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In order to deal with complex risk scenarios involving claims, uncertainty, and investments, we consider the ruin problems in a compound Poisson risk model with liquid reserves and proportional investments and study the expected discounted penalty function under threshold dividend strategies. Firstly, the integral differential equation of the expected discounted penalty function is derived. Secondly, since the closed-form solution of the equation cannot be obtained, a sinc method is used to obtain the numerical approximation solution of the equation. Finally, the feasibility and superiority of the sinc method are illustrated by error analysis. In addition, based on a symmetric jump risk market, we discuss the influence of some parameters on the ruin probability with some examples. This study can help actuaries develop more robust risk management strategies and ensure the long-term stability and profitability of insurance companies. It provides a theoretical basis for actuaries to carry out risk management. [ABSTRACT FROM AUTHOR]

Background: Pigeon circovirus infections in pigeons (Columba livia domestica) have been reported worldwide. Pigeons should be PiCV-free when utilized as qualified experimental animals. However, pigeons can be freely purchased as experimental animals without any clear guidelines to follow. Herein, we investigated the status quo of PiCV infections on a pigeon farm in Beijing, China, which provides pigeons for experimental use. Results: PiCV infection was verified in at least three types of tissues in all forty pigeons tested. A total of 29 full-length genomes were obtained and deposited in GenBank. The whole genome sequence comparison among the 29 identified PiCV strains revealed nucleotide homologies of 85.8–100%, and these sequences exhibited nucleotide homologies of 82.7–98.9% as compared with those of the reference sequences. The cap gene displayed genetic diversity, with a wide range of amino acid homologies ranging from 64.5% to 100%. Phylogenetic analysis of the 29 full-genome sequences revealed that the PiCV strains in this study could be further divided into four clades: A (17.2%), B (10.4%), C (37.9%) and D (34.5%). Thirteen recombination events were also detected in 18 out of the 29 PiCV genomes obtained in this study. Phylogenetic research using the rep and cap genes verified the recombination events, which occurred between clades A/F, A/B, C/D, and B/D among the 18 PiCV strains studied. Conclusions: In conclusion, PiCV infection, which is highly genetically varied, is extremely widespread on pigeon farms in Beijing. These findings indicate that if pigeons are to be used as experimental animals, it is necessary to evaluate the impact of PiCV infection on the results. [ABSTRACT FROM AUTHOR]

Aim: Similar environmental selection pressures drive the occurrence of convergent evolution among species. However, studies on this phenomenon are scarce at the population level. Here, we used two waist‐shaped bugs to test the hypothesis that similar high‐elevation habitat environments could lead to similar genetic adaptations among populations of different species. Location: East Asia. Taxa: Malcus sinicus Štys, 1967 & Malcus insularis Štys, 1967. Methods: Population genetic structure was determined by phylogenetic and phylogeographical analyses. Demographic history was inferred by comparing simulated history models. Suitable habitat from the last interglacial period (LIG) to the present was predicted by ecological niche modelling (ENM). Convergent evolutionary processes were jointly assessed by the comparison of population ecological differences and the principal component analysis of environmentally related single‐nucleotide polymorphisms (SNPs). Results: Our results showed that the land bridge in the Pleistocene helped ancestral populations of M. sinicus and M. insularis diffuse from mainland China to Taiwan Island. Subsequently, the geographical barrier imposed by the Taiwan Strait promoted the species differentiation. Geographic isolation and adaptive evolution jointly promoted the population differentiation in M. sinicus. Genetic similarity was found between the populations of M. sinicus in southwestern China (sin‐YN) and M. insularis on Taiwan Island (ins‐TW). Temperature‐related environmental factors and elevation were found to similarly and significantly clustered with ins‐TW and sin‐YN and were clearly distinguished from the other low−/mid‐elevation populations of M. sinicus (sin‐EA). Furthermore, the SNPs related to these environmental factors presented the same clustering results. Main Conclusions: Our study revealed a novel disjunct distribution pattern between southwestern China and Taiwan Island at the population level and provided evidence of convergent evolution of local populations in high‐elevation environments. Here, we revealed that similar environmental selection pressures can drive the occurrence of convergent evolution at the population level among different species. [ABSTRACT FROM AUTHOR]

Purpose: Claudin 18.2 (CLDN18.2) is a reliable target for lesion detection and could have clinical implications for epithelial tumors, especially digestive system neoplasms. However, there is no predictive technology for accurate whole-body mapping of CLDN18.2 expression in patients. This study assessed the safety of the 124I-18B10(10L) tracer and the feasibility of mapping whole-body CLDN18.2 expression using PET functional imaging. Methods: The 124I-18B10(10L) probe was synthesized manually, and preclinical experiments including binding affinity and specific targeting ability were conducted after testing in vitro model cells. Patients with pathologically confirmed digestive system neoplasms were enrolled in an ongoing, open-label, single-arm, first-in-human (FiH) phase 0 trial (NCT04883970). 124I-18B10(10L) PET/CT or PET/MR and 18F-FDG PET were performed within one week. Results: 124I-18B10(10L) was successfully constructed with an over 95% radiochemical yield. The results of preclinical experiments showed that it had high stability in saline and high affinity in CLDN18.2 overexpressing cells (Kd = 4.11 nM). Seventeen patients, including 12 with gastric cancers, 4 with pancreatic cancers, and 1 with cholangiocarcinoma were enrolled. 124I-18B10(10L) displayed high uptake in the spleen and liver, and slight uptake in the bone marrow, lung, stomach and pancreas. The tracer uptake SUVmax in tumor lesions ranged from 0.4 to 19.5. Compared with that in lesions that had been treated with CLDN18.2-targeted therapy, 124I-18B10(10L) uptake was significantly higher in lesions that had not. Regional 124I-18B10(10L) PET/MR in two patients showed high tracer uptake in metastatic lymph nodes. Conclusions: 124I-18B10(10L) was successfully prepared and exhibited a high binding affinity and CLDN18.2 specificity in preclinical studies. As an FiH CLDN18.2 PET tracer, 124I-18B10(10L) was shown to be safe with acceptable dosimetry and to clearly reveal most lesions overexpressing CLDN18.2. Trial registration: NCT04883970; URL: https://register.clinicaltrials.gov/. Registered 07 May 2021. [ABSTRACT FROM AUTHOR]

Since the beginning of the Holocene era, human activities have seriously impacted animal habitats and vegetative environments. Species that are dependent on natural habitats or with narrow niches might be more severely affected by habitat changes. Malcus inconspicuus is distributed in subtropical China and highly dependent on the mountain environment. Our study investigated the role of the mountainous landscape in the historical evolution of M. inconspicuus and the impact of Holocene human activities on it. A phylogeographical approach was implemented with integrative datasets including double‐digest restriction site‐associated DNA (ddRAD), mitochondrial data, and distribution data. Three obvious clades and an east–west phylogeographical pattern were found in subtropical China. Mountainous landscape has "multifaceted" effects on the evolutionary history of M. inconspicuus, it has contributed to population differentiation, provided glacial refuges, and provided population expansion corridors during the postglacial period. The effective population size (Ne) of M. inconspicuus showed a sharp decline during the Holocene era, which revealed a significantly negative correlation with the development of cropland in a hilly area at the same time and space. It supported that the species which are highly dependent on natural habitats might undergo greater impact when the habitat was damaged by agricultural activities and we should pay more attention to them, especially in the land development of their distribution areas. [ABSTRACT FROM AUTHOR]

