Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet.

BACKGROUND: Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended. RESULTS: In this study, geese exhibited more pronounced changes in the liver index and triglyceride (TG) content following the consumption of the high-fat diet (HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues (5 HFD, 5 normal), including generating high-resolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake. CONCLUSIONS: We examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.

Assessment of different enrichment methods revealed the optimal approach to identify bovine circRnas.

Although circular RNAs (circRNAs) play important roles in regulating gene expression, the understanding of circRNAs in livestock animals is scarce due to the significant challenge to characterize them from a biological sample. In this study, we assessed the outcomes of bovine circRNA identification using six enrichment approaches with the combination of ribosomal RNAs removal (Ribo); linear RNAs degradation (R); linear RNAs and RNAs with structured 3' ends degradation (RTP); ribosomal RNAs coupled with linear RNAs elimination (Ribo-R); ribosomal RNA, linear RNAs and RNAs with poly (A) tailing elimination (Ribo-RP); and ribosomal RNA, linear RNAs and RNAs with structured 3' ends elimination (Ribo-RTP), respectively. RNA-sequencing analysis revealed that different approaches led to varied ratio of uniquely mapped reads, false-positive rate of identifying circRNAs, and the number of circRNAs per million clean reads (Padj <0.05). Out of 2,285 and 2,939 highly confident circRNAs identified in liver and rumen tissues, respectively, 308 and 260 were commonly identified from five methods, with Ribo-RTP method identified the highest number of circRNAs. Besides, 507 of 4,051 identified bovine highly confident circRNAs had shared splicing sites with human circRNAs. The findings from this work provide optimized methods to identify bovine circRNAs from cattle tissues for downstream research of their biological roles in cattle.

Diversity and host interaction of the gut microbiota in specific pathogen-free pigs.

Pigs are widely used as animal models in various studies related to humans. The interaction between the gut microbiota and the host has significant effects on the host's health and disease status. However, although there have been many studies investigating the pig gut microbiota, the findings have been inconsistent due to variations in rearing conditions. Interactions between the gut microbiota and host have not been fully explored in pigs. Specific pathogen-free (SPF) pigs are ideal non-primate large animals to study the interactions between the gut microbiota and the host. In this study, we performed high-throughput sequencing analysis of the gut microbiota and the gut tissue transcriptome of six SPF pigs to provide a systematic understanding of the composition, function, and spatial distribution of gut microbiota in SPF pigs. We identified significant differences in microbial diversity and functionality among different gastrointestinal tract sites. Metagenomics data analysis revealed significant differences in alpha diversity and beta diversity of microbiota in different gastrointestinal sites of SPF pigs. Additionally, transcriptomic data indicated significant differences in gene expression as well as KEGG and GO functional enrichment between the small intestine and large intestine. Furthermore, by combining microbial metagenomics and host transcriptomics analyses, specific correlations were found between gut microbiota and host genes. These included a negative correlation between the TCN1 gene and Prevotella dentalis, possibly related to bacterial metabolic pathways involving vitamin B12, and a positive correlation between the BDH1 gene and Roseburia hominis, possibly because both are involved in fatty acid metabolism. These findings lay the groundwork for further exploration of the co-evolution between the microbiota and the host, specifically in relation to nutrition, metabolism, and immunity. In conclusion, we have elucidated the diversity of the gut microbiota in SPF pigs and conducted a detailed investigation into the interactions between the gut microbiota and host gene expression. These results contribute to our understanding of the intricate dynamics between the gut microbiota and the host, offering important references for advancements in life science research, bioproduct production, and sustainable development in animal husbandry.

Building Haplotype-Resolved 3D Genome Maps of Chicken Skeletal Muscle.

