An upstream signaling gene calmodulin regulates the synthesis of insect wax via activating fatty acid biosynthesis pathway.

Insect wax accumulates on the surface of insect cuticle, which acts as an important protective barrier against rain, ultraviolet light radiation, pathogens, etc. The waxing behavior, wax composition and molecular mechanism underling wax biosynthesis are unclear in dustywings. Herein, the current study determined the vital developmental stage for waxing behavior in dustywings, examined the components of waxy secretions, and identified key regulatory genes for wax biosynthesis. The wax glands were mainly located on the thorax and abdomen of dustywing adults. The adults spread the waxy secretions over their entire body surface. The metabolomics analysis identified 32 lipids and lipid-like molecules, 15 organic acids and derivatives, 7 benzenoids, etc. as the main components of waxy secretions. The fatty acids represented the largest proportion of the category of lipid and lipid-like molecules. The conjoint analysis of metabolomics and transcriptomics identified two crucial genes fatty acyl-CoA reductase (CsFAR) and calmodulin (CsCaM) for wax biosynthesis. The down-regulation of these genes via nanocarrier-mediated RNA interference technology significantly reduced the amount of wax particles. Notably, the RNAi of CsCaM apparently suppressed the expression of most genes in fatty acid biosynthesis pathway, indicating the CsCaM might act as a main upstream regulator of fatty acid biosynthesis pathway.

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma.

BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. RESULTS: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. CONCLUSIONS: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).

Retracted: Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Mei Mei Guan, Qun Xian Rao, Miao Ling Huang, Li Juan Wang, Shao Dan Lin, Qing Chen, Chang Hao Liu. Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines. Med Sci Monit, 2019; 25: 8131-8141. DOI: 10.12659/MSM.916292.

Expression characteristics of peripheral lymphocyte programmed death 1 and FoxP3+ Tregs in gastric cancer during surgery and chemotherapy.

BACKGROUND: Programmed death 1 (PD-1) and CD4+CD25+FoxP3+ expression in peripheral blood T-cells has been previously reported in various types of cancer. However, the specific variation tendency during surgery and chemotherapy, as well as their relationship in gastric cancer patients, still remain unclear. Understanding this aspect may provide some novel insights for future studies on tumor recurrence and tumor immune escape, and also serve as a reference for determining the optimal timing and dose of clinical anti-PD-1 antibodies. AIM: To observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3+ regulatory T cells (FoxP3+ Tregs) before and after surgery or chemotherapy in gastric cancer patients. METHODS: Twenty-nine stomach cancer patients undergoing chemotherapy after a D2 gastrectomy provided 10 mL peripheral blood samples at each phase of the perioperative period and during chemotherapy. This study also included 29 age-matched healthy donors as a control group. PD-1 expression was detected on lymphocytes, including CD4+CD8+CD45RO+, CD4+CD45RO+, and CD8+CD45RO+ lymphocytes as well as regulatory T cells. RESULTS: We observed a significant increase of PD-1 expression on immune subsets and a larger number of FoxP3+ Tregs in gastric cancer patients (P < 0.05). Following D2 gastrectomy, peripheral lymphocytes PD-1 expression and the number of FoxP3+ Tregs notably decrease (P < 0.05). However, during postoperative chemotherapy, we only observed a decrease in PD-1 expression on lymphocytes in the CD8+CD45RO+ and CD8+CD45RO+ populations. Additionally, linear correlation analysis indicated a positive correlation between PD-1 expression and the number of CD4+CD45RO+FoxP3high activated Tregs (aTregs) on the total peripheral lymphocytes (r = 0.5622, P < 0.0001). CONCLUSION: The observed alterations in PD-1 expression and the activation of regulatory T cells during gastric cancer treatment may offer novel insights for future investigations into tumor immune evasion and the clinical application of anti-PD-1 antibodies in gastric cancer.

Prunolactones A-G, proangiogenic isocoumarin derivatives with an unusual 6/6/6/6/6 spiropentacyclic skeleton from the endophytic fungus Phomopsis prunorum.

Seven novel isocoumarins, prunolactones A-G (1-7), featuring an unusual 6/6/6/6/6 spiropentacyclic skeleton, together with two biosynthetic precursors phomopsilactone (8) and methyl 3-epi-shikimate (9), were isolated from the endophytic fungus Phomopsis prunorum guided by UPLC-QTOF-MS and 1H NMR spectroscopic analytical techniques. Their structures including absolute configurations of 1-7 were elucidated based on extensive spectroscopic data, X-ray diffraction analysis, and ECD calculations. Biogenetically, compounds 1-7 are proposed to be derived from polyketide and shikimate pathways via key intermolecular Diels - Alder reactions. Compounds 2, 3, and 7 showed significant in vivo proangiogenic activity in transgenic zebrafish.

