Overview of chicken embryo genes related to sex differentiation.

Sex determination in chickens at an early embryonic stage has been a longstanding challenge in poultry production due to the unique ZZ:ZW sex chromosome system and various influencing factors. This review has summarized the genes related to the sex differentiation of chicken early embryos (mainly Dmrt1, Sox9, Amh, Cyp19a1, Foxl2, Tle4z1, Jun, Hintw, Ube2i, Spin1z, Hmgcs1, Foxd1, Tox3, Ddx4, cHemgn and Serpinb11 in this article), and has found that these contributions enhance our understanding of the genetic basis of sex determination in chickens, while identifying potential gene targets for future research. This knowledge may inform and guide the development of sex screening technologies for hatching eggs and support advancements in gene-editing approaches for chicken embryos. Moreover, these insights offer hope for enhancing animal welfare and promoting conservation efforts in poultry production.

Mutual Information Driven Equivariant Contrastive Learning for 3D Action Representation Learning.

Self-supervised contrastive learning has proven to be successful for skeleton-based action recognition. For contrastive learning, data transformations are found to fundamentally affect the learned representation quality. However, traditional invariant contrastive learning is detrimental to the performance on the downstream task if the transformation carries important information for the task. In this sense, it limits the application of many data transformations in the current contrastive learning pipeline. To address these issues, we propose to utilize equivariant contrastive learning, which extends invariant contrastive learning and preserves important information. By integrating equivariant and invariant contrastive learning into a hybrid approach, the model can better leverage the motion patterns exposed by data transformations and obtain a more discriminative representation space. Specifically, a self-distillation loss is first proposed for transformed data of different intensities to fully utilize invariant transformations, especially strong invariant transformations. For equivariant transformations, we explore the potential of skeleton mixing and temporal shuffling for equivariant contrastive learning. Meanwhile, we analyze the impacts of different data transformations on the feature space in terms of two novel metrics proposed in this paper, namely, consistency and diversity. In particular, we demonstrate that equivariant learning boosts performance by alleviating the dimensional collapse problem. Experimental results on several benchmarks indicate that our method outperforms existing state-of-the-art methods.

The Effect of Ethephon on Ethylene and Chlorophyll in Zoysia japonica Leaves.

Zoysia japonica (Zoysia japonica Steud.) is a kind of warm-season turfgrass with many excellent characteristics. However, the shorter green period and longer dormancy caused by cold stress in late autumn and winter are the most limiting factors affecting its application. A previous transcriptome analysis revealed that ethephon regulated genes in chlorophyll metabolism in Zoysia japonica under cold stress. Further experimental data are necessary to understand the effect and underlying mechanism of ethephon in regulating the cold tolerance of Zoysia japonica. The aim of this study was to evaluate the effects of ethephon by measuring the enzyme activity, intermediates content, and gene expression related to ethylene biosynthesis, signaling, and chlorophyll metabolism. In addition, the ethylene production rate, chlorophyll content, and chlorophyll a/b ratio were analyzed. The results showed that ethephon application in a proper concentration inhibited endogenous ethylene biosynthesis, but eventually promoted the ethylene production rate due to its ethylene-releasing nature. Ethephon could promote chlorophyll content and improve plant growth in Zoysia japonica under cold-stressed conditions. In conclusion, ethephon plays a positive role in releasing ethylene and maintaining the chlorophyll content in Zoysia japonica both under non-stressed and cold-stressed conditions.

Captive ERVWE1 triggers impairment of 5-HT neuronal plasticity in the first-episode schizophrenia by post-transcriptional activation of HTR1B in ALKBH5-m6A dependent epigenetic mechanisms.

