Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure.

There is a regional preference around lymph nodes (LNs) for adipose beiging. Here, we show that local LN removal within inguinal white adipose tissue (iWAT) greatly impairs cold-induced beiging, and this impairment can be restored by injecting M2 macrophages or macrophage-derived C-C motif chemokine (CCL22) into iWAT. CCL22 injection into iWAT effectively promotes iWAT beiging, while blocking CCL22 with antibodies can prevent it.

Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity.

Background: Mitochondrial dysfunction is a primary driver of cardiac contractile failure; yet, the cross talk between mitochondrial energetics and signaling regulation remains obscure. Ponatinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia, is among the most cardiotoxic tyrosine kinase inhibitors and causes mitochondrial dysfunction. Whether ponatinib-induced mitochondrial dysfunction triggers the integrated stress response (ISR) to induce ponatinib-induced cardiotoxicity remains to be determined.

Long non-coding RNA regulates cardiomyocyte differentiation through H2A.Z-mediated LHX1 transcriptional activation.

Long non-coding RNAs (lncRNAs) play widespread roles in various processes. However, there is still limited understanding of the precise mechanisms through which they regulate early stage cardiomyocyte differentiation. In this study, we identified a specific lncRNA called , which is transcribed from a bidirectional promoter of LIM Homeobox 1 (LHX1) gene.

PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.

Background: Atrial fibrillation (AF)-the most common sustained cardiac arrhythmia-increases thromboembolic stroke risk 5-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C (protein phosphatase 1 regulatory subunit 12C)-the PP1 (protein phosphatase 1) regulatory subunit targeting MLC2a (atrial myosin light chain 2)-causes hypophosphorylation of MLC2a and results in atrial hypocontractility.

Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.

Aims: Novel cancer therapies leading to increased survivorship of cancer patients have been negated by a concomitant rise in cancer therapies-related cardiovascular toxicities. Sunitinib, a first line multi-receptor tyrosine kinase inhibitor, has been reported to cause vascular dysfunction although the initiating mechanisms contributing to this side effect remain unknown. Long non-coding RNAs (lncRNAs) are emerging regulators of biological processes in endothelial cells (ECs); however, their roles in cancer therapies-related vascular toxicities remain underexplored.

Myosin Light Chain Dephosphorylation by PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.

Background: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, increases thromboembolic stroke risk five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C, the PP1 regulatory subunit targeting atrial myosin light chain 2 (MLC2a), causes hypophosphorylation of MLC2a and results in atrial hypocontractility.

Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance.

Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance.

Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance.

Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance.

3D multi-view squeeze-and-excitation convolutional neural network for lung nodule classification.

Purpose: Early screening is crucial to improve the survival rate and recovery rate of lung cancer patients. Computer-aided diagnosis system (CAD) is a powerful tool to assist clinicians in early diagnosis. Lung nodules are characterized by spatial heterogeneity.

Alteration of the N-methyladenosine epitranscriptomic profile in synthetic phthalate-treated human induced pluripotent stem cell-derived endothelial cells.

This study aimed to characterize the N-methyladenosine epitranscriptomic profile induced by mono(2-ethylhexyl) phthalate (MEHP) exposure using a human-induced pluripotent stem cell-derived endothelial cell model. A multiomic approach was employed by performing RNA sequencing in parallel with an N-methyladenosine-specific microarray to identify mRNAs, lncRNAs, and miRNAs affected by MEHP exposure. An integrative multiomic analysis identified relevant biological features affected by MEHP, while functional assays provided a phenotypic characterization of these effects.

[Research on classification of benign and malignant lung nodules based on three-dimensional multi-view squeeze-and-excitation convolutional neural network].

Lung cancer is the most threatening tumor disease to human health. Early detection is crucial to improve the survival rate and recovery rate of lung cancer patients. Existing methods use the two-dimensional multi-view framework to learn lung nodules features and simply integrate multi-view features to achieve the classification of benign and malignant lung nodules.

ALKBH5-mediated mA mRNA methylation governs human embryonic stem cell cardiac commitment.

N6-methyladenosine (mA), as the most abundant modification of mammalian messenger RNAs, is essential for tissue development and pathogenesis. However, the biological significance of mA methylation in cardiac differentiation and development remains largely unknown. Here, we identify that the downregulation of mA demethylase ALKBH5 is responsible for the increase of mA methylation and cardiomyocyte fate determination of human embryonic stem cells (hESCs) from mesoderm cells (MESs).

Loss of mA methyltransferase METTL3 promotes heart regeneration and repair after myocardial injury.

Aims: N6-Methyladenosine (mA), one of the important epigenitic modifications, is very commom in messenger RNAs (mRNAs) of eukaryotes, and has been involved in various diseases. However, the role of mA modification in heart regeneration after injury remains unclear. The study was conducted to investigate whether targeting methyltransferase-like 3 (METTL3) could replenish the loss of cardiomyocytes (CMs) and improve cardiac function after myocardial infarction (MI).

ALKBH5 regulates cardiomyocyte proliferation and heart regeneration by demethylating the mRNA of YTHDF1.

