Construction of an M2 macrophage-related prognostic model in hepatocellular carcinoma

BackgroundM2 macrophages play a crucial role in promoting tumor angiogenesis and proliferation, as well as contributing to chemotherapy resistance and metastasis. However, their specific role in the tumor progression of hepatocellular carcinoma (HCC) and their impact on the clinical prognosis remain to be further elucidated.Materials and methodsM2 macrophage-related genes were screened using CIBERSORT and weighted gene co-expression network analysis (WGCNA), while subtype identification was performed using unsupervised clustering. Prognostic models were constructed using univariate analysis/least absolute shrinkage selector operator (LASSO) Cox regression. In addition, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and mutation analysis were used for further analysis. The relationship between the risk score and tumor mutation burden (TMB), microsatellite instability (MSI), the efficacy of transcatheter arterial chemoembolization (TACE), immunotype, and the molecular subtypes were also investigated. Moreover, the potential role of the risk score was explored using the ESTIMATE and TIDE (tumor immune dysfunction and exclusion) algorithms and stemness indices, such as the mRNA expression-based stemness index (mRNAsi) and the DNA methylation-based index (mDNAsi). In addition, the R package “pRRophetic” was used to examine the correlation between the risk score and the chemotherapeutic response. Finally, the role of TMCC1 in HepG2 cells was investigated using various techniques, including Western blotting, RT-PCR and Transwell and wound healing assays.ResultsThis study identified 158 M2 macrophage-related genes enriched in small molecule catabolic processes and fatty acid metabolic processes in HCC. Two M2 macrophage-related subtypes were found and a four-gene prognostic model was developed, revealing a positive correlation between the risk score and advanced stage/grade. The high-risk group exhibited higher proliferation and invasion capacity, MSI, and degree of stemness. The risk score was identified as a promising prognostic marker for TACE response, and the high-risk subgroup showed higher sensitivity to chemotherapeutic drugs (e.g., sorafenib, doxorubicin, cisplatin, and mitomycin) and immune checkpoint inhibitor (ICI) treatments. The expression levels of four genes related to the macrophage-related risk score were investigated, with SLC2A2 and ECM2 showing low expression and SLC16A11 and TMCC1 exhibiting high expression in HCC. In vitro experiments showed that TMCC1 may enhance the migration ability of HepG2 cells by activating the Wnt signaling pathway.ConclusionWe identified 158 HCC-related M2 macrophage genes and constructed an M2 macrophage-related prognostic model. This study advances the understanding of the role of M2 macrophages in HCC and proposes new prognostic markers and therapeutic targets

Research Frontier of Accurate Diagnosis and Treatment Guided by Molecular Typing of Hepatocellular Carcinoma

Liver cancer will continue to be a major disease threatening the lives and health of our people in the next few decades. In recent years, with the development of early diagnosis and treatment of liver cancer, precise liver resection, and the development of targeted and immunotherapeutic drugs, the survival rate of liver cancer patients has been improved. Nevertheless, due to the high heterogeneity of liver cancer, patients with liver cancer in the same clinical stage still have great differences in response to treatment and prognosis. New staging and classification indicators are urgently needed to facilitate accurate diagnosis and treatment of liver cancer, so as to further improve the survival rate of patients. The continuous progress and development of multi-omics technology, single-cell technology, tumor molecular visualization technology and medical artificial intelligence, etc., make the molecular classification of liver cancer more and more approaching the true nature of tumor biological characteristics, thus contributing to the accurate diagnosis and treatment of liver cancer

RXR negatively regulates ex vivo expansion of human cord blood hematopoietic stem and progenitor cells

