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Collagen XVII (COL17) is a transmembrane protein that mediates skin homeostasis. Due to expression of full length collagen was hard to achieve in microorganisms, arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis. Here, COL17 fragments (27-33 amino acids) were extracted and replicated 16 times for recombinant expression in Escherichia coli. Five variants were soluble expressed, with the highest yield of 223 mg/L. The fusion tag was removed for biochemical and biophysical characterization. Circular dichroism results suggested one variant (sample-1707) with a triple-helix structure at >37 °C. Sample-1707 can assemble into nanofiber (width, 5.6 nm) and form hydrogel at 3 mg/mL. Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation. Furthermore, sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration, demonstrating a high capacity to induce skin cell regeneration and promote wound healing. A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of >30 % higher than simply using chitosan. Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L. These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry. [ABSTRACT FROM AUTHOR]

Introduction: Inonotus hispidus, commonly referred to as the Sanghuang mushroom, is a species that is consumed as a tea. To date, this is the only species of the same fungus that has been successfully cultivated. Methods: A single-factor test was conducted using Inonotus hispidus MS-5 and MS-9 as test materials. The response surface methodology was adopted to design and optimise the liquid fermentation medium for them. Results: As indicated in the results, the optimum fermentation conditions for MS-5 include 24.09g/L glucose, 7.88g/L yeast extract, 0.99g/L dandelion powder, 1.5g MgSO4, 2g KH2PO4, 0.01g vitamin B1, and 1L deionized water; the optimum fermentation conditions for MS-9 include 24.64g/L glucose, 7.77g/L yeast extract, 0.98g/L dandelion powder, 1.5g MgSO4, 2g KH2PO4, 0.01g vitamin B1, and 1L deionized water. Under such conditions, the mycelial biomass (dry weight) values were able to reach 16.02g/L and 14.91g/L for MS-5 and MS-9, respectively, which were 1.6 and 1.54 times those measured before optimization. Discussion: As revealed in the antioxidant and anticancer experiment, Inonotus hispidus exopolysaccharides has corresponding functional effects at the cellular level. This research optimised the liquid culture formulation of Inonotus hispidus and demonstrated that the function of it as a traditional Sanghuang herbal tea is well-documented. [ABSTRACT FROM AUTHOR]

The incidence of liver disease continues to rise, encompassing a spectrum from simple steatosis or non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary habits in individuals with liver disease may significantly impact the treatment and prevention of these conditions. This article examines the role of chili peppers, a common dietary component, in this context, focusing on capsaicin, the active ingredient in chili peppers. Capsaicin is an agonist of the transient receptor potential vanilloid subfamily 1 (TRPV1) and has been shown to exert protective effects on liver diseases, including liver injury, NAFLD, liver fibrosis and liver cancer. These protective effects are attributed to capsaicin's anti-oxidant, anti-inflammatory, anti-steatosis and anti-fibrosis effects. This article reviewed the different molecular mechanisms of the protective effect of capsaicin on liver diseases. [ABSTRACT FROM AUTHOR]

The establishment of a cost model for complex energy systems based on thermoeconomics can provide technical and economic evaluation indicators for complex energy systems. At the same time, to integrate more renewable energy into the grid, complex energy systems must participate in deep peak shaving. To evaluate the technical-economic performance of complex energy systems involved in deep peak shaving, a novel thermoeconomic cost construction method is proposed based on the production structure diagram, using the gas-steam combined cycle system as an example. These can effectively avoid the derivation error of high-dimensional models, improve the modeling and calculation speed, and obtain the variation trend of system thermoeconomics cost under load changes and operating parameter changes. The results show that the external and internal factor can change the power generator thermoeconomic cost. The power generation cost of the system increases with increasing natural gas price and environmental temperature. When the compressor pressure ratio increases, the power generation cost of the system also increases. At 100% load, the power generation cost reaches its lowest value when the exhaust temperature is equal to 615 °C. [ABSTRACT FROM AUTHOR]

Gibberellin (GA) functions in plant growth and development. However, genes involved in the biosynthesis and regulation of GA in crop plants are poorly understood. We isolated the mutant gad5-1 (GAAssociated Dwarf 5), characterized by dwarfing, short internodes, and dark green and short leaves. Map-based gene cloning and allelic verification confirmed that ZmGAD5 encodes ent-kaurenoic acid oxidase (KAO), which catalyzes KA (ent-kaurenoic acid) to GA12 conversion during GA biosynthesis in maize. ZmGAD5 is localized to the endoplasmic reticulum and is present in multiple maize organs. In gad5-1, the expression of ZmGAD5 is severely reduced, and the levels of the direct substrate of KAO, KA, is increased, leading to a reduction in GA content. The abnormal phenotype of gad5-1 was restored by exogenous application of GA3. The biomass, plant height, and levels of GA12 and GA3 in transgenic Arabidopsis overexpressing ZmGAD5 were increased in comparison with the corresponding controls Col-0. These findings deepen our understanding of genes involved in GA biosynthesis, and could lead to the development of maize lines with improved architecture and higher planting-density tolerance. [ABSTRACT FROM AUTHOR]

