Can we predict the risk of venous thromboembolism in patients with Cushing's syndrome: a nationwide cohort analysis.

Purpose: Patients with Cushing's syndrome (CS) have an increased venous thromboembolism (VTE) risk with most studies focusing on the perioperative period. The purpose of this study was to assess the 5-year VTE risk and identify predictors of VTE at CS diagnosis.

Methods: A comparative nationwide retrospective cohort study of 609 patients (mean age 48.

Comparative analysis of PI3K-AKT and MEK-ERK1/2 signaling-driven molecular changes in granulosa cells.

In Brief: PI3K-AKT signaling activates steroidogenesis by inducing estradiol and progesterone production, while MEK-ERK1/2 signaling regulates steroidogenesis by inhibiting estradiol and inducing progesterone production in granulosa cells (GCs). Both pathways are essential for glycolytic and mitochondrial metabolism in these cells.

Abstract: The PI3K-AKT and MEK-ERK1/2 signaling pathways are integral to fundamental cellular processes, such as proliferation, viability and differentiation.

Application of Sortase-Mediated Ligation for the Synthesis of Block Copolymers and Protein-Polymer Conjugates.

Sortase-mediated ligation (SML) has become a powerful tool for site-specific protein modification. However, sortase A (SrtA) suffers from low catalytic efficiency and mediates an equilibrium reaction. Therefore, ligations with large macromolecules may be challenging.

A flexible loop in the paxillin LIM3 domain mediates its direct binding to integrin β subunits.

Integrins are fundamental for cell adhesion and the formation of focal adhesions (FA). Accordingly, these receptors guide embryonic development, tissue maintenance, and haemostasis but are also involved in cancer invasion and metastasis. A detailed understanding of the molecular interactions that drive integrin activation, FA assembly, and downstream signalling cascades is critical.

SLFN11 and ATR as targets for overcoming cisplatin resistance in ovarian cancer cells.

The levels and activities of the DNA/RNA helicase schlafen11 (SLFN11) and the serine/threonine-protein kinase ataxia telangiectasia and Rad3-related protein (ATR) may determine cancer cell sensitivity to DNA damaging agents, including platinum drugs. Here, we studied the roles of SLFN11 and ATR in cisplatin resistance of ovarian cancer using cell lines displaying acquired or intrinsic cisplatin resistance. W1CR, the cisplatin-resistant subline of W1 ovarian cancer cells, displayed reduced SLFN11 levels.

Influence of Cavity Lining on the 3-Year Clinical Outcome of Posterior Composite Restorations: A Randomized Controlled Clinical Trial.

The purpose of this randomized, split-mouth-designed controlled and single-blinded clinical study was to evaluate the 3-year clinical performance of Class I and Class II resin composite restorations placed with or without cavity lining with a flowable composite. Fifty patients with treatment needs in two premolars or molars were included. One of the teeth was restored using the nanohybrid composite (GrandioSO, control group), in the test group a high viscosity flowable composite was additionally applied as a first layer.

Saturated fatty acids inhibit unsaturated fatty acid induced glucose uptake involving GLUT10 and aerobic glycolysis in bovine granulosa cells.

Fatty acids have been shown to modulate glucose metabolism in vitro and in vivo. However, there is still a need for substantial evidence and mechanistic understanding in many cell types whether both saturated and unsaturated fatty acids (SFAs and UFAs) pose a similar effect and, if not, what determines the net effect of fatty acid mixes on glucose metabolism. In the present study, we asked these questions by treating granulosa cells (GCs) with the most abundant non-esterified fatty acid species in bovine follicular fluid.

Traumatic Brain Injury Alters the Trajectory of Age-Related Mitochondrial Change.

Background: Some epidemiologic studies associate traumatic brain injury (TBI) with Alzheimer's disease (AD).

Objective: To test whether a TBI-induced acceleration of age-related mitochondrial change could potentially mediate the reported TBI-AD association.

Methods: We administered unilateral controlled cortical impact (CCI) or sham injuries to 5-month-old C57BL/6J and tau transgenic rTg4510 mice.

Trifluridine for treatment of mpox infection in drug combinations in ophthalmic cell models.

The Mpox virus can cause severe disease in the susceptible population with dermatologic and systemic manifestations. Furthermore, ophthalmic manifestations of mpox infection are well documented. Topical trifluridine (TFT) eye drops have been used for therapy of ophthalmic mpox infection in patients, however, its efficacy against mpox virus infection in this scenario has not been previously shown.

Increases in anterograde axoplasmic transport in neurons of the hyper-glutamatergic, glutamate dehydrogenase 1 (Glud1) transgenic mouse: Effects of glutamate receptors on transport.

The excitatory neurotransmitter glutamate has a role in neuronal migration and process elongation in the central nervous system (CNS). The effects of chronic glutamate hyperactivity on vesicular and protein transport within CNS neurons, that is, processes necessary for neurite growth, have not been examined previously. In this study, we measured the effects of lifelong hyperactivity of glutamate neurotransmission on axoplasmic transport in CNS neurons.

