Heterogeneity of neutrophils in cancer:one size does not fit all

Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells are at the forefront of immune responses,and have gained attention in recent years because of their presence in tumor sites.Neutrophil involvement pertains to tumor cells'ability to construct a suitable tumor microenvironment(TME)that accelerates their own growth and malignancy,by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems,thereby influencing tumor development and progression.Studies have indicated both pro-and anti-tumor properties of infiltrating neutrophils.The TME can exploit neutrophil function,recruitment,and even production,thus resulting in pro-tumor properties of neutrophils,including promotion of genetic instability,tumor cell proliferation,angiogenesis and suppression of anti-tumor or inflammatory response.In contrast,neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions via crosstalk with T cells.Here,we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions,including neutrophil phenotype and function,in cancer biology.

Non-seismic geophysical analysis of potential geothermal resources in the Longgang Block,Northeast China

Although geothermal energy has many clear advantages,including its sustainability and environmentally friendly nature,research into potential geothermal resources across the Longgang Block,Northeast China,has been limited.Here we present the first analysis of the potential geothermal resources in this region that employs joint geological and non-seismic geophysical methods to identify target areas that may be economically viable.We acquire and analyze high-precision gravity,magnetic,and magnetotelluric sounding data,which are constrained using the petrophysical parameters of outcropping rocks across the Longgang Block,to conduct a comprehensive evaluation of the region’s deep geological structures and their geothermal resources potential,with a focus on identifying faults,rock masses,and thermal storage structures.We find that Archean granitic gneiss and Mesozoic rock masses in the deeper section of the Longgang Block possess weak gravity anomalies and high resistivities.We also identify thermal storage structures near these deeper geological units based on their extremely low resistivities.The data are used to infer the dip and depth of known or hidden faults,to constrain the spatial distribution of intrusive rock masses,and to determine the spatial distribution of subsurface thermal storage structures.The potential of the target areas for geothermal resources exploitation is divided into three grades based on contact depths between faults and thermal storage structures,and the scale of their thermal storage structures.Our results suggest that a joint non-seismic geophysical approach can be effective in locating and evaluating geothermal resources in complex geological settings.

Cloning and Bioinformatics Analysis of tye A Gene of Vibrio alginolyticus

[Objectives]This study aimed to clone the tye A gene of Vibrio alginolyticus HY9901 strain and analyze its sequence by bioinformatics.[Methods] By referring to the entire genome sequence of Ⅴ.alginolyticus on Gen Bank,specific primers were designed.According to the principle of PCR amplification,the target gene tye A was amplified.By means of bioinformatics,the sequence of tye A was further analyzed,and the phylogenetic tree of tye A genes of Vibrio spp.and the corresponding subunit three-dimensional structure models were constructed.[Results] The length of the tye A gene of Ⅴ.alginolyticus strain HY9901 is 285 bp,and its theoretical molecular weight is 10.98 kD.According to prediction,there is no signal peptide or transmembrane region at the N-terminus of the sequence,and the amino acid sequence contains two casein kinase Ⅱ phosphorylation sites.The results of protein subcellular localization prediction show that the Tye A protein is located in the cell membrane.The protein is unstable and non-hydrophilic.The tertiary structure of Tye A protein of Ⅴ.alginolyticus is similar to that of Yersinia sp.According to prediction,Tye A has a major functional domain Pfam.In terms of secondary structure,alpha helix,random coil,extended strand and beta turn account for 85.11%,7.45%,4.26% and 3.19%,respectively.The homology of Tye A between Ⅴ.alginolyticus and Vibrio parahaemolyticus is up to 83%,so they are classified into one cluster.[Conclusions]This study will help to further understand the regulation mechanism of type Ⅲ secretion system in Ⅴ.alginolyticus.