Simple Summary: Blissidae is a group with high species richness in Lygaeoidea, and most of them live in the leaf sheaths of Poaceae plants. Here, 10 new mitogenomes from 10 species of eight genera from Blissidae were sequenced and analyzed. Gene rearrangement is only found in Pirkimeru japonicus (PiGXBS1), which is formed as the duplication of tRNA-H. Coupled with published data, phylogenetic analyses and divergence time were performed in Blissidae. The divergence within Blissidae began about 56 million years ago (Ma), in which the genus level divergence was concentrated at 30–51 Ma, slightly later than the diversification of Poaceae. The consistency of the divergence time between Blissidae and Poaceae might hint at the coevolutionary relationship between them. Our study provides a valuable resource for understanding insect–host relationships. Blissidae (the Chinch bug) is a group with high species richness in Lygaeoidea, but there are only a few descriptions of mitochondrial genomes available. We obtained mitogenomes from 10 species of eight genera from Blissidae through second-generation sequencing technology. The length of the mitochondrial genome (excluding the control region) is between 14643 and 14385 bp; the content of AT is between 74.1% and 77.9%. The sequence of the evolution rate of protein coding genes was as follows: ND5 > ATP8 > ND6 > ND2 > ND4 > ND4L > ND1 > ATP6 > ND3 > COIII > COII > CYTB > COI. The mitogenomic structure of Blissidae is highly conservative. Gene rearrangement is only found in Pirkimeru japonicus (PiGXBS1), which is formed as the duplication of tRNA-H. The intergenic spacer between ND4 and tRNA-H, which form an obvious stem-and-loop structure, was found in all samples in this study. The phylogenetic trees generated by BI and ML indicated that Blissidae can be divided into three major clades: Clade A (only included Macropes); Clade B ((Pirkimerus + Bochrus) + Iphicrates); and Clade C ((Ischnodemus + Capodemus) + (Cavelerius + Dimorphopterus)). The divergence within the Blissidae began at about 56 Ma. At the genus level, the divergence was concentrated at 30–51 Ma, slightly later than the diversification of Poaceae. The consistency of divergence time between Blissidae and Poaceae might hint at the coevolutionary relationship between them, but further molecular and biological evidence is still needed to prove it. [ABSTRACT FROM AUTHOR]

[Display omitted] • Erthesina fullo with a strong east–west differentiation phylogeographical structure in East Asia. • The violent climate fluctuation might cause population divergence during the Middle and Upper Pleistocene. • The coastal populations of the east lineage were identified as the source of invasion in Europe. • The coastal populations of the east lineage were identified as the source of invasion in Europe. • The widest geographical distribution, a star-like haplotype network with the main haplotype as the core and rapid population expansion history, indicates the source lineage might have stronger diffusion ability and adaptability than the other lineages. The yellow spotted stink bug (YSSB), Erthesina fullo (Thunberg, 1783) is an important Asian pest that has recently successfully invaded Europe and an excellent material for research on the initial stage of biological invasion. Here, we reported the native evolutionary history, recent invasion history, and potential invasion threats of YSSB for the first time based on population genetic methods [using double digest restriction-site associated DNA (ddRAD) data and mitochondrial COI and CYTB] and ecological niche modelling. The results showed that four lineages (east, west, southwest, and Hainan Island) were established in the native range with a strong east–west differentiation phylogeographical structure, and the violent climate fluctuation might cause population divergence during the Middle and Upper Pleistocene. In addition, land bridges and monsoon promote dispersal and directional genetic exchanging between island populations and neighboring continental populations. The east lineage (EA) was identified as the source of invasion in Albania. EA had the widest geographical distribution among all other lineages, with a star-like haplotype network with the main haplotype as the core. It also had a rapid population expansion history, indicating that the source lineage might have stronger diffusion ability and adaptability. Our findings provided a significant biological basis for fine tracking of invasive source at the lineage or population level and promote early invasion warning of potential invasive species on a much subtler lineage level. [ABSTRACT FROM AUTHOR]

Escherichia coli can cause gastrointestinal infection, urinary tract infection and other infectious diseases. Accurate detection of Escherichia coli 16S rDNA (Ec-16S rDNA) in clinical practice is of great significance for the identification and treatment of related diseases. At present, there are various types of sensors that can achieve accurate detection of Ec-16S rDNA. Electrochemiluminescence (ECL) has attracted considerable attention from researchers, which causes excellent performance in bioanalysis. Based on the previous research, it is significance to develop a novel, sensitive and efficient ECL biosensor. In this work, an ECL biosensor for the detection of Ec-16S rDNA was constructed by integrating CRISPR/Cas12a technology with the cascade signal amplification strategy consisting of strand displacement amplification (SDA) and dual-particle three-dimensional (3D) DNA rollers. The amplification products of SDA triggered the operation of the DNA rollers, and the products generated by the DNA rollers activated CRISPR/Cas12a to cleave the signal probe, thereby realizing the change of the ECL signal. The cascade amplification strategy realized the exponential amplification of the target signal and greatly improved the sensitivity. Manganese dioxide nanoflowers (MnO 2 NFs) as a co-reaction promoter effectively enhanced the ECL intensity of tin disulfide quantum dots (SnS 2 QDs). A new ternary ECL system (SnS 2 QDs/S 2 O 8 2−/MnO 2 NFs) was prepared, which made the change of ECL intensity of biosensor more significant. The proposed biosensor had a response range of 100 aM-10 nM and a detection limit of 27.29 aM (S/N = 3). Herein, the cascade signal amplification strategy formed by SDA and dual-particle 3D DNA rollers enabled the ECL biosensor to have high sensitivity and low detection limit. At the same time, the cascade signal amplification strategy was integrated with CRISPR/Cas12a to enable the biosensor to efficiently detect the target. It can provide a new idea for the detection of Ec-16S rDNA in disease diagnosis and clinical analysis. [Display omitted] • 3D DNA rollers and SDA greatly enhanced the signal amplification. • CRISPR/Cas12a system improved the sensitivity and accuracy of biosensors. • Programmable T-type structure-assisted CRISPR/Cas12a improved the selectivity. [ABSTRACT FROM AUTHOR]

A signed graph Γ (G) is a graph with a sign attached to each of its edges, where G is the underlying graph of Γ (G). The energy of a signed graph Γ (G) is the sum of the absolute values of the eigenvalues of the adjacency matrix A (Γ (G)) of Γ (G). The random signed graph model G n (p , q) is defined as follows: Let p , q ≥ 0 be fixed, 0 < p + q < 1. Given a set of n vertices, between each pair of distinct vertices there is either a positive edge with probability p or a negative edge with probability q , or else there is no edge with probability 1 − (p + q). The edges between different pairs of vertices are chosen independently. In this paper, we obtain an exact estimate of energy for almost all signed graphs. Furthermore, we establish lower and upper bounds to the energy of random multipartite signed graphs. [ABSTRACT FROM AUTHOR]

A signed graph Γ (G) is a graph with a sign attached to each of its edges, where G is the underlying graph of Γ (G). Let A (Γ (G)) denote the adjacency matrix of Γ (G) , and A (G) be the adjacency matrix of G. The rank of G (resp. Γ (G)), written as r (G) (resp. r (Γ (G))), refers to the rank of A (G) (resp. A (Γ (G))). A natural and interesting problem is: What is the relation between the rank of a signed graph and the rank of its underlying graph? In this paper, we focus our attention on this problem. Sharp lower bounds and upper bounds on r (Γ (G)) − r (G) are determined. All the corresponding extremal signed graphs Γ (G) are characterized, respectively. [ABSTRACT FROM AUTHOR]