Protection against Aβ-induced neuronal damage by KU-32: PDHK1 inhibition as important target.

A feature of most neurodegenerative diseases is the presence of "mis-folded proteins" that form aggregates, suggesting suboptimal activity of neuronal molecular chaperones. Heat shock protein 90 (Hsp90) is the master regulator of cell responses to "proteotoxic" stresses. Some Hsp90 modulators activate cascades leading to upregulation of additional chaperones.

Functional mimicry of sea urchin biomineralization proteins with CaCO-binding peptides selected by phage display.

The intricate process of biomineralization, in sea urchins, involves the precise interplay of highly regulated mineralization proteins and the spatiotemporal coordination achieved through compartmentalization. However, the investigation of biomineralization effector molecules, proteins, is challenging, due to their very low abundance. Therefore, we investigate the functional mimicry in the bioinspired precipitation of calcium carbonate (CaCO) with artificial peptides selected from a peptide library by phage display based on peptide-binding to calcite and aragonite, respectively.

Loss of Key EMT-Regulating miRNAs Highlight the Role of ZEB1 in EGFR Tyrosine Kinase Inhibitor-Resistant NSCLC.

Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), acquired drug resistance to targeted therapy remains a major obstacle. Epithelial-mesenchymal transition (EMT) has been identified as a key resistance mechanism in NSCLC. Here, we investigated the mechanistic role of key EMT-regulating small non-coding microRNAs (miRNAs) in sublines of the NSCLC cell line HCC4006 adapted to afatinib, erlotinib, gefitinib, or osimertinib.

Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma.

Background: Neuroblastoma is a paediatric cancer that is characterised by poor prognosis for chemoresistant disease, highlighting the need for better treatment options. Here, we asked whether BH3-mimetics inhibiting BCL2 proteins may eliminate chemoresistant neuroblastoma cells.

Methods: We utilised cisplatin-adapted neuroblastoma cell lines as well as patient tissues before and after relapse to study alterations of BCL2 proteins upon chemoresistance.

Man versus machine: Automatic pedicle screw planning using registration-based techniques compared with manual screw planning for thoracolumbar fusion surgeries.

Objective: This study evaluates the precision of a commercially available spine planning software in automatic spine labelling and screw-trajectory proposal.

Methods: The software uses automatic segmentation and registration of the vertebra to generate screw proposals. 877 trajectories were compared.

Parental perspectives about information and deferred versus two-stage consent in studies of neonatal asphyxia.

Objective: The ALBINO Trial (NCT03162653) investigates effects of very early postnatal allopurinol on neurocognitive outcome following perinatal asphyxia where prenatal informed consent (IC) is impossible. Ethically and legally, waiver of consent and/or deferred consent (DC) is acceptable in such an emergency. Short oral/two-step consent (SOC, brief information and oral consent followed by IC) has recently been investigated.

Tidying up the conformational ensemble of a disordered peptide by computational prediction of spectroscopic fingerprints.

The most advanced structure prediction methods are powerless in exploring the conformational ensemble of disordered peptides and proteins and for this reason the "protein folding problem" remains unsolved. We present a novel methodology that enables the accurate prediction of spectroscopic fingerprints (circular dichroism, infrared, Raman, and Raman optical activity), and by this allows for "tidying up" the conformational ensembles of disordered peptides and disordered regions in proteins. This concept is elaborated for and applied to a dodecapeptide, whose spectroscopic fingerprint is measured and theoretically predicted by means of enhanced-sampling molecular dynamics coupled with quantum mechanical calculations.

ERK1/2-SOX9/FOXL2 axis regulates ovarian steroidogenesis and favors the follicular-luteal transition.

Estradiol and progesterone are the primary sex steroids produced by the ovary. Upon luteinizing hormone surge, estradiol-producing granulosa cells convert into progesterone-producing cells and eventually become large luteal cells of the corpus luteum. Signaling pathways and transcription factors involved in the cessation of estradiol and simultaneous stimulation of progesterone production in granulosa cells are not clearly understood.

Anti-NGF treatment worsens subchondral bone and cartilage measures while improving symptoms in floor-housed rabbits with osteoarthritis.

Osteoarthritis (OA) is a common joint disorder often affecting the knee. It is characterized by alterations of various joint tissues including subchondral bone and by chronic pain. Anti-nerve growth factor (NGF) antibodies have demonstrated improvement in pain associated with OA in phase 3 clinical trials but have not been approved due to an increased risk of developing rapidly progressive OA.

The Imitation of the Ovarian Fatty Acid Profile of Superfertile Dummerstorf Mouse Lines during IVM of Control Line Oocytes Could Influence Their Maturation Rates.

Declining human fertility worldwide is an attractive research target for the search for "high fertility" genes and pathways to counteract this problem. To study these genes and pathways for high fertility, the superfertile Dummerstorf mouse lines FL1 and FL2 are two unique model organisms representing an improved fertility phenotype. A direct reason for this remarkable characteristic of increased litter size, which reaches >20 pups/litter in both FLs, is the raised ovulation rate by approximately 100%, representing an impressive record in this field.

Omicron-induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection.

Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.