Multiple factors interact in editing of PPR-E+-targeted sites in maize mitochondria and plastids

RNA cytidine-to-uridine editing is essential for plant organellar gene expression.Pentatricopeptide repeat(PPR)-E+proteins have been proposed to bind to target sites and recruit the cytidine deaminase AtDYW2,facilitated by AtNUWA.Here we analyze the function of ZmNUWA,ZmDYW2A,and ZmDYW2B and their re-lationships with other editing factors in maize.The zmdyw2a and zmdyw2b single mutants are normal,but the zmdyw2a::zmdyw2b and zmnuwa mutants are severely arrested in seed development.ZmNUWA,ZmDYW2A,and ZmDYW2B are dual localized in mitochondria and plastids.Loss of ZmNUWA decreases the editing at 99 mitochondrial sites and 8 plastid sites.Surprisingly,loss of ZmDYW2A:ZmDYW2B affects almost the same set of sites targeted by PPR-E+proteins.ZmNUWA interacts with ZmDYW2A and ZmDYW2B,suggesting that ZmNUWA recruits ZmDYW2A/2B in the editing of PPR-E+-targeted sites in maize.Further protein interaction analyses show that ZmNUWA and ZmDYW2A/2B interact with ZmMORF1,ZmMORF8,ZmMORF2,and ZmMORF9 and that ZmOZ1 interacts with ZmORRM1,ZmDYW2A,ZmDYW2B,ZmMORF8,and ZmMORF9.These results suggest that the maize mitochondrial PPR-E+editosome contains PPR-E+,ZmDYW2A/2B,ZmNUWA,and ZmMORF1/8,whereas the plastid PPR-E+editosome is composed of PPR-E+,ZmDYW2A/2B,ZmNUWA,ZmMORF2/8/9,ZmORRM1,and ZmOZ1.

The DEAD-box RNA helicase ZmRH48 is required for the splicing of multiple mitochondrial introns,mitochondrial complex biosynthesis,and seed development in maize

RNA helicases participate in nearly all aspects of RNA metabolism by rearranging RNAs or RNA–protein complexes in an adenosine triphosphatedependent manner.Due to the large RNA helicase families in plants,the precise roles of many RNA helicases in plant physiology and development remain to be clarified.Here,we show that mutations in maize(Zea mays)DEAD-box RNA helicase48(Zm RH48)impair the splicing of mitochondrial introns,mitochondrial complex biosynthesis,and seed development.Loss of Zm RH48 function severely arrested embryogenesis and endosperm development,leading to defective kernel formation.Zm RH48 is targeted to mitochondria,where its deficiency dramatically reduced the splicing efficiency of five cis-introns(nad5 intron 1;nad7 introns 1,2,and 3;and ccm Fc intron 1)and one trans-intron(nad2 intron 2),leading to lower levels of mitochondrial complexes I andⅢ.Zm RH48 interacts with two unique pentatricopeptide repeat(PPR)proteins,PPR-SMR1 and SPR2,which are required for the splicing of over half of all mitochondrial introns.PPR-SMR1 interacts with SPR2,and both proteins interact with P-type PPR proteins and Zm-m CSF1 to facilitate intron splicing.These results suggest that Zm RH48 is likely a component of a splicing complex and is critical for mitochondrial complex biosynthesis and seed development.

A systematic survey of LU domain-containing proteins reveals a novel human gene,LY6A,which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

The Ly-6 and uPAR(LU)domain-containing proteins represent a large family of cell-surface markers.In particular,mouse Ly-6A/Sca-1 is a widely used marker for various stem cells;however,its human ortholog is missing.In this study,based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins,we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1.This gene,hereby named LY6A,reversely overlaps with a lncRNA gene in the majority of exonic sequences.We found that LY6A is aberrantly expressed in pituitary tumors,but not in normal pituitary tissues,and may contribute to tumorigenesis.Similar to mouse Ly-6A/Sca-1,human LY6A is also upregulated by interferon,suggesting a conserved transcriptional regulatory mechanism between humans and mice.We cloned the full-length LY6A cDNA,whose encoded protein sequence,domain architecture,and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1.Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane.Collectively,these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

The squeeze flow of a bi-viscosity fluid between two rigid spheres with wall slip

In this paper,the squeeze flow between two rigid spheres with a bi-viscosity fluid is examined.Based on lubrication theory,the squeeze force is calculated by deriving the pressure and velocity expressions.The results of the normal squeeze force are discussed,and fitting functions of the squeeze and correction coefficients are given.The squeeze force between the rigid spheres increases linearly or logarithmically with the velocity when most or part of the boundary fluid reaches the yield state,respectively.Furthermore,the slip correction coefficient decreases with the increase in the velocity.The investigation may contribute to the further study of bi-viscosity fluids between rigid spheres with wall slip.