The revised Szeged index of a graph G is defined as S z ∗ ( G ) = ∑ e = u v ∈ E ( n u ( e ) + n 0 ( e ) 2 ) ( n v ( e ) + n 0 ( e ) 2 ) , where n u ( e ) and n v ( e ) are, respectively, the number of vertices of G lying closer to vertex u than to vertex v and the number of vertices of G lying closer to vertex v than to vertex u , and n 0 ( e ) is the number of vertices equidistant to u and v . A cactus is a graph in which any two cycles have at most one common vertex. Let C ( n , k ) denote the class of all cacti with n vertices and k cycles. In this paper, sharp lower bound on revised Szeged index of graph G in C ( n , k ) is established and the corresponding extremal graph is determined. Furthermore, the graph G in C ( n , k ) with the second minimal revised Szeged index is identified as well. [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation (LLPS) has long been observed during the physical stability investigation of therapeutic protein formulations. The buffer conditions and the presence of various excipients are thought to play important roles in the formulation development of monoclonal antibodies (mAbs). In this study, the effects of several small-molecule excipients (histidine, alanine, glycine, sodium phosphate, sodium chloride, sorbitol and sucrose) with diverse physical-chemical properties on LLPS of a model IgG1 (JM2) solutions were investigated by multiple techniques, including UV–vis spectroscopy, circular dichroism, differential scanning calorimetry/fluorimetry, size exclusion chromatography and dynamic light scattering. The LLPS of JM2 was confirmed to be a thermodynamic equilibrium process with no structural changes or irreversible aggregation of proteins. Phase diagrams of various JM2 formulations were constructed, suggesting that the phase behavior of JM2 was dependent on the solution pH, ionic strength and the presence of other excipients such as glycine, alanine, sorbitol and sucrose. Furthermore, we demonstrated that for this mAb, the interaction parameter ( k D ) determined at low protein concentration appeared to be a good predictor for the occurrence of LLPS at high concentration. [ABSTRACT FROM AUTHOR]

The Szeged index of a graph G is defined as S z ( G ) = ∑ e = u v ∈ E n u ( e ) n v ( e ) , where n u ( e ) and n v ( e ) are, respectively, the number of vertices of G lying closer to vertex u than to vertex v and the number of vertices of G lying closer to vertex v than to vertex u . A cactus is a graph in which any two cycles have at most one common vertex. Let C ( n , k ) denote the class of all cacti with order n and k cycles, and C n t denote the class of all cacti with order n and t pendant vertices. In this paper, a lower bound of the Szeged index for cacti of order n with k cycles is determined, and all the graphs that achieve the lower bound are identified. As well, the unique graph in C n t with minimum Szeged index is characterized. [ABSTRACT FROM AUTHOR]

Recently, increasing research efforts have been devoted into developing high-concentration protein drugs for subcutaneous injection, especially for those with short half-lives and high-dose requirement. Proteins at high concentrations normally present increased colloidal and structural instability, such as aggregation, fibrillation and gelation, which significantly challenges the high-concentration formulation development of protein drugs. Here we used endostatin, a 20 kD recombinant protein, as a model drug for high-concentration formulation optimization. The colloidal and conformational stability of endostatin at high concentration of 30 mg/mL were investigated in formulations containing various excipients, including saccharides (mannitol, sorbitol and sucrose), salts (ArgHCl and NaCl), and surfactants (tween 20 and 80). Protein fibrillation was characterized and semi-quantified by optical polarized light microscopy and transmission electron microscopy, and the amount of fiber formation at elevated temperature of 40 °C was determined. The soluble protein aggregates were characterized by dynamic and static light scattering before and after dilution. The conformational stability were characterized by polyacrylamide gel electrophoresis, fluorescence, circular dichroism, and differential scanning calorimetry. We observed that the soluble aggregation, fibrillation and gelation, induced by conformational and colloidal instabilities of the protein solution, could be substantially optimized by using suitable stabilizers such as combinations of saccharides and surfactants; while formation of gel and soluble aggregates at high protein concentration ( e.g. , 30 mg/mL) and elevated temperature (40 °C) could be prevented by avoiding the usage of salts. It’s worth emphasizing that some stabilizers, such as salts and surfactants, could show opposite contributions in conformational and colloidal stabilities of endostatin. Therefore, cautions are needed when one attempts to correlate the colloidal stability of high-concentration proteins with their conformational stability, and the colloidal and conformational protein stabilities must be harmonized by a balanced selection of various types of excipients. [ABSTRACT FROM AUTHOR]

A novel one-dimensional CoMnO x /N-CNT composite was synthesized by binding Mn-Co nanoparticles on nitrogen doped carbon nanotubes (N-CNT) through solvothermal method and followed by high temperature pyrolysis. The as-made Mn-Co/N-CNT as LIBs anode material exhibits excellent rechargeable capability, i.e. 1028 mAh·g −1 at 200 mA·g −1 . Doped nitrogen on CNT effectively increase the conductivity of the complex and the binding energy between Mn-Co nanoparticles and CNT, which lead to more stable and higher conductive complex during charge/discharge cycling process. [ABSTRACT FROM AUTHOR]

Purpose: To identify the key formulation factors controlling the initial drug and polymer dissolution rates from an amorphous solid dispersion (ASD). Methods: Ketoconazole (KTZ) ASDs using PVP, PVP-VA, HMPC, or HPMC-AS as polymeric matrix were prepared. For each drug-polymer system, two types of formulations with the same composition were prepared: 1. Spray dried dispersion (SDD) that is homogenous at molecular level, 2. Physical blend of SDD (80% drug loading) and pure polymer (SDD-PB) that is homogenous only at powder level. Flory-Huggins interaction parameters (χ) between KTZ and the four polymers were obtained by Flory-Huggins model fitting. Solution C NMR and FT-IR were conducted to investigate the specific drug-polymer interaction in the solution and solid state, respectively. Intrinsic dissolution of both the drug and the polymer from ASDs were studied using a Higuchi style intrinsic dissolution apparatus. PXRD and confocal Raman microscopy were used to confirm the absence of drug crystallinity on the tablet surface before and after dissolution study. Results: In solid state, KTZ is completely miscible with PVP, PVP-VA, or HPMC-AS, demonstrated by the negative χ values of −0.36, −0.46, −1.68, respectively; while is poorly miscible with HPMC shown by a positive χ value of 0.23. According to solution C NMR and FT-IR studies, KTZ interacts with HPMC-AS strongly through H-bonding and dipole induced interaction; with PVPs and PVP-VA moderately through dipole-induced interactions; and with HPMC weakly without detectable attractive interaction. Furthermore, the 'apparent' strength of drug-polymer interaction, measured by the extent of peak shift on NMR or FT-IR spectra, increases with the increasing number of interacting drug-polymer pairs. For ASDs with the presence of considerable drug-polymer interactions, such as KTZ/PVPs, KTZ/PVP-VA, or KTZ /HPMC-AS systems, drug released at the same rate as the polymer when intimate drug-polymer mixing was ensured (i.e., the SDD systems); while drug released much slower than the polymer when molecular level mixing or drug-polymer interaction was absent (SDD-PB systems). For ASDs without drug-polymer interaction (i.e., KTZ/HPMC systems), the mixing homogeneity had little impact on the release rate of either the drug or the polymer thus SDD and SDD-PB demonstrated the same drug or polymer release rate, while the drug released slowly and independently of polymer release. Conclusions: The initial drug release from an ASD was controlled by 1) the polymer release rate; 2) the strength of drug-polymer interaction, including the intrinsic interaction caused by the chemistry of the drug and the polymer (measured by the χ value), as well as that the apparent interaction caused by the drug-polymer ratio (measure by the extent of peak shift on spectroscopic analysis); and 3) the level of mixing homogeneity between the drug and polymer. In summary, the selection of polymer, drug-polymer ratio, and ASD processing conditions have profound impacts on the dissolution behavior of ASDs. [ABSTRACT FROM AUTHOR]

