3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages.

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate the defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14.

Stem-cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens.

Trophoblast organoids derived from placental villi provide a 3D model system of human placental development, but access to first-trimester tissues is limited. Here, we report that trophoblast stem cells isolated from naive human pluripotent stem cells (hPSCs) can efficiently self-organize into 3D stem-cell-derived trophoblast organoids (SC-TOs) with a villous architecture similar to primary trophoblast organoids. Single-cell transcriptome analysis reveals the presence of distinct cytotrophoblast and syncytiotrophoblast clusters and a small cluster of extravillous trophoblasts, which closely correspond to trophoblast identities in the post-implantation embryo.

Effects of the Anterolateral Ligament and Anterior Cruciate Ligament on Knee Joint Mechanics: A Biomechanical Study Using Computational Modeling.

Background: Recent studies on lateral knee anatomy have reported the presence of a true ligament structure, the anterolateral ligament (ALL), in the anterolateral region of the knee joint. However, its biomechanical effects have not been fully elucidated.

Purpose: To investigate, by using computer simulation, the association between the ALL and anterior cruciate ligament (ACL) under dynamic loading conditions.

OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human.

Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their interactome in human ESCs (hESCs) has not to date been explored. Here we mapped the OCT4 interactomes in naïve and primed hESCs, revealing extensive connections to mammalian ATP-dependent nucleosome remodeling complexes.

Probing the signaling requirements for naive human pluripotency by high-throughput chemical screening.

Naive human embryonic stem cells (hESCs) have been isolated that more closely resemble the pre-implantation epiblast compared to conventional "primed" hESCs, but the signaling principles underlying these discrete stem cell states remain incompletely understood. Here, we describe the results from a high-throughput screen using ∼3,000 well-annotated compounds to identify essential signaling requirements for naive human pluripotency. We report that MEK1/2 inhibitors can be replaced during maintenance of naive human pluripotency by inhibitors targeting either upstream (FGFR, RAF) or downstream (ERK1/2) kinases.

Diversification in Functions and Expressions of Soybean Genes Fine-Tunes Seasonal Flowering.

The proper timing of flowering in response to environmental changes is critical for ensuring crop yields. () homologs of the phosphatidylethanolamine-binding protein family play important roles as floral integrators in many crops. In soybean, we identified 17 genes of this family, and characterized biological functions in flowering for ten homologs.

Finite element analysis of the influence of the posterior tibial slope on mobile-bearing unicompartmental knee arthroplasty.

Background: The most common modes of failure reported in unicompartmental knee arthroplasty (UKA) in its first two decades were wear on the polyethylene (PE) insert, component loosening, and progressive osteoarthritis in the other compartment. The rates of implant failure due to poor component positioning in patients who have undergone UKA have been reported. However, the effect of the posterior tibial slope on the biomechanical behavior of mobile-bearing Oxford medial UKA remains unknown.

Finite Element Study on the Preservation of Normal Knee Kinematics with Respect to the Prosthetic Design in Patient-Specific Medial Unicompartmental Knee Arthroplasty.

Alterations in native knee kinematics in medial unicompartmental knee arthroplasty (UKA) are caused by the nonanatomic articular surface of conventional implants. Technology for an anatomy mimetic patient-specific (PS) UKA has been introduced. However, there have been no studies on evaluating the preservation of native knee kinematics with respect to different prosthetic designs in PS UKA.

Derivation of trophoblast stem cells from naïve human pluripotent stem cells.

Naïve human pluripotent stem cells (hPSCs) provide a unique experimental platform of cell fate decisions during pre-implantation development, but their lineage potential remains incompletely characterized. As naïve hPSCs share transcriptional and epigenomic signatures with trophoblast cells, it has been proposed that the naïve state may have enhanced predisposition for differentiation along this extraembryonic lineage. Here we examined the trophoblast potential of isogenic naïve and primed hPSCs.

Prediction of wear performance in femoral and tibial conformity in patient-specific cruciate-retaining total knee arthroplasty.

