Pan-cancer analysis of oncogenic role of Programmed Cell Death 2 Like (PDCD2L) and validation in colorectal cancer.

BACKGROUND: Programmed Cell Death 2 Like (PDCD2L) correlates with cell proliferation, apoptosis and mouse embryonic development. However, the role of PDCD2L in human cancers is unclear. METHODS: Multiple bioinformatic methods, in vitro function experiments and validation were performed to clarify the oncogenic role of PDCD2L in human cancers. RESULTS: Our study found that PDCD2L was aberrantly expressed in multiple types of human cancers, and associated with clinical stage and molecular subtype. Furthermore, overexpression of PDCD2L predicted poor overall survival in adrenocortical carcinoma(ACC), kidney chromophobe(KICH), acute myeloid leukemia(LAML), brain lower grade glioma(LGG),liver hepatocellular carcinoma(LIHC), mesothelioma(MESO), uveal melanoma(UVM) and poor diseases free survival in ACC, bladder urothelial carcinoma(BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), kidney renal clear cell carcinoma(KIRC), kidney renal papillary cell carcinoma(KIRP), LGG, LIHC, and UVM. PDCD2L expression was negatively associated with cancer associated fibroblast in breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), sarcoma (SARC), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). Mechanically, we found that PDCD2L expression was associated with apoptosis, invasion and cell cycle by investigating single cell sequencing data. For further validation, PDCD2Lwas highly expressed in colorectal cancer (CRC) cell lines and tissue samples compared with the normal colon cell line and non-tumor adjacent colorectal mucosa tissues. PDCD2L knockdown induced the apoptosis and proliferation of CRC cells. CONCLUSIONS: Our study shows that the oncogenic role of PDCD2L in various cancers and PDCD2L could be served as a biomarker of CRC.

A diagnosis model in nasopharyngeal carcinoma based on PET/MRI radiomics and semiquantitative parameters.

BACKGROUND: The staging of nasopharyngeal carcinoma (NPC) is of great value in treatment and prognosis. We explored whether a positron emission tomography/ magnetic resonance imaging (PET/MRI) based comprehensive model of radiomics features and semiquantitative parameters was useful for clinical evaluation of NPC staging. MATERIALS AND METHODS: A total of 100 NPC patients diagnosed with non-keratinized undifferentiated carcinoma were divided into early-stage group (I-II) and advanced-stage group (III-IV) and divided into the training set (n = 70) and the testing set (n = 30). Radiomics features (n = 396 × 2) of the primary site of NPC were extracted from MRI and PET images, respectively. Three major semiquantitative parameters of primary sites including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) in all NPC patients were measured. After feature selection, three diagnostic models including the radiomics model, the metabolic parameter model, and the combined model were established using logistic regression model. Finally, internal validation was performed, and a nomogram for NPC comprehensive diagnosis has been made. RESULTS: The radiomics model and metabolic parameter model showed an area under the curve (AUC) of 0.83 and 0.80 in the testing set, respectively. The combined model based on radiomics and semiquantitative parameters showed an AUC of 0.90 in the testing set, with the best performance among the three models. CONCLUSION: The combined model based on PET/MRI radiomics and semiquantitative parameters is of great value in the evaluation of clinical stage (early-stage group and advanced-stage group) of NPC.

Premeiotic and meiotic failures lead to hybrid male sterility in the Anopheles gambiae complex.

Hybrid male sterility (HMS) contributes to speciation by restricting gene flow between related taxa. Detailed cytological characterization of reproductive organs in hybrid males is important for identifying phenotypes that can help guide searches of speciation genes. To investigate possible cellular causes of HMS, we performed crosses between closely related species of the Anopheles gambiae complex: An. merus with An. gambiae or An. coluzzii. We demonstrate that HMS in African malaria mosquitoes involves two defects in the reciprocal crosses: a premeiotic arrest of germline stem cells in degenerate testes and a failure of the reductional meiotic division of primary spermatocytes in normal-like testes. The premeiotic arrest in degenerate testes of hybrids is accompanied by a strong suppression of meiotic and postmeiotic genes. Unlike pure species, sex chromosomes in normal-like testes of F1 hybrids are largely unpaired during meiotic prophase I and all chromosomes show various degrees of insufficient condensation. Instead of entering reductional division in meiosis I, primary spermatocytes prematurely undergo an equational mitotic division producing non-motile diploid sperm. Thus, our study identified cytogenetic errors in interspecies hybrids that arise during the early stages of postzygotic isolation.

