MicroRNA (miRNA) is small non-coding RNAs that play vital roles in post-transcriptional gene regulation by inhibiting mRNA translation or promoting mRNA degradation. Dysregulation of miRNA has been implicated in numerous human diseases, including cancers. The family members of miR-34 (miR-34s), composed of miR-34a, miR-34b, and miR-34c, have emerged as the most extensively studied tumor-suppressive miRNAs. In this comprehensive review, we aim to provide an overview of the major signaling pathways and gene networks regulated by the miR-34s in various cancers and highlight the critical tumor suppressor role of miR-34s. Furthermore, we will discuss the potential of using miR-34 mimics as a novel therapeutic approach against cancer, while also addressing the challenges associated with their development and delivery. It is anticipated that gaining a deeper understanding of the functions and mechanisms of miR-34s in cancer will greatly contribute to the development of effective miR-34-based cancer therapeutics.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

Cervical Cancer affects a large part of female population that makes the prediction of this disease based on Machine Learning (ML) by outmost importance. ML algorithms can be integrated in complex intelligent agent-based systems that can offer decision support to the resident medical doctors or even to experienced medical doctors. For instance can be mentioned the situation when an experienced medical doctor diagnose a case but he/she needs expertise support that is related to another medical specialty. Data imbalance is frequent in healthcare data and has a negative influencing effect in making predictions using ML algorithms. Cancer data generally and cervical cancer data particularly are frequently imbalanced. Based on this fact the study of data imbalance impact on diverse state-of-the-art ML prediction algorithms is important. This research subject is also motivated by the fact that in many research are presented experimental evaluations of algorithms without characterization of the data on that they have been applied. Such characterizations could give clear indication to other researchers regarding the applicability of the algorithms on their specific data. Specifically, if the data have the respective characteristics than are expectable the same performance evaluation results like those in the reported research. For the study we chosed a messy real-life Cervical Cancer dataset available in a recognized data repository included a large amount of missing and noisy values. To identify the best imbalanced technique for this medical dataset, it is compared the performance of eleven important resampling methods combined with the following state-of-the-art ML models: K-Nearest Neighbours (with k values of 2 and 3), binary Logistic Regression, and Random Forest, that are frequently applied in prediction types of researches in healthcare. The studied resampling methods includes seven undersampling methods namely Condensed Nearest Neighbour, Tomek Links, Edited Nearest Neighbours, Repeated Edited Nearest Neighbours, All K-Nearest Neighbours, NearMiss, Neighbourhood Cleaning Rule, and Instance Hardness Threshold, and four oversampling methods namely Synthetic Minority Oversampling Technique (SMOTE), Adaptive Synthetic Sampling Approach for Imbalanced Learning SMOTE, Support Vector Machine SMOTE and Borderline SMOTE. In the case of the dataset for the confidence interval with 95% confidence level was between 9.23 and 16.22, while the imbalance ratio is 12.73. The obtained results show that resampling methods help the learning models to improve the classification ability of cervical cancer. The applied oversampling techniques generally showed better results than undersampling methods. In the case of Logistic Regression classifier had the highest impact on balanced techniques, while Random Forest had promising performance, even before balancing techniques and KNN2 was generally better than KNN3.

Abstract：Objective: To compare the effects of fermentation on the chemical composition of Gastrodia Tuder Halimasch Powder, and to provide a basis for the processing, processing and clinical application of this medicinal material. Methods: UHPLC-Q-Orbitrap HRMS was used to identify compound structure by comparing excimer ions, characteristic fragment ions and reference substances, and referring to relevant literature and database search. The main differential components were screened by orthogonal partial least squares-discriminant analysis (OPLS-DA), and the differential components were quantitatively studied by high performance liquid chromatography, and the differences in the types and contents of chemical components before and after fermentation were compared. Results: A total of 77 compounds were identified or preliminarily derived after fermentation, including 21 terpenes, 18 organic acids, 9 flavonoids, 7 nucleosides, 6 amides, 4 amino acids, 2 pyrrolidone derivatives, 2 sterols, 2 alkaloids and 6 others.Through high performance liquid chromatography, it was found that the content of daidzein genistein and ergosterol was significantly increased after fermentation, and a new component ergosterol was produced. Compared with Gastrodia Tuder Halimasch Powder before fermentation, the content of genistin and other components was significantly reduced, and there may be a process of genistin conversion to genistein.Conclusion: The fermentation process will have a certain influence on the types and contents of the chemical components of Gastrodia Tuder Halimasch Powder, and ergosterol, genistein and .daidzein may be the main pharmacodynamic components, which can provide a useful reference for the clinical rational application, quality control and mechanism of action of Gastrodia Tuder Halimasch Powder.