Lactylation-driven molecular taxonomy of melanoma: linking epigenetic modifications to immune evasion and clinical outcomes.

Lactylation, a post-translational modification derived from elevated lactate levels, has gained attention as a potential regulator of melanoma's tumor metabolism and immune responses. Here, we combined single-cell RNA sequencing and bulk transcriptome profiling of cutaneous melanoma samples to establish a lactation-centric prognostic model. Our analyses revealed melanocytes as the most acetylation-enriched cell population and identified a six-gene lactylation signature that stratified patients into high- and low-risk groups with distinct survival outcomes.

Ertugliflozin induces vasodilation by inhibiting AMPK-mediated mitochondrial fission in vascular smooth muscle cells.

Hypertension is a primary risk factor for cardiovascular disease. Recently, Ertugliflozin (Ertu), a new sodium-glucose cotransporter-2 (SGLT2) inhibitor, though primarily approved by the FDA as an antidiabetic agent, has been reported to lower blood pressure. However, whether Ertu directly regulates the contractility of arteries remains unknown.

A critical role for IL-21/IL-21 receptor signaling in isoproterenol-induced cardiac remodeling.

Increased cytokine secretion from immune cells is often associated with cardiac remodeling and heart failure due to pressure overload. Several reports suggest that the IL-21/IL-21 receptor (IL-21R) signaling pathway may play a critical role in heart failure progression, but the exact mechanism remains unclear. In this study, isoproterenol (ISO) was used to induce heart failure in mice and found that ISO injection caused significant upregulation of IL-21 and the IL-21R in the heart of mice.

Inhibition of CAV1 attenuates diabetic cardiomyopathy through reducing ferroptosis via activating NRF2/GCLC signaling pathway.

: Diabetic cardiomyopathy (DCM), a prevalent complication of diabetes, is a major cause of heart failure and death among patients with diabetes. However, the pathological mechanisms underlying the development of DCM remain unclear. This study aims to investigate the role and underlying mechanisms of caveolin-1 (CAV1) in DCM.

Single-cell profiling reveals monocyte heterogeneity and association with liver fibrosis in patients with chronic HBV.

Background: Chronic hepatitis B (CHB) infection results in persistent liver inflammation, which ultimately leads to liver fibrosis and increases the risk of cirrhosis. Recruitment of circulating monocytes to the liver is an essential aspect that exacerbates liver fibrosis; however, the mechanism underlying their dysregulation, which contributes to this progression, remains unclear.

Methods: Single-cell RNA sequencing was performed to characterize the landscape of circulating monocytes from patients with CHB and liver fibrosis (CHB group) and healthy controls (HC group).

Beta-catenin/sirtuin 1/farnesoid X receptor pathway promotion of portal vein ligation and parenchymal transection-induced rapid liver regeneration.

Background: By accelerating the regeneration of the future liver remnant, portal vein ligation and parenchymal transection allows for more extensive hepatectomy. Given that the mechanism remains poorly understood, the aim of this study was to investigate the mechanism of portal vein ligation and parenchymal transection-induced liver regeneration.

Methods: A portal vein ligation and parenchymal transection-induced liver regeneration mouse model was established, followed by RNA microarray analysis to identify candidate molecules.

Exploring the protective mechanisms of syringaresinol against myocardial infarction by experimental validation and network pharmacology.

Myocardial Infarction (MI) is a leading cause of mortality worldwide. Currently, effective treatments are still lacking. Increasing evidence supports the benefits of Syringaresinol (SYR) for the treatment of cardiovascular disease is accumulating.

Cuproplasia and cuproptosis, two sides of the coin.

Copper is an essential micronutrient in the human body, mainly acting as a crucial cofactor required for a wide range of physiological processes across nearly all cell types. Recent advances revealed that tumor cells seize copper to fulfill their rapid proliferation, metastasis, immune evasion, and so on by reprogramming the copper regulatory network, defined as cuproplasia. Thus, targeting copper chelation to reduce copper levels has been considered a rational tumor therapy strategy.

Low contact resistance in carbon nanotube devices: metal-induced gap states.

Designing devices with low contact resistance, especially those based on carbon-based materials, is becoming increasingly important. In this work, we investigated the electronic structure and transport properties of two-types of structures based on carbon nanotubes connecting graphene electrodes by combining density functional theory with the non-equilibrium Green's function method. The directly connected structure exhibits ohmic contact and has a lower contact resistance compared to the typical van der Waals-connected structure.

Impaired cyclin D3 protein degradation contributes to trastuzumab resistance in HER2 positive breast cancer.

As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance.

NiS/NiS/MnO Nanofibers with Enhanced Oxygen Evolution Reaction Activity.

