Distribution of Heavy Metals in Core Sediments from Baihua Lake

AbstractIn the present research, five core sediments from Baihua Lake, a man-made reservoir located in the karst area on the Yunnan-Guizhou Plateau in China, were analyzed to study the distribution, origin and contamination of three selected heavy metals (Cu, Zn and Mn). The results showed that the concentrations of these heavy metals in sediments varied from different sampling locations and layers. The average concentrations of these heavy metals at the same sampling location followed the order of Mn>Zn>Cu. The mean concentrations of Zn and Mn in the samples at the depth of 0-5cm and the depth of 5-10cm of the core sediments were higher than those in the other layers. All of Cu, Zn and Mn presented similar distribution characteristics at sampling site CFZ, and different distribution characteristics from the other four sampling locations. A statistical analysis indicated that there were some correlations between the concentrations of these three heavy metals and other studied six elements occurring in the core sediment samples. Three components were obtained with principal component analysis (PCA) analysis of heavy metals concentrations in core sediment samples

Inhibition of HDAC activity directly reprograms murine embryonic stem cells to trophoblast stem cells

Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.</p

Hematopoietic stem cell quiescence and DNA replication dynamics maintained by the resilient β-catenin/Hoxa9/Prmt1 axis

Maintenance of quiescence and DNA replication dynamics are two paradoxical requirements for the distinct states of dormant and active hematopoietic stem cells (HSCs), which are required to preserve the stem cell reservoir and replenish the blood cell system in response to hematopoietic stress respectively. Here, we show that key self-renewal factors, β-catenin or Hoxa9, largely dispensable for HSC integrity in fact have dual functions in maintaining quiescence and enabling efficient DNA replication fork dynamics to preserve the functionality of hematopoietic stem and progenitor cells (HSPCs). While β-catenin or Hoxa9 single knockout (KO) exhibited mostly normal hematopoiesis, their co-inactivation led to severe hematopoietic defects stemmed from aberrant cell cycle, DNA replication and damage in HSPCs. Mechanistically, β-catenin and Hoxa9 function in a compensatory manner to sustain key transcriptional programs that converge on the pivotal downstream target and epigenetic modifying enzyme, Prmt1, which protects the quiescent state and ensures an adequate supply of DNA replication and repair factors to maintain robust replication fork dynamics. Inactivation of Prmt1 phenocopied both cellular and molecular phenotypes of β-catenin/Hoxa9 combined KO, which at the same time could also be partially rescued by Prmt1 expression. The discovery of the highly resilient β-catenin/Hoxa9/Prmt1 axis in protecting both quiescence and DNA replication dynamics essential for HSCs at different key states provides not only novel mechanistic insights into their intricate regulation but also a potential tractable target for therapeutic intervention

Clinical efficacy and tendon integrity of patients with subscapularis tear by the technique of arthroscopic single external row repair

BackgroundWith the development of arthroscopic technology and equipment, arthroscopy can effectively repair the tear of the subscapular muscle. However, it is difficult to expose the subscapular muscle and operate it under a microscope. In this study, the SwiveLock® C external row anchor under arthroscopy was applied to repair the tear of the subscapular muscle in a single row, which is relatively easy to operate with reliable suture and fixation, and its efficacy was evaluated.PurposeThis study aimed to assess the clinical efficacy and the tendon integrity of patients who had subscapularis tears by adopting the single-row repair technique with a SwiveLock® C external row anchor.MethodsPatients who had the subscapular muscle tear either with or without retraction were included, and their follow-up time was at least 1 year. The degree of tendon injury was examined by magnetic resonance imaging (MRI) and confirmed by arthroscopy. The tendon was repaired in an arthroscopic manner by utilizing the single-row technique at the medial margin of the lesser tuberosity. One double-loaded suture SwiveLock® C anchor was applied to achieve a strong fixation between the footprint and tendon. The range of motion, pain visual simulation score, American Shoulder and Elbow Surgeons (ASES) score, and Constant score of shoulder joint were evaluated for each patient before the operation, 3 months after the operation, and at least 1 year after the operation.ResultsIn total, 110 patients, including 31 males and 79 females, with an average age of 68.28 ± 8.73 years were included. Arthroscopic repair of the subscapular tendon with SwiveLock® C external anchor can effectively improve the range of motion of the shoulder joint. At the last follow-up, the forward flexion of the shoulder joint increased from 88.97 ± 26.33° to 138.38 ± 26.48° (P &lt; 0.05), the abduction range increased from 88.86 ± 25.27° to 137.78 ± 25.64° (P &lt; 0.05), the external rotation range increased from 46.37 ± 14.48° to 66.49 ± 14.15° (P &lt; 0.05), and the internal rotation range increased from 40.03 ± 9.01° to 57.55 ± 7.43° (P &lt; 0.05). The clinical effect is obvious. The constant shoulder joint score increased from 40.14 ± 15.07 to 81.75 ± 11.00 (P &lt; 0.05), the ASES score increased from 37.88 ± 13.24 to 82.01 ± 9.65 (P &lt; 0.05), and the visual analog scale score decreased from 5.05 ± 2.11 to 1.01 ± 0.85 (P &lt; 0.05). In the 6th month after the operation, two cases (1.81%) were confirmed to have re-tears via MRI.ConclusionIn this study, we repaired the subscapularis muscle with a single-row technique fixed by SwiveLock® C anchor and FiberWire® sutures and evaluated its efficacy. The results showed that the clinical effect of single-row arthroscopic repair was satisfactory and that reliable tendon healing could be achieved

