DNA methylation analysis in plasma for early diagnosis in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) represents the most prevalent type of lung cancer. SHOX2 and RASSF1A methylation have been identified as important biomarkers for diagnosis and prognosis of lung cancer. Bronchoalveolar lavage fluid (BALF) exhibits good specificity and sensitivity in diagnosing pulmonary diseases, but its acquisition is challenging and may cause discomfort to patients. In clinical, plasma samples are more convenient to obtain than BALF; however, there is little research on the concurrent detection of SHOX2 and RASSF1A methylation in plasma. This study aims to assess the diagnostic value of a combined promoter methylation assay for SHOX2 and RASSF1A in early-stage LUAD using plasma samples. METHODS: BALF and blood samples were obtained from 36 early-stage LUAD patients, with a control group of nineteen non-tumor individuals. The promoter methylation levels of SHOX2 and RASSF1A in all subjects were assessed using the human SHOX2 and RASSF1A gene methylation kit. RESULTS: The methylation detection rate of SHOX2 and RASSF1A in plasma was 61.11%, slightly lower than that in BALF (66.7%). The Chi-square test revealed no significant difference in the methylation rate between BALF and plasma (P > 0.05). The area under the receiver operating characteristic (ROC) curve analysis for blood was 0.806 (95% CI, 0.677 to 0.900), while for BALF it was 0.781 (95% CI, 0.649 to 0.881). Additionally, we conducted an analysis on the correlation between SHOX2 and RASSF1A methylation levels in plasma with gender, age, tumor differentiation, pathologic classification, and other clinicopathological variables; however, no significant correlations were observed. CONCLUSIONS: Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.

The diagnostic potential role of thioredoxin reductase and TXNRD1 in early lung adenocarcinoma: A cohort study.

Background: Lung adenocarcinoma (LUAD) is the primary form of lung cancer, yet the reliable biomarkers for early diagnosis remain insufficient. Thioredoxin reductase (TrxR) is strongly linked to the occurrence, development, and drug resistance of lung cancer, making it a potential biomarker. However, further research is required to assess its diagnostic value in LUAD. Methods: A retrospective analysis was performed on patients who underwent pulmonary nodule resection at our center from 2018 to 2022. Clinical data, including preoperative TrxR levels, imaging, and laboratory characteristics, were identified as study variables. Two prediction models were constructed using multiple logistic regression, and their prediction performance was evaluated comprehensively. Besides, bioinformatics analyses of TrxR coding genes including differential expression, functional enrichment, immune infiltration, drug sensitivity, and single-cell landscape were performed based on TCGA database, which were subsequently validated by Human Protein Atlas. Results: A total of 506 eligible patients (72 benign lesions, 77 AISs, 185 MIAs and 172 IACs) were identified in the clinical cohort. Two TrxR-based models were developed, which were able to distinguish between benign and malignant pulmonary nodules, as well as pathological subtypes of LUAD, respectively. The models exhibited good predictive ability with all AUC values ranging from 0.7 to 0.9. Based on calibration curves and clinical decision analysis, the nomogram models showed high reliability. Functional analysis indicated that TXNRD1 primarily participated in cell cycle and lipid metabolism. Immune infiltration analysis showed that TXNRD1 has a strong association with immune cells and could impact immunotherapy. Then, we identified small molecular compounds that inhibit TXNRD1 and confirmed TXNRD1 expression by single-cell landscape and immunohistochemistry. Conclusion: This study validated the diagnostic value of TrxR and TXNRD1 in clinical cohorts and transcriptional data, respectively. TrxR and TXNRD1 could be used in the risk diagnosis of early LUAD and facilitate personalized treatment strategies.

