Soybean-mediated suppression of BjaI/BjaR1 quorum sensing in Bradyrhizobium diazoefficiens impacts symbiotic nitrogen fixation.

The acyl-homoserine lactones (AHLs)-mediated LuxI/LuxR quorum sensing (QS) system orchestrates diverse bacterial behaviors in response to changes in population density. The role of the BjaI/BjaR1 QS system in Bradyrhizobium diazoefficiens USDA 110, which shares homology with LuxI/LuxR, remains elusive during symbiotic interaction with soybean. Here this genetic system in wild-type (WT) bacteria residing inside nodules exhibited significantly reduced activity compared to free-living cells, potentially attributed to soybean-mediated suppression. The deletion mutant strain ΔbjaR1 showed significantly enhanced nodulation induction and nitrogen fixation ability. Nevertheless, its ultimate symbiotic outcome (plant dry weight) in soybeans was compromised. Furthermore, comparative analysis of the transcriptome, proteome, and promoter activity revealed that the inactivation of BjaR1 systematically activated and inhibited genomic modules associated with nodulation and nitrogen metabolism. The former appeared to be linked to a significant decrease in the expression of NodD2, a key cell-density-dependent repressor of nodulation genes, while the latter conferred bacterial growth and nitrogen fixation insensitivity to environmental nitrogen. In addition, BjaR1 exerted a positive influence on the transcription of multiple genes involved in a so-called central intermediate metabolism within the nodule. In conclusion, our findings highlight the crucial role of the BjaI/BjaR1 QS circuit in positively regulating bacterial nitrogen metabolism and emphasize the significance of the soybean-mediated suppression of this genetic system for promoting efficient symbiotic nitrogen fixation by B. diazoefficiens.IMPORTANCEThe present study demonstrates, for the first time, that the BjaI/BjaR1 QS system of Bradyrhizobium diazoefficiens has a significant impact on its nodulation and nitrogen fixation capability in soybean by positively regulating NodD2 expression and bacterial nitrogen metabolism. Moreover, it provides novel insights into the importance of suppressing the activity of this QS circuit by the soybean host plant in establishing an efficient mutual relationship between the two symbiotic partners. This research expands our understanding of legumes' role in modulating symbiotic nitrogen fixation through rhizobial QS-mediated metabolic functioning, thereby deepening our comprehension of symbiotic coevolution theory. In addition, these findings may hold great promise for developing quorum quenching technology in agriculture.

Increased Expression of Holliday Junction-Recognizing Protein (HJURP) as an Independent Prognostic Biomarker in Advanced-Stage Serous Ovarian Carcinoma.

BACKGROUND Advanced-stage serous ovarian carcinoma results in the majority of deaths from ovarian carcinoma. The histone chaperone, Holliday junction-recognizing protein (HJURP), binds with centromere protein-A (CENP-A) and its expression has been shown to be a prognostic biomarker in some cancers. The aim of this study was to investigate the role of HJURP expression in advanced-stage serous ovarian carcinoma. MATERIAL AND METHODS Ninety-eight patients with advanced-stage serous ovarian carcinoma, who had tumor tissue samples available, were studied. Expression levels of HJURP were detected using immunohistochemistry (IHC) and were correlated with HJURP expression and patient clinicopathological factors. Fisher's correlation coefficient, Kaplan-Meier survival curves, the log-rank test, and Cox's regression proportional hazards model were performed to analyze the significance of factors affecting survival rate and independent prognostic factors. RESULTS Increased expression levels of HJURP in advanced-stage serous ovarian carcinoma were found in 33.67% (33/98) of cases; low expression levels of HJURP were found in 66.33% (65/98) of cases. High expression levels of HJURP were significantly associated with lymph node metastases (P=0.018), and lower overall survival (P=0.002). HJURP expression was identified as an independent prognostic biomarker for patients with advanced serous ovarian cancer in this study group of 98 patients (P=0.013). CONCLUSIONS Increased expression of HJURP was identified as an independent negative prognostic biomarker for patients with advanced serous ovarian cancer in this study. Further studies are required to determine whether HJURP expression in serous ovarian carcinoma may have a role in guiding clinical management by stratifying patients according to risk.

High Expression of S100A6 Predicts Unfavorable Prognosis of Lung Squamous Cell Cancer.

