Deciphering PDH1's role in mung bean domestication: a genomic perspective on pod dehiscence.

Mung bean (Vigna radiata) stands as a crucial legume crop in Asia, contributing to food security. However, our understanding of the underlying genetic foundation governing domesticated agronomic traits, especially those linked to pod architecture, remains largely unexplored. In this study, we delved into the genomic divergence between wild and domesticated mung bean varieties, leveraging germplasm obtained from diverse sources. Our findings unveiled pronounced variation in promoter regions (35%) between the two mung bean subpopulations, suggesting substantial changes in gene expression patterns during domestication. Leveraging transcriptome analysis using distinct reproductive stage pods and subpopulations, we identified candidate genes responsible for pod and seed architecture development, along with Genome-Wide Association Studies (GWAS) and Quantitative Trait Locus (QTL) analysis. Notably, our research conclusively confirmed PDH1 as a parallel domesticated gene governing pod dehiscence in legumes. This study imparts valuable insights into the genetic underpinnings of domesticated agronomic traits in mung bean, and simultaneously highlighting the parallel domestication of pivotal traits within the realm of legume crops.

Biased gene introgression and adaptation in the face of chloroplast capture in Aquilegia amurensis.

Chloroplast capture, a phenomenon that can occur through interspecific hybridization and introgression, is frequently invoked to explain cytonuclear discordance in plants. However, relatively few studies have documented the mechanisms of cytonuclear coevolution and its potential for driving species differentiation and possible functional differences in the context of chloroplast capture. To address this crucial question, we chose the Aquilegia genus, which is known for having minimal sterility among species, and inferred that A. amurensis captured the plastome of A. parviflora based on cytonuclear discordance and gene flow between the two species. We focused on the introgression region and its differentiation from corresponding regions in closely related species, especially its composition in a chloroplast capture scenario. We found that nuclear genes encoding cytonuclear enzyme complexes (CECs; i.e., organelle-targeted genes) of chloroplast donor species were selectively retained and displaced the original CEC genes in chloroplast-receiving species due to cytonuclear interactions during introgression. Notably, the intrinsic correlation of CEC introgression was a greater degree of evolutionary distance for these CECs between A. amurensis and A. parviflora. Terpene synthase activity genes (GO: 0010333) were overrepresented among the introgressed genes, and more than 30% of these genes were CEC genes. These findings support our observations that floral terpene release pattern is similar between A. amurensis and A. parviflora compared with A. japonica. Our study clarifies the mechanisms of cytonuclear coevolution, species differentiation and functional differences in the context of chloroplast capture and highlights the potential role of chloroplast capture in adaptation.

Characterizing complete mitochondrial genome of Aquilegia amurensis and its evolutionary implications.

BACKGROUND: Aquilegia is a model system for studying the evolution of adaptive radiation. However, very few studies have been conducted on the Aquilegia mitochondrial genome. Since mitochondria play a key role in plant adaptation to abiotic stress, analyzing the mitochondrial genome may provide a new perspective for understanding adaptive evolution. RESULTS: The Aquilegia amurensis mitochondrial genome was characterized by a circular chromosome and two linear chromosomes, with a total length of 538,736 bp; the genes included 33 protein-coding genes, 24 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. We subsequently conducted a phylogenetic analysis based on single nucleotide polymorphisms (SNPs) in the mitochondrial genomes of 18 Aquilegia species, which were roughly divided into two clades: the European-Asian clade and the North American clade. Moreover, the genes mttB and rpl5 were shown to be positively selected in European-Asian species, and they may help European and Asian species adapt to environmental changes. CONCLUSIONS: In this study, we assembled and annotated the first mitochondrial genome of the adaptive evolution model plant Aquilegia. The subsequent analysis provided us with a basis for further molecular studies on Aquilegia mitochondrial genomes and valuable information on adaptive evolution in Aquilegia.

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.

IL-17A-induced cancer-associated fibroblasts releases CXCL12 to promote lung adenocarcinoma progression via Wnt/ß-Catenin signaling pathway.