Comparative physical genome mapping of malaria vectors Anopheles sinensis and Anopheles gambiae.

BACKGROUND: Anopheles sinensis is a dominant natural vector of Plasmodium vivax in China, Taiwan, Japan, and Korea. Recent genome sequencing of An. sinensis provides important insights into the genomic basis of vectorial capacity. However, the lack of a physical genome map with chromosome assignment and orientation of sequencing scaffolds hinders comparative analyses with other genomes to infer evolutionary changes relevant to the vector capacity. RESULTS: Here, a physical genome map for An. sinensis was constructed by assigning 52 scaffolds onto the chromosomes using fluorescence in situ hybridization (FISH). This chromosome-based genome assembly composes approximately 36% of the total An. sinensis genome. Comparisons of 3955 orthologous genes between An. sinensis and Anopheles gambiae identified 361 conserved synteny blocks and 267 inversions fixed between these two lineages. The rate of gene order reshuffling on the X chromosome is approximately 3.2 times higher than that on the autosomes. CONCLUSIONS: The physical map will facilitate detailed genomic analysis of An. sinensis and contribute to understanding of the patterns and mechanisms of large-scale genome rearrangements in anopheline mosquitoes.

[Genetic Polymophism and Evolution of SRPN14 Gene in Anopheles sinensis (Diptera : Culicidae)].

OBJECTIVE: To identify and locate the serine protease inhibitor 14 (SRPN14) gene of Anopheles sinensis, and analyze its genetic polymorphism among populations as well as the selective pressure during evolution. METHODS: Primers were designed based on the genomic sequencing data of An. sinensis, and PCR amplification system for the SRPN14 gene was established. The chromosomal location of SRPN14 gene was determined by fluorescence in situ hybridization. The SRPN14 gene of An. sinensis populations collected from 18 sampling sites in 12 provinces (municipality) was sequenced, its genetic variations within and among populations calculated, and the selective pressure during adaptive evolution evaluated. RESULTS: The amplified part of the SRPN14 gene of An. sinensis was 429 bp in length, and had 77%(nt) and 88% (aa)similarities with An. gambiae. The SRPN14 gene located on 2L: 23C of salivary gland chromosomes of An. sinensis. The sequences of 411 individuals from 13 An. sinensis populations were analyzed. In the 411 individuals, the total number of alleles of the SRPN14 gene was 204, among which 51 (25.00% ) showed inter-population consistency. The ranges of SRPN14 allel number and genetic polymorphism were from 11 (Liaoning) to 33 (Chongqing), and from 0.008 (Liaoning) to 0.024 (Hainan), respectively. AMOVA result showed that genetic divergence within populations was significantly higher than that among populations; variation within populations was 95.79% of the total variation. The genetic divergence among populations was small, with FST value of 0.042. The number of synonymous substitutions in SRPN14 was significantly higher than that of non-synonymous substitutions sites, and ω was less than 1 in all populations. CONCLUSION: Genetic polymorphism occurs in SRPN14 gene of An. sinensis populations, and its evolution is under the negative selective pressure.

Hybridization between Aedes aegypti and Aedes mascarensis mosquitoes leads to disruption of male sex determination.