BACKGROUND S100 family of proteins is mainly involved in regulation of intracellular calcium homeostasis. Aberrant expression of S100 family members has been reported in many types of cancers. However, as a member of S100 family, the prognostic value of S100A6 for lung squamous cell carcinoma (SCC) has not been well-studied. MATERIAL AND METHODS Using immunohistochemistry, we investigated the expression of S100A6 in 177 patients with SCC and further divided the cohort into a high S100A6 expression group and a low S100A6 expression group. The chi-square test was applied to analyze the correlation between S100A6 expression and clinicopathological factors. Univariate analysis using the Kaplan-Meier method was performed to compare the difference in survival rates between the high S100A6 expression group and the low S100A6 expression group; multivariate analysis with Cox regression model was used to identify independent prognostic risk factors. RESULTS In our experiment, we demonstrated that the expression of S100A6 was significantly associated with patient age and tumor differentiation. High-expression of S100A6 was shown to be substantially related to the unfavorable prognosis of SCC. Moreover, our results confirmed that S100A6 was an independent risk factor for SCC prognosis, and could predict unfavorable prognosis. CONCLUSIONS High-expression of S100A6 was identified as an independent unfavorable prognostic factor for SCC, suggesting that targeting S100A6 may result in the development of potential targeted drug for SCC.

Integrin ß6 can be translationally regulated by eukaryotic initiation factor 4E: Contributing to colonic tumor malignancy.

It is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin αvß6 can contribute to malignant behavior of colon cancer. We have found that integrin αvß6 and eIF4E were co-expressed and positively correlated in colon cancer tissues. Recently, deregulation of the protein synthesis apparatus has begun to gain attention as a major participant in cancer development and progression. However, the regulation of integrin ß6 expression at translational level has never been investigated before. In present study, gene-silencing technique for eIF4E by small interfering RNA (siRNA) was used in all the subsequent experiments, in order to investigate whether eIF4E could translationally regulate expression of integrin ß6 in colon cancer SW480 and HT-29 cell lines. Additionally, the subsequent effects of eIF4E knockdown on cellular malignant behavior were observed. siRNA in SW480 and HT-29 transfectants. Subsequently, protein expression of ß6 was markedly suppressed, while mRNA expression of ß6 showed no significant variation before and after eIF4E RNA interfering. Therefore, it could be seen that eIF4E could upregulate the expression of ß6, without effect on ß6 mRNA expression. More importantly, after treated with eIF4E siRNA, cellular migratory capacity on fibronectin of HT-29 and ß6-transfected SW480 as well as their survival to 5-FU was decreased distinctly. Expression of integrin ß6 could be translationally regulated by eIF4E, which subsequently contributed to tumor malignancy through enhancing cellular migration, survival, anti-apoptosis, and chemoresistance of colon cancer in vitro. Thus, targeting eIF4E in integrin αvß6 expressing tumors can be a potential therapeutic strategy for patients with colon cancer.

A novel fusion of genetic grey wolf optimization and kernel extreme learning machines for precise diabetic eye disease classification.

In response to the growing number of diabetes cases worldwide, Our study addresses the escalating issue of diabetic eye disease (DED), a significant contributor to vision loss globally, through a pioneering approach. We propose a novel integration of a Genetic Grey Wolf Optimization (G-GWO) algorithm with a Fully Convolutional Encoder-Decoder Network (FCEDN), further enhanced by a Kernel Extreme Learning Machine (KELM) for refined image segmentation and disease classification. This innovative combination leverages the genetic algorithm and grey wolf optimization to boost the FCEDN's efficiency, enabling precise detection of DED stages and differentiation among disease types. Tested across diverse datasets, including IDRiD, DR-HAGIS, and ODIR, our model showcased superior performance, achieving classification accuracies between 98.5% to 98.8%, surpassing existing methods. This advancement sets a new standard in DED detection and offers significant potential for automating fundus image analysis, reducing reliance on manual examination, and improving patient care efficiency. Our findings are crucial to enhancing diagnostic accuracy and patient outcomes in DED management.

Transvaginal laparoscopically assisted endoscopic cholecystectomy: preliminary clinical results for a series of 43 cases in China.

