Restoring Mitochondrial Quantity and Quality to Reverse Warburg Effect and Drive Tumor Differentiation.

Reduced mitochondrial quality and quantity in tumors is associated with dedifferentiation and increased malignancy. However, it remains unclear how to restore mitochondrial quantity and quality in tumors, and whether mitochondrial restoration can drive tumor differentiation. Our study shows that restoring mitochondrial function using retinoic acid (RA) to boost mitochondrial biogenesis and a mitochondrial uncoupler to enhance respiration synergistically drives neuroblastoma differentiation and inhibits proliferation.

Pulmonary Effects of Traumatic Brain Injury in Mice: A Gene Set Enrichment Analysis.

Acute lung injury occurs in 20-25% of cases following traumatic brain injury (TBI). We investigated changes in lung transcriptome expression post-TBI using animal models and bioinformatics. Employing unilateral controlled cortical impact for TBI, we conducted microarray analysis after lung acquisition, followed by gene set enrichment analysis of differentially expressed genes.

Mitochondrial uncoupler and retinoic acid synergistically induce differentiation and inhibit proliferation in neuroblastoma.

Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods.

Endoplasmic Reticulum Protein 72 Regulates Integrin Mac-1 Activity to Influence Neutrophil Recruitment.

Background: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement.

Safety and immunogenicity of SARS-CoV-2 vaccine MVC-COV1901 in Taiwanese adolescents: a randomized phase 2 trial.

Adolescents and children play an important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has received emergency use approval (EUA) for adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents.

Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma.

Unlabelled: The Warburg effect is the major metabolic hallmark of cancer. According to Warburg himself, the consequence of the Warburg effect is cell dedifferentiation. Therefore, reversing the Warburg effect might be an approach to restore cell differentiation in cancer.

Environmental Factors Associated with Severe Motorcycle Crash Injury in University Neighborhoods: A Multicenter Study in Taiwan.

University neighborhoods in Taiwan have high-volume traffic, which may increase motorcyclists' risk of injury. However, few studies have analyzed the environmental factors affecting motorcycle crash injury severity in university neighborhoods. In this multicenter cross-sectional study, we explored the factors that increase the severity of such injuries, especially among young adults.

Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer.

Background: Trastuzumab emtansine is the current standard treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer whose disease progresses after treatment with a combination of anti-HER2 antibodies and a taxane.

Methods: We conducted a phase 3, multicenter, open-label, randomized trial to compare the efficacy and safety of trastuzumab deruxtecan (a HER2 antibody-drug conjugate) with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. The primary end point was progression-free survival (as determined by blinded independent central review); secondary end points included overall survival, objective response, and safety.

Endothelial Yin Yang 1 Phosphorylation at S118 Induces Atherosclerosis Under Flow.

Rationale: Disturbed flow occurring in arterial branches and curvatures induces vascular endothelial cell (EC) dysfunction and atherosclerosis. We postulated that disturbed flow plays important role in modulating phosphoprotein expression profiles to regulate endothelial functions and atherogenesis.

Objective: The goal of this study is to discover novel site-specific phosphorylation alterations induced by disturbed flow in ECs to contribute to atherosclerosis.

The impact of immune checkpoint therapy on the latent reservoir in HIV-infected individuals with cancer on antiretroviral therapy.

Objective: The aim of this study was to quantify HIV-specific immunological and virological changes in people with HIV (PWH) on antiretroviral therapy (ART) with malignancy who received immune checkpoint blockade (ICB).

Design: An observational cohort study.

Methods: Blood samples were collected before and after four cycles of ICB in HIV-positive adults on ART.

Small fiber pathology in autism and clinical implications.

Objective: To investigate small fiber innervation of the skin and its relationships with clinicometry of autism and peripheral afferents for contact heat-evoked potential (CHEP) and psychophysical measures of thermal thresholds.

Methods: We recruited 32 men with autism (26.5 ± 5.

Frequency and Distribution of Chest Radiographic Findings in Patients Positive for COVID-19.

Background Current coronavirus disease 2019 (COVID-19) radiologic literature is dominated by CT, and a detailed description of chest radiography appearances in relation to the disease time course is lacking. Purpose To describe the time course and severity of findings of COVID-19 at chest radiography and correlate these with real-time reverse transcription polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, nucleic acid. Materials and Methods This is a retrospective study of patients with COVID-19 confirmed by using RT-PCR and chest radiographic examinations who were admitted across four hospitals and evaluated between January and March 2020.