Fatty acid metabolism decreased while sexual selection increased in brown rats spreading south.

For mammals that originate in the cold north, adapting to warmer environments is crucial for southwards invasion. The brown rat (Rattus norvegicus) originated in Northeast China and has become a global pest. R. n. humiliatus (RNH) spread from the northeast, where R. n. caraco (RNC) lives, to North China and diverged to form a subspecies. Genomic analyses revealed that subspecies differentiation was promoted by temperature but impeded by gene flow and that genes related to fatty acid metabolism were under the strongest selection. Transcriptome analyses revealed downregulated hepatic genes related to fatty acid metabolism and upregulated those related to pheromones in RNH vs. RNC. Similar patterns were observed in relation to cold/warm acclimation. RNH preferred mates with stronger pheromone signals intra-populationally and more genetic divergence inter-populationally. We concluded that RNH experienced reduced fat utilization and increased pheromone-mediated sexual selection during its invasion from the cold north to warm south.

Study on the Efficacy of "Information Platform + Self-Care Model" on the Health Status of Discharged Patients Following Vaginal Natural Orifice Transluminal Endoscopic Surgery.

Objective: To discuss the impact of the "information platform + self-care model" on the health status of discharged patients following vaginal natural orifice transluminal endoscopic surgery (vNOTES). Methods: Patients underwent vNOTES at a tertiary specialized women's and children's hospital in Chengdu. They were randomly assigned to one of two groups-the intervention group (29 patients) and the control group (29 patients). The control group received standard education after discharge, while the intervention group received guidance based on an "information platform + self-care model" on discharge; a questionnaire survey was conducted for both groups one month after discharge. Results: The quality of life score in the intervention group was higher than that in the control group, and the difference was statistically significant (P < 0.05); the scores of the intervention group on dimensions such as vitality, general health perceptions, physical role functioning, social role functioning, emotional role functioning, and mental health, except for physical functioning (Z = 0.034, P = 0.973) and bodily pain (Z = 1.470, P = 0.141), were higher than those in the control group one month after discharge, and the difference was statistically significant (P < 0.05). There was no patient (0) in the intervention group who had an unscheduled visit/admission, and there was 1 patient (3.6%) in the control group who had unscheduled visit/admission; there were no statistical differences between the two groups in the number of patients who had an unscheduled visit/admission 1 month after discharge (P = 0.491). Conclusion: The application of the "information platform + self-care model" can, to a certain extent, improve the health status of patients following vNOTES after discharge, and it can also reduce unscheduled visits/admissions, but more research with a larger sample size is required.

Insights into the adverse effects of prepubertal chronic ethanol exposure on adult female reproduction.

Heavy drinking in women is known to adversely affect pregnancy and fertility. However, pregnancy is a complex process, and the adverse effects of ethanol on pregnancy does not mean that ethanol will have adverse effects on all stages from gamete to fetal formation. Similarly, the adverse effects of ethanol before and after adolescence cannot be generalized. To focus on the effects of prepubertal ethanol on female reproductive ability, we established a mouse model of prepubertal ethanol exposure by changing drinking water to 20% v/v ethanol. Some routine detections were performed on the model mice, and details such as mating, fertility, reproductive organ and fetal weights were recorded day by day after discontinuation of ethanol exposure. Prepubertal ethanol exposure resulted in decreased ovarian weight and significantly reduced oocyte maturation and ovulation after sexual maturation, however, normal morphology oocytes with discharged polar body showed normal chromosomes and spindle morphology. Strikingly, oocytes with normal morphology from ethanol exposed mice showed reduced fertilization rate, but once fertilized they had the ability to develop to blastocysts. RNA-seq analysis showed that the gene expression of the ethanol exposed oocytes with normal morphology had been altered. These results show the adverse effects of prepubertal alcohol exposure on adult female reproductive health.

Predictive model of chemotherapy-related toxicity in elderly Chinese cancer patients.

