MicroRNA-483 amelioration of experimental pulmonary hypertension.

Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-β (TGF-β), TGF-β receptor 2 (TGFBR2), β-catenin, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses

Physiological Hypoxia Enhances Stemness Preservation, Proliferation, and Bidifferentiation of Induced Hepatic Stem Cells

Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their self-renewal and bipotential differentiation properties. However, the efficiency of bidifferentiation and repopulation efficiency of iHepSCs is relatively low. Recent evidence shows that physiological hypoxia, a vital factor within stem cell “niche” microenvironment, plays key roles in regulating tissue stem cell biological behaviors including proliferation and differentiation. In this study, we found that physiological hypoxia (10% O2) enhanced the stemness properties and promoted the proliferation ability of iHepSCs by accelerating G1/S transition via p53-p21 signaling pathway. In addition, short-term hypoxia preconditioning improved the efficiency of hepatic differentiation of iHepSCs, and long-term hypoxia promoted cholangiocytic differentiation but inhibited hepatic differentiation of iHepSCs. These results demonstrated the potential effects of hypoxia on stemness preservation, proliferation, and bidifferentiation of iHepSCs and promising perspective to explore appropriate culture conditions for therapeutic stem cells

Unraveling the mechanisms of intervertebral disc degeneration: an exploration of the p38 MAPK signaling pathway

Intervertebral disc (IVD) degeneration (IDD) is a worldwide spinal degenerative disease. Low back pain (LBP) is frequently caused by a variety of conditions brought on by IDD, including IVD herniation and spinal stenosis, etc. These conditions bring substantial physical and psychological pressure and economic burden to patients. IDD is closely tied with the structural or functional changes of the IVD tissue and can be caused by various complex factors like senescence, genetics, and trauma. The IVD dysfunction and structural changes can result from extracellular matrix (ECM) degradation, differentiation, inflammation, oxidative stress, mechanical stress, and senescence of IVD cells. At present, the treatment of IDD is basically to alleviate the symptoms, but not from the pathophysiological changes of IVD. Interestingly, the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is involved in many processes of IDD, including inflammation, ECM degradation, apoptosis, senescence, proliferation, oxidative stress, and autophagy. These activities in degenerated IVD tissue are closely relevant to the development trend of IDD. Hence, the p38 MAPK signaling pathway may be a fitting curative target for IDD. In order to better understand the pathophysiological alterations of the intervertebral disc tissue during IDD and offer potential paths for targeted treatments for intervertebral disc degeneration, this article reviews the purpose of the p38 MAPK signaling pathway in IDD

Basket Credit Derivative Pricing in a Markov Chain Model with Interacting Intensities

In this paper, we propose a Markov chain model to price basket credit default swap (BCDS) and basket credit-linked note (BCLN) with counterparty and contagion risks. Suppose that the default intensity processes of reference entities and the counterparty are driven by a common external shock as well as defaults of other names in the contracts. The stochastic intensity of the external shock is a Cox process with jumps. We derive recursive formulas for the joint distribution of default times and obtain closed-form premium rates for BCDS and BCLN. Numerical experiments are performed to show how the correlated default risks may affect the premium rates

Outcomes of radial head fractures treated with pre-curved metacarpal plate

Abstract Objective To explore the clinical outcomes of MasonII/III radial head fractures without the neck involvement treated with pre-curved metacarpal plates. Methods Ninety cases of Mason typeII/III radial head fractures without the neck involvement were retrospectively collected from the department of orthopaedics of our hospital from September 2015 to May 2021. Group A (n = 44) underwent open reduction and internal fixation with pre-curved metacarpal plate, and Group B (n = 46) were fixed by traditional T-shaped plates. The operation time and the incision length were recorded during the operation. The Mayo Elbow Performance Score (MEPS), Disability of Arm, Shoulder and Hand (DASH) score, visual analogue scale (VAS) for pain, range of motion (ROM) and post-operative complications were evaluated at the last follow-up. Results All the patients were followed up for at least 12 months. There were no significant difference between two groups regarding operation time (54.2 ± 12.1 v.s 51.3 ± 7.2, mins), MEPS (88.9 ± 4.2 v.s 87.8 ± 4.4), DASH score (7.3 ± 4.6 v.s 9.0 ± 4.0), VAS (1.6 ± 0.8 v.s 1.7 ± 0.7), and ROM. However, the incision length was shorter in Group A (5.6 ± 0.5 v.s 6.6 ± 0.5, cm, P < 0.01). The postoperative complication rate was also lower in Group A (1/44 v.s 8/46, P = 0.02). Conclusion Masson II/III radial head fractures without the neck involvement treated with pre-curved metacarpal plates could achieve satisfactory outcomes comparable to traditional T-shaped plates. Moreover, the invasiveness and postoperative complications are less in patients with pre-curved metacarpal plates. Level of evidence III, retrospective comparison study

Distinct charge dynamics in battery electrodes revealed by in situ and operando soft X-ray spectroscopy.