The Estrada index of a graph G is defined as EE ( G ) = ∑ i = 1 n e λ i , where λ 1 , λ 2 , … , λ n are the eigenvalues of the adjacency matrix of G . Let T n k be the set of the k -trees of order n . In this paper, we characterize the graphs among T n k having the first (resp. the second) largest Estrada index. [ABSTRACT FROM AUTHOR]

Simple Summary: The stalk-eyed seed bug Chauliops fallax is an important agricultural pest of soybean and was first reported to occur outside East Asia. Here, the native evolutionary history, recent invasion history, and potential invasion threats of C. fallax were reported for the first time based on population genetic methods and ecological niche modelling. Four native genetic groups (EA, WE, TL, and XZ) and an east–west differentiation pattern consistent with the geographical characteristics of three-step landforms were well supported in China. The Kashmir sample was found to come from a recent invasion event, and the invasive source was determined to be the populations of the coastal areas of southern China. North America might have high a risk of invasion, which poses a serious threat to local soybean production. Our results provided new insights into the monitoring and management of Chauliops fallax in the early invasion stage. The short stay at the beginning of the invasion process is a critical time for invasive species identification and preventing invasive species from developing a wider distribution and significant economic impact. The stalk-eyed seed bug Chauliops fallax is an important agricultural pest of soybean and was first reported to occur outside East Asia. Here, we reported the native evolutionary history, recent invasion history, and potential invasion threats of C. fallax for the first time based on population genetic methods and ecological niche modelling. The results showed that four native East Asian genetic groups (EA, WE, TL, and XZ) were well supported, showing an east-west differentiation pattern consistent with the geographical characteristics of three-step landforms in China. Two main haplotypes existed: Hap1 might have experienced a rapid northwards expansion process after the LGM period, and Hap5 reflected local adaptation to the environment in southeastern China. The Kashmir sample was found to come from the recent invasion of populations in the coastal areas of southern China. Ecological niche modelling results suggested that North America has a high risk of invasion, which might pose a serious threat to local soybean production. In addition, with future global warming, the suitable habitat in Asia will move towards the higher latitude region and gradually deviate from the soybean planting area, which indicates the threat of C. fallax to soybean production in Asia will decrease in the future. The results could provide new insights into the monitoring and management of this agricultural pest in the early invasion stage. [ABSTRACT FROM AUTHOR]

Obesity and type 2 diabetes are chronic metabolic diseases, and those affected could benefit from the use of a-amylase inhibitors to manage starch intake. The pseudocyclics, wrightides Wr-AI1 to Wr-AI3, isolated from an Apocynaceae plant show promise for further development as orally active a-amylase inhibitors. These linear peptides retain the stability known for cystine-knot peptides in the presence of harsh treatment. They are resistant to heat treatment and endopeptidase and exopeptidase degradation, which is characteristic of cyclic cystine-knot peptides. Our NMR and crystallography analysis also showed that wrightides, which are currently the smallest proteinaceous a-amylase inhibitors reported, contain the backbone-twisting cis-proline, which is preceded by a nonaromatic residue rather than a conventional aromatic residue. The modeled structure and a molecular dynamics study of Wr-AI1 in complex with yellow mealworm α-amylase suggested that, despite having a similar structure and cystine- knot fold, the knottin-type a-amylase inhibitors may bind to insect a-amylase via a different set of interactions. Finally, we showed that the precursors of pseudocyclic cystine-knot a-amylase inhibitors and their biosynthesis in plants follow a secretory protein synthesis pathway. Together, our findings provide insights for the use of the pseudocyclic a-amylase inhibitors as useful leads for the development of orally active peptidyl bioactives, as well as an alternative scaffold for cyclic peptides for engineering metabolically stable human a-amylase inhibitors. [ABSTRACT FROM AUTHOR]

Proteases are ubiquitous in nature, whereas naturally occurring peptide ligases, enzymes catalyzing the reverse reactions of proteases, are rare occurrences. Here we describe the discovery of butelase 1, to our knowledge the first asparagine/aspartate (Asx) peptide ligase to be reported. This highly efficient enzyme was isolated from Clitoria ternatea, a cyclic peptide-producing medicinal plant. Butelase 1 shares 71% sequence identity and the same catalytic triad with legumain proteases but does not hydrolyze the protease substrate of legumain. Instead, butelase 1 cyclizes various peptides of plant and animal origin with yields greater than 95%. With Kcat values of up to 17 s−1 and catalytic efficiencies as high as 542,000 M−1 s−1, butelase 1 is the fastest peptide ligase known. Notably, butelase 1 also displays broad specificity for the N-terminal amino acids of the peptide substrate, thus providing a new tool for C terminus-specific intermolecular peptide ligations. [ABSTRACT FROM AUTHOR]

The Notch signalling pathway is essential for proper cell growth and development. Many factors interact in the cellular context to bring about its effects. Critical to this process is the influence of Pofut1 whose function is to fucosylate Notch receptors and ligands on the cell surface for proper interaction. Of the three liver cell lines, HepG2, SMMC-7721 (hepatoma cell lines) and L-02 (normal fetal liver cell line) were investigated. In the current study, Pofut1 was silenced in L-02 due to its significantly high level of expression, ( P < 0.05) using transient SiRNA. Notch1, Cyclin D1 and p53 were significantly suppressed consequently. The effect on cell cycle, proliferation, adhesion and migration were investigated. Evidence adduced, indicate a general modification of cellular function. While proliferation and adhesion were significantly inhibited, the cell cycle arrest was obvious ( P < 0.05), migration was not affected. The effects seen are akin to those reported in previous studies in hepatoma cells mimicking some of the effects of notch1 silencing. Results of this study indicate a possible role of Pofut1 conferring a tumor suppressor role through the Notch signalling pathway. [ABSTRACT FROM AUTHOR]

• Mitogenomes of Aschiphasmatidae (Insecta: Phasmatodea) were firstly reported. • The phylogenetic result indicating Aschiphasmatidae and other groups of Euphasmatodea are sister groups. • The mitochondrial gene rearrangement structure seems to represent the synapomorphy of Aschiphasmatidae. The mitochondrial genome (mitogenome) has been regarded as significant source of data to better understand the phylogenetic relationships within the Euphasmatodea, but no mitogenome in Aschiphasmatoidea has been sequenced to date. In this study, two mitogenomes of Orthomeria smaragdinum and Nanhuaphasma hamicercum of Aschiphasmatidae were sequenced and annotated for the first time. The same mitochondrial gene rearrangement structure was present in the two mitogenomes sequenced, showing as the translocation of tRNA-Arg and tRNA-Asn , which conformed to the tandem duplication-random loss and could be used as a possible synapomorphy for Aschiphasmatidae. The phylogenetic results based on the maximum likelihood (ML) and bayesian inference (BI) methods both showed that Aschiphasmatidae and Neophasmatodea in Euphasmatodea are sister taxa. Although the monophyly of Oriophasmata, Occidophasmata, Diapheromeridae, Phasmatidae, Lonchodidae and Bacilloidea has not been solved, the monophyly of Neophasmatodea and Phyllioidea was well supported. [ABSTRACT FROM AUTHOR]

