Pluripotent stem cells (PSCs) hold great promise in cell-based therapy, but the genomic instability seen in culture hampers their full application. A greater understanding of the factors that ...regulate genomic stability in PSCs could help address this issue. Here we describe the identification of Filia as a specific regulator of genomic stability in mouse embryonic stem cells (ESCs). Filia expression is induced by genotoxic stress. Filia promotes centrosome integrity and regulates the DNA damage response (DDR) through multiple pathways, including DDR signaling, cell-cycle checkpoints and damage repair, ESC differentiation, and apoptosis. Filia depletion causes ESC genomic instability, induces resistance to apoptosis, and promotes malignant transformation. As part of its role in DDR, Filia interacts with PARP1 and stimulates its enzymatic activity. Filia also constitutively resides on centrosomes and translocates to DNA damage sites and mitochondria, consistent with its multifaceted roles in regulating centrosome integrity, damage repair, and apoptosis.
Display omitted
•Loss of Filia promotes genomic instability and transformation in ESCs•Filia is induced by genotoxic stress and regulates repair responses•Filia is regulated by post-translational modification and sub-cellular translocation•Filia interacts with PARP1 and stimulates its enzymatic activity
Zhao et al. identify Filia as an ESC-specific regulator of genomic stability that is induced by genotoxic stress. Functional characterization highlights dynamic subcellular translocation and roles in governing multiple DNA damage response pathways, including stimulation of PARP1 enzymatic activity.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Reasonable nitrogen fertilizer application is an important strategy to maintain optimal growth of grasslands, thereby enabling them to better fulfil their ecological functions while reducing ...environmental pollution caused by high nitrogen fertilizer production and application. Optimizing the ammonium (NH
):nitrate (NO
) ratio is a common approach for growth promotion in crops and vegetables, but research on this topic in grass plants has not received sufficient attention. Centipedegrass, which is widely used in landscaping and ecological protection, was used as the experimental material. Different NH
:NO
ratios (0: 100, 25:75, 50:50, 75:25, 100:0) were used as the experimental treatments under hydroponic conditions. By monitoring the physiological and morphological changes under each treatment, the appropriate NH
:NO
ratio for growth and its underlying mechanism were determined. As the proportion of ammonium increased, the growth showed a "bell-shaped" response, with the maximum biomass and total carbon and nitrogen accumulation achieved with the NH
:NO
ratio of 50:50 treatment. Compared with the situation where nitrate was supplied alone, increasing the ammonium proportion increased the whole plant biomass by 93.2%, 139.7%, 59.0%, and 30.5%, the whole plant nitrogen accumulation by 44.9%, 94.6%, 32.8%, and 54.8%, and the whole plant carbon accumulation by 90.4%, 139.9%, 58.7%, and 26.6% in order. As a gateway for nitrogen input, the roots treated with an NH
:NO
ratio of 50:50 exhibited the highest ammonium and nitrate uptake rate, which may be related to the maximum total root length, root surface area, average root diameter, root volume, and largest root xylem vessel. As a gateway for carbon input, leaves treated with an NH
:NO
ratio of 50:50 exhibited the highest stomatal aperture, stomatal conductance, photosynthetic rate, transpiration rate, and photosynthetic products. The NH
:NO
ratio of 50:50 treatment had the largest stem xylem vessel area. This structure and force caused by transpiration may synergistically facilitate root-to-shoot nutrient translocation. Notably, the change in stomatal opening occurred in the early stage (4 hours) of the NH
:NO
ratio treatments, indicating that stomates are structures that are involved in the response to changes in the root NH
:NO
ratio. In summary, we recommend 50:50 as the appropriate NH
:NO
ratio for the growth of centipedegrass, which not only improves the nitrogen use efficiency but also enhances the carbon sequestration capacity.