The development of efficient and cost-effective electrocatalysts is crucial for achieving a green hydrogen economy through electrocatalytic water splitting. Herein, we report an excellent catalyst, one-dimensional NiS/NiS/MnO nanofibers prepared by electrospinning, which exhibits outstanding electrochemical performance in an alkaline solution. We explored effective strategies to construct one-dimensional nanostructures and composite oxides to promote the electrocatalytic performance of transition metal dichalcogenides.

The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.

Ferroptosis is an iron-dependent programmed cell death process that involves lipid oxidation via the Fenton reaction to produce lipid peroxides, causing disruption of the lipid bilayer, which is essential for cellular survival. Ferroptosis has been implicated in the occurrence and treatment response of various types of cancer, and targeting ferroptosis has emerged as a promising strategy for cancer therapy. However, cancer cells can escape cellular ferroptosis by activating or remodeling various signaling pathways, including oxidative stress pathways, thereby limiting the efficacy of ferroptosis-activating targeted therapy.

PRMT6-mediated ADMA promotes p62 phase separation to form a negative feedback loop in ferroptosis.

Due to intrinsic defensive response, ferroptosis-activating targeted therapy fails to achieve satisfactory clinical benefits. Though p62-Keap1-Nrf2 axis is activated to form a negative feedback loop during ferroptosis induction, how p62 is activated remains largely unknown. MTS assay was applied to measure cell growth.

A novel histone deacetylase inhibitor Se-SAHA attenuates isoproterenol-induced heart failure via antioxidative stress and autophagy inhibition.

Heart failure is associated with histone deacetylase (HDAC) regulation of gene expression, the inhibition of which is thought to be beneficial for heart failure therapy. Here, we explored the cardioprotective effects and underlying mechanism of a novel selenium-containing HDAC inhibitor, Se-SAHA, on isoproterenol (ISO)-induced heart failure. We found that pretreatment with Se-SAHA attenuated ISO-induced cardiac hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs).

Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF-1α/VEGF via Activating Nrf2 Antioxidant Pathway.

Scope: Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant properties. The present study focuses on exploring the effect of SYR on hyperglycemia-induced early DR as well as the underlying mechanisms.

Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway.

Aims: Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, the underlying mechanism remains unclear. The role of vascular endothelial growth factor-B (VEGF-B) in DCM is little known.

Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance.

Estrogen receptor positive (ER+) breast cancer patients exhibit poorer responsiveness to nab-paclitaxel compared to ER negative (ER-) patients, with the underlying mechanisms remaining unknown. Caveolin 1 (CAV1) is a membrane invagination protein critical for the endocytosis of macromolecules including albumin-bound chemotherapeutic agents. Here, we demonstrate that ERα limits the efficacy of nab-paclitaxel in breast cancer cells while genetic or pharmacological inhibition of ERα increased the sensitivity of ER+ breast cancer cells to nab-paclitaxel.

RNautophagic regulation of DNMT3a-dependent DNA methylation by Linc00942 enhances chemoresistance in gastric cancer.

Background: Energy balance has long been known to extend lifespans and inhibit carcinogenesis in multiple species by slowing age-related epigenetic changes while the underlying mechanisms remain largely unknown. Herein, we found that starvation activated autophagy to remodel the DNA methylation profile by inhibiting DNMT3a expression.

Methods: Illumina Infinium MethylationEPIC BeadChip and dot blot assay were performed to quantify the global DNA methylation level.

Establishment and Validation of a Nomogram Prediction Model for the Severe Acute Pancreatitis.

Background: Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis.

Methods: The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected.

Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer.

Introduction: Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, the crosstalk between cuproptosis and ferroptosis is obscure.

Materials And Methods: We analyzed the effect of ferroptosis inducers on copper ionophores-induced cell death through CCK-8 assay.

GSDME-dependent pyroptosis signaling pathway in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the serious chronic microvascular complications of diabetes, and leads to the increased morbidity and mortality in diabetic patients. Gasdermin E (GSDME)-dependent pyroptosis signaling pathway plays important roles in a variety of physiological and pathological processes. However, its role and mechanism in DN are still unclear.

HSF1 promotes CD69 Treg differentiation to inhibit colitis progression.

Regulatory T cells (Tregs) are critical for generating and maintaining peripheral tolerance. Treg-based immunotherapy is valuable for the clinical management of diseases resulting from dysregulation of immune tolerance. However, the lack of potency is a potential limitation of Treg therapy.

Syringaresinol protects against diabetic nephropathy by inhibiting pyroptosis via NRF2-mediated antioxidant pathway.

Diabetic nephropathy (DN) is one of the serious complications of diabetes that has limited treatment options. As a lytic inflammatory cell death, pyroptosis plays an important role in the pathogenesis of DN. Syringaresinol (SYR) possesses anti-inflammatory and antioxidant properties.