A dumbbell graph B n (p , l , q) is a bicyclic graph of order n consisting of two vertex-disjoint cycle C p and C q with a path of length l - 1 jointing them. In this paper, explicit formulas of the (reverse) cover costs, the additive degree-Kirchhoff index (resp. multiplicative degree-Kirchhoff index) in terms of the effective resistance-based invariants and distance-based invariants for dumbbell graphs is displayed. The corresponding extremal graphs for the minimum and maximum cover cost and reverse cover cost of a vertex in a dumbbell graph B n (p , l , q) are determined, and the extremal graphs for the minimum and maximum additive degree-Kirchhoff index (resp. multiplicative degree-Kirchhoff index) of dumbbell graphs B n (p , l , q) are also characterized. [ABSTRACT FROM AUTHOR]

C-terminal domains (CTDs) of variousspidroins are relatively conservedin the amino acid sequence and have been suggested to perform similarfunctions. Here, we solved the structure of the CTD of an aciniformspidroin using NMR spectroscopy with a two-point mutant and studiedits functional role with several constructs. The CTDs of aciniform,major, and minor ampullate spidroins adopt the same domain-swappingdimeric folding although their sequence identities are 24–40%.Unlike CTDs of major and minor ampullate spidroins, the aciniformCTD had no obvious effects on preventing spidroins from aggregationin storage but slightly enhanced protein assembly under shear force.The differential functions may result from significant differencesin detailed structures and properties of repetitive regions of varioustypes of spidroins. Nevertheless, all CTDs may have a common functionalrole: dimerization of the CTD doubles the size of silk proteins, reducesthe number of chain ends, and thus leads to fewer chain end defectsin the fibers formed. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor in Chief. This paper is being retracted due to many inaccuracies in the original data in Figures 1D, 1E, 2A, 2B, 2E, 3B, 4B, 5A being identified that have raised concerns over the validity of the overall findings. [ABSTRACT FROM AUTHOR]

The L -index (resp. Q -index) of a graph G is the largest eigenvalue of the Laplacian matrix (resp. signless Laplacian matrix) of G. Very recently, Lou, Guo and Wang [6] determined the graph with fixed size and diameter having the maximum Q -index (resp. L -index). As a continuance of their result, in this paper we order all the graphs with given size and diameter from the second to the (⌊ d 2 ⌋ + 1) th via their Q -indices. Consequently, we identify all the graphs of given size and diameter from the second to the ⌊ d 2 ⌋ th via their L -indices. Furthermore, the graph of given size and diameter with at least one cycle having the largest Q -index is also characterized. [ABSTRACT FROM AUTHOR]

Abstract: Let be the set of the complements of trees on n vertices. In this paper we characterize the unique graph whose least eigenvalue of the signless Laplacian attains the minimum among all graphs in , where is the complement of the star graph on n vertices. [Copyright &y& Elsevier]

Mouse hepatoma cellular carinoma cell line (Hca-F) cells have highly invasive and lymphatic metastasis potential in vitro and in vivo. Curcumin (diferuloylmethane) is an active component of the spice turmeric and has a diversity of antitumor activities. However, there is no available information to address the effects of curcumin on migration and invasion of mouse hepatoma Hca-F cells. In this study, we found that curcumin exerted a concentration- and time-dependent inhibitory effect on the migration and invasion of Hca-F cells in vitro. Curcumin inhibited the expression of the tumor promoter caveolin-1 (Cav-1) in Hca-F cells. Up-regulation of Cav-1 expression by pcDNA3.1/Cav-1 plasmid was able to reverse the curcumin-induced antimigration and anti-invasion effects in vitro. Curcumin down-regulated the expression of cluster of differntiation (CD)147, matrix metalloproteinase 2, and matrix metalloproteinase 9 and inhibited the phosphorylation of epidermal growth factor receptor (EGFR), the phosphoinositilde 3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase (MAPK), and p44/42MAPK in Hca-F cells. Taken together, our findings suggest that curcumin can suppress the migratory and invasive ability of mouse hepatoma Hca-F cells, and this action is mediated through a novel mechanism involving inactivation of Cav-1 and EGFR signaling pathways. © 2011 IUBMB IUBMB Life, 63(9): 775-782, 2011 [ABSTRACT FROM AUTHOR]

Let T n , k be the set of k -ary trees of order n = (k − 1) t + 2 , where k -ary trees are trees in which every vertex has degree 1 or k. For a connected graph G = (V (G) , E (G)) , the cover cost (resp. reverse cover cost) of a vertex u in G is defined as C C G (u) = ∑ v ∈ V (G) H u v (resp. R C G (u) = ∑ v ∈ V (G) H v u), where H u v is the expected hitting time for random walk beginning at u to visit v. In this paper, we consider extremal problems on k -ary trees with respect to the cover cost and reverse cover cost. In particular, the maximum (resp. minimum) cover cost and reverse cover cost among all k -ary trees with given order are identified. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the present investigation was to clarify the mechanism by which Labrafac Lipophile WL 1349 (WL 1349) enhanced the oral bioavailability (BA) of hydroxysafflor yellow A (HSYA), the representative low permeable hydrophilic (biopharmaceutic classification system (BCS) Class III) drug. HSYA–phospholipid complex was prepared, and dissolved into WL 1349 with a certain surfactant to form a stable oil solution. Oral administration of HSYA aqueous solution at a dosage of 4.5mg/kg resulted a low plasma HSYA concentration with C max and AUC0–8h values of 0.105μg/ml and 10.29μgmin/ml, respectively. HSYA–phospholipid complex oil solution with the same administration and dosage increased the plasma HSYA concentration significantly with C max and AUC0–8h values of 2.063μg/ml and 381.145μgmin/ml, respectively. The results showed that WL 1349 could improve oral absorption of HSYA remarkably. Bioavailability investigations were performed to show WL 1349 dosage independent from HSYA absorption within the dosage from 1ml/kg to 9ml/kg. The test of bile duct ligation in rats showed that the oil solution containing WL 1349 did not result in detectable plasma HSYA concentration, but HSYA aqueous solution had the same AUC0–8h as the bile duct was not ligated. The in vitro lipolysis experiments of WL 1349 showed that WL 1349 was emulsified by deoxycholate, and then was hydrolyzed to fatty acids and monoglycerides by pancreatic lipase rapidly. The lipolysis products of WL 1349, caprylic acid, capric acid and caprylic and capric acid monoglycerides all improved the BA of HSYA in vivo. The results above indicated the emulsifying by bile, and hydrolysis to fatty acids and monoglycerides by pancreatic lipase was one of the enhancing mechanisms of HSYA–phospholipid complex oil solution absorption. [Copyright &y& Elsevier]

Abstract: Matrix metalloproteinase-11 (MMP-11) belongs to the particular member of MMP family, a group of zinc-dependent endopeptidases involved in tumor progression, invasion and metastasis. MMP-11 is strongly expressed in tumor cells and stromal fibroblasts located in the immediate vicinity of tumor. This study investigated the possible role of MMP-11 expression in mouse hepatocarcinoma cell line Hca-F with highly lymphatic metastasis potential by RNA interference (RNAi) approach. The results showed that a small interfering RNA (siRNA) targeted against MMP-11 significantly impeded Hca-F cells proliferation and colony formation in soft agar, as well as resulted in Hca-F cell apoptosis. This reduction of MMP-11 expression also led to the decreased migration and adhesion of Hca-F cells dramatically both in vitro and in vivo. Furthermore, in vivo metastasis assay indicated that down-regulation of MMP-11 expression in Hca-F cells attenuated the metastatic potential of Hca-F cells to peripheral lymph nodes. These data together provide compelling evidence into the function of MMP-11 and suggest that MMP-11 act as a tumor lymphatic metastasis-associated gene, and could represent a new potential target for gene therapy. [Copyright &y& Elsevier]