BACKGROUND: Abnormalities in the 5-HT system and synaptic plasticity are hallmark features of schizophrenia. Previous studies suggest that the human endogenous retrovirus W family envelope (ERVWE1) is an influential risk factor for schizophrenia and inversely correlates with 5-HT4 receptor in schizophrenia. To our knowledge, no data describes the effect of ERVWE1 on 5-HT neuronal plasticity. N6-methyladenosine (m6A) regulates gene expression and impacts synaptic plasticity. Our research aims to systematically investigate the effects of ERVWE1 on 5-HT neuronal plasticity through m6A modification in schizophrenia. RESULTS: HTR1B, ALKBH5, and Arc exhibited higher levels in individuals with first-episode schizophrenia compared to the controls and showed a strong positive correlation with ERVWE1. Interestingly, HTR1B was also correlated with ALKBH5 and Arc. Further analyses confirmed that ALKBH5 may be an independent risk factor for schizophrenia. In vitro studies, we discovered that ERVWE1 enhanced HTR1B expression, thereby activating the ERK-ELK1-Arc pathway and reducing the complexity and spine density of 5-HT neurons. Furthermore, ERVWE1 reduced m6A levels through ALKBH5 demethylation. ERVWE1 induced HTR1B upregulation by improving its mRNA stability in ALKBH5-m6A-dependent epigenetic mechanisms. Importantly, ALKBH5 mediated the observed alterations in 5-HT neuronal plasticity induced by ERVWE1. CONCLUSIONS: Overall, HTR1B, Arc, and ALKBH5 levels were increased in schizophrenia and positively associated with ERVWE1. Moreover, ALKBH5 was a novel risk gene for schizophrenia. ERVWE1 impaired 5-HT neuronal plasticity in ALKBH5-m6A dependent mechanism by the HTR1B-ERK-ELK1-Arc pathway, which may be an important contributor to aberrant synaptic plasticity in schizophrenia.

A retrospective comparative study on the diagnostic efficacy and the complications: between CassiII rotational core biopsy and core needle biopsy.

Accurate pathologic diagnosis and molecular classification of breast mass biopsy tissue is important for determining individualized therapy for (neo)adjuvant systemic therapies for invasive breast cancer. The CassiII rotational core biopsy system is a novel biopsy technique with a guide needle and a "stick-freeze" technology. The comprehensive assessments including the concordance rates of diagnosis and biomarker status between CassiII and core needle biopsy were evaluated in this study. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed through immunohistochemistry. In total, 655 patients with breast cancer who underwent surgery after biopsy at Sir Run Run Shaw Hospital between January 2019 to December 2021 were evaluated. The concordance rates (CRs) of malignant surgical specimens with CassiII needle biopsy was significantly high compared with core needle biopsy. Moreover, CassiII needle biopsy had about 20% improvement in sensitivity and about 5% improvement in positive predictive value compared to Core needle biopsy. The characteristics including age and tumor size were identified the risk factors for pathological inconsistencies with core needle biopsies. However, CassiII needle biopsy was associated with tumor diameter only. The CRs of ER, PgR, HER2, and Ki67 using Cassi needle were 98.08% (kappa, 0.941; p<.001), 90.77% (kappa, 0.812; p<.001), 69.62% (kappa, 0.482; p<.001), and 86.92% (kappa, 0.552; p<.001), respectively. Post-biopsy complications with CassiII needle biopsy were also collected. The complications of CassiII needle biopsy including chest stuffiness, pain and subcutaneous ecchymosis are not rare. The underlying mechanism of subcutaneous congestion or hematoma after CassiII needle biopsy might be the larger needle diameter and the effect of temperature on coagulation function. In summary, CassiII needle biopsy is age-independent and has a better accuracy than CNB for distinguishing carcinoma in situ and invasive carcinoma.

Cushioning Performance of the Biomimetic Cobweb Cushioning Silicone Pad.

At present, the packing method of "plastic bag-buffer packing-packing paper box" is adopted for bearing packaging. However, the common packing method has a poor packing effect and poor versatility. In this study, a new biomimetic cobweb cushion is proposed to solve the problem of insufficient cushioning capacity of high-precision bearing cushion packaging pads. First, according to the nature of cobweb form, the cobweb cushion structure configuration is determined. Next, based on the structure of the cushion and the relationship between the parameters of radial thread and spiral thread, a mechanical and target optimization model is established. The stress nephogram of bearing and the cobweb cushion are analyzed under three drop heights of 381, 610, and 700 mm, in the finite element simulation software to ensure that the maximum bearings stress is not beyond the material yield strength. Via the 3D printing technology, a cobweb cushion shell cast is made. Drop tests of the bearing were performed, and the results were verified with the finite element simulation analysis. This research can provide technical support for the protection of high-precision bearings from accidental drops during transportation.