Role of TET1-mediated epigenetic modulation in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder influenced by a complex interplay of environmental, epigenetic, and genetic factors. DNA methylation (5mC) and hydroxymethylation (5hmC) are DNA modifications that serve as tissue-specific and temporal regulators of gene expression. TET family enzymes dynamically regulate these epigenetic modifications in response to environmental conditions, connecting environmental factors with gene expression. Previous epigenetic studies have identified 5mC and 5hmC changes associated with AD. In this study, we performed targeted resequencing of TET1 on a cohort of early-onset AD (EOAD) and control samples. Through gene-wise burden analysis, we observed significant enrichment of rare TET1 variants associated with AD (p = 0.04). We also profiled 5hmC in human postmortem brain tissues from AD and control groups. Our analysis identified differentially hydroxymethylated regions (DhMRs) in key genes responsible for regulating the methylome: TET3, DNMT3L, DNMT3A, and MECP2. To further investigate the role of Tet1 in AD pathogenesis, we used the 5xFAD mouse model with a Tet1 KO allele to examine how Tet1 loss influences AD pathogenesis. We observed significant changes in neuropathology, 5hmC, and RNA expression associated with Tet1 loss, while the behavioral alterations were not significant. The loss of Tet1 significantly increased amyloid plaque burden in the 5xFAD mouse (p = 0.044) and lead to a non-significant trend towards exacerbated AD-associated stress response in 5xFAD mice. At the molecular level, we found significant DhMRs enriched in genes involved in pathways responsible for neuronal projection organization, dendritic spine development and organization, and myelin assembly. RNA-Seq analysis revealed a significant increase in the expression of AD-associated genes such as Mpeg1, Ctsd, and Trem2. In conclusion, our results suggest that TET enzymes, particularly TET1, which regulate the methylome, may contribute to AD pathogenesis, as the loss of TET function increases AD-associated pathology.

Reference genomes of channel catfish and blue catfish reveal multiple pericentric chromosome inversions.

BACKGROUND: Channel catfish and blue catfish are the most important aquacultured species in the USA. The species do not readily intermate naturally but F1 hybrids can be produced through artificial spawning. F1 hybrids produced by mating channel catfish female with blue catfish male exhibit heterosis and provide an ideal system to study reproductive isolation and hybrid vigor. The purpose of the study was to generate high-quality chromosome level reference genome sequences and to determine their genomic similarities and differences. RESULTS: We present high-quality reference genome sequences for both channel catfish and blue catfish, containing only 67 and 139 total gaps, respectively. We also report three pericentric chromosome inversions between the two genomes, as evidenced by long reads across the inversion junctions from distinct individuals, genetic linkage mapping, and PCR amplicons across the inversion junctions. Recombination rates within the inversional segments, detected as double crossovers, are extremely low among backcross progenies (progenies of channel catfish female × F1 hybrid male), suggesting that the pericentric inversions interrupt postzygotic recombination or survival of recombinants. Identification of channel catfish- and blue catfish-specific genes, along with expansions of immunoglobulin genes and centromeric Xba elements, provides insights into genomic hallmarks of these species. CONCLUSIONS: We generated high-quality reference genome sequences for both blue catfish and channel catfish and identified major chromosomal inversions on chromosomes 6, 11, and 24. These perimetric inversions were validated by additional sequencing analysis, genetic linkage mapping, and PCR analysis across the inversion junctions. The reference genome sequences, as well as the contrasted chromosomal architecture should provide guidance for the interspecific breeding programs.

Gene Editing of the Follicle-Stimulating Hormone Gene to Sterilize Channel Catfish, Ictalurus punctatus, Using a Modified Transcription Activator-like Effector Nuclease Technology with Electroporation.

