Nephrotoxicity of immune checkpoint inhibitor combination therapy in patients with advanced renal cell carcinoma: a meta-analysis.

PURPOSE: Few data are available regarding the nephrotoxicity of immune checkpoint inhibitor (ICI) combination therapy in advanced renal cell carcinoma (RCC). This study aimed to investigate the nephrotoxicity of ICI-based combination therapy versus standard of care sunitinib in patients with advanced RCC. METHODS: We searched Embase/PubMed/Cochrane Library for relevant randomized controlled trials (RCTs). Treatment-related nephrotoxicities including increase of creatinine and proteinuria were analyzed by Review Manager 5.4 software. RESULTS: Seven RCTs involving 5239 patients were included. The analysis showed that ICI combination therapy had similar risks of any grade (RR = 1.03, 95% CI: 0.77-1.37, P = 0.87) and grade 3-5 (RR = 1.48, 95% CI: 0.19-11.66, P = 0.71) increased creatinine compared with sunitinib monotherapy. However, ICI combination therapy was associated with significantly higher risks of any grade (RR = 2.33, 95% CI: 1.54-3.51, P < 0.0001) and grade 3-5 proteinuria (RR = 2.25, 95% CI: 1.21-4.17, P = 0.01). CONCLUSIONS: This meta-analysis suggests that ICI combination therapy shows more nephrotoxicity of proteinuria than sunitinib in advanced RCC, which deserves a high attention in the clinic.

Arabidopsis DXO1 possesses deNADding and exonuclease activities and its mutation affects defense-related and photosynthetic gene expression.

RNA capping and decapping tightly coordinate with transcription, translation, and RNA decay to regulate gene expression. Proteins in the DXO/Rai1 family have been implicated in mRNA decapping and decay, and mammalian DXO was recently found to also function as a decapping enzyme for NAD+ -capped RNAs (NAD-RNA). The Arabidopsis genome contains a single gene encoding a DXO/Rai1 protein, AtDXO1. Here we show that AtDXO1 possesses both NAD-RNA decapping activity and 5'-3' exonuclease activity but does not hydrolyze the m7 G cap. The atdxo1 mutation increased the stability of NAD-RNAs and led to pleiotropic phenotypes, including severe growth retardation, pale color, and multiple developmental defects. Transcriptome profiling analysis showed that the atdxo1 mutation resulted in upregulation of defense-related genes but downregulation of photosynthesis-related genes. The autoimmunity phenotype of the mutant could be suppressed by either eds1 or npr1 mutation. However, the various phenotypes associated with the atdxo1 mutant could be complemented by an enzymatically inactive AtDXO1. The atdxo1 mutation apparently enhances post-transcriptional gene silencing by elevating levels of siRNAs. Our study indicates that AtDXO1 regulates gene expression in various biological and physiological processes through its pleiotropic molecular functions in mediating RNA processing and decay.

Arabidopsis DXO1 activates RNMT1 to methylate the mRNA guanosine cap.

Eukaryotic messenger RNA (mRNA) typically contains a methylated guanosine (m7G) cap, which mediates major steps of mRNA metabolism. Recently, some RNAs in both prokaryotic and eukaryotic organisms have been found to carry a non-canonical cap such as the NAD cap. Here we report that Arabidopsis DXO family protein AtDXO1, which was previously known to be a decapping enzyme for NAD-capped RNAs (NAD-RNA), is an essential component for m7G capping. AtDXO1 associates with and activates RNA guanosine-7 methyltransferase (AtRNMT1) to catalyze conversion of the guanosine cap to the m7G cap. AtRNMT1 is an essential gene. Partial loss-of-function mutations of AtRNMT1 and knockout mutation of AtDXO1 reduce m7G-capped mRNA but increase G-capped mRNAs, leading to similar pleiotropic phenotypes, whereas overexpression of AtRNMT1 partially restores the atdxo1 phenotypes. This work reveals an important mechanism in m7G capping in plants by which the NAD-RNA decapping enzyme AtDXO1 is required for efficient guanosine cap methylation.

Revealing the fundamental role of MoO2 in promoting efficient and stable activation of persulfate by iron carbon based catalysts: Efficient Fe2+/Fe3+ cycling to generate reactive species.