Mid-high-frequency error suppression of small optical aspheric molds.

To suppress the mid-high-frequency error of small optical tungsten carbide aspheric molds, it is proposed to quickly select the critical process parameters by simulating the residual error after convolution of the tool influence function (TIF). After polishing for 10.47 min by the TIF, two simulation optimizations, RMS and Ra, converge to 9.3 and 5.347 nm, respectively. Their convergence rates are improved by 40% and 7.9%, respectively, compared to ordinary TIF. Then, a faster and more high-quality multi-tool combination smoothing suppression method is proposed, and the corresponding polishing tools are designed. Finally, the global Ra of the aspheric surface converges from 5.9 to 4.5 nm after smoothing for 5.5 min with a disc-shaped polishing tool with a fine microstructure and maintains an excellent low-frequency error (PV 0.0781 µm).

Design and Study of a Reflector-Separated Light Dispersion-Compensated 3D Microscopy System.

The secondary-phase grating-based tomographic microscopy system, which is widely used in the biological and life sciences, can observe all the sample multilayer image information simultaneously because it has multifocal points. However, chromatic aberration exists in the grating diffraction, which seriously affects the observation of the image. To correct the chromatic aberration of the tomographic microscope system, this paper proposes a system that adopts blazed gratings and angle-variable reflectors as chromatic aberration correction devices according to the principle of dispersion compensation and Fourier phase-shift theory. A reflector-separated light dispersion-compensated 3D microscopy system is presented to achieve chromatic aberration correction while solving the problem of multilayer image overlap. The theoretical verification and optical design of the system were completed using ZEMAX software. The results show that the proposed system reduced the chromatic aberration of ordinary tomographic microscopy systems by more than 90%, retaining more wavelengths of light information. In addition, the system had a relatively wide range in the color difference compensation element installation position, reducing the difficulty of dispersion compensation element installation. Overall, the results indicate that the proposed system is effective in reducing chromatic aberration in grating diffraction.

Noncoding RNA circBtnl1 suppresses self-renewal of intestinal stem cells via disruption of Atf4 mRNA stability.

Intestinal stem cells (ISCs) at the crypt base are responsible for the regeneration of the intestinal epithelium. However, how ISC self-renewal is regulated still remains unclear. Here we identified a circular RNA, circBtnl1, that is highly expressed in ISCs. Loss of circBtnl1 in mice enhanced ISC self-renewal capacity and epithelial regeneration, without changes in mRNA and protein levels of its parental gene Btnl1. Mechanistically, circBtnl1 and Atf4 mRNA competitively bound the ATP-dependent RNA helicase Ddx3y to impair the stability of Atf4 mRNA in wild-type ISCs. Furthermore, ATF4 activated Sox9 transcription by binding to its promoter via a unique motif, to enhance the self-renewal capacity and epithelial regeneration of ISCs. In contrast, circBtnl1 knockout promoted Atf4 mRNA stability and enhanced ATF4 expression, which caused Sox9 transcription to potentiate ISC stemness. These data indicate that circBtnl1-mediated Atf4 mRNA decay suppresses Sox9 transcription that negatively modulates self-renewal maintenance of ISCs.

A Two-Step Simulated Annealing Algorithm for Spectral Data Feature Extraction.

To address the shortcomings in many traditional spectral feature extraction algorithms in practical application of low modeling accuracy and poor stability, this paper introduces the "Boruta algorithm-based local optimization process" based on the traditional simulated annealing algorithm and proposes the "two-step simulated annealing algorithm (TSSA)". This algorithm combines global optimization and local optimization. The Boruta algorithm ensures that the feature extraction results are all strongly correlated with the dependent variable, reducing data redundancy. The accuracy and stability of the algorithm model are significantly improved. The experimental results show that compared with the traditional feature extraction method, the accuracy indexes of the inversion model established by using the TSSA algorithm for feature extraction were significantly improved, with the determination coefficient R2 of 0.9654, the root mean square error (RMSE) of 3.6723 µg/L, and the mean absolute error (MAE) of 3.1461 µg/L.