Follicle-stimulating hormone (fsh) plays an important role in sexual maturation in catfish. Knocking out the fsh gene in the fish zygote should suppress the reproduction of channel catfish (Ictalurus punctatus). In this study, transcription activator-like effector nuclease (TALEN) plasmids targeting the fsh gene were electroporated into fertilized eggs with the standard double electroporation technique. Targeted fsh cleavage efficiency was 63.2% in P1fsh-knockout catfish. Ten of fifteen (66.7%) control pairs spawned, and their eggs had 32.3-74.3% average hatch rates in 2016 and 2017. Without hormone therapy, the spawning rates of P1 mutants ranged from 33.3 to 40.0%, with an average egg hatching rate of 0.75%. After confirmation of the low fertility of P1 mutants in 2016, human chorionic gonadotropin (HCG) hormone therapy improved the spawning rates by 80% for female mutants and 88.9% for male mutants, and the mean hatch rate was 35.0% for F1 embryos, similar to that of the controls (p > 0.05). Polymerase chain reaction (PCR) identification showed no potential TALEN plasmid integration into the P1 channel catfish genome. Neither the P1 nor the F1 mutant fish showed any noticeable changes in in body weight, survival rate, and hatching rate when the reproductive gene was knocked out. F1 families had a mean inheritance rate of 50.3%. The results brought us one step closer to allowing implementation of certain genetic techniques to aquaculture and fisheries management, while essentially eliminating the potential environment risk posed by transgenic, hybrid, and exotic fish as well as domestic fish.

Cell type-specific DNA methylome signatures reveal epigenetic mechanisms for neuronal diversity and neurodevelopmental disorder.

DNA methylation plays a critical function in establishing and maintaining cell identity in brain. Disruption of DNA methylation-related processes leads to diverse neurological disorders. However, the role of DNA methylation characteristics in neuronal diversity remains underexplored. Here, we report detailed context-specific DNA methylation maps for GABAergic, glutamatergic (Glu) and Purkinje neurons, together with matched transcriptome profiles. Genome-wide mCH levels are distinguishable, while the mCG levels are similar among the three cell types. Substantial CG-differentially methylated regions (DMRs) are also seen, with Glu neurons experiencing substantial hypomethylation events. The relationship between mCG levels and gene expression displays cell type-specific patterns, while genic CH methylation exhibits a negative effect on transcriptional abundance. We found that cell type-specific CG-DMRs are informative in terms of represented neuronal function. Furthermore, we observed that the identified Glu-specific hypo-DMRs have a high level of consistency with the chromatin accessibility of excitatory neurons and the regions enriched for histone modifications (H3K27ac and H3K4me1) of active enhancers, suggesting their regulatory potential. Hypomethylation regions specific to each cell type are predicted to bind neuron type-specific transcription factors. Finally, we show that the DNA methylation changes in a mouse model of Rett syndrome, a neurodevelopmental disorder caused by the de novo mutations in MECP2, are cell type- and brain region-specific. Our results suggest that cell type-specific DNA methylation signatures are associated with the functional characteristics of the neuronal subtypes. The presented results emphasize the importance of DNA methylation-mediated epigenetic regulation in neuronal diversity and disease.

Selective kernel convolution deep residual network based on channel-spatial attention mechanism and feature fusion for mechanical fault diagnosis.

This paper proposes a selective kernel convolution deep residual network based on the channel-spatial attention mechanism and feature fusion for mechanical fault diagnosis. First, adjacent channel attention modules are connected with the spatial attention mechanism module, then all channel features and spatial features are fused and a channel-spatial attention mechanism is constructed to form the feature enhancement module. Second, the feature enhancement module is embedded in a series model based on selective kernel convolution and deep residual network and combined with multi-layer feature fusion information. The model can more effectively extract fault features from the vibration signal, compared with traditional deep learning methods, and the fault recognition efficiency is improved. Finally, the proposed method was used to experimentally diagnose bearing and gear faults, and identification accuracies of 99.87% and 97.77%, respectively, were achieved. Compared with similar algorithms, the proposed method has higher fault identification ability, thereby demonstrating the advantages of the channel-spatial attention mechanism network. In addition, the accuracy and robustness of the model were verified.

Exploring surface urban heat island (SUHI) intensity and its implications based on urban 3D neighborhood metrics: An investigation of 57 Chinese cities.

