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Valvular heart disease (VHD) is a significant public health threat, with heart valve replacement surgery being the standard treatment for severe cases. Despite of advancements in artificial heart valves, their longevity remains limited due to in vivo degeneration. In consequence, there is an urgent need for effective methods to enhance the durability of artificial heart valves. Because oxidative stress (OS) is a key driving factor contributing to the failure of cardiovascular implants, this review focuses on how OS plays a critical role in heart valve degeneration, and its relationship with four major physiological mechanisms: extracellular matrix (ECM) degradation, immune response, thrombosis and lipid metabolism. By highlighting OS as a potential therapeutic target, we explore surface modification strategies that incorporate these fundamental mechanisms, refer to passive approaches including OS elimination, immunosuppression, blocking surface-degradation active groups, and anticoagulation, and active approaches such as regulating biological function recovery, and surface endothelial remodeling. These strategies aim to delay or reverse artificial valves degeneration via combining with the perspective of OS regulation, ultimately extending the prognosis period after heart valve replacement surgeries.

Lithium cobalt oxide (LiCoO2) is an irreplaceable cathode material for lithium‐ion batteries with high volumetric energy density. The prevailing O3 phase LiCoO2 adopts the ABCABC (A, B, and C stand for lattice sites in the close‐packed plane) stacking modes of close‐packed oxygen atoms. Currently, the focus of LiCoO2 development is application at high voltage (>4.55 V versus Li+/Li) to achieve a high specific capacity (>190 mAh g−1). However, cycled with a high cutoff voltage, O3–LiCoO2 suffers from rapid capacity decay. The causes of failure are mostly attributed to the irreversible transitions to H1‐3/O1 phase after deep delithiation and severe interfacial reactions with electrolytes. In addition to O3, LiCoO2 is also known to crystalize in an O2 phase with ABAC stacking. Since its discovery, little is known about the high‐voltage behavior of O2–LiCoO2. Herein, through systematic comparison between electrochemical performances of O3 and O2 LiCoO2 at high voltage, the significantly better stability of O2–LiCoO2 (>4.5 V) than that of O3–LiCoO2 in the same micro‐sized particle morphology is revealed. Combining various characterization techniques and multiscale simulation, the outstanding high‐voltage stability of O2–LiCoO2 is attributed to the high Li diffusivity and ideal mechanical properties. Uniform Li+ distribution and balanced internal stress loading may hold the key to improving the high‐voltage performance of LiCoO2.

Abstract All-solid-state lithium batteries have attracted widespread attention for next-generation energy storage, potentially providing enhanced safety and cycling stability. The performance of such batteries relies on solid electrolyte materials; hence many structures/phases are being investigated with increasing compositional complexity. Among the various solid electrolytes, lithium halides show promising ionic conductivity and cathode compatibility, however, there are no effective guidelines when moving toward complex compositions that go beyond ab-initio modeling. Here, we show that ionic potential, the ratio of charge number and ion radius, can effectively capture the key interactions within halide materials, making it possible to guide the design of the representative crystal structures. This is demonstrated by the preparation of a family of complex layered halides that combine an enhanced conductivity with a favorable isometric morphology, induced by the high configurational entropy. This work provides insights into the characteristics of complex halide phases and presents a methodology for designing solid materials.

Abstract Reversible lattice oxygen redox reactions offer the potential to enhance energy density and lower battery cathode costs. However, their widespread adoption faces obstacles like substantial voltage hysteresis and poor stability. The current research addresses these challenges by achieving a non-hysteresis, long-term stable oxygen redox reaction in the P3-type Na2/3Cu1/3Mn2/3O2. Here we show this is accomplished by forming spin singlet states during charge and discharge. Detailed analysis, including in-situ X-ray diffraction, shows highly reversible structural changes during cycling. In addition, local CuO6 Jahn-Teller distortions persist throughout, with dynamic Cu-O bond length variations. In-situ hard X-ray absorption and ex-situ soft X-ray absorption study, along with density function theory calculations, reveal two distinct charge compensation mechanisms at approximately 3.66 V and 3.99 V plateaus. Notably, we observe a Zhang-Rice-like singlet state during 3.99 V charging, offering an alternative charge compensation mechanism to stabilize the active oxygen redox reaction.