BACKGROUND: Cancer-associated fibroblasts (CAFs) and their secretion, C-X-C motif chemokine ligand 12 (CXCL12), play an important role in the development of lung adenocarcinoma (LUAD). Interleukin 17A (IL-17A) is also crucial in regulating tumor progression. Herein, we explored the specific relationships between these two factors and their mechanisms in the progression of LUAD. METHODS: Immunohistochemistry was utilized to assess the differential expression levels of IL-17A and CXCL12 in tumor versus normal tissues of LUAD patients, followed by gene correlation analysis. Cell counting kit-8 (CCK8), wound-healing and transwell assays were performed to investigate the effect of IL-17A on the function of LUAD cells. qPCR, immunofluorescence, immunohistochemistry and western blot analyses were conducted to elucidate the potential mechanism by which IL-17A facilitates the development of LUAD via CXCL12. Male BALB-C nude mice were used to explore the role of IL-17A in subcutaneous LUAD mouse models. RESULTS: Elevated expression levels of IL-17A and CXCL12 were observed in LUAD tissues, exhibiting a positive correlation. Further studies revealed that IL-17A could stimulate CAFs to enhance the release of CXCL12, thereby facilitating the growth, proliferation, and metastasis of LUAD. The binding of CXCL12 to its specific receptor influences the activation of the Wnt/ß-Catenin pathway, which in turn affects the progression of LUAD. In vivo experiments have demonstrated that IL-17A enhances the growth of LUAD tumors by facilitating the secretion of CXCL12. Conversely, inhibiting CXCL12 has been demonstrated to impede tumor growth. CONCLUSIONS: We discovered that IL-17A promotes the release of CAFs-derived CXCL12, which in turn facilitates the development of LUAD via the Wnt/ß-Catenin signaling pathway.

Clinical application of FIGO 2023 staging system of endometrial cancer in a Chinese cohort.

OBJECTIVE: The International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system for endometrial cancer (EC) was released with incorporating histology, lympho-vascular space invasion, and molecular classification together. Our objective is to further explore the clinical utility and prognostic significance of the 2023 FIGO staging system in China. METHODS: A retrospective analysis was conducted for patients who received standard surgeries and underwent genetic testing using multigene next-generation sequencing (NGS) panels between December 2018 and December 2023 at Fudan University Shanghai Cancer Center, Shanghai, China. The genomic and clinical data of all patients were analyzed, and stages were determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. RESULTS: A total of 547 patients were enrolled in the study. After the restaged by the FIGO 2023 staging system, stage shifts occurred in 147/547 (26.9%) patients. In patients with early stages in FIGO 2009 (stage I-II), 63 cases were rearranged to IAmPOLEmut and 53 cases to IICmp53abn due to the molecular classification of POLEmut and p53abn. Altogether 345 cases were in stage I, 107 cases in stage II, 69 cases in stage III, and 26 cases in stage IV according to the FIGO 2023 staging criteria. For stage I diseases, the 3-year PFS rate was 92.7% and 95.3% in 2009 and 2023 FIGO staging systems, respectively. The 3-year PFS of stage II in 2023 FIGO was lower than that of FIGO 2009 (3-year PFS: 85.0% versus 90.9%), especially in substage IIC and IICmp53abn. Three cases (12%) of stage IIIA in FIGO 2009 were shifted to stage IA3 FIGO 2023, with 3-year PFS rates of 90.9% versus 100%, respectively. In NGS analysis, the most prevalent gene alterations were observed in PTEN and PIK3CA. CONCLUSION: The FIGO 2023 staging system was proved to be a good predictor of survival for EC patients with enhanced precision compared to FIGO 2009. Predominant stage shifts were observed in early-stage diseases. Distinct gene alterations of different subtypes may help to explore more accurate target therapies.

STING/ACSL4 axis-dependent ferroptosis and inflammation promote hypertension-associated chronic kidney disease.