Wheat is an important contributor to global food security, and further improvements are required to feed a growing human population. Functional genetics and genomics tools can help us to understand the function of different genes and to engineer beneficial changes. In this study, we used a promoter capture assay to sequence 2-kb regions upstream of all high-confidence annotated genes from 1,513 mutagenized plants from the tetraploid wheat variety Kronos. We identified 4.3 million induced mutations with an accuracy of 99.8%, resulting in a mutation density of 41.9 mutations per kb. We also remapped Kronos exome capture reads to Chinese Spring RefSeq v1.1, identified 4.7 million mutations, and predicted their effects on annotated genes. Using these predictions, we identified 59% more nonsynonymous substitutions and 49% more truncation mutations than in the original study. To show the biological value of the promoter dataset, we selected two mutations within the promoter of the VRN-A1 vernalization gene. Both mutations, located within transcription factor binding sites, significantly altered VRN-A1 expression, and one reduced the number of spikelets per spike. These publicly available sequenced mutant datasets provide rapid and inexpensive access to induced variation in the promoters and coding regions of most wheat genes. These mutations can be used to understand and modulate gene expression and phenotypes for both basic and commercial applications, where limited governmental regulations can facilitate deployment. These mutant collections, together with gene editing, provide valuable tools to accelerate functional genetic studies in this economically important crop. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Plant height is an important agronomic trait with a significant impact on grain yield, as demonstrated by the positive effect of the REDUCED HEIGHT(RHT) dwarfing alleles (Rht1b) on lodging and harvest index in the "Green Revolution" wheat varieties. However, these gibberellic acid (GA)-insensitive alleles also reduce coleoptile length, biomass production, and yield potential in some environments, triggering the search for alternative GA-sensitive dwarfing genes. Here we report the identification, validation, and characterization of the gene underlying the GA-sensitive dwarfing locus RHT25 in wheat. This gene, designated as PLATZ-A1 (TraesCS6A02G156600), is expressed mainly in the elongating stem and developing spike and encodes a plant-specific AT-rich sequence- and zinc-binding protein (PLATZ). Natural and induced loss-of-function mutations in PLATZ-A1 reduce plant height and its overexpression increases plant height, demonstrating that PLATZ-A1 is the causative gene of RHT25. PLATZ-A1 and RHT1 show a significant genetic interaction on plant height, and their encoded proteins interact with each other in yeast and wheat protoplasts. These results suggest that PLATZ1 can modulate the effect of DELLA on wheat plant height. We identified four natural truncation mutations and one promoter insertion in PLATZ-A1 that are more frequent in modern varieties than in landraces, suggesting positive selection during wheat breeding. These mutations can be used to fine-tune wheat plant height and, in combination with other GA-sensitive dwarfing genes, to replace the GA-insensitive Rht1b alleles and search for grain yield improvements beyond those of the Green Revolution varieties. [ABSTRACT FROM AUTHOR]

Background: While the tumor microenvironment (TME) affects immune checkpoint blockade (ICB) efficacy, ICB also reshapes the characteristics of TME. Thus far, studies have focused on the TME evolution during neoadjuvant or adjuvant ICB therapy in gastric cancer (GC). However, the interaction between TME characteristics and neoadjuvant immunotherapy plus chemotherapy remains to be elucidated. Methods: We performed single-cell RNA sequencing on ten GC specimens pre- and post-neoadjuvant camrelizumab plus mFOLFOX6 to determine the impact of the TME on the efficacy of the combination therapy and the remodeling of TME by the therapy. Results: A high baseline interferon gamma (IFN-γ) signature in CD8+ T cells predicts better responses to the combination therapy. We also observed that the IFN-γ signature significantly decreased in multiple cell types, and the exhausted signature of CD8+ T cells was significantly suppressed during the neoadjuvant therapy. Conclusions: Our data reveal interactions between the TME and neoadjuvant immunotherapy plus chemotherapy in GC. Importantly, it also highlights the signature of CD8+ T cells in predicting response to the combination therapy in GC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is always deemed a deadly malignancy worldwide. Non-coding RNAs, including circRNAs, are becoming more widely recognized as essential regulators of the malignant development of HCC. Thus, we elaborated the regulating role of hsa_circ_0119412 in HCC advancement. The qRT-PCR was done to estimate the expressions of hsa_circ_0119412, miR-526b-5p, and Stathmin 1 (STMN1) in HCC (clinical samples and cell lines), and immunoblotting was used to detect STMN1 protein level in HCC cell lines. The stability of the circRNA was checked by processing with ribonuclease R. The proliferative potential of HCC cells was examined via the CCK-8 assay and the migratory potential by the wound healing assay. Immunoblotting was done to examine Bax and Bcl-2 (apoptosis-related proteins). Luciferase and RIP assays were employed to establish the direct interactions among miR-526b-5p and hsa_circ 0119412/STMN1. In vivo tumor growth was measured by doing a xenograft tumor experiment. In the tissues of HCC patients and cell lines derived from HCC cells, hsa_circ_0119412 was distinctly overexpressed. Knocking down hsa_circ_0119412 impeded proliferation and migration while inducing apoptosis in HCC cells. Moreover, silencing hsa_circ_0119412 diminished tumor weight and volume in vivo. Interestingly, miR-526b-5p inhibition partially restored the anti-tumor effects of silencing hsa_- circ_0119412. STMN1 expression was also abundant in HCC, suggesting that it play a tumor-promoting role. Mechanistically, hsa_circ_0119412 sponged miR-526b-5p, resulting in STMN1 upregulation and thus facilitating the progression of HCC. In conclusion, this study reveals that hsa_circ_0119412 knockdown attenuates the progression of HCC by targeting miR-526b-5p/STMN1 axis. [ABSTRACT FROM AUTHOR]

