Ubiquitin-specific-processing proteases (USPs), the largest deubiquitinating enzyme (DUB) subfamily, play critical roles in cancer. However, clinical utility of USPs is hindered by limited knowledge ...about their varied and substrate-dependent actions. Here, we performed a comprehensive investigation on pan-cancer impacts of USPs by integrating multi-omics data and annotated data resources, especially a deubiquitination network. Meaningful insights into the roles of 54 USPs in 29 types of cancers were generated. Although rare mutations were observed, a majority of USPs exhibited significant expressional alterations, prognostic impacts and strong correlations with cancer hallmark pathways. Notably, from our DUB-substrate interaction prediction model, additional USP-substrate interactions (USIs) were recognized to complement knowledge gap about cancer-relevant USIs. Intriguingly, expression signatures of the USIs revealed clinically meaningful cancer subtypes, where key USPs and substrates cooperatively contributed to significant prognosis differences among subtypes. Overall, this investigation provides a valuable resource to assist mechanism research and clinical utility about USPs.
Metastable structures are promising candidates for efficient catalysis owing to abundant active electronic states, strong electronic coupling with reactants, and energetic preference. Exerting the ...value of metastable structures while evading the difficulty in direct synthesis remains challenging. Herein, it is reported that light irradiation enables the generation and maintenance of the metastable state over copper single atoms for efficient carbon dioxide reduction. Under irradiation with light, photogenerated electrons transit to Cu‐3d orbits and initiate d‐orbital rearrangement. The initial symmetric Cu1─O4 coordination converts to the metastable asymmetric structure of Cu1─O2+1, and is reversibly restored after removing the light. The photoinduced metastable intermediate of Cu1─O2+1 promotes the Cu single‐atom catalyst to deliver an ethylene yield rate of 60.4 µmol gcat.−1 h−1. Mechanistic studies reveal that Cu1─O2+1 possesses stronger adsorption capability for reactants and intermediates. The reaction energy barrier over Cu1─O2+1 also shows an obvious decline compared to that over Cu1─O4.
Phyllosilicate minerals are the important components in soils and an important source of activated aluminum (Al) during soil acidification. However, the mechanisms for Al activation in phyllosilicate ...minerals were not understood well. In this paper, the effect of phyllosilicate surface hydroxyl groups on Al activation during acidification was studied after the minerals were modified with inorganic and organic materials. After modification of kaolinite, montmorillonite, and illite with fulvic acid (FA-), iron oxide (Fe-), Fe combined with FA (Fe-FA-), and siloxane (Si–O-), the interlayer spaces were altered. For instance, when modified with Fe, Fe entered the interlayer spaces of kaolinite and montmorillonite and changed the interlayer spaces of both minerals but did not affect that of illite. Also, the other modification methods had significant effects on the interlayer space of montmorillonite but not on kaolinite and illite. It was observed that all the modification strategies inhibited Al activation during acidification by reducing the number of hydroxyl groups on the mineral surfaces and inhibiting protonation reactions between H+ and hydroxyl groups. Nevertheless, the inhibition effect varies with the type of phyllosilicate mineral. For kaolinite (Kao), the inhibition effect of the different modification methods on Al activation during acidification followed: Fe-FA-Kao > Fe-Kao > Si–O-Kao > FA-Kao. Additionally, for montmorillonite (Mon), the inhibition effect was in the order: Si–O-Mon > Fe-Mon > Fe-FA-Mon > FA-Mon, while for illite, it was: Fe-illite > Si–O-illite ≈ Fe-FA-illite > FA-illite. Thus, the hydroxyl groups on the surfaces and edges of phyllosilicate minerals play an important role in the activation of Al from the mineral structure. Also, the protonation of hydroxyl groups may be the first step during Al activation in these minerals. The results of this study can serve as a reference for the development of new technologies to inhibit soil acidification and Al activation.
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•Surface –OH of phyllosilicate minerals plays an important role in Al mobilization.•Surface modification reduced active hydroxyl groups on phyllosilicate minerals.•Surface modification inhibited Al activation in minerals induced by acidification.
