GmSABP2-1 encodes methyl salicylate esterase and functions in soybean defense against soybean cyst nematode.

KEY MESSAGE: The soybean gene GmSABP2-1 encodes methyl salicylate esterase and its overexpression led to significant reduction in development of pathogenic soybean cyst nematode. Soybean cyst nematode (SCN, Heterodera glycines) is one of the most devastating pests of soybean (Glycine max L. Merr.). In searching for SCN-defense genes, a soybean gene of the methylesterase (MES) family was found to be upregulated in an SCN-resistant soybean line and downregulated in an SCN-susceptible line upon SCN infection. This gene was designated as GmSABP2-1. Here, we report on biochemical and overexpression studies of GmSABP2-1 to examine its possible function in SCN resistance. The protein encoded by GmSABP2-1 is closely related to known methyl salicylate esterases. To determine the biochemical function of GmSABP2-1, a full-length cDNA of GmSABP2-1 was cloned into a protein expression vector and expressed in Escherichia coli. The resulting recombinant GmSABP2-1 was demonstrated to catalyze the demethylation of methyl salicylate. The biochemical properties of GmSABP2-1 were determined. Its apparent Km value was 46.2 ± 2.2 µM for methyl salicylate, comparable to those of the known methyl salicylate esterases. To explore the biological significance of GmSABP2-1 in soybean defense against SCN, we first overexpressed GmSABP2-1 in transgenic hairy roots of an SCN-susceptible soybean line. When infected with SCN, GmSABP2-1-overexpressing hairy roots showed 84.5% reduction in the development of SCN beyond J2 stage. To provide further genetic evidence for the role of GmSABP2-1 in SCN resistance, stable transgenic soybean plants overexpressing GmSABP2-1 were produced. Analysis of the GmSABP2-1-overexpressing lines showed a significant reduction in SCN development compared to non-transgenic plants. In conclusion, we demonstrated that GmSABP2-1 encodes methyl salicylate esterase and functions as a resistance-related gene against SCN.

Microbiota metabolites in bone: Shaping health and Confronting disease.

The intricate interplay between the gut microbiota and bone health has become increasingly recognized as a fundamental determinant of skeletal well-being. Microbiota-derived metabolites play a crucial role in dynamic interaction, specifically in bone homeostasis. In this sense, short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, indirectly promote bone formation by regulating insulin-like growth factor-1 (IGF-1). Trimethylamine N-oxide (TMAO) has been found to increase the expression of osteoblast genes, such as Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein-2 (BMP2), thus enhancing osteogenic differentiation and bone quality through BMP/SMADs and Wnt signaling pathways. Remarkably, in the context of bone infections, the role of microbiota metabolites in immune modulation and host defense mechanisms potentially affects susceptibility to infections such as osteomyelitis. Furthermore, ongoing research elucidates the precise mechanisms through which microbiota-derived metabolites influence bone cells, such as osteoblasts and osteoclasts. Understanding the multifaceted influence of microbiota metabolites on bone, from regulating homeostasis to modulating susceptibility to infections, has the potential to revolutionize our approach to bone health and disease management. This review offers a comprehensive exploration of this evolving field, providing a holistic perspective on the impact of microbiota metabolites on bone health and diseases.

Oncologic and reproductive outcomes after fertility-sparing surgery for bilateral borderline ovarian tumors: A retrospective study.

OBJECTIVES: To investigate the oncological safety and fertility outcomes of different fertility-sparing surgery procedures for bilateral borderline ovarian tumors (BOTs) and to identify the safest and most effective approach to help patients conceive with minimal risk. STUDY DESIGN: A retrospective study of 144 patients (≤40 years) with pathologically confirmed bilateral BOTs were included in the study.The effects of surgery type on fertility outcome and recurrence were compared. Cox regression analysis was employed to determine potential prognostic factors. Survival analysis utilized the Kaplan-Meier method. RESULTS: Three therapeutic modalities were applied in our study, including bilateral ovarian cystectomy (BOC; n = 29), unilateral adnexectomy + contralateral cystectomy (UAC; n = 4) and radical surgery (n = 61). Totally 33 cases (22.9 %) relapsed during the follow-up period. In 37 % of cases administered conservative surgery, relapses were diagnosed in the first 2 years. Only conservative surgery and adjuvant chemotherapy were risk factors for recurrence. Meanwhile, a pregnancy rate of 55.4 % was obtained in patients with bilateral BOTs. The pregnancy rate was slightly higher but no significant (P = 0.539) difference in patients treated with BOC (n = 17, 63 %) compared with UAC (n = 29, 55.8 %) group. GnRHa treatment significantly improved the clinical pregnancy rate in this study(P = 0.029). CONCLUSIONS: Satisfactory pregnancy rate can be achieved after conservative surgery in patients with bilateral BOTs. BOC is worth recommending for bilateral borderline ovarian tumors and a critical factor in fertility is the preservation of maximum healthy ovarian tissue. Patients should make a pregnancy plan in 2 years after the first surgery. GnRHa increase the rate of successful clinical pregnancies.

