Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Roles of miR319-regulated TCPs in plant development and response to abiotic stress

Elaborate regulation of gene expression is required for plants to maintain normal growth,development,and reproduction.MicroRNAs(miRNAs)and transcription factors are key players that control gene expression in plant regulatory networks.The TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR(TCP)family comprises plantspecific transcription factors that contain a conserved TCP domain of 59 amino acids.Some members of this family are targeted by miR319,one of the most ancient and evolutionarily conserved miRNAs in plants.Accumulating evidence has revealed that miR319-regulated TCP(MRTCP)genes participate extensively in plant development and responses to environmental stress.In this review,the structural characteristics and classifications of TCP transcription factors and the regulatory relationships between TCP transcription factors and miRNAs are introduced.Current knowledge of the regulatory functions of MRTCP genes in multiple biological pathways including leaf development,vascular formation,flowering,hormone signaling,and response to environmental stresses such as cold,salt,and drought is summarized.This review will be beneficial for understanding the roles of the MRTCP-mediated regulatory network and its molecular mechanisms in plant development and stress response,and provides a theoretical basis for plant genetic improvement.

Co-location of QTL for Sclerotinia stem rot resistance and flowering time in Brassica napus

Sclerotinia stem rot(SSR) caused by Sclerotinia sclerotiorum(Lib.) de Bary is one of the most devastating diseases of Brassica napus worldwide. Both SSR resistance and flowering time(FT) adaptation are major breeding goals in B. napus. However, early maturing rapeseed varieties, which are important for rice-rapeseed rotation in China, are often highly susceptible to SSR. Here, we found that SSR resistance was significantly negatively correlated with FT in a natural population containing 521 rapeseed inbred lines and a double haploid(DH) population with 150 individual lines, both of which had great variation in FT. Four chromosomal regions on A2, A6, C2, and C8 affecting both SSR resistance and FT were identified using quantitative trait loci(QTL) mapping after constructing a high-density genetic map based on single nucleotide polymorphism markers in the DH population.Furthermore, we aligned QTL for the two traits identified in the present and previous studies to the B. napus reference genome, and identified four colocalized QTL hotspots of SSR resistance and FT on A2(0–7.7 Mb), A3(0.8–7.5 Mb), C2(0–15.2 Mb), and C6(20.2–36.6 Mb). Our results revealed a genetic link between SSR resistance and FT in B.napus, which should facilitate the development of effective strategies in both early maturing and SSR resistance breeding and in map-based cloning of SSR resistance QTL.

Host-induced gene silencing of multiple pathogenic factors of Sclerotinia sclerotiorum confers resistance to Sclerotinia rot in Brassica napus

Sclerotinia sclerotiorum is generally considered one of the most economically damaging pathogens in oilseed rape(Brassica napus).Breeding for Sclerotinia resistance is challenging,as no immune germplasm available in B.napus.It is desirable to develop new breeding strategies.In the present study,hostinduced gene silencing(HIGS),developed based on RNA interference(RNAi),was applied to protect B.napus from S.sclerotiorum infection.Three pathogenicity genes,the endo-polygalacturonase gene(Ss PG1),cellobiohydrolase gene(Ss CBH),and oxaloacetate acetylhydrolase gene(Ss OAH1),were chosen as HIGS targets.Co-incubation of synthesized double-stranded RNAs(ds RNAs)with S.sclerotiorum in liquid medium significantly reduced the transcript levels of the target genes.Application to plant surfaces of ds RNA targeting the three genes conferred effective protection against S.sclerotiorum.Stable transgenic B.napus plants expressing small interfering RNAs with sequence identity to Ss PG1,Ss CBH,and Ss OAH1 were generated.HIGS transgenic B.napus prevented the expression of S.sclerotiorum target genes,slowed pathogenicity-factor accumulation,impeded fungal growth,and suppressed appressorium formation,thereby conferring resistance to S.sclerotiorum.Simultaneous silencing of Ss PG1,Ss CBH,and Ss OAH1 by stable expression of a chimeric hairpin RNAi construct in B.napus led to enhanced protection phenotypes(with disease lesion size reduced by 36.8%–43.7%).We conclude that HIGS of pathogenic-factor genes of S.sclerotiorum is a promising strategy for controlling Sclerotinia rot in oilseed rape.

Control Effects of Four Kinds of Insecticides against Empoasca vitis Gothe

Field test results showed that 24% Chlorfenapyr SC and 15% Indoxacarb EC had quick availability and long duration against Empoasca vitis Gothe. The control effects of 450 mL/hm2 24% Chlorfenapyr SC and 330 mL/hm2 15% Indoxacarb were significantly higher than that of 450 g/hm2 10% Imidacloprid WP ,which were ideal pesticides against E. vitis and could be popularized and applied in large area.

Applied Technology of Botanical Pesticides against Empoasca pirisuga Matumura

[Objectives] The paper was to explore the control effects of different botanical pesticides against Empoasca pirisuga Matumura. [Methods] 5% Eucalyptol SL, 0.5% matrine SL and 50% thiacloprid WDG were used to control E. pirisuga , and the decline rate of insect population was investigated. [Results] Eucalyptol had good control effect on E. pirisuga , with slow effect but long duration. It was harmless to natural enemies in tea gardens, with high safety and no chemical injury. [Conclusions] The study provides a theoretical basis for the application of botanical pesticides in tea production.