N-methyladenosine (mA) RNA modification, a dynamic and reversible process, is essential for tissue development and pathogenesis. However, the potential involvement of mA in the regulation of cardiomyocyte (CM) proliferation and cardiac regeneration remains unclear. In this study, we aimed to investigate the essential role of mA modification in heart regeneration during postnatal and adult injury.

Melatonin promotes cardiomyocyte proliferation and heart repair in mice with myocardial infarction via miR-143-3p/Yap/Ctnnd1 signaling pathway.

The neonatal heart possesses the ability to proliferate and the capacity to regenerate after injury; however, the mechanisms underlying these processes are not fully understood. Melatonin has been shown to protect the heart against myocardial injury through mitigating oxidative stress, reducing apoptosis, inhibiting mitochondrial fission, etc. In this study, we investigated whether melatonin regulated cardiomyocyte proliferation and promoted cardiac repair in mice with myocardial infarction (MI), which was induced by ligation of the left anterior descending coronary artery.

Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity.

Ribavirin has been proven to be an antiviral treatment, whereas there are still risks of hemolysis and congenital malformation. Abnormal cardiac development contributes to the occurrence and development of many heart diseases. However, there is so far no evidence that ribavirin induces human cardiac developmental toxicity.

Iron overload inhibits self-renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species.

Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ferric ammonium citrate (FAC) in a concentration-dependent manner. In addition, deferoxamine protected hESCs/hiPSCs against FAC-induced cell-cycle arrest.

Targeting LncDACH1 promotes cardiac repair and regeneration after myocardium infarction.

Neonatal mammalian heart maintains a transient regeneration capacity after birth, whereas this regeneration ability gradually loses in the postnatal heart. Thus, the reactivation of cardiomyocyte proliferation is emerging as a key strategy for inducing heart regeneration in adults. We have reported that a highly conserved long noncoding RNA (lncRNA) LncDACH1 was overexpressed in the failing hearts.

YAP/TEAD3 signal mediates cardiac lineage commitment of human-induced pluripotent stem cells.

Cardiomyocytes differentiated from human-induced pluripotent stem cells (hiPSCs) hold great potential for therapy of heart diseases. However, the underlying mechanisms of its cardiac differentiation have not been fully elucidated. Hippo-YAP signal pathway plays important roles in cell differentiation, tissue homeostasis, and organ size.

Human induced pluripotent stem cell line HMUi001-A derived from corneal stromal cells.

A human corneal stroma induced pluripotent stem cell (HMUi001-A) line was created from primary cultured human corneal fibroblasts. Reprogramming was performed using episomal vector delivery of OCT4, SOX2, KLF4, L-MYC and LIN28. Further characterization of the HMUi001-A confirmed that the cell line was pluripotent, free from Epstein Barr viral genome, and retained normal karyotype.

Irradiation-induced dynamic changes of gene signatures reveal gain of metastatic ability in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC), arising from the nasopharynx epithelium, is prevalent among South and East Asia. The radiotherapy is the primary treatment for NPC patients. However, the acquired radioresistance dramatically diminishes the therapeutic effect of radiotherapy.

Arsenic trioxide blocked proliferation and cardiomyocyte differentiation of human induced pluripotent stem cells: Implication in cardiac developmental toxicity.

Arsenic trioxide (ATO) has been recommended as the first-line agent for the treatment of acute promyelocytic leukaemia (APL), due to its substantial anticancer effect. Numerous clinical reports have indicated that ATO is a developmental toxicant which can result in birth defects of human beings. But whether arsenic trioxide can lead to human cardiac developmental toxicity remains largely unknown.

The Long Non-coding RNA-ORLNC1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Fate.

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts or adipocytes, and the shift between osteogenic and adipogenic differentiation determines bone mass. The aim of this study was to identify whether lncRNAs are involved in the differentiation commitment of BMSCs during osteoporosis. Here, we found ORLNC1, a functionally undefined lncRNA that is highly conserved, which exhibited markedly higher expression levels in BMSCs, bone tissue, and the serum of OVX-induced osteoporotic mice than sham-operated counterparts.

Iron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids-Epigenetic Circuit.

Iron homeostasis is crucial for a variety of biological processes, but the biological role of iron homeostasis in pluripotent stem cells (PSCs) remains largely unknown. The present study aimed to determine whether iron homeostasis is involved in maintaining the pluripotency of human PSCs (hPSCs). We found that the intracellular depletion of iron leads to a rapid downregulation of NANOG and a dramatic decrease in the self-renewal of hPSCs as well as spontaneous and nonspecific differentiation.

Potential Applications of Induced Pluripotent Stem Cells for Cardiovascular Diseases.

Owning the high incidence and disability rate in the past decades, to be expected, cardiovascular diseases (CVDs) have become one of the leading death causes worldwide. Currently, induced pluripotent stem cells (iPSCs), with the potential to form fresh myocardium and improve the functions of damaged hearts, have been studied widely in experimental CVD therapy. Moreover, iPSC-derived cardiomyocytes (CMs), as novel disease models, play a significant role in drug screening, drug safety assessment, along with the exploration of pathological mechanisms of diseases.