Purpose: Older cancer patients are more likely to develop and die from chemotherapy-related toxicity. However, evidence on drug safety and optimal effective doses is relatively limited in this group. The aim of this study was to develop a tool to identify elderly patients vulnerable to chemotherapy toxicity. Patients and methods: Elderly cancer patients ≥60 years old who visited the oncology department of Peking Union Medical College Hospital between 2008 and 2012 were included. Each round of chemotherapy was regarded as a separate case. Clinical factors included age, gender, physical status, chemotherapy regimen and laboratory tests results were recorded. Severe (grade ≥3) chemotherapy-related toxicity of each case was captured according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Univariate analysis was performed by chi-square statistics to determine which factors were significantly associated with severe chemotherapy toxicity. Logistic regression was used to build the predictive model. The prediction model was validated by calculating the area under the curve of receiver operating characteristic (ROC). Results: A total of 253 patients and 1,770 cases were included. The average age of the patients was 68.9 years. The incidence of grade 3-5 adverse events was 24.17%. Cancer type (non-GI cancers), BMI<20 kg/m2, KPS<90%, severe comorbidity, polychemotherapy, standard dose chemotherapy, low white blood cells count, anemia, low platelet cells count, low creatine level and hypoalbuminemia were associated with severe chemotherapy-related toxicity. We used these factors to construct a chemotherapy toxicity prediction model and the area under the ROC curve was 0.723 (95% CI, 0.687-0.759). Risk of toxicity increased with higher risk score (11.98% low, 31.51% medium, 70.83% high risk; p < 0.001). Conclusion: We constructed a predictive model of chemotherapy toxicity in elderly cancer patients based on a Chinese population. The model can be used to guide clinicians to identify vulnerable population and adjust treatment regimens accordingly.

Inheritance of social dominance is associated with global sperm DNA methylation in inbred male mice.

Dominance relationships between males and their associated traits are usually heritable and have implications for sexual selection in animals. In particular, social dominance and its related male pheromones are heritable in inbred mice; thus, we wondered whether epigenetic changes due to altered levels of DNA methylation determine inheritance. Here, we used C57BL/6 male mice to establish a social dominance-subordination relationship through chronic dyadic encounters, and this relationship and pheromone covariation occurred in their offspring, indicative of heritability. Through transcriptome sequencing and whole-genome DNA methylation profiling of the sperm of both generations, we found that differential methylation of many genes was induced by social dominance-subordination in sires and could be passed on to the offspring. These methylated genes were mainly related to growth and development processes, neurodevelopment, and cellular transportation. The expression of the genes with similar functions in whole-genome methylation/bisulfite sequencing was also differentiated by social dominance-subordination, as revealed by RNA-seq. In particular, the gene Dennd1a, which regulates neural signaling, was differentially methylated and expressed in the sperm and medial prefrontal cortex in paired males before and after dominance-subordination establishment, suggesting the potential epigenetic control and inheritance of social dominance-related aggression. We suggest that social dominance might be passed on to male offspring through sperm DNA methylation and that the differences could potentially affect male competition in offspring by affecting the development of the nervous system.

Integrated Analysis of lncRNA-mRNA Regulatory Networks Related to Lipid Metabolism in High-Oleic-Acid Rapeseed.

A high oleic acid content is considered an essential characteristic in the breeding of high-quality rapeseed in China. Long-chain non-coding RNA (lncRNA) molecules play an important role in the plant's growth and its response to stress. To better understand the role of lncRNAs in regulating plant reproductive development, we analyzed whole-transcriptome and physiological data to characterize the dynamic changes in lncRNA expression during the four representative times of seed development of high- and low-oleic-acid rapeseed in three regions. We identified 21 and 14 lncRNA and mRNA modules, respectively. These modules were divided into three types related to region, development stages, and material. Next, we analyzed the key modules related to the oil content and the oleic acid, linoleic acid, and linolenic acid contents with physiological data and constructed the key functional network analysis on this basis. Genes related to lipid metabolism, such as 3-ketoacyl-CoA synthase 16 (KCS16) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), were present in the co-expression network, suggesting that the effect of these genes on lipid metabolism might be embodied by the expression of these lncRNAs. Our results provide a fresh insight into region-, development-stage-, and material-biased changes in lncRNA expression in the seeds of Brassica napus. Some of these lncRNAs may participate in the regulatory network of lipid accumulation and metabolism, together with regulated genes. These results may help elucidate the regulatory system of lncRNAs in the lipid metabolism of high-oleic-acid rapeseed seeds.

Flavonoid Synthesis-Related Genes Determine the Color of Flower Petals in Brassica napus L.

