Segetalin B promotes bone formation in ovariectomized mice by activating PLD1/SIRT1 signaling to inhibit γ-secretase-mediated Notch1 overactivation.

Segetalin B (SB) has shown promise in mitigating osteoporosis in ovariectomized (OVX) mice, though its underlying mechanisms remain unclear. This study investigates how SB promotes bone formation through Phospholipase D1 (PLD1) activation in OVX models. In vitro, bone marrow-derived mesenchymal stem cells (BMSCs) from OVX mice were cultured for osteogenic differentiation.

The relationship between crustal deformation characteristics and strong earthquakes in western China revealed by GNSS.

To clarify the relationship between GNSS (Global Navigation Satellite System) crustal deformation and the preparation of strong earthquakes in the western Chinese Mainland, a series of methods including velocity field, strain rate field, and strain parameter time series are adopted based on the GNSS observation data from the CMONOC (Crustal Movement Observation Network of China). The abnormal characteristics of crustal deformation movement before the M ≥ 5 earthquakes in the area since 1999 are studied. The corresponding variety of the crustal movement before earthquakes is discussed in combination with the seismogenic structure of earthquakes.

Sevoflurane postconditioning attenuates cardiomyocytes hypoxia/reoxygenation injury via PI3K/AKT pathway mediated HIF-1α to regulate the mitochondrial dynamic balance.

Background: Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects.

Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases.

SegT: Separated edge-guidance transformer network for polyp segmentation.

Accurate segmentation of colonoscopic polyps is considered a fundamental step in medical image analysis and surgical interventions. Many recent studies have made improvements based on the encoder-decoder framework, which can effectively segment diverse polyps. Such improvements mainly aim to enhance local features by using global features and applying attention methods.

Multigranularity Surrogate Modeling for Evolutionary Multiobjective Optimization With Expensive Constraints.

Multiobjective optimization problems (MOPs) with expensive constraints pose stiff challenges to existing surrogate-assisted evolutionary algorithms (SAEAs) in a very limited computational cost, due to the fact that the number of expensive constraints for an MOP is often large. For existing SAEAs, they always approximate constraint functions in a single granularity, namely, approximating the constraint violation (CV, coarse-grained) or each constraint (fine-grained). However, the landscape of CV is often too complex to be accurately approximated by a surrogate model.

Pharmacokinetic and bioequivalence study of two capecitabine tablets in Chinese patients with breast, colorectal or gastric cancer under fed condition: A multicentric, randomized, open-label, single-dose, two-period, two-way crossover clinical trial.

Objective: The aim of this study was to examine the pharmacokinetics, bioequivalence, and safety of two tablet formulations of capecitabine 500 mg in Chinese patients with breast, colorectal or gastric cancer under fed condition.

Methods: A multicentric, randomized, open-label, single-dose, two-period, two-way crossover trial was conducted by randomizing a single oral dose of test (T) or reference (R, Xeloda®) capecitabine (500 mg) to patients of either sex with colon, colorectal or breast cancer under fed condition (high-fat and high-calorie diet). Pharmacokinetic parameters were calculated using non-compartmental methods.

SIRT1/Notch1 signal axis involves in the promoting effect of Segetalin B on bone formation.

Phytoestrogens are a class of potential natural medicines for treating postmenopausal osteoporosis (PMOP). Segetalin B (SB) is a cyclic peptide compound showing estrogenic activity. This study reports the effect of SB on bone formation among ovariectomized (OVX) rats.

Bone marrow mesenchymal stem cells-derived exosomes mediate nuclear receptor coactivator-3 expression in osteoblasts by delivering miR-532-5p to influence osteonecrosis of the femoral head development.

Exosomes (Exo) originated from bone marrow mesenchymal stem cells (BMSCs) have therapeutic impacts on osteonecrosis of the femoral head (ONFH), and microRNA (miR)-532-5p has been confirmed to participate in ONFH progression. In the research, it was figured out whether BMSCs-Exo could relieve ONFH by delivering miR-532-5p. MG-63 cells were treated with DEX to construct an ONFH cell model in vitro.

miR-3064-5p and miR-4745-5p affect heparin sensitivity in patients undergoing cardiac surgery by regulating AT-III and factor X mRNA levels.

Perioperative regulation of coagulation function through heparin in patients undergoing cardiac surgery with cardiopulmonary bypass is an important part of performing cardiac surgery, and postoperative bleeding due to abnormal coagulation function caused by differences in heparin sensitivity in different individuals is an independent risk factor for postoperative complications and death. Using an online database, 10 miRNAs interacting with AT-III and FX genes were predicted. Patients were divided into three groups according to the difference in activated clotting time (ACT) after the first dose of heparin (2.

Effect of Etomidate vs Propofol for Total Intravenous Anesthesia on Major Postoperative Complications in Older Patients: A Randomized Clinical Trial.

Importance: Older patients may benefit from the hemodynamic stability of etomidate for general anesthesia. However, it remains uncertain whether the potential for adrenocortical suppression with etomidate may increase morbidity.

Objective: To test the primary hypothesis that etomidate vs propofol for anesthesia does not increase in-hospital morbidity after abdominal surgery in older patients.

Long Noncoding RNA Zinc Finger Antisense 1 Affects Glucocorticoid-Induced Osteonecrosis of the Femoral Head by Performing as a ceRNA for MicroRNA-124-3p and Accelerating Transforming Growth Factor Type III Receptor.

In recent years, plentiful studies have uncovered the long noncoding RNA's (lncRNA's) momentous functions in osteonecrosis of the femoral head (ONFH), but the specific mechanism has not been fully illustrated. The study was to figure out lncRNA Zinc finger antisense 1 (LncZFAS1)'s biological function and its latent downstream molecular mechanism in glucocorticoid- (GC-) induced ONFH. The results manifested LncZFAS1 and transforming growth factor type III receptor (TGFBR3) were elevated, while microRNA- (miR-) 124-3p was reduced in ONFH tissues and cells.

