Hydrogen inhibits the osteoclastogenesis of mouse bone marrow mononuclear cells.

Hydrogen (H) is one of the major biodegradation products of magnesium (Mg) alloys implanted for bony fracture healing and reconstruction; H thus plays a significant role in the regulation of local microenvironment and the biology of resident cells. The interactions between the H and the local cells are of great interest, and a full understanding of the effect of H on bone marrow mononuclear cells (BMMCs) would accelerate the development of effective strategies for successful bony healing. This study investigates how H, with different concentrations and durations, regulates the osteoclastogenesis of mouse BMMCs.

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

Background: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

Methods: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao) to the fraction of inspired oxygen (Fio) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone.

Effect of postdose fasting duration on hetrombopag olamine pharmacokinetics and pharmacodynamics in healthy volunteers.

Aims: Hetrombopag olamine is a novel small-molecule, nonpeptide thrombopoietin receptor agonist developed for immune thrombocytopenia treatment. This study aims to determine the safety and the effect of fasting duration after administration of hetrombopag on pharmacokinetics and pharmacodynamics in Chinese healthy subjects.

Methods: A randomized, open-label, single-dose, 3-period crossover, self-control trial was conducted.

Small Bowel Crohn Disease at CT and MR Enterography: Imaging Atlas and Glossary of Terms.

Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society for Pediatric Radiology, the American Gastroenterological Association, and other international experts recently reported consensus recommendations for standardized nomenclature for the interpretation and reporting of CT enterography and MR enterography findings of small bowel Crohn disease. The consensus recommendations included CT enterography and MR enterography bowel wall findings that are associated with Crohn disease, findings that occur with penetrating Crohn disease, and changes that occur in the mesentery related to Crohn disease. Also included were recommended radiology report impression statements that summarize the findings of small bowel Crohn disease at CT enterography and MR enterography.

Mechanoresponse of stem cells for vascular repair.

Stem cells have shown great potential in vascular repair. Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion, proliferation, migration, and differentiation of stem cells serious signaling pathways. The enrichment and differentiation of stem cells play an important role in the angiogenesis and maintenance of vascular homeostasis.

Delayed Dopamine Dysfunction and Motor Deficits in Female Parkinson Model Mice.

This study analyzed gender differences in the progressive dopamine (DA) deficiency phenotype in the MitoPark (MP) mouse model of Parkinson's disease (PD) with progressive loss of DA release and reuptake in midbrain DA pathways. We found that the progressive loss of these DA presynaptic parameters begins significantly earlier in male than female MP mice. This was correlated with behavioral gender differences of both forced and spontaneous motor behavior.

Renewed proliferation in adult mouse cochlea and regeneration of hair cells.

The adult mammalian inner ear lacks the capacity to divide or regenerate. Damage to inner ear generally leads to permanent hearing loss in humans. Here, we present that reprogramming of the adult inner ear induces renewed proliferation and regeneration of inner ear cell types.

Identification of Racial Inequities in Access to Specialized Inpatient Heart Failure Care at an Academic Medical Center.

Background: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race.

Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1-deficient mice.

Polycystic kidney disease (PKD) is characterized by the expansion of fluid-filled cysts in the kidney, which impair the function of kidney and eventually leads to end-stage renal failure. It has been previously demonstrated that transgenic overexpression of prothymosin α (ProT) induces the development of PKD; however, the underlying mechanisms remain unclear. In this study, we used a mouse PKD model that sustains kidney-specific low-expression of to illustrate that aberrant up-regulation of ProT occurs in cyst-lining epithelial cells, and we further developed an cystogenesis model to demonstrate that the suppression of ProT is sufficient to reduce cyst formation.

NKT Cells Coexpressing a GD2-Specific Chimeric Antigen Receptor and IL15 Show Enhanced Persistence and Antitumor Activity against Neuroblastoma.

Purpose: Vα24-invariant natural killer T cells (NKT) are attractive carriers for chimeric antigen receptors (CAR) due to their inherent antitumor properties and preferential localization to tumor sites. However, limited persistence of CAR-NKTs in tumor-bearing mice is associated with tumor recurrence. Here, we evaluated whether coexpression of the NKT homeostatic cytokine IL15 with a CAR enhances the persistence and therapeutic efficacy of CAR-NKTs.

Sodium butyrate alleviates high-glucose-induced renal glomerular endothelial cells damage via inhibiting pyroptosis.

We recently found that Sodium butyrate (NaB) possesses anti-inflammatory effects in diabetic nephropathy (DN) mouse model and in high-glucose induced mouse glomerular mesangial cells. Pyroptosis is a programmed cell death accompanied with the release of pro-inflammatory factors. Gasdermin D (GSDMD) is a novel discovered pivotal executive protein of pyroptosis, which can be cleaved by inflammatory caspases.

Use of Cryopreserved Hepatocytes as Part of an Integrated Strategy to Characterize In Vivo Clearance for Peptide-Antibody Conjugate Inhibitors of Nav1.7 in Preclinical Species.

The identification of nonopioid alternatives to treat chronic pain has received a great deal of interest in recent years. Recently, the engineering of a series of Nav1.7 inhibitory peptide-antibody conjugates has been reported, and herein, the preclinical efforts to identify novel approaches to characterize the pharmacokinetic properties of the peptide conjugates are described.