Cryptococcus spp. is a complex species that often causes cryptococcosis, which is one of the most common opportunistic infections in adults living with HIV and has very high morbidity and mortality rates. This study aimed to investigate the antifungal susceptibility profiles and epidemiological characteristics of the Cryptococcus neoformans species complex (CNSC) and the Cryptococcus gattii species complex (CGSC) in Zhejiang Province, China. A total of 177 CNSC and 3 CGSC isolates were collected, and antifungal susceptibility was tested by FUNGUS 3 and verified with an E-test. Moreover, multiple classification methods and genomic analyses were performed. The majority of the isolates (96.11%) were C. neoformans (formerly C. neoformans var. grubii) (ST5-VNI-A-α). Our study highlights that most of the patients with cryptococcosis were non-HIV patients in China, and nearly half of them did not have underlying diseases that led to immune insufficiency. Most of the Cryptococcus spp. isolates in this study were sensitive to common antifungal drugs. Two 5-flucytosine (5-FC)-resistant strains were identified, and FUR1 mutation was detected in the 5-FC-resistant isolates. Typing based on whole-genome sequencing (WGS) showed better discrimination than that achieved with multilocus sequence typing (MLST) and indicated a clear population structure. A phylogenetic analysis based on WGS included more genomic information than traditional classification methods. [ABSTRACT FROM AUTHOR]

With the widespread of colonoscopy, colorectal cancer remains to be one of the most detrimental types of cancer. Though there were multiple studies investigating the genomic landscape of colorectal cancer, a comprehensive analysis uncovering the differences between various types of colorectal cancer is still lacking. In our study, we performed genomic analysis on 133 patients with colorectal cancer. Mutated FAT1 and PKHD1 and altered Hippo pathway genes were found to be enriched in early-onset colorectal cancer. APOBEC signature was prevalent in microsatellite stable (MSS) patients and was related to lymph node metastasis. ZNF217mutations were significantly associated with early-stage colorectal cancer. In all, this study represents a comprehensive genomic analysis uncovering potential molecular mechanisms underneath different subgroups of colorectal cancer thus providing new targets for precision treatment development. [ABSTRACT FROM AUTHOR]

Leaf angle (LA) is a key component of maize plant architecture that can simultaneously govern planting density and improve final yield. However, the genetic mechanisms underlying LA have not been fully addressed. To broaden our understanding of its genetic basis, we scored three LA-related traits on upper, middle, and low leaves of 492 maize inbred lines in five environments. Phenotypic data revealed that the three LA-related traits were normally distributed, and significant variation was observed among environments and genotypes. A genome-wide association study (GWAS) was then performed to dissect the genetic factors that control natural variation in maize LA. In total, 85 significant SNPs (involving 32 non-redundant QTLs) were detected (p ≤ 2.04 × 10-6), and individual QTL explained 4.80%-24.09% of the phenotypic variation. Five co-located QTL were detected in at least two environments, and two QTLs were co-located with multiple LA-related traits. Forty-seven meta-QTLs were identified based on meta-analysis combing 294 LA-related QTLs extracted from 18 previously published studies, 816 genes were identified within these meta-QTLs, and seven co-located QTLs were jointly identified by both GWAS and meta-analysis. ZmULA1 was located in one of the co-located QTLs, qLA7, and its haplotypes, hap1 and hap2, differed significantly in LA-related traits. Interestingly, the temperate materials with hap2 had smallest LA. Finally, we also performed haplotype analysis using the reported genes that regulate LA, and identified a lot of maize germplasms that aggregated favorable haplotypes. These results will be helpful for elucidating the genetic basis of LA and breeding new maize varieties with ideal plant architecture. [ABSTRACT FROM AUTHOR]

Background: The association between hematologic parameters and antiprogrammed death-1 (PD-1) inhibitors was generally examined without considering therapy lines and medicine types. The study was aimed to identify potential hematologic biomarkers associated with clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab and subsequent-line nivolumab. Materials and methods: 161 NSCLC patients were categorized into first-line pembrolizumab group (pembrolizumab group) and subsequent-line nivolumab group (nivolumab group). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of hematologic parameters for clinical outcomes. Results: The median progression-free survival (mPFS) was 9.6 months in the pembrolizumab group and 4.1 months in the nivolumab group (HR =1.61; P = 0.012); the median overall survival (mOS) was not reached in the pembrolizumab group and 17.7 months in the nivolumab group (HR =1.37; P = 0.23). Of the 79 patients in the pembrolizumab group, baseline PD-L1 tumor proportion score (TPS)=1% was an independent factor of longer PFS and OS. Age=60 years, absolute platelet count (APC)=220×109/L and platelet-tolymphocyte ratio (PLR)=120 were associated with inferior PFS. Of the 82 patients in the nivolumab group, absolute neutrophil count (ANC)=3×109/L was associated with longer PFS, while LDH (lactate dehydrogenase)=160 U/L was associated with inferior PFS and derived neutrophil-to-lymphocyte ratio (dNLR)=1.2 was associated with longer OS. Conclusion: Our study identified multiple clinically accessible prognostic biomarkers in the peripheral blood in both the pembrolizumab and nivolumab subgroups. [ABSTRACT FROM AUTHOR]

Zanthoxylum armatum is a prominent plant for food industries. Its male flowers often occur in gynogenesis plants; however, the potential mechanism remains poorly understood. Herein, a total of 26 floral sex differentiation stages were observed to select four vital phases to reveal key factors by using RNA-seq, phytohormones and carbohydrates investigation. The results showed that a selective abortion of stamen or pistil primordia could result in the floral sex differentiation in Z. armatum. Carbohydrates might collaborate with cytokinin to effect the male floral differentiation, whereas female floral differentiation was involved in SA, GA1, and ABA biosynthesis and signal transduction pathways. Meanwhile, these endogenous regulators associated with reproductive growth might be integrated into ABCDE model to regulate the floral organ differentiation in Z. armatum. Furthermore, the 21 crucial candidates were identified in co-expression network, which would contribute to uncovering their roles in floral sex differentiation of Z. armatum in further studies. To the best of our knowledge, this study was the first comprehensive investigation to link floral sex differentiation with multi-level endogenous regulatory factors in Z. armatum. It also provided new insights to explore the regulatory mechanism of floral sex differentiation, which would be benefited to cultivate high-yield varieties in Z. armatum. [ABSTRACT FROM AUTHOR]