Hypertension is a primary modifiable risk factor for cardiovascular diseases, which often induces renal end-organ damage and complicates chronic kidney disease (CKD). In the present study, histological analysis of human kidney samples revealed that hypertension induced mtDNA leakage and promoted the expression of stimulator of interferon genes (STING) in renal epithelial cells. We used angiotensin II (AngII)- and 2K1C-treated mouse kidneys to elucidate the underlying mechanisms. Abnormal renal mtDNA packing caused by AngII promoted STING-dependent production of inflammatory cytokines, macrophage infiltration, and a fibrogenic response. STING knockout significantly decreased nuclear factor-κB activation and immune cell infiltration, attenuating tubule atrophy and extracellular matrix accumulation in vivo and in vitro. These effects delayed CKD progression. Immunoprecipitation assays and liquid chromatography-tandem mass spectrometry showed that STING and ACSL4 were directly combined at the D53 and K412 amino acids of ACSL4. Furthermore, STING induced renal inflammatory response and fibrosis through ACSL4-dependent ferroptosis. Last, inhibition of ACSL4 using small interfering RNA, rosiglitazone, or Fer-1 downregulated AngII-induced mtDNA-STING-dependent renal inflammation. These results suggest that targeting the STING/ACSL4 axis might represent a potential strategy for treating hypertension-associated CKD.

The Circular RNA circFOXK2 Enhances the Tumorigenesis of Non-Small Cell Lung Cancer Through the miR-149-3p/IL-6 Axis.

Circular RNAs (circRNAs) are the non-coding types of RNAs and are thoughts to be linked with human cancer progression. circFOXK2 is believed to be associated with cancers, however, the molecular mechanisms of circFOXK2 in non-small cell lung cancer (NSCLC) are still unclear. Here we firstly reported that circFOXK2 enhances the tumorigenesis of NSCLC through the miR-149-3p/IL-6 axis. The expression of circFOXK2, microRNA-149-3p (miR-149-3p) and IL-6 were assessed by qRT-PCR and western blot. Transwell, colony formation, wound healing, and CCK-8 assays were used to elucidate NSCLC cells' proliferation, migration, and invasion. MiR-149-3p interaction with circFOXK2 was confirmed by dual-luciferase reporter gene assay (DLRGA). Furthermore, the biological effect of circFOXK2 on NSCLC progression was detected by tumor xenograft assay. CircFOXK2 were upregulated in NSCLC tissues and cells, miR-149-3p were downregulated in NSCLC tissues and cells. In addition, circFOXK2 stimulated NSCLC cell proliferation, migration and invasion in vitro. Mechanical analysis indicated that circFOXK2 modulated IL-6 via miR-149-3p sponging. Furthermore, circFOXK2 overexpression promoted tumor growth in vivo. Overall, this research verified that circFOXK2 enhances the tumorigenesis of NSCLC through the miR-149-3p/IL-6 axis.

Anlotinib in patients with recurrent platinum resistant/refractory ovarian cancer: a prospective, single arm, phase II study.

OBJECTIVE: This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. METHODS: In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1-14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. RESULTS: 33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5-17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand-foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4-5 events or deaths were observed. CONCLUSION: Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.

Effects of growth years on ginsenoside biosynthesis of wild ginseng and cultivated ginseng.

BACKGROUND: Ginsenoside, as the main active substance in ginseng, has the function of treating various diseases. However, the ginsenosides content of cultivated ginseng is obviously affected by the growth years, but the molecular mechanism is not clear. In addition, there are significant differences in morphology and physiology between wild ginseng and cultivated ginseng, and the effect of growth years on ginsenoside synthesis not yet understood in wild ginseng. RESULTS: Transcriptome sequencing on the roots, stems and leaves of cultivated ginseng and wild ginseng with different growth years was performed in this study, exploring the effect of growth years on gene expression in ginseng. The number of differentially expressed genes (DEGs) from comparison groups in cultivated ginseng was higher than that in wild ginseng. The result of weighted gene co-expression network analysis (WGCNA) showed that growth years significantly affected the gene expression of Mitogen-activated protein kinases (MAPK) signaling pathway and terpenoid backbone biosynthesis pathway in cultivated ginseng, but had no effects in wild ginseng. Furthermore, the growth years had significant effects on the genes related to ginsenoside synthesis in cultivated ginseng, and the effects were different in the roots, stems and leaves. However, it had little influence on the expression of genes related to ginsenoside synthesis in wild ginseng. Growth years might affect the expression of genes for ginsenoside synthesis by influencing the expression of these transcription factors (TFs), like my elob lastosis (MYB), NAM, ATAF1 and 2, and CUC2 (NAC), APETALA2/ethylene-responsive factor (AP2/ERF), basic helix-loop-helix (bHLH) and WRKY, etc., thereby affecting the content of ginsenosides. CONCLUSIONS: This study complemented the gaps in the genetic information of wild ginseng in different growth periods and helped to clarify the potential mechanisms of the effect of growth years on the physiological state in wild ginseng and cultivated ginseng, which also provided a new insight into the mechanism of ginsenoside regulation.

