Unveiling the multifaceted roles of microRNAs in extracellular vesicles derived from mesenchymal stem cells: implications in tumor progression and therapeutic interventions.

Mesenchymal stem/stromal cells (MSCs) have the capacity to migrate to tumor sites in vivo and transmit paracrine signals by secreting extracellular vesicles (EVs) to regulate tumor biological behaviors. MSC-derived EVs (MSC-EVs) have similar tumor tropism and pro- or anti-tumorigenesis as their parental cells and exhibit superior properties in drug delivery. MSC-EVs can transfer microRNAs (miRNAs) to tumor cells, thereby manipulating multiple key cancer-related pathways, and further playing a vital role in the tumor growth, metastasis, drug resistance and other aspects. In addition, tumor cells can also influence the behaviors of MSCs in the tumor microenvironment (TME), orchestrating this regulatory process via miRNAs in EVs (EV-miRNAs). Clarifying the specific mechanism by which MSC-derived EV-miRNAs regulate tumor progression, as well as investigating the roles of EV-miRNAs in the TME will contribute to their applications in tumor pharmacotherapy. This article mainly reviews the multifaceted roles and mechanism of miRNAs in MSC-EVs affecting tumor progression, the crosstalk between MSCs and tumor cells caused by EV-miRNAs in the TME. Eventually, the clinical applications of miRNAs in MSC-EVs in tumor therapeutics are illustrated.

AVBAE-MODFR: A novel deep learning framework of embedding and feature selection on multi-omics data for pan-cancer classification.

Integration analysis of cancer multi-omics data for pan-cancer classification has the potential for clinical applications in various aspects such as tumor diagnosis, analyzing clinically significant features, and providing precision medicine. In these applications, the embedding and feature selection on high-dimensional multi-omics data is clinically necessary. Recently, deep learning algorithms become the most promising cancer multi-omic integration analysis methods, due to the powerful capability of capturing nonlinear relationships. Developing effective deep learning architectures for cancer multi-omics embedding and feature selection remains a challenge for researchers in view of high dimensionality and heterogeneity. In this paper, we propose a novel two-phase deep learning model named AVBAE-MODFR for pan-cancer classification. AVBAE-MODFR achieves embedding by a multi2multi autoencoder based on the adversarial variational Bayes method and further performs feature selection utilizing a dual-net-based feature ranking method. AVBAE-MODFR utilizes AVBAE to pre-train the network parameters, which improves the classification performance and enhances feature ranking stability in MODFR. Firstly, AVBAE learns high-quality representation among multiple omics features for unsupervised pan-cancer classification. We design an efficient discriminator architecture to distinguish the latent distributions for updating forward variational parameters. Secondly, we propose MODFR to simultaneously evaluate multi-omics feature importance for feature selection by training a designed multi2one selector network, where the efficient evaluation approach based on the average gradient of random mask subsets can avoid bias caused by input feature drift. We conduct experiments on the TCGA pan-cancer dataset and compare it with four state-of-the-art methods for each phase. The results show the superiority of AVBAE-MODFR over SOTA methods.

Genome-Wide Identification and Expression Pattern Analysis of TIFY Family Genes Reveal Their Potential Roles in Phalaenopsis aphrodite Flower Opening.

The TIFY gene family (formerly known as the zinc finger proteins expressed in inflorescence meristem (ZIM) family) not only functions in plant defense responses but also are widely involved in regulating plant growth and development. However, the identification and functional analysis of TIFY proteins remain unexplored in Orchidaceae. Here, we identified 19 putative TIFY genes in the Phalaenopsis aphrodite genome. The phylogenetic tree classified them into four subfamilies: 14 members from JAZ, 3 members from ZML, and 1 each from PPD and TIFY. Sequence analysis revealed that all Phalaenopsis TIFY proteins contained a TIFY domain. Exon-intron analysis showed that the intron number and length of Phalaenopsis TIFY genes varied, whereas the same subfamily and subgroup genes had similar exon or intron numbers and distributions. The most abundant cis-elements in the promoter regions of the 19 TIFY genes were associated with light responsiveness, followed by MeJA and ABA, indicating their potential regulation by light and phytohormones. The 13 candidate TIFY genes screened from the transcriptome data exhibited two types of expression trends, suggesting their different roles in cell proliferation and cell expansion of floral organ growth during Phalaenopsis flower opening. Overall, this study serves as a background for investigating the underlying roles of TIFY genes in floral organ growth in Phalaenopsis.