Background: Articular surface curvature design is important in tibiofemoral kinematics and the contact mechanics of total knee arthroplasty (TKA). Thus far, the effects of articular surface curvature have not been adequately discussed with respect to conforming, nonconforming, and medial pivot designs in patient-specific TKA. Therefore, this study evaluates the underlying relationship between the articular surface curvature geometry and the wear performance in patient-specific TKA.

The anterolateral ligament is a secondary stabilizer in the knee joint: A validated computational model of the biomechanical effects of a deficient anterior cruciate ligament and anterolateral ligament on knee joint kinematics.

Objectives: The aim of this study was to investigate the biomechanical effect of the anterolateral ligament (ALL), anterior cruciate ligament (ACL), or both ALL and ACL on kinematics under dynamic loading conditions using dynamic simulation subject-specific knee models.

Methods: Five subject-specific musculoskeletal models were validated with computationally predicted muscle activation, electromyography data, and previous experimental data to analyze effects of the ALL and ACL on knee kinematics under gait and squat loading conditions.

Results: Anterior translation (AT) significantly increased with deficiency of the ACL, ALL, or both structures under gait cycle loading.

Influence of Preservation of Normal Knee Contact Stress on Other Compartments with respect to the Tibial Insert Design for Unicompartmental Knee Arthroplasty.

Recent advances in imaging technology and additive manufacturing have led to the introduction of customized unicompartmental knee arthroplasty (UKA) that can potentially improve functional performance due to customized geometries, including customized sagittal and coronal curvature and enhanced bone preservation. The purpose of this study involved evaluating the biomechanical effect of the tibial insert design on the customized medial UKA using computer simulations. We developed sagittal and coronal curvatures in a native knee mimetic femoral component design.

The biomechanical effect of tibiofemoral conformity design for patient-specific cruciate retainging total knee arthroplasty using computational simulation.

Background: Alterations to normal knee kinematics performed during conventional total knee arthroplasty (TKA) focus on the nonanatomic articular surface. Patient-specific TKA was introduced to provide better normal knee kinematics than conventional TKA. However, no study on tibiofemoral conformity has been performed after patient-specific TKA.

Total knee arthroplasty application of polyetheretherketone and carbon-fiber-reinforced polyetheretherketone: A review.

Polyetheretherketone (PEEK) and carbon-fiber-reinforced PEEK (CFR-PEEK) have been successfully used in the field of orthopedic implants. The polymers PEEK and CFR-PEEK are resistant to fatigue strain and radiologically transparent. These have mechanical properties and are therefore suitable for a range of orthopedic applications.

Biomechanical effect with respect to the sagittal positioning of the femoral component in unicompartmental knee arthroplasty.

Background: Component malalignment in unicompartmental knee arthroplasty (UKA) has been related to the concentration in tibiofemoral joint of contact stress and to poor post-operative outcomes. Few studies investigated a biomechanical effect of femur component position in sagittal plane. The purpose of this study was to evaluate the biomechanical effect of the femoral components on the sagittal alignment under flexion and extension conditions using computational simulations.

Biomechanical analysis of a changed posterior condylar offset under deep knee bend loading in cruciate-retaining total knee arthroplasty.

Background: The conservation of the joint anatomy is an important factor in total knee arthroplasty (TKA). The restoration of the femoral posterior condylar offset (PCO) has been well known to influence the clinical outcome after TKA.

Objective: The purpose of this study was to determine the mechanism of PCO in finite element models with conservation of subject anatomy and different PCO of ±1, ±2, ±3 mm in posterior direction using posterior cruciate ligament-retaining TKA.

A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes.

Background: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart.

Near-infrared angiography for critical limb ischemia in a diabetic murine model.

Peripheral arterial disease (PAD) is a highly prevalent disease process that afflicts more than 20% of individuals with diabetes. Progression of PAD in the setting of diabetes can lead to critical limb ischemia (CLI), which is associated with increased risk of wounds, gangrene, and limb loss. Prompt noninvasive evaluation of limbs affected by PAD progression and CLI is currently limited.