Distributed authorization is an essential issue in computer security. Recent research shows that trust management is a promising approach for the authorization in distributed environments. There are two key issues for a trust management system: how to design an expressive high-level policy language and how to solve the compliance-checking problem (Blaze et al. in Proceedings of the Symposium on Security and Privacy, pp. 164–173, 1996; Proceedings of 2nd International Conference on Financial Cryptography (FC’98). LNCS, vol.1465, pp. 254–274, 1998), where ordinary logic programming has been used to formalize various distributed authorization policies (Li et al. in Proceedings of the 2002 IEEE Symposium on Security and Privacy, pp. 114–130, 2002; ACM Trans. Inf. Syst. Secur. (TISSEC) 6(1):128–171, 2003). In this paper, we employ Answer Set Programming to deal with many complex issues associated with the distributed authorization along the trust management approach. In particular, we propose a formal authorization language $$\mathcal {AL}$$ providing its semantics through Answer Set Programming. Using language $$\mathcal {AL}$$ , we cannot only express nonmonotonic delegation policies which have not been considered in previous approaches, but also represent the delegation with depth, separation of duty, and positive and negative authorizations. We also investigate basic computational properties related to our approach. Through two case studies. we further illustrate the application of our approach in distributed environments. [ABSTRACT FROM AUTHOR]

Abstract: CD147 which is a regulator of matrix metalloproteinase (MMP) production on the surface of many malignant tumor cells, shows a highly specific association with caveolin-1 (Cav-1). As a result of heterogeneous N-glycosylation, CD147 exists in both highly glycosylated form, HG-CD147 (∼40–60kDa) and lowly glycosylated form, LG-CD147 (∼32kDa). This study investigated the possible role of Cav-1 in CD147 glycosylation in the HcaF, HcaP and Hepa1-6 mouse hepatocarcinoma cell lines, which have high, low and no metastatic potential in the lymph nodes, respectively, and in the normal mouse liver cell line IAR-20. Using an RNA interference (RNAi) strategy, we showed that the down-regulation of Cav-1 in Hca-F/RNAi cells could suppress the conversion of LG-CD147 to HG-CD147, down-regulate MMP-11 expression and decrease Hca-F/RNAi cell invasion. Conversely, a stable high expression of Cav-1 in Hepa1-6/Cav-1 cell could cause a specific increase of HG-CD147, up-regulate MMP-11 protein expression and enhance Hepa1-6/Cav-1 cell invasion. In conclusion, Cav-1 expression leads to an increased proportion of HG-CD147 relative to LG-CD147, increased production of MMP-11 and a higher invasive capability. Cav-1 is therefore proposed to act as both an oncogene and a tumor suppressor gene, and could represent a new potential target for gene therapy. [Copyright &y& Elsevier]

Drought can cause severe agricultural economic losses and hinder social and economic development. To manage drought, the process of drought events needs to be described with the help of an effective drought indicator. As a comprehensive variable, soil moisture is an essential indicator for describing agricultural drought. In this work, the extreme drought events in southwest China were analysed by the Global Land Data Assimilation System (GLDAS) root zone soil moisture data set. To define the drought quantitatively, a Standardized Soil Moisture Drought Index (SSMI) was calculated using the soil moisture data, then used to get the duration, frequency, and severity of drought events in southwest China. The results showed that the frequency and intensity of drought in southwest China had an apparent upward trend before 2014 and an apparent downward trend since 2014. Moreover, there are apparent differences in the frequency and intensity of drought in various regions of southwest China. Yunnan Province is prone to spring drought events. Guangxi Province and Guizhou Province are prone to spring, autumn and winter droughts, and the intensity of autumn and winter droughts is significantly higher than that of spring droughts. The Sichuan-Chongqing border area is prone to summer drought. We found that the monthly variation of soil moisture in different provinces in southwest China is consistent, but the seasonal variation of drought is different. Meanwhile, the performance of the SSMI was compared to the commonly used drought indices, the Standardized Precipitation Evapotranspiration Index (SPEI) and the Palmer Drought Severity Index (PDSI). The results showed that the SSMI is more sensitive to drought than both SPEI and PDSI in southwest China. The results also demonstrate that GLDAS soil moisture data can be used to study drought at a small regional scale. [ABSTRACT FROM AUTHOR]

A segment of a tree T is a path whose end vertices have degree 1 or at least 3, while all internal vertices have degree 2. The lengths of all the segments of T form its segment sequence, in analogy to the degree sequence. For a connected graph G = (V (G) , E (G)) , the cover cost (resp. reverse cover cost) of a vertex u in G is defined as C C G (u) = ∑ v ∈ V (G) H u v (resp. R C G (u) = ∑ v ∈ V (G) H v u ), where H u v is the expected hitting time for random walk beginning at u to visit v. In this paper, the unique tree with the minimum cover cost and minimum reverse cover cost among all trees with given segment sequence are characterized. Furthermore, the unique tree with the maximal reverse cover cost among all trees with given segment sequence are also identified. [ABSTRACT FROM AUTHOR]

MicroRNA-21 has been determined to be the only microRNA overexpressed in 11 types of solid tumors, making it an excellent candidate as a biomarker for disease diagnosis and therapy. Photoelectrochemical (PEC) biosensors have been widely used for quantification of microRNA-21. However, most PEC biosensing processes still suffer from some problems, such as the difficulty of avoiding the influence of interferents in complex matrices and the false-positive signals. There is a pressing need for establishing a sensitive and stable PEC method to detect microRNA-21. Herein, a nicking endonuclease-mediated rolling circle amplification (RCA)-assisted CRISPR/Cas12a PEC biosensor was fabricated for ultrasensitive detection of microRNA-21. The p-p type heterojunction PbS QDs/Co 3 O 4 polyhedra were prepared as the quencher, thus the initial PEC signal attained the "off" state. Furthermore, the target was specifically identified and amplified by the RCA process. Then, its product single-stranded DNA S1 activated the cis- and trans-cleavage abilities of CRISPR/Cas12a, leading to almost all of the PbS QDs/Co 3 O 4 polyhedra to leave the electrode surface, the p-n semiconductor quenching effect to be disrupted, and the signal achieving the "super-on" state. This pattern of PEC signal changed from "off" to "on" eliminated the interference of false-positive signals. The proposed PEC biosensor presented a satisfactory linear relationship ranging from 1 fM to 10 nM with a detection limit of 0.76 fM (3 Sb/N). With innovatively synthesized PbS QDs/Co 3 O 4 polyhedra as the effective quencher for PEC signal, the CRISPR/Cas12a dual-cleavage PEC biosensor possessed excellent selectivity, stability and repeatability. Furthermore, the detection of various miRNAs can be realized by changing the relevant base sequences in the constructed PEC biosensor. It also provides a powerful strategy for early clinical diagnosis and biomedical research. [Display omitted] • PbS QDs/Co 3 O 4 polyhedra was fabricated as the effective quencher for PEC signal. • The cis- and trans-dual cleavage of CRISPR/Cas12a improved the sensitivity. • RCA-assisted "off-on-super on" PEC biosensor realized detection of miRNA-21. [ABSTRACT FROM AUTHOR]