Ripk3 signaling regulates HSCs during stress and represses radiation-induced leukemia in mice

Receptor-interacting protein kinase 3 (Ripk3) is one of the critical mediators of inflammatory cytokine-stimulated signaling. Here we show that Ripk3 signaling selectively regulates both the number and the function of hematopoietic stem cells (HSCs) during stress conditions. Ripk3 signaling is not required for normal homeostatic hematopoiesis. However, in response to serial transplantation, inactivation of Ripk3 signaling prevents stress-induced HSC exhaustion and functional HSC attenuation, while in response to fractionated low doses of ionizing radiation (IR), inactivation of Ripk3 signaling accelerates leukemia/lymphoma development. In both situations, Ripk3 signaling is primarily stimulated by tumor necrosis factor-α. Activated Ripk3 signaling promotes the elimination of HSCs during serial transplantation and pre-leukemia stem cells (pre-LSCs) during fractionated IR by inducing Mlkl-dependent necroptosis. Activated Ripk3 signaling also attenuates HSC functioning and represses a pre-LSC-to-LSC transformation by promoting Mlkl-independent senescence. Furthermore, we demonstrate that Ripk3 signaling induces senescence in HSCs and pre-LSCs by attenuating ISR-mediated mitochondrial quality control

Abnormal focal segments in left uncinate fasciculus in adults with obsessive–compulsive disorder

BackgroundAlthough the specific role of the uncinate fasciculus (UF) in emotional processing in patients with obsessive–compulsive disorder (OCD) has been investigated, the exact focal abnormalities in the UF have not been identified. The aim of the current study was to identify focal abnormalities in the white matter (WM) microstructure of the UF and to determine the associations between clinical features and structural neural substrates.MethodsIn total, 71 drug-naïve patients with OCD and 81 age- and sex-matched healthy controls (HCs) were included. Automated fiber quantification (AFQ), a tract-based quantitative approach, was adopted to measure alterations in diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), along the trajectory of the UF. Additionally, we utilized partial correlation analyses to explore the relationship between the altered diffusion parameters and clinical characteristics.ResultsOCD patients showed significantly higher FA and lower RD at the level of the temporal and insular portions in the left UF than HCs. In the insular segments of the left UF, increased FA was positively correlated with the Hamilton Anxiety Scale (HAMA) score, while decreased RD was negatively correlated with the duration of illness.ConclusionWe observed specific focal abnormalities in the left UF in adult patients with OCD. Correlations with measures of anxiety and duration of illness underscore the functional importance of the insular portion of left UF disturbance in OCD patients

Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells

TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2-/- mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2-/- tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies. Single-cell-targeted sequencing of wild-type and premalignant Tet2-/- Lin-c-Kit+ cells shows higher mutation frequencies in Tet2-/- cells. We further show that the increased mutational burden is particularly high at genomic sites that gained 5-hydroxymethylcytosine, where TET2 normally binds. Furthermore, TET2-mutated myeloid malignancy patients have significantly more mutational events than patients with wild-type TET2. Thus, Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells, suggesting a novel TET2 loss-mediated mechanism of haematological malignancy pathogenesis

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe