Young, female and scientist: exploring barriers, challenges and opportunities.

Different societal, systemic and personal barriers exist at various stages along a female researcher's career that can potentially undermine their success. The equation for women to reach higher positions in STEM is a multivariable one, and while there has been considerable progress towards addressing some of these compared with the past, current solutions are inadequate and do not address all facets. Here, we asked female winners of the FEBS Open Bio poster prize about their experiences regarding barriers they have faced at the predoctoral and postdoctoral stages, their opinions on how these can be addressed and their advice to new students entering a PhD degree.

Structure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.

Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how variants contribute to the spectrum of axial skeletal disorders is not well understood.

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

Lipid-induced condensate formation from the Alzheimer's Aβ peptide triggers amyloid aggregation.

The onset and development of Alzheimer's disease is linked to the accumulation of pathological aggregates formed from the normally monomeric amyloid-β peptide within the central nervous system. These Aβ aggregates are increasingly successfully targeted with clinical therapies at later stages of the disease, but the fundamental molecular steps in early stage disease that trigger the initial nucleation event leading to the conversion of monomeric Aβ peptide into pathological aggregates remain unknown. Here, we show that the Aβ peptide can form biomolecular condensates on lipid bilayers both in molecular assays and in living cells.

Co-option of mitochondrial nucleic acid-sensing pathways by HSV-1 UL12.5 for reactivation from latent infection.

Although viruses subvert innate immune pathways for their replication, there is evidence they can also co-opt antiviral responses for their benefit. The ubiquitous human pathogen, Herpes simplex virus-1 (HSV-1), encodes a protein (UL12.5) that induces the release of mitochondrial nucleic acid into the cytosol, which activates immune-sensing pathways and reduces productive replication in nonneuronal cells.

Altered Effective Connectivity Within a Thalamocortical Corollary Discharge Network in Individuals With Schizophrenia.

Background And Hypothesis: Sequential saccade planning requires corollary discharge (CD) signals that provide information about the planned landing location of an eye movement. These CD signals may be altered among individuals with schizophrenia (SZ), providing a potential mechanism to explain passivity and anomalous self-experiences broadly. In healthy controls (HC), a key oculomotor CD network transmits CD signals from the thalamus to the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and also remaps signals from FEF to IPS.

Artificial Intelligence for Optical Coherence Tomography in Glaucoma.

Purpose: The integration of artificial intelligence (AI), particularly deep learning (DL), with optical coherence tomography (OCT) offers significant opportunities in the diagnosis and management of glaucoma. This article explores the application of various DL models in enhancing OCT capabilities and addresses the challenges associated with their clinical implementation.

Methods: A review of articles utilizing DL models was conducted, including convolutional neural networks (CNNs), recurrent neural networks (RNNs), generative adversarial networks (GANs), autoencoders, and large language models (LLMs).

Establishment of an Ex Vivo Human Corneal Endothelium Wound Model.

Purpose: A human model able to simulate the manifestation of corneal endothelium decompensation could be advantageous for wound healing and future cell therapy assessment. The study aimed to establish an ex vivo human cornea endothelium wound model where endothelium function can be evaluated by measuring corneal thickness changes.

Methods: The human cornea was maintained in an artificial anterior chamber, with a continuous culture medium infusion system designed to sustain corneal endothelium and epithelium simultaneously.

Apoptosis in Cancer Biology and Therapy.

Since its inception, the study of apoptosis has been intricately linked to the field of cancer. The term apoptosis was coined more than five decades ago following its identification in both healthy tissues and malignant neoplasms. The subsequent elucidation of its molecular mechanisms has significantly enhanced our understanding of how cancer cells hijack physiological processes to evade cell death.

Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis.

The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine cellular neighborhoods and understand their crucial roles in disease pathogenesis.

Targeting Protein-Protein Interactions in Hematologic Malignancies.

Over the last two decades, there have been extensive efforts to develop small-molecule inhibitors of protein-protein interactions (PPIs) as novel therapeutics for cancer, including hematologic malignancies. Despite the numerous challenges associated with developing PPI inhibitors, a significant number of them have advanced to clinical studies in hematologic patients in recent years. The US Food and Drug Administration approval of the very first PPI inhibitor, venetoclax, demonstrated the real clinical value of blocking protein-protein interfaces.

Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders.

Focal segmental glomerulosclerosis (FSGS) is the morphologic manifestation of a spectrum of kidney diseases that primarily impact podocytes, cells that create the filtration barrier of the glomerulus. As its name implies, only parts of the kidney and glomeruli are affected, and only a portion of the affected glomerulus may be sclerosed. Although the diagnosis is based primarily on microscopic features, patient stratification relies on clinical data such as proteinuria and etiological criteria.

Diffuse expression of p16 in pancreatic neuroendocrine tumors (PanNETs) and the association of morphology variants.

Objective: Distinguishing grade 3 pancreatic neuroendocrine tumors (PanNETs) from neuroendocrine carcinomas (PanNECs) is sometimes challenging. Recently, a diffuse p16-positive pattern was reported in PanNECs but not in grade 3 PanNETs, suggesting that p16 could help differentiate these entities. This study aimed to investigate p16 expression in PanNETs of various grades and its association with clinicopathologic features.