Serum cell division cycle 42 reflects the treatment response and survival in patients with advanced cervical cancer who receive immune checkpoint inhibitor treatment.

Cell division cycle 42 (CDC42) regulates immune escape, which predicts immune checkpoint inhibitor (ICI) treatment response in several types of cancer. The present study aimed to evaluate the potential of serum CDC42 in predicting the ICI treatment outcome in patients with advanced cervical cancer. A total of 46 patients with advanced cervical cancer who received ICI treatment with or without antiangiogenic agents were enrolled. Serum CDC42 was detected in all patients before treatment (baseline) and following two treatment cycles by enzyme-linked immunosorbent assay. CDC42 at baseline was elevated in patients with target lesion size ≥5 cm (P=0.020), pelvis metastasis (P=0.031) and lung metastasis (P=0.043). Following treatment, the objective response rate (ORR) and disease control rate (DCR) were 30.4 and 78.3%, respectively. Meanwhile, the median progression-free survival (PFS) and overall survival (OS) were 5.8 and 13.1 months. CDC42 at baseline was decreased in patients achieving ORR (P=0.042) but not DCR (P=0.055). PFS (P=0.006) and OS (P=0.019) were decreased in patients with baseline CDC42 ≥600 pg/ml. After two treatment cycles, CDC42 was generally reduced (P<0.001). CDC42 following two treatment cycles was more significantly decreased in patients with ORR (P=0.032) and DCR (P=0.019). Multivariate Cox's regression analysis showed that CDC42 ≥600 pg/ml following two treatment cycles was associated with the shorter PFS (P=0.022, hazard ratio=2.469) and OS (P=0.013, hazard ratio=4.166). Serum CDC42 was reduced after treatment; high expression following treatment reflected a lower possibility of achieving treatment response and poorer survival in patients with advanced cervical cancer.

A novel hypoxia-stimulated lncRNA HIF1A-AS3 binds with YBX1 to promote ovarian cancer tumorigenesis by suppressing p21 and AJAP1 transcription.

Hypoxia is characteristic of the ovarian tumor (OC) microenvironment and profoundly affects tumorigenesis and therapeutic response. Long noncoding RNAs (lncRNAs) play various roles in tumor progression; however, the characteristics of lncRNAs in pathological responses of the OC microenvironment are not entirely understood. Through high-throughput sequencing, lncRNA expression in hypoxia (1% O2 ) and normoxia (21% O2 ) SKOV3 cells was explored and analyzed. The 5'- and 3'-rapid amplification of complementary DNA ends was used to detect the full length of the novel HIF1A-AS3 transcript. Real-time quantitative polymerase chain reaction was used to assess HIF1A-AS3 expression in OC cells and tissues. In vitro and in vivo evaluations of the biological functions of hypoxic HIF1A-AS3 were conducted. To clarify the underlying mechanisms of HIF1A-AS3 in hypoxic OC, a dual-luciferase assay, chromatin immunoprecipitation, RNA pull-down, RNA immunoprecipitation, and RNA-sequencing were used. We used high-throughput sequencing to investigate a novel lncRNA, HIF1A-AS3, as a hypoxic candidate significantly elevated in OC cells/tissues. HIF1A-AS3 was predominantly localized in the nucleus and promoted in vitro and in vivo OC growth and tumorigenesis. Hypoxia-inducible factor 1α bound to hypoxia response elements in the HIF1A-AS3 promoter region and stimulated its expression in hypoxia. Under hypoxia, HIF1A-AS3 directly integrated with Y-Box binding protein 1 and inhibited its ability to bind to the promoters of p21 and AJAP1 to repress their transcriptional activity, thereby promoting hypoxic OC progression. Our results revealed the crucial role and mechanism of the novel hypoxic HIF1A-AS3 in the oncogenesis of OC. The novel HIF1A-AS3 could be a crucial biomarker and therapeutic target for future OC treatments.

Low expression of acyl-CoA thioesterase 13 is associated with poor prognosis in ovarian serous cystadenocarcinoma.