Chemo-radiotherapy (CRT) remains the main treatment modality for non-small-cell lung cancer (NSCLC). However, its clinical efficacy is largely limited by individual variations in radio-sensitivity and radiotherapy-associated toxicity. There is an urgent need to identify genetic determinants that can explain patients' likelihood to develop recurrence and radiotherapy-associated toxicity following CRT. In this study, we performed comprehensive genomic profiling, using a 474-cancer- and radiotherapy-related gene panel, on pretreatment biopsy samples from patients with unresectable stage III NSCLCs who underwent definitive CRT. Patients' baseline clinical characteristics and genomic features, including tumor genetic, genomic and molecular pathway alterations, as well as single nucleotide polymorphisms (SNPs), were correlated with progression-free survival (PFS), overall survival (OS), and radiotherapy-associated pneumonitis and/or esophagitis development after CRT. A total of 122 patients were enrolled between 2014 and 2019, with 84 (69%) squamous cell carcinomas and 38 (31%) adenocarcinomas. Genetic analysis confirmed the association between the KEAP1-NRF2 pathway gene alterations and unfavorable survival outcome, and revealed alterations in FGFR family genes, MET, PTEN, and NOTCH2 as potential novel and independent risk factors of poor post-CRT survival. Combined analysis of such alterations led to improved stratification of the risk populations. In addition, patients with EGFR activating mutations or any oncogenic driver mutations exhibited improved OS. On the other hand, we also identified genetic markers in relation to radiotherapy-associated thoracic toxicity. SNPs in the DNA repair-associated XRCC5 (rs3835) and XRCC1 (rs25487) were associated with an increased risk of highgrade esophagitis and pneumonitis respectively. MTHFR (rs1801133) and NQO1 (rs1800566) were additional risk alleles related to higher susceptibility to pneumonitis and esophagitis overall. Moreover, through their roles in genome integrity and replicative fidelity, somatic alterations in ZNF217 and POLD1 might also serve as risk predictors of high-grade pneumonitis and esophagitis. Taken together, leveraging targeted nextgenerating sequencing, we identified a set of novel clinically applicable biomarkers that might enable prediction of survival outcomes and risk of radiotherapy-associated thoracic toxicities. Our findings highlight the value of pre-treatment genetic testing to better inform CRT outcomes and clinical actions in stage III unresectable NSCLCs. [ABSTRACT FROM AUTHOR]

Tan sheep industry is a characteristic and superior agricultural industry in Ningxia, and it is also an enriching industry that helps in poverty alleviation and increases farmers' income. The local government has been committing to building the "Yanchi Tan Sheep" brand and has made remarkable achievements. In order to explore the resource efficiency and quality of Tan sheep industry, the current situations and advantages of brand development, this paper made an empirical research through field investigations. The research was mainly concentrated on breeding scale, industrial integration, brand building, breeding benefits, and policy support. After a comprehensive evaluation, it came up with the recommendation that the Tan sheep industry should take the high-quality, high-end and green development road. [ABSTRACT FROM AUTHOR]

Plants are vulnerable to disease through pathogen manipulation of phytohormone levels, which otherwise regulate development, abiotic, and biotic responses. Here, we show that the wheat pathogen Xanthomonas translucens pv. undulosa elevates expression of the host gene encoding 9-cis-epoxycarotenoid dioxygenase (TaNCED-5BS), which catalyzes the rate-limiting step in the biosynthesis of the phytohormone abscisic acid and a component of a major abiotic stress-response pathway, to promote disease susceptibility. Gene induction is mediated by a type III transcription activator-like effector. The induction of TaNCED-5BS results in elevated abscisic acid levels, reduced host transpiration and water loss, enhanced spread of bacteria in infected leaves, and decreased expression of the central defense gene TaNPR1. The results represent an appropriation of host physiology by a bacterial virulence effector. [ABSTRACT FROM AUTHOR]

A matrix modelling method based on the production structure is proposed and a general exergy matrix model for the multi-energy integrated system is established, which provides a simple and effective tool for the contribution rate calculation of the external fuel exergy to the multi-energy integrated system. The proposed method is verified by a case study of a solar-aided 600 MW coal-fired power generation system. The influence of two fuel product definitions and different simplified systems on the calculation results is analyzed. The results show that the contribution rate of solar exergy is 4.24% when the product is defined as the output exergy. But the solar exergy contribution rate is only 1.77% when the product is defined as the exergy increment and output power. Inappropriate system simplification can also cause the contribution rate of external fuel to deviate from the original value. [ABSTRACT FROM AUTHOR]