Transcriptome reveals insights into biosynthesis of ginseng polysaccharides.

BACKGROUND: Ginseng polysaccharides, have been used to treat various diseases as an important active ingredient. Nevertheless, the biosynthesis of ginseng polysaccharides is poorly understood. To elucidate the biosynthesis mechanism of ginseng polysaccharides, combined the transcriptome analysis and polysaccharides content determination were performed on the roots, stems, and leaves collected from four cultivars of ginseng. RESULTS: The results indicated that the total contents of nine monosaccharides were highest in the roots. Moreover, the total content of nine monosaccharides in the roots of the four cultivars were different but similar in stems and leaves. Glucose (Glc) was the most component of all monosaccharides. In total, 19 potential enzymes synthesizing of ginseng polysaccharides were identified, and 17 enzymes were significantly associated with polysaccharides content. Among these genes, the expression of phosphoglucomutase (PGM), glucose-6-phosphate isomerase (GPI), UTP-glucose-1-phosphate uridylyltransferase (UGP2), fructokinase (scrK), mannose-1-phosphate guanylyltransferase (GMPP), phosphomannomutase (PMM), UDP-glucose 4-epimerase (GALE), beta-fructofuranosidase (sacA), and sucrose synthase (SUS) were correlated with that of MYB, AP2/ERF, bZIP, and NAC transcription factors (TFs). These TFs may regulate the expression of genes involved in ginseng polysaccharides synthesis. CONCLUSION: Our findings could provide insight into a better understanding of the regulatory mechanism of polysaccharides biosynthesis, and would drive progress in genetic improvement and plantation development of ginseng.

Diversity and structure of the rhizosphere microbial communities of wild and cultivated ginseng.

BACKGROUND: The resources of wild ginseng have been reducing sharply, and it is mainly dependent on artificial cultivation in China, Korea and Japan. Based on cultivation modes, cultivated ginseng include understory wild ginseng (the seeds or seedlings of cultivated ginseng were planted under the theropencedrymion without human intervention) and farmland cultivated ginseng (grown in farmland with human intervention). Cultivated ginseng, can only be planted on the same plot of land consecutively for several years owing to soilborne diseases, which is mainly because of the variation in the soil microbial community. In contrast, wild ginseng can grow for hundreds of years. However, the knowledge of rhizosphere microbe communities of the wild ginseng is limited. RESULT: In the present study, the microbial communities in rhizosphere soils of the three types of ginseng were analyzed by high-throughput sequencing of 16 S rRNA for bacteria and internal transcribed spacer (ITS) region for fungi. In total, 4,381 bacterial operational taxonomic units (OTUs) and 2,679 fungal OTUs were identified in rhizosphere soils of the three types of ginseng. Among them, the shared bacterial OTUs was more than fungal OTUs by the three types of ginseng, revealing fungal communities were to be more affected than bacterial communities. In addition, the composition of rhizosphere microbial communities and bacterial diversity were similar between understory wild ginseng and wild ginseng. However, higher bacterial diversity and lower fungal diversity were found in rhizosphere soils of wild ginseng compared with farmland cultivated ginseng. Furthermore, the relative abundance of Chloroflexi, Fusarium and Alternaria were higher in farmland cultivated ginseng compared to wild ginseng and understory wild ginseng. CONCLUSIONS: Our results showed that composition and diversity of rhizosphere microbial communities were significantly different in three types of ginseng. This study extended the knowledge pedigree of the microbial diversity populating rhizospheres, and provided insights into resolving the limiting bottleneck on the sustainable development of P. ginseng crops, and even the other crops of Panax.

Fast and high-accuracy measurement of particle size and location from a linear interferogram.

