Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

Campylotropis xinfeniae (Fabaceae, Papilionoideae), a new species from Yunnan, China, based on morphological and molecular evidence.

Campylotropis xinfeniae, a new species from the dry-hot valley of the Jinsha River in the Yunnan province, China, is described and illustrated. It is morphologically similar to C. wilsonii and C. brevifolia in having glabrescent old branches, absent stipels, 3-foliolate leaves, and adaxially puberulent leaflets, while it differs from the latter two in having often paniculate inflorescences, obviously white standard, not incurved sickle keel, larger narrowly oblique legumes, and longer legume beak. The complete chloroplast genome of this new species is 149,073 bp in length and exhibits a typical quadripartite structure. Phylogenetic analyses based on the complete chloroplast genome also supported C. xinfeniae as a new species located at the basal distinct clade of the genus Campylotropis, clearly separated from the remaining members of the genus and its allied genera. A conservation assessment of data deficient (DD) is recommended for the new species without extensive exploring of similar habitats according to the IUCN Categories and Criteria.

Complete Chloroplast Genomes Provide Insights Into Evolution and Phylogeny of Campylotropis (Fabaceae).

The genus Campylotropis Bunge (Desmodieae, Papilionoideae) comprises about 37 species distributed in temperate and tropical Asia. Despite the great potential in soil conservation, horticulture, and medicine usage, little is known about the evolutionary history and phylogenetic relationships of Campylotropis due to insufficient genetic resources. Here, we sequenced and assembled 21 complete chloroplast genomes of Campylotropis species. In combination with the previously published chloroplast genomes of C. macrocarpa and closely related species, we conducted comparative genomics and phylogenomic analysis on these data. Comparative analysis of the genome size, structure, expansion and contraction of inverted repeat (IR) boundaries, number of genes, GC content, and pattern of simple sequence repeats (SSRs) revealed high similarities among the Campylotropis chloroplast genomes. The activities of long sequence repeats contributed to the variation in genome size and gene content in Campylotropis chloroplast genomes. The Campylotropis chloroplast genomes showed moderate sequence variation, and 13 highly variable regions were identified for species identification and further phylogenetic studies. We also reported one more case of matK pseudogene in the legume family. The phylogenetic analysis confirmed the monophyly of Campylotropis and the sister relationship between Lespedeza and Kummerowia, the latter two genera were then sister to Campylotropis. The intrageneric relationships of Campylotropis based on genomic scale data were firstly reported in this study. The two positively selected genes (atpF and rps19) and eight fast-evolving genes identified in this study may help us to understand the adaptation of Campylotropis species. Overall, this study enhances our understanding of the chloroplast genome evolution and phylogenetic relationships of Campylotropis.

Chromosome-level de novo genome assembly and whole-genome resequencing of the threatened species Acanthochlamys bracteata (Velloziaceae) provide insights into alpine plant divergence in a biodiversity hotspot.

The Hengduan Mountains region is an important hotspot of alpine plant diversity and endemism. Acanthochlamys bracteata is a species of a threatened monotypic genus endemic to the Hengduan Mountains. In this study, we present a high-quality, chromosome-level reference genome for A. bracteata, constructed using long reads, short reads and Hi-C technology. We characterized its genetic diversity, population structure, demographic history and gene flow by resequencing individuals collected across its distribution. Comparative genomics analyses based on sequence information from single-copy orthologous genes revealed that A. bracteata and Dioscorea rotundata diverged ~104.5 million years ago. Whole-genome resequencing based on population genetic analysis revealed that the division of the 14 populations into 10 distinct clusters reflected geographical divergence, and three separate high levels of gene flow occurred sequentially between isolated populations of the Hengduan Mountains, a finding which is consistent with the turnover between ice ages and interglacial periods. Our findings indicate that Quaternary climatic changes played an important role in shaping the genetic structure and demographic trajectories of A. bracteata, and provide critical insights into the genetic status and evolutionary history of this poorly understood species, and possibly other alpine plants with a similar distribution. This study demonstrates the usefulness of population genomics for evaluating the effects of past climatic changes and identifying conservation units for the conservation and management of threatened species. Our high-quality genome represents a valuable resource for future studies of the underlying molecular mechanisms of adaptive evolution and provides insight for further comparative genomic analysis with other Velloziaceae species.

Titer dynamic analysis of D29 within MTB-infected macrophages and effect on immune function of macrophages.

The use of mycobacteriophage D29 to treat Mycobacterium tuberculosis (MTB)-infected macrophages results in significant inhibitory activity. This study aims to explore the novel treatment strategy of intracellular mycobacterial infection from the point of view of phages. We investigated the dynamic phagocytosis and elimination of D29 by macrophages, measured the titer of D29 inside and outside MTB within macrophages by fluorescence quantitative PCR, and detected the levels of interleukin 12 (IL-12) and nitric oxide (NO) in the culture supernatants of D29-infected macrophages by ELISA. Results showed that the activity of D29 phagocytosed by macrophages was significantly lower than that of D29 phagocytosed by MTB-infected macrophages. The titer of D29 that infected intracellular MTB ranged from 10(9) pfu to 10(4) pfu. The titer of D29 inside and outside intracellular MTB transiently increased when MTB-infected macrophages were incubated with D29 for 40 and 50 min; then, a large number of D29 were eliminated by macrophages. The levels of IL-12 and NO had no significant differences versus the negative control but were significantly lower compared with the lipopolysaccharide (LPS) positive control. These results suggest D29 has no effect on the immune function of macrophages and that high phage titer must be administered repeatedly if D29 is applied to treat intracellular MTB infection.

[The influence of heartbeat acceptance window settings on left ventricular function and perfusion parameters].

OBJECTIVE: To evaluate the influence of heartbeat acceptance window settings on left ventricular function and perfusion parameters of the arrhythmia patients during gated myocardial perfusion imaging. METHODS: Twenty eight fibrillation patients were consecutively recruited to undergo myocardial perfusion SPECT. The Concurrent Imaging software was used to create 3 separate SPECT studies with heartbeat acceptance window of 20%, 60% and 100% respectively. The software created the 3 studies separately rather than a rearrangement of an original list-mode acquisition. After reconstruction by Astonish, end-diastole volume (EDV) and end-systolic volume (ESV), left ventricular ejection fraction (LVEF), sum stress score (SSS), and sum rest score (SRS) were calculated with Quantitative Gated SPECT (QGS). Analyses of variance were performed using SPSS to compare the differences in EDV, ESV, EF, SSS, and SRS among the three studies. RESULTS: 85.7% of the 28 patients had abnormal perfusing. No statistical differences were found in EDV, ESV, EF, SSS, and SRS among the 3 studies. But the collection time was 40.5 min, 25.6 min and 15.0 min for heartbeat acceptance window of 20%, 60% and 100% respectively. CONCLUSION: Heartbeat acceptance window setting does not have a significant effect on EDV, ESV, EF, SSS, and SRS values. The wider the window is set, the shorter the collection time is.