Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns.

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.

High-quality genome assembly enables prediction of allele-specific gene expression in hybrid poplar.

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.

Telomere-to-telomere and haplotype-resolved genome assembly of the Chinese cork oak (Quercus variabilis).

The Quercus variabilis, a deciduous broadleaved tree species, holds significant ecological and economical value. While a chromosome-level genome for this species has been made available, it remains riddled with unanchored sequences and gaps. In this study, we present a nearly complete comprehensive telomere-to-telomere (T2T) and haplotype-resolved reference genome for Q. variabilis. This was achieved through the integration of ONT ultra-long reads, PacBio HiFi long reads, and Hi-C data. The resultant two haplotype genomes measure 789 Mb and 768 Mb in length, with a contig N50 of 65 Mb and 56 Mb, and were anchored to 12 allelic chromosomes. Within this T2T haplotype-resolved assembly, we predicted 36,830 and 36,370 protein-coding genes, with 95.9% and 96.0% functional annotation for each haplotype genome. The availability of the T2T and haplotype-resolved reference genome lays a solid foundation, not only for illustrating genome structure and functional genomics studies but also to inform and facilitate genetic breeding and improvement of cultivated Quercus species.

Study on soil hydraulic properties of slope farmlands with different degrees of erosion degradation in a typical black soil region.

In order to explore the impact of soil erosion degradation on soil hydraulic properties of slope farmland in a typical black soil region, typical black soils with three degrees of erosion degradation (light, moderate and heavy) were selected as the research objects. The saturated hydraulic conductivity, water holding capacity and water supply capacity of the soils were analyzed, as well as their correlations with soil physicochemical properties. The results showed that the saturated hydraulic conductivity of black soils in slope farmlands decreased with erosion degradation degree, which was higher in 0-10 cm soil layer than in 10-20 cm soil layer. The water holding capacity and water supplying capacity of typical black soils also decreased with the increase of erosion degradation degree, and both of them were stronger in the upper soil than in the lower soil. With the aggravation of erosion degradation of black soils, soil organic matter content decreased while soil bulk density increased, leading to the decline of soil hydraulic conductivity. The increase of soil bulk density and the decrease of contents of organic matter and >0.25 mm water stable aggregates were the main factors leading to the decrease of soil water holding capacity. These findings provide scientific basis and basic data for rational utilization of soil water, improvement of land productivity and prevention of soil erosion.

Unraveling the evolutionary dynamics of the TPS gene family in land plants.

Terpenes and terpenoids are key natural compounds for plant defense, development, and composition of plant oil. The synthesis and accumulation of a myriad of volatile terpenoid compounds in these plants may dramatically alter the quality and flavor of the oils, which provide great commercial utilization value for oil-producing plants. Terpene synthases (TPSs) are important enzymes responsible for terpenic diversity. Investigating the differentiation of the TPS gene family could provide valuable theoretical support for the genetic improvement of oil-producing plants. While the origin and function of TPS genes have been extensively studied, the exact origin of the initial gene fusion event - it occurred in plants or microbes - remains uncertain. Furthermore, a comprehensive exploration of the TPS gene differentiation is still pending. Here, phylogenetic analysis revealed that the fusion of the TPS gene likely occurred in the ancestor of land plants, following the acquisition of individual C- and N- terminal domains. Potential mutual transfer of TPS genes was observed among microbes and plants. Gene synteny analysis disclosed a differential divergence pattern between TPS-c and TPS-e/f subfamilies involved in primary metabolism and those (TPS-a/b/d/g/h subfamilies) crucial for secondary metabolites. Biosynthetic gene clusters (BGCs) analysis suggested a correlation between lineage divergence and potential natural selection in structuring terpene diversities. This study provides fresh perspectives on the origin and evolution of the TPS gene family.

Retinoic acid delays murine palatal shelf elevation by inhibiting Wnt5a-mediated noncanonical Wnt signaling and downstream Cdc-42/F-actin remodeling in mesenchymal cells.