Abstract Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor‐specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix‐loop‐helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation‐seq, RNA‐seq, and high‐throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element‐binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40‐SREBF1‐stearoyl‐CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40‐mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa.

Abstract Background Tumor cells exhibited phenotypic and molecular characteristics similar to their lineage progenitor cells. Liver developmental signaling pathways are showed to be associated with HCC development and oncogenesis. The similarities of expression profiling between liver progenitors (LPs) and HCC suggest that understanding the molecular mechanism during liver development could provide insights into HCC. Methods To profile the dynamic gene expression during liver development, cells from an in vitro liver differentiation model and two paired hepatocellular carcinoma (HCC) samples were analyzed using deep RNA sequencing. The expression levels of selected genes were analyzed by qRT-PCR. Moreover, the role of a key transcription factor, pituitary homeobox 2 (PITX2), was characterized via in vitro and vivo functional assays. Furthermore, molecular mechanism studies were performed to unveil how PITX2C regulate the key developmental factors in LPs, thereby increasing the stemness of HCC. Results PITX2 was found to exhibit a similar expression pattern to specific markers of LPs. PITX2 consists of three isoforms (PITX2A/B/C). The expression of PITX2 is associated with tumor size and overall survival rate, whereas only PITX2C expression is associated with AFP and differentiation in clinical patients. PITX2A/B/C has distinct functions in HCC tumorigenicity. PITX2C promotes HCC metastasis, self-renewal and chemoresistance. Molecular mechanism studies showed that PITX2C could up-regulate RALYL which could enhance HCC stemness via the TGF-β pathway. Furthermore, ChIP assays confirmed the role of PITX2C in regulating key developmental factors in LP. Conclusion PITX2C is a newly discovered transcription factor involved in hepatic differentiation and could increase HCC stemness by upregulating key transcriptional factors related to liver development.

Acetylation and tri-methylation of histone H3 lysine 9 (H3K9ac and H3K9me3) play an interactive regulatory role in the epigenetic regulation of gene expression during heart development and cardiovascular disease, but little is known about their possible role in heart regeneration. Here we utilized genome-wide high-throughput RNA sequencing (RNA-seq) and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) for H3K9ac and H3K9me3, carried out on regenerative cardiac tissues at different days post amputation in zebrafish (Danio rerio) to investigate dynamic changes in gene expression and the epigenetic landscape of H3K9ac and H3K9me3. The STAR, Bowtie2, MACS2, and deepTools2 were mainly used for RNA-Seq or ChIP-seq data analysis. In this article, we present detailed information on experiment design, data generation, quality assessment and processing pipeline. Raw reads of the RNA-seq and ChIP-seq data have been deposited at the NCBI GEO repository with the accession number GSE158104. Our data will be a valuable resource for the elucidation of H3K9ac and H3K9me3 involvement in the regulation of gene transcription during cardiac regeneration.

Abstract Background DNA methylation alteration is frequently observed in Lung adenocarcinoma (LUAD) and may play important roles in carcinogenesis, diagnosis, and prognosis. Thus, this study aimed to construct a reliable methylation-based nomogram, guiding prognostic classification screening and personalized medicine for LUAD patients. Method The DNA methylation data, gene expression data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) database. Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were obtained and then calculated correlation by pearson correlation coefficient. Functional enrichment analysis and Protein-protein interaction network were used to explore the biological roles of aberrant methylation genes. A prognostic risk score model was constructed using univariate Cox and LASSO analysis and was assessed in an independent cohort. A methylation-based nomogram that included the risk score and the clinical risk factors was developed, which was evaluated by concordance index and calibration curves. Result We identified a total of 1362 DMSs corresponding to 471 DEGs with significant negative correlation, including 752 hypermethylation sites and 610 hypomethylation sites. Univariate cox regression analysis showed that 59 DMSs were significantly associated with overall survival. Using LASSO method, we constructed a three-DMSs signature that was independent predictive of prognosis in the training cohort. Patients in high-risk group had a significant shorter overall survival than patients in low-risk group classified by three-DMSs signature (log-rank p = 1.9E-04). Multivariate cox regression analysis proved that the three-DMSs signature was an independent prognostic factor for LUAD in TCGA-LUAD cohort (HR = 2.29, 95%CI: 1.47–3.57, P = 2.36E-04) and GSE56044 cohort (HR = 2.16, 95%CI: 1.19–3.91, P = 0.011). Furthermore, a nomogram, combining the risk score with clinical risk factors, was developed with C-indexes of 0.71 and 0.70 in TCGA-LUAD and GSE56044 respectively. Conclusions The present study established a robust three-DMSs signature for the prediction of overall survival and further developed a nomogram that could be a clinically available guide for personalized treatment of LUAD patients.