Electron-rich iron sites are the main sites for iron-based catalysts to activate persulfate (PS) to generate reactive species, while blocked Fe2+/Fe3+ cycling usually reduces the catalytic performance of iron-based materials and hinders the generation of reactive species in the reaction. To solve the bottleneck, we synthesized an iron-carbon nanocomposite catalyst loaded with MoO2 (Fe/Mo-CNs). The promotion of MoO2 on the Fe2+/Fe3+ cycle in the system allowed Fe/Mo-CNs to exhibit excellent catalytic performance and environmental adaptability. The degradation rate of bisphenol S (BPS) by the Fe/Mo-CNs/PS system was significantly increased to 0.080 min-1 compared with the iron-carbon based catalyst/persulfate system, and the degradation efficiency of BPS was maintained at around 85% after four cycles. Density functional theory (DFT) calculations showed that the introduction of MoO2 reduced the reaction energy barrier of persulfate activated by catalysts to produce reactive species, especially promoted the production of more high valent iron (Fe(IV)). Fe(IV) and reactive oxygen species (SO4·-, ·OH, ·O2- and 1O2) worked together on the efficient degradation of BPS. In addition, the test of an automatic circulating degradation plant had proved that Fe/Mo-CNs had a good practical application prospect. BPS was mainly degraded by ring cleavage and O=S=O bond cleavage, and the toxicity of BPS and its intermediates were also evaluated. This work clarifies the mechanism of improving the catalytic performance of heterogeneous iron-based catalysts by MoO2 in sulfate radical-based advanced oxidation processes (SR-AOPs), providing a new idea for solving the blockage of Fe2+/Fe3+ cycle in SR-AOPs.

Di-µ-hydroxido-bis-({2,2'-[propane-1,3-diylbis(nitrilo-methyl-idyne)]diphenolato}iron(III)) dimethyl-formamide disolvate.

The structure of the title compound, [Fe(2)(C(17)H(16)N(2)O(2))(2)(OH)(2)]·2C(3)H(7)N, consists of centrosymmetric dimeric units in which crystallographically equivalent Fe(III) ions are doubly bridged by hydroxide groups. Each Fe(III) center in the complex has a six-coordinated distorted cis-FeN(2)O(4) octa-hedral geometry.

Fast-suppressor screening for new components in protein trafficking, organelle biogenesis and silencing pathway in Arabidopsis thaliana using DEX-inducible FREE1-RNAi plants.

Membrane trafficking is essential for plant growth and responses to external signals. The plant unique FYVE domain-containing protein FREE1 is a component of the ESCRT complex (endosomal sorting complex required for transport). FREE1 plays multiple roles in regulating protein trafficking and organelle biogenesis including the formation of intraluminal vesicles of multivesicular body (MVB), vacuolar protein transport and vacuole biogenesis, and autophagic degradation. FREE1 knockout plants show defective MVB formation, abnormal vacuolar transport, fragmented vacuoles, accumulated autophagosomes, and seedling lethality. To further uncover the underlying mechanisms of FREE1 function in plants, we performed a forward genetic screen for mutants that suppressed the seedling lethal phenotype of FREE1-RNAi transgenic plants. The obtained mutants are termed as suppressors of free1 (sof). To date, 229 putative sof mutants have been identified. Barely detecting of FREE1 protein with M3 plants further identified 84 FREE1-related suppressors. Also 145 mutants showing no reduction of FREE1 protein were termed as RNAi-related mutants. Through next-generation sequencing (NGS) of bulked DNA from F2 mapping population of two RNAi-related sof mutants, FREE1-RNAi T-DNA inserted on chromosome 1 was identified and the causal mutation of putative sof mutant is being identified similarly. These FREE1- and RNAi-related sof mutants will be useful tools and resources for illustrating the underlying mechanisms of FREE1 function in intracellular trafficking and organelle biogenesis, as well as for uncovering the new components involved in the regulation of silencing pathways in plants.

[Adsorption kinetics of phosphate from aqueous solutions onto modified corn residue].

The adsorption kinetics of phosphate from aqueous solutions onto modified corn residue was studied in a hatch reactor. The influence of initial pH, concentration and temperature to adsorption effect were investigated. In addition, the kinetic data were fitted by pseudo-first-order equation, pseudo-second-order equation, modified pseudo-first-order equation and intra-particle diffusion model, and the respective characteristic rate constants were presented. The results showed that the adsorption data fitted Freundlich isotherm model, and the maximum adsorption capacity of phosphate would decrease with the temperature increasing. Furthermore, the adsorption process could reached equilibrium in 30 minutes, and the pseudo-second-order equation and intra-particle diffusion model generated the best agreement with the experimental data for the adsorption systems. The intra-particle diffusion was the main rate-controlling step. With increasing initial concentration, the rate constant of pseudo-second-order equation decreases and that of intra-particle diffusion model increases. The adsorption kinetic analyses could be of a great practical value for the technological applications of phosphate removal from aqueous solutions.