Haplotype-resolved 3D chromatin architecture related to allelic differences in avian skeletal muscle development has not been addressed so far, although chicken husbandry for meat consumption has been prevalent feature of cultures on every continent for more than thousands of years. Here, high-resolution Hi-C diploid maps (1.2-kb maximum resolution) are generated for skeletal muscle tissues in chicken across three developmental stages (embryonic day 15 to day 30 post-hatching). The sequence features governing spatial arrangement of chromosomes and characterize homolog pairing in the nucleus, are identified. Multi-scale characterization of chromatin reorganization between stages from myogenesis in the fetus to myofiber hypertrophy after hatching show concordant changes in transcriptional regulation by relevant signaling pathways. Further interrogation of parent-of-origin-specific chromatin conformation supported that genomic imprinting is absent in birds. This study also reveals promoter-enhancer interaction (PEI) differences between broiler and layer haplotypes in skeletal muscle development-related genes are related to genetic variation between breeds, however, only a minority of breed-specific variations likely contribute to phenotypic divergence in skeletal muscle potentially via allelic PEI rewiring. Beyond defining the haplotype-specific 3D chromatin architecture in chicken, this study provides a rich resource for investigating allelic regulatory divergence among chicken breeds.

PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.

A chromosome-level genome of Chenghua pig provides new insights into the domestication and local adaptation of pigs.

As a country with abundant genetic resources of pigs, the domestication history of pigs in China and the adaptive evolution of Chinese pig breeds at different latitudes have rarely been elucidated at the genome-wide level. To fill this gap, we first assembled a high-quality chromosome-level genome of the Chenghua pig and used it as a benchmark to analyse the genomes of 272 samples from three genera of three continents. The divergence of the three species belonging to three genera, Phacochoerus africanus, Potamochoerus porcus, and Sus scrofa, was assessed. The introgression of pig breeds redefined that the migration routes were basically from southern China to central and southwestern China, then spread to eastern China, arrived in northern China, and finally reached Europe. The domestication of pigs in China occurred ∼12,000 years ago, earlier than the available Chinese archaeological domestication evidence. In addition, FBN1 and NR6A1 were identified in our study as candidate genes related to extreme skin thickness differences in Eurasian pig breeds and adaptive evolution at different latitudes in Chinese pig breeds, respectively. Our study provides a new resource for the pig genomic pool and refines our understanding of pig genetic diversity, domestication, migration, and adaptive evolution at different latitudes.

Haplotype-resolved 3D chromatin architecture of the hybrid pig.

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter-enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.

An intronic enhancer of Cebpa regulates adipocyte differentiation and adipose tissue development via long-range loop formation.

Cebpa is a master transcription factor gene for adipogenesis. However, the mechanisms of enhancer-promoter chromatin interactions controlling Cebpa transcriptional regulation during adipogenic differentiation remain largely unknown. To reveal how the three-dimensional structure of Cebpa changes during adipogenesis, we generated high-resolution chromatin interactions of Cebpa in 3T3-L1 preadipocytes and 3T3-L1 adipocytes using circularized chromosome conformation capture sequencing (4C-seq). We revealed dramatic changes in chromatin interactions and chromatin status at interaction sites during adipogenic differentiation. Based on this, we identified five active enhancers of Cebpa in 3T3-L1 adipocytes through epigenomic data and luciferase reporter assays. Next, epigenetic repression of Cebpa-L1-AD-En2 or -En3 by the dCas9-KRAB system significantly down-regulated Cebpa expression and inhibited adipocyte differentiation. Furthermore, experimental depletion of cohesin decreased the interaction intensity between Cebpa-L1-AD-En2 and the Cebpa promoter and down-regulated Cebpa expression, indicating that long-range chromatin loop formation was mediated by cohesin. Two transcription factors, RXRA and PPARG, synergistically regulate the activity of Cebpa-L1-AD-En2. To test whether Cebpa-L1-AD-En2 plays a role in adipose tissue development, we injected dCas9-KRAB-En2 lentivirus into the inguinal white adipose tissue (iWAT) of mice to suppress the activity of Cebpa-L1-AD-En2. Repression of Cebpa-L1-AD-En2 significantly decreased Cebpa expression and adipocyte size, altered iWAT transcriptome, and affected iWAT development. We identified functional enhancers regulating Cebpa expression and clarified the crucial roles of Cebpa-L1-AD-En2 and Cebpa promoter interaction in adipocyte differentiation and adipose tissue development.

Laminated structural Al2O3/YAG:Ce composite ceramic phosphor with high front light emission for transmissive laser lighting.