Comparative Analysis of Six Complete Plastomes of Tripterospermum spp.

The Tripterospermum, comprising 34 species, is a genus of Gentianaceae. Members of Tripterospermum are mostly perennial, entwined herbs with high medicinal value and rich in iridoids, xanthones, flavonoids, and triterpenes. However, our inadequate understanding of the differences in the plastid genome sequences of Tripterospermum species has severely hindered the study of their evolution and phylogeny. Therefore, we first analyzed the 86 Gentianae plastid genomes to explore the phylogenetic relationships within the Gentianae subfamily where Tripterospermum is located. Then, we analyzed six plastid genomes of Tripterospermum, including two newly sequenced plastid genomes and four previously published plastid genomes, to explore the plastid genomes' evolution and phylogenetic relationships in the genus Tripterospermum. The Tripterospermum plastomes have a quadripartite structure and are between 150,929 and 151,350 bp in size. The plastomes of Tripterospermum encoding 134 genes were detected, including 86 protein-coding genes (CDS), 37 transfer RNA (tRNA) genes, eight ribosomal RNA (rRNA) genes, and three pseudogenes (infA, rps19, and ycf1). The result of the comparison shows that the Tripterospermum plastomes are very conserved, with the total plastome GC content ranging from 37.70% to 37.79%. In repeat sequence analysis, the number of single nucleotide repeats (A/T) varies among the six Tripterospermum species, and the identified main long repeat types are forward and palindromic repeats. The degree of conservation is higher at the SC/IR boundary. The regions with the highest divergence in the CDS and the intergenic region (IGS) are psaI and rrn4.5-rrn5, respectively. The average pi of the CDS and the IGS are only 0.071% and 0.232%, respectively, indicating that the Tripterospermum plastomes are highly conserved. Phylogenetic analysis indicated that Gentianinae is divided into two clades, with Tripterospermum as a sister to Sinogeniana. Phylogenetic trees based on CDS and CDS + IGS combined matrices have strong support in Tripterospermum. These findings contribute to the elucidation of the plastid genome evolution of Tripterospermum and provide a foundation for further exploration and resource utilization within this genus.

The Complete Chloroplast Genomes of Bulbophyllum (Orchidaceae) Species: Insight into Genome Structure Divergence and Phylogenetic Analysis.

Bulbophyllum is one of the largest genera and presents some of the most intricate taxonomic problems in the family Orchidaceae, including species of ornamental and medical importance. The lack of knowledge regarding the characterization of Bulbophyllum chloroplast (cp) genomes has imposed current limitations on our study. Here, we report the complete cp genomes of seven Bulbophyllum species, including B. ambrosia, B. crassipes, B. farreri, B. hamatum, B. shanicum, B. triste, and B. violaceolabellum, and compared with related taxa to provide a better understanding of their genomic information on taxonomy and phylogeny. A total of 28 Bulbophyllum cp genomes exhibit typical quadripartite structures with lengths ranging from 145,092 bp to 165,812 bp and a GC content of 36.60% to 38.04%. Each genome contained 125-132 genes, encompassing 74-86 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The genome arrangements, gene contents, and length were similar, with differences observed in ndh gene composition. It is worth noting that there were exogenous fragment insertions in the IR regions of B. crassipes. A total of 18-49 long repeats and 38-80 simple sequence repeats (SSRs) were detected and the single nucleotide (A/T) was dominant in Bulbophyllum cp genomes, with an obvious A/T preference. An analysis of relative synonymous codon usage (RSCU) revealed that leucine (Leu) was the most frequently used codon, while cysteine (Cys) was the least used. Six highly variable regions (rpl32-trnLUAG > trnTUGU-trnLUAA > trnFGAA-ndhJ > rps15-ycf1 > rbcL-accD > psbI-trnSGCU) and five coding sequences (ycf1 > rps12 > matK > psbK > rps15) were identified as potential DNA markers based on nucleotide diversity. Additionally, 31,641 molecular diagnostic characters (MDCs) were identified in complete cp genomes. A phylogenetic analysis based on the complete cp genome sequences and 68 protein-coding genes strongly supported that 28 Bulbophyllum species can be divided into four branches, sects. Brachyantha, Cirrhopetalum, and Leopardinae, defined by morphology, were non-monophyly. Our results enriched the genetic resources of Bulbophyllum, providing valuable information to illustrate the complicated taxonomy, phylogeny, and evolution process of the genus.