BACKGROUND: Mammalian palatal shelves erupted from maxillary prominences undergo vertical extention, transient elevation, and horizontal growth to fuse. Previous studies in mice reported that the retinoic acid (RA) contributed to cleft palate in high incidence by delaying the elevating procedure, but little was known about the underlying biological mechanisms. METHODS: In this study, hematoxylin-eosin and immunofluorescence staining were employed to evaluate the phenotypes and the expression of related markers in the RA-treated mice model. In situ hybridization and RT-qPCR were used to detect the expression of genes involved in Wnt signaling pathway. The palatal mesenchymal cells were cultured in vitro, and stimulated with RA or CASIN, and co-treated with Foxy5. Wnt5a and Ccd42 expression were evaluated by immunofluorescence staining. Phalloidin was used to label the microfilament cytoskeleton (F-actin) in cultured cells. RESULTS: We revealed that RA resulted in 100% incidence of cleft palate in mouse embryos, and the expression of genes responsible for Wnt5a-mediated noncanonical Wnt signal transduction were specifically downregulated in mesenchymal palatal shelves. The in vitro study of palatal mesenchymal cells indicated that RA treatment disrupted the organized remodeling of cytoskeleton, an indicative structure of cell migration regulated by the small Rho GTPase Cdc42. Moreover, we showed that the suppression of cytoskeleton and cell migration induced by RA was partially restored using the small molecule Foxy-5-mediated activation of Wnt5A, and this restoration was attenuated by CASIN (a selective GTPase Cdc42 inhibitor) again. CONCLUSIONS: These data identified a crucial mechanism for Wnt5a-mediated noncanonical Wnt signaling in acting downstream of Rho GTPase Cdc42 to regulate cytoskeletal remodeling and cell migration during the process of palate elevation. Our study provided a new explanation for the cause of cleft palate induced by RA.

Haplotype-resolved genome assembly of Coriaria nepalensis a non-legume nitrogen-fixing shrub.

Coriaria nepalensis Wall. (Coriariaceae) is a nitrogen-fixing shrub which forms root nodules with the actinomycete Frankia. Oils and extracts of C. nepalensis have been reported to be bacteriostatic and insecticidal, and C. nepalensis bark provides a valuable tannin resource. Here, by combining PacBio HiFi sequencing and Hi-C scaffolding techniques, we generated a haplotype-resolved chromosome-scale genome assembly for C. nepalensis. This genome assembly is approximately 620 Mb in size with a contig N50 of 11 Mb, with 99.9% of the total assembled sequences anchored to 40 pseudochromosomes. We predicted 60,862 protein-coding genes of which 99.5% were annotated from databases. We further identified 939 tRNAs, 7,297 rRNAs, and 982 ncRNAs. The chromosome-scale genome of C. nepalensis is expected to be a significant resource for understanding the genetic basis of root nodulation with Frankia, toxicity, and tannin biosynthesis.

Unique gene duplications and conserved microsynteny potentially associated with resistance to wood decay in the Lauraceae.

Wood decay resistance (WDR) is marking the value of wood utilization. Many trees of the Lauraceae have exceptional WDR, as evidenced by their use in ancient royal palace buildings in China. However, the genetics of WDR remain elusive. Here, through comparative genomics, we revealed the unique characteristics related to the high WDR in Lauraceae trees. We present a 1.27-Gb chromosome-level assembly for Lindera megaphylla (Lauraceae). Comparative genomics integrating major groups of angiosperm revealed Lauraceae species have extensively shared gene microsynteny associated with the biosynthesis of specialized metabolites such as isoquinoline alkaloids, flavonoid, lignins and terpenoid, which play significant roles in WDR. In Lauraceae genomes, tandem and proximal duplications (TD/PD) significantly expanded the coding space of key enzymes of biosynthesis pathways related to WDR, which may enhance the decay resistance of wood by increasing the accumulation of these compounds. Among Lauraceae species, genes of WDR-related biosynthesis pathways showed remarkable expansion by TD/PD and conveyed unique and conserved motifs in their promoter and protein sequences, suggesting conserved gene collinearity, gene expansion and gene regulation supporting the high WDR. Our study thus reveals genomic profiles related to biochemical transitions among major plant groups and the genomic basis of WDR in the Lauraceae.

Gapless genome assembly of azalea and multi-omics investigation into divergence between two species with distinct flower color.

The genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle. Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy, has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle, while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii. This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.

Differential gene expression and potential regulatory network of fatty acid biosynthesis during fruit and leaf development in yellowhorn (Xanthoceras sorbifolium), an oil-producing tree with significant deployment values.

