A homozygote mutation in RPA2 associated with bone marrow failure, immunodeficiency, and telomere biology disorder.

Telomere biology disorders (TBDs) are characterized by bone marrow failure (BMF) and dysfunctional telomeres. So far, inherited mutations in 18 genes have been identified in TBDs. Here, we describe a child presenting with early BMF, …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Aging, Faith, and Religious Coping: A Phenomenological Study of Older Adults in a Muslim Cultural Context in Turkiye.

This study explored how older adults experience aging, religious practices, and religious coping, and how faith is reconstructed in later life within a Muslim cultural context in Turkiye. Employing an interpretative phenomenological qualitative design, data …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Validating raloxifene-mediated restoration of DNMT-TET epigenetic balance in breast and lung cancer.

The aberrant DNA methylation is a characteristic feature of solid tumours, but the imbalance of DNA methyltransferases and demethylases has not been studied at the network level across breast and lung cancers. To determine the …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Dual-plane Deep Reduction Neck Lift for Cervical Lengthening in Short-neck Patients.

BACKGROUND: Short-neck morphology remains a challenging problem in cervicofacial rejuvenation because conventional neck contouring techniques do not consistently improve neck length perception. OBJECTIVES: To evaluate a dual-plane deep reduction neck lift combining complete platysma transection …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Nanotechnology in dermatologic therapy: clinical advances and emerging translational perspectives over the past decade.

Nanotechnology has been revolutionizing science for at least five decades, with continuous expansion into various medical fields and the introduction of innovative strategies for the management of cutaneous conditions, particularly over the past decade. This …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Reprogramming of Cellular Plasticity via ETS and MYC Core-regulatory Circuits During Response to MAPK Inhibition in BRAF-mutant Colorectal Cancer.

PURPOSE: Aberrant enhancer dynamics play a critical role in the initiation and progression of colorectal cancer (CRC), particularly in the BRAFV600E-mutated metastatic subtype, which uniquely exhibits a strong epigenetic phenotype. Building on this epigenetic vulnerability, …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Control theory of aging and longevity for gerotherapeutic drug discovery: state space, vector fields, modalities, safety, and the minimum safe cost of functional restoration.

Existing aging theories describe what changes with age but do not prescribe how to intervene. We propose a control-theoretic framework that is not merely descriptive but prescriptive: it specifies which intervention, at which dose and …

44 Early
Design 5
Sample 7
Peer Review 16
Replication 6
Transparency 10

Cell-based screen identifies translation state modulators that extend lifespan in D. melanogaster and C. elegans.

Aging is associated with declining mitochondrial function and translational regulation-processes modulated by interventions such as dietary restriction (DR) and cold-induced longevity (CHIL). Both DR and CHIL inhibit global protein synthesis but selectively enhance translation of …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

O-GlcNAcylation is a mitochondrial-nuclear signal that regulates passive transport through the nuclear pore complex.

The nuclear pore complex (NPC) is the single gateway between the nucleus and the cytoplasm, and in healthy cells there is a size threshold for passive diffusion across the NPC. In aging and disease, the …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

YIF1A activates mTORC1 signaling to promote cellular senescence.

The mechanistic target of rapamycin complex 1 (mTORC1) serves as a central metabolic hub that integrates nutrient signals and orchestrates cellular metabolism to regulate many fundamental cell processes. While mTORC1 activation is known to occur …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Gut microbiota dysbiosis drives depression-like behavior in adolescent rats via lysine-regulated mTOR autophagy pathway.

The prevalence of major depressive disorder (MDD) is increasing globally, particularly among adolescents. Although gut-brain axis dysfunction has been implicated in adolescent depression, the mechanisms by which gut microbiota dysbiosis drives depressive behaviors and potential …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Occurrence of Biased mTOR Signaling in Hepatocellular Carcinoma

Background: mTOR signaling promotes cell growth and anabolic processes in all eukaryotes. Hyperactivation of mTOR signaling is associated with various cancers along with hepatocellular carcinoma (HCC). HCC is a highly lethal malignancy with multiple aetiologies …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

Autologous fibroblast therapy for facial rejuvenation: A randomized open-label controlled study.

BACKGROUND: The aging process of the face is characterized by dermal thinning, loss of elasticity, and wrinkle formation. Injection of autologous micrografts containing fibroblasts (Am-FBs) has emerged as a promising regenerative technique. OBJECTIVES: This trial …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Development and Clinical Application of a Thermally Reconstructed Platelet-Rich Plasma Concentrate-Based Biofiller (ExoFiller).

AIMS AND BACKGROUND: Autologous plasma-based fillers have gained interest in regenerative aesthetics as biologically active alternatives to conventional dermal fillers. However, conventional PRP-Gel formulations may be limited by rapid degradation, variable bioactivity, and insufficient structural …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

A new compound that extends the lifespan of worms, with favorable in vitro properties and a lack of toxicity in rodents.

The development of geroprotectors, compounds that slow the biological aging process, is an important goal in modern medicine. These interventions hold the promise not only of extending lifespan, but more importantly, of extending healthspan-the period …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Personalized phosphoproteomics establish mTORC1 as a regulator of exercise-induced insulin sensitization in human skeletal muscle

Exercise enhances skeletal muscle insulin sensitivity, but the signaling mechanisms responsible are poorly understood. Understanding them may open new therapeutic avenues for individuals with limited exercise capacity. Here, we used rapamycin to inhibit mTORC1 in …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

ESCRT Machinery Dysfunction in Motor Neurone Disease: TSG101, CHMP2B, and VPS4a Differentially Regulate TDP-43 Pathology, Autophagy, and Exosome Biogenesis

Motor Neurone Disease (MND) is characterised by progressive degeneration of upper and lower motor neurons, accompanied by cytoplasmic mislocalisation and hyperphosphorylation of TDP-43, hallmarks that implicate failure of endolysosomal proteostasis. The Endosomal Sorting Complexes Required …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

Dormancy and reactivation of disseminated tumor cells: From molecular mechanisms to therapeutic implications.

Metastasis and cancer recurrence post-treatment continue to pose significant challenges to patients' long-term survival. This phenomenon can be ascribed to metastatic tumor dormancy. Dormant tumor cells, as a critical stage in malignant tumor progression, are …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Distinct Roles of Working Memory and Inhibitory Control in Speech-in-Noise Perception

Difficulty perceiving speech in noise is the primary complaint of patients seeking hearing healthcare, even absent overt losses in audiometric thresholds. Yet current clinical practice largely focuses on sensory function while ignoring the potentially outsized …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

Resistance mechanisms and therapeutic strategies after menin inhibitor failure in acute myeloid leukemia.

INTRODUCTION: Menin inhibitors, including the FDA-approved agents revumenib and ziftomenib, have emerged as transformative targeted therapies in acute myeloid leukemia (AML), particularly in KMT2A-rearranged (KMT2Ar) and NPM1-mutated (NPM1m) disease. Despite high initial response rates, durability …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10