-Acetylcysteine accelerates amputation stump healing in the setting of diabetes.

Over 60% of lower extremity amputations are performed in patients with diabetes and peripheral arterial disease, and at least 25% require subsequent reamputation due to poor surgical site healing. The mechanisms underlying poor amputation stump healing in the setting of diabetes are not understood. -acetylcysteine (NAC) is known to promote endothelial cell function and angiogenesis and may have therapeutic benefits in the setting of diabetes.

Effects of measurement methods for tibial rotation axis on the morphometry in Korean populations by gender.

Background: There have been arguments for methodology in tibial rotation axis measurement, which accordingly determines the morphometry of the proximal tibia in total knee arthroplasty. The morphometry of the proximal tibia for the Korean population is determined by gender, based on the anatomical tibial axis and reliable rotational orientation in knee replacements, to evaluate the size suitability of the currently available prostheses in Korea.

Methods: This study reconstructed the MRI images in three-dimensions for identification and measurement of the mediolateral (ML) and anteroposterior (AP) lengths of the proximal tibia and the tibial aspect ratio (ML/AP) using proximal tibial anthropometric data for 700 osteoarthritic knees (587 females and 113 males).

Morphometry of femoral rotation for total knee prosthesis according to gender in a Korean population using three-dimensional magnetic resonance imaging.

Background: We aimed to evaluate differences in femoral arthometric data for 700 osteoarthritic knees (587 females and 113 males) with respect to gender in a Korean population.

Methods: We identified and measured the mediolateral (ML) and anteroposterior (AP) lengths, femoral aspect ratio (ML/AP), surgical epicondylar axis (SEA), and Whiteside's line (WL). In addition, the anterior, posterior, and distal bone resections of the implanted femurs were evaluated using SEA and WL as references using a three-dimensional analysis method.

Carvedilol-responsive microRNAs, miR-199a-3p and -214 protect cardiomyocytes from simulated ischemia-reperfusion injury.

The nonselective β-adrenergic receptor antagonist (β-blocker) carvedilol has been shown to protect against myocardial injury, but the detailed underlying mechanisms are unclear. We recently reported that carvedilol stimulates the processing of microRNA (miR)-199a-3p and miR-214 in the heart via β-arrestin1-biased β1-adrenergic receptor (β1AR) cardioprotective signaling. Here, we investigate whether these β-arrestin1/β1AR-responsive miRs mediate the beneficial effects of carvedilol against simulated ischemia/reperfusion (sI/R).

The Differences in Chemical Composition, Physical Quality Traits and Nutritional Values of Horse Meat as Affected by Various Retail Cut Types.

The effects of retail cut type on chemical, quality and nutritional characteristics of horse meat were studied. Jeju female breed horses (n = 9) at 32-mo-old were slaughtered and the carcasses at 24 h post-mortem were fabricated into 10 retail cuts including: tender-loin, loin, strip-loin, shoulder-chuck-roll, shoulder-clod, top-round, outside-round, brisket, short-plate-brisket, and shank. The results revealed that all of parameters (chemical, meat quality and nutritional composition) examined significantly (p<0.

Identification of gene signatures regulated by carvedilol in mouse heart.

Chronic treatment with the β-blocker carvedilol has been shown to reduce established maladaptive left ventricle (LV) hypertrophy and to improve LV function in experimental heart failure. However, the detailed mechanisms by which carvedilol improves LV failure are incompletely understood. We previously showed that carvedilol is a β-arrestin-biased β1-adrenergic receptor ligand, which activates cellular pathways in the heart independent of G protein-mediated second messenger signaling.

MicroRNA-150 deletion in mice protects kidney from myocardial infarction-induced acute kidney injury.

Despite greater understanding of acute kidney injury (AKI) in animal models, many of the preclinical studies are not translatable. Most of the data were derived from a bilateral renal pedicle clamping model with warm ischemia. However, ischemic injury of the kidney in humans is distinctly different and does not involve clamping of renal vessel.