Xanthoceras sorbifolium (yellowhorn) is a woody oil plant with super stress resistance and excellent oil characteristics. The yellowhorn oil can be used as biofuel and edible oil with high nutritional and medicinal value. However, genetic studies on yellowhorn are just in the beginning, and fundamental biological questions regarding its very long-chain fatty acid (VLCFA) biosynthesis pathway remain largely unknown. In this study, we reconstructed the VLCFA biosynthesis pathway and annotated 137 genes encoding relevant enzymes. We identified four oleosin genes that package triacylglycerols (TAGs) and are specifically expressed in fruits, likely playing key roles in yellowhorn oil production. Especially, by examining time-ordered gene co-expression network (TO-GCN) constructed from fruit and leaf developments, we identified key enzymatic genes and potential regulatory transcription factors involved in VLCFA synthesis. In fruits, we further inferred a hierarchical regulatory network with MYB-related (XS03G0296800) and B3 (XS02G0057600) transcription factors as top-tier regulators, providing clues into factors controlling carbon flux into fatty acids. Our results offer new insights into key genes and transcriptional regulators governing fatty acid production in yellowhorn, laying the foundation for efforts to optimize oil content and fatty acid composition. Moreover, the gene expression patterns and putative regulatory relationships identified here will inform metabolic engineering and molecular breeding approaches tailored to meet biofuel and bioproduct demands.

Potential allopolyploid origin of Ericales revealed with gene-tree reconciliation.

Few incidents of ancient allopolyploidization (polyploidization by hybridization or merging diverged genomes) were previously revealed, although there is significant evidence for the accumulation of whole genome duplications (WGD) in plants. Here, we focused on Ericales, one of the largest and most diverse angiosperm orders with significant ornamental and economic value. Through integrating 24 high-quality whole genome data selected from ~ 200 Superasterids genomes/species and an algorithm of topology-based gene-tree reconciliation, we explored the evolutionary history of in Ericales with ancient complex. We unraveled the allopolyploid origin of Ericales and detected extensive lineage-specific gene loss following the polyploidization. Our study provided a new hypothesis regarding the origin of Ericales and revealed an instructive perspective of gene loss as a pervasive source of genetic variation and adaptive phenotypic diversity in Ericales.

Efficient synthesis of N-acetyllactosamine using immobilized ß-galactosidase on a novel 3D polymer support.

A novel polymer support was prepared by curing of epoxy resin in ethanol solution in the macropores of a melamine sponge. The produced polymer gel could uniformly deposit on the surface of melamine in either porous or nonporous morphology. The composite sponge with porous coating can be used as a large-sized and well-mass transferred support for the immobilization of ß-galactosidase from Bacillus circulans through method of adsorption and crosslinking, and a column reactor was made for the preparation of N-acetyllactosamine in a sealed circulation way. The porosity and specific surface area of the support were 91.6 % and 46 m2/g, respectively. The loading amount and the specific activity of immobilized ß-galactosidase under the optimal immobilization conditions were 41.2 mg/gsupport and 16.5 U/mgprotein, respectively. In the biosynthesis of N-acetyllactosamine lactose and N-acetylglucosamine were used as donor and acceptor, respectively. Under optimized conditions the N-acetyllactosamine yield reached 54 % within 150 min at 50 °C. After 10 cycles, the immobilized ß-galactosidase retained 70 % of the original activity.

[Compositions and metabolic footprints of soil nematode communities under different alfalfa-crop planting patterns in semi-arid region of the Loess Plateau, Northwest China.] / 黄土高原半干旱区不同苜蓿-作物种植方式下土壤线虫群落组成及代谢足迹.

Soil nematode communities play an important role in ecosystem material cycling and energy flow. In this study, soil samples were collected from three rotation systems in southern Ningxia mountainous region, including alfalfa continuous cropping (A-A), alfalfa-corn rotation (A-C), alfalfa-potato rotation (A-P). Soil physicochemical properties, nematode community composition and their metabolic footprints were measured. Compared with the A-A plot, the concentrations of soil organic carbon (SOC) and total nitrogen (TN) were significantly increased by 4.6% and 7.4% for SOC, 4.0% and 5.2% for TN in the A-C and A-P plots, respectively. Soil microbial biomass carbon and nitrogen were significantly higher in the A-C and A-P plots when compared with the A-A plot. The total abundance of soil nematodes in the A-C and A-P plots was higher by 49.5% and 93.7% than that in the A-A plot, respectively, with the dominant trophic group being changed to omnivores-predators from plant parasite. Compared to the A-A plot, the plant parasite index (PPI) was decreased significantly in the A-C and A-P plots, indicating that the harm of plant-parasites was reduced in soil food web. The nematode channel ratio (NCR) in the A-C and A-P plots were higher than that in the A-A plot, indicating that the role of bacterial decomposition was enhanced in soil organic matter decomposition. The maturity index (MI), the total nematode metabolic footprint, enrichment footprint, structure footprint in the A-C and A-P plots were all significantly higher than those in the A-A plot, suggesting that the structure and function of soil food web were more mature and stable, and the productivity and metabolic activity of nematodes were significantly enhanced. In general, the alfalfa-crop rotations improved soil nutrient status and reduced the disturbance degree of soil food web. Furthermore, soil ecosystem developed in the stable and healthy direction, which would be beneficial to the sustainable development of agriculture.