In this paper, we propose, to the best of our knowledge, a novel method of simultaneously detecting and evaluating the location and size of particles from a compression particle interferogram. The 2D position of the particle can be determined with high accuracy, as evaluated by the unidirectional gradient-match with the conjoint to centroid method. The fast-Rife method provides sub-pixel accuracy and high speed for estimating the fringe frequency from the Fourier spectrum of a particle interferogram. The capability mentioned above is well verified using synthetic and experimental data. The computational load falls almost 50%, and the relative error of the measured particle diameter is less than 1.12% for homogeneous solutions of polystyrene spheres of 50 µm and 70 µm. The results demonstrate that the method presented here is considerably promising for its application to a high-density particle field, such as spray, in accurately measuring both the particle size and its location.

Spatiotemporal coherent modulation imaging for dynamic quantitative phase and amplitude microscopy.

The single-shot capability of coherent modulation imaging (CMI) makes it have great potential in the investigation of dynamic processes. Its main disadvantage is the relatively low signal-to-noise ratio (SNR) which affects the spatial resolution and reconstruction accuracy. Here, we propose the improvement of a general spatiotemporal CMI method for imaging of dynamic processes. By making use of the redundant information in time-series reconstructions, the spatiotemporal CMI can achieve robust and fast reconstruction with higher SNR and spatial resolution. The method is validated by numerical simulations and optical experiments. We combine the CMI module with an optical microscope to achieve quantitative phase and amplitude reconstruction of dynamic biological processes. With the reconstructed complex field, we also demonstrate the 3D digital refocusing ability of the CMI microscope. With further development, we expect the spatiotemporal CMI method can be applied to study a range of dynamic phenomena.

Promoter Methylation-mediated Silencing of the MiR-192-5p Promotes Endometrial Cancer Progression by Targeting ALX1.

Background: Epigenetic regulation by promoter methylation-mediated silencing of cancer-related microRNAs plays vital roles in tumorigenesis. MiR-192-5p promotes tumor progression in various human cancers with conflicting biological effects. However, its expression levels and biological functions in endometrial carcinoma (EC) have not been reported. Methods: The methylation status of miR-192-5p in tissue samples and cell lines, was examined using bisulfite sequencing PCR. miR-192-5p expression was also measured. EC cell lines transfected with specifically designed vectors overexpressing miR-192-5p, its target gene ALX1 or both, were constructed. Tumorigenicity of these cell lines were examined by in vitro and in vivo experiments. Dual-luciferase reporter assay were employed to verify the target of miR-192-5p. Results: The promoter region of miR-192-5p gene was highly methylated and its expression significantly repressed in EC samples. Moreover, a higher level of promoter methylation as well as a lower expression of miR-192-5p, was significantly associated with advanced Federation of Gynecology and Obstetrics stage and shorter disease-free survival in patients with curatively resected EC. Functional studies demonstrated that miR-192-5p overexpression inhibited in vitro tumor progression, in vivo tumorigenicity and the expression of several oncoproteins that was highly related to epithelial-to-mesenchymal transition. ALX1 was verified as a direct target of miR-192-5p and demonstrated to mediate the tumor-suppressive function of miR-192-5p. Conclusion: miR-192-5p is a tumor suppressor miRNA that is epigenetically silenced by promoter methylation and may serve as a potential prognostic biomarker in EC.

Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy.

BACKGROUND: Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. RESULTS: Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. CONCLUSIONS: Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.

Clinical characteristics and risk factors of invasion in extramammary Paget's disease of the vulva.

PURPOSE: This study aimed to evaluate the risk factors of recurrence and invasive disease in patients with extramammary Paget's disease of the vulva (EPDV). METHODS: We performed a retrospective analysis of patients who were initially diagnosed with EPDV in Fudan University Shanghai Cancer Center between May 2006 and March 2019. RESULTS: Thirty-eight patients were initially diagnosed with EPDV in our institution. Among them, 29 had intraepithelial EPDV, 8 had intraepithelial EPDV with stromal invasion, and 1 had an underlying vulvar adenocarcinoma. In total, 8 (21%) patients had 12 recurrences. Of these eight patients, four had one recurrence, while other four had two recurrences. Intraepidermal EPDV recurred nine times, while intraepidermal EPDV with invasive disease recurred thrice. The first and second recurrence intervals were 62.1 (9-146) months and 22 (15-28) months, respectively. The rate of invasive disease was 23.7% (9/38) for primary EPDV and 25% (3/12) for recurrent ones. We determined that the presence of invasive disease was associated with a history of more than 10 years (p = 0.02) and inversely correlated with positive margins (p = 0.037), However, invasive disease had no statistical relations with age (p = 0.438), recurrence (p = 0.642), and lesion diameter (p = 0.08). CONCLUSIONS: EPDV with a history of more than 10 years was associated with invasive disease. Close and long-term follow-up are recommended to identify those who require further treatment.

