Lasso-Cox interpretable model of AFP-negative hepatocellular carcinoma.

BACKGROUND: In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction. METHODS: We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system. RESULTS: The AUC values of the Lasso-Cox model at 1, 2, and 3 years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3 years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups. CONCLUSION: The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.

Comparative and phylogenetic analysis of Chiloschista (Orchidaceae) species and DNA barcoding investigation based on plastid genomes.

BACKGROUND: Chiloschista (Orchidaceae, Aeridinae) is an epiphytic leafless orchid that is mainly distributed in tropical or subtropical forest canopies. This rare and threatened orchid lacks molecular resources for phylogenetic and barcoding analysis. Therefore, we sequenced and assembled seven complete plastomes of Chiloschista to analyse the plastome characteristics and phylogenetic relationships and conduct a barcoding investigation. RESULTS: We are the first to publish seven Chiloschista plastomes, which possessed the typical quadripartite structure and ranged from 143,233 bp to 145,463 bp in size. The plastomes all contained 120 genes, consisting of 74 protein-coding genes, 38 tRNA genes and eight rRNA genes. The ndh genes were pseudogenes or lost in the genus, and the genes petG and psbF were under positive selection. The seven Chiloschista plastomes displayed stable plastome structures with no large inversions or rearrangements. A total of 14 small inversions (SIs) were identified in the seven Chiloschista plastomes but were all similar within the genus. Six noncoding mutational hotspots (trnNGUU-rpl32 > rpoB-trnCGCA > psbK-psbI > psaC-rps15 > trnEUUC-trnTGGU > accD-psaI) and five coding sequences (ycf1 > rps15 > matK > psbK > ccsA) were selected as potential barcodes based on nucleotide diversity and species discrimination analysis, which suggested that the potential barcode ycf1 was most suitable for species discrimination. A total of 47-56 SSRs and 11-14 long repeats (> 20 bp) were identified in Chiloschista plastomes, and they were mostly located in the large single copy intergenic region. Phylogenetic analysis indicated that Chiloschista was monophyletic. It was clustered with Phalaenopsis and formed the basic clade of the subtribe Aeridinae with a moderate support value. The results also showed that seven Chiloschista species were divided into three major clades with full support. CONCLUSION: This study was the first to analyse the plastome characteristics of the genus Chiloschista in Orchidaceae, and the results showed that Chiloschista plastomes have conserved plastome structures. Based on the plastome hotspots of nucleotide diversity, several genes and noncoding regions are suitable for phylogenetic and population studies. Chiloschista may provide an ideal system to investigate the dynamics of plastome evolution and DNA barcoding investigation for orchid studies.

Characteristics and Comparative Analysis of Seven Complete Plastomes of Trichoglottis s.l. (Aeridinae, Orchidaceae).

Trichoglottis exhibits a range of rich variations in colors and shapes of flower and is a valuable ornamental orchid genus. The genus Trichoglottis has been expanded by the inclusion of Staurochilus, but this Trichoglottis sensu lato (s.l.) was recovered as a non-monophyletic genus based on molecular sequences from one or a few DNA regions. Here, we present phylogenomic data sets, incorporating complete plastome sequences from seven species (including five species sequenced in this study) of Trichoglottis s.l. (including two species formerly treated as Staurochilus), to compare plastome structure and to reconstruct the phylogenetic relationships of this genus. The seven plastomes possessed the typical quadripartite structure of angiosperms and ranged from 149,402 bp to 149,841 bp with a GC content of 36.6-36.7%. These plastomes contain 120 genes, which comprise 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes, all ndh genes were pseudogenized or lost. A total of 98 (T. philippinensis) to 134 (T. ionosma) SSRs and 33 (T. subviolacea) to 46 (T. ionosma) long repeats were detected. The consistent and robust phylogenetic relationships of Trichoglottis were established using a total of 25 plastid genomes from the Aeridinae subtribe. The genus Trichoglottis s.l. was strongly supported as a monophyletic group, and two species formerly treated as Staurochilus were revealed as successively basal lineages. In addition, five mutational hotspots (trnNGUU-rpl32, trnLUAA, trnSGCU-trnGUCC, rbcL-accD, and trnTGGU-psbD) were identified based on the ranking of PI values. Our research indicates that plastome data is a valuable source for molecular identification and evolutionary studies of Trichoglottis and its related genera.