Surface properties and suspension stability of low-temperature pyrolyzed biochar nanoparticles: Effects of solution chemistry and feedstock sources.

Intensive application of biochar requires better understanding of their environmental behaviors such as stability, fate, and mobility. The release of bulk biochar into biochar nanoparticles (NPs) may bring risks because of their potential flowing into downstream water bodies with nutrients/containments attached. Low-temperature pyrolyzed biochars, namely fruit tree branch biochar of 350/450/550 °C (FB350, FB450 and FB550), corn straw biochar of 350 °C (CB350) and peanut straw biochar of 350 °C (PB350), were produced, and their NPs were extracted. The yield, elemental composition, mineral composition, surface functional groups and zeta potential of biochar NPs were characterized. Subsequently their suspension stability was evaluated in NaCl and CaCl2 solutions by dynamic light scattering technique. The Hamaker constants and particle interaction energy of the biochar NPs were calculated by adopting Derjaguin-Landau-Verwey-Overbeek theory. For biochar NPs of same feedstock, the stability of FB350/450/550-NPs could be predicted well by their zeta potential values. The types of their surface functional groups were the same while their adsorption intensity differed. The scenarios for biochar NPs of different feedstock sources were different, that is, inconsistent variation was observed between their zeta potential and suspension stability, which were rooted in the variable type and quantity of surface functional groups. In conclusion, feedstock was the most significant factor that influenced the suspension stability of biochar NPs, followed by the pyrolysis temperature and solution chemistry, which were highly dependent on surface potential. The findings provide references for the environmental risk evaluation of biochar NPs and reasonable application of biochar in field.

[Characteristics of soil microbial and nematode communities under artificial Medicago sativa grasslands with different cultivation years in semi-arid region of Loess Plateau, Northwest China]. / 黄土高原半干旱区不同种植年限紫花苜蓿人工草地土壤微生物和线虫群落特征.

The establishment of Medicago sativa artificial grasslands is an important practice of grassland vegetation restoration in the Loess Plateau. Understanding community characteristics of soil microbes and nematodes can provide important information for evaluating and controlling ecolo-gical and environmental effects of vegetation restoration. In this study, we used M. sativa artificial grasslands with four different cultivation years (1, 2, 6 and 12 years) in southern Ningxia mountainous region, with a farmland and a natural grassland as control, to explore changing trends of the two biological communities during artificial grassland restoration in semi-arid region of the Loess Plateau. The results showed that: 1) After the conversion of farmland to M. sativa grassland, Chao1, ACE and Shannon diversity indices of soil bacterial community increased firstly and then decreased, which reached the maximum after six years of M. sativa grassland establishment. For soil fungal community, Shannon diversity index was lower in 6 and 12 year-old M. sativa grasslands than in the other two artificial grasslands, and the community composition differed across restoration years. 2) With the increases of restoration years, the abundance of soil nematodes showed a similar changing trend with Shannon diversity index of bacterial community. The composition of nematode community did not greatly differ between the 6-year-old M. sativa grassland and farmland, while that in 12-year-old artificial grassland was more similar to that in natural grassland. The proportion of bacterivorous and plant-feeding nematodes, as well as plant parasitic index and nematode channel index of nematode community,were increased, while the proportion of fungivores and omnivores-predators and maturity index were decreased. 3) During the restoration, changes in soil organic carbon, total nitrogen and available phosphorus greatly affected soil microbial community, which could further influence soil nematode community. There were significant correlations between dominant microbial phyla and trophic groups of soil nematodes, implying the possible effects of soil microbes on nematode community. In M. sativa artificial grassland with different establishment years, changes in plant biomass and diversity might significantly affect soil nematode and microbial communities through affecting their food conditions.

[Effects of soil surface electric field on aggregates breakdown and water erosion in black soil region of Northeast China]. / åœŸå£¤è¡¨é¢ç”µåœºå¯¹é»‘åœŸå›¢èšä½“ç ´ç¢Žå’Œä¾µèš€çš„å½±å“.