Two dinuclear Ni (II) and Zn (II) salamo‐type complexes, Ni2(L)(μ‐OAc)(MeOH)·2CHCl3 (1) and {Zn2(L)(μ‐OMe)}3·3CHCl3·MeOH (2), have been successfully synthesized by wet‐chemical method and ...characterized by elemental analyses, IR spectra, UV–Vis spectra and single crystal X‐ray diffraction. Complex 1 consists of two closely related dinuclear units 1A and 1B, and complex 2 consists of three closely related dinuclear units 2A, 2B and 2C. The five units are unique example of crystallographically independent but chemically identical molecules. The Ni (II) atoms of complex 1 are located in the N2O4 coordination cavities, possessing six‐coordinated distorted octahedral geometries, but all Zn (II) atoms in complex 2 are located in the N2O3 coordination cavities, possessing five‐coordinated distorted square‐pyramid and triangular bipyramid geometries, the geometries about the Zn (II) atoms (Zn3 and Zn6) that obtain in 2B and 2C where τ5 is very close to 0.500, which is τ5Zn3 = 0.5006 and τ5Zn6 = 0.4941, respectively. The interactions were quantitatively determined by Hirshfeld surfaces analyses. Significantly, fluorescence properties were also investigated.
Two dinuclear Ni (II) and Zn (II) complexes based on a salamo‐type ligand H3L, Ni2(L)(μ‐OAc)(MeOH)·2CHCl3 (1) and {Zn2(L)(μ‐OMe)}3·3CHCl3·MeOH (2), have been successfully synthesized by wet‐chemical method. Complexes 1 and 2 are unique example of crystallographically independent but chemically identical molecules. The interactions were quantitatively determined by Hirshfeld surfaces analyses, and fluorescence properties were also investigated.
Biochar was prepared from rice straw and modified with 15% H2O2 and 1:1 HNO3/H2SO4, respectively. The unmodified biochars and HCl treated biochars for carbonate removal were used as control. The ...biochars were added to the acid paddy soil collected from Langxi, Anhui Province, China at the rate of 30 g/kg. The paddy soil was flooded and then air-dried, and soil pH and Eh were measured in situ with pH electrode and platinum electrode during wet-dry alternation. Soil pH buffering capacity (pHBC) was determined by acid-base titration after the wet-dry treatment. Then, the simulated acidification experiments were carried out to study the changing trends of soil pH, base cations and exchangeable acidity. The results showed that soil pHBC was effectively increased and the resistance of the paddy soil to acidification was apparently enhanced with the incorporation of H2O2- and HNO3/H2SO4-modified biochars. Surface functional groups on biochars were mainly responsible for enhanced soil resistance to acidification. During soil acidification, the protonation of organic anions generated by dissociation of these functional groups effectively retarded the decline of soil pH. The modification of HNO3/H2SO4 led to greater increase in carboxyl functional groups on the biochars than H2O2 modification and thus HNO3/H2SO4-modified biochars showed more enhancement in soil resistance to acidification than H2O2-modified biochars. After a wet-dry cycle, the pH of the paddy soil incorporated with HNO3/H2SO4-modified biochar increased apparently. Consequently, the addition of HNO3/H2SO4-modified biochar can be regarded as a new method to alleviate soil acidification. In short, the meaning of this paper is to provide a new method for the amelioration of acid paddy soils.
Increase the soil pHBC, slow down the decline of soil pH, and improve the resistance to acidification. Display omitted
•The addition of modified biochars obviously increased pHBC of an acid paddy soil.•HNO3/H2SO4-modified biochar increased soil resistance to acidification more evident.•Modified biochars increased the pH of the paddy soil after a wet-dry cycle.•Protonation of organic anions on biochars was main mechanism for soil pHBC increase.
Epigenetic modifications affect the differentiation of T cell subsets and the pathogenesis of autoimmune diseases, but many mechanisms of epigenetic regulation of T cell differentiation are unclear. ...Here we show reduced expression of the transcription factor RFX1 in CD4
T cells from patients with systemic lupus erythematosus, which leads to IL-17A overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 tri-methylation. Conditional deletion of Rfx1 in mice exacerbates experimental autoimmune encephalomyelitis and pristane-induced lupus-like syndrome and increases induction of Th17 cells. In vitro, Rfx1 deficiency increases the differentiation of naive CD4
T cells into Th17 cells, but this effect can be reversed by forced expression of Rfx1. Importantly, RFX1 functions downstream of STAT3 and phosphorylated STAT3 can inhibit RFX1 expression, highlighting a non-canonical pathway that regulates differentiation of Th17 cells. Collectively, our findings identify a unique role for RFX1 in Th17-related autoimmune diseases.