Background: Doxorubicin resistance remains a major therapeutic challenge leading to poor survival prognosis and treatment failure in breast cancer. Although doxorubicin induces massive changes in the transcriptional landscape are well known, potential diagnostic or therapeutic targets associated with the reorganization of three-dimensional (3D) chromatin architecture have not yet been systematically investigated.Methods: Here we performed in situ high-throughput chromosome conformation capture (Hi-C) on parental and doxorubicin-resistant MCF7 (MCF7-DR) human breast cancer cells, followed by integrative analysis of HiC, ATAC-seq, RNA-seq and TCGA data.Results: It revealed that A/B compartment switching was positively correlated to genome-wide differential gene expression. The genome of MCF7-DR cells was spatially reorganized into smaller topologically associating domains (TADs) and chromatin loops. We also revealed the contribution of increased chromatin accessibility and potential transcription factor families, including CTCF, AP-1 and bHLH, to gained TADs or loops. Intriguingly, we observed two condensed genomic regions (∼20 kb) with decreased chromatin accessibility flanking TAD boundaries, which might play a critical role in the formation or maintenance of TADs. Finally, combining data from TCGA, we identified a number of gained and lost enhancer-promoter interactions and their corresponding differentially expressed genes involved in chromatin organization and breast cancer signaling pathways, including FA2H, FOXA1 and JRKL, which might serve as potential treatment targets for breast cancer.Conclusion: These data uncovered a close connection between 3D genome reorganization, chromatin accessibility as well as gene transcription and provide novel insights into the epigenomic mechanisms involving doxorubicin resistance in breast cancer.

Lithium-rich layered material deserves in-depth understanding because it has large capacity enabled by both cation and anion activities. Here, authors apply 3D spectro-tomography with nano resolution to reveal the multi-layer morphology and depth-dependent transition metal valence distribution associated with oxygen redox.

Abstract The aging of population has resulted in a significant increase in the prevalence of rheumatoid arthritis (RA), which is a persistent and recurrent synovial inflammation caused by abnormal immune activation. Herein, the authors designed an inflammation‐triggered disassembly (ITD) nanoplatform by a supramolecular assembly method, which controls the decomposition and drug release through changes in cytokine concentrations and redox potentials during the onset of arthritis, and its dual‐targeted synergistic effect on collagen‐induced arthritis (CIA) rats resulted in higher cell death rate and immunosuppressive rate. Meanwhile, they propose the local dynamic dependent imaging (LDDI) technology to diagnose the disease status, which may produce corresponding changes with the fluctuation of inflammatory activity and improve the accuracy of dual‐target therapy by monitoring the synovial changes through in situ photoactivation of the second near infrared light (NIR‐II). Very importantly, histological analysis shows that ITD strategy relieved joint destruction and cartilage degeneration and its clinical score is similar to that of the healthy group. Their work provides an effective strategy for the early diagnosis and treatment of acute and chronic inflammation diseases, which can interfere to abnormal immune activation, rather than affecting the normal function of immune system.

