neural network to identify transportation modes from trajectory data. First, this approach extracts the motion features at each time-stamped location based on foundation geospatial data and spatiotemporal trajectory data, including the speed, acceleration, change of direction, rate of change in direction, and distance from each basic transportation facility. The second step uses information entropy to identify the features that play key roles in identifying transportation modes. The third step weighs each attribute in the feature vector consisting of the selected features and normalizes it to prepare it as input data. The fourth step constructs, trains, and tests a multi-layer neural network with seven-fold cross-validation. The final step includes a post-processing method to optimize the identification result. We use F-measure metric to evaluate the performance. Experimental results on a real trajectory dataset show that the proposed approach can identify the transportation mode at each time-stamped location and outperforms existing transportation-mode identification methods in terms of accuracy and stability. [ABSTRACT FROM AUTHOR]

To realize large lithium storage capacity and excellent rate capability lithium ion batteries, highly electrochemically active materials and rational design of structure are desirable. Here, we successfully synthesized CoO@N-doped carbon nanowire arrays derived from zeolitic imidazolate frameworks-67 (ZIF-67) on Ni foam (denoted as CoO@N-C/NF). Each CoO@N-C nanowire was built up of numerous ordered in-situ nitrogen-doped carbon coated CoO nanoparticles (around 20 nm) after annealing treatment. Benefited from the unique structural features, when served as anode for lithium ion batteries, the CoO@N-C/NF exhibit superior initial Coulombic efficiency of 78.04%, and excellent electrochemical cyclability (1884.1 mAh g−1 at 1 A g−1 after 100 cycles) and good rate capability (1169.2 mAh g−1 at the rate of 5000 mA g−1). To our knowledge, this is the highest capacity with similar electric current density that has been reported for CoO-based materials. Our results indicate that the CoO@N-C/NF electrode without any auxiliary materials are expected to open up new opportunities for CoO-based material to power electronic devices. [ABSTRACT FROM AUTHOR]

Objective: There is a lack of standard salvage treatment options for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that has failed platinum-containing regimens. Breakthroughs in immunotherapy have opened up new options for these patients. However, the efficacy and safety of immunotherapy have not been clarified. This study aimed to summarize and assess the efficacy and safety of PD-1 inhibitors in patients with RM-NPC who failed platinum-containing chemotherapy. Methods: Up to August 25, 2022, clinical trials of PD-1 inhibitors in RM-NPC patients who failed platinum-containing regimens were searched in the PubMed, Embase, Cochrane, and Web of Science databases. Retrieval subject terms included "nasopharyngeal carcinoma", "metastatic", "recurrence", "PD-1", and "PD-L1". The clinical trials eligible for inclusion were systematically reviewed and meta-analyzed. Results: A total of 9 studies including 842 patients with RM-NPC were included in this meta-analysis. The results showed that PD-1 inhibitors had promising efficacy in patients with RM-NPC who failed platinum-containing regimens: objective response rate (ORR) was 24% (95% confidence interval [CI] 21–26%), disease control rate (DCR) was 52% (95% CI 45–58%), 1-year progression-free survival (PFS) rate was 25% (95% CI 18–32%), and 1-year overall survival (OS) rate was 53% (95% CI 37–68%). In terms of treatment-related adverse events (AEs), the incidence of grade ≥ 3 treatment-related AEs was 19% (95% CI 13–24%). In addition, we found that PD-1 inhibitors were more effective in patients with PD-L1 positive than in patients with PD-L1 negative nasopharyngeal carcinoma who had failed platinum-containing regimens (ORR 31% (95%CI 26–35%) vs. 21% (95% CI 17–25%)). Conclusion: PD-1 inhibitors may provide a survival benefit for patients with RM-NPC who have failed platinum-containing regimens and have the advantage of a good safety profile, making them a promising treatment option. [ABSTRACT FROM AUTHOR]

