DNA damage elicits a cellular signaling response that initiates cell cycle arrest and DNA repair. Here, we find that DNA damage triggers a critical block in glutamine metabolism, which is required ...for proper DNA damage responses. This block requires the mitochondrial SIRT4, which is induced by numerous genotoxic agents and represses the metabolism of glutamine into tricarboxylic acid cycle. SIRT4 loss leads to both increased glutamine-dependent proliferation and stress-induced genomic instability, resulting in tumorigenic phenotypes. Moreover, SIRT4 knockout mice spontaneously develop lung tumors. Our data uncover SIRT4 as an important component of the DNA damage response pathway that orchestrates a metabolic block in glutamine metabolism, cell cycle arrest, and tumor suppression.
► DNA damage induces SIRT4 and inhibits mitochondrial glutamine metabolism ► SIRT4 is required for proper repression of glutamine metabolism after DNA damage ► SIRT4 loss promotes genomic instability ► SIRT4 represses tumor growth, and SIRT4 knockout mice develop tumors with age
Fatty acid uptake is the first step in fatty acid utilization, but it remains unclear how the process is regulated. Protein palmitoylation is a fatty acyl modification that plays a key regulatory ...role in protein targeting and trafficking; however, its function in regulating fatty acid metabolism is unknown. Here, we show that two of the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 and DHHC5, regulate fatty acid uptake. DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. Depletion of either DHHC4 or DHHC5 in cells disrupts CD36-dependent fatty acid uptake. Furthermore, both Dhhc4−/− and adipose-specific Dhhc5 knockout mice show decreased fatty acid uptake activity in adipose tissues and develop severe hypothermia upon acute cold exposure. These findings demonstrate a critical role of DHHC4 and DHHC5 in regulating fatty acid uptake.
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•CD36 is a physiological substrate of palmitoyl acyltransferases DHHC4/5•Palmitoylation of CD36 targets it to the plasma membrane•DHHC4/5 are required for the cellular fatty acid uptake activity of CD36•DHHC4/5 regulate fatty acid uptake activity in adipose tissues
Regulation of fatty acid uptake remains unclear. Wang et al. show that palmitoylation of CD36 by DHHC4 and DHHC5 is required for its plasma membrane localization and fatty acid uptake activity. Deficiency in DHHC4 or DHHC5 leads to decreased fatty acid uptake and increased susceptibility to cold.
The exploitation of new titanium‐based coordination polymers (Ti CPs) with high crystallinity is difficult but highly desirable for their potential applications in photocatalysis. Herein, a ...cluster‐cooperative assemble strategy is developed to synthesize Ti CPs. By utilizing various bifunctional ligands containing carboxylate acids and N‐donor groups, we successfully assembled the zero‐dimensional (0D) (Ti3O)(iPrO)82+ or (Ti4O2)(iPrO)66+ clusters into one‐dimensional (1D) tube‐, ribbon‐, or helical chain‐shape architectures, two‐dimensional (2D) layered structures, and a rare parallel 2D→three‐dimensional (3D) polycatenation framework with various copper iodide dopants, including rhombus‐ or wing‐shaped Cu2I2 and tetrahedron‐ or ladder‐shaped Cu4I4. The as‐synthesized compounds display strong absorption in the visible region with narrow band gaps ranging from 1.70 to 2.72 eV and exhibit good photocatalytic activities in the degradation of organic pollutants.
TiC, TOC: By employing a cluster‐cooperative assemble strategy, a family of heterometallic Ti‐based coordination polymers (see figure) with interesting structural topologies and high photocatalytic activities has been synthesized and structurally characterized.
Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), ...systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia.
Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis.
A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147).
Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.
The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments ...and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.
In thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which ...induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism. To test this hypothesis, we examined erythroblast transcriptome profiles from 15 healthy, nonthalassemic donors. Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, showed increased expression and secretion during erythroblast maturation. Healthy volunteers had mean GDF15 serum concentrations of 450 +/- 50 pg/ml. In comparison, individuals with beta-thalassemia syndromes had elevated GDF15 serum levels (mean 66,000 +/- 9,600 pg/ml; range 4,800-248,000 pg/ml; P < 0.05) that were positively correlated with the levels of soluble transferrin receptor, erythropoietin and ferritin. Serum from thalassemia patients suppressed hepcidin mRNA expression in primary human hepatocytes, and depletion of GDF15 reversed hepcidin suppression. These results suggest that GDF15 overexpression arising from an expanded erythroid compartment contributes to iron overload in thalassemia syndromes by inhibiting hepcidin expression.
Neddylation, the covalent attachment of ubiquitin-like protein Nedd8, of the Cullin-RING E3 ligase family regulates their ubiquitylation activity. However, regulation of HECT ligases by neddylation ...has not been reported to date. Here we show that the C2-WW-HECT ligase Smurf1 is activated by neddylation. Smurf1 physically interacts with Nedd8 and Ubc12, forms a Nedd8-thioester intermediate, and then catalyses its own neddylation on multiple lysine residues. Intriguingly, this autoneddylation needs an active site at C426 in the HECT N-lobe. Neddylation of Smurf1 potently enhances ubiquitin E2 recruitment and augments the ubiquitin ligase activity of Smurf1. The regulatory role of neddylation is conserved in human Smurf1 and yeast Rsp5. Furthermore, in human colorectal cancers, the elevated expression of Smurf1, Nedd8, NAE1 and Ubc12 correlates with cancer progression and poor prognosis. These findings provide evidence that neddylation is important in HECT ubiquitin ligase activation and shed new light on the tumour-promoting role of Smurf1.