Abstract A method is proposed that uses the metal casing of an oil and gas production well to construct a long dipole emission line source and applies pseudorandom multifrequency excitation signals to it to identify reservoir characteristics of interwell reservoirs. This method can significantly improve the work efficiency and precision of electrical prospecting. The cross‐well pseudorandom response signal contains multiple main frequency components, as well as various measuring frequency points. Targeting the frequency components with different amplitudes and initial phases in the pseudorandom signal, the digital coherent detection method and its noise resistance are studied. Using this method can effectively extract the amplitude and phase information of each frequency component in different noise environments and has a strong ability to suppress signals of other frequencies. In the heterogeneous interwell reservoir detection model, the amplitude characteristics of each frequency component of the pseudorandom electromagnetic response at the measuring line with different well spacings are extracted. Numerical results show that the curve of equal‐frequency measurement appears downwardly "concave" at the interface of the low‐resistivity interlayer, and upwardly "convex" at the interface of the high‐resistivity interlayer. With the increase in the resistivity of the low‐resistivity interlayer, the dynamic range of the extraction component of the same frequency decreases gradually, and the family of equal‐frequency response curves overlap with each other. By contrast, for the high‐resistivity interlayer, as its resistivity gradually increases, the dynamic range of the extraction component of same frequency also increases gradually. Moreover, as well spacing varies, the response characteristics of the equal‐frequency curve family on different measuring lines are also obviously different. The digital coherent detection method significantly simplifies the receiving circuit system. In practical application, response information of different discrete frequency components can be extracted according to requirements. This thus provides a theoretical basis for the extraction of resistivity and characteristic identification of interwell heterogeneous oil and gas reservoirs.

Background: 5-Fluorouracil (5-FU) is one of the most effective and widely used chemotherapeutic drugs in the treatment of colon cancer, yet chemoresistance is a common feature of colon cancer treatment, resulting in poor prognosis and short survival. Dynamic reprogramming of chromatin accessibility is crucial for proper regulation of gene transcription associated with cancer drug resistance by providing the gene regulatory machinery with rapid access to the open genomic DNA.Methods: Here, we explored the global chromatin accessibility and transcription changes by the assay for transposase-accessible chromatin using sequencing (ATAC-seq) in combination with transcriptome sequencing of both parental and 5-FU-resistant HCT15 cells, followed by integrative analysis to better understand the regulatory network underlying 5-FU resistance in colon cancer cells.Results: A total of 3,175 differentially expressed mRNAs (DEGs), lncRNAs (DELs), and miRNAs (DEMs) related to 5-FU resistance were identified, including significantly upregulated IL33, H19, and miR-17-5p; the downregulated AKR1B10, LINC01012, and miR-125b-5p; and chromatin modifiers such as INO80C, HDAC6, and KDM5A. The construction of the ceRNA regulatory network revealed that H19, HOXA11-AS, and NEAT1 might function as ceRNAs associated with 5-FU resistance in HCT15 cells. Moreover, 9,868 differentially accessible regions (DARs) were obtained, which were positively (r = 0.58) correlated with their nearest DEGs and DELs. The upregulated genes related to 4,937 hyper-accessible regions were significantly enriched in signaling pathways of MAPK, FOX, and WNT, while the 4,931 hypo-accessible regions were considered to be involved in declined biosynthesis of amino acids and nucleotide sugars, signaling pathways of Notch, and HIF-1. Analyses of the DAR sequences revealed that besides the AP-1 family, the TF motifs of FOX and KLF family members were highly enriched in hyper- and hypo-accessible regions, respectively. Finally, we obtained several critical TFs and their potential targets associated with DARs and 5-FU resistance, including FOXA1 and KLF3.Conclusion: These data provided clear insights and valuable resources for an improved understanding of the non-genetic landscape of 5-FU-resistant colon cancer cells based on chromatin accessibility and transcript levels, which allowed for genome-wide detection of TF binding sites, potential cis-regulatory elements and therapeutic targets.