The electrochemical transformation of biomass to high value‐added products is attractive. Herein, Cu sulfide‐mediated in‐situ synthesis of Cu oxide was achieved for efficient electro‐oxidation of ...biomass derived 5‐hydroxymethylfurfural (HMF) to 2,5‐furandicarboxylic acid (FDCA). The copper foam‐supported Cu sulfide (Cu−S/CF) was in‐situ converted to Cu oxide during the electro‐oxidation process. The in‐situ formed Cu oxide presented high HMF conversion, FDCA yield, and faradaic efficiency in 1 m KOH with HMF concentration up to 100 mm. The oxidation of HMF on Cu oxide started with the formation of high‐valence Cu species with the assistance of OH−, which then oxidized HMF spontaneously. An anion exchange membrane (AEM) electrolyzer with Cu−S/CF as the anode was assembled to continuously produce FDCA with H2 generation at the cathode. The AEM electrolyzer ran stably for 60 h with FDCA content higher than 85 % at a cell voltage between 1.50 and 1.60 V.
Biomass electrochemical oxidation: Copper foam‐supported Cu sulfide (Cu−S/CF) is in‐situ converted to Cu oxide during electrochemical oxidation of 5‐hydroxymethylfurfural. The anion exchange membrane electrolyzer with Cu−S/CF as the anode can work stably for at least 60 h, and the 2,5‐furandicarboxylic acid content in the product can be higher than 90 %.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Alpha-fetoprotein (AFP) is a well-established biomarker for hepatocellular carcinoma (HCC). Here, we investigated the acetylation state of AFP in vivo. AFP acetylation was regulated by the ...acetyltransferase CBP and the deacetylase SIRT1. Acetylation of AFP at lysines 194, 211, and 242 increased the stability of AFP protein by decreasing its ubiquitination and proteasomal degradation. AFP acetylation promoted its oncogenic role by blocking binding to the phosphatase PTEN and the pro-apoptotic protein caspase-3, which increased signaling for proliferation, migration, and invasion and decreased apoptosis. High levels of acetylated AFP in HCC tissues were associated with HBV infection and correlated with poor prognosis and decreased patient survival. In HCC cells, hepatitis B virus X protein (HBx) and palmitic acid (PA) increased the level of acetylated AFP by disrupting SIRT1-mediated deacetylation. AFP acetylation plays an important role in HCC progression and provides a new potential prognostic marker and therapeutic target for HCC.
•AFP acetylation status is regulated by CBP and SIRT1.•Acetylation stabilizes AFP protein levels by inhibiting its ubiquitination.•AFP acetylation inhibits apoptosis and promotes HCC oncogenesis.•HBx and PA promote AFP acetylation.•High expression of acetylated AFP in HCC tissues correlates with poor prognosis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To build and validate a radiomics nomogram based on preoperative CT scans and clinical data for detecting synchronous ovarian metastasis (SOM) in female gastric cancer (GC) cases.
Pathologically ...confirmed GC cases in 2 cohorts were retrospectively enrolled. All cases had presurgical abdominal contrast-enhanced CT and pelvis contrast-enhanced MRI and pathological examinations for any suspicious ovarian lesions detected by MRI. Cohort 1 cases (n = 101) were included as the training set. Radiomics features were obtained to develop a radscore. A nomogram combining the radscore and clinical factors was built to detect SOM. The bootstrap method was carried out in cohort 1 as internal validation. External validation was carried out in cohort 2 (n = 46). Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) and the confusion matrix were utilized to assess the performances of the radscore, nomogram and subjective evaluation model.
The nomogram, which combined age and the radscore, displayed a higher AUC than the radscore and subjective evaluation (0.910 vs 0.827 vs 0.773) in the training cohort. In the external validation cohort, the nomogram also had a higher AUC than the radscore and subjective evaluation (0.850 vs 0.790 vs 0.675). DCA and the confusion matrix confirmed the nomogram was superior to the radscore in both cohorts.
This pilot study showed that a nomogram model combining the radscore and clinical characteristics is useful in detecting SOM in female GC cases. It may be applied to improve clinical treatment and is superior to subjective evaluation or the radscore alone.
Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after ...propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery.
This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65–90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days.
A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 35% women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 95% confidence interval {CI}: 0.48–0.95; P=0.023; adjusted relative risk 0.59 95% CI: 0.39–0.90; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 95% CI: 0.33–0.75; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups.
Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium.
Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).
