Olsonalbertsen1568

embrane transporter of ferric citrate.

The FciTABC and FeoABI systems contribute to ferric citrate acquisition in S. maltophilia.

The FciTABC and FeoABI systems contribute to ferric citrate acquisition in S. maltophilia.Articular cartilage damage is a universal health problem. Despite recent progress, chondrocyte dedifferentiation has severely compromised the clinical outcomes of cell-based cartilage regeneration. Loss-of-function changes are frequently observed in chondrocyte expansion and other pathological conditions, but the characteristics and intermediate molecular mechanisms remain unclear. In this study, we demonstrate a time-lapse atlas of chondrocyte dedifferentiation to provide molecular details and informative biomarkers associated with clinical chondrocyte evaluation. We performed various assays, such as single-cell RNA sequencing (scRNA-seq), live-cell metabolic assays, and assays for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), to develop a biphasic dedifferentiation model consisting of early and late dedifferentiation stages. Early-stage chondrocytes exhibited a glycolytic phenotype with increased expression of genes involved in metabolism and antioxidation, whereas late-stage chondrocytes exhibited ultrastructural changes involving mitochondrial damage and stress-associated chromatin remodeling. Using the chemical inhibitor BTB06584, we revealed that early and late dedifferentiated chondrocytes possessed distinct recovery potentials from functional phenotype loss. Notably, this two-stage transition was also validated in human chondrocytes. An image-based approach was established for clinical use to efficiently predict chondrocyte plasticity using stage-specific biomarkers. Overall, this study lays a foundation to improve the quality of chondrocytes in clinical use and provides deep insights into chondrocyte dedifferentiation.

Sleep duration is associated with mortality. However, prior studies exploring whether sleep duration predicts subsequent long-term mortality in patients with diabetes are limited. This study aims to examine whether metabolic factors affect the associations between baseline sleep duration and subsequent risks of all-cause, expanded, and non-expanded cardiovascular disease (CVD) mortalities among patients with type 2 diabetes (T2D).

A total of 12,526 T2D patients aged 30years and older, with a follow-up period ≥ 3years, were identified from the Diabetes Case Management Program of a medical center in Taiwan. Sleep duration was measured using computerized questionnaires by case managers, and the time frame for this question was 1month prior to the interview date. Sleep duration in relation to subsequent mortality from all causes, expanded CVD, and non-expanded CVD was examined using Cox proportional hazard models.

Within 10years of follow-up, 2918 deaths (1328 CVD deaths and 1590 non-CVD deaths) were recordween sleep duration and all-cause and expanded CVD mortality, and a sleep duration of 5-7 h had the lowest mortality risk. Sleep duration also showed significant synergistic interactions with diabetes duration but shared an antagonistic interaction with age and obesity.

We aimed to determine the rate and predictors of correctly diagnosed concussions in the pediatric emergency department and to describe the characteristics, presentation, and management of concussions in children presenting for minor head injury.

We included 186 patients aged 5 to 18 years presenting within 24 hours of minor head injuries and met our diagnostic criteria for concussion. We compared patients correctly diagnosed with a concussion with those who were not. Our main outcome was the rate and predictors of misdiagnoses.

Of the patients, 5.4% were correctly diagnosed. Amnesia was the only variable associated with correct diagnoses (40.0% vs 10.2%, P = 0.02). The most common mechanism of injury was fall (8.4%); the most frequent symptoms were nausea/vomiting (42.5%), and 48.4% had a brain computed tomography scan done.

The high rate of concussion misdiagnosis puts into question the usability of current concussion guidelines, their accuracy, and barriers to translation into clinical practice.

The high rate of concussion misdiagnosis puts into question the usability of current concussion guidelines, their accuracy, and barriers to translation into clinical practice.

Preterm birth is defined as live birth before 37 completed weeks of pregnancy, and it is a major problem worldwide. The molecular mechanisms that lead to onset of spontaneous preterm birth are incompletely understood. Prediction and evaluation of the risk of preterm birth is challenging as there is a lack of accurate biomarkers. In this study, our aim was to identify placental proteins that associate with spontaneous preterm birth.

We analyzed the proteomes from placentas to identify proteins that associate with both gestational age and spontaneous labor. Next, rare and potentially damaging gene variants of the identified protein candidates were sought for from our whole exome sequencing data. Further experiments we performed on placental samples and placenta-associated cells to explore the location and function of the spontaneous preterm labor-associated proteins in placentas.

Exome sequencing data revealed rare damaging variants in SERPINA1 in families with recurrent spontaneous preterm deliveries. Prble to proteases and inflammatory activation. This may lead to spontaneous premature birth.

Lung cancer is a kind of malignancy with high morbidity and mortality worldwide. Paclitaxel (PTX) is the main treatment for non-small cell lung cancer (NSCLC), and resistance to PTX seriously affects the survival of patients. However, the underlying mechanism and potential reversing strategy need to be further explored.