Abstract Background Tumour‐associated macrophages (TAMs) play an important role in promoting the progression of pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to study the epigenetic mechanisms in regulating pro‐tumour M2‐polarised TAMs in the PDAC tumour microenvironment. Methods This study was conducted based on ex vivo TAMs isolated from PDAC tissues and in vitro THP1‐derived TAM model. RNA‐sequencing (RNA‐seq), assay for transposase‐accessible chromatin with sequencing and chromatin immunoprecipitation sequencing were performed to investigate gene expression, chromatin accessibility, transcription factor binding sites and histone modifications. Gene knockdown in THP1‐derived TAMs was performed with lentivirus, and the impact of THP1‐derived TAMs on invasion and metastasis ability of PDAC cells were investigated with in vitro and in vivo functional assays. RNA‐chromatin interaction was analysed by chromatin isolation through RNA purification with sequencing. RNA‐protein interaction was studied by RNA immunoprecipitation and RNA pull‐down. Results Our data showed that the transcription factor CTCF (CCCTC‐binding factor) was highly expressed in TAMs and predicted to be significantly enriched in hyper‐accessible chromatin regions when compared to monocytes. High infiltration of CTCF+ TAMs was significantly associated with poor prognosis in PDAC patients. Knockdown of CTCF in THP1‐derived TAMs led to the down‐regulation of specific markers for M2‐polarised TAMs, including CD206 and CD163. When THP1‐derived TAMs with CTCF knockdown, they showed a decreased ability of invasion and metastasis. Further integrative analysis of multi‐omics data revealed that prostaglandin‐endoperoxide synthase 2 (PTGS2) and PTGS2 antisense NF‐κB1 complex‐mediated expression regulator RNA (PACERR) were critical downstream targets of CTCF and positively correlated with each other, which are closely situated on a chromosome. Knockdown of PACERR exhibited a similar phenotype as observed in CTCF knockdown THP1‐derived TAMs. Moreover, PACERR could directly bind to CTCF and recruit histone acetyltransferase E1A binding protein p300 to the promoter regions of PACERR and PTGS2, thereby enhancing histone acetylation and gene transcription, promoting the M2 polarization of TAMs in PDAC. Conclusions Our study demonstrated a novel epigenetic regulation mechanism of promoting pro‐tumour M2‐polarised TAMs in the PDAC tumour microenvironment.

BackgroundDoxorubicin is one of the most effective chemotherapeutic drugs for breast cancer while its common drug resistance leads to poor patient prognosis and survival. Growing evidence indicate dynamically reorganized chromatin allows rapid access of the gene regulatory machinery to open genomic regions facilitating subsequent gene expression through direct transcription factor (TF) activation and regulatory element binding.MethodsTo better understand the regulatory network underlying doxorubicin resistance in breast cancer cells, we explored the systematic alterations of chromatin accessibility and gene expression by the assay for transposase-accessible chromatin using sequencing (ATAC-seq) in combination with RNA sequencing, followed by integrative analysis to identify potential regulators and their targets associated with differentially accessible regions (DARs) in doxorubicin-resistant MCF7 (MCF7-DR) cells.ResultsA total of 3,963 differentially expressed genes (DEGs) related to doxorubicin resistance were identified, including dramatically up-regulated MT1E, GSTP1, LDHB, significantly down-regulated TFF1, UBB, DSCAM-AS1, and histone-modifying enzyme coding genes HDAC2, EZH2, PRMT5, etc. By integrating with transcriptomic datasets, we identified 18,228 DARs in MCF7-DR cells compared to control, which were positively correlated with their nearest DEGs (r = 0.6). There were 11,686 increased chromatin-accessible regions, which were enriched in up-regulated genes related to diverse KEGG pathways, such as the cell cycle, regulation of actin cytoskeleton, signaling pathways of MAPK, PI3K/Akt and Hippo, which play essential roles in regulating cell apoptosis, proliferation, metabolism, and inflammatory responses. The 6,542 decreased chromatin-accessible regions were identified for the declined doxorubicin-associated biological processes, for instance, endocrine and insulin resistance, central carbon metabolism, signaling pathways of TGF-beta and P53. Combining data from TCGA, analyses of the DAR sequences associated with the DNA-binding motifs of significantly enriched TF families including AP-1, TEAD and FOX, indicated that the loss-function of FOXA1 might play a critical role in doxorubicin-resistant breast cancer cells (DOX-R BCCs).ConclusionThese data exhibit the non-genetic landscape of chromatin accessibility and transcript levels in the DOX-R BCCs, and provide clear insights and resources for the detection of critical TFs and potential cis-regulatory elements-based putative therapeutic targets.

Background: Toxoplasma gondii is an obligate intracellular parasite, which can infect all nucleated cells in a variety of vertebrate animals, including human, causing toxoplasmosis. Although a number of studies have reported on the seroprevalence of T. gondii infection in dogs in China, however, information about T. gondii infection in pet dogs in Anhui, China is not available. Methods: The modified agglutination test (MAT) was used to detect antibodies in sera samples from 468 pet dogs at Anhui Province in China from November 2013 to April 2017. Results: 18.6% animals were T. gondii seropositive, indicating a slightly higher prevalence of T. gondii infection in pet dogs in Anhui, China in comparison with other provinces in China. Conclusion: Our present study provided epidemiological data on T. gondii seroprevalence in pet dogs in Anhui, China for the effective prevention and control of the parasite prevalence in this area.