This paper proposes a first principle dynamic model of the Nuclear Steam Supply System (NSSS) for the Double-Reactor and Multi-Turbine Nuclear Power Plant (DMNPP). The main devices within the nuclear steam supply system, such as Once Through Steam Generator (OTSG), Steam Main Pipe (SMP)and Steam Turbine (ST) are modelled using the movable boundary approach and discrete approximate distributed modelling method. Dynamic behaviour analysis is then carried out on the developed model, through which, the dynamic characteristics of key variables, such as the distribution pressures in the SMP are investigated in detail. The simulation results show that when the opening degree of the ST regulating valve or the OTSG steam valve change, the fluctuations of the pressure at each point in the SMP are different. The maximum fluctuation value of the pressure is 0.12 MPa when the opening degree of the third ST regulating valve is increased by 20% and is 0.015 MPa when the opening degree of the second OTSG steam valve is increased by 10%. It is discovered that the steam pressure of the SMP has a self-stabilizing ability and the NSSS of the DMNPP is of highly nonlinearity and strongly coupled among multi-variables. [ABSTRACT FROM AUTHOR]

HIV-1 evolved into various genetic subtypes and circulating recombinant forms (CRFs) in the global epidemic. The same subtype or CRF is usually considered to have similar phenotype. Being one of theworld's major CRFs, CRF01_AE infection was reported to associate with higher prevalence of CXCR4 (X4) viruses and faster CD4 decline. However, the underlying mechanisms remain unclear. We identified eight phylogenetic clusters of CRF01_AE in China and hypothesized that they may have different phenotypes. In the National HIV Molecular Epidemiology Survey, we discovered that people infected by CRF01_AE cluster 4 had significantly lower CD4 counts (391 vs. 470, P < 0.0001) and higher prevalence of X4-using viruses (17.1% vs. 4.4%, P < 0.0001) compared with those infected by cluster 5. In an MSM cohort, X4-using viruses were only isolated from seroconvertors in cluster 4, which was associated with low a CD4 count within the first year of infection (141 vs. 440, P = 0.003). Using a coreceptor binding model, we identified unique V3 signatures in cluster 4 that favor CXCR4 use. We demonstrate that the HIV-1 phenotype and pathogenicity can be determined at the phylogenetic cluster level in the same subtype. Since its initial spread to humans from chimpanzees, estimated to be the first half of the 20th century, HIV-1 continues to undergo rapid evolution in larger and more diverse populations. The divergent phenotype evolution of two major CRF01_AE clusters highlights the importance of monitoring the genetic evolution and phenotypic shift of HIV-1 to provide early warning of the appearance of more pathogenic strains. [ABSTRACT FROM AUTHOR]

The present study aimed at investigating the selective enrichment of surface marker and functional microRNA (miRNA) profiles of cluster of differentiation (CD)34+ blast-derived microvesicles (MVs) from parental cells in chronic myelogenous leukemia (CML), thus providing an experimental basis for MVs to be used to predict characteristics of CD34+ blasts. Magnetic activated cell sorting and continuous differential centrifugation were used to isolate primary CML CD34+ blasts and MVs, in addition to utilizing flow cytometry to identify surface markers of CD34+ blasts and blast-derived MVs. Microarray analysis and the reverse transcription-quantitative polymerase chain reaction were performed to analyze miRNA profiles of CD34+ blasts and MVs. The results of the present study indicated that primary CML CD34+ blasts were able to release MVs, which were selectively enriched with the surface markers CD34 and CD123, and functional miRNAs from parental cells. A total of 15 miRNAs were upregulated in CD34+ blast derived-MVs compared with in CD34+ cells. Distinct Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms characterized by altered gene expression and potentially associated miRNA were identified. Upregulated miRNAs in MVs were associated with cell development, tumorigenesis and signaling pathways involving ErbB and phosphoinositide 3-kinase/protein kinase B. The present study provides evidence, which increases the understanding of physiological functions of cancer-derived MVs, and aids the understanding of the roles of CD34+ blast-derived MVs in CML-associated processes. [ABSTRACT FROM AUTHOR]

Transcription activator-like (TAL) effectors are bacterial type III secretion proteins that function as transcription factors in plants during Xanthomonas/plant interactions, conditioning either host susceptibility and/or host resistance. Three types of TAL effector associated resistance (R) genes have been characterized--recessive, dominant non-transcriptional, and dominant TAL effector-dependent transcriptional based resistance. Here, we discuss the last type of R genes, whose functions are dependent on direct TAL effector binding to discrete effector binding elements in the promoters. Only five of the so-called executor R genes have been cloned, and commonalities are not clear. We have placed the protein products in two groups for conceptual purposes. Group 1 consists solely of the protein from pepper, BS3, which is predicted to have catalytic function on the basis of homology to a large conserved protein family. Group 2 consists of BS4C-R, XA27, XA10, and XA23, all of which are relatively short proteins from pepper or rice with multiple potential transmembrane domains. Group 2 members have low sequence similarity to proteins of unknown function in closely related species. Firm predictions await further experimentation on these interesting new members to the R gene repertoire, which have potential broad application in new strategies for disease resistance. [ABSTRACT FROM AUTHOR]

The toxicities of conventional chemotherapeutic agents to normal cells restrict their dosage and clinical efficacy in acute leukemia; therefore, it is important to develop novel chemotherapeutics, including natural products, which selectively target cancer-specific pathways. The present study aimed to explore the effect of the chemopreventive agent asiatic acid (AA) on the proliferation and apoptotic rate of the leukemia cell line HL-60 and investigated the mechanisms underlying its anti-tumor activity. The effect of AA on the proliferation of HL-60 cells was evaluated using the MTT assay. Annexin V-fluorescein isothiocyanate/propidium iodide double staining followed by flow cytometric analysis as well as Hoechst 33258 staining were used to analyze the apoptotic rate of the cells. Furthermore, changes of survivin, B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 expressions were detected by western blot analysis. AA blocked the growth of HL-60 cells in a dose- and time-dependent manner. The IC50-value of AA on HL-60 cells was 46.67±5.08 µmol/l for 24 h. AA induced apoptosis in a dose-dependent manner, which was inhibited in the presence of Z-DEVD-FMK, a specific inhibitor of caspase. The anti-apoptotic proteins Bcl-2, Mcl-1 and survivin were downregulated by AA in a dose-dependent manner. Concurrently, AA inhibited ERK and p38 phosphorylation in a dose-dependent manner, while JNK phosphorylation was not affected. In conclusion, the present study indicated that the p38 and ERK pathways, as well as modulation of Bcl-2 family and survivin proteins were key regulators of apoptosis induced in HL-60 cells in response to AA. [ABSTRACT FROM AUTHOR]

