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Abstract The deconfinement quantum critical point (DQCP), a paradigm beyond the Landau-Ginzburg-Wilson framework to classify states of matters, has been attracting extensive attention over the past two decades. Experimentally, SrCu2(BO3)2 plays key roles in verifying the DQCP between an antiferromagnetic (AF) Néel phase and a plaquette-singlet (PS) phase. However, the verification of the DQCP of the PS-AF transition lies in 2.4 - 3.1 GPa, which is unreachable previously due to technical limitations. Here, through the advanced high-pressure heat capacity measurements, we demonstrate that the PS-AF phase transition of SrCu2(BO3)2 at zero field is clearly first-order. Our result clarifies the two-decade-long debates about this key issue and resonates nicely with recent theoretical consensus that the previously predicted DQCPs in representative models are actually first-order transitions. Besides, the PS and AF phases transit at the same pressure-temperature point, a bi-critical point found in frustrated magnets.

Summary: Folliculin interacting protein 1 (FNIP1) primarily participates in regulating cellular energy metabolism and is associated with Birt-Hogg-Dubé (BHD) syndrome. Although FNIP1 has been demonstrated to function as both a tumor suppressor and promoter, its role in colorectal cancer (CRC) remains unclear. Our study demonstrated a significant downregulation of FNIP1 in CRC, correlating with shorter overall and disease-specific survival. FNIP1 may potentially serve as an independent prognostic factor in CRC. Moreover, FNIP1 inhibited CRC progression in vitro and in vivo. Mechanistically, FNIP1 bound to phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and downregulated its expression. FNIP1 deletion increased STAT3 phosphorylation and nuclear localization, thereby promoting CRC progression. The use of p-STAT3-specific chemical inhibitors successfully mitigated excessive tumorigenesis resulting from FNIP1 absence. Thus, our results suggest that FNIP1 hinders CRC progression by suppressing STAT3 phosphorylation and nuclear translocation. FNIP1 may be a candidate prognostic indicator and a therapeutic target for intervention in CRC.

Abstract Glioblastoma (GBM) is the most common malignant primary brain tumor. Despite comprehensive treatment with traditional surgery, radiotherapy, and chemotherapy, the median survival rate is

Abstract Many types of cancer cells, including colorectal cancer cells (CRC), can simultaneously enhance glycolysis and repress the mitochondrial tricarboxylic acid (TCA) cycle, which is called the Warburg effect. However, the detailed mechanisms of abnormal activation of the glycolysis pathway in colorectal cancer are largely unknown. In this study, we reveal that the protein arginine methyltransferase 1 (PRMT1) promotes glycolysis, proliferation, and tumorigenesis in CRC cells. Mechanistically, PRMT1-mediated arginine asymmetric dimethylation modification of phosphoglycerate kinase 1 (PGK1, the first ATP-producing enzyme in glycolysis) at R206 (meR206-PGK1) enhances the phosphorylation level of PGK1 at S203 (pS203-PGK1), which inhibits mitochondrial function and promotes glycolysis. We found that PRMT1 and meR206-PGK1 expression were positively correlated with pS203-PGK1 expression in tissues from colorectal cancer patients. Furthermore, we also confirmed that meR206-PGK1 expression is positively correlated with the poor survival of patients with colorectal cancer. Our findings show that PRMT1 and meR206-PGK1 may become promising predictive biomarkers for the prognosis of patients with CRC and that arginine methyltransferase inhibitors have great potential in colorectal cancer treatment.

Abstract Background Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear. Methods The XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients. Results TRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis. Conclusion The findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC.

Abstract Protein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.

Tripartite motif containing-21 (TRIM21), an E3 ubiquitin ligase, was initially found to be involved in antiviral responses and autoimmune diseases. Recently studies have reported that TRIM21 plays a dual role in cancer promoting and suppressing in the occurrence and development of various cancers. Despite the fact that TRIM21 has effects on multiple metabolic processes, inflammatory responses and the efficacy of tumor therapy, there has been no systematic review of these topics. Herein, we discuss the emerging role and function of TRIM21 in cancer metabolism, immunity, especially the immune response to inflammation associated with tumorigenesis, and also the cancer treatment, hoping to shine a light on the great potential of targeting TRIM21 as a therapeutic target.

Abstract Enhancer of zeste homolog 2 (EZH2), as a main component of Polycomb Repressive Complex 2, catalyzes histone H3K27me3 to silence its target gene expression. EZH2 upregulation results in cancer development and poor prognosis of cancer patients. Post-translational modifications (PTMs) are important biological events in cancer progression. PTMs regulate protein conformation and diversity functions. Recently, mounting studies have demonstrated that EZH2 stability, histone methyltransferase activity, localization, and binding partners can be regulated by PTMs, including phosphorylation, O-GlcNAcylation, acetylation, methylation and ubiquitination. However, the detailed molecular mechanisms of the EZH2-PTMs and whether other types of PTMs occur in EZH2 remain largely unclear. This review presents an overview of different roles of EZH2 modification and EZH2-PTMs crosstalk during tumorigenesis and cancer metastasis. We also discussed the therapeutic potential of targeting EZH2 modifications for cancer therapy.

Abstract Background Traditional Chinese medicine (TCM) is a highly important complement to modern medicine and is widely practiced in China and in many other countries. The work of Chinese medicine is subject to the two factors of the inheritance and development of clinical experience of famous Chinese medicine practitioners and the difficulty in improving the service capacity of basic Chinese medicine practitioners. Heterogeneous information networks (HINs) are a kind of graphical model for integrating and modeling real-world information. Through HINs, we can integrate and model the large-scale heterogeneous TCM data into structured graph data and use this as a basis for analysis. Methods Mining categorizations from TCM data is an important task for precision medicine. In this paper, we propose a novel structured learning model to solve the problem of formula regularity, a pivotal task in prescription optimization. We integrate clustering with ranking in a heterogeneous information network. Results The results from experiments on the Pharmacopoeia of the People’s Republic of China (ChP) demonstrate the effectiveness and accuracy of the proposed model for discovering useful categorizations of formulas. Conclusions We use heterogeneous information networks to model TCM data and propose a TCM-HIN. Combining the heterogeneous graph with the probability graph, we proposed the TCM-Clus algorithm, which combines clustering with ranking and classifies traditional Chinese medicine prescriptions. The results of the categorizations can help Chinese medicine practitioners to make clinical decision.

The purpose of this study is to grasp the current situation of the pneumoconiosis incidence and prevention in coal chemical workers, and find out the countermeasures of pneumoconiosis control. To this end, questionnaires were used in this paper to carry out research on occupational disease health survey and disease prevention work, and in-depth statistical analysis was also conducted about the occupational health status and protection of coal chemical workers. The study found that the age of workers was statistically significant for the probability of pneumoconiosis, and chemical workers aged 40-50 years and older were more likely to suffer pneumoconiosis, reaching 5.84% and 12.77%, respectively; the probability of workers suffering from pneumoconiosis varies significantly for different work types, length of service, and smoking index, and smoking can also increase the probability of pneumoconiosis; the detection rate of cardiovascular system, liver and lung function and abnormal electrocardiogram (ECG) in patients with pneumoconiosis is significantly higher than that of non-pneumoconiosis workers; most workers have a certain understanding of the hazards and protective knowledge of productive dust, but chemical enterprise should still pay attention to and strengthen the safety knowledge education and training of workers. The above research provides theoretical guidance for controlling and preventing coal chemical workers from suffering from pneumoconiosis.