Understanding the sex determination pathway and its disruptions in mosquitoes is critical for the effective control of disease vectors through genetic manipulations based on sex separation. When male hybrids of Aedes aegypti females and Ae. mascarensis males are backcrossed to Ae. aegypti females, a portion of the backcross progeny manifests as males with abnormal sexual differentiation. We discovered a significant correlation between pupal abnormalities and the feminization of subsequent adults exemplified by the relative abundance of ovarian and testicular tissues. All intersex individuals were genetic males as they expressed a male determining factor, Nix. Further, our analysis of the sex-specific splicing of doublesex and fruitless transcripts demonstrated the presence of both male and female splice variants indicating that sex determination is disrupted. A comparative transcriptomic analysis revealed similar expression levels of most female-associated genes in reproductive organs and carcasses between intersexual males and normal females. Moreover, intersexes had largely normal gene expression in testes but significant gene downregulation in male accessory glands when compared with normal males. We conclude that evolving hybrid incompatibilities between Ae. aegypti and Ae. mascarensis involve disruption of sex determination and are accompanied by changes in gene expression associated with sexual differentiation.

Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts.

AIMS: To clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma. METHODS: Immunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and CLDN18 gene rearrangement in adenocarcinoma from different organs. RESULTS: The results showed that claudin18.2 expression was found in 68% (27 of 40) of lung mucinous adenocarcinoma, 52% (16 of 31) of cholangiocarcinoma, 2% (10 of 423) of colorectal adenocarcinoma tissue microarray, 27% (6 of 22) of colorectal mucinous adenocarcinoma and 30% (3 of 10) of cervical adenocarcinoma, but not in all 39 cases of invasive breast adenocarcinoma by immunohistochemistry staining. There was significantly positive correlation between ratio of claudin18.2-positive carcinoma cells and staining intensity in lung mucinous adenocarcinoma and cholangiocarcinoma. Claudin18.2 expression was much more in female patients than male patients with lung mucinous adenocarcinoma. In addition, cholangiocarcinoma with claudin18.2 expression was more aggressive and had perineural invasion. Intraductal papillary neoplasm of the bile duct and epithelial dysplasia of the adjacent bile in cholangiocarcinoma also showed claudin18.2 expression. All three cases of cervical adenocarcinoma with claudin18.2 expression were moderately differentiated adenocarcinoma including one human papillomavirus (HPV)-associated carcinoma, two non-HPV-associated and gastric-type carcinoma. CLDN18 gene rearrangement was not found in all 22 cases with high claudin18.2 expression by FISH. CONCLUSIONS: Our results suggest claudin18.2 might be a potential biomarker for targeted therapy on lung mucinous adenocarcinoma, cholangiocarcinoma, colorectal mucinous adenocarcinoma and gastric-type cervical adenocarcinoma.

Whole-Mount Fluorescence In Situ Hybridization to Study Spermatogenesis in the Anopheles Mosquito.

Spermatogenesis is a complex biological process during which diploid cells undergo successive mitotic and meiotic division followed by large structural changes to form haploid spermatozoa. Besides the biological aspect, studying spermatogenesis is of paramount importance for understanding and developing genetic technologies such as gene drive and synthetic sex ratio distorters, which, by altering Mendelian inheritance and the sperm sex ratio, respectively, could be used to control pest insect populations. These technologies have proven to be very promising in lab settings and could potentially be used to control wild populations of Anopheles mosquitoes, which are vectors of malaria. Due to the simplicity of the testis anatomy and their medical importance, Anopheles gambiae, a major malaria vector in sub-Saharan Africa, represents a good cytological model for studying spermatogenesis. This protocol describes how whole-mount fluorescence in situ hybridization (WFISH) can be used to study the dramatic changes in cell nuclear structure through spermatogenesis using fluorescent probes that specifically stain the X and Y chromosomes. FISH usually requires the disruption of the reproductive organs to expose mitotic or meiotic chromosomes and allow the staining of specific genomic regions with fluorescent probes. WFISH enables the preservation of the native cytological structure of the testis, coupled with a good level of signal detection from fluorescent probes targeting repetitive DNA sequences. This allows researchers to follow changes in the chromosomal behavior of cells undergoing meiosis along the structure of the organ, where each phase of the process can clearly be distinguished. This technique could be particularly useful for studying chromosome meiotic pairing and investigating the cytological phenotypes associated with, for example, synthetic sex ratio distorters, hybrid male sterility, and the knock-out of genes involved in spermatogenesis.

Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway.

RNA binding proteins (RBPs) contributes to cancer progression, but the underlying mechanism reminds unclear. Here, we find that DDX21, a representative RBP, is highly expressed in colorectal cancer (CRC), which leads to CRC cell migration and invasion in vitro, and CRC to liver metastasis and lung metastasis in vivo. This effect of DDX21 on CRC metastasis is correlated to the activation of Epithelial-mesenchymal transition (EMT) pathway. Moreover, we reveal that DDX21 protein is phase separated in vitro and in CRC cells, which controls CRC metastasis. Phase-separated DDX21 highly binds on MCM5 gene locus, which is markedly reduced when phase separation is disrupted by mutations on its intrinsically disordered region (IDR). The impaired metastatic ability of CRC upon DDX21 loss is restored by ectopic expression of MCM5, indicating MCM5 is a key downstream target of DDX21 for CRC metastasis. Furthermore, co-higher expressions of DDX21 and MCM5 is significantly correlated with poor survival outcomes of stage III and IV CRC patients, indicating the importance of this mechanism in CRC late and metastatic stage. Altogether, our results elucidate a new model of DDX21 in regulating CRC metastasis via phase separation.

Obtaining Polytene, Meiotic, and Mitotic Chromosomes from Mosquitoes for Cytogenetic Analysis.

Chromosome visualization is a key step for developing cytogenetic maps and idiograms, analyzing inversion polymorphisms, and identifying mosquito species. Three types of chromosomes-polytene, mitotic, and meiotic-are used in cytogenetic studies of mosquitoes. Here, we describe a detailed method for obtaining high-quality polytene chromosome preparations from the salivary glands of larvae and the ovaries of females for Anopheles mosquitoes. We also describe how to obtain mitotic chromosomes from imaginal discs of fourth-instar larvae and meiotic chromosomes from the testes of male pupae for all mosquitoes. These chromosomes can be used for fluorescence in situ hybridization (FISH), a fundamental technique in cytogenetic research that is used for physical genome mapping, detecting chromosomal rearrangements, and studying chromosome organization.

Visualization of Polytene Chromatin in Mosquito Cell Nuclei Using Three-Dimensional Fluorescence In Situ Hybridization.

Chromosomes are intricately folded within the cell nucleus and interact with peripheral nuclear proteins. The chromatin architecture has a profound effect on how the genome is organized. 3D-FISH is a powerful technique that can reveal the structural and functional organization of chromosomes in the nuclear space. Here, we present a protocol for visualizing specific genomic regions in whole-mount paraformaldehyde-fixed cell nuclei of Anopheles mosquitoes. This protocol was tested in our laboratories and has been showed to be effective and reliable for visualizing genomic regions of various lengths-from 1-kb gene-scale fragments to chromosome-scale segments of DNA.

Visualization of the Linear and Spatial Organization of Chromosomes in Mosquitoes.

Mosquitoes are vectors of dangerous human diseases such as malaria, dengue, Zika, West Nile fever, and lymphatic filariasis. Visualization of the linear and spatial organization of mosquito chromosomes is important for understanding genome structure and function. Utilization of chromosomal inversions as markers for population genetics studies yields insights into mosquito adaptation and evolution. Cytogenetic approaches assist with the development of chromosome-scale genome assemblies that are useful tools for studying mosquito biology and for designing novel vector control strategies. Fluorescence in situ hybridization is a powerful technique for localizing specific DNA sequences within the linear chromosome structure and within the spatial organization of the cell nucleus. Here, we introduce protocols used in our laboratories for chromosome visualization and their application in mosquitoes.