Excessive urban temperature exerts a substantially negative impact on urban sustainability. Three-dimensional (3D) landscapes have a great impact on urban thermal environments, while their heat conditions and driving factors still remain unclear. This study mapped urban 3D neighborhoods and their associated SUHI (surface urban heat island) intensities in summer daytime across 57 Chinese cities, and then explored their relationships, driving factors as well as implications. Nine categories of urban 3D neighborhoods existed in Chinese cities and the 3D neighborhood of High Density & Medium Rise (HDMR) contributed the largest share of urban areas. The distribution of 3D neighborhoods varied among cities due to their distinct natural and economic traits. The average SUHI intensity can amount to 4.27 °C across all Chinese 3D neighborhoods. High Density & Low Rise (HDLR) and HDMR presented higher SUHI intensities than other 3D neighborhoods in China. Urban green space (UGI) and building height (BH) had great influences on SUHI intensities. The relative contribution of UGI decreased with the increase of building density and building height, but BH presented the opposite trend. The interaction of urban 3D landscapes and function zones led to highly complicated urban thermal environments, with higher SUHI intensities in industrial zones. Besides, the SUHI intensities of 3D neighborhoods presented great diurnal and seasonal variations, with higher SUHI intensities in HDHR and HDMR at nighttime in winter and summer. What's more, urban residents may suffer unequal heat risk inside cities due to the deviations of SUHI intensities among different 3D neighborhoods. It could be a highly effective way to mitigate SUHI effects in cities by increasing urban greening and improving urban ventilation.

A homozygous exonic variant leading to exon skipping in ABCC8 as the cause of severe congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is genetically heterogeneous, caused by pathogenic variants in multiple known genes regulating insulin secretion from the pancreatic ß-cells. The ABCC8 gene encodes the sulfonylurea receptor 1 (SUR1), a key player in insulin secretion, and pathogenic variants in ABCC8 are the most common cause of CHI. With increased application of genetic testing in clinical practice, variants of unknown clinical significance (VUS) are commonly reported. Additional functional investigation for variant pathogenicity is fundamental in establishing definitive molecular diagnosis and in guiding clinical management. However, due to the lack of ubiquitous tissue expression of these genes, obtaining functional studies on affected tissue has been challenging. We present a case of severe congenital hyperinsulinism which required a near-total pancreatectomy. CHI gene sequencing identified a homozygous silent variant in ABCC8 located on the last nucleotide of exon 38, c.4608G>A (p.Ala1536Ala). The total RNA was isolated from pancreas resected at the time of pancreatectomy. RNA sequencing and expression analysis demonstrated exon 38 skipping and decreased RNA expression, which supports the pathogenicity of this variant. This case highlights the feasibility of functional studies of VUS on resected pancreatic tissue. The result expands the mutation spectrum in ABCC8 and allows precise genetic counseling to affected families.

Allelically and Differentially Expressed Genes After Infection of Edwardsiella ictaluri in Channel Catfish as Determined by Bulk Segregant RNA-Seq.

Identification of genetic markers associated with resistance against enteric septicemia of catfish (ESC) is of great interest for genetic enhancement programs of catfish. In the present study, bulk segregant RNA-Seq analysis was applied to determine differentially expressed genes and alleles after ESC infection. Here we report three genomic regions on LG1, LG12, and LG26, containing significant single-nucleotide polymorphisms (SNPs). These genomic regions aligned well with quantitative trait loci (QTL) previously identified. Within the QTL regions, eleven genes were found to be differentially regulated between phenotypic bulks. Importantly, the QTL on linkage group 1 (LG1) were found to be expressed in the liver, whereas the QTL on LG12 and LG26 were expressed in the intestine, suggesting multiple mechanisms of ESC resistance. It is apparent that apolipoproteins may be important for ESC resistance as the QTL on LG1 included the 14-kDa apolipoprotein genes that are both allelically expressed and differentially expressed between the resistant and susceptible bulks. Traf2 and NCK-interacting protein kinase (TNIK) were found in the QTL on LG12, and it was downregulated in resistant fish, suggesting the importance of NCK downregulation in ESC resistance, as previously reported. In addition, we observed divergent gene expression patterns between the liver and intestine after infection. Immune/inflammatory-related processes were overrepresented from liver DEGs, while those DEGs identified from intestine were enriched for proteolysis and wounding processes. Taken together, the BSR-Seq analysis presented here advanced the knowledge of ESC resistance, providing information of not only positions of QTL but also genes and their differential expression between resistant and susceptible fish, making it one step closer to the identification of the causal genes for ESC resistance.