The color of rapeseed (Brassica napus L.) petal is usually yellow but can be milky-white to orange or pink. Thus, the petal color is a popular target in rapeseed breeding programs. In his study, metabolites and RNA were extracted from the yellow (Y), yellow/purple (YP), light purple (LP), and purple (P) rapeseed petals. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), RNA-Seq, and quantitative real-time (qRT-PCR) analyses were performed to analyze the expression correlation of differential metabolites and differential genes. A total of 223 metabolites were identified in the petals of the three purple and yellow rapeseed varieties by UPLC-MS/MS. A total of 20511 differentially expressed genes (DEGs) between P, LP, YP, versus Y plant petals were detected. This study focused on the co-regulation of 4898 differential genes in the three comparison groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and quantitative RT-PCR analysis showed that the expression of BnaA10g23330D (BnF3'H) affects the synthesis of downstream peonidin and delphinidin and is a key gene regulating the purple color of petals in B. napus. L. The gene may play a key role in regulating rapeseed flower color; however, further studies are needed to verify this. These results deepen our understanding of the molecular mechanisms underlying petal color and provide the theoretical and practical basis for flower breeding targeting petal color.

Comparative study on abortion characteristics of Nsa CMS and Pol CMS and analysis of long non-coding RNAs related to pollen abortion in Brassica napus.

Cytoplasmic male sterile system (CMS) is one of the important methods for the utilization of heterosisin Brassica napus. The involvement of long non-coding RNAs (lncRNAs) in anther and pollen development in B.napus has been recognized, but there is little data on the involvement of lncRNAs in pollen abortion in different types of rapeseed CMS. The present study compared the cytological, physiological and biochemical characteristics of Nsa CMS (1258A) and Pol CMS (P5A) during pollen abortion, and high-throughput sequencing of flower buds of different sizes before and after pollen abortion. The results showed that insufficient energy supply was an important physiological basis for 1258A and P5A pollen abortion, and 1258A had excessive ROS (reactive oxygen species) accumulation in the stage of pollen abortion. Functional analysis showed that Starch and sucrose metabolism and Sulfur metabolism were significantly enriched before and after pollen abortion in 1258A and P5A, and a large number of genes were down-regulated. In 1258A, 227 lncRNAs had cis-targeting regulation, and 240 cis-target genes of the lncRNAs were identified. In P5A, 116 lncRNAs had cis-targeting regulation, and 101 cis-target genes of the lncRNAs were identified. There were five lncRNAs cis-target genes in 1258A and P5A during pollen abortion, and LOC106445716 encodes ß-D-glucopyranosyl abscisate ß-glucosidase and could regulate pollen abortion. Taken together, this study, provides a new perspective for lncRNAs to participate in the regulation of Nsa CMS and Pol CMS pollen abortion.

Tissue-Specific Transcriptome and Metabolome Analysis Reveals the Response Mechanism of Brassica napus to Waterlogging Stress.

During the growth period of rapeseed, if there is continuous rainfall, it will easily lead to waterlogging stress, which will seriously affect the growth of rapeseed. Currently, the mechanisms of rapeseed resistance to waterlogging stress are largely unknown. In this study, the rapeseed (Brassica napus) inbred lines G230 and G218 were identified as waterlogging-tolerant rapeseed and waterlogging-sensitive rapeseed, respectively, through a potted waterlogging stress simulation and field waterlogging stress experiments. After six days of waterlogging stress at the seedling stage, the degree of leaf aging and root damage of the waterlogging-tolerant rapeseed G230 were lower than those of the waterlogging-sensitive rapeseed G218. A physiological analysis showed that waterlogging stress significantly increased the contents of malondialdehyde, soluble sugar, and hydrogen peroxide in rape leaves and roots. The transcriptomic and metabolomic analysis showed that the differential genes and the differential metabolites of waterlogging-tolerant rapeseed G230 were mainly enriched in the metabolic pathways, biosynthesis of secondary metabolites, flavonoid biosynthesis, and vitamin B6 metabolism. Compared to G218, the expression levels of some genes associated with flavonoid biosynthesis and vitamin B metabolism were higher in G230, such as CHI, DRF, LDOX, PDX1.1, and PDX2. Furthermore, some metabolites involved in flavonoid biosynthesis and vitamin B6 metabolism, such as naringenin and epiafzelechin, were significantly up-regulated in leaves of G230, while pyridoxine phosphate was only significantly down-regulated in roots and leaves of G218. Furthermore, foliar spraying of vitamin B6 can effectively improve the tolerance to waterlogging of G218 in the short term. These results indicate that flavonoid biosynthesis and vitamin B6 metabolism pathways play a key role in the waterlogging tolerance and hypoxia stress resistance of Brassica napus and provide new insights for improving the waterlogging tolerance and cultivating waterlogging-tolerant rapeseed varieties.

Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients.

INTRODUCTION: Combining lenvatinib with a programmed cell death protein-1 (PD-1) inhibitor has been explored for the treatment of un-resectable hepatocellular carcinoma (uHCC). This study aimed to investigate the real-world efficacy of and prognostic factors for survival associated with lenvatinib plus PD-1 inhibitor treatment in a large cohort of Asian uHCC patients even the global LEAP-002 study failed to achieve the primary endpoints. METHODS: Patients with uHCC treated with lenvatinib and PD-1 inhibitors were included. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and adverse events (AEs). Prognostic factors for survival were also analyzed. RESULTS: A total of 378 uHCC patients from two medical centers in China were assessed retrospectively. The median patient age was 55 years, and 86.5% of patients were male. Hepatitis B virus (HBV) infection (89.9%) was the dominant etiology of uHCC. The median OS was 17.8 (95% confidence interval (CI) 14.0-21.6) months. The median PFS was 6.9 (95% CI 6.0-7.9) months. The best ORR and disease control rate (DCR) were 19.6% and 73.5%, respectively. In multivariate analysis, Child‒Pugh grade, Barcelona Clinic Liver Cancer stage, Eastern Cooperative Oncology Group performance status score, involved organs, tumor burden score, and combination with local therapy were independent prognostic factors for OS. A total of 100% and 57.9% of patients experienced all-grade and grade 3/4 treatment-emergent AEs, respectively. CONCLUSION: This real-world study of lenvatinib plus PD-1 inhibitor treatment demonstrated long survival and considerable ORRs and DCRs in uHCC patients in China. The tolerability of combination therapy was acceptable but must be monitored closely.

Transcriptome and Regional Association Analyses Reveal the Effects of Oleosin Genes on the Accumulation of Oil Content in Brassica napus.

Rapeseed stores lipids in the form of oil bodies. Oil bodies in the seeds of higher plants are surrounded by oleosins. Adjusting oleosin protein levels can prevent the fusion of oil bodies and maintain oil body size during seed development. However, oil contents are affected by many factors, and studies on the complex molecular regulatory mechanisms underlying the variations in seed oil contents of B. napus are limited. In this study, a total of 53 BnOLEO (B. napus oleosin) genes were identified in the genome of B. napus through a genome-wide analysis. The promoter sequences of oleosin genes consisted of various light-, hormone-, and stress-related cis-acting elements, along with transcription factor (TF) binding sites, for 25 TF families in 53 BnOLEO genes. The differentially expressed oleosin genes between two high- and two low-oil-content accessions were explored. BnOLEO3-C09, BnOLEO4-A02, BnOLEO4-A09, BnOLEO2-C04, BnOLEO1-C01, and BnOLEO7-A03 showed higher expressions in the high-oil-content accessions than in low-oil-content accessions, at 25, 35, and 45 days after pollination (DAP) in two different environments. A regional association analysis of 50 re-sequenced rapeseed accessions was used to further analyze these six BnOLEO genes, and it revealed that the nucleotide variations in the BnOLEO1-C01 and BnOLEO7-A03 gene regions were related to the phenotypic variations in seed oil content. Moreover, a co-expression network analysis revealed that the BnOLEO genes were directly linked to lipid/fatty acid metabolism, TF, lipid transport, and carbohydrate genes, thus forming a molecular network involved in seed oil accumulation. These favorable haplotypes can be utilized in molecular marker-assisted selection in order to further improve seed oil contents in rapeseed.

Genome-Wide Identification and Characterization of Oil-Body-Membrane Proteins in Polyploid Crop Brassica napus.

Oil-body-membrane proteins (OBMPs) are essential structural molecules of oil bodies and also versatile metabolic enzymes involved in multiple cellular processes such as lipid metabolism, hormone signaling and stress responses. However, the global landscape for OBMP genes in oil crops is still lacking. Here, we performed genome-wide identification and characterization of OBMP genes in polyploid crop Brassica napus. B. napus contains up to 88 BnaOBMP genes including 53 oleosins, 20 caleosins and 15 steroleosins. Both whole-genome and tandem duplications have contributed to the expansion of the BnaOBMP gene family. These BnaOBMP genes have extensive sequence polymorphisms, and some harbor strong selection signatures. Various cis-acting regulatory elements involved in plant growth, phytohormones and abiotic and biotic stress responses are detected in their promoters. BnaOBMPs exhibit differential expression at various developmental stages from diverse tissues. Importantly, some BnaOBMP genes display spatiotemporal patterns of seed-specific expression, which could be orchestrated by transcriptional factors such as EEL, GATA3, HAT2, SMZ, DOF5.6 and APL. Altogether, our data lay the foundations for studying the regulatory mechanism of the seed oil storage process and provide candidate genes and alleles for the genetic improvement and breeding of rapeseed with high seed oil content.