Ex vivo expansion of human cord blood (CB) hematopoietic stem cells (HSCs) is one approach to overcome limited numbers of HSCs in single CB units. However, there is still no worldwide acceptable HSC ex vivo expansion system. A main reason is that we still have very limited knowldege regarding mechanisms underlying maintenance and expansion of CB HSCs. Here we report that retinoid X receptor (RXR) activity is of significance for CB HSC ex vivo expansion. RXR antagonist HX531 significantly promoted ex vivo expansion of CB HSCs and progenitor cells (HPCs). RXR agonist Bexarotene notably suppressed ex vivo expansion of CB HSCs. Activation of RXR by Bexarotene significantly blocked expansion of phenotypic HSCs and HPCs and expressed increased functional HPCs as assessed by colony formation induced by UM171 and SR1. In vivo transplantation experiments in immune-deficient mice demonstrated that HX531 expanded CB HSCs possess long-term reconstituting capacities, and Bexarotene treatment inhibited expansion of functional CB HSCs. RNA-seq analysis revealed that RXR regulates expression of FBP1 (a negative regulator of glucose metabolism) and many genes involved in differentation. ECAR analysis showed that HX531 significantly promoted glycolytic activity of CB CD34+ HSCs and HPCs. Our studies suggest that RXR is a negative regulator of ex vivo expansion of CB HSCs and HPCs

Direct observation of spin polarization in epitaxial Fe3O4(001)/MgO thin films grown by magnetron sputtering

We obtained epitaxial single-crystal Fe3O4(001)/MgO(001) thin films by magnetron sputtering. The high quality of the grown Fe3O4 films was confirmed by reflection high-energy electron diffraction and x-ray photoelectron spectroscopy. Atomic magnetic properties of Fe3O4(001)/MgO(001) were investigated using vibrating sample magnetometry and x-ray magnetic circular dichroism. The values of saturation magnetization and magnetic moment are 407 ± 5 emu/cm3 (3.26 ± 0.04 μ B / (f. u.)) and 3.31 ± 0.15 μ B / (f. u.), respectively, in the Fe3O4 film as thin as 5 nm, which are close to the bulk values. The spin polarization was directly measured using spin-resolved photoemission spectroscopy. The measured spin polarization has a maximum value of -42% ± 3%, which is comparable to the theoretical value for the (2 × 2)R45° reconstructed Fe3O4(001) surface. Furthermore, the film thickness-dependent measurements indicate that the anti-phase boundaries significantly decrease the spin polarization rather than the lattice mismatch. Our results demonstrate that epitaxial Fe3O4(001)/MgO thin films grown by magnetron sputtering have desired magnetic properties, facilitating the potential application of Fe3O4-based spintronic devices

Characterization of LIMA1 and its emerging roles and potential therapeutic prospects in cancers

Actin is the most abundant and highly conserved cytoskeletal protein present in all eukaryotic cells. Remodeling of the actin cytoskeleton is controlled by a variety of actin-binding proteins that are extensively involved in biological processes such as cell motility and maintenance of cell shape. LIM domain and actin-binding protein 1 (LIMA1), as an important actin cytoskeletal regulator, was initially thought to be a tumor suppressor frequently downregulated in epithelial tumors. Importantly, the deficiency of LIMA1 may be responsible for dysregulated cytoskeletal dynamics, altered cell motility and disrupted cell-cell adhesion, which promote tumor proliferation, invasion and migration. As research progresses, the roles of LIMA1 extend from cytoskeletal dynamics and cell motility to cell division, gene regulation, apical extrusion, angiogenesis, cellular metabolism and lipid metabolism. However, the expression of LIMA1 in malignant tumors and its mechanism of action have not yet been elucidated, and many problems and challenges remain to be addressed. Therefore, this review systematically describes the structure and biological functions of LIMA1 and explores its expression and regulatory mechanism in malignant tumors, and further discusses its clinical value and therapeutic prospects

The emerging roles of circHECTD1 in human diseases and the specific underlying regulatory mechanisms

Circular RNAs (circRNAs) are a class of single-stranded closed-loop RNAs that have become a popular research subject in biology. Compared to linear RNAs, they are more stable, more conserved, and more widely distributed, and they play crucial biological functions in many diseases. CircHECTD1, a newly identified member of the circRNA family, is widely distributed in humans. Recent studies have shown that circHECTD1 is abnormally expressed in various human diseases, including glioma, hepatocellular carcinoma, gastric cancer, acute ischaemic stroke, silicosis, acute lung injury, ulcerative colitis, atherosclerosis, and hypertrophic scarring. In malignant tumours, circHECTD1 is thought to be an oncogene that promotes malignant tumour behaviours and influences tumour prognosis. In nontumour diseases, it plays a dual role, promoting disease in silicosis, stroke, and other diseases, while alleviating the disease process in ulcerative colitis, acute lung injury, and atherosclerosis. This article provides a review of the regulatory roles and mechanisms of action of circHECTD1 in different diseases. We also discuss and prospectively evaluate the clinical potential of circHECTD1 as a diagnostic biomarker and a therapeutic target for related diseases, providing new insights for developing new therapeutic strategies