In this study we report the results of a decade-long breeding program for japonica super rice made by Nanjing Branch of Chinese National Center for Rice Improvement in Jiangsu Academy of Agricultural ...Sciences. We concluded that selection of parents with good comprehensive traits and complementary advantages and disadvantages of both parents in the hybrid combination, and early selection of high heritability traits in earlier segregating generations could significantly improve the breeding efficiency. The use of closely-linked functional markers in pyramiding of multiple genes could greatly increase breeding efficiency, avoiding time-consuming and laborious steps that were used in traditional breeding program. It is also important to coordinate the yield components with variety characteristics such as yield stability, wide adaptability, lodging resistance, and an attractive grain appearance during late growth stage of rice.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the thermodynamic evolution of black holes, the generalized uncertainty principle and quantum tunneling effect prevent the complete evaporation of black holes and produce remnants, and ...thermodynamic phase transition occurs during evaporation. Based on the generalized uncertainty principle and the method of quantum tunneling, we study the phase transition of the quantum–corrected black hole. Using the modified Hamiltonian–Jacobi equation to analyze the corrected thermodynamic quantity, we find that the thermodynamic phase transition of the black hole is not only depending on the nature of the black hole itself, it also depends on quantum parameter
ξ
, generalized uncertainty parameter β and parameter
λ
.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background To explore the changes of neuroinflammatory factors in cerebrospinal fluid (CSF) of Parkinson’s disease (PD) with depression (PD-D) patients, and their correlation with monoamine ...neurotransmitters in PD-D. Methods Neuroinflammatory factors and neurotransmitters in CSF were measured and compared between PD without depression (PD-ND) patients and PD-D patients. The relationship between PD-D and neuroinflammatory factors was studied by binary logistic regression equation, and the related factors of PD-D were adjusted. The correlations of the levels of neuroinflammatory factors and neurotransmitters in PD-D group were analyzed. Results The levels of TNF-α in the CSF of PD-D group were significantly higher and there were no significant differences in the levels of interleukin-1β, prostaglandin E2, hydrogen peroxide and nitric oxide. The 24-item Hamilton Depression Scale (HAMD-24) score was positively correlated with the level of TNF-α in CSF. Binary logistic regression showed that the OR of CSF TNF-α level was 1.035 (95% CI 1.002-1.069). The levels of DA in the CSF of the PD-D group were significantly lower than those in the PD-ND group. TNF-α level were negatively correlated with the DA levels in CSF of PD patients (r=-0.320，P=0.003). Conclusions Neuroinflammatory factors, especially TNF-α, may play an important role in PD-D. It may cause damage to DA neurons and lead to the depletion of DA, which is related to the occurrence and development of PD-D.
This study was designed to evaluate the distribution of Tregs/Th17/Th1 cells in type 2 diabetic patients with foot disease before and after human umbilical cord blood mesenchymal stem cell ...(hUCB-MSCs) transplantation. Fifteen diabetic patients with foot disease under insulin therapy received hUCB-MSC transplantation. The hUCB-MSCs were directly injected into the quadriceps thigh muscles in patients with foot disease (cell quantity at 2 x 10⁶ per point). Physical attributes, blood cytokines, blood glucose and insulin dosage were evaluated before treatment and 1, 2, 4, 8, and 12 weeks thereafter. The ratios of Treg/Th17, Treg/Th1, and Th17/Th1 cells were measured using flow cytometry and their correlation with various cytokines (FoxP3, IL-17, INF-γ, C-RP, TNF-α, and VEGF) was scrutinized. Levels of blood glucose and insulin dosage were significantly reduced in all 15 patients following hUCB-MSC transplantation. The ratios of CD4⁺CD25(hi)FoxP3⁺ Treg/Th17 and CD4⁺CD25(hi)FoxP3⁺ Treg/Th1 cells were significantly increased 4 weeks after transplantation (p < 0.01), while the ratio of Th17/Th1 cells remained unchanged. Serum levels of VEGF peaked at 4 weeks following transplantation. Levels of C-RP and TNF-α were significantly reduced 4 weeks after transplantation. Intriguingly, the ratios of Treg/Th17 were positively correlated with VEGF levels, and were inversely correlated with plasma IL-6 levels. Our data indicated that immune disorders are associated with the development of type 2 diabetes and its complications. Levels of blood glucose and required insulin dosage were reduced after hUCB-MSC transplantation accompanied with improved clinical profiles in diabetic patients. These data favor a role for Treg cells in the onset and progression of T2D.
PDF
