Arthropods are the largest group in the animal kingdom and are morphologically characterized by heterorhythmic segments. Brachyuran decapod crustaceans undergo brachyurization metamorphosis in the ...early developmental process, characterized by a reduced abdomen that is folded beneath the cephalothorax and inserted between the pereiopods or in a special cavity. As the main cause of major alterations in the evolution of animal body plans, Hox genes encode transcription factors and are involved in bilaterian anterior-posterior axis patterning.
We found eight Hox genes (labial, proboscipedia, Deformed, zerknüllt, Sex combs reduced, Antennapedia, Ultrabithorax, fushi tarazu, abdominal-A and Abdominal-B) in Eriocheir sinensis. The phylogenetic topology of 13 arthropod Hox genes was closely related to traditional taxonomic groupings. Genome collinearity analysis was performed using genomic data and chromosomal location data of E. sinensis and Portunus trituratus. We found that their chromosomes were highly collinear, and there was a corresponding collinear relationship between the three Hox genes (lab, ftz and Abd-B). The mRNA expression levels of Scr and Antp fluctuated significantly in different developmental stages of E. sinensis, especially in the brachyurization stages. Evolutionary analysis indicated the presence of positively selected sites in Ubx.
In this study, we used genome-wide analysis to identify and analyze all members of the Hox genes in E. sinensis. Our data will contribute to a better understanding of Hox genes in E. sinensis and provide useful molecular evolutionary information for further investigation on their roles in the brachyurization of crabs.
Setae on the pad lamellae of the Japanese gecko Gekko japonicus (Schlegel, 1836), a vital epidermal derivative, are primarily composed of cornified beta-proteins (CBPs) and play a pivotal role in ...adhesion and climbing. The amino acid composition of CBPs might be a determining factor influencing their functional properties. However, the molecular mechanisms governed by CBP genes with diverse amino acid compositions in setae development remain unexplored.
Based on RNA-seq analyses, this study confirmed that all G. japonicus CBPs (GjCBPs) are involved in setae formation. Cysteine-rich CBPs encoding genes (ge-cprp-17 to ge-cprp-26) and glycine-rich CBPs encoding genes (ge-gprp-17 to ge-gprp-22) were haphazardly selected, with quantitative real-time PCR revealing their expression patterns in embryonic pad lamellae and dorsal epidermis. It is inferred that glycine-rich CBPs are integral to the formation of both dorsal scales and lamellar setae, cysteine-rich CBPs are primarily associated with setae development. Additionally, fluorescence in situ hybridization revealed spatiotemporal differences in the expression of a glycine-rich CBP encoding gene (ge-gprp-19) and a cysteine-rich CBP encoding gene (ge-cprp-17) during dorsal scales and/or lamellar development.
All 66 CBPs are involved in the formation of setae. Glycine-rich CBPs hold a significant role in the development of dorsal scales and lamellar setae, whereas most cysteine-rich CBPs appear to be essential components of G. japonicus setae. Even GjCBPs with similar amino acid compositions may play diverse functions. The clear spatio-temporal expression differences between the glycine-rich and cysteine-rich CBP encoding genes during epidermal scale and/or setae formation were observed. Embryonic developmental stages 39 to 42 emerged as crucial phases for setae development. These findings lay the groundwork for deeper investigation into the function of GjCBPs in the development of G. japonicus setae.
This meta-analysis aimed to evaluate the comparative diagnostic efficacy of
FFDG PET/CT and
F FDG PET/MRI in detecting bone metastases in breast cancer patients.
An extensive search was conducted ...in the PubMed, Embase, Web of Science, and Cochrane Library databases to identify available publications up to February 2023. Studies were included if they evaluated the diagnostic efficacy of
FFDG PET/CT and
FFDG PET/MRI in patients with breast cancer bone metastases. Sensitivity and specificity were assessed using the DerSimonian and Laird method, followed by transformation via the Freeman-Tukey double inverse sine transformation.