Accessions of common wheat (Triticum aestivum L. subsp. aestivum) from the USDA-ARS National Small Grains Collection (NSGC) are a resource for wheat scientists worldwide. The genetic diversity of the wheat core subset, representing approximately 10% of the collection's 42,138 T. aestivum accessions, was examined using 390 diversity arrays technology (DArT) markers, 4941 single nucleotide polymorphisms (SNPs), and descriptor data. The marker profiles revealed duplicates, which were excluded to form an informative core (iCore) of 3230 accessions. The iCore population structure and diversity within various subgroups were examined with analysis of molecular variance, principal coordinate analysis, cluster analysis, and by ranking the contribution of individual accessions to overall diversity. Accession groups based on molecular marker data corresponded well to their geographic origin, and population structure was accounted for primarily by differences between Iranian landrace accessions and the rest of the accessions. Accessions classified as breeding lines were overrepresented among those ranked as most diverse based on SNP data, whereas Iranian landraces were underrepresented. Although less diverse as a group, Iranian landrace accessions had a higher frequency of resistance to bunt diseases and Russian wheat aphid compared with the iCore as a whole. The present study provides support for establishing core subsets based on geographic origin of accessions and will be a basis for further study of diversity among NSGC wheats. [ABSTRACT FROM AUTHOR]

Nickel hydroxide/hydroxyapatite (Ni(OH)2/HAP) nanoparticles (NPs) coated with rhodamine B hydrazide (RBH) were successfully synthesized in three steps. First, Ni(OH)2/HAP-COOH NPs were synthesized by a facile hydrothermal route in the presence of citric acid. Second, rhodamine B was reacted with hydrazine hydrate to obtain rhodamine B hydrazide (RBH). Finally, RBH was conjugated on the surface of Ni(OH)2/HAP-COOH NPs to form Ni(OH)2/HAP-RBH. As affinity adsorbents, these NPs can directly purify histidine-tagged (His-tagged) proteins from a mixture of lysed cells, and exhibit high protein adsorption capacity with a maximum value of 115 mg g-1. A prominent fluorescence enhancement at 578 nm was observed in the presence of Pt2+, accompanied by a change in absorption spectrum. These NPs display excellent selectivity and sensitive recognition of Pt2+ in comparison with other metal ions and anions with a detection limit of 0.03 µM. These NPs exhibit low cytotoxicity and can be used as a probe for Pt2+ and living cell imaging. [ABSTRACT FROM AUTHOR]

Jagged2 is closely associated with numerous congenital diseases and has an important role in multiple malignancies. It has been identified that Jagged2 is a sonic hedgehog-regulated factor. However, its expression and correlation with Gli1 in hepatocellular carcinoma (HCC) remain unknown. A total of 58 samples of surgically resected paired HCC and normal tumor-adjacent tissues were collected, and the Jagged2 and Gli1 expression was detected in the samples using immunohistochemical staining. The correlation between Jagged2 and Gli1 protein expression, and their correlation with the clinicopathological features of HCC were analyzed. The protein expression of Jagged2 and Gli1 were significantly upregulated in HCC tissues compared with the normal tumor-adjacent tissues (P<0.001, respectively), and Jagged2 expression was positively correlated with Gli1 protein in HCC tissues (r=0.643, P<0.001). Jagged2 and Gli1 protein were expressed at significantly higher levels in patients with intrahepatic metastasis, high histological grade and advanced tumor-node-metastasis stage (TNM) stage (P<0.05, respectively). With the Cox proportional hazard regression mode, the independent factors predictive of poor long-term HCC survival following radical liver resection included high expression of Jagged2, advanced TNM stage and high histological grade (P<0.05). In HCC, high expression of Jagged2 was closely correlated with poor clinicopathological features, and it may therefore be a potential prognosis predictor for patients with HCC. [ABSTRACT FROM AUTHOR]

Sterol regulatory element-binding protein 1 (SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC), is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05). SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM) stage (p < 0.05). The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05). Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05). In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05). Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05). These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis. [ABSTRACT FROM AUTHOR]

Hagberg falling number (FN) is an important quality trait used for grain grading. The FN test can only be measured in the late stages of variety development when progeny are homogeneous and sufficient grain is available for testing. The FN is strongly influenced by environmental conditions during reproductive growth stages, including excess moisture, extreme temperature, and biotic and abiotic stresses. The objective of this study was to identify potential genomic regions that influence FN in a subset of 110 hard white spring (HWS) wheat (Triticum aestivum L.) accessions from the National Small Grain Collection (NSGC) using genomewide association mapping. The FN tests were conducted using grain flour samples of these accessions grown in five environments. A total of 1740 single nucleotide polymorphism (SNP) markers were used to detect SNP-FN associations using both the general linear model (GLM) and the mixed linear model (MLM). Thirteen quantitative trait loci (QTL) located in nine chromosomal regions were identified in both GLM and MLM approaches. Pyramiding these QTL could explain up to 45% of the phenotypic variation of FN. The present study identified several potential markers for use in marker-assisted selection for high FN lines in wheat breeding. [ABSTRACT FROM AUTHOR]