Methylglyoxal, a reactive dicarbonyl compound, is mainly formed from glycolysis. Methylglyoxal can lead to the dysfunction of mitochondria, the depletion of cellular anti-oxidation enzymes and the ...formation of advanced glycation ends. Previous studies showed that the accumulation of methylglyoxal and advanced glycation ends can impair the oocyte maturation and reduce the oocyte quality in aged and diabetic females. In this study, we showed that resveratrol, a kind of phytoalexin found in the skin of grapes, red wine and other botanical extracts, can alleviate the adverse effects caused by methylglyoxal, such as inhibition of oocyte maturation and disruption of spindle assembly. Besides, methylglyoxal-treated oocytes displayed more DNA double strands breaks and this can also be decreased by treatment of resveratrol. Further investigation of these processes revealed that methylglyoxal may affect the oocyte quality by resulting in excessive reactive oxygen species production, aberrant mitochondrial distribution and high level lipid peroxidation, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can protect the oocytes from methylglyoxal-induced cytotoxicity and this was mainly through the correction of the abnormity of cellular reactive oxygen species metabolism.
Excessive amounts of copper (Cu) in soils causes toxic effects on plants. In this study, 58 rice cultivars were classified into tolerant, moderately tolerant, and susceptible types for Cu(II) ...toxicity based on 50% germination (LC50). Nine japonica rice varieties (three each from the tolerant, moderately tolerant, and susceptible groups) and six indica rice varieties (three from the moderately tolerant and susceptible groups) were selected for the hydroponics experiments. In the short-term adsorption experiment, Cu(II) adsorbed on rice roots was differentiated into exchangeable, complexed, and precipitated forms. Similarly, it was done for long-term culture. Absorption of Cu(II) by rice roots and shoots was also measured. The results indicated that adsorbed Cu(II) mainly existed as complexed and exchangeable forms on rice roots in the short-term adsorption experiment, and the exchangeable and complexed Cu(II) levels were greater for indica rice than for japonica rice due to the larger negative charge on the indica rice roots. The adsorbed Cu(II) mainly existed as a complexed form in the long-term culture experiment, and the exchangeable Cu(II) level was much lower than that in the short-term adsorption experiment due to the absorption of Cu(II) by rice plants. The indica varieties absorbed more Cu(II) than the japonica varieties. Furthermore, the absorption and accumulation of Cu(II) by the susceptible varieties were greater than by the tolerant and moderately tolerant varieties for both the japonica and indica rice. The absorption and accumulation of Cu(II) in rice roots were much greater than in the shoots. Chlorophyll content, and the lengths and dry matter weights of the rice roots and shoots decreased with increasing Cu(II) concentration. The Cu(II) showed greater toxicity toward indica varieties than japonica varieties, and the greater negative charge on indica roots was one of reasons for the greater exchangeable Cu(II) on the roots, the increase in Cu(II) toxicity, and the higher uptake of Cu(II) by indica rice varieties compared to japonica rice varieties.
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•The roots of indica rice carry more negative charge compared to japonica rice.•Indica rice roots adsorbed more exchangeable Cu(II) than japonica rice roots.•Indica rice accumulated more Cu(II) in the roots and shoots than japonica rice.•Cu(II) showed greater toxicity to indica rice than japonica rice varieties.
Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient ...product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes
(MS-AOE
) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250-1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.
A series of hydrogen-air, ethylene-air, and methane-air continuous rotating detonation (CRD) tests are performed in the hollow chamber with the variations on nozzle contraction ratio and equivalence ...ratio. Hydrogen-air, ethylene-air, and methane-air CRDs are achieved with low velocity deficit and high stability in the same laboratory hollow chamber. Larger combustor width, flame stabilization and mixing quality promotion benefited from the hollow chamber, and the prolongation of residence time impacted by the hollow chamber and nozzle are key factors for significant enhancement. Generally, the operating range, propagation frequency, propagationvelocityC−Jdetonationvelocity, and stability increase with the fuel detonability increasing. The quantitative analysis approaches, the integral of chemiluminescence intensity and axial distribution of chemiluminescence intensity ratio on high-speed photography images, and flowfield reconstruction based on the time difference calculation method, are proposed and applied. Multiple analysis approaches all show that the length of CRD wave increases with the fuel detonability decreasing, which is mainly attributed to that the hydrocarbon fuels release heat in longer axial distance with relatively lower intensity. In addition, two dominant peak one-wave mode is verified as the single wave coupled with the reflected shock wave, which propagates upstream from nozzle to combustor forepart.
•H2-air, C2H4-air and CH4-air CRDs are achieved in the laboratory hollow chamber.•Operating range, frequency and stability increases with fuel detonability increasing.•Lengths of CRDs are estimated by axial distribution of chemiluminescence intensity.•Length variation is verified by flowfield reconstruction and pressure distribution.•Two dominant peak one-wave mode has been verified as single wave.
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