The value of combined PET/MRI, CT and clinical metabolic parameters in differentiating lung adenocarcinoma from squamous cell carcinoma.

Objective: This study aimed to study the diagnostic efficacy of positron emission tomography (PET)/magnetic resonance imaging (MRI), computed tomography (CT) and clinical metabolic parameters in predicting the histological classification of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Methods: PET/MRI, CT and clinical metabolic data of 80 patients with lung ADC or SCC were retrospectively collected. According to the pathological results from surgery or fiberscopy, the patients were diagnosed with lung ADC (47 cases) or SCC (33 cases). All 80 patients were divided into a training group (64 cases), an internal testing group (8 cases) and an external testing group (8 cases) in the ratio of 8:1:1. Nine models were constructed by integrating features from different modalities. The Gaussian classifier was used to differentiate ADC and SCC. The prediction ability was evaluated using the receiver operating characteristic curve. The area under the curve (AUC) of the models was compared using Delong's test. Based on the best composite model, a nomogram was established and evaluated with a calibration curve, decision curve and clinical impact curve. Results: The composite model (PET/MRI + CT + Clinical) owned the highest AUC values in the training, internal testing and external testing sets, respectively. In the training set, significant differences in the AUC were found between the composite model and other models except for the PET/MRI + CT model. The calibration curves showed good consistency between the predicted output and actual disease. The decision curve analysis and clinical impact curves demonstrated that the composite model increased the clinical net benefit for predicting lung cancer subtypes. Conclusion: The composite prediction model of PET/MRI + CT + Clinical better distinguished ADC from SCC pathological subtypes preoperatively and achieved clinical benefits, thus providing an accurate clinical diagnosis.

A clinicopathologic study of 13 cases of primary lymphoma in soft tissue and review of literature.

Primary lymphoma in soft tissue is very rare. In order to understand the clinicopathological features of primary lymphoma in soft tissue, we found 13 cases (0.3%) of primary lymphoma in soft tissue by reviewing 4303 lymphomas diagnosed in our institution from 2010 to 2019. Tumors were found in the following sites: 8 in lower extremity (2 in leg, 1 in calf, 1 in knee and 4 in buttock), 1 in upper extremity (left shoulder) and 4 in the trunk (3 in waist and 1 in thoracolumbar). The most common histologic type was DLBCL (7/13, 54.8%). 6 cases of which had follow-up information. 25 patients were also selected by screening the English literature search (from Jan 2010 to December 2019) including 1102 studies. Compared to the results of literature review, our results are similar with them. The tumor sites were as follows: 10 in lower extremity, 4 in upper extremity, 9 in the trunk and 2 in masticatory muscle. The most common histological type was also DLBCL (n=11/25, 44%). Overall survival analysis of all 31 patients including our 6 cases with primary lymphoma in soft tissue showed no significant difference between different histological type (Log Rank P=0.120, Breslow P=0.157). The differential diagnosis includes malignant melanoma, rhabdomyosarcoma and metastatic carcinoma in soft tissue.

Retrogene Duplication and Expression Patterns Shaped by the Evolution of Sex Chromosomes in Malaria Mosquitoes.

Genes that originate during evolution are an important source of novel biological functions. Retrogenes are functional copies of genes produced by retroduplication and as such are located in different genomic positions. To investigate retroposition patterns and retrogene expression, we computationally identified interchromosomal retroduplication events in nine portions of the phylogenetic history of malaria mosquitoes, making use of species that do or do not have classical sex chromosomes to test the roles of sex-linkage. We found 40 interchromosomal events and a significant excess of retroduplications from the X chromosome to autosomes among a set of young retrogenes. These young retroposition events occurred within the last 100 million years in lineages where all species possessed differentiated sex chromosomes. An analysis of available microarray and RNA-seq expression data for Anopheles gambiae showed that many of the young retrogenes evolved male-biased expression in the reproductive organs. Young autosomal retrogenes with increased meiotic or postmeiotic expression in the testes tend to be male biased. In contrast, older retrogenes, i.e., in lineages with undifferentiated sex chromosomes, do not show this particular chromosomal bias and are enriched for female-biased expression in reproductive organs. Our reverse-transcription PCR data indicates that most of the youngest retrogenes, which originated within the last 47.6 million years in the subgenus Cellia, evolved non-uniform expression patterns across body parts in the males and females of An. coluzzii. Finally, gene annotation revealed that mitochondrial function is a prominent feature of the young autosomal retrogenes. We conclude that mRNA-mediated gene duplication has produced a set of genes that contribute to mosquito reproductive functions and that different biases are revealed after the sex chromosomes evolve. Overall, these results suggest potential roles for the evolution of meiotic sex chromosome inactivation in males and of sexually antagonistic conflict related to mitochondrial energy function as the main selective pressures for X-to-autosome gene reduplication and testis-biased expression in these mosquito lineages.