Field Excursion Introduction for IGCP 679 1^stInternational Symposium: Progress in Cretaceous Geology in Shandong Province, China

The non-marine Cretaceous sequences are well developed in the relict basins, i.e. the Luxi basin in the west, and the Jiaolai basin in the east of Shandong Province. The Lower Cretaceous Santai Formation (140 - 136 Ma) in the Luxi basin contains aeolian dune deposits, which were formed under the control by westerly. The Cretaceous strata of the Jiaolai basin are divided into three groups: i.e. in ascending order, the Laiyang, Qingshan and Wangshi groups. New SHRIMP zircon U-Pb radiometric dating data demonstrated six Cretaceous volcanism episodes. The lower part of the Wangshi Group should be assigned to the upper Lower Cretaceous. An Ir anomaly recovered in the lower Jiaozhou Formation suggests that the Cretaceous/Palaeogene boundary would be in the interval between 537.3 - 537.4 m in the borehole JK1. At last the detailed information about the pre-symposium field excursion was introduced.

Effects of Sinochem Microbial Organic Fertilizer on Tea Plants

[Objectives]This study was conducted to explore the application effects of Sinochem microbial organic fertilizer on tea plants.[Methods]Through the experiment and demonstration of Sinochem microbial organic fertilizer,its effects on the yield and quality of tea and the physical and chemical quality of soil were explored.[Results]Compared with the conventional organic fertilizer cake fertilizer,the fertilizer could increase the weight of freshly picked bud leaves,increase the yield of tea,and thus promote the growth of tea plants.It increased the contents of chlorophyll components,amino acids and tea polyphenols,the main functional substances of tea,which was conducive to improving the internal quality of tea.It improved the physical and chemical properties of soil,and increased the contents of organic matter,alkali-hydrolyzable nitrogen and available phosphorus in tea garden soil.It also had a good effect in improving soil environmental health indexes and physical and chemical properties,and did not contain heavy metals and plant growth hormones.[Conclusions]This study provides a theoretical basis for the popularization and application of Sinochem microbial organic fertilizer.

Expression Patterns of ABA and GA Metabolism Genes and Hormone Levels during Rice Seed Development and Imbibition: A Comparison of Dormant and Non-Dormant Rice Cultivars

Seed dormancy is an important agronomic trait in cereals. Using deep dormant （N22）, medium dormant （ZH11）, and non-dormant （G46B） rice cultivars, we correlated seed dormancy phenotypes with abscisic acid （ABA） and gibberellin （GA） metabolism gene expression profiles and phytohormone levels during seed development and imbibition. A time course analysis of ABA and GA content during seed development showed that N22 had a high ABA level at early and middle seed developmental stages, while at late developmental stage it declined to the level of ZHll; however, its ABA/GA ratio maintained at a high level throughout seed development. By contrast, G46B had the lowest ABA content during seed development though at early developmental stage its ABA level was close to that of ZH11, and its ABA/GA ratio peaked at late developmental stage that was at the same level of ZHll. Compared with N22 and G46B, ZH11 had an even and medium ABA level during seed development and its ABA/GA ratio peaked at the middle developmental stage. Moreover, the seed development time-point having high ABA/GA ratio also had relatively high transcript levels for key genes in ABA and GA metabolism pathways across three cultivars. These indicated that the embryo-imposed dormancy has been induced before the late developmental stage and is determined by ABA/GA ratio. A similar analysis during seed imbibition showed that ABA was synthesized in different degrees for the three cultivars. In addition, water uptake assay for intact mature seeds suggested that water could permeate through husk barrier into seed embryo for all three cultivars; however, all three cultivars showed distinct colors by vanillin-staining indicative of the existence of flavans in their husks, which are dormancy inhibition compounds responsible for the husk-imposed dormancy.

Phenolic Composition Analysis and Gene Expression in Developing Seeds of Yellow-and Black-seeded Brassica napus

Breeders have focused on yellow-seeded Brassica napus （rapeseed） for its better quality com- pared with the black-seeded variety. Moreover, flavonoids have been associated with this kind of rapeseed. In this study, we applied lipid chromatography-electrospray ionization mass spec- trometry （LC-ESI-MSn ） to compare flavonoids in developing seeds of natural black-seeded B. na- pus and yellow-seeded introgression lines selected from progenies of B. napus–Sinapis alba so- matic hybrids. Aside from the most abundant phenolic compounds （sinapine and sinapic acid） and 1, 2-disinapoylglucose, 16 different flavonoids were identified and quantified, including （-）- epicatechin, five monocharged oligomers of （-）-epicatechin （[DP 2]- , [DP 3]- , [DP 4] [DP 2]- B2 and [DP 2]- B5）, quercetin, kaempferol, isorhamnetin-dihexoside, kaempferol-sinapoyl-trihexoside, isorhamnetin- sinapoyl-trihexoside, isorhamnetin-hexoside-sulfate, and isorhamnetin-3-O-glucoside. Most of the flavonoids accumulated with seed development, whereas some rapidly decreased during maturation. The content of these flavonoids was lower in the yellow-seeded materials than in the black seeds. In addition, variations of insoluble procyanidin oligomers and soluble phenolic acids were observed among both rapeseed varieties. Transcriptome changes of genes participating in the flavonoid pathway were discovered by quantitative reverse transcription polymerase chain reaction analysis. Consistent with flavonoid changes identified by high performance liquid chromatography analysis, the expression of most genes in the flavonoid biosynthetic pathway was also downregulated.

Characterization of seedling proteomes and development of markers to distinguish the Brassica A and C genomes

The diploid species Brassica rapa （genome AA） and B. oleracea （genome CC） were compared by full-scale proteome analyses of seedling. A total of 28.2% of the proteins was common to both species, indicating the existence of a basal or ubiquitous proteome. However, a number of discriminating proteins （32.0%） and specific proteins （39.8%） of the Brassica A and C genomes, respectively, were identified, which could represent potentially species-specific functions. Based on these A or C genome-specific proteins, a number of PCR-based markers to distinguish B. rapa and B. oleracea species were also developed.