BACKGROUND: Transvaginal cholecystectomy has been performed successfully at several research institutions worldwide using natural orifice transluminal endoscopic surgery (NOTES) techniques. However, it is a growing new surgical concept in China. Several technical challenges hinder the safe clinical application of NOTES. This study investigated transvaginal endoscopic cholecystectomy performed with the assistance of a single umbilical trocar and achieved helpful initial clinical experience. METHODS: From May 2009 to April 2010, a total of 43 transvaginal human cholecystectomies were performed. A single umbilical trocar was used for safe access and laparoscopic assistance during the operation. After the gallbladder had been removed through the vagina, the colpotomy was closed with absorbable stitches under direct vision. In addition, Student's t-test was performed for two samples to estimate the superiority of NOTES over a conventional laparoscopic cholecystectomy (LC) operation. RESULTS: The procedure was successfully completed for all the patients. No intra- or post-operative complications occurred. The patients recovered promptly after surgery, and all were satisfied with ideal cosmetic outcomes. The postoperative pain, hospital stay, and cost of hospitalization with NOTES were much less than with conventional LC operations. CONCLUSIONS: Although endoscopic instruments specifically designed for NOTES are not available, the addition of an umbilical trocar is an optimal way to allow safe performance of NOTES procedures in an easily reproducible manner. The authors' initial experience demonstrates that this hybrid technique is potentially feasible and effective for reducing postoperative pain and recovery times while improving the cosmetic results of transvaginal cholecystectomy.

Transvaginal Laparoscopically Assisted Endoscopic Appendectomy: a major Hybrid Natural Orifice Transluminal Endoscopic Surgery case series in Asia.

OBJECTIVE: Evaluation of a Hybrid Approach to NOTES and its performance relative to conventional procedures. BACKGROUND: Globally, numerous institutions have successfully implemented minimally invasive surgeries by applying natural orifice translumenal endoscopic surgery (NOTES) techniques and achieved decreased morbidity while performing incision-less surgery. However, these techniques are still not common in surgical practice in China and Pakistan. Documenting the experiences and challenges encountered in implementing NOTES in such environments can provide guidance for NOTES implementation elsewhere. METHODS: From May 2010 to April 2012, 16 human transvaginal appendectomies were carried out applying a hybrid NOTES technique using a solo-umbilical trocar, which provided a safe access for laparoscopic assistance during surgical procedure. After removal of the appendix transvaginally, the colpotomy was sutured under direct vision with absorbable stitches. The outcomes of cases treated with hybrid NOTES techniques were compared to those of conventional laparoscopic appendectomy. RESULTS: All patients underwent a successful surgical procedure with no intra- or post-operative complications and provided no specific complaints during the tenth day and a monthly follow-up for 2 years. The patients convalesced promptly with healthy and satisfactory cosmetic results. Compared to conventional laparoscopic appendectomy, the hybrid NOTES operation had less post-operative pain, lower cost, and shorter hospitalization. CONCLUSIONS: Hybrid NOTES procedures can be performed safely using a solo-umbilical trocar. Our initial experience reveals that this hybrid technique is practically feasible and associated with minimal post-operative pain, reasonable convalescence time, and improved cosmetic outcomes.

The ß6-integrin-ERK/MAP kinase pathway contributes to chemo resistance in colon cancer.

5-Fluorouracil (5-FU) is the most widely used chemo drug for the treatment of colon cancer. However, a sub-population of colon cancer patients do not respond to 5-FU and this treatment does not provide survival benefit due to chemo resistance. The mechanisms involved in 5-FU resistance are not fully understood and multiple factors have been involved in the sensitivity of cancer cells to 5-FU. We previously reported that ß6-integrin plays an important role in invasion, metastasis and degradation of extracellular matrix of colon cancer. In this study, we investigated whether ß6-integrin is associated with chemo resistance in colon cancer. We found that over-expression of ß6-integrin protected SW480 and HT-29 colon cancer cells from 5-FU-induced growth inhibition and apoptosis, which were accompanied by changes in cytochrome C released from the mitochondria and activity of caspase-3 and caspase-9. Moreover, ß6-integrin resulted in up-regulation of Bcl-2 and down-regulation of Bax. We also found that ß6-integrin induced 5-FU resistance through the ERK/MAP kinase pathway and the ß6-ERK2 direct binding. The results indicate ß6-integrin might be a novel therapeutic target in colon cancer therapy.