Clinicopathologic and molecular features of vascular tumors in a series of 118 cases.

AIMS: Vascular tumors are composed of benign, intermediate, and malignant lesions. The diagnosis is challenging because some entities demonstrate overlapping morphologies and harbor the same genetic alterations. We describe herein a cohort of vascular tumors with clinicopathologic, immunohistochemical, and molecular features. METHODS AND RESULTS: 118 vascular tumors including 56 angiosarcomas, 18 epithelioid haemangioendotheliomas (EHE), 25 epithelioid haemangiomas (EH), 8 pseudomyogenic haemangioendotheliomas (PHE), 1 papillary intralymphatic angioendothelioma (PILA), 2 kaposiform haemangioendotheliomas (KHE), 3 Kaposi sarcomas, 2 retiform haemangioendotheliomas (RHE), and 3 anastomosing haemangiomas were assessed. FOSB, c-Fos, CAMTA1, and TFE3 expression and gene rearrangements were analyzed by immunohistochemical staining and FISH, respectively. Our results showed that FOSB expression was diffusely positive in all 8 PHEs, focally or sparsely in 12 EHs, and in 2 angiosarcomas. C-FOS expression was sparsely to diffusely positive in 15 EHs, focally or sparsely in 17 angiosarcomas, 1 EHE, 1 Kaposi sarcoma, and 1 PHE. CAMTA1 expression was positive in only 12 EHEs. TFE3 expression was focally or sparsely positive in all 8 PHEs, 22 angiosarcomas, 6 EHEs, 3 EHs, 2 Kaposi sarcomas, and 2 AHs. FOSB rearrangement was found in 5 PHEs, FOS rearrangement only in 1 EH, CAMTA1 rearrangement in 4 EHEs. CONCLUSIONS: FOSB and CAMTA1 are useful diagnostic markers for PHE and EHE, respectively. FOSB and FOS fusion represent a subset of epithelioid haemangioma. TFE3 is not a diagnostically meaningful marker in a majority of vascular tumors. The combined utility of these markers will facilitate the differential diagnosis in vascular tumors with morphologic overlap.

Molecular characterization and genetic authentication assay for Anopheles 'hemocyte-like' cell lines 4a-3A and 4a-3B.