We use the analytic methods and the properties of Gauss sums to study the computational problem of one kind hybrid mean value involving the general Dedekind sums and the two-term exponential sums, and give an interesting computational formula for it. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate whether asiatic acid (AA), a pentacyclic triterpene derived from Centella asiatica, exerts anti-proliferative effects on multiple myeloma RPMI 8226 cells and to determine the molecular mechanism underlying the anticancer action of AA. The study sought to analyze the potential role of AA on the proliferation of the RPMI 8226 cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium assay. Cell cycle arrest was detected by low cytometry, and the expression levels of focal adhesion kinase (FAK) in the myeloma cells induced by AA were analyzed using the western blotting and immunoprecipitation methods. The results indicated that AA signiicantly inhibited cell proliferation in a time- and dose-dependent manner and led to G2/M phase arrest at concentrations of 35 and 40 µmol/l in the RPMI 8226 cells. The expression levels of FAK and p-FAK were distinctly decreased following AA treatment (at the concentration of 40 µmol/l) for 24 h compared with that of the control groups. Taken together, these results demonstrated that AA was able to regulate cell cycle progression in RPMI 8226 cells, thereby signiicantly inhibiting cell growth. Furthermore, AA decreased the expression levels of FAK, indicating that the antitumor mechanism of AA may be associated with the inhibition of signal transduction mediated by FAK. [ABSTRACT FROM AUTHOR]

A highly improved Pd-catalyzed cyanation of aryl chlorides to corresponding benzonitriles was demonstrated in aqueous media. Moreover, Pd-catalyzed cyanation of aryl tosylates and benzenesulfonates with K[Fe(CN)] was developed under the similar conditions, which extended application scope of the cyanation. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Probability distributions for carbon burning, atmospheric CO2, and global average temperature are produced by time series calibration of models of utility optimization and carbon and heat balance using log-linear production functions. Population growth is used to calibrate a logistically evolving index of development that influences production efficiency. Energy production efficiency also includes a coefficient that decreases linearly with decreasing carbon intensity of energy production. This carbon intensity is a piecewise linear function of fossil carbon depletion. That function is calibrated against historical data and extrapolated by sampling a set of hypotheses about the impact on the carbon intensity of energy production of depleting fluid fossil fuel resources and increasing cumulative carbon emissions. Atmospheric carbon balance is determined by a first order differential equation with carbon use rates and cumulative carbon use as drivers. Atmospheric CO2 is a driver in a similar heat balance. Periodic corrections are included where required to make residuals between data and model results indistinguishable from independently and identically distributed normal distributions according to statistical tests on finite Fourier power spectrum amplitudes and nearest neighbor correlations. Asymptotic approach to a sustainable non-fossil energy production is followed for a global disaggregation into a tropical/developing and temperate/more-developed Electronic supplementary material The online version of this article region. The increase in the uncertainty of global average temperature increases nearly quadratically with the increase in the temperature from the present through the next two centuries. [ABSTRACT FROM AUTHOR]

The deficits in Alzheimer disease (AD) stem at least partly from neurotoxic β-amyloid peptides generated from the amyloid precursor protein (APP). APP may also be cleaved intracellularly at Asp664 to yield a second neurotoxic peptide, C31. Previously, we showed that cleavage of APP at the C-terminus is required for the impairments seen in APP transgenic mice, by comparing elements of the disease in animals modeling AD, with (platelet-derived growth factor B-chain promoter-driven APP transgenic mice; PDAPP) versus without (PDAPP D664A) a functional Asp664 caspase cleavage site. However, the signaling mechanism(s) by which Asp664 contributes to these deficits remains to be elucidated. In this study, we identify a kinase protein, recently shown to bind APP at the C-terminus and to contribute to AD, whose activity is modified in PDAPP mice, but normalized in PDAPP D664A mice. Specifically, we observed a significant increase in nuclear p21-activated kinase (isoforms 1, 2, and or 3; PAK-1/2/3) activation in hippocampus of 3 month old PDAPP mice compared with non-transgenic littermates, an effect completely prevented in PDAPP D664A mice. In contrast, 13 month old PDAPP mice displayed a significant decrease in PAK-1/2/3 activity, which was once again absent in PDAPP D664A mice. Similarly, in hippocampus of early and severe AD subjects, there was a progressive and subcellular-specific reduction in active PAK-1/2/3 compared with normal controls. Interestingly, total PAK-1/2/3 protein was increased in early AD subjects, but declined in moderate AD and declined further, to significantly below that of control levels, in severe AD. These findings are compatible with previous suggestions that PAK may be involved in the pathophysiology of AD, and demonstrate that both early activation and late inactivation in the murine AD model require the cleavage of APP at Asp664. [ABSTRACT FROM AUTHOR]

In addition to the proteolytic cleavages that give rise to amyloid-β (Aβ), the amyloid-β protein precursor (AβPP) is cleaved at Asp664 intracytoplasmically. This cleavage releases a cytotoxic peptide, APP-C31, removes AβPP-interaction motifs required for signaling and internalization, and is required for the generation of AD-like deficits in a mouse model of the disease. Although we and others had previously shown that Asp664 cleavage of AβPP is increased in AD brains, the distribution of the Asp664-cleaved forms of AβPP in non-diseased and AD brains at different ages had not been determined. Confirming previous reports, we found that Asp664-cleaved forms of AβPP were increased in neuronal cytoplasm and nuclei in early-stage AD brains but were absent in age-matched, non-diseased control brains and in late-stage AD brains. Remarkably, however, Asp664-cleaved AβPP was prominent in neuronal somata and in processes in entorhinal cortex and hippocampus of non-diseased human brains at ages <45 years. Our observations suggest that Asp664 cleavage of AβPP may be part of the normal proteolytic processing of AβPP in young (<45 years) human brain and that this cleavage is down-regulated with normal aging, but is aberrantly increased and altered in location in early AD. [ABSTRACT FROM AUTHOR]