We identified ALDH2 as a PTX resistance-related gene using gene microarray analysis. Subsequently, a series of functional analysis in cell lines, patient samples and xenograft models were performed to explore the functional role, clinical significance and the aberrant regulation mechanism of ALDH2 in PTX resistance of NSCLC. Furthermore, the pharmacological agents targeting ALDH2 and epigenetic enzyme were used to investigate the diverse reversing strategy against PTX resistance.

Upregulation of ALDH2 expression is highly associated with resistance to PTX using in vitro and in vivo analyses of NSCLC cells along with clinicopathological analyses of NSCLC patients. ALDH2-overexpressing NSCLC cells exhibited significantly reduced PTX sensitivity and increased biological characteristics of malignancy in vitro and tumor growth and metastasis in vivo. EHMT2 (euchromatic histone lysine methyltransferase 2) inhibition and NFYA (nuclear transcription factor Y subunit alpha) overexpression had a cooperative effect on the regulation of ALDH2. Mechanistically, ALDH2 overexpression activated the RAS/RAF oncogenic pathway. NSCLC/PTX cells re-acquired sensitivity to PTX in vivo and in vitro when ALDH2 was inhibited by pharmacological agents, including the ALDH2 inhibitors Daidzin (DZN)/Disulfiram (DSF) and JIB04, which reverses the effect of EHMT2.

Our findings suggest that ALDH2 status can help predict patient response to PTX therapy and ALDH2 inhibition may be a promising strategy to overcome PTX resistance in the clinic.

Our findings suggest that ALDH2 status can help predict patient response to PTX therapy and ALDH2 inhibition may be a promising strategy to overcome PTX resistance in the clinic.Nonalcoholic steatohepatitis (NASH) is a state of simple steatosis that progresses to inflammation and liver injury accompanied by ferroptosis. Bone morphogenetic protein 4 (BMP4) plays an important role in adipogenesis and differentiation, as well as in hepatic steatosis and iron regulation. Dibenzazepine inhibitor However, the direct impact of BMP4 on NASH remains unclear. In this study, our aim was to investigate the effect of BMP4 on NASH and its underlying mechanism. We first explored BMP4 expression in vivo in mice and patients and in vitro in HepG2 and LO2 cell lines, and then, determined whether ferroptosis occurs in NASH. Further overexpression or inhibition of BMP4 was induced to observe the effect of BMP4 on liver ferroptosis in NASH. BMP4 expression was upregulated in patients and mice with nonalcoholic fatty liver disease, and free fatty acid (FFA)-induced HepG2 and LO2 cell lines. We observed ferroptosis in high-fat diet and high-fructose diet-fed mice and FFA-induced HepG2 and LO2 cell lines. BMP4 overexpressing plasm

Smoke from solid biomass cooking is often stated to reduce household mosquito levels and, therefore, malarial transmission. However, household air pollution (HAP) from solid biomass cooking is estimated to be responsible for 1.67 times more deaths in children agedunder 5years compared to malaria globally. This cross-sectional study investigates the association between malaria and (i) cleaner fuel usage; (ii) wood compared to charcoal fuel; and, (iii) household cooking location, among children aged under 5years in sub-Saharan Africa (SSA).

Population-based data was obtained from Demographic and Health Surveys (DHS) for 85,263 children within 17 malaria-endemic sub-Saharan countries who were who were tested for malaria with a malarial rapid diagnostic test (RDT) or microscopy. To assess the independent association between malarial diagnosis (positive, negative), fuel type and cooking location (outdoor, indoor, attached to house), multivariable logistic regression was used, controlling for individual, househher mixed-methods research will be required to further strengthen the evidence base concerning this risk paradigm and to support appropriate public health messaging in this context.

Cleaner fuels and outdoor cooking practices associated with reduced smoke exposure were not observed to have an adverse effect upon malarial infection among children under 5 years in SSA. Further mixed-methods research will be required to further strengthen the evidence base concerning this risk paradigm and to support appropriate public health messaging in this context.

Ghana has adopted and implemented intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) and insecticide-treated nets (ITNs) in an antenatal care (ANC) context to prevent malaria among pregnant women. However, the increased ANC attendance and its frequency facilitated by a free maternal health care policy in Ghana does not correspond with the uptake of IPTp-SP and ITN use among pregnant women. This study sought to elucidate the contextual health system factors influencing the delivery of IPTp-SP and ITN from a related quantitative study conducted in Ghana.

This is the qualitative section of a mixed-methods study design, where audio recorded key informant interviews (KIIs) were conducted with health workers from across health facilities, districts, regional and national health directorates. The KIIs elicited information on health worker knowledge, perceptions, and rationale for the delivery practices of IPTp-SP and ITN revealed in the quantitative findings. The interviews were transcriining strategy led to delayed delivery of IPTp-SP to eligible pregnant women. Supply chain management challenges related to stock of SP and ITN resulted in missed opportunities to deliver the interventions to pregnant women attending ANC.

Poor health worker knowledge on policy directives, a consequence of ineffective training strategy led to delayed delivery of IPTp-SP to eligible pregnant women. Supply chain management challenges related to stock of SP and ITN resulted in missed opportunities to deliver the interventions to pregnant women attending ANC.