Effect of intradiscal local anesthetic injection on intraoperative pain during percutaneous transforaminal endoscopic discectomy: A retrospective study.

OBJECTIVE: Patients undergoing percutaneous transforaminal endoscopic discectomy (PTED) often complain of unbearable intraoperative pain. This study is to observe clinical effectiveness and safety of intradiscal local anesthetic injection for intraoperative pain relief. METHODS: Total 268 patients who underwent PTED were analyzed. Patients were divided into intradiscal saline injection group (group C) and intradiscal local anesthetic injection group (group L). Intradiscal mixture was consisted of saline or local anesthetic + methylene blue, the amount of injected mixture was 3 mL. Demographic data, visual analog scale (VAS) and Quebec Back Pain Disability Scale (QBPDS) scores, mean arterial pressure (MAP) and heart rate (HR), total dosage of fentanyl, satisfaction rate of anesthesia and complications were collected at different timepoints. RESULTS: Compared with group C (3.94 ± 0.57), there was a significant reduction of VAS in group L (2.83 ± 0.28) during fibrous annular operation phase (T2). Group L had a lower total dosage of fentanyl (71 [63, 78] µg) and a higher anesthesia satisfaction rate (95.3%) than group C (82 [70, 132] µg and 73.6%, respectively) (P < 0.001). MAP and HR were lower in group L than in group C at T2 (P < 0.001). Baseline characteristics and QBPDS scores showed no meaningful intergroup differences. Four cases of complications were reported in this study. CONCLUSION: Intradiscal local anesthetic injection significantly alleviated intraoperative back pain and increased the satisfaction rate of anesthesia, without severe complications, indicating that this technique is a feasible method for intraoperative back pain relief for patients undergoing PTED.

Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer. METHODS: We measured the levels of PLAC8 in breast cancer cell lines and found that PLAC8 is post-translationally modified by ubiquitin-fold modifier 1 (UFM1). Then, we revealed a new regulatory system of PD-L1 by PLAC8 in triple-negative breast cancer. We also tested the molecular functions of PLAC8 in triple-negative breast cancer cell lines and measured the expression of PLAC8 and PD-L1 in breast cancer tissues. RESULTS: PLAC8 was generally highly expressed in triple-negative breast cancer and could be modified by UFM1, which maintains PLAC8 protein stability. Moreover, PLAC8 could promote cancer cell proliferation and affect the immune response by regulating the level of PD-L1 ubiquitination. Additionally, among patients with breast cancer, the expression of PLAC8 was higher in triple-negative breast cancer than in non-triple-negative breast cancer and positively correlated with the level of PD-L1. CONCLUSIONS: Our current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.

Anesthetic sevoflurane simultaneously regulates autophagic flux and pyroptotic cell death-associated cellular inflammation in the hypoxic/re-oxygenated cardiomyocytes: Identification of sevoflurane as putative drug for the treatment of myocardial ischemia-reperfusion injury.

PRE: and post-conditioning of sevoflurane attenuate cardiomyocyte death and protects against myocardial ischemia/reperfusion (I/R) injury, and this process is considered to be associated with cell autophagy and pyroptosis, but the detailed molecular mechanisms regarding to this issue have not been fully studied. In this study, we verified that sevoflurane exerted its protective effects in myocardial I/R injury by synergistically regulating the AMPK/ULK1 pathway-mediated autophagy and NLRP3-mediated pyroptotic cell death, and the interplays between cell autophagy and pyroptosis were also preliminarily investigated. Specifically, sevoflurane conditioning suppressed NLRP3 and cleaved caspase-1 expressions to inactivate cell pyroptosis, upregulated LC3B-II/I ratio, facilitated autophagosome formation and accelerated p62 degradation to trigger autophagy, and promoted the expressions of CDK2, CDK6 and Cyclin D1 to recover cell cycle in I/R mouse myocardial tissues in vivo and hypoxic/re-oxygenated (H/R) cardiomyocytes in vitro. Further experiments validated that sevoflurane promoted the phosphorylation of both AMPK (p-AMPK) and ULK1 (p-ULK1) to activate the AMPK/ULK1 pathway, and the promoting effects of sevoflurane on cell autophagy in H/R cardiomyocytes were abrogated by co-treating cells with AMPK inhibitor (compound C) and ULK1 inhibitor (SBI-0206965). Moreover, it was verified that compound C, SBI-0206965 and autophagy blocker chloroquine reversed H/R-induced cell death and pyroptosis in cardiomyocytes. Taken together, we concluded that sevoflurane activated the AMPK/ULK1 pathway to trigger autophagic flux and suppress NLRP3-mediated pyroptotic cell death in I/R or H/R-treated cardiomyocytes, which further ameliorated myocardial I/R injury.

