The biogenesis and regulation of animal microRNAs.

MicroRNAs (miRNAs) are small, yet profoundly influential, non-coding RNAs that base-pair with mRNAs to induce RNA silencing. Although the basic principles of miRNA biogenesis and function have been established, recent breakthroughs have yielded important new insights into the molecular mechanisms of miRNA biogenesis. In this Review, we discuss the metazoan miRNA biogenesis pathway step-by-step, focusing on the key biogenesis machinery, including the Drosha-DGCR8 complex (Microprocessor), exportin-5, Dicer and Argonaute.

A prospective comparison of two computer aided detection systems with different false positive rates in colonoscopy.

This study evaluated the impact of differing false positive (FP) rates in two computer-aided detection (CADe) systems on the clinical effectiveness of artificial intelligence (AI)-assisted colonoscopy. The primary outcomes were adenoma detection rate (ADR) and adenomas per colonoscopy (APC). The ADR in the control, system A (3.

Delivering evidence-based treatment via telehealth for Anorexia Nervosa in rural health settings: a multi-site feasibility implementation study.

Background: Access to evidence-based treatments such as family-based therapy (FBT) is difficult for adolescents diagnosed with Anorexia Nervosa (AN) living in rural or regional areas due to a limited trained workforce, high staff turnover and inconsistent treatment fidelity. Telehealth offers a potential access solution by facilitating care irrespective of family or service location. The disruption to the health system caused by COVID-19 amplified an existing need and increased the use of telehealth to deliver FBT before its efficacy and safety was fully evaluated.

Lumped parameter simulations of cervical lymphatic vessels: dynamics of murine cerebrospinal fluid efflux from the skull.

Background: Growing evidence suggests that for rodents, a substantial fraction of cerebrospinal fluid (CSF) drains by crossing the cribriform plate into the nasopharyngeal lymphatics, eventually reaching the cervical lymphatic vessels (CLVs). Disruption of this drainage pathway is associated with various neurological disorders.

Methods: We employ a lumped parameter method to numerically model CSF drainage across the cribriform plate to CLVs.

Mechanical stability of the proximal tibia with different bone formations after plate removal in medial opening-wedge high tibial osteotomy: a finite element analysis.

Background: No clear agreement exists on the degree of bone formation required to remove a metal plate without correction loss after medial opening-wedge high tibial osteotomy (MOWHTO). We aimed to investigate the mechanical stability of the proximal tibia with different bone formations after plate removal in MOWHTO using finite element models and determine the extent of bone formation when the plate can be removed without correction loss.

Methods: The MOWHTO models with 5, 10, and 15 mm opening gaps were generated.

New Insights into AMPK, as a Potential Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatic Fibrosis.

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis.

Proapoptotic role of CDK1 in overcoming paclitaxel resistance in ovarian cancer cells in response to combined treatment with paclitaxel and duloxetine.

Background: Paclitaxel resistance and recurrence are major obstacles in ovarian cancer, which is the leading cause of death among gynecologic cancers. During cancer cell progression, cyclin-dependent kinase 1 (CDK1) drives cells through the G2 phase and into mitosis. In this study, we demonstrated that CDK1 played a crucial role in switching paclitaxel-resistant ovarian cancer cells from mitotic arrest to apoptosis following combined treatment with paclitaxel and duloxetine, an antidepressant known as a serotonin-norepinephrine reuptake inhibitor (SNRI).

Efficacy of cold and cryo-preserved nerve allografts with low-dose FK506 for motor nerve regeneration: a preclinical study.

Background: Despite their ability to regenerate as well as autografts, the use of nerve allografts is limited by the need for immunosuppression and the risk of disease transmission. Further, decellularized allografts lacking Schwann cells limit axonal regeneration in long nerve defects. This study evaluated sciatic nerve regeneration in rats implanted with cold- or cryopreserved allografts, and examined the effects of FK506, an immunosuppressant that targets calcineurin function, on motor recovery.

Clinical evaluation of usefulness and effectiveness of sitting-type continuous passive motion machines in patients with total knee arthroplasty: a dual-center randomized controlled trial.

Background: Total knee arthroplasty (TKA) is a treatment option for osteoarthritis of the knee. After undergoing TKA, patients can be treated with continuous passive motion (CPM); however, inconsistent results have been reported on the effectiveness of CPM as part of a rehabilitation strategy. This discrepancy may be due to the difference between the set-arc of CPM and real arcs of knee motion.

Impact of diversity representation in art on pre-health professions students' sense of belonging: A randomized experimental study.

Background: For learners underrepresented in medicine (UIM), a heightened sense of belonging may be critical to creating shared awareness of diversity and fostering an inclusive educational environment. Despite ongoing efforts from academic medical institutions to promote and retain diverse individuals, few studies have investigated the foundational role of pre-health professions education in shaping students' sense of belonging, and fewer still have leveraged the potential of arts- and humanities-based approaches in doing so. This study aimed to evaluate the perceived impact of race- and gender-diverse visual representations of health professionals on pre-health students' sense of belonging.

Elucidation of molecular function of phage protein responsible for optimization of host cell lysis.

Background: Bacteriophages (or phages) replicate by utilizing bacterial resources and destroy their host cells at the end of the replication cycle. Phages employ multiple proteins to optimize host cell lysis, thereby maximizing the production of phage particles. However, elucidating the entire lysis process is challenging due to the abundance of uncharacterized genes in the phage genome.

Exosomal miR-6126 as a novel therapeutic target for overcoming resistance of anti-cancer effect in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) stands as the sixth most prevalent cancer globally, presenting a substantial health challenge, particularly due to late-stage diagnoses that limit treatment effectiveness. Sorafenib, a multi-kinase inhibitor, is the primary chemotherapeutic agent for advanced HCC, but it only extends survival by 2-3 months. However, drug resistance remains a major clinical challenge, necessitating the exploration of new molecular mechanisms, including the role of microRNAs (miRNAs) in sorafenib resistance.