Phase I clinical trial of HC-1119 soft capsule in Chinese healthy adult male subjects: Pharmacokinetics and safety of single-dose proportionality and effects of food.

Background: Preclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide.

Methods: To evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119.

Sevoflurane Postconditioning Attenuates Hypoxia/Reoxygenation Injury of Cardiomyocytes Under High Glucose by Regulating HIF-1α/MIF/AMPK Pathway.

Cardiovascular disease, as a very common and serious coexisting disease in diabetic patients, and is one of the risk factors that seriously affect the prognosis and complications of surgical patients. Previous studies have shown that sevoflurane post-conditioning (SPostC) exerts a protective effect against myocardial ischemia/reperfusion injury by HIF-1α, but the protective effect is weakened or even disappeared under hyperglycemia. This study aims to explore whether regulating the HIF-1α/MIF/AMPK signaling pathway can restore the protective effect and reveal the mechanism of SPostC on cardiomyocyte hypoxia/reoxygenation injury under high glucose conditions.

The risk factors of postoperative delirium in patients with hip fracture: implication for clinical management.

Background: Delirium is a common complication of hip surgery patients. It is necessary to investigate the epidemiological characteristics and related risk factors of delirium after hip fracture surgery, to provide evidence supports for the prevention and management of delirium.

Methods: Hip fracture patients admitted to our hospital for surgical treatment from March 2018 to March 2020 were identified as participants.

Evaluation of a novel Cardiac Peri-Operative Transfusion Trigger Scoring system in patients with coronary artery disease.

Background: A simple and accurate scoring system to guide perioperative blood transfusion in patients with coronary artery disease (CAD) undergoing cardiac surgery is lacking. The trigger point for blood transfusions for these patients may be different from existing transfusion guidelines. This study aimed to evaluate the safety and efficacy of a new scoring strategy for use in guiding transfusion decisions in patients with CAD.

Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway.

Background: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning (IPC). However, the underlying molecular mechanism of SPC remains unclear. Studies confirm that hypoxia-inducible factor-1 (HIF-1) can transform cells from aerobic oxidation to anaerobic glycolysis by activating the switch protein pyruvate dehydrogenase kinase-1 (PDK-1), thus providing energy for the normal life activities of cells under hypoxic conditions.

Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats.

Mitochondrial autophagy is involved in myocardial protection of sevoflurane postconditioning (SPostC) and in diabetic state this protective effect is weakened due to impaired HIF-1 signaling pathway. Previous studies have proved that deferoxamine (DFO) could activate impaired HIF-1α in diabetic state to restore the cardioprotective of sevoflurane, while the specific mechanism is unclear. This study aims to investigate whether HIF-1/BNIP3-mediated mitochondrial autophagy is involved in the restoration of sevoflurane postconditioning cardioprotection in diabetic state.

Heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass.

Background: Heparin-associated coagulation disorder is an important factor related to postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Currently, the relationship between heparin sensitivity and postoperative bleeding is unknown.

Objective: To investigate the relationship between individual heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery.

Context-Aware Mouse Behavior Recognition Using Hidden Markov Models.

Automated recognition of mouse behaviors is crucial in studying psychiatric and neurologic diseases. To achieve this objective, it is very important to analyze the temporal dynamics of mouse behaviors. In particular, the change between mouse neighboring actions is swift in a short period.

A Multipopulation-Based Multiobjective Evolutionary Algorithm.

Multipopulation is an effective optimization component often embedded into evolutionary algorithms to solve optimization problems. In this paper, a new multipopulation-based multiobjective genetic algorithm (MOGA) is proposed, which uses a unique cross-subpopulation migration process inspired by biological processes to share information between subpopulations. Then, a Markov model of the proposed multipopulation MOGA is derived, the first of its kind, which provides an exact mathematical model for each possible population occurring simultaneously with multiple objectives.

Downregulation of lncRNA TUG1 is involved in ankylosing spondylitis and is related to disease activity and course of treatment.

Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) promotes osteosarcoma, while its involvement in other bone diseases, such as ankylosing spondylitis (AS) is unknown. Expression of TUG1 in serum and open sacroiliac biopsies of AS patents and healthy controls was detected by real-time quantitative PCR (qRT-PCR). Ankylosing spondylitis disease activity score (ASDAS) system was used to evaluate disease activity.

The key role of microtubules in hypoxia preconditioning-induced nuclear translocation of HIF-1α in rat cardiomyocytes.

Background: Hypoxia-inducible factor (HIF)-1 is involved in the regulation of hypoxic preconditioning in cardiomyocytes. Under hypoxic conditions, HIF-1α accumulates and is translocated to the nucleus, where it forms an active complex with HIF-1β and activates transcription of approximately 60 kinds of hypoxia-adaptive genes. Microtubules are hollow tubular structures in the cell that maintain cellular morphology and that transport substances.

The influence of rapamycin on the early cardioprotective effect of hypoxic preconditioning on cardiomyocytes.

Introduction: The purpose of this study was to examine the effects of rapamycin on the cardioprotective effect of hypoxic preconditioning (HPC) and on the mammalian target of rapamycin (mTOR)-mediated hypoxia-inducible factor 1 (HIF-1) signaling pathway.

Material And Methods: Primary cardiomyocytes were isolated from rat pups and underwent rapamycin and/or HPC, followed by hypoxia/re-oxygenation (H/R) injury. Cell viability and cell injury were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and qRT-PCR was used to measure HIF-1α and mTOR mRNA expression.