Through quantitatively adjust soil electric field, we investigated the effect of soil electric field on aggregate stability and soil erosion in black soil region of Northeast China with the experiments of wet sieving and rainfall simulation. Results showed that: 1) Soil surface potential absolute value and electric field strength increased with the decreases of electrolyte concentration in bulk solution. Soil electric field strength could reach to 108 V·m-1. 2) With the increase of soil electric field strength, the degree of fragmentation of soil aggregates increased and the mean weight diameter (MWD) decreased sharply first and then kept constant. 3) With decreasing electrolyte concentration and increasing surface potential, the amount of soil loss increased. As the electrolyte concentration was <0.01 mol·L-1, the corresponding soil surface potential was > 210 and 209 mV for Bin-xian and Keshan, respectively, the cumulative amounts of soil loss with rainfall time almost overlapped, suggesting that the electrolyte concentration of 0.01 mol·L-1 was the threshold for soil erosion. 4) There was a linear relationship between soil cumulative loss and MWD. Our results indicated that soil electric field strength increased as the rain enters into the soil, which could induce soil aggregate breakdown and release amounts of fine soil particles. Finally, soil erosion occurred under the driving of flowing water. Our results provided insights into the mechanism underlying soil erosion in the black soil region of Northeast China.

A meta-analysis of surgical decompression in the treatment of diabetic peripheral neuropathy.

BACKGROUND: Over the last decade, surgical decompression procedures have been commonly used in the treatment of diabetic peripheral neuropathy (DPN). However, the effectiveness of them remains to be proved. METHODS: A comprehensive literature search of databases including PubMed-Medline, Ovid-Embase, and Cochrane Library was performed to collect the related literatures. The Medical Subject Headings used were "diabetic neuropathy," "surgical decompression," and "outcomes." The methodological index for nonrandomized studies was adopted for assessing the studies included in this review. Analyses were performed with Review Manager (Version 5.3, The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, 2014). RESULTS: A total of 12 literatures (including 8 prospective and 4 retrospective) encompassing 1825 patients with DPN were included in the final analysis. Only 1 literature was identified as a randomized-controlled trial. The remaining 11 literatures were observational studies; 7 of them were classified as upper-extremity nerve decompression group and 4 of them were classified as lower-extremity nerve decompression group. Meta-analysis shows that Boston questionnaire symptom severity and functional status of upper extremities, and distal motor latency and sensory conduction velocity of median nerve of DPN patients are significantly improved after carpal tunnel release. Besides, visual analog scale and 2-point discrimination are considered clinically and statistically significant in lower extremities after operation. CONCLUSIONS: The findings from our review have shown the efficacy of surgical decompression procedures in relieving the neurologic symptoms and restoring the sensory deficits in DPN patients. As there are few high-quality randomized-controlled trials or well-designed prospective studies, more data are needed to elucidate the role of surgical procedures for DPN treatment in the future.

PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer.

Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the PIK3CA gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with PIK3A mutation showed worse response to first-line chemotherapy than those without PIK3CA mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5+ CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore, PIK3CA mutation/LGR5+ expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA mutation/LGR5+ expression was a potential biomarker for monitoring chemotherapy resistance in CRC.

[Analysis of Spatio-temporal Distribution and Variation Characteristics of Aerosol Optical Depth over the Northwest of China by MODIS C6 Product].

This work compared the collection 6 MODIS aerosol optical depth products with sun photometer data from AERONET, and evaluated the applicability of C6 merged data in the northwest of China. The spatio-temporal variation characteristics and influencing factors of AOD over northwest of China were analyzed by MODIS/AQUA C6 MYD08-M3 products from 2006 to 2015, and the results showed that Southern Xinjiang and Guanzhong region of Shanxi province had relatively high AOD, whereas the south of Qinghai and Gansu province had low values; Junggar Basin was the incremental area of AOD for the first 5 years and second 5 years, whereas converse result existed in Qaidam Basin and Hetao area. Temporally, the yearly mean AOD ranged from 0.18 to 0.22, and the declined trend occurred in 2011, and the annual decrease rate was about 0.32%; Because of different intensity and frequency of dust weather, the south of Xinjiang showed a significant interannual variation characteristic; East of the northwest displayed an obviously declining trend from 2011 to 2015, and the yearly mean decrease was about 1.1%. The AOD in north of Xinjiang and Qinghai-Tibet remained stable. The seasonal changes of AOD among different areas over the northwest had the same trend, all gradually declined from spring to autumn, and increased in winter.