16 articles (including 4 head-to-head comparison articles) involving 1,261 patients were included in the meta-analysis. The overall sensitivity of
FFDG PET/CT in patient-based analysis, lesion-based analysis, and head-to-head comparison were 0.73, 0.89, and 0.87, respectively, while the overall sensitivity of
FFDG PET/MRI were 0.99, 0.99, and 0.99. The results indicated that
FFDG PET/MRI appears to a higher sensitivity in comparison to
FFDG PET/CT(all
< 0.05). In contrast, the overall specificity of
FFDG PET/CT in patient-based analysis, lesion-based analysis, and head-to-head comparison were 1.00, 0.99, and 1.00, respectively, while the overall specificity of
FFDG PET/MRI were 1.00, 0.99, and 0.98. These results suggested that
FFDG PET/CT has a similar level of specificity compared to
FFDG PET/MRI.
Our meta-analysis indicates that
FFDG PET/MRI demonstrates superior sensitivity and similar specificity to
FFDG PET/CT in detecting bone metastases in breast cancer patients. Further prospective research is required to confirm these findings and assess the clinical application of these techniques.
Body size is one of the most important traits of an organism. Among reptiles, both lizards and snakes show body size differences that span a similar six orders of magnitude variation. However, the ...molecular mechanisms underlying body size variation in squamates remain obscure. Here, we performed comparative genomic analyses of 101 body-size-related genes from 28 reptilian genomes. Phylogenetic analysis by maximum likelihood (PAML) revealed that snakes showed higher evolutionary rates in body-size-related genes, and had an almost two-fold increase in the number of positively selected genes (∼20.3%) compared with lizards (∼8.9%). The high similarities in dN/dS values were obtained between the branches of large-bodied lizards and large-bodied snakes by Spearman correlation analysis. Combining the results from site model, branch-site model and clade model analyses, we found some key genes regulating the evolution of body size in squamates, such as
COL10A1
,
GHR
,
NPC1
,
GALNS
,
CDKN2C
,
FBN1
, and
LCORL
. Phylogenetic generalized least squares (PGLS) indicated that
AKT1
,
BMP1
,
IGF1
,
SOX5
,
SOX7
in lizards and
BMP5
,
BMP7
,
GPC6
,
SH2B3
,
SOX17
in snakes were significantly correlated with body length and body mass. Furthermore, ecological factors had varying degrees of impact on body size and the evolutionary rate of body-size-related genes in squamates. Intriguingly, climate had little effect on body size of lizards and snakes, but the contribution of climate-related factors to the variation in evolutionary rate of body-size-related genes were relatively higher. Our study lays a foundation for a comprehensive understanding of genetic mechanisms of body size evolution in squamates during the process of adapting to terrestrial life.
, i.e., Schlegel's Japanese Gecko, is an important species which is widely distributed in East Asia. However, the information about population genetics of this species from China remains unclear. To ...address this issue, we used sequences from a fragment of the mitochondrial protein-coding gene cytochrome c oxidase I to estimate genetic diversity, genetic structure, and historical demography of
populations from China. Phylogenetic analysis indicated that
had a close relationship with
. A total of 14 haplotypes were obtained, of which haplotype 1 was the most common and widely distributed. The genetic diversity of
was comparatively low across different geographic populations. The populations of
were divided into four groups which exhibited low levels of genetic differentiation, and expressed an unclear pattern of population structuring. In addition, potential population expansion of
has occurred as well. Overall, these results demonstrate that the populations of
reveal low genetic diversity in China, which is attributed to the founder and bottleneck events among populations. Our results will provide meaningful information on the population genetics of
and will provide some insights into the study of origin of populations.