Safety and effectiveness of apatinib in elderly patients with metastatic gastric cancer: a sub-analysis from the large-scale, prospective observational study of apatinib for gastric cancer treatment in a real-world clinical setting (AHEAD-G202).

Background: Apatinib was shown to improve the survival of Chinese patients with refractory metastatic gastric cancer (mGC). As an orally administered drug, it has been widely used in elderly patients because the dosing schedule can be adjusted flexibly. However, data on the efficacy and safety of apatinib in elderly patients is scarce. The aim of this study was to evaluate the toxicity and effectiveness of apatinib for elderly patients with mGC in a real-world setting. Methods: Data from the sub-population of patients who were ≥65 years enrolled in the AHEAD-G202 trial were analyzed. Patients with mGC were prospectively registered and initially received ≤850 mg oral apatinib daily combined or not combined with chemotherapy, at the investigator's discretion. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 117 patients were included. There were 51 (43.59%) patients in the low-dose (250 mg) group, 60 (51.28%) patients in the mid-dose (425 to 500 mg) group, and 6 (5.13%) patients in the high-dose (850 mg) group according to the initial daily doses. Hypertension (6.84%) was the only grade 3-4 adverse event (AE) with a prevalence of more than 5% and across the low-dose (11.76%), mid-dose (3.33%) and high-dose group (0%). The median OS and PFS were 7.13 months (95% CI: 5.04 to 9.22 months) and 4.27 months (95% CI: 3.24 to 5.29 months), respectively. The OS and PFS were similar among the 65-74 and ≥75 years groups (χ2=1.406, P=0.306; χ2=0.378, P=0.066, respectively). The OS and PFS were also comparable among the 3 dose groups. Conclusions: Elderly patients with mGC can tolerate and benefit from apatinib therapy. A lower initial daily dosing strategy may be a suitable choice for elderly patients in clinical practice.

Comprehensive evaluation of high-oleic rapeseed (Brassica napus) based on quality, resistance, and yield traits: A new method for rapid identification of high-oleic acid rapeseed germplasm.

To scientifically evaluate and utilize high-oleic acid rape germplasm resources and cultivate new varieties suitable for planting in the Hunan Province, 30 local high-oleic acid rape germplasms from Hunan were used as materials. The 12 personality indices of quality, yield, and resistance were comprehensively evaluated by variability, correlation, principal component, and cluster analyses. The results of variability showed that except for oleic acid, the lowest coefficient of variation was oil content, which was 0.06. Correlation analysis showed that oil content was positively correlated with main traits such as yield per plant and oleic acid, which could be used in the early screening of high-oleic rape germplasm. The results of principal component analysis showed that the 12 personality indicators were integrated into four principal components, and the cumulative contribution rate was 62.487%. The value of comprehensive coefficient 'F' was positively correlated with the first, second, and fourth principal components and negatively correlated with the third principal component. Cluster analysis showed that 30 high-oleic rape germplasms could be divided into four categories consisting of 9 (30%), 6 (20%), 7 (23%), and 8 (27%) high-oleic rape germplasms, each with the characteristics of "high disease resistance", "high yield", "high protein", and "more stability". This study not only provides a reference basis for high-oleic rape breeding but also provides a theoretical basis for their early screening.

Hyperparathyroidism Caused by Coexisting Parathyroid Hyperplasia and Unilateral Bifocal Parathyroid Carcinoma.

ABSTRACT: The coexistence of parathyroid hyperplasia and carcinoma is uncommon. Here we report findings of 99m Tc-sestamibi SPECT/CT study in a case of unilateral bifocal parathyroid carcinoma coexisting with parathyroid hyperplasia in a 49-year-old man. The images showed 4 foci of elevated activity around the thyroid. Histopathology confirmed the 2 lesions of the left side as parathyroid hyperplasia and the other 2 lesions of the right side as parathyroid carcinoma.