The role of lncRNA H19 in tumorigenesis and drug resistance of human Cancers.

Systemic therapy is one of the most significant cancer treatments. However, drug resistance often appears and has become the primary cause of cancer therapy failure. Regulation of drug target, drug metabolism and drug efflux, cell death escape (apoptosis, autophagy, et al.), epigenetic changes, and many other variables are complicatedly involved in the mechanisms of drug resistance. In various types of cancers, long non-coding RNA H19 (lncRNA H19) has been shown to play critical roles in tumor development, proliferation, metastasis, and multiple drug resistance as well. The efficacy of chemotherapy, endocrine therapy, and targeted therapy are all influenced by the expression of H19, especially in breast cancer, liver cancer, lung cancer and colorectal cancer. Here, we summarize the relationship between lncRNA H19 and tumorigenesis, and illustrate the drug resistance mechanisms caused by lncRNA H19 as well. This review may provide more therapeutic potential targets for future cancer treatments.

Detection of circulating tumor cells: opportunities and challenges.

Circulating tumor cells (CTCs) are cells that shed from a primary tumor and travel through the bloodstream. Studying the functional and molecular characteristics of CTCs may provide in-depth knowledge regarding highly lethal tumor diseases. Researchers are working to design devices and develop analytical methods that can capture and detect CTCs in whole blood from cancer patients with improved sensitivity and specificity. Techniques using whole blood samples utilize physical prosperity, immunoaffinity or a combination of the above methods and positive and negative enrichment during separation. Further analysis of CTCs is helpful in cancer monitoring, efficacy evaluation and designing of targeted cancer treatment methods. Although many advances have been achieved in the detection and molecular characterization of CTCs, several challenges still exist that limit the current use of this burgeoning diagnostic approach. In this review, a brief summary of the biological characterization of CTCs is presented. We focus on the current existing CTC detection methods and the potential clinical implications and challenges of CTCs. We also put forward our own views regarding the future development direction of CTCs.

Study of the Off-Axis Fresnel Zone Plate of a Microscopic Tomographic Aberration.

A tomographic microscopy system can achieve instantaneous three-dimensional imaging, and this type of microscopy system has been widely used in the study of biological samples; however, existing chromatographic microscopes based on off-axis Fresnel zone plates have degraded image quality due to geometric aberrations such as spherical aberration, coma aberration, and image scattering. This issue hinders the further development of chromatographic microscopy systems. In this paper, we propose a method for the design of an off-axis Fresnel zone plate with the elimination of aberrations based on double exposure point holographic surface interference. The aberration coefficient model of the optical path function was used to solve the optimal recording parameters, and the principle of the aberration elimination tomography microscopic optical path was verified. The simulation and experimental verification were carried out utilizing a Seidel coefficient, average gradient, and signal-to-noise ratio. First, the aberration coefficient model of the optical path function was used to solve the optimal recording parameters. Then, the laminar mi-coroscopy optical system was constructed for the verification of the principle. Finally, the simulation calculation results and the experimental results were verified by comparing the Seidel coefficient, average gradient, and signal-to-noise ratio of the microscopic optical system before and after the aberration elimination. The results show that for the diffractive light at the orders 0 and ±1, the spherical aberration W040 decreases by 62-70%, the coma aberration W131 decreases by 96-98%, the image dispersion W222 decreases by 71-82%, and the field curvature W220 decreases by 96-96%, the average gradient increases by 2.8%, and the signal-to-noise ratio increases by 18%.

Transcriptome Analysis Revealed a Positive Role of Ethephon on Chlorophyll Metabolism of Zoysia japonica under Cold Stress.