Developing high-performance batteries relies on material breakthroughs. During the past few years, various in situ characterization tools have been developed and have become indispensible in studying and the eventual optimization of battery materials. However, soft X-ray spectroscopy, one of the most sensitive probes of electronic states, has been mainly limited to ex situ experiments for battery research. Here we achieve in situ and operando soft X-ray absorption spectroscopy of lithium-ion battery cathodes. Taking advantage of the elemental, chemical and surface sensitivities of soft X-rays, we discover distinct lithium-ion and electron dynamics in Li(Co(¹/₃)Ni(¹/₃)Mn(¹/₃))O₂ and LiFePO₄ cathodes in polymer electrolytes. The contrast between the two systems and the relaxation effect in LiFePO₄ is attributed to a phase transformation mechanism, and the mesoscale morphology and charge conductivity of the electrodes. These discoveries demonstrate feasibility and power of in situ soft X-ray spectroscopy for studying integrated and dynamic effects in batteries

Uric Acid Levels and All-Cause Mortality in Peritoneal Dialysis Patients

Background: Epidemiological studies have shown that hyperuricemia is associated with all-cause and cardiovascular mortality in chronic kidney disease (CKD) and hemodialysis patients. Our study investigated the influence of serum uric acid (UA) levels on survival in peritoneal dialysis (PD) patients. Methods: This was a retrospective study involving 156 subjects who had undergone PD. The patient demographics, etiology of ESRD, comorbid conditions and other laboratory parameters were collected. The subjects were divided into three groups according to their serum UA concentrations (group 1, the lowest quartile; group 2, the middle quartiles; group 3, the highest quartile). The risk of death was calculated using a multivariate Cox regression model. Results: There were 41 deaths during a follow-up period of 31.3±17.5 months. Compared with group 2, which had a mortality rate of 5.7 per 1000 person-months, the mortality rates were higher in group 1 (14.3 per 1000 person-months, p0.05) for group 1 and 2.96 (95% CI 1.29-6.80, p=0.01) for group 3. Conclusions: In PD patients, a higher serum UA level is related to increased mortality and is an independent risk factor for all-cause mortality. Uric acid levels and all-cause mortality in peritoneal dialysis patients

Risk Factor Analysis of Calcification in Aortic and Mitral Valves in Maintenance Peritoneal Dialysis Patients

Background/Aims: This study aimed to investigate potential risk factors for calcification in aortic and mitral valves in maintenance peritoneal dialysis (MPD) patients. Methods: We enrolled MPD patients who had undergone over 18 months of dialysis in our dialysis center, examined their cardiac valve calcification status by echocardiography, and recorded their biochemical data and dialysis-related indicators. These results were compared by logistic regression analyses to identify the risk factors associated with calcification in aortic and mitral valves. Results: Among the 117 enrolled MPD patients, 41 exhibited calcification in aortic or mitral valves, including 38 with aortic valve calcification (AVC) and 17 with mitral valve calcification (MVC); 14 of them had calcification in both aortic and mitral valves. Multivariate logistic regression analysis revealed that age (OR=1.965, p=0.01), diabetes history (OR=4.693, p=0.029), calcium-phosphorus product (OR=2.373, p=0.001) and prealbumin (OR=0.908, p=0.012) were independently related to AVC, whereas age (OR=3.179, p=0.023), calcium-phosphorus product (OR=6.512, p=0.001), prealbumin (OR=0.885, p=0.033), high-density lipoprotein (OR=19.540, p=0.011) and diabetes history (OR=6.948, p=0.038) were independently related to MVC. Conclusions The incidence of cardiac valve calcification in MPD patients is high, and the incidence of AVC is higher than MVC. Age, diabetes history, calcium-phosphorus product and hypo-prealbuminemia are independent risk factors for AVC, whereas age, calcium-phosphorus product and hypo-prealbuminemia are independent risk factors for MVC