An unbalanced PD-L1/CD86 ratio in CD14^＋＋CD16^＋ monocytes is correlated with HCV viremia during chronic HCV infection

Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus （HCV） infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets--CD14^＋＋CD16^-, CD14^＋＋CD16^＋ and CD14^＋＋mCD16^——in chronic HCV-infected patients, HCV spontaneous resolvers and healthy controls, and we evaluated the possible link between HCV viremia and disease progression. Our results indicated that the frequency of the CD 14^＋＋CD 16^＋ monocyte subset was decreased, and negatively correlated with HCV RNA and core antigen levels during chronic HCV infection. PD-L1 expression and the PD-L1/CD86 ratio in CD14^＋＋CD16^＋ monocytes were higher during chronic HCV infection than in spontaneous HCV resolvers and healthy controls. The PD-L1/CD86 ratio positively correlated with HCV viral load and core antigen levels. Finally, PD-L1 was significantly increased, while cytokine secretions were dramatically decreased upon Toll-like receptor （TLR） ligand binding and HCV JFH-lstimulation. These findings indicates the compromised immune status of the CD14^＋＋CD16^＋ monocytes during chronic HCV infection and provides new insights into the specific role of the CD14^＋＋CD16^＋ monocytes and their significance in chronic HCV infection.

Plane Analysis for an Inclusion in ID Hexagonal Quasicrys tai Using the Hyp er singular Integral Equation Method

A model of a thin elastic inclusion embedded in an infinite ID hexagonal quasicrystal is discussed. The atomic arrangements of the matrix and the inclusion are both periodic along the xi-direction and quasiperiodic along the a;2-direction in the oxiX2-coordinate system. Using the hypersingular integral equation method, the inclusion problem is reduced to solving a set of hypersingular integral equations. Based on the exact analytical solution of the singular phonon and phason stresses near the inclusion front, a numerical method of the hypersingular integral equation is proposed using the finite-part integral method. Finally, the numerical solutions for the phonon and phason stress intensity factors of some examples are given.

Comparative tribological behavior of friction composites containing natural graphite and expanded graphite

In this study, expanded graphite and natural graphite were introduced into resin-based friction materials, and the tribological behavior of the composites was investigated. The tribo-performance of the two friction composites was evaluated using a constant speed friction tester. The results showed that the expanded graphite composite (EGC) displayed better lubricity in both the fading and the recovery processes. The wear rate of the EGC decreased by 22.43%more than that of the natural graphite composite (NGC). In the fading process, and the EGC enhanced the stability of the coefficient of friction. The recovery maintenance rate of the NGC was 4.66% higher than that of the EGC. It can be concluded that expanded graphite plays an important role in the formation of a stable contact plateau and can effectively reduce the wear.

A New Method of Portfolio Optimization Under Cumulative Prospect Theory

In this paper, the portfolio selection problem under Cumulative Prospect Theory （CPT） is investigated and a model of portfolio optimization is presented. This model is solved by coupling scenario generation techniques with a genetic algorithm. Moreover, an Adaptive Real-Coded Genetic Algorithm （ARCGA） is developed to find the optimal solution for the proposed model. Computational results show that the proposed method solves the portfolio selection model and that ARCGA is an effective and stable algorithm. We compare the portfolio choices of CPT investors based on various bootstrap techniques for scenario generation and empirically examine the effect of reference points on investment behavior.

Hexyl substitution of pentathienoacene toward a significant improvement in charge transport

A novel semiconductor, dihexyl-substituted pentathienoacene(C6-PTA) is designed and synthesized in five steps with the total yield up to 25.2%. The introduction of hexyl chains endow the thin film semiconductor with about threefold increase in carrier mobility and one to three orders of magnitude improvement in current on/off ratio. Furthermore, single crystal FETs based on C6-PTA exhibited mobility up to 0.64 cm^2 V^(-1) s^(-1), which is over 50 times higher than the thin film counterpart. The results indicate clearly that C6-PTA is a promising organic semiconductor with high stability.