Single or double lipid-modified ultra-short antimicrobial peptides for treating infections caused by resistant bacteria.

Unmodified ultra-short antimicrobial peptides (AMPs) have difficulty attaining high antimicrobial activity and low toxicity concurrently. Our previous studies have shown that single-site lipid modification can enhance the antimicrobial activity of AMPs. However, research on multi-site modification is scarce.

The novel β-hairpin antimicrobial peptide D-G(RF)3 demonstrates exceptional antibacterial efficacy.

The clinical application of most natural antimicrobial peptides (AMPs) is hindered by their lack of a synergistic combination of high antibacterial efficacy, low toxicity, and stability, necessitating frequent complex modifications that incur significant labor and economic costs. Therefore, it is imperative to optimize the antibacterial properties of AMPs using some simplified approach. In this study, we designed a library of β-hairpin AMPs with identical β-turn sequences (-D-Pro-Gly-) and varying repetition units (IR, FR, and WK).

Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing.

While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile.

Stabilized Cell Membrane-Derived Vesicles by Lipid Anchoring for Enhanced Drug Delivery.

A cell membrane-derived vesicle (MV) that has cell-mimicking features with characteristic functionalities holds vast appeal for biomimetic nanomedicine and drug delivery but suffers from a major limitation of innate fragility and poor stability. Herein, we report a lipid-anchoring strategy for stabilizing MV for enhanced drug delivery. An array of amphiphilic mono-acyl phosphatidylcholines (MPCs) with specific hydrophobic moieties are synthesized and readily engineered on MV based on their commendable aqueous solubility and efficient membrane insertability.

Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function.

A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21 (p21) improves cardiac and metabolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the health and physical function of these mice monthly until death, we show that clearance of p21 cells improves physical function at all remaining stages of life, suggesting healthspan extension.

Cellular Senescence as a Targetable Risk Factor for Cardiovascular Diseases: Therapeutic Implications: Family Series.

The prevalence of cardiovascular diseases markedly rises with age. Cellular senescence, a hallmark of aging, is characterized by irreversible cell cycle arrest and the manifestation of a senescence-associated secretory phenotype, which has emerged as a significant contributor to aging, mortality, and a spectrum of chronic ailments. An increasing body of preclinical and clinical research has established connections between senescence, senescence-associated secretory phenotype, and age-related cardiac and vascular pathologies.

LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity.

Cellular senescence is associated with pleiotropic physiopathological processes, including aging and age-related diseases. The persistent DNA damage is a major stress leading to senescence, but the underlying molecular link remains elusive. Here, we identify La Ribonucleoprotein 7 (LARP7), a 7SK RNA binding protein, as an aging antagonist.

LARP7 Protects Against Heart Failure by Enhancing Mitochondrial Biogenesis.

Background: Heart failure (HF) is among the leading causes of morbidity and mortality, and its prevalence continues to rise. LARP7 (La ribonucleoprotein domain family member 7) is a master regulator that governs the DNA damage response and RNAPII (RNA polymerase II) pausing pathway, but its role in HF pathogenesis is incompletely understood.

Methods: We assessed LARP7 expression in human HF and in nonhuman primate and mouse HF models.

L ARP7 Is a BRCA1 Ubiquitinase Substrate and Regulates Genome Stability and Tumorigenesis.

Attenuated DNA repair leads to genomic instability and tumorigenesis. BRCA1/BARD1 are the best-known tumor suppressors that promote homology recombination (HR) and arrest cell cycle. However, it remains ambiguous whether and how their E3 ligase activity regulates HR.

Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis.

The bivalent domain (BD) at promoter region is an unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of BDs in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA (vascular endothelial growth factor A) stimulation, we discovered that BDs are widespread in endothelial cells and preferentially marked genes responsive to VEGFA.

A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA.

Cell behaviors are dictated by epigenetic and transcriptional programs. Little is known about how extracellular stimuli modulate these programs to reshape gene expression and control cell behavioral responses. Here, we interrogated the epigenetic and transcriptional response of endothelial cells to VEGFA treatment and found rapid chromatin changes that mediate broad transcriptomic alterations.