Integration of Gastric Cancer RNA-Seq Datasets Along With PPI Network Suggests That Nonhub Nodes Have the Potential to Become Biomarkers.

Background: The breakthrough discovery of novel biomarkers with prognostic and diagnostic value enables timely medical intervention for the survival of patients diagnosed with gastric cancer (GC). Typically, in studies focused on biomarker analysis, highly connected nodes (hubs) within the protein-protein interaction network (PPIN) are proposed as potential biomarkers. However, this study revealed an unexpected finding following the clustering of network nodes.

Educational attainment, Aβ, tau, and structural brain reserve in Alzheimer's disease.

Introduction: Alzheimer's disease (AD) patients with higher educational attainment (EA) often exhibit better cognitive function. However, the relationship among EA status, AD pathology, structural brain reserve, and cognitive decline requires further investigation.

Methods: We compared cognitive performance across different amyloid beta (Aβ) positron emission tomography (A ±) statuses and EA levels (High EA/Low EA).

CRYAB is upregulated and predicts clinical prognosis in kidney renal clear cell carcinoma.

Clear cell renal cell carcinoma (KIRC) is the most prevalent subtype of renal cell carcinoma (RCC), accounting for 70% to 80% of all RCC cases. The CRYAB (αB-crystallin) gene is broadly expressed across various human tissues, yet its role in KIRC progression remains unclear. This study aims to elucidate the function of CRYAB in KIRC progression and to assess its potential as a biomarker for early diagnosis, therapeutic targeting, and prognosis.

Effectiveness of Mobile Health-Based Gamification Interventions for Improving Physical Activity in Individuals With Cardiovascular Diseases: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Gamification refers to using game design elements in nongame contexts. Promoting physical activity (PA) through gamification is a novel and promising avenue for improving lifestyles and mitigating the advancement of cardiovascular diseases (CVDs). However, evidence of its effectiveness remains mixed.

Usage of Milan System in Risk Stratification of Submandibular Gland Fine Needle Aspiration Cytology.

Objectives: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) categorizes fine needle aspiration and cytology (FNAC) results into 6 tiers and assigns a risk of malignancy (ROM) to each category. Its utility in submandibular gland lesions remains unclear. Our article aims to study (1) the utility of the MSRSGC in classifying FNAC of submandibular gland masses, (2) describe the demographics and incidence of submandibular gland malignancy in our population, and (3) analyze the accuracy of FNAC in diagnosis of benign and malignant submandibular gland tumors.

Single-Cell Transcriptomic Analysis Reveals Biomechanical Loading-Induced Imbalance in Bone and Fat, Leading to Ossification in Lumbar Intervertebral Disc Nucleus Pulposus Degeneration.

In this study, we explored the impact of different biomechanical loadings on lumbar spine motion segments, particularly concerning intervertebral disc degeneration (IVDD). We aimed to uncover the cellular milieu and mechanisms driving ossification in the nucleus pulposus (NP) during IVDD, a process whose underlying mechanisms have remained elusive. The study involved the examination of fresh NP tissue from the L3-S1 segment of five individuals, either with IVDD or healthy.

Betaine-homocysteine methyltransferase attenuates liver ischemia-reperfusion injury by targeting TAK1.

Liver ischemia-reperfusion (IR) injury is a common complication following liver surgery, significantly impacting the prognosis of liver transplantation and other liver surgeries. Betaine-homocysteine methyltransferase (BHMT), a crucial enzyme in the methionine cycle, has been previously confirmed the pivotal role in hepatocellular carcinoma, and it has also been demonstrated that BHMT inhibits inflammation, apoptosis, but its role in liver IR injury remains unknow. Following I/R injury, we found that BHMT expression was significantly upregulated in human liver transplant specimens, mice and hepatocytes.

Transanal Minimally Invasive Surgery for a Gastrointestinal Stromal Tumor of the Lower Rectum: A Case Report.

Rectal gastrointestinal stromal tumors (GISTs) are prevalent in the lower rectum, and the existing literature suggests that transanal interventions are advantageous for anorectal preservation. Herein, we present a case of rectal GIST resection using transanal minimally invasive surgery. A 75-year-old woman reported vaginal discomfort and was subsequently diagnosed with GIST via transanal tumor biopsy.

Indole-3-Lactic Acid Inhibits Doxorubicin-Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway.

The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which is primarily attributed to its interaction with iron in mitochondria, leading to lipid peroxidation and myocardial ferroptosis. This study aimed to investigate the role of the gut microbiota-derived metabolite, indole-3-lactic acid (ILA), in mitigating DOX-induced cardiotoxicity (DIC). Cardiac function, pathological changes, and myocardial ferroptosis were assessed in vivo.

Simvastatin-Induced Ferroptosis in Orbital Fibroblasts in Graves' Ophthalmopathy.

Purpose: Graves' ophthalmopathy (GO), the most common extrathyroidal manifestation of Graves' disease, is disabling and disfiguring. Recent studies have shown that statins have a protective effect on individuals with GO. Statins were reported to trigger ferroptosis in some disorders, but little is known about whether statins protect against GO via ferroptosis.