Hyper-spectra imaging analysis of PLGA microspheres via machine learning enhanced Raman spectroscopy.

Long-acting injectables (LAI) offer a cost-effective and patient-centric approach by reducing pill burden and improving compliance, leading to better treatment outcomes. Among various types of long-acting injectables, poly (lactic-co-glycolic acid) (PLGA) microspheres have been extensively investigated and reported in the literature. However, microsphere formulation development is still challenging due to the complexity of PLGA polymer, formulation screening, and processing, as well as time-consuming and cumbersome physicochemical characterization. A further challenge is the limited availability of drug substances in early formulation development. Therefore, there is a need to develop novel and advanced tools that can accelerate the early formulation development. In this manuscript, a novel comprehensive physicochemical characterization approach was developed by integrating Raman microscopy and the machine learning process. The physicochemical properties such as drug loading, particle size and size distribution, content uniformity/heterogeneity, and drug polymorphism of the microspheres can be obtained in a single run, without requiring separate methods for each attribute (e.g., liquid chromatography, particle size analyzer, thermal analysis, X-ray powder diffraction). This approach is non-destructive and can significantly reduce material consumption, sample preparation, labor work, and analysis time/cost, which will greatly facilitate the formulation development of PLGA microsphere products. In addition, the approach will potentially be beneficial in enabling automated high throughput screening of microsphere formulations.

Identification and Analysis of PEPC Gene Family Reveals Functional Diversification in Orchidaceae and the Regulation of Bacterial-Type PEPC.

Phosphoenolpyruvate carboxylase (PEPC) gene family plays a crucial role in both plant growth and response to abiotic stress. Approximately half of the Orchidaceae species are estimated to perform CAM pathway, and the availability of sequenced orchid genomes makes them ideal subjects for investigating the PEPC gene family in CAM plants. In this study, a total of 33 PEPC genes were identified across 15 orchids. Specifically, one PEPC gene was found in Cymbidium goeringii and Platanthera guangdongensis; two in Apostasia shenzhenica, Dendrobium chrysotoxum, D. huoshanense, Gastrodia elata, G. menghaiensis, Phalaenopsis aphrodite, Ph. equestris, and Pl. zijinensis; three in C. ensifolium, C. sinense, D. catenatum, D. nobile, and Vanilla planifolia. These PEPC genes were categorized into four subgroups, namely PEPC-i, PEPC-ii, and PEPC-iii (PTPC), and PEPC-iv (BTPC), supported by the comprehensive analyses of their physicochemical properties, motif, and gene structures. Remarkably, PEPC-iv contained a heretofore unreported orchid PEPC gene, identified as VpPEPC4. Differences in the number of PEPC homolog genes among these species were attributed to segmental duplication, whole-genome duplication (WGD), or gene loss events. Cis-elements identified in promoter regions were predominantly associated with light responsiveness, and circadian-related elements were observed in each PEPC-i and PEPC-ii gene. The expression levels of recruited BTPC, VpPEPC4, exhibited a lower expression level than other VpPEPCs in the tested tissues. The expression analyses and RT-qPCR results revealed diverse expression patterns in orchid PEPC genes. Duplicated genes exhibited distinct expression patterns, suggesting functional divergence. This study offered a comprehensive analysis to unveil the evolution and function of PEPC genes in Orchidaceae.

Organelle Genomes of Epipogium roseum Provide Insight into the Evolution of Mycoheterotrophic Orchids.

Epipogium roseum, commonly known as one of the ghost orchids due to its rarity and almost transparent color, is a non-photosynthetic and fully mycoheterotrophic plant. Given its special nutritional strategies and evolutionary significance, the mitogenome was first characterized, and three plastomes sampled from Asia were assembled. The plastomes were found to be the smallest among Orchidaceae, with lengths ranging from 18,339 to 19,047 bp, and exhibited high sequence variety. For the mitogenome, a total of 414,552 bp in length, comprising 26 circular chromosomes, were identified. A total of 54 genes, including 38 protein-coding genes, 13 tRNA genes, and 3 rRNA genes, were annotated. Multiple repeat sequences spanning a length of 203,423 bp (45.47%) were discovered. Intriguingly, six plastid regions via intracellular gene transfer and four plastid regions via horizontal gene transfer to the mitogenome were observed. The phylogenomics, incorporating 90 plastomes and 56 mitogenomes, consistently revealed the sister relationship of Epipogium and Gastrodia, with a bootstrap percentage of 100%. These findings shed light on the organelle evolution of Orchidaceae and non-photosynthetic plants.

Characterization of Angraecum (Angraecinae, Orchidaceae) Plastomes and Utility of Sequence Variability Hotspots.

Angraecum, commonly known as Darwin's orchid, is the largest genus of Angraecinae (Orchidaceae). This genus exhibits a high morphological diversity, making it as a good candidate for macroevolutionary studies. In this study, four complete plastomes of Angraecum were firstly reported and the potential variability hotspots were explored. The plastomes possessed the typical quadripartite structure and ranged from 150,743 to 151,818 base pair (bp), with a guanine-cytosine (GC) content of 36.6-36.9%. The plastomes all contained 120 genes, consisting of 74 protein-coding genes (CDS), 38 transfer RNA (tRNA) genes and 8 ribosomal RNA (rRNA) genes; all ndh genes were pseudogenized or lost. A total of 30 to 46 long repeats and 55 to 63 SSRs were identified. Relative synonymous codon usage (RSCU) analysis indicated a high degree of conservation in codon usage bias. The Ka/Ks ratios of most genes were lower than 1, indicating that they have undergone purifying selection. Based on the ranking of Pi (nucleotide diversity) values, five regions (trnSGCU-trnGGCC, ycf1-trnNGGU, trnNGUU-rpl32, psaC-ndhE and trnSGCU-trnGGCC) and five protein-coding genes (rpl32, rps16, psbK, rps8, and ycf1) were identified. The consistent and robust phylogenetic relationships of Angraecum were established based on a total of 40 plastomes from the Epidendroideae subfamily. The genus Angraecum was strongly supported as a monophyletic group and sister to Aeridinae. Our study provides an ideal system for investigating molecular identification, plastome evolution and DNA barcoding for Angraecum.

Mucoepidermoid carcinoma arising in Warthin’s tumor of the upper lip: a case report and review / 口腔疾病防治

Objective @#To provide a reference for the diagnosis and treatment of mucoepidermoid carcinoma arising in Warthin’s tumor of the lip by investigating the diagnosis, treatment and prognosis of the disease.@*Methods @# A case of mucoepidermoid carcinoma arising in Warthin’s tumor of lip was reported, including the clinical manifestation, treatment, pathological characteristics and prognosis. The related literature was also reviewed and analyzed.@*Results@# A painless mass on the left lip lasting more than one month was found. Resection of the left lip was performed. Pathological examination showed that the tumor was a hybridoma composed of mucoepidermoid carcinoma and Warthin’s tumor. There was no recurrence or distant metastasis after 34 months. To date, this type of disease has been rarely reported. After thorough resection, the prognosis and survival rate are promising in most cases, with no recurrence or metastasis.@*Conclusion@#Mucoepidermoid carcinoma in Warthin’s tumor of the lip is rare. Clinical manifestations, imaging features and histological examination are useful when diagnosing the disease. Thorough resection will reduce the risk of disease recurrence.