The realization of high front light emission in laser lighting under transmissive modes is heavily constrained by low thermal stability and light extraction efficiency of color converter materials. Therefore, it is necessary to improve the heat dissipation capacity and light utilization efficiency of the color converter through appropriate microstructural adjustments. In this study, what we believe to be a novel laminated structure consisting of Al2O3 and YAG:Ce was designed and fabricated for transmissive laser lighting. Through this design, it was possible to change the phosphor emission angle, overcoming the limitations of total internal reflection and enabling maximal emission of yellow phosphor from the ceramic surface. This laminated structure enhanced the front light emission efficiency by 24.4% compared to composite ceramic phosphor. In addition, the thermal conduction area between the phosphor layer and the heat dissipation layer have been effectively enhanced. Ultimately, under a high-power density of 47.6 W/mm2, all ceramics showed no luminous saturation threshold. A high-brightness front light with a luminous flux of 651 lm, a luminous efficiency of 144 lm/W, a correlated color temperature of 6419 K and the operating temperature as low as 84.9 °C was obtained. These results suggest that laminated structural Al2O3/YAG:Ce composite ceramic is a promising candidate for transmissive mode laser lighting.

Identification of a Novel Long Non-Coding RNA G8110 That Modulates Porcine Adipogenic Differentiation and Inflammatory Responses.

Long non-coding RNAs (lncRNAs) have been extensively studied, and their crucial roles in adipogenesis, lipid metabolism, and gene expression have been revealed. However, the exact regulatory or other mechanisms by which lncRNAs influence the functioning of mesenteric adipose tissue (MAT) remain largely unknown. In this paper, we report the identification of a new lncRNA, named G8110, from the MAT of Bama pigs. The coordinated expression levels of lncRNA G8110 and NFE2L1 were significantly decreased in the MAT of obese Bama pigs compared with those in the MAT of lean pigs. Using a bone mesenchymal stem cell adipogenic differentiation model, we found that lncRNA G8110 played a role in adipocyte differentiation by positively regulating NFE2L1. We also found that lncRNA G8110 inhibited the formation of intracellular lipid synthesis, promoted lipid metabolism, and inhibited the expression of inflammatory cytokines. Our findings regarding lipid synthesis may further promote the role of lncRNAs in driving adipose tissue remodeling and maintaining metabolic health.

Dynamic changes of fecal microbiota in a weight-change model of Bama minipigs.

Introduction: Obesity is closely related to gut microbiota, however, the dynamic change of microbial diversity and composition during the occurrence and development process of obesity is not clear. Methods: A weight-change model of adult Bama pig (2 years, 58 individuals) was established, and weight gain (27 weeks) and weight loss (9 weeks) treatments were implemented. The diversity and community structures of fecal microbiota (418 samples) was investigated by using 16S rRNA (V3-V4) high-throughput sequencing. Results: During the weight gain period (1~27 week), the alpha diversity of fecal microbiota exhibited a "down-up-down" fluctuations, initially decreasing, recovering in the mid-term, and decreasing again in the later stage. Beta diversity also significantly changed over time, indicating a gradual deviation of the microbiota composition from the initial time point. Bacteroides, Clostridium sensu stricto 1, and Escherichia-Shigella showed positive correlations with weight gain, while Streptococcus, Oscillospira, and Prevotellaceae UCG-001 exhibited negative correlations. In the weight loss period (30~38 week), the alpha diversity further decreased, and the composition structure underwent significant changes compared to the weight gain period. Christensenellaceae R-7 group demonstrated a significant increase during weight loss and showed a negative correlation with body weight. Porphyromonas and Campylobacter were positively correlated with weight loss. Discussion: Both long-term fattening and weight loss induced by starvation led to substantial alterations in porcine gut microbiota, and the microbiota changes observed during weight gain could not be recovered during weight loss. This work provides valuable resources for both obesity-related research of human and microbiota of pigs.

Characterization of the tumor microenvironment and identification of spatially predictive biomarkers associated with beneficial neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). However, 20-40% of patients with LARC show little to no response to nCRT. Thus, comprehensively understanding the tumor microenvironment (TME), which might influence therapeutic efficacy, and identifying robust predictive biomarkers is urgently needed. Pre-treatment tumor biopsy specimens from patients with LARC were evaluated in detail through digital spatial profiling (DSP), public RNA sequencing datasets, and multiplex immunofluorescence (mIF). DSP analysis revealed distinct characteristics of the tumor stroma compared to the normal stroma and tumor compartments. We identified high levels of human leukocyte antigen-DR/major histocompatibility complex class II (HLA-DR/MHC-II) in the tumor compartment and B cells in the stroma as potential spatial predictors of nCRT efficacy in the Discovery cohort. Public datasets validated their predictive capacity for clinical outcomes. Using mIF in an independent nCRT cohort and/or the total cohort, we validated that a high density of HLA-DR/MHC-II+ cells in the tumor and CD20 + B cells in the stroma was associated with nCRT efficacy (all p ≤ 0.021). Spatial profiling successfully characterized the LARC TME and identified robust biomarkers with the potential to accurately predict nCRT response. These findings have important implications for individualized therapy.