Brain volumes, cognitive, and adaptive skills in school-age children with Down syndrome.

Background: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

Relationship Between Adverse Childhood Experiences and Resilience: The Indirect Effect of a Sense of Purpose in Life.

Purpose: This study examined the association between adverse childhood experiences (ACEs) and resilience through a sense of purpose in life (SP) among 578 college students, applying resilience theory and positive psychology.

Materials And Methods: Using a cross-sectional, online survey design, data were collected. Most respondents were female (71.

Denatonium inhibits RANKL-induced osteoclast differentiation and rescues the osteoporotic phenotype by blocking p65 signaling pathway.

Background: Bone remodeling is a critical process that maintains skeletal integrity, orchestrated by the balanced activities of osteoclasts, which resorb bone, and osteoblasts, which form bone. Osteoclastogenesis, the formation of osteoclasts, is primarily driven by NFATc1, a process activated through c-Fos and NF-κB signaling pathways in response to receptor activator of nuclear factor κB ligand (RANKL). Dysregulation of RANKL signaling is a key contributor to pathological bone loss, as seen in conditions such as osteoporosis.

More than carriers, orosomucoids are key metabolic modulators.

Orosomucoids (ORMs) have historically been considered as carriers involved in drug and lipid delivery. However, recent studies indicate ORM2 as a hepatokine involved in metabolic regulation. Here, we highlight the functions of ORM2 in controlling metabolic health and disease, focusing on its newly discovered regulatory mechanisms.

A review on the characterization of edible scaffolds for cultured meat: Physical, chemical, biocompatibility, and food safety evaluation methods.

Scaffolds are three-dimensional biomaterials that act as structural blueprint for cultured meat precursor cells. The advancement of scaffold fabrication techniques and the development of novel scaffolds specifically designed for cultured meat are evident in numerous scaffold-based cultured meat reports, highlighting the advantages of the scaffolds using different characterization and evaluation techniques encompassing the physical, mechanical, chemical, and biological features of the scaffolds. Considering the potential of scaffolds to be included in cultured meat products, standardization of evaluation techniques could aid in preventing misrepresentation and possible food safety concerns in cultured meat production.

Stem Cell-Laden Engineered Patch: Advances and Applications in Tissue Regeneration.

Stem cell-based therapies are emerging as significant approaches in tissue engineering and regenerative medicine, applicable to both fundamental scientific research and clinical practice. Despite remarkable results in clinical studies, challenges such as poor standardization of graft tissues, limited sources, and reduced functionality have hindered the effectiveness of these therapies. In this review, we summarize the engineering approaches involved in fabricating stem cell assisted patches and the substantial strategies for designing stem cell-laden engineered patches (SCP) to complement the existing stem cell-based therapies.

Obesity and Polycystic Ovary Syndrome.

The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance. Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance.

Histological Validation of Multi-Echo Gradient Echo (MGRE)-Derived Myelin Water Fraction (MWF) at 9.4 T and the Influence of Orientation on Quantification.

Myelin is essential in the nervous system of mammals. As the location and degree of myelin loss can reflect varied pathophysiological status, noninvasive measurement of myelin is of high importance. The magnetic resonance imaging (MRI) technique of myelin water fraction (MWF) derived from multi-echo gradient echo (MGRE) sequence is a promising tool for the quantification of myelin content due to the low specific absorption rate (SAR) compared with the spin-echo sequence, time efficiency, and wide availability.

Generation and validation of a D1 dopamine receptor Flpo knock-in mouse.

Background: Dopamine is a powerful neuromodulator of diverse brain functions, including movement, motivation, reward, and cognition. D1-type dopamine receptors (D1DRs) are the most prevalently expressed dopamine receptors in the brain. Neurons expressing D1DRs are heterogeneous and involve several subpopulations.

Validity and Reliability of the Korean Version of Supportive Care Needs Survey-Short Form 34 for Patients with Cancer: A Methodological Study.

Purpose: The Supportive Care Needs Survey-Short Form 34 (SCNS-SF34) measures the perceived care needs of patients with cancer. This study aimed to evaluate the reliability and validity of the Korean version of the SCNS-SF34 (i.e.

Release-modulating mechanism and comparative pharmacokinetics in beagle dogs of bethanechol-loaded oral dosage forms.

Bethanechol chloride (BTC), a quaternary ammonium compound used in bladder dysfunction treatment, requires challenges in developing optimal oral dosage forms due to its high water-solubility, short half-life, rapid elimination and four times a day administration. The aim of this study was to develop optimal BTC-loaded oral dosage forms that could provide both rapid onset and sustained therapeutic effects while reducing the frequency of conventional four-times-daily dosing (Mytonin® tablets). Four different BTC-loaded oral dosage forms were designed including gastro-retentive tablet (GRT), controlled-release tablet (CRT), bilayer tablet (BLT), and tablet-in-tablet (TIT).

In situ forming and self-crosslinkable protein hydrogels for localized cancer therapy and topical wound healing.

Proteins, inherently biocompatible and biodegradable, face a challenge in forming stable hydrogels without external chemical crosslinkers. Here, we construct a ring-shaped trimeric SpyTag-fused Proliferating Cell Nuclear Antigen Protein (ST-PCNA) as a core protein building block, and a dumbbell-shaped tandem dimeric SpyCatcher (SC-SC) as a bridging component. Self-crosslinked PCNA/SC-SC Protein (2SP) hydrogels are successfully formed by simply mixing the solutions of ST-PCNA and SC-SC, without chemical crosslinkers.