Flexible sensors have been tremendously attractive in wearable electronics, soft robots and human-machine interaction devices. In this work, conductive silicon rubber (CSR) filled with silver-coated-glass fiber (AGF) and carbon fiber (CF) was embedded into polydimethylsiloxane (PDMS) matrix to fabricate a flexible strain sensor (FSS) in a 3D-printing (3DP) process. It was found that the addition of CF and plasticizer synergistically formed a support-structure which guaranteed the CSR to be extruded out easily in the 3DP process. The printed FSS demonstrated its highly stable properties with a gauge factor (GF) of 8–10 at different strain rate, the coincident resistance recovery process in cyclic load of different strain, as well as the stable durability with monotonous peak in 600 strain-release cycles. Furthermore, it was able to distinguish a superimposed load at frequencies of 1/12 Hz and 1/36 Hz with aids of Fast Fourier Transformation (FFT) analysis. Migrating evolution of AGFs in a stretched CSR was observed to further explore and paraphrase the mechanism of resistance response and the high GF of the FSS. The printed FSS was capable to monitor the movement of various joints and further distinguish a superimposed human motion, showing its potentially practical application in soft robots and wearable electronics.

Abstract: Carbonate dissolution during the process of burial and evolution by percolating acid fluid was simulated using core plugs to analyze the characteristics and controlling factors of Cambrian carbonate rock dissolution in the Tarim Basin. The results showed that mineral composition and reservoir space type control selective dissolution. In the carbonate rock strata with high calcite content, the calcite is likely to dissolve first to form secondary dissolution pores; gypsum and anhydrite in the carbonate rock can be dissolved to form mold pores in contemporaneous and penecontemporaneous stages. Porous carbonate has mainly enlargement of matrix pores, with porosity and permeability increasing correspondingly, but not obviously. In comparison, dominant channels for fluid are likely to occur in fractured carbonate or porous carbonate forming cracks under high pressure, resulting in a relative reduction in the dissolution volume, but great increase of permeability. With the rise of temperature and pressure, corrosion ability of acid fluid to carbonate rock increases first and then decreases, there exists an optimum range of temperature and pressure for dissolution, which corresponds to the buried depth of 2 250−3 750 m of the Cambrian. Considering reservoir characteristics of the study area, it is concluded that calcite in the penecontemporaneous period is the material basis for the development of dissolution pore, and carbonate rock were mainly dissolved by early atmospheric fresh water, superimposed and reformed to form high quality reservoirs by multiple acid fluids including deep hydrothermal fluid and acid fluid generated during the process of organic thermal evolution under burial condition. Key words: Tarim Basin, Cambrian, carbonate rock, dissolution, dissolution mechanism, simulation experiment

In this paper, we report a method through the combination of ab-initio calculations and partial least squares (PLS) analysis to develop the Quantitative Structure –Activity Relationship (QSAR) formulations of cathode volume changes in lithium ion batteries. The PLS analysis is based on ab-initio calculation data of 14 oxide cathodes with spinel structure LiX2O4 and 14 oxide cathodes with layered-structure LiXO2 (X = Ti, V, Cr, Mn, Fe, Co, Ni, Nb, Mo, Ru, Rh, Pd, Ta, Ir). Five types of descriptors, describing the characteristics of each compound from crystal structure, element, composition, local distortion and electronic level, with 34 factors in total, are adopted to obtain the QSAR formulation. According to the variable importance in projection analysis, the radius of X4+ ion, and the X octahedron descriptors make major contributions to the volume change of cathode during delithiation. The analysis is hopefully applied to the virtual screening and combinatorial design of low-strain cathode materials for lithium ion batteries.