12-Lipoxygenase Regulates Cold Adaptation and Glucose Metabolism by Producing the Omega-3 Lipid 12-HEPE from Brown Fat.

Distinct oxygenases and their oxylipin products have been shown to participate in thermogenesis by mediating physiological adaptations required to sustain body temperature. Since the role of the lipoxygenase (LOX) family in cold adaptation remains elusive, we aimed to investigate whether, and how, LOX activity is required for cold adaptation and to identify LOX-derived lipid mediators that could serve as putative cold mimetics with therapeutic potential to combat diabetes. By utilizing mass-spectrometry-based lipidomics in mice and humans, we demonstrated that cold and β3-adrenergic stimulation could promote the biosynthesis and release of 12-LOX metabolites from brown adipose tissue (BAT).

Dynamic Changes in Long-Term Exposure to Ambient Particulate Matter and Incidence of Hypertension in Adults.

Many countries dedicated in mitigation of air pollution in the past several decades. However, little is known about how air quality improvement affects health. Therefore, we conducted current study to investigate dynamic changes in long-term exposure to ambient particulate matter (PM) and incidence of hypertension in a large longitudinal cohort.

Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2.

We reveal by high-throughput screening that activating transcription factor 1 (ATF1) is a novel pluripotent regulator in human embryonic stem cells (hESCs). The knockdown of ATF1 expression significantly up-regulated neuroectoderm (NE) genes but not mesoderm, endoderm, and trophectoderm genes. Of note, down-regulation or knockout of ATF1 with short hairpin RNA (shRNA), small interfering RNA (siRNA), or clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) was sufficient to up-regulate sex-determining region Y-box (SOX)2 and paired box 6 (PAX6) expression under the undifferentiated or differentiated conditions, whereas overexpression of ATF1 suppressed NE differentiation.

The vaginal microbiome and preterm birth.

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project.

Antihypertensive Medication Nonpersistence and Low Adherence for Adults <65 Years Initiating Treatment in 2007-2014.

Previous evidence suggests modest improvements in antihypertensive medication adherence occurred from 2007 to 2012 among US adults ≥65 years of age. Whether adherence improved over time among adults <65 years of age is unknown. We assessed trends in antihypertensive medication nonpersistence and low adherence among 379 658 commercially insured adults <65 years of age initiating treatment in 2007-2014 using MarketScan claims.

A safe and potent anti-CD19 CAR T cell therapy.

Anti-CD19 chimeric antigen receptor (CAR) T cell therapies can cause severe cytokine-release syndrome (CRS) and neurotoxicity, impeding their therapeutic application. Here we generated a new anti-CD19 CAR molecule (CD19-BBz(86)) derived from the CD19-BBz prototype bearing co-stimulatory 4-1BB and CD3ζ domains. We found that CD19-BBz(86) CAR T cells produced lower levels of cytokines, expressed higher levels of antiapoptotic molecules and proliferated more slowly than the prototype CD19-BBz CAR T cells, although they retained potent cytolytic activity.

Dietary Modification Is Associated with Normalization of Penile Hemodynamics in Rats Fed a High-Fat Diet.

Background: Diet is associated with self-reported indices of sexual health. The mechanisms responsible for these changes remain poorly understood.

Aim: To investigate the hemodynamic and histological impact of dietary change in a rat model of hyperlipidemia-associated erectile dysfunction.

Effects of PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial.

This four-week, randomized, double-blind, placebo-controlled study investigated the effects of PS128 (PS128) on boys with autism spectrum disorder (ASD) aged 7-15 in Taiwan. All subjects fulfilled the criteria for ASD diagnosis of DSM-V and the Autism Diagnostic Interview-Revised (ADI-R). Questionnaires used for the primary outcome measure include the Autism Behavior Checklist-Taiwan version (ABC-T), the Social Responsiveness Scale (SRS) and the Child Behavior Checklist (CBCL).

Preparation of Pt-Catalyst by Poly(-phenylenediamine) Nanocomposites Assisted by Microwave Radiation for Proton Exchange Membrane Fuel Cell.

The Pt elements are prepared via the redox reaction with microwave (MW) irradiation in the presence of poly(p-phenylenediamine) (PpPD) which is polymerized on XC72 carbon matrix (PpPD/XC72), behaving as reducing agent. The free primary amines of PpPD are actually converted (oxidized) to secondary ones (5,10-dihydrophenazine) after MW irradiation. Transmission electronic microscopy (TEM) micrographs reveal the prepared Pt nanoparticles are well-dispersed on the carbon matrix like commercial Pt-implanted carbon nanocomposite (Pt/C).

Assessing Vascularity of Osseous Spinal Metastases with Dual-Energy CT-DSA: A Pilot Study Compared with Catheter Angiography.

Background And Purpose: Spine debulking surgery in patients with hypervascular spinal metastasis is associated with massive intraoperative blood loss, but currently, the vascularity of tumor is determined by invasive conventional angiography or dynamic contrast MR imaging. We aimed to investigate the usefulness of noninvasive dual-energy CT-DSA, comparing it with conventional angiography in evaluating the vascularity of spinal metastasis.

Materials And Methods: We conducted a retrospective study from January to December 2018.