Comparative Analysis of Plastomes in Elsholtzieae: Phylogenetic Relationships and Potential Molecular Markers.

The Elsholtzieae, comprising ca. 7 genera and 70 species, is a small tribe of Lamiaceae (mint family). Members of Elsholtzieae are of high medicinal, aromatic, culinary, and ornamentals value. Despite the rich diversity and value of Elsholtzieae, few molecular markers or plastomes are available for phylogenetics. In the present study, we employed high-throughput sequencing to assemble two Mosla plastomes, M. dianthera and M. scabra, for the first time, and compared with other plastomes of Elsholtzieae. The plastomes of Elsholtzieae exhibited a quadripartite structure, ranging in size from 148,288 bp to 152,602 bp. Excepting the absence of the pseudogene rps19 in Elsholtzia densa, the exhaustive tally revealed the presence of 132 genes (113 unique genes). Among these, 85 protein-coding genes (CDS), 37 tRNA genes, 8 rRNA genes, and 2 pseudogenes (rps19 and ycf1) were annotated. Comparative analyses showed that the plastomes of these species have minor variations at the gene level. Notably, the E. eriostchya plastid genome exhibited increased GC content regions in the LSC and SSC, resulting in an increased overall GC content of the entire plastid genome. The E. densa plastid genome displayed modified boundaries due to inverted repeat (IR) contraction. The sequences of CDS and intergenic regions (IGS) with elevated variability were identified as potential molecular markers for taxonomic inquiries within Elsholtzieae. Phylogenetic analysis indicated that four genera formed monophyletic entities, with Mosla and Perilla forming a sister clade. This clade was, in turn, sister to Collinsonia, collectively forming a sister group to Elsholtzia. Both CDS, and CDS + IGS could construct a phylogenetic tree with stronger support. These findings facilitate species identification and DNA barcoding investigations in Elsholtzieae and provide a foundation for further exploration and resource utilization within this tribe.

Comparative Phylogenetic Analysis for Aerides (Aeridinae, Orchidaceae) Based on Six Complete Plastid Genomes.

Aerides Lour. (Orchidaceae, Aeridinae) is a group of epiphytic orchids with high ornamental value, mainly distributed in tropical and subtropical forests, that comprises approximately 20 species. The species are of great value in floriculture and garden designing because of their beautiful flower shapes and colors. Although the morphological boundaries of Aerides are clearly defined, the relationship between Aerides and other closely related genera is still ambiguous in terms of phylogeny. To better understand their phylogenetic relationships, this study used next-generation sequencing technology to investigate the phylogeny and DNA barcoding of this taxonomic unit using genetic information from six Aerides plastid genomes. The quadripartite-structure plastomes ranged from 147,244 bp to 148,391 bp and included 120 genes. Among them, 74 were protein coding genes, 38 were tRNA genes and 8 were rRNA genes, while the ndh genes were pseudogenized or lost. Four non-coding mutational hotspots (rpl20-rpl33, psbM, petB, rpoB-trnCGCA, Pi > 0.06) were identified. A total of 71-77 SSRs and 19-46 long repeats (>30 bp) were recognized in Aerides plastomes, which were mostly located in the large single-copy region. Phylogenetic analysis indicated that Aerides was monophylic and sister to Renanthera. Moreover, our results confirmed that six Aerides species can be divided into three major clades. These findings provide assistance for species identification and DNA barcoding investigation in Aerides, as well as contributes to future research on the phylogenomics of Orchidaceae.

Comparison of the efficacy and safety of selective internal radiotherapy and sorafenib alone or combined for hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Selective internal radiation therapy (SIRT) is a developing technique and its efficacy and modality of application in hepatocellular carcinoma (HCC) are still controversial. This network meta-analysis aims to determine whether the efficacy and safety of SIRT alone and in combination are superior to that of sorafenib. METHODS: Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched before August 2022. Cochrane Randomized Trial Risk of Bias Assessment Tool and the Newcastle-Ottawa scale were used to assess the quality. The outcomes of interest included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). RESULTS: A total of 9 eligible trials involving 1954 patients were included, and SIRT ranked first among the three treatment modalities in terms of both OS (probability, 52.3%) and PFS (probability, 68.6%). The combination of SIRT and sorafenib did not improve OS or PFS in patients with HCC. Although the combination of SIRT and sorafenib did not raise the risk of grade 3 or higher AEs, it may have introduced more AEs than either alone. CONCLUSIONS: SIRT alone was found to be superior to sorafenib and the combination of the two in improving OS or PFS in patients with non-surgical HCC, especially in patients with combined portal vein tumor thrombus. The AEs induced by SIRT were different from those of sorafenib, but the overall toxicity was manageable, the combination of the two may cause an increase in the types of AEs that occur.

Comparative Analysis of Luisia (Aeridinae, Orchidaceae) Plastomes Shed Light on Plastomes Evolution and Barcodes Investigation.

Luisia, a genus of the subtribe Aeridinae of Orchidaceae, comprises ca. 40 species. Members of Luisia exhibit unique morphological characteristics and represent a valuable ornamental orchid genus. However, due to the scarcity of distinct morphological characters, species identification within this genus is ambiguous and controversial. In the present study, next-generation sequencing (NGS) methods were used to assemble the plastomes of five Luisia species and compare them with one publicly available Luisia plastid genome data. The plastomes of Luisia possessed a quadripartite structure, with sizes ranging from 146,243 bp to 147,430 bp. The plastomes of six Luisia species contained a total of 120 genes, comprising 74 protein-coding genes, 38 tRNA genes and eight rRNA genes. Notably, all ndh genes were pseudogenized or lost. An analysis of codon usage bias showed that leucine (Leu) exhibited the highest frequency, while cysteine (Cys) exhibited the lowest frequency. A total of 57 to 64 SSRs and 42 to 49 long repeats were identified. Five regions and five coding sequences were identified for DNA barcodes, based on the nucleotide diversity (Pi) analysis. The species of Luisia constituted a monophyletic group and were sister to Paraphalaenopsis with strong support. Our study deepens the understanding of species identification, plastome evolution and the phylogenetic positions of Luisia.

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.

Plastid phylogenomics improves resolution of phylogenetic relationship in the Cheirostylis and Goodyera clades of Goodyerinae (Orchidoideae, Orchidaceae).

Goodyerinae are one of phylogenetically unresolved groups of Orchidaceae. The lack of resolution achieved through the analyses of previous molecular sequences from one or a few markers has long confounded phylogenetic estimation and generic delimitation. Here, we present large-scale phylogenomic data to compare the plastome structure of the two main clades (Goodyera and Cheirostylis) in this subtribe and further adopt two strategies, combining plastid coding sequences and the whole plastome, to investigate phylogenetic relationships. A total of 46 species in 16 genera were sampled, including 39 species in 15 genera sequenced in this study. The plastomes of heterotrophic species are not drastically reduced in overall size, but display a pattern congruent with a loss of photosynthetic function. The plastomes of autotrophic species ranged from 147 to 165 kb and encoded from 132 to 137 genes. Three unusual structural features were detected: a 1.0-kb inversion in the large single-copy region of Goodyera schlechtendaliana; the loss and/or pseudogenization of ndh genes only in two species, Cheirostylis chinensis and C. montana; and the expansion of inverted repeat regions and contraction of small single-copy region in Hetaeria oblongifolia. Phylogenomic analyses provided improved resolution for phylogenetic relationships. All genera were recovered as monophyletic, except for Goodyera and Hetaeria, which were each recovered as non-monophyletic. Nomenclatural changes are needed until the broader sampling and biparental inherited markers. This study provides a phylogenetic framework of Goodyerinae and insight into plastome evolution of Orchidaceae.