For a vertex x $x$ of a digraph, d+(x) ${d}^{+}(x)$ (d−(x) ${d}^{-}(x)$, respectively) is the number of vertices at distance 1 from (to, respectively) x $x$ and d++(x) ${d}^{++}(x)$ is the number of vertices at distance 2 from x $x$. In 1995, Seymour conjectured that for any oriented graph D $D$ there exists a vertex x $x$ such that d+(x)≤d++(x) ${d}^{+}(x)\le {d}^{++}(x)$. In 2006, Sullivan conjectured that there exists a vertex x $x$ in D $D$ such that d−(x)≤d++(x) ${d}^{-}(x)\le {d}^{++}(x)$. We give a sufficient condition in terms of the number of transitive triangles for an oriented graph to satisfy Sullivan's conjecture. In particular, this implies that Sullivan's conjecture holds for all orientations of planar graphs and triangle‐free graphs. An oriented graph D $D$ is an oriented split graph if the vertices of D $D$ can be partitioned into vertex sets X $X$ and Y $Y$ such that X $X$ is an independent set and Y $Y$ induces a tournament. We also show that the two conjectures hold for some families of oriented split graphs, in particular, when Y $Y$ induces a regular or an almost regular tournament. [ABSTRACT FROM AUTHOR]

Based on the density functional theory, the stereoselectivity of the asymmetric synthesis of tetrahydroisoquinolinopyrazole derivatives by the cycloaddition reaction of C, N‐cyclic azomethine imines with allyl alkyl ketones which was catalyzed using a chiral primary amine is studied theoretically. The results demonstrate that the four chiral transition states (TS‐1R2R, TS‐1R2S, TS‐1S2R and TS‐1S2S) are formed by the reaction of dienamine intermediate with C, N‐cyclic azomethine imine, and the reaction barrier of TS‐1R2S is in the lowest level (ΔG=6.98 kcal/mol). The consequence reveal that the 1R2S configuration product is formed by TS‐1R2S transition state. Non‐covalent interaction and electron density topology analysis show that the stereoselectivity of the chiral product is determined through van der Waals forces and hydrogen bond interaction of the transition state molecules. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) is a rare but severe disease with high morbidity and mortality. Cardiac surgery plays a major role in the contemporary clinical management of IE patients. During cardiac surgery, cardiopulmonary bypass significantly contributes to an increased risk of organ dysfunction and mortality by inducing an acute inflammatory response, vascular endothelial cell injury, impairment of the coagulation cascade, and ischemia–reperfusion injury. During the past decade, the use of extracorporeal hemoadsorption therapy with the CytoSorb® hemoadsorber (CytoSorbents Europe GmbH, Berlin, Germany) has been proposed as an adjuvant therapy to mediate inflammatory responses in IE patients undergoing cardiac surgery with cardiopulmonary bypass. However, there is currently no systematic evaluation of the effect of CytoSorb® hemoadsorption on clinical outcomes such as hemodynamics, organ dysfunction, and mortality in patients with IE. Therefore, in this review, we exclusively discuss contemporary findings concerning the rationale, clinical evidence, and future perspectives for CytoSorb® hemoadsorption therapy in IE patients. [ABSTRACT FROM AUTHOR]

A CRISPR/Cas12a electrochemiluminescence (ECL) biosensor based on the multiple sites DNA walker with controlled swing arm position, integrating Tribulus terrestris-like AuCu nanoterrestris (AuCu NTs) and DNA tetrahedral nanostructures (DTNs) is constructed for ultrasensitive detection of miRNA-21. The AuCu NTs was served as a co-reaction accelerant to promote the reduction of S 2 O 8 2- at the cathode, which can be rapidly converted with S 2 O 8 3•- and significantly enhance the ECL signal from graphitic carbon nitride nanosheets. Meanwhile, by virtue of the excellent stability of DNA tetrahedral nanostructure, the binding efficiency between single strand DNA and luminescent materials was improved. Afterward, DNA walker signal amplifier converted and amplified the target miRNA-21 into transitional DNA under the activity of Nt. Bsm AI nicking endonuclease, thereby activating trans-cleavage ability of CRISPR/Cas12a and achieving the efficient annihilation of ECL signals was employed. As a proof of concept, the as-constructed biosensor demonstrated well specificity and sensitivity towards miRNA-21 with the range of 1.0 fM to 10 nM and the detection limit was 0.339 fM (S/N = 3). Therefore, the proposed strategy expanded the scope of application of CRISPR/Cas12a and demonstrated potential of diagnostic analysis. • AuCu nanoterrestris as the co-reaction accelerator were constructed to improve electron transfer efficiency. • The DNA Tetrahedron Nanostructures were utilized to enhance the stability of electrochemical system. • DNA walker-mediated CRISPR/Cas12a system improved the selectivity and sensitivity of the ECL biosensor. [ABSTRACT FROM AUTHOR]

Background: CD56 has been observed in malignant tumours exhibiting neuronal or neuroendocrine differentiation, such as breast cancer, small-cell lung cancer, and neuroblastoma. Abnormal glycosylation modifications are thought to play a role in regulating tumour cell proliferation, migration, and invasion. Nevertheless, the exact roles and molecular mechanisms of CD56 and polysialylated CD56 (PSA-CD56) in the development and progression of clear cell renal cell carcinoma (ccRCC) remain elusive. Here we unveil the biological significance of CD56 and PSA-CD56 in ccRCC. Methods: In this study, we employed various techniques, including immunohistochemistry (IHC), RT-qPCR, and western blot, to examine the mRNA and protein expression levels in both human ccRCC tissue and cell lines. Lentivirus infection and CRISPR/Cas9 system were utilized to generate overexpression and knockout cell lines of CD56. Additionally, we conducted several functional assays, such as CCK-8, colony formation, cell scratch, and transwell assays to evaluate cell growth, proliferation, migration, and invasion. Furthermore, we established a xenograft tumor model to investigate the role of CD56 in ccRCC in vivo. To gain further insights into the molecular mechanisms associated with CD56, we employed the Hedgehog inhibitor JK184 and the β-catenin inhibitor Prodigiosin. Results: CD56 was significantly overexpressed in both human ccRCC tissues and renal cancer cell lines compared to adjacent normal tissues and normal renal epithelial cells. In vitro and in vivo experiments revealed that the knockout of CD56 inhibited the proliferation, migration, and invasion capabilities of ccRCC cells, whereas the overexpression of PSA-CD56 promoted these capacities. Finally, PSA-CD56 overexpression was found to activate both the Hedgehog and Wnt/β-catenin signaling pathways. Conclusion: Our findings demonstrate that the oncogenic function of CD56 polysialylation plays a vital role in the tumorigenesis and progression of ccRCC, implying that targeting PSA-CD56 might be a feasible treatment target for ccRCC. [ABSTRACT FROM AUTHOR]

Among many topological indices of trees the sum of distances σ (T) and the number of subtrees F (T) have been a long standing pair of graph invariants that are well known for their negative correlation. That is, among various given classes of trees, the extremal structures maximizing one usually minimize the other, and vice versa. By introducing the "local" versions of these invariants, σ T (v) for the sum of distance from v to all other vertices and F T (v) for the number of subtrees containing v , extremal problems can be raised and studied for vertices within a tree. This leads to the concept of "middle parts" of a tree with respect to different indices. A challenging problem is to find extremal values of the ratios between graph indices and corresponding local functions at middle parts or leaves. This problem also provides new opportunities to further verify the the correlation between different indices such as σ (T) and F (T). Such extremal ratios, along with the extremal structures, were studied and compared for the distance and subtree problems for general trees (Barefoot, 1997; Székely and Wang, 2013, 2014). In this paper, this study is extended to binary trees, a class of trees with numerous practical applications in which the extremal ratio problems appear to be even more complicated. After justifying some basic properties on the distance and subtree problems in trees and binary trees, characterizations are provided for the extremal structures achieving two extremal ratios in binary trees of given order. The generalization of this work to k -ary trees is also briefly discussed. The findings are compared with the previous established extremal structures in general trees. Lastly some potential future work is mentioned. [ABSTRACT FROM AUTHOR]

With the rapid development of edge computing and the Internet of Things, the problem of information resource sharing can be effectively solved through multi-party collaboration, but the risk of data leakage is also increasing. To address the above issues, we propose an efficient multi-party private set intersection (MPSI) protocol via a multi-point oblivious pseudorandom function (OPRF). Then, we apply it to work on a specific commercial application: edge caching. The proposed MPSI uses oblivious transfer (OT) together with a probe-and-XOR of strings (PaXoS) as the main building blocks. It not only provides one-sided malicious security, but also achieves a better balance between communication and computational overhead. From the communication pattern perspective, the client only needs to perform OT with the leader and send a data structure PaXoS to the designated party, making the protocol extremely efficient. Moreover, in the setting of edge caching, many parties hold a set of items containing an identity and its associated value. All parties can identify a set of the most frequently accessed common items without revealing the underlying data. [ABSTRACT FROM AUTHOR]

The sum of distances between all pairs of vertices (denoted by σ (⋅) and called the Wiener index) and the number of subtrees (denoted by F (⋅) and called the subtree index) of a graph G are two representative graph invariants that have been extensively studied. The "local" version of these graph invariants (i.e. sum of distances from a given vertex, called the distance of the vertex, and the number of subtrees containing such a vertex, called the local subtree index of the vertex) have been studied. The distance of a vertex v in a tree T , denoted by σ T (v) , attains its minimum at one or two adjacent vertices called the centroid while the maximum σ T (v) occurs at one or more leaves. On the other hand, the local subtree index, denoted by F T (v) , attains its maximum at one or two adjacent vertices called the subtree core and the minimum F T (v) occurs at one ore more leaves. In this paper we study the difference between the values of σ T (v) at a centroid vertex and a leaf, called the σ -span, and similarly the F -span for the difference in values of the local subtree index at the subtree core and at a leaf. Among trees and full binary trees (trees in which each vertex has degree 1 or 3) on a given number of vertices we study the maximum and minimum possible values of the σ -span and F -span. The extremal structures corresponding to some of these extremal values are also presented. Some unsolved problems are also discussed and proposed as open questions. [ABSTRACT FROM AUTHOR]

A path P in an edge-colored graph G is called a proper path if no two adjacent edges of P are colored the same, and G is proper connected if every two vertices of G are connected by a proper path in G. The proper connection number of a connected graph G, denoted by pc(G), is the minimum number of colors that are needed to make G proper connected. In this paper, we investigate the proper connection number of the complement of a graph G according to some constraints of G itself. Also, we characterize the graphs on n vertices that have proper connection number n-2. Using this result, we give a Nordhaus-Gaddum-type theorem for the proper connection number. We prove that if G and G¯ are both connected, then 4≤pc(G)+pc(G¯)≤n, and the upper bound holds if and only if G or G¯ is the n-vertex tree with maximum degree n-2. [ABSTRACT FROM AUTHOR]

In this paper, we consider a risk model with two-sided jumps and proportional investment. The upward jumps and downward jumps represent gains and claims, respectively. Suppose the company invests all of its surplus in a certain proportion in two types of investments, one is risk-free (such as bank accounts) and the other is risky (such as stocks). Our aim is to find the optimal admissible strategy (including the optimal dividend rate and the optimal ratio of investment in risky assets), to maximize the dividend value function, and discuss the effects of a number of parameters on dividend payments. Firstly, the HJB equation of the dividend value function is obtained by the stochastic analysis theory and the dynamic programming method, and the optimal admissible strategy is obtained. Since the integro-differential equation satisfied by the dividend value function is difficult to solve, we turn to the sinc numerical method to approximate solve it. Then, the error between the exact solution (ES) and the sinc approximate solution (SA) is analyzed. Finally, the relative error of a special numerical solution and an ES is given, and some examples of sensitivity analysis are discussed. This study provides a theoretical basis for insurance companies to prevent risks better. [ABSTRACT FROM AUTHOR]

Living erythrocyte (red blood cell, RBC) membranes present rich ultrastructural and dynamic details, which require synchronous super‐resolution imaging and single‐molecule tracking to be revealed. Yet, it poses a serious challenge to achieve these dual functions in a single probe, due to the rigid and conflicting photophysical demands of the different techniques. Herein, we rationally developed a far‐red boron dipyrromethene membrane probe with blinking capability and persistent single‐molecule emission, and constructed a microfluidic platform for noninvasive trapping and long‐term imaging of RBCs. By combining them, multi‐dimensional super‐resolution reconstructions and single‐molecule tracking were achieved at the molecular scale on living human RBC membranes in a high‐throughput manner. Our integrated system defines a quantitative method for analyzing RBC membranes under physiological and pathological conditions, improving precision and revealing new perspectives for future disease diagnostics. [ABSTRACT FROM AUTHOR]

Living erythrocyte (red blood cell, RBC) membranes present rich ultrastructural and dynamic details, which require synchronous super‐resolution imaging and single‐molecule tracking to be revealed. Yet, it poses a serious challenge to achieve these dual functions in a single probe, due to the rigid and conflicting photophysical demands of the different techniques. Herein, we rationally developed a far‐red boron dipyrromethene membrane probe with blinking capability and persistent single‐molecule emission, and constructed a microfluidic platform for noninvasive trapping and long‐term imaging of RBCs. By combining them, multi‐dimensional super‐resolution reconstructions and single‐molecule tracking were achieved at the molecular scale on living human RBC membranes in a high‐throughput manner. Our integrated system defines a quantitative method for analyzing RBC membranes under physiological and pathological conditions, improving precision and revealing new perspectives for future disease diagnostics. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN), also known as the F-2 toxin, is a common contaminant in cereal crops and livestock products. This experiment aimed to reveal the changes in the proteomics of ZEN-induced intestinal damage in weaned piglets by tandem mass spectrometry tags. Sixteen weaned piglets either received a basal diet or a basal diet supplemented with 3.0 mg/kg ZEN in a 32 d study. The results showed that the serum levels of ZEN, α-zearalenol, and β-zearalenol were increased in weaned piglets exposed to ZEN (p < 0.05). Zearalenone exposure reduced apparent nutrient digestibility, increased intestinal permeability, and caused intestinal damage in weaned piglets. Meanwhile, a total of 174 differential proteins (DEPs) were identified between control and ZEN groups, with 60 up-regulated DEPs and 114 down-regulated DEPs (FC > 1.20 or <0.83, p < 0.05). Gene ontology analysis revealed that DEPs were mainly involved in substance transport and metabolism, gene expression, inflammatory, and oxidative stress. The Kyoto Encyclopedia of Genes and Genomes analysis revealed that DEPs were significantly enriched in 25 signaling pathways (p < 0.05), most of which were related to inflammation and amino acid metabolism. Our study provides valuable clues to elucidate the possible mechanism of ZEN-induced intestinal injury. [ABSTRACT FROM AUTHOR]