A simultaneous power and data transmission technology based on coil multiplexing in domino-resonator WPT systems

To achieve parallel power and data transmission in domino-resonator wireless power transfer (WPT) systems, a novel simultaneous power, and data transfer (SPDT) technology based on coil multiplexing is proposed in this letter. Benefiting from the magnetic field characteristics of the bipolar coil structure, the power and data can be injected into multiplexed coils with different flow directions, leading to opposite induced voltage polarities in each coupling coil. Subsequently, a corresponding resonator circuit is developed to form independent power and data resonance loops. In addition, an injected data transmission scheme is developed for domino-resonator WPT systems. Compared with traditional SPDT methods, additional wave trappers and coupling structures are avoided by this proposed technology, and the interference between power and data transfer is significantly eliminated. A 23.6 W laboratory prototype with five domino resonators is built to validate the feasibility of this proposed technology. The experimental results show that the power transfer efficiency reaches 70% at 50 kb/s data transfer rate. © 1986-2012 IEEE

A reconfigurable rectifier-based power improving method of free-standing two-coil magnetic field energy harvesters over a wide load range

Free-standing magnetic field energy harvesters (FSMFEHs) have promising potential in charging sensors used in electrical power grids. The output power of the FSMFEH is highly dependent on the load resistance. However, the load resistance of the sensors varies over a wide range during the operation process. Therefore, a crucial challenge for an FSMFEH system is to maintain high output power over a wide load range. In this letter, an innovative reconfigurable rectifier-based FSMFEH system with two coils connected in parallel is proposed. First, a new structure of two identical coils in parallel is proposed in magnetic energy harvesting applications. Then, a reconfigurable rectifier with two operation modes is developed to incorporate the new coil structure. By switching between the full-bridge mode and the half-bridge mode according to the actual load demand, the proposed FSMFEH can maintain high output power over a wide load range. In addition, the mode transition can be easily achieved by shorting one of the diodes, leading to a simple and low-loss control. The effectiveness of the proposed FSMFEH system is verified based on a laboratory prototype. It is provided that the experimental result is consistent with the theoretical analysis. The output power can be maintained above 8.19 mW within the 50-150

Clinical Effect of Preservation or Nonpreservation of Left Colic Artery in Total Mesorectal Excision under Laparoscopy: A Meta-analysis

Background and Aims. To investigate the clinical effect of preservation or nonpreservation of the left colic artery (LCA) in total mesorectal excision (TME) under laparoscopy. Methods. The words, like “rectal cancer,” “left colonic artery,” and “laparoscopy,” were used as the retrieval terms, and the keyword retrieval method was adopted. The retrieval period was set as from January 1, 2013, to June 1, 2018. We searched databases including PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) to collect randomized and controlled trials which compared the effect of preservation or nonpreservation of the LCA in TME under laparoscopy. Two researchers independently carried out literature screening, data extraction, and literature quality evaluation; Review Manager 5.3 was used for the meta-analysis. Results. Seven studies including 1467 cases were identified for the meta-analysis. As showed by the meta-analysis, compared with the LCA nonpreservation group, the LCA preservation group had significantly reduced incidence of anastomotic leakage (OR=0.44, CI=0.30,0.65, P<0.0001) and postoperative urinary and sexual dysfunction (OR=0.26, CI=0.09,0.78, P=0.02) and significantly shorter time for intestinal function recovery (WMD=−0.26, CI=−0.41,−0.11, P=0.0008). There were no significant differences between the two groups in the duration of surgery, blood loss, number of dissected lymph nodes, or postoperative hospital stay. Conclusions. From the results, the LCA preservation group seems to achieve comparable success with acceptable safety outcomes. Therefore, this surgical method can be recommended in the clinical practice