Zoysia japonica is a warm-season turfgrass with a good tolerance and minimal maintenance requirements. However, its use in Northern China is limited due to massive chlorophyll loss in early fall, which is the main factor affecting its distribution and utilization. Although ethephon treatment at specific concentrations has reportedly improved stress tolerance and extended the green period in turfgrass, the potential mechanisms underlying this effect are not clear. In this study, we evaluated and analyzed chlorophyll changes in the physiology and transcriptome of Z. japonica plants in response to cold stress (4 °C) with and without ethephon pretreatment. Based on the transcriptome and chlorophyll content analysis, ethephon pretreatment increased the leaf chlorophyll content under cold stress by affecting two processes: the stimulation of chlorophyll synthesis by upregulating ZjMgCH2 and ZjMgCH3 expression; and the suppression of chlorophyll degradation by downregulating ZjPAO, ZjRCCR, and ZjSGR expression. Furthermore, ethephon pretreatment increased the ratio of chlorophyll a to chlorophyll b in the leaves under cold stress, most likely by suppressing the conversion of chlorophyll a to chlorophyll b due to decreased chlorophyll b synthesis via downregulation of ZjCAO. Additionally, the inhibition of chlorophyll b synthesis may result in energy redistribution between photosystem II and photosystem I.

Transcriptome analysis of Kentucky bluegrass subject to drought and ethephon treatment.

Kentucky bluegrass (Poa pratensis L.) is an excellent cool-season turfgrass utilized widely in Northern China. However, turf quality of Kentucky bluegrass declines significantly due to drought. Ethephon seeds-soaking treatment has been proved to effectively improve the drought tolerance of Kentucky bluegrass seedlings. In order to investigate the effect of ethephon leaf-spraying method on drought tolerance of Kentucky bluegrass and understand the underlying mechanism, Kentucky bluegrass plants sprayed with and without ethephon are subjected to either drought or well watered treatments. The relative water content and malondialdehyde conent were measured. Meanwhile, samples were sequenced through Illumina. Results showed that ethephon could improve the drought tolerance of Kentucky bluegrass by elevating relative water content and decreasing malondialdehyde content under drought. Transcriptome analysis showed that 58.43% transcripts (254,331 out of 435,250) were detected as unigenes. A total of 9.69% (24,643 out of 254,331) unigenes were identified as differentially expressed genes in one or more of the pairwise comparisons. Differentially expressed genes due to drought stress with or without ethephon pre-treatment showed that ethephon application affected genes associated with plant hormone, signal transduction pathway and plant defense, protein degradation and stabilization, transportation and osmosis, antioxidant system and the glyoxalase pathway, cell wall and cuticular wax, fatty acid unsaturation and photosynthesis. This study provides a theoretical basis for revealing the mechanism for how ethephon regulates drought response and improves drought tolerance of Kentucky bluegrass.

Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive. METHODS: CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology. RESULTS: CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development. CONCLUSION: Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.

Classification and gene selection of triple-negative breast cancer subtype embedding gene connectivity matrix in deep neural network.

Triple-negative breast cancer (TNBC) has been a challenging breast cancer subtype for oncological therapy. Normally, it can be classified into different molecular subtypes. Accurate and stable classification of the six subtypes is essential for personalized treatment of TNBC. In this study, we proposed a new framework to distinguish the six subtypes of TNBC, and this is one of the handful studies that completed the classification based on mRNA and long noncoding RNA expression data. Particularly, we developed a gene selection approach named DGGA, which takes correlation information between genes into account in the process of measuring gene importance and then effectively removes redundant genes. A gene scoring approach that combined GeneRank scores with gene importance generated by deep neural network (DNN), taking inter-subtype discrimination and inner-gene correlations into account, was came up to improve gene selection performance. More importantly, we embedded a gene connectivity matrix in the DNN for sparse learning, which takes additional consideration with weight changes during training when obtaining the measurement of the relative importance of each gene. Finally, Genetic Algorithm was used to simulate the natural evolutionary process to search for the optimal subset of TNBC subtype classification. We validated the proposed method through cross-validation, and the results demonstrate that it can use fewer genes to obtain more accurate classification results. The implementation for the proposed method is available at https://github.com/RanSuLab/TNBC.