Using a pseudo-random sequence to encode the transmitted waveform can significantly improve the working efficiency and depth of detection of electromagnetic exploration. The selection of parameters of pseudo-random sequence plays an important role in correlation identification and noise suppression. A discrete cycle correlation identification method for extracting the earth impulse response is proposed. It can suppress the distortion in the early stage of the excitation field and the glitches of the cross correlation function by traditional method. This effectively improves the accuracy of correlation identification. The influence of the order and the cycles of m-series pseudo-random coding on its autocorrelation properties is studied. The numerical results show that, with the increase of the order of m-sequence, the maximum out-of-phase periodic autocorrelation function decreases rapidly. Therefore, it is very beneficial to achieve synchronization. The limited-cycle m-sequences have good autocorrelation properties. As the period of the m-sequence increases and the width of the symbol decreases, the overall autocorrelation becomes closer to the impact function. The discussion of the influence of symbol width and period of m-sequence on its frequency bandwidth and power spectral density shows that the narrower the symbol width, the wider its occupied band. The longer the period, the smaller the power spectral line spacing. The abilities of m-sequence to suppress DC (Direct-current) interference, Schumann frequency noise, and sine-wave noise are analyzed. Numerical results show that the m-sequence has excellent ability to suppress DC interference and Schumann frequency noise. However, for high-order harmonic noise, the correlation identification error appears severe oscillation in the middle and late stages of the impulse response. It indicates that the ability of m-sequence to suppress high-frequency sinusoidal noise is deteriorated. In practical applications, the parameters of the transmitted waveform should be reasonably selected in combination with factors including transmitter performance, hardware noise, and ambient noise level to achieve the best identification effect.

The Sonic hedgehog (Shh) signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

BACKGROUND: Recent population structure studies of T. gondii revealed that a few major clonal lineages predominated in different geographical regions. T. gondii in South America is genetically and biologically divergent, whereas this parasite is remarkably clonal in North America and Europe with a few major lineages including Types I, II and III. Information on genotypes and mouse virulence of T. gondii isolates from China is scarce and insufficient to investigate its population structure, evolution, and transmission. METHODOLOGY/PRINCIPAL FINDINGS: Genotyping of 23 T. gondii isolates from different hosts using 10 markers for PCR-restriction fragment length polymorphism analyses (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) revealed five genotypes; among them three genotypes were atypical and two were archetypal. Fifteen strains belong to the Chinese 1 lineage, which has been previously reported as a widespread lineage from swine, cats, and humans in China. Two human isolates fall into the type I and II lineages and the remaining isolates belong to two new atypical genotypes (ToxoDB#204 and #205) which has never been reported in China. Our results show that these genotypes of T. gondii isolates are intermediately or highly virulent in mice except for the strain TgCtwh6, which maintained parasitemia in mice for 35 days post infection although it possesses the uniform genotype of Chinese 1. Additionally, phylogenetic network analyses of all isolates of genotype Chinese 1 are identical, and there is no variation based on the sequence data generated for four introns (EF1, HP2, UPRT1 and UPRT7) and two dense granule proteins (GRA6 and GRA7). CONCLUSION/SIGNIFICANCE: A limited genetic diversity was found and genotype Chinese 1 (ToxoDB#9) is dominantly circulating in mainland China. The results will provide a useful profile for deep insight to the population structure, epidemiology and biological characteristics of T. gondii in China.

Zebrafish possess a remarkable ability to regenerate complicated structures by formation of a mass of undifferentiated mesenchymal cells called blastema. To understand how the blastema retains the original structural form, we investigate cellular transitions and transcriptional characteristics of cell identity genes during all stages of regeneration of an amputated lower jaw. We find that mesenchymal blastema originates from multiple sources including nucleated blood cells, fibroblasts, damaged muscle cells and pigment cells. These cells are transformed into two populations of blastemal progenitors: foxi1-expression and isl1-expression, before giving rise to cartilage, bone, and muscle. Time point- based transcriptomal analysis of 45 annotated Hox genes reveal that five 3'-end Hox genes and an equal number of 5'-end Hox genes are activated largely at the stage of blastema reformation. RNA in situ hybridization shows that foxi1 and pax3a are respectively expressed in the presumptive mandible skeletal region and regenerating muscle at 5 dpa. In contrast, hoxa2b and hoxa11b are widely expressed with different domain in chondrogenic blastema and blastema mesenchyme. Knockdown foxi1 changes the expression patterns of sox9a and hoxa2b in chondrogenic blastema. From these results we propose that two origins of blastemal progenitors define blastema skeleton and muscle respecifications through distinct signaling pathways. Meanwhile, the positional identity of blastema reformation is implicated in mesenchymal segmentation and characteristic expression pattern of Hox genes.