Single-Cell RNA-Sequencing Provides Insight into Skeletal Muscle Evolution during the Selection of Muscle Characteristics.

Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism that controls myogenic development in response to artificial selection. Different pig (Sus scrofa) breeds exhibit distinct muscle phenotypes resulting from domestication and selective breeding. Using unbiased single-cell transcriptomic sequencing analysis (scRNA-seq), the impact of artificial selection on cell profiles is investigated in neonatal skeletal muscle of pigs. This work provides panoramic muscle-resident cell profiles and identifies novel and breed-specific cells, mapping them on pseudotime trajectories. Artificial selection has elicited significant changes in muscle-resident cell profiles, while conserving signs of generational environmental challenges. These results suggest that fibro-adipogenic progenitors serve as a cellular interaction hub and that specific transcription factors identified here may serve as candidate target regulons for the pursuit of a specific muscle phenotype. Furthermore, a cross-species comparison of humans, mice, and pigs illustrates the conservation and divergence of mammalian muscle ontology. The findings of this study reveal shifts in cellular heterogeneity, novel cell subpopulations, and their interactions that may greatly facilitate the understanding of the mechanism underlying divergent muscle phenotypes arising from artificial selection.

A cell transcriptomic profile provides insights into adipocytes of porcine mammary gland across development.

BACKGROUND: Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes. RESULTS: Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages (d 90 of gestation, G90; d 0 after lactation, L0; d 20 after lactation, L20; 2 d post natural involution, PI2; 7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation (G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation (L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution (PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle. CONCLUSION: The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.

The updates on metastatic mechanism and treatment of colorectal cancer.

Colorectal cancer (CRC) is a main cause of cancer death worldwide. Metastasis is a major cause of cancer-related death in CRC. The treatment of metastatic CRC has progressed minimally. However, the potential molecular mechanisms involved in CRC metastasis have remained to be comprehensively clarified. An improved understanding of the CRC mechanistic determinants is needed to better prevent and treat metastatic cancer. In this review, based on evidence from a growing body of research in metastatic cancers, we discuss the cellular and molecular mechanisms involved in CRC metastasis. This review reveals both the molecular mechanisms of metastases and identifies new opportunities for developing more effective strategies to target metastatic relapse and improve CRC patient outcomes.

Transcriptome analysis of norepinephrine-induced lipolysis in differentiated adipocytes of Bama pig.

Sympathetic innervation of white adipose tissue (WAT) plays a key role in the regulation of lipid metabolism. Sympathetic activation promotes release of norepinephrine (NE), which binds to adrenergic receptors on adipocytes, promoting adipocyte lipolysis and enhanced oxidative metabolism. However, the mechanism by which sympathetic nerves regulate lipid metabolism in pig adipose tissue remains unclear. We used NE to simulate the process of sympathetic driving in pig adipocytes. RNA sequencing (RNA-seq) was used to determine the gene expression profile of pig adipocytes responding to NE stimulation. Our data suggests that the lipolytic signaling pathway is activated in pig adipocytes upon acute stimulation of NE, resulting in enhanced lipid metabolism and lipolysis, consistent with the phenomena found in humans and mice. Specifically, differentially expressed protein coding genes (PCGs) (SIRT4, SLC27A1) are mainly associated with functions that inhibit fatty acid oxidation and promote lipid synthesis. Similarly, we investigated the changes in regulatory transcripts such as long non-coding RNAs (lncRNAs) and transcripts of uncertain coding potential (TUCP) in response to NE and found that differentially expressed lncRNAs (lncG47338, lncG30660, lncG29516, lncG3790) and TUCP (TUCP_G38001) were co-expressed with target genes related to the promotion of fatty acid ß-oxidation, lipolysis and oxidative metabolism, thus acting as regulators. These results indicate a broad suite of gene expression alterations in response to NE stimulation and promote the understanding of the molecular mechanisms by which NE regulates lipid metabolism in pigs.