Arachidonate lipoxygenase12 (Alox12) and its metabolites 12S-hydroxyeicosatetraenoic acid (12S-HETE) have been implicated in influencing tumor transformation and progression. In this study, we have ...systematically evaluated the expression, function and the downstream effectors of Alox12 in breast cancer using loss- and gain-of-function approaches. We demonstrated that both mRNA and protein levels of Alox12 were significantly increased in multiple breast cancer cell lines compared to normal breast cells. The upregulation of Alox12 expression was also observed in breast cancer tissues and their matched normal breast tissues obtained from patients. Functionally, we demonstrated that Alox12 overexpression was sufficient to stimulate growth in normal breast cells but not breast cancer cells. This also protects breast cancer cell from chemotherapy-induced growth arrest and apoptosis. In contrast, Alox12 depletion inhibited breast cancer growth and survival, and significantly enhanced the chemotherapeutic agents’ efficacy. Mechanism studies showed that Alox12 depletion activated AMP-activated protein kinase (AMPK), leading to the inhibition of acetyl-CoA carboxylase1 (ACC1) enzyme activity and lipid synthesis. The recuse of the effects of Alox12 depletion using Alox12 metabolites 12S-HETE further confirmed that AMPK and its subsequent inhibition of ACC1 activity and lipid synthesis were the downstream signaling of Alox12 inhibition. Our findings highlighted the important role of Alox12 in breast cancer, particularly in response to chemotherapy. Our work also demonstrate that inhibiting Alox12 is a possible alternative therapeutic strategy to overcome chemoresistance in breast cancer.
•Alox12 is aberrantly activated in breast cancer tissues and cells.•Alox12 increases normal breast cell growth and breast cancer cell chemoresistance.•Alox12 depletion negatively affects breast cancer cell.•Alox12 depletion activates AMPK and inhibits lipid synthesis.
Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer‐related deaths. Unfortunately, many patients face the issue of inoperability at the ...diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single‐cell RNA sequencing (scRNA‐seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co‐localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha‐smooth muscle actin (α‐SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis‐associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.
Epidermal appendages of birds and reptiles, including claws, feathers, scales, and setae, are primarily composed of alpha keratins (KRTs) and corneous beta-proteins (CBPs). A comprehensive and ...systematic knowledge of KRTs and CBPs in Schlegel's Japanese gecko (Gekko japonicus) is still lacking. In this study, 22 candidate Gecko japonicus keratin (GjKRT) family genes (12 type I genes, 10 type II genes) were identified in the G. japonicus genome. The majority of GjKRT genes across various subgroups had undergone a prolonged and highly conservative evolutionary process. Through a combination of morphological observation, RNA-seq analysis, and qRT-PCR assay, it was possible to discern the dynamic alterations in the expression of GjKRTs and Gecko japonicus corneous beta-proteins genes (GjCBPs). These findings strongly indicate that GjKRTs gradually accumulate to constitute an α-layer, which is subsequently succeeded by the formation of the corneous beta layer containing GjCBPs at late stages (40-42) of embryonic development. The epidermal appendages in G. japonicus may result from the joint accumulation of KRTs and CBPs, with stages 40-42 being critical for their development. These findings provide novel insights into KRTs and CBPs of G. japonicus and offer a foundation for investigating the functions of GjKRT and GjCBP gene families. Furthermore, this knowledge contributes to unraveling the molecular mechanisms underlying the formation of epidermal appendages in G. japonicus.