An adaptive fractional stochastic resonance method based on weighted correctional signal-to-noise ratio and its application in fault feature enhancement of wind turbine.

Stochastic resonance (SR) is an effective tool to enhance weak signal by utilizing noise to reach a certain synergistic effect, which has been widely studied in the field of weak signal detection. Currently, using SR to enhance the weak fault feature of wind turbine faces two challenges: First, it is difficult for SR to select the optimal system parameters, while the traditional adaptive method based on SNR needs to predict the precise frequency of the target signal. Second, the wind turbine load changes frequently, making the vibration and noise large. As a result, the traditional SR cannot effectively highlight the target fault feature by inducing a stable resonance phenomenon at the target frequency. To improve the ability of SR to enhance the weak fault feature of wind turbine under strong noise, this paper proposes an adaptive fractional SR method based on weighted correctional signal-to-noise ratio (WCSNR). Firstly, the proposed method considers the adiabatic approximation applicable condition in the SR system and combines characteristics of the expected output signal to construct the WCSNR evaluation index to quantify the system output response, so that the system can adaptively obtain optimal parameters without predicting the accurate frequency of the target signal. Then, the fractional-order theory is applied to the SR system to overcome the shortcoming that the integer-order SR cannot induce stable resonance phenomenon at the target frequency when enhancing the fault feature of wind turbine, and use WCSNR to search for the optimal fractional order to further enhance the weak fault characteristics. Simulation and engineering actual data analysis results verify the effectiveness and superiority of the proposed method in the fault feature enhancement of wind turbine. The analysis results show that compared with the traditional SR method, the method proposed in this paper can more effectively reduce the interference of background noise and accurately enhance the weak fault feature.

Instantaneous frequency estimation for wheelset bearings weak fault signals using second-order synchrosqueezing S-transform with optimally weighted sliding window.

The second-order synchrosqueezing S-transform (SSST2) is an important method for instantaneous frequency (IF) estimation of non-stationary signals. Based on the synchrosqueezing S-transform, the instantaneous frequency calculation method is modified using the second-order partial derivatives of time and frequency to achieve higher frequency resolution. However, weak multi-frequency signals with strong background noise are often drowned out during the transformation process. To achieve enhanced extraction of weak fault characteristic signals due to mechanical faults, this paper proposes an optimally weighted sliding window signal segmentation algorithm based on the SSST2. The results of simulations and experiments show that the time-frequency aggregation of the second-order synchrosqueezing S-transform based on the optimally weighted sliding window (OWSW-SSST2) is not only significantly higher than that of commonly used time-frequency transforms, but it also has better operational efficiency than the second-order synchrosqueezing S-transform. In this paper, the proposed algorithm is used to analyze fault signals from actual high-speed railway wheelset bearings. The results show that the OWSW-SSST2 algorithm greatly improves the spectral aggregation of the signal, and crucially, that high-precision IF estimates for signals can be obtained in low signal-to-noise ratio environments. This research is both of academic interest and significant for practical engineering use to ensure safe high-speed rail operations. It helps enable monitoring the status of wheelset bearings, correctly estimating the locations and causes of failures, and providing up-to-date systematic maintenance and system improvement strategies.

Directional culture of petroleum hydrocarbon degrading bacteria for enhancing crude oil recovery.

