A novel mitochondria-related core gene signature to predict the prognosis and evaluate tumour microenvironment in CESC single-cell validation.

Mitochondria and their related genes (MTRGs) are pivotal in the tumour microenvironment (TME) of cervical cancer, influencing prognosis and treatment response. This study developed a prognostic model using MTRGs to predict overall survival (OS) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), aiming for personalized therapy. Analysing 14 MTRGs like ISCU and NDUFA11 through techniques such as univariate Cox regression, we found that a low mitochondrial (MT) score is associated with better survival, while a high MT score predicts poorer outcomes. The TME score, particularly influenced by CD8 T cells, also correlates with prognosis, with a high score indicating favourable outcomes. The interplay between MT and TME subtypes revealed that the best prognosis is seen in patients with a low MT and high TME score. Our findings highlight the role of MTRGs as potential biomarkers and therapeutic targets in cervical cancer, offering a novel approach to improving patient outcomes through a more nuanced understanding of mitochondrial function and immune interactions within the TME. This model presents a promising avenue for enhancing the precision of prognostic assessments in CESC.

Uppermost global tree elevations are primarily limited by low temperature or insufficient moisture.

The impact of anthropogenic global warming has induced significant upward dispersal of trees to higher elevations at alpine treelines. Assessing vertical deviation from current uppermost tree distributions to potential treeline positions is crucial for understanding ecosystem responses to evolving global climate. However, due to data resolution constraints and research scale limitation, comprehending the global pattern of alpine treeline elevations and driving factors remains challenging. This study constructed a comprehensive quasi-observational dataset of uppermost tree distribution across global mountains using Google Earth imagery. Validating the isotherm of mean growing-season air temperature at 6.6 ± 0.3°C as the global indicator of thermal treeline, we found that around two-thirds of uppermost tree distribution records significantly deviated from it. Drought conditions constitute the primary driver in 51% of cases, followed by mountain elevation effect which indicates surface heat (27%). Our analyses underscore the multifaceted determinants of global patterns of alpine treeline, explaining divergent treeline responses to climate warming. Moisture, along with temperature and disturbance, plays the most fundamental roles in understanding global variation of alpine treeline elevation and forecasting alpine treeline response to ongoing global warming.

Recombinant Viral Capsid Protein L2 (rVL2) of HPV 16 Suppresses Cell Proliferation and Glucose Metabolism via ITGB7/C/EBPß Signaling Pathway in Cervical Cancer Cell Lines.

PURPOSE: Capsid protein L2 is the minor capsid protein of human papillomavirus 16 (HPV16). Although L2-based vaccines were developed, the therapeutic effect of recombinant viral capsid protein L2 (rVL2) was still to be illustrated. METHODS: We used glucose uptake and lactate production assay to verify the inhibitory effect of rVL2 on the glucose metabolism in cervical cancer cells. Secondly, we performed gene-chip assay, RT-PCR, and Western blot to determine the role of ITGB7/C/EBPß signaling pathway in rVL2-mediated glucose metabolism in vitro. Finally, we used an animal model to verify the function of rVL2 in cervical cancer. RESULTS: We found that rVL2 reduced glucose uptake and lactate production levels in cervical cancer cells, which caused the inhibition of cell proliferation. rVL2 decreased the expression levels of key metabolic enzymes, including GLUT1, LDHA, and ALDOA, to affect cell metabolism in cervical cancer cells by inhibiting ITGB7/C/EBPß signaling pathway in vitro and in vivo. CONCLUSION: These results demonstrated the vital role of rVL2 in the glycolysis-induced cell growth and proliferation via suppressing ITGB7/C/EBPß signaling axis.

Hotspot analyses indicate significant conservation gaps for evergreen broadleaved woody plants in China.

Evergreen broadleaved woody plants (EBWPs) are dominant components in forests and savanna of the global tropic and subtropic regions. Southern China possesses the largest continuous area of subtropical EBWPs distribution, harboring a high proportion of endemic species. Hotspot and gap analyses are effective methods for analyzing the spatial pattern of biodiversity and conservation and were used here for EBWPs in China. Based on a distribution data set of 6,265 EBWPs with a spatial resolution of 50 × 50 km, we measured diversity of EBWPs in China using four indices: species richness, corrected weighted endemism, relative phylogenetic diversity, and phylogenetic endemism. According to the results based on 10% threshold, 15.73% of China's land area was identified as hotspots using at least one diversity index. Only 2.14% of China's land area was identified as hotspots for EBWPs by all four metrics simultaneously. Most of the hotspots locate in southern mountains. Moreover, we found substantial conservation gaps for Chinese EBWPs. Only 25.43% of the hotspots are covered by existing nature reserves by more than 10% of their area. We suggest to promote the establishment and management of nature reserve system within the hotspot gaps.

The phylogeography of Fagus hayatae (Fagaceae): genetic isolation among populations.

The beech species Fagus hayatae is an important relict tree species in subtropical China, whose biogeographical patterns may reflect floral responses to climate change in this region during the Quaternary. Previous studies have revealed phylogeography for three of the four Fagus species in China, but study on F. hayatae, the most sparsely distributed of these species, is still lacking. Here, molecular methods based on eight simple sequence repeat (SSR) loci of nuclear DNA (nDNA) and three chloroplast DNA (cpDNA) sequences were applied for analyses of genetic diversity and structure in 375 samples from 14 F. hayatae populations across its whole range. Both nDNA and cpDNA indicated a high level of genetic diversity in this species. Significant fixation indexes and departures from the Hardy-Weinberg equilibrium, with a genetic differentiation parameter of R st of 0.233, were detected in nDNA SSR loci among populations, especially those on Taiwan Island, indicating strong geographic partitioning. The populations were classified into two clusters, without a prominent signal of isolation-by-distance. For the 15 haplotypes detected in the cpDNA sequence fragments, there was a high genetic differentiation parameter (G st = 0.712) among populations. A high G st of 0.829 was also detected outside but not within the Sichuan Basin. Consistent with other Fagus species in China, no recent population expansion was detected from tests of neutrality and mismatch distribution analysis. Overall, genetic isolation with limited gene flow was prominent for this species and significant phylogeographic structures existed across its range except for those inside the Sichuan Basin. Our study suggested long-term geographic isolation in F. hayatae with limited population admixture and the existence of multiple refugia in the mountainous regions of the Sichuan Basin and southeast China during the Quaternary. These results may provide useful information critical for the conservation of F. hayatae and other Chinese beech species.

Kctd10 regulates heart morphogenesis by repressing the transcriptional activity of Tbx5a in zebrafish.

The T-box transcription factor Tbx5 (Tbx5a in zebrafish) plays a crucial role in the formation of cardiac chambers in a dose-dependent manner. Its deregulation leads to congenital heart disease. However, little is known regarding its regulation. Here we isolate a zebrafish mutant with heart malformations, called 34c. The affected gene is identified as kctd10, a member of the potassium channel tetramerization domain (KCTD)-containing family. In the mutant, the expressions of the atrioventricular canal marker genes, such as tbx2b, hyaluronan synthase 2 (has2), notch1b and bmp4, are changed. The knockdown of tbx5 rescues the ectopic expression of has2, and knockdown of either tbx5a or has2 alleviates the heart defects. We show that Kctd10 directly binds to Tbx5 to repress its transcriptional activity. Our results reveal a new essential factor for cardiac development and suggest that KCTD10 could be considered as a new causative gene of congenital heart disease.