Core-shell heterostructured BiVO4@Fe2O3 photocatalysts are fabricated through a facile solution combustion and in-situ precipitation methods. Transmission electron microscopy (TEM) and ...high-resolution TEM (HRTEM) images verify their core-shell structure. X-ray photoelectron spectroscopy (XPS) results indicate there are interaction between BiVO4 and Fe2O3, confirming the formation of heterojunction. Mott–Schottky measurements exhibit that hybridizing with Fe2O3 makes the conduction band of BiVO4 to be shifted up by 1.05 V from 0.21 to −0.84 V, which endows BiVO4 to be effective for photocatalytic H2 generation. Meanwhile, photoluminescence spectra show that the heterosturcture decreases the recombination efficiency of photo-induced electrons and holes. Hydrogen experiments indicate that BiVO4@Fe2O3 composite containing 10 wt% Fe2O3 has the highest catalytic activity.
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•Core-shell heterostructured BiVO4@Fe2O3 composites are fabricated via solution combustion and precipitation methods.•Hybridizing with Fe2O3 makes conduction band of BiVO4 to be shifted up by 1.05 V from 0.21 to −0.84 V.•Elevation of conduction band endows BiVO4 to be effective for photocatalytic H2 generation.•H2 evolution can reach 139.0 μmol g−1 over BiVO4@Fe2O3 composite containing 10 wt% Fe2O3.
Aims
To determine psychological symptoms of patients with mild symptoms of coronavirus disease 2019 in China and to explore the influencing factors.
Design
A cross‐sectional study.
Methods
A ...convenience sample of 296 mild coronavirus disease 2019 patients were recruited from a Fangcang hospital in Wuhan, Hubei Province, from 3–5 March, 2020. Participants were assessed using a sociodemographic and clinical characteristics questionnaire, and Symptom Check List 90. The binary logistic regression was utilized to explore the influencing factors of psychological symptoms of patients with mild symptoms of coronavirus disease 2019.
Results
In total, 296 of 299 patients with mild symptoms of coronavirus disease 2019 participated in the study (response rate: 99.0%). The findings revealed that 12.8% patients with mild symptoms have mental health problems; the most common psychological symptoms are phobic anxiety (58.4%), paranoid ideation (50.7%) and psychoticism (40.2%). Female patients OR = 3.587, 95% CI (1.694–7.598) and those having physical symptoms currently OR = 2.813, 95% CI (1.210–6.539) are at higher risk, while those in the middle duration of hospitalization OR = 0.278, 95% CI (0.121–0.639) protect against mental‐health problems.
Conclusions
The minority of patients with mild symptoms of coronavirus disease 2019 were still suffering from psychological symptoms. Healthcare providers are recommended to pay particular attention to screening these high‐risk groups (women, those in the initial stages of hospitalization and those with physical symptoms currently) and implement targeted psychological care as required.
Impact
This study found that most patients of coronavirus disease 2019 in Fangcang hospital exhibited normal mental health at par with the general Chinese norm and the minority of them were suffering from psychological symptoms. The findings can provide a reference for healthcare providers to screen high‐risk psychological symptoms groups and implement targeted psychological intervention for patients with coronavirus disease 2019.
摘要
目的
了解中国新冠病毒肺炎轻度症状患者的心理症状, 并探讨影响因素。
设计
一项横截面研究。
方法
2020年3月3日至3月5日, 在湖北省武汉市方仓医院招募296例新冠病毒肺炎轻度症状患者作为便利样本。采用社会人口学和临床特征调查问卷以及症状自评量表90对参与者进行评估。利用二元逻辑回归探讨了新冠病毒肺炎患者心理症状的影响因素。
结果
在299例新冠病毒肺炎轻度症状患者中, 共有296例参与研究 (有效率: 99.0%) 。研究结果显示, 12.8%的轻度症状患者存在心理健康问题; 最常见的心理症状是恐惧焦虑 (58.4%) 、偏执(50.7%) 和精神质 (40.2%) 。女性患者【OR=3.587,95%CI(1.694‐7.598) 】和目前有体症的患者【OR=2.813,95%CI(1.210‐6.539) 】风险较高, 而住院中期的患者【OR=0.278,95%CI(0.121‐0.639) 】可以预防心理健康问题。
结论
在新冠病毒肺炎病症状较轻的患者中, 少数患者仍有心理症状。建议医疗服务提供者特别注意筛查这些高危人群 (女性、住院初期和目前有身体症状的人群) , 并根据需要实施针对性的心理护理。
影响
本研究发现, 方仓医院新冠病毒肺炎病患者大多表现为心理健康正常, 与中国一般常态持平, 少数患者存在心理症状。该研究结果可为医疗服务提供者筛选高危心理症状群体并对新冠病毒肺炎患者实施针对性的心理干预提供参考。
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