Models of Variability and Circadian Rhythm in Heart Rate, Blood Pressure, and QT Interval for Healthy Subjects Who Received Placebo in Phase I Trials.

This work characterized the time-course, circadian rhythm, and inherent variability in key cardiovascular variables (heart rate, corrected QT interval, and systolic and diastolic blood pressure) that are routinely collected as part of safety monitoring in phase I trials. Longitudinal data from 1,035 healthy volunteers who received placebo in 65 single-dose and multiple-dose phase I trials conducted by AbbVie were compiled and analyzed using nonlinear mixed-effects modeling. An independent nonlinear mixed-effects model was developed for each variable, and combinations of cosine functions were used to capture circadian oscillations.

Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin.

The membrane-bound serine proteases prostasin and matriptase and the Kunitz-type protease inhibitors HAI-1 and HAI-2 are all expressed in human skin and may form a tightly regulated proteolysis network, contributing to skin pathophysiology. Evidence from other systems, however, suggests that the relationship between matriptase and prostasin and between the proteases and the inhibitors can be context-dependent. In this study the in vivo zymogen activation and protease inhibition status of matriptase and prostasin were investigated in the human skin.

Agonist-Dependent and -Independent κ Opioid Receptor Phosphorylation: Distinct Phosphorylation Patterns and Different Cellular Outcomes.

We reported previously that the selective agonist U50,488H promoted phosphorylation of the mouse κ opioid receptor (KOPR) at residues S356, T357, T363, and S369. Here, we found that agonist (U50,488H)-dependent KOPR phosphorylation at all the residues was mediated by Gi/o proteins and multiple protein kinases [GRK2, GRK3, GRK5, GRK6 and protein kinase C (PKC)]. In addition, PKC activation by phorbol ester induced agonist-independent KOPR phosphorylation.

Natural Endogenous Human Matriptase and Prostasin Undergo Zymogen Activation via Independent Mechanisms in an Uncoupled Manner.

The membrane-associated serine proteases matriptase and prostasin are believed to function in close partnership. Their zymogen activation has been reported to be tightly coupled, either as a matriptase-initiated proteolytic cascade or through a mutually dependent mechanism involving the formation of a reciprocal zymogen activation complex. Here we show that this putative relationship may not apply in the context of human matriptase and prostasin.

The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders.

Objective: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for other specified bipolar disorder with short duration hypomania patients were similar to bipolar II disorder patients from a biological marker perspective.

Methods: We enrolled patients with bipolar I disorder (n=234), bipolar II disorder (n=260), other specified bipolar disorder with short duration hypomania (n=243), and healthy controls (n=140).

Repolarization Alternans and Ventricular Arrhythmia in a Repaired Tetralogy of Fallot Animal Model.

Background: Ventricular arrhythmia is an important cause of late death in patients with repaired tetralogy of Fallot (rTOF). By using an rTOF canine model, we investigated the role of repolarization alternans and its electrophysiological mechanisms.

Methods And Results: Six dogs received right ventricular outflow tract (RVOT) transannular patch, pulmonary valve destruction, and right bundle branch ablation to simulate rTOF.

Nonalcoholic Fatty Liver Disease Is Associated With QT Prolongation in the General Population.

Background: Nonalcoholic fatty liver disease (NAFLD) is independently associated with QT prolongation among patients with diabetes. It has not yet been determined whether this association remains valid in the general population. We designed an observational study to explore this association.

Differences in liver fibrosis between patients with chronic hepatitis B and C: evaluation by acoustic radiation force impulse measurements at 2 locations.

Objectives: The purpose of this study was to evaluate liver fibrosis by acoustic radiation force impulse (ARFI) measurements at 2 locations in patients with chronic hepatitis B and C.

Methods: A total of 204 consecutive patients (146 male and 58 female) with chronic hepatitis B (n = 121) and C (n = 83) who underwent liver biopsy were enrolled. All patients received ARFI measurements at 2 locations in the right intercostal space on the same day as biopsy.

Susceptibility-weighted MRI in mild traumatic brain injury.

Objective: To compare the frequency of microbleeds identified by susceptibility-weighted MRI (SWMRI) in patients with mild traumatic brain injury (mTBI) and normal controls, and correlate these findings with neuropsychological tests.

Methods: Research ethics committee approval and patient written informed consents were obtained. One hundred eleven patients with mTBI without parenchymal hemorrhage on CT and conventional MRI received SWMRI as well as a digit span and continuous performance test.