An oxygen-constrained system of crude oil reservoir environment was constructed to stimulate the growth of indigenous microbes, such as petroleum hydrocarbon-degrading bacteria. Addition of nitrogen and phosphorus sources was investigated for the growth of petroleum hydrocarbon-degrading bacteria. The results show that nitrates and phosphates stimulated the growth of the bacteria and promoted the biodegradation of crude oil as the sole carbon source in this process. The minimum surface tension was 29.63 mN/m when the amounts of the nitrogen (NaNO3: [Formula: see text]  = 2:1) and phosphorus (KH2PO4: NaH2PO4 = 5:2) sources added were 0.8 wt% and 1.4 wt%, respectively. Furthermore, the dominant petroleum hydrocarbon-degrading bacteria were shifted from Arcobacter in production water to Pseudomonas after the first subculture and then to Bacillus after the sixth subculture. The heteroatom groups in the crude oil were biodegraded simultaneously with normal alkanes and alkyl cyclohexanes. Addition of the nutrients resulted in microbial growth, microbial community shift, and enhanced microbial degradation.

Diverse and dynamic DNA modifications in brain and diseases.

DNA methylation is a class of epigenetic modification essential for coordinating gene expression timing and magnitude throughout normal brain development and for proper brain function following development. Aberrant methylation changes are associated with changes in chromatin architecture, transcriptional alterations and a host of neurological disorders and diseases. This review highlights recent advances in our understanding of the methylome's functionality and covers potential new roles for DNA methylation, their readers, writers, and erasers. Additionally, we examine novel insights into the relationship between the methylome, DNA-protein interactions, and their contribution to neurodegenerative diseases. Lastly, we outline the gaps in our knowledge that will likely be filled through the widespread use of newer technologies that provide greater resolution into how individual cell types are affected by disease and the contribution of each individual modification site to disease pathogenicity.

GWAS Analysis Indicated Importance of NF-κB Signaling Pathway in Host Resistance Against Motile Aeromonas Septicemia Disease in Catfish.

Motile Aeromonas septicemia (MAS) disease caused by a bacterial pathogen, Aeromonas hydrophila, is an emerging but severe disease of catfish. Genetic enhancement of disease resistance is considered to be effective to control the disease. To provide an insight into the genomic basis of MAS disease resistance, in this study, we conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL). A total of 1820 interspecific backcross catfish of 7 families were challenged with A. hydrophila, and 382 phenotypic extremes were selected for genotyping with the catfish 690 K SNP arrays. Three QTL on linkage group (LG) 2, 26 and 29 were identified to be significantly associated with MAS resistance. Within these regions, a total of 24 genes had known functions in immunity, 10 of which were involved in NF-κB signaling pathway, suggesting the importance of NF-κB signaling pathway in MAS resistance. In addition, three suggestively significant QTL were identified on LG 11, 17, and 20. The limited numbers of QTL involved in MAS resistance suggests that marker-assisted selection may be a viable approach for catfish breeding.

Heat stress induced alternative splicing in catfish as determined by transcriptome analysis.

Heat tolerance is increasingly becoming an important trait for aquaculture species with a changing climate. Transcriptional studies on responses to heat stress have been conducted in catfish, one of the most important economic aquaculture species around the world. The molecular mechanisms underlying heat tolerance is still poorly understood, especially at the post-transcriptional level including regulation of alternative splicing. In this study, existing RNA-Seq datasets were utilized to characterize the change of alternative splicing in catfish following heat treatment. Heat-tolerant and -intolerant catfish were differentiated by the time to lost equilibrium after heat stress. With heat stress, alternative splicing was generally increased. In heat-intolerant fish, the thermal stress induced 29.2% increases in alternative splicing events and 25.8% increases in alternatively spliced genes. A total of 282, 189, and 44 differential alternative splicing (DAS) events were identified in control-intolerant, control-tolerant, and intolerant-tolerant comparisons, corresponding to 252, 171, and 42 genes, respectively. Gene ontology analyses showed that genes involved in the molecular function of RNA binding were significantly enriched in DAS gene sets after heat stress in both heat-intolerant and -tolerant catfish compared with the control group. Similar results were also observed in the DAS genes between heat-intolerant and -tolerant catfish, and the biological process of RNA splicing was also enriched in this comparison, indicating the involvement of RNA splicing-related genes underlying heat tolerance. This is the first comprehensive study of alternative splicing in response to heat stress in fish species, providing insights into the molecular mechanisms of responses to the abiotic stress.

Altered expression of circular RNAs in human placental chorionic plate-derived mesenchymal stem cells pretreated with hypoxia.

BACKGROUND: Hypoxic preconditioning alters the biological properties of mesenchymal stem cells (MSCs). It is not known whether this process has an effect on circular RNAs (circRNAs) in MSCs. METHODS: Human placental chorionic plate-derived MSCs (hpcpMSCs) isolated from the same placentae were classed into two groups: hypoxic pretreated (hypoxia) group and normally cultured (normoxia) group. The comparative circRNA microarray analysis was used to determine circRNAs expression and verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in the two groups. RESULTS: One hundred and two differentially expressed circRNAs in the hypoxia group were found compared to that in the normoxia group (fold change >1.5-fold and P < 0.05). The expression levels of circRNAs by qRT-PCR were consistent with those evaluated by microarray analysis. Gene ontology (GO) analysis showed that the putative function of their target genes for those differentially expressed circRNAs was primarily involved in cell development and its differentiation and regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that transcriptional misregulation in cancer and mitogen-activated protein kinase (MAPK) signaling pathway were the most significant. MAPK signaling pathway was found to be the core regulatory pathway triggered by hypoxia. CONCLUSIONS: The results indicate that the altered expression of specific circRNAs in MSCs is associated with hypoxic preconditioning. This finding provides further exploration of underlying mechanisms of the characteristic changes of MSCs with hypoxic preconditioning.

Genome sequence of walking catfish (Clarias batrachus) provides insights into terrestrial adaptation.

BACKGROUND: Walking catfish (Clarias batrachus) is a freshwater fish capable of air-breathing and locomotion on land. It usually inhabits various low-oxygen habitats, burrows inside the mudflat, and sometimes "walks" to search for suitable environments during summer. It has evolved accessory air-breathing organs for respiring air and corresponding mechanisms to survive in such challenging environments. Thereby, it serves as a great model for understanding adaptations to terrestrial life. RESULTS: Comparative genomics with channel catfish (Ictalurus punctatus) revealed specific adaptations of C. batrachus in DNA repair, enzyme activator activity, and small GTPase regulator activity. Comparative analysis with 11 non-air-breathing fish species suggested adaptive evolution in gene expression and nitrogenous waste metabolic processes. Further, myoglobin, olfactory receptor related to class A G protein-coupled receptor 1, and sulfotransferase 6b1 genes were found to be expanded in the air-breathing walking catfish genome, with 15, 15, and 12 copies, respectively, compared to non-air-breathing fishes that possess only 1-2 copies of these genes. Additionally, we sequenced and compared the transcriptomes of the gill and the air-breathing organ to characterize the mechanism of aerial respiration involved in elastic fiber formation, oxygen binding and transport, angiogenesis, ion homeostasis and acid-base balance. The hemoglobin genes were expressed dramatically higher in the air-breathing organ than in the gill of walking catfish. CONCLUSIONS: This study provides an important genomic resource for understanding the adaptive mechanisms of walking catfish to terrestrial environments. It is possible that the coupling of enhanced abilities for oxygen storage and oxygen transport through genomic expansion of myoglobin genes and transcriptomic up-regulation of hemoglobin and angiogenesis-related genes are important components of the molecular basis for adaptation of this aquatic species to terrestrial life.