BeiDou Satellite-based Augmentation System (BDSBAS) has come into the trial operation stage since July, 2020. To evaluate the characteristic of the augmentation message in BDSBAS-B1C signal, the effectiveness of the message content was firstly analyzed, and then the validity of the broadcasting strategy was estimated. Finally, the accuracy of the user equivalent ranging error (UERE) and the single frequency positioning error with different correction parameters in BDSBAS-B1C message was evaluated. Based on the above analysis, the effectiveness of the augmentation message was preliminarily verified with the results showing that: (1) the BDSBAS-B1C message type, information content and update interval have basically met the international standard; (2) the accuracy of the UERE obtained with the augmentation message had an obvious improvement in contrast to that of the UERE obtained with the usual navigation message of the GPS satellites, and the ionospheric delay was one of the important factors which affected the accuracy of the UERE; (3) the positioning accuracy obtained with the augmentation message was also improved, and the improvement was more obvious in the service areas with high availability of the ionospheric parameters. [ABSTRACT FROM AUTHOR]

This study aimed to investigate Hippo pathway-related prognostic long noncoding RNAs (lncRNAs) and their prognostic value in liver hepatocellular carcinoma (LIHC). Expression and clinical data regarding LIHC were acquired from The Cancer Genome Atlas and European Bioinformatics Institute array databases. Hippo pathway-related lncRNAs and their prognostic value were revealed, followed by molecular subtype investigations. Differences in survival, clinical characteristics, immune cell infiltration, and checkpoint expression between the subtypes were explored. LASSO regression was used to determine the most valuable prognostic lncRNAs, followed by the establishment of a prognostic model. Survival and differential expression analyses were conducted between two groups (high- and low-risk). A total of 313 Hippo pathway-related lncRNAs were identified from LIHC, of which 88 were associated with prognosis, and two molecular subtypes were identified based on their expression patterns. These two subtypes showed significant differences in overall survival, pathological stage and grade, vascular invasion, infiltration abundance of seven immune cells, and expression of several checkpoints, such as CTLA-4 and PD-1/L1 (P < 0.05). LASSO regression identified the six most valuable independent prognostic lncRNAs for establishing a prognosis risk model. Risk scores calculated by the risk model assigned patients into two risk groups with an AUC of 0.913 and 0.731, respectively, indicating that the high-risk group had poor survival. The risk score had an independent prognostic value with an HR of 2.198. In total, 3007 genes were dysregulated between the two risk groups, and the expression of most genes was elevated in the high-risk group, involving the cell cycle and pathways in cancers. Hippo pathway-related lncRNAs could stratify patients for personalized treatment and predict the prognosis of patients with LIHC. [ABSTRACT FROM AUTHOR]

The classification of White blood cells (WBCs) plays an important role. However, the traditional method of blood smear analysis is laborious. This paper presented a classification method of WBCs based on hyperspectral images and Deep learning (DL). The U-net network was proposed to extract spectral features of WBCs region of interest (ROI) under the pseudo-color images with specific hyperspectral images (420.8, 557.2 and 667.4 nm). For spectral features and the pseudo-colour images of hyperspectral data, attention-aided one and two-dimensional convolutional neural networks were applied to establish WBCs classification models, respectively. The overall average accuracy can reach 94.20% and 92.60%, respectively. A fusion network was constructed to make full use of the spectral and image spatial features, and its classification accuracy reached 96.20%. In terms of overall average accuracy, the fusion network model was the optimal, but for individual types of WBCs, each network had its own unique advantages. [ABSTRACT FROM AUTHOR]

Here we report a study of ZnO nanorod array (ZNA) treated by twice low-temperature hydrothermal process with precursor solution of Zn(NO 3 ) 2 ·6H 2 O and C 6 H 12 N 4 (1:1 M ratio) at varying concentrations. Thin and uniform ZnO nanorods were first grown on a substrate with a ZnO seed layer through a hydrothermal process with the concentration of precursor solution at 0.02 wt%. After a second hydrothermal process, they were transformed into distinct structures, dependent on the precursor concentration during the hydrothermal process. At higher precursor concentration (0.1 wt%), syringe needle-shaped nanocolumns with an inverted hexagonal pyramid head were obtained, while the high aspect ratio nanowires were formed at lower concentration (0.02 wt%). The probable transformation mechanisms of the ZNA associated with precursor concentration were proposed and discussed with SEM results. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs) cause the disease called botulism, which can be lethal. BoNTs are proteins secreted by some species of clostridia and are known to cause paralysis by interfering with nerve impulse transmission. Although the human lethal dose of BoNT is not accurately known, it is estimated to be between 0.1 μg to 70 μg, so it is important to enable detection of small amounts of these toxins. Our laboratory previously reported on the development of Endopep-MS, a mass-spectrometric-based endopeptidase method to detect, differentiate, and quantify BoNT immunoaffinity purified from complex matrices. In this work, we describe the application of Endopep-MS for the analysis of thirteen blinded samples supplied as part of the EQuATox proficiency test. This method successfully identified the presence or absence of BoNT in all thirteen samples and was able to successfully differentiate the serotype of BoNT present in the samples, which included matrices such as buffer, milk, meat extract, and serum. Furthermore, the method yielded quantitative results which had z-scores in the range of -3 to +3 for quantification of BoNT/A containing samples. These results indicate that Endopep-MS is an excellent technique for detection, differentiation, and quantification of BoNT in complex matrices. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article Inclusion of deuterated glycopeptides provides increased sequence coverage in hydrogen/deuterium exchange mass spectrometry analysis of SARS‐CoV‐2 spike glycoprotein by Jby Christopher A. Haynes et al., https://doi.org/10.1002/rcm.9690..By Christopher A. Haynes; Theodore R. Keppel; Betlehem Mekonnen; Sarah H. Osman; Yu Zhou; Adrian R. Woolfitt; Jakub Baudys; John R. Barr and Dongxia WangReported by Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Abstract: The explosive growth and wide-spread accessibility of community-contributed multimedia contents on the Internet have led to a surging research activity in social image search. However, the existing tag-based search methods frequently return irrelevant or redundant results. To quickly target user''s intention in the result returned by an ambiguous query, we first put forward that the top-ranked search results should meet some criteria, i.e., relevance, typicality and diversity. With the three criteria, a novel ranking scheme for social image search is proposed which incorporates both semantic similarity and visual similarity. The ranking list with relevance, typicality and diversity is returned by optimizing a measure named Average Diverse Precision. The typicality score of samples is estimated via the probability density in the space of visual features. The diversity among the top-ranked list is achieved by fusing both semantic and visual similarities of images. A comprehensive approach for calculating visual similarity is considered by fusing the similarity values according to different features. To further benefit ranking performance, a data-driven method is implemented to refine the tags of social image. Comprehensive experiments demonstrate the effectiveness of the approach proposed in this paper. [Copyright &y& Elsevier]

Cervical cancer is among the most common cancers in women worldwide. Discovery of biomarkers for the early detection of cervical cancer would improve current screening practices and reduce the burden of disease. In this study, we report characterization of the human cervical mucous proteome as the first step towards protein biomarker discovery. The protein composition was characterized using one- and two-dimensional gel electrophoresis, and liquid chromatography coupled with mass spectrometry. We chose to use this combination of traditional biochemical techniques and proteomics to allow a more comprehensive analysis. A total of 107 unique proteins were identified, with plasma proteins being most abundant. These proteins represented the major functional categories of metabolism, immune response, and cellular transport. Removal of high molecular weight abundant proteins by immunoaffinity purification did not significantly increase the number of protein spots resolved. We also analyzed phosphorylated and glycosylated proteins by fluorescent post-staining procedures. The profiling of cervical mucous proteins and their post-translational modifications can be used to further our understanding of the cervical mucous proteome. [ABSTRACT FROM AUTHOR]

Summary: Heat-shock protein 90 (Hsp90) chaperones a key subset of signaling proteins and is necessary for malignant transformation. Hsp90 is subject to an array of posttranslational modifications that affect its function, including acetylation. Histone deacetylase (HDAC) inhibitors and knockdown of HDAC6 induce Hsp90 acetylation and inhibit its activity. However, direct determination of the functional consequences of Hsp90 acetylation has awaited mapping of specific sites. We now demonstrate that Hsp90 K294 is acetylated. Mutational analysis of K294 shows that its acetylation status is a strong determinant of client protein and cochaperone binding. In yeast, Hsp90 mutants that cannot be acetylated at K294 have reduced viability and chaperone function compared to WT or to mutants that mimic constitutive acetylation. These data suggest that acetylation/deacetylation of K294 plays an important role in regulating the Hsp90 chaperone cycle. [Copyright &y& Elsevier]

Abstract: The curved-field reflectron (CFR), developed initially to improve focusing of product ions in a dual reflectron tandem time-of-flight (RTOF/RTOF) mass spectrometer, has been used for several years in single analyzer instruments for the focusing of ions produced by post-source decay (PSD) without stepping the reflectron voltage. More recently, the addition of a collision chamber to a commercial instrument that incorporates the CFR enables both PSD and collision-induced dissociation (CID) mass spectra to be obtained in a tandem instrument without decelerating the primary ions or reaccelerating product ions to accommodate the limited energy bandwidth of the reflectron. In the PSD or laser-induced dissociation (LID) mode, i.e., without a collision gas, nearly complete b- and y-series ions are observed, which is illustrated here in the MS/MS spectra of peptides obtained in the determination of the lysine acetylation sites in a histone acetyl transferase (HAT) protein. Addition of the collision gas produces similar mass spectra, though higher collision gas pressure increases the intensities of lower mass and internal fragments, both of which appear to result from multiple collisions. In addition N-terminal sulfonation of the peptides obtained from tryptic digests produces exclusive y-series ions in the product ion mass. [Copyright &y& Elsevier]

Resveratrol has been found to improve ethanol-induced diabetes. Although pancreatic β-cell senescence-induced β-cell mass loss plays a critical role in the progression of diabetes, the exact mechanism by which resveratrol improves ethanol-triggered β-cell senescence and its role in ethanol-induced diabetes remains unknown. Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 2.4 g/kg·bw ethanol with or without 100 mg/kg·bw resveratrol for 22 weeks. Resveratrol decreased the ethanol-induced augmentation in senescence-associated β-galactosidase (SA-β-gal)-positive area and attenuated reduction in β-cell mass, which were based on elevated levels of SIRT1 and proliferation marker Ki67 and reduced levels of senescence-associated markers (p-p38MAPK and p16INK4a). Similarly, resveratrol rescued the reduction in NAD+/NADH ratio and SIRT1 and inhibited the upregulation of p-p38MAPK and p16INK4a in ethanol-treated INS-1 cells. Furthermore, supplementation with NAD+ inducer nicotinamide mononucleotide, SIRT1 activator SRT1720 or p38MAPK inhibitor SB203580 effectively reversed ethanol-induced β-cell senescence, while supplementation with SIRT1 inhibitor Ex527 or NAD+ inhibitor FK866 abrogated resveratrol-mediated antisenescence effects in INS-1 cells. Together, our results indicate that resveratrol improves ethanol-triggered β-cell senescence and consequently recovers β-cell mass loss by inhibiting p38MAPK/p16 pathway through an NAD+/SIRT1 dependent pathway. [ABSTRACT FROM AUTHOR]