• Background and Aims A central goal of biogeography and ecology is to uncover and understand distributional patterns of organisms. China has long been a focus of attention because of its rich biota, especially with respect to plants. Using 290 floras from across China, this paper quantitatively characterizes the composition of floristic elements at multiple scales (i.e. national, provincial and local), and explores the extent to which climatic and geographical factors associated with each flora can jointly and independently explain the variation in floristic elements in local floras.• Methods A study was made of 261 local floras, 28 province-level floras and one national-level flora across China. Genera of seed plants in each flora were assigned to 14 floristic elements according to their worldwide geographical distributions. The composition of floristic elements was related to climatic and geographical factors.• Key Results and Conclusions Variations in percentages of cosmopolitan, tropical and temperate genera among local floras tend to be greater at higher latitudes than at lower latitudes. Latitude is strongly correlated with the proportions of 13 of the 14 floristic elements. Correlations of the proportions of floristic elements with longitude are much weaker than those with latitude. Climate represented by the first principal component of a principal component analysis was strongly correlated with the proportions of floristic elements in local floras (|r| = 0·75 ± 0·18). Geographical coordinates independently explained about four times as much variation in floristic elements as did climate. Further research is necessary to examine the roles of water–energy dynamics, geology, soils, biotic interactions, and historical factors such as land connections between continents in the past and at present in creating observed floristic patterns. [ABSTRACT FROM AUTHOR]

The spectro-temporal receptive field (STRF) of an auditory neuron describes the linear relationship between the sound stimulus in a time-frequency representation and the neural response. Time-frequency representations of a sound in turn require a nonlinear operation on the sound pressure waveform and many different forms for this non-linear transformation are possible. Here, we systematically investigated the effects of four factors in the non-linear step in the STRF model: the choice of logarithmic or linear filter frequency spacing, the time-frequency scale, stimulus amplitude compression and adaptive gain control. We quantified the goodness of fit of these different STRF models on data obtained from auditory neurons in the songbird midbrain and forebrain. We found that adaptive gain control and the correct stimulus amplitude compression scheme are paramount to correctly modelling neurons. The time-frequency scale and frequency spacing also affected the goodness of fit of the model but to a lesser extent and the optimal values were stimulus dependant. [ABSTRACT FROM AUTHOR]

The effect of interfacial scattering on anomalous Hall effect (AHE) was studied in the multilayers. Field-dependent Hall resistivity was measured in the temperature range of 5–300 K with the magnetic field up to 50 kOe. The anomalous Hall resistivity () was enhanced by more than six times at 5 K from n  =  1 to n  =  12 due to the increased interfacial scattering, whereas the longitudinal resistivity () was increased nearly three times. A scaling relation with was obtained for and measured at 5 K, indicating that the dominant mechanism(s) of the AHE in these multilayers should be side-jump or/and intrinsic in nature. The new scaling relation (Tian et al 2009 Phys. Rev. Lett. 103 087206) has been applied to our data to identify the origin of the AHE in this type of multilayer. [ABSTRACT FROM AUTHOR]

Understanding phenomena at the nanometre scale is of fundamental importance for future improvements of desired properties of nanomaterials. We report a detailed investigation of the microstructure and the resulting magnetic anisotropy by magnetic, transmission electron microscopy (TEM) and Mossbauer measurements of electrospun Cu1[?]xZnxFe2O4 nanofibres. Our results show that the electrospun Cu1[?]xZnxFe2O4 nanofibres exhibit nearly isotropic magnetic anisotropy. TEM measurements indicate that the nanofibres are composed of loosely connected and randomly aligned nanograins. As revealed by the Henkel plot, these nanofibres and the nanograins within the nanofibres are dipolar coupled, which reduces the effective shape anisotropy leading to a nearly random configuration of the magnetic moments inside the nanofibres; hence, the observed nearly isotropic magnetic anisotropy can be easily understood. [ABSTRACT FROM AUTHOR]

: Objectives The multiresistance plasmid pKP96 from Klebsiella pneumoniae was sequenced completely and analysed concerning its genetic environment and distributing of antimicrobial resistance genes. : Methods The complete sequence of the plasmid was determined using a whole-genome shotgun approach. MICs of 13 antimicrobial agents were determined using Etests. A conjugation experiment was performed in liquid medium. : Results pKP96 is a circularly closed 67 850 bp multiresistance plasmid with an IncN incompatibility group. Seventy putative genes were identified according to the annotation of the finished sequence. The backbone region of the plasmid, comprising the conjugal transfer and plasmid replication regions, showed 91% identity to the IncN plasmid R46. Several mobile elements were found to be inserted into pKP96 together with antimicrobial resistance genes, including qnrA1, aac(6′)-Ib-cr and blaCTX-M-24. : Conclusions Plasmid pKP96 is a chimera that has acquired its multiple antimicrobial resistance determinants horizontally from different sources. It may have evolved from an ancestor plasmid similar to R46 through the stepwise events of integration or recombination. [ABSTRACT FROM AUTHOR]