Objective: Acyl-CoA thioesterase 13 (ACOT13) encodes a member of the thioesterase superfamily. It has not been reported in ovarian cancer. This research aimed at evaluating the expression and prognostic value of ACOT13 in ovarian serous cystadenocarcinoma (OSC). Methods: We extracted and analyzed TCGA, GEPIA, THPA, GTEx, miRWalk, and GDSC databases to investigate the potential carcinogenic mechanism of ACOT13 in OSC, including the correlation of ACOT13 with prognosis, immune checkpoint, tumor mutational burden (TMB), and 50% inhibition concentration (IC50) score. The incidence of endpoint events was compared with Kaplan-Meier survival analysis. Independent prognostic factors for OSC were evaluated with univariate and multivariate Cox regression analyses, and a nomogram was established. Results: The expression of ACOT13 was increased in OSC and correlated with tumor stage, with higher expression in stages I and II than in stages III and IV. Besides, it was observed that low expression of ACOT13 is correlated with poor overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) in patients with OSC. There was a positive correlation between ACOT13 expression and immune checkpoint sialic acid-binding Ig-like lectin (SIGLEC) 15 and TMB. Patients with low ACOT13 expression had higher cisplatin IC50 scores. Conclusion: ACOT13 is an independent prognostic factor and a promising clinical target for OSC. In the future, the carcinogenic mechanism and clinical application value of ACOT13 in ovarian cancer need to be further studied.

Clinical analysis of total endoscopic thyroidectomy via breast areola approach in early differentiated thyroid cancer.

PURPOSE: The purpose of this study was to explore the efficacy and safety of total endoscopic thyroidectomy (TET) via breast areola approach in the treatment of early differentiated thyroid cancer. METHODS: The clinical data of 134 patients with early differentiated thyroid cancer were retrospectively analyzed. The patients underwent different treatments, including TET via breast areola approach in endoscope group (n=67), and conventional small incision open surgery in control group (n=67). The surgery-related indexes, complications, postoperative incision recovery, visual analogue scale (VAS) pain score, postoperative patients' satisfaction, tumor recurrence and survival conditions were compared between the two groups. RESULTS: Compared with control group, the endoscope group showed significantly longer operation time, smaller intraoperative bleeding, less postoperative drainage, shorter duration of postoperative catheter indwelling and shorter postoperative length of stay. Meanwhile, in the endoscope group, the postoperative VAS pain score was markedly lower than that in control group, and the postoperative patients' satisfaction was higher than that in control group. The neurological severity score (NSS) had statistically significant differences between the two groups at 3 months and 6 months after operation. Moreover, no tumor recurrence and metastasis were found during the follow-up period. CONCLUSIONS: TET via breast areola approach is safe and effective in the treatment of early differentiated thyroid cancer, and it can achieve a better cosmetic effect and high satisfaction of patients, which is worthy of clinical application.

[Preparation and thermo-sensitivity behavior of polymer liposomes made of poly(2-ethylacrylic acid) alkylamide derivatives].

The temperature-sensitive liposomes were constructed by poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives that were synthesized for partially modification of carboxylic groups. The thermal characteristics of liposomes were investigated by using fluorescent indicator, particle size device and fluorescence spectrophotometer system. The results showed that the liposome made of fatty amine-modified poly(2-ethylacrylate) had a marked thermal sensitive release of drugs, which is correlated with the structure of molecular of polymer and the initial ratio of composition of phospholipid. The PEAA-associated-liposomes were also shown pH-sensitive drug release under acidic condition. The poly (2-ethylacrylate) for the preparation of medium-induced thermal liposomes in vitro experiments showed a good thermal characteristics and the methods of preparing temperature-sensitive liposomes were convenient and stability.

Polyethylenimine-DNA solid particles for gene delivery.

Polyethylenimine (PEI), a cationic polymer, was used to develop a non-viral vector for gene delivery. A simple, reproducible process is described with which to condense plasmid DNA with PEI. When prepared at the optimum charge ratio of 6.3 ( +/- ; PEI:DNA, 5:1 w/w), PEI-DNA complexes were 30-60 nm in diameter and excluded intercalating dyes from the plasmid DNA. The particles were stable for more than one month at 4 degrees C with respect to size and transfection activity. PEI-condensed DNA transfected a broad range of murine and human tumor cell lines (B16, Lewis Lung, SK-OV-3 and LS180) in vitro in the presence of fetal calf serum. Intraperitoneal administration of PEI-condensed DNA resulted in significant gene expression in a human ovarian cancer peritoneal xenograft model.