Neuroendocrine carcinoma of the breast (NECB) is a rare subtype of breast cancer, comprising only 0.1% to 5% of all breast cancer cases. Despite its rarity, it is important to gain a better ...understanding of the epidemiological, clinical, and prognostic features of NECB. The purpose of the study was to obtain population-based evaluations of the epidemiological and survival outcomes of NECB.BackgroundNeuroendocrine carcinoma of the breast (NECB) is a rare subtype of breast cancer, comprising only 0.1% to 5% of all breast cancer cases. Despite its rarity, it is important to gain a better understanding of the epidemiological, clinical, and prognostic features of NECB. The purpose of the study was to obtain population-based evaluations of the epidemiological and survival outcomes of NECB.The data of patients with neuroendocrine carcinoma diagnosed and enrolled between 2000 and 2017 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive statistical analyses were used to assess the distribution and tumor-related characteristics of these patients. Kaplan-Meier curves and univariate and multivariate Cox proportional risk models were used to analyze variables that might be associated with prognosis.MethodsThe data of patients with neuroendocrine carcinoma diagnosed and enrolled between 2000 and 2017 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive statistical analyses were used to assess the distribution and tumor-related characteristics of these patients. Kaplan-Meier curves and univariate and multivariate Cox proportional risk models were used to analyze variables that might be associated with prognosis.This study included 7,856 patients with neuroendocrine carcinoma. The median age of the patients was 64 years, and most of them were female, White, and diagnosed at ≥60 years old. The most common pathological type was neoplasm. Survival analysis indicated that there were significant differences in age, marital status, registration location, American Joint Committee on Cancer (AJCC) stage, breast subtype, surgery of primary tumor, and no cancer cause surgery patients with NECB. The results also indicated that treatment with surgery, including surgery of primary tumor, surgery combined with radiation, and no cancer cause surgery, were all effective in improving the prognosis compared with not providing surgical treatment.ResultsThis study included 7,856 patients with neuroendocrine carcinoma. The median age of the patients was 64 years, and most of them were female, White, and diagnosed at ≥60 years old. The most common pathological type was neoplasm. Survival analysis indicated that there were significant differences in age, marital status, registration location, American Joint Committee on Cancer (AJCC) stage, breast subtype, surgery of primary tumor, and no cancer cause surgery patients with NECB. The results also indicated that treatment with surgery, including surgery of primary tumor, surgery combined with radiation, and no cancer cause surgery, were all effective in improving the prognosis compared with not providing surgical treatment.In conclusion, NECB is a very rare lesion for which age, marital status, registration location, and surgery, AJCC stage, breast subtype were found to be independent prognostic factors.ConclusionsIn conclusion, NECB is a very rare lesion for which age, marital status, registration location, and surgery, AJCC stage, breast subtype were found to be independent prognostic factors.
To investigate the association between the recurrence score (RS) obtained by Oncotype
test and long non-coding RNA (lncRNA)
expression in early and estrogen receptor-positive (ER
) breast cancer.
The ...Oncotype
test and
expression detection were performed in tumor samples from 76 ER
and early breast cancer patients with the Surplex liquid chip. The RS value was calculated based on the expression of total 21 genes. The level of
was measured in both tumor tissue and para-tumor tissue, and relatively quantified with an internal control gene. Mann-Whitney
-test or Kruskal-Wallis test were used to analyze the association between
level and different clinical pathological characteristics, including age, tumor stage, disease grade, lymph node status, Ki-67 expression, and progesterone receptor (PR) status. The association between the RS and different characteristics was analyzed by Wilcoxon rank-sum test. Correlation between two parameters was analyzed by Spearman's rank correlation analysis.
The expression of
was more abundant in tumor tissue (2.992 ± 2.256) than that in adjacent normal tissue (1.641±1.438,
=-2.594,
0.009), and it was not correlated with any clinical pathological characteristics. According to the old criteria for RS stratification, 52.7% of patients were in low risk (RS<18), 36.8% of patients were in medium risk (18≤RS≤30), and 10.5% of patients were in high risk (RS>30). While under the new criteria, 18.4% were in low risk group (RS<11), 63.2% were in a medium risk group (11≤RS≤26), and 18.4% were in a high risk group (RS>26). The Oncotype
results only correlated with Ki-67 expression under both new and old criteria, and it was not related with other cancer characteristics. The expression of lncRNA
was significantly correlated with the Oncotype
results under the old criteria.
is a novel breast cancer biomarker independent of tumor stage, disease grade and lymph node status.
level is associated with the Oncotype
RS value. Therefore, combination of
and the Oncotype
test may be used to predict prognosis in ER
and early stage breast cancer.