Plasma omega-3 polyunsaturated fatty acids and recurrence of endometrial cancer.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality. METHOD: Women diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs. RESULTS: Median follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HRT3vsT1 = 6.02; 95%CI = 0.7-52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06-10.95; P-interaction = 0.04). CONCLUSIONS: Higher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings. TRIAL REGISTRATION: ChiCTR1900025418; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.

A preoperative prediction model for predicting coexisting adnexa malignancy of patients with G1/G2 endometrioid endometrial cancer.

OBJECTIVE: To identify the predictors of coexisting adnexa malignancy (CAM) before surgery for patients with G1/G2 endometrioid endometrial cancer (EEC). METHODS: Patients with G1/G2 EEC who received surgery in Fudan University Shanghai Cancer Center from 1996 to 2017 were enrolled. Univariate and multivariate logistic regression were performed to identify the predictors for CAM, and the nomogram was constructed and evaluated the discrimination and calibration. RESULTS: Among the 1511 patients in the study cohort, 66 (4.4%) coexisted adnexa malignancy (51 metastatic and 15 synchronous primaries). In the univariate logistic regression analysis, CA125 level (>35 U/ml), histologic grades, myometrial invasion depth in magnetic resonance imaging (MRI), adnexal involvement in MRI/surgical exploration (SEP) were found to be significant predictors for CAM (P < .001, 0.047, 0.011, <0.001, respectively). The multivariate analysis demonstrated that high CA125 level (P < .001; OR: 2.945; 95%CI: 1.700-5.101), deep myometrial invasion (P = .011; OR: 2.194; 95%CI: 1.200-4.011), and suspected adnexal involvement in MRI/SEP (P < .001; OR: 11.524; 95%CI: 6.726-19.744) were independent predictors for CAM (AUC = 0.786). In 338 patients with MMR results, eighty-seven (25.7%) were detected MSI-high. There were 5.7% (5/87) patients diagnosed with CAM in the MSI-high group compared with 4.4% (11/251) in the MSS group. CONCLUSIONS: A nomogram with pre- and intra-operative factors was constructed to predict CAM in G1/G2 EEC patients, which may help clinicians in decision-making for ovarian preservation for these patients.

Isolated cell-bound membrane vesicles (CBMVs) as a novel class of drug nanocarriers.

BACKGROUND: Cell-bound membrane vesicles (CBMVs) are a type of membrane vesicles different from the well-known extracellular vesicles (EVs). In recent years, the applications of EVs as drug delivery systems have been studied widely. A question may arise whether isolated CBMVs also have the possibility of being recruited as a drug delivery system or nanocarrier? METHODS: To test the possibility, CBMVs were isolated/purified from the surfaces of cultured endothelial cells, loaded with a putative antitumor drug doxorubicin (Dox), and characterized. Subsequently, cellular experiments and animal experiments using mouse models were performed to determine the in vitro and in vivo antitumor effects of Dox-loaded CBMVs (Dox-CBMVs or Dox@CBMVs), respectively. RESULTS: Both Dox-free and Dox-loaded CBMVs were globular-shaped and nanometer-sized with an average diameter of ~ 300-400 nm. Dox-CBMVs could be internalized by cells and could kill multiple types of cancer cells. The in vivo antitumor ability of Dox-CBMVs also was confirmed. Moreover, Quantifications of blood cells (white blood cells and platelets) and specific enzymes (aspartate aminotransferase and creatine kinase isoenzymes) showed that Dox-CBMVs had lower side effects compared with free Dox. CONCLUSIONS: The data show that the CBMV-entrapped Doxorubicin has the antitumor efficacy with lower side effects. This study provides evidence supporting the possibility of isolated cell-bound membrane vesicles as a novel drug nanocarrier.