Structure and function of extreme TLS DNA polymerase TTEDbh from Thermoanaerobacter tengcongensis.

Translesion synthesis (TLS) is a kind of DNA repair that maintains the stability of the genome and ensures the normal growth of life in cells under emergencies. Y-family DNA polymerases, as a kind of error-prone DNA polymerase, mainly perform TLS. Previous studies have suggested that the occurrence of tumors is associated with the overexpression of human DNA polymerase of the Y family. And the combination of Y-family DNA polymerase inhibitors is promising for cancer therapy. Here we report the functional and structural characterization of a member of the Y-family DNA polymerases, TTEDbh. We determine TTEDbh is an extreme TLS polymerase that can cross oxidative damage sites, and further identify the amino acids and novel structures that are critical for DNA binding, synthesis, fidelity, and oxidative damage bypass. Moreover, previously unnoticed structural elements with important functions have been discovered and analyzed. These studies provide a more experimental basis for further elucidating the molecular mechanisms of DNA polymerase in the Y family. It could also shed light on the design of drugs to target tumors.

Revisiting Assessment of Computational Methods for Hi-C Data Analysis.

The performances of algorithms for Hi-C data preprocessing, the identification of topologically associating domains, and the detection of chromatin interactions and promoter-enhancer interactions have been mostly evaluated using semi-quantitative or synthetic data approaches, without utilizing the most recent methods, since 2017. In this study, we comprehensively evaluated 24 popular state-of-the-art methods for the complete end-to-end pipeline of Hi-C data analysis, using manually curated or experimentally validated benchmark datasets, including a CRISPR dataset for promoter-enhancer interaction validation. Our results indicate that, although no single method exhibited superior performance in all situations, HiC-Pro, DomainCaller, and Fit-Hi-C2 showed relatively balanced performances of most evaluation metrics for preprocessing, topologically associating domain identification, and chromatin interaction/promoter-enhancer interaction detection, respectively. The comprehensive comparison presented in this manuscript provides a reference for researchers to choose Hi-C analysis tools that best suit their needs.

Intense and Superflat White Laser with 700-nm 3-dB Bandwidth and 1-mJ Pulse Energy Enabling Single-Shot Subpicosecond Pulse Laser Spectroscopy.

An optical spectrometer is a basic spectral instrument that probes microscopic physical and chemical properties of macroscopic objects but generally suffers from difficulty in broadband time-resolved measurement. In this work, we report the creation of ultrabroadband white-light laser with a 3-dB bandwidth covering 385 to 1,080 nm, pulse energy of 1.07 mJ, and pulse duration of several hundred femtoseconds by passing 3-mJ pulse energy, 50-fs pulse duration Ti:Sapphire pulse laser through a cascaded fused silica plate and chirped periodically poled lithium niobate crystal. We utilize this unprecedented superflat, ultrabroadband, and intense femtosecond laser light source to build a single-shot (i.e., single-pulse) subpicosecond pulse laser ultraviolet-visible-near-infrared spectrometer and successfully measure various atomic and molecular absorption spectra. The single-shot ultrafast spectrometer may open up a frontier to monitor simultaneously the ultrafast dynamics of multiple physical and chemical processes in various microscopic systems.

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response.

Background: Colon adenocarcinoma (COAD) is a common malignancy with high morbidity and mortality rates. The immune system plays a crucial role in CRC development and progression, making it a potential therapeutic target. In this study, we analyzed transcriptomic data from CRC patients to investigate immune infiltration and identify potential therapeutic targets. Method and results: we used CIBERSORT to analyze the immune infiltration in COAD samples and found that the high infiltration of M2 macrophages and neutrophils was associated with poor prognosis. Next, we identified NR4A1 as a potential therapeutic target based on its protective effect in two predict models. Using cancer therapeutics response analysis, we found that high expression levels of NR4A1 were sensitive to OSI-930, a tyrosine kinase inhibitor with anti-tumor effects. Conclusion: Our findings suggest that targeting NR4A1 with OSI-930 may be a promising therapeutic strategy for COAD patients with high levels of immune infiltration. However, further studies are needed to investigate the clinical efficacy of this approach.