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Background Long noncoding RNA ANRIL has been found to be involved in the pathogenesis of diabetic kidney disease (DKD) and is expected to be a new target for prevention of DKD. However, the circulating expression and clinical significance of ANRIL in DKD patients is uncertain. This study aims to explore this issue. Methods The study consisted of 20 healthy controls, 22 T2DM patients (normalbuminuria) and 66 DKD patients (grouped as follows: microalbuminuria, n = 23; macroalbuminuria, n = 22 and renal dysfunction, n = 21). The expressions of ANRIL in peripheral whole blood of all participants were measured by RT-qPCR. Results The expression of ANRIL was significantly up-regulated in DKD patients (microalbuminuria, macroalbuminuria and renal dysfunction groups) than that in healthy control group. ANRIL was also over-expressed in macroalbuminuria and renal dysfunction groups in comparison with normalbuminuria group. ANRIL expression was positively correlated with Scr, BUN, CysC, urine β2-MG and urine α1-MG; while negatively correlated with eGFR in DKD patients. In addition, ANRIL was the risk factor for DKD with OR value of 1.681. The AUC of ANRIL in identifying DKD was 0.922, and the sensitivity and specificity of DKD diagnosis were 83.3% and 90.5%, respectively. Conclusion Our results indicated that highly expressed ANRIL in peripheral blood is associated with progression of DKD. Circulating ANRIL is an independent risk factor of DKD and has a highly predictive value in identifying DKD.

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.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 epidemic is worsening. Binding of the Spike1 protein of SARS-CoV-2 with the angiotensin-converting enzyme 2 (ACE2) receptor mediates entry of the virus into host cells. Many reports show that protein arginine methylation by protein arginine methyltransferases (PRMTs) is important for the functions of these proteins, but it remains unclear whether ACE2 is methylated by PRMTs. Here, we show that PRMT5 catalyses ACE2 symmetric dimethylation at residue R671 (meR671-ACE2). We indicate that PRMT5-mediated meR671-ACE2 promotes SARS-CoV-2 receptor-binding domain (RBD) binding with ACE2 probably by enhancing ACE2 N-glycosylation modification. We also reveal that the PRMT5-specific inhibitor GSK3326595 is able to dramatically reduce ACE2 binding with RBD. Moreover, we discovered that meR671-ACE2 plays an important role in ACE2 binding with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants; and we found that GSK3326595 strongly attenuates ACE2 interaction with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants. Finally, SARS-CoV-2 pseudovirus infection assays uncovered that PRMT5-mediated meR671-ACE2 is essential for SARS-CoV-2 infection in human cells, and pseudovirus infection experiments confirmed that GSK3326595 can strongly suppress SARS-CoV-2 infection of host cells. Our findings suggest that as a clinical phase II drug for several kinds of cancers, GSK3326595 is a promising candidate to decrease SARS-CoV-2 infection by inhibiting ACE2 methylation and ACE2-Spike1 interaction.

Tripartite motif-containing 21 (TRIM21) has been reported to have a cancer-promoting or anticancer effect in various tumors; however, its role in ovarian cancer (OC) remains to be elucidated. In this study, we explored the biological function of TRIM21 in OC progression and investigated the potential mechanisms. We found that TRIM21 was remarkably decreased in OC tissues and cell lines compared with adjacent-cancerous tissues and normal ovarian epithelium cell. Decreased expression of TRIM21 in OC patients was significantly correlated with shorter overall and disease-specific survival by The Cancer Genome Atlas database (TCGA) analysis. Functional assays revealed that TRIM21 inhibited the migration and invasion of OC cells; and that TRIM21 also obviously impaired cell proliferation by inhibiting cell cycle progression

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.

Heterogeneous information network (HIN)-structured data provide an effective model for practical purposes in real world. Network embedding is fundamental for supporting the network-based analysis and prediction tasks. Methods of network embedding that are currently popular normally fail to effectively preserve the semantics of HIN. In this study, we propose AGA2Vec, a generative adversarial model for HIN embedding that uses attention mechanisms and meta-paths. To capture the semantic information from multi-typed entities and relations in HIN, we develop a weighted meta-path strategy to preserve the proximity of HIN. We then use an autoencoder and a generative adversarial model to obtain robust representations of HIN. The results of experiments on several real-world datasets show that the proposed approach outperforms state-of-the-art approaches for HIN embedding.

Tripartite motif-containing 21 (Trim21) is mainly involved in antiviral responses and autoimmune diseases. Although Trim21 has been reported to have a cancer-promoting or anticancer effect in various tumours, its role in renal cell cancer (RCC) remains to be elucidated. In this study, we demonstrate that Trim21 is downregulated in primary RCC tissues. Low Trim21 expression in RCC is correlated with poor clinicopathological characteristics and short overall survival. Moreover, we illustrate that Trim21 inhibits RCC cells glycolysis through the ubiquitination-mediated degradation of HIF-1α, which inhibits the proliferation, tumorigenesis, migration, and metastasis of RCC cells in vitro and in vivo. Our findings show that Trim21 may become a promising predictive biomarker for the prognosis of patients with RCC.

Tumor-associated macrophages (TAMs) are important monocytes in the breast cancer microenvironment. They facilitate the distant metastasis of breast cancer. However, the detailed mechanisms of TAM-derived cancer metastasis have not been clearly elucidated. Here, we demonstrate that PRMT1 is essential for TAM-mediated breast cancer cell migration and metastasis. TAMs increase EZH2 stability by stimulating PRMT1-mediated meR342-EZH2 formation through the secretion of interleukin-6 (IL-6) cytokine. Moreover, high expression levels of TAMs are positively correlated with PRMT1, meR342-EZH2, and EZH2 expression in breast cancer patients. Our study presents a novel mechanism of TAM-induced breast cancer metastasis via the IL-6-PRMT1-meR342-EZH2 axis.