The complete plastid genome of Thrixspermum centipeda (Orchidaceae, Aeridinae).

The complete plastid genome of the type species of Thrixspermum, Th. centipeda, was determined and analyzed in this work. The plastome was 147,888 bp in length with 85,899 bp of the large single-copy (LSC) region, 11,055 bp of the small single-copy (SSC) region and 25,467 bp of the invert repeats (IR) regions. The genome contained 120 genes, including 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analysis divided 18 Aeridinae plastomes into four groups, and Th. centipeda was sister to Th. tsii.

SCYL1-BP1 affects cell cycle arrest in human hepatocellular carcinoma cells via Cyclin F and RRM2.

The cell cycle is regulated via important biological mechanisms. Controlled expression of cell cycle regulatory proteins is crucial to maintain cell cycle progression. However, unbalanced protein expression leads to many diseases, such as cancer. Previous research suggests that SCYL1-BP1 function might be related to cell cycle progression and SCYL1-BP1 dysfunction to diseases through undefined mechanisms. In this research, an unbiased yeast two-hybrid screen was used to find protein(s) with potential biological relevance to SCYL1-BP1 function, and a novel interaction was recognized between SCYL1-BP1 and Cyclin F. This interaction was chosen as a paradigm to study SCYL1-BP1 function in cell cycle progression and its possible role in tumorigenesis. We found that SCYL1-BP1 binds to Cyclin F both in vivo and in vitro. SCYL1-BP1 overexpression promoted expression of the CCNF gene and simultaneously delayed Cyclin F protein degradation. SCYL1-BP1 knockdown reduced the expression of endogenous Cyclin F. It was also demonstrated in functional assays that SCYL1-BP1 overexpression induces G2/M arrest in cultured liver cells. Furthermore, SCYL1-BP1 sustained RRM2 protein expression by reducing its ubiquitination. Thus, we propose that SCYL1- BP1 affects the cell cycle through increasing steady state levels of Cyclin F and RRM2 proteins, thus constituting a dual regulatory circuit. This study provides a possible mechanism for SCYL1-BP1-mediated cell cycle regulation and related diseases.

Measurement for natural dental neck data of normal adults and its clinical significance on guiding implant restoration.

OBJECTIVE: Provide reference basis for the clinical implant restoration to select implant diameter through measuring each data of 7 teeth in the dental neck of bilateral upper and lower jaws of the young volunteers with normal dentition. METHODS: Select 30 healthy young volunteers with complete dentition but no malocclusion, take cone beam CT (CBCT), measure the mesiodistal and buccolingual distance of the tooth root at 1.5 mm from 14 teeth (bilateral upper and lower jaws) to alveolar crest, trace out the outline of each tooth neck in this layer, calculate the cross sectional area and roundness of each tooth neck according to pixel value calibration, and then carry out statistical processing. RESULTS: Complete the data collection and processing of mesiodistal length, buccolingual width, cross sectional area, and cross sectional roundness of the dental neck at 1.5 mm from these seven teeth of the bilateral upper and lower jaws to the alveolar crest of 30 volunteers, and calculate the mean value, variance, and reference value range of medical science of each index. CONCLUSION: CBCT can effectively obtain the image information of the dental neck. Through mimics 10.0 and Photoshop CS3, it is possible to accurately calculate the dental neck length and width, and cross sectional area of each tooth according to CBCT image information. This result can provide reference basis for the implant restoration of the clinical teeth.