Furan is a widespread endogenous contaminant in heat-processed foods that can accumulate rapidly in the food chain and has been widely detected in foods, such as wheat, bread, coffee, canned meat products, and baby food. Dietary exposure to this chemical may bring health risk. Furan is classified as a possible category 2B human carcinogen by the International Agency for Research on Cancer, with the liver as its primary target organ. Hepatic fibrosis is the most important nontumoral harmful effect of furan and also an important event in the carcinogenesis of furan. Although the specific mechanism of furan-induced liver fibrosis is still unclear, it may involve oxidative stress and genetic toxicity, in which the activation of cytochrome P450 2E1 (CYP2E1) may be the key event. Thus, we conducted a study using an integrating multi-endpoint genotoxicity platform in 120-day in vivo subchronic toxicity test in rats. Results showed that the rats with activated CYP2E1 exhibited DNA double-strand breaks in D4, gene mutations in D60, and increased expression of reactive oxygen species and nuclear factor erythroid 2-related factor 2 in D120. Necrosis, apoptosis, hepatic stellate cell activation, and fibrosis also occurred in the liver, suggesting that furan can independently affect liver fibrosis through oxidative stress and genotoxicity pathways. Point of Departure (PoD) was obtained by benchmark-dose (BMD) method to establish health-based guidance values. The human equivalent dose of PoD derived from BMDL 05 was 2.26 μg/kg bw/d. The findings laid a foundation for the safety evaluation and risk assessment of furan and provided data for the further construction and improvement of the adverse outcome pathway network in liver fibrosis. [Display omitted] • An integrated genotoxicity platform was applied to explore the AOP of furan. • Furan may induce gene mutation in a cumulative way, independent of oxidative stress. • The AOP of CYP2E1 activation leading to liver fibrosis was preliminary established. • BMDLs of key events from AOP are more protective than values from apical endpoints. [ABSTRACT FROM AUTHOR]

Precise point positioning (PPP) service is of great significance for BDS. The design and implementation of the service are presented. The PPP‐B2b signal of the service is constructed, which is efficient multiplexed with other signal components, and achieves compatibility between two service phases. A customized message format that can augment all visible satellites of four core constellations in mainland China is proposed. The high‐gain, 64‐ary, low‐density parity check (LDPC) coding is used, which facilitates the integrated design of the receivers. A signal quality test has revealed that the S‐curve bias (SCB) of PPP‐B2b does not exceed 0.0165 ns and the coherence between the code and the carrier of the signal is only 0.137∘. A performance evaluation has indicated that at its current stage, the positioning accuracy in the horizontal and vertical directions is better than 0.15 m and 0.3 m, respectively, and the convergence time does not exceed 800 s. [ABSTRACT FROM AUTHOR]

SIRT1 has been proposed to enhance insulin secretion in β-cell through repressing the expression of uncoupling protein2 (UCP2), but whether ethanol-induced β-cell dysfunction is mediated by the disrupted SIRT1-UCP2 axis remains unknown. This study was conducted to explore the underlying mechanisms by which ethanol resulted in β-cell dysfunction and the potential protective effects of resveratrol in this process. INS-1 cells (rat pancreatic β-cell line) were cultured with ethanol in the presence or absence of resveratrol (2.5, 12.5 μmol/L). The results showed that ethanol exposure reduced glucose-stimulated insulin secretion, ATP production and SIRT1 expression but increased UCP2 expression, while supplementation with resveratrol restored the function of INS-1 cell by upregulating SIRT1 and inhibiting UCP2. Moreover, the critical role of SIRT1-UCP2 axis was further supported by the results that SIRT1 activator SRT1720 reversed ethanol-induced impairment of glucose-stimulated insulin secretion by decreasing UCP2, while SIRT1 inhibitor Ex527 abolished the beneficial effects of resveratrol. Meanwhile, NAD+ booster nicotinamide mononucleotide also counteracted the deleterious effects of ethanol by increasing SIRT1, suggesting the regulation of SIRT1-UCP2 axis may be associated with cellular NAD+/NADH ratio. In conclusion, our observations imply that ethanol induces impaired insulin secretion from INS-1 cell through disrupting SIRT1-UCP2 axis, while resveratrol may reverse this process by augmenting SIRT1 and inhibiting UCP2. • Ethanol exposure could induce β-cell dysfunction via disrupting SIRT1-UCP2 axis. • Resveratrol counteracts ethanol induced β-cell dysfunction via regulating SIRT1-UCP2 axis. • The regulation of SIRT1-UCP2 axis is likely to be associated with NAD+/NADH ratio. [ABSTRACT FROM AUTHOR]