The treatment of cancer has made great progress. However, drug resistance remains problematic. Multiple physiologic processes of tumor development can be dominated by central and sympathetic nervous systems. The interactions between the nervous system, immune system, and tumor occur consistently and dynamically. Recent evidence suggests that nerves and neural signals are intimately involved in the development of resistance to cancer therapies. In this review, we will provide an overview of the recent progress in this rapidly growing area and discuss the potential new strategies for targeting the neural signaling pathway to improve the effectiveness of chemotherapies, targeted therapies, and immunotherapies.

A diode-pumped Tm,Ho:YAP laser utilizing a self-made LiNbO 3 (LN) electro-optically modulator (EOM) at room temperature is demonstrated for the first time. A minimum pulse duration of 107.4 ns was obtained at a pulse repetition rate (PRR) of 200 Hz, giving a maximum single pulse energy of 1.65 mJ. At a PRR of 1 kHz, pulse duration of 145.8 ns was achieved under the absorbed pump power of 7.4 W, corresponding to a maximum single pulse energy of 0.546 mJ, and the pulse to pulse amplitude instabilities were measured to be about 4.6% and 5.83% for PRRs of 200 Hz and 1 kHz, respectively.

Traditional Chinese medicine (TCM) is a highly important complement to modern medicine and is widely practiced in China and in many other countries. For TCM, herbal therapies are generally formula based, and individual herbs are rarely used. Unfortunately, due to the empirical nature of TCM, effective diagnosis and prescription methods are not well defined. 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. 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.

Proinflammatory macrophage (M1) is now being suggested as a potential therapeutic strategy for cancer because of its tumoricidal capacity. However, few studies have been focused directly on the effects of M1 macrophages on cancer cells. Here, we found that M1 induced a subpopulation of CD44high/CD24-/low or ALDH1+ cells with CSC-like phenotypes from different types of breast cancer cells (BCCs) in a paracrine manner. Stat3/NF-κB pathways in BCCs were activated by proinflammatory cytokines, igniting Lin-28B-let-7-HMGA2 axis to induce CSC through epithelial-mesenchymal transition (EMT). Previously, we reported that Stat3-coordinated Lin-28B-let-7-HMGA2 axis initiated EMT in BCCs. Here, inhibition of Stat3/NF-κB pathways or Lin-28B-let-7-HMGA2 axis suppressed EMT/CSCs program. Notably, HMGA2 knockdown directly repressed M1-induced CSC formation and expression of Klf-4 and Nanog. Meanwhile, prolonged coculture with BCCs endowed M1 with M2 properties. M1 supernatant induced CSC from non-stem cancer cells, while M2 supernatant sustained a higher proportion of ALDH1+ cells. Our data suggest that macrophages might modulate CSC formation and maintenance by transferring between M1/M2 phenotype. Given that M1 are being considered as a promising immunotherapy tool, it is important to inhibit their CSC-inducing potential by targeting key molecules and pathways.

An electro-optical modulator (EOM) made of a z -cut LiNbO 3 (LN) crystal with size of 9×9×25 mm 3 was designed to work in transverse-field regime. The extinction ratio of the EOM was measured to be 324:1. With the EOM operating in off Q-switching regime, a diode pumped all-solid-state actively Q-switched Tm:LuAG laser at 2 μm was realized. At repetition rate of 200 Hz, 2.5 mJ pulses with duration of 88.2 ns were generated. A maximum pulse energy of 2.51 mJ was achieved at repetition rate of 50 Hz, corresponding to a minimum pulse duration of 88 ns.

We report the first demonstration of a diode-pumped passively Q-switched Nd:LuAG laser with a multi-walled carbon nanotube (MWCNT) as saturable absorber. A maximum average output power of 844 mW and pulses as short as 78 ns under a repetition rate of about 100 kHz were generated. A MWCNT Q-switched Nd:YAG laser was comparatively investigated, in comparison with which the Nd:LuAG laser showed lower threshold absorbed pump power and higher pulse energy, indicating a better energy storage ability of Nd:LuAG crystal than Nd:YAG.

We have investigated the passive q-switching characteristics of graphene oxide (go) and single walled carbon nanotubes (swcnts) d2o (heavy water, deuteroxide) based on a diode-pumped yvo4/nd:yvo4 laser for the first time as far as we know. by using 20 mg/10 ml go d2o dispersion, pulses with minimum duration of 344 ns under a repetition rate of 550 khz were obtained. with 0.3 mg/10 ml swcnts d2o dispersion, a maximum pulse energy of 1.2 mu j with duration of 530 ns was achieved at a repetition rate of 178 khz. (c) 2014 elsevier b.v. all rights reserved.

We report the characteristics of a diode-pumped continuous-wave (CW) and passively Q-switched Nd:LuAG laser emitting 1.3 μm wavelength. A maximum average output power of 954 mW was obtained under CW operation, giving a slope efficiency of 14.7%. With an V3+:YAG crystal wafer employed as saturable absorber, the passively Q-switched Nd:LuAG laser produced a minimum pulse duration of 17 ns under a repetition rate of 8 kHz, and a maximum single pulse energy of 18.9 μJ. A rate equation model is introduced to theoretically analyze the results obtained in the experiment, in which the Gaussian spatial distribution of the intracavity photon density and the longitudinal distribution of the photon density along the cavity axis are taken into account. The results of numerical calculations of the rate equations are consistent with the experimental results. The results indicated the Nd:LuAG crystal as a promising gain medium for achieving short pulses with high energy at 1.3 μm.