BACKGROUND: Anopheles cell lines are used in a variety of ways to better understand the major vectors of malaria in sub-Saharan Africa. Despite this, commonly used cell lines are not well characterized, and no tools are available for cell line identification and authentication. METHODS: Utilizing whole genome sequencing, genomes of 4a-3A and 4a-3B 'hemocyte-like' cell lines were characterized for insertions and deletions (indels) and SNP variation. Genomic locations of distinguishing sequence variation and species origin of the cell lines were also examined. Unique indels were targeted to develop a PCR-based cell line authentication assay. Mitotic chromosomes were examined to survey the cytogenetic landscape for chromosome structure and copy number in the cell lines. RESULTS: The 4a-3A and 4a-3B cell lines are female in origin and primarily of Anopheles coluzzii ancestry. Cytogenetic analysis indicates that the two cell lines are essentially diploid, with some relatively minor chromosome structural rearrangements. Whole-genome sequence was generated, and analysis indicated that SNPs and indels which differentiate the cell lines are clustered on the 2R chromosome in the regions of the 2Rb, 2Rc and 2Ru chromosomal inversions. A PCR-based authentication assay was developed to fingerprint three indels unique to each cell line. The assay distinguishes between 4a-3A and 4a-3B cells and also uniquely identifies two additional An. coluzzii cell lines tested, Ag55 and Sua4.0. The assay has the specificity to distinguish four cell lines and also has the sensitivity to detect cellular contamination within a sample of cultured cells. CONCLUSIONS: Genomic characterization of the 4a-3A and 4a-3B Anopheles cell lines was used to develop a simple diagnostic assay that can distinguish these cell lines within and across research laboratories. A cytogenetic survey indicated that the 4a-3A and Sua4.0 cell lines carry essentially normal diploid chromosomes, which makes them amenable to CRISPR/Cas9 genome editing. The presented simple authentication assay, coupled with screening for mycoplasma, will allow validation of the integrity of experimental resources and will promote greater experimental reproducibility of results.

Positron Emission Tomography/Magnetic Resonance Imaging Radiomics in Predicting Lung Adenocarcinoma and Squamous Cell Carcinoma.

OBJECTIVE: To investigate the diagnostic value of positron emission tomography (PET)/magnetic resonance imaging (MRI) radiomics in predicting the histological classification of lung adenocarcinoma and lung squamous cell carcinoma. METHODS: PET/MRI radiomics and clinical data were retrospectively collected from 61 patients with lung cancer. According to the pathological results of surgery or fiberscope, patients were divided into two groups, lung adenocarcinoma and squamous cell carcinoma group, which were set as positive for adenocarcinoma (40 cases) and negative for squamous cell carcinoma (21 cases). The radiomics characteristics most related to lung cancer classification were calculated and selected using radiomics software, and the two lung cancer groups were randomly assigned into a training set (70%) and a test set (30%). Maximum relevance and minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) methods in the uAI Research Portal software (United Imaging Intelligence, China) were used to select the desired characteristics from 2600 features extracted from MRI and PET. Eight optimal features were finally retained through 5-fold cross-validation, and a PET/MRI fusion model was constructed. The predictive ability of this model was evaluated by the difference in area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve. RESULTS: AUC of PET/MRI model for the training group and test group were 0.886 (0.787-0.985) and 0.847 (0.648-1.000), respectively. PET/MRI radiomics features revealed different degrees of correlation with the classification of lung adenocarcinoma and squamous cell carcinoma, with significant differences. CONCLUSION: The prediction model constructed based on PET/MRI radiomics features can predict the preoperative histological classification of lung adenocarcinoma and squamous cell carcinoma without seminality and repeatability. It can also provide an objective basis for accurate clinical diagnosis and individualized treatment, thus having important guiding significance for clinical treatment.

Anopheles mosquitoes reveal new principles of 3D genome organization in insects.

Chromosomes are hierarchically folded within cell nuclei into territories, domains and subdomains, but the functional importance and evolutionary dynamics of these hierarchies are poorly defined. Here, we comprehensively profile genome organizations of five Anopheles mosquito species and show how different levels of chromatin architecture influence each other. Patterns observed on Hi-C maps are associated with known cytological structures, epigenetic profiles, and gene expression levels. Evolutionary analysis reveals conservation of chromatin architecture within synteny blocks for tens of millions of years and enrichment of synteny breakpoints in regions with increased genomic insulation. However, in-depth analysis shows a confounding effect of gene density on both insulation and distribution of synteny breakpoints, suggesting limited causal relationship between breakpoints and regions with increased genomic insulation. At the level of individual loci, we identify specific, extremely long-ranged looping interactions, conserved for ~100 million years. We demonstrate that the mechanisms underlying these looping contacts differ from previously described Polycomb-dependent interactions and clustering of active chromatin.