Detrimental phase evolution triggered by Ni in perovskite-type cathodes for CO2 electroreduction

Perovskite oxides are popular as cathode materials of solid oxide electrolysis cells, because of their good redox stability and high resistance to coke formation.Unexpectedly, a negative effect of Ni doping is found on Sr2Fe(1.5-x)NixMo(0.5)O(x = 0, 0.05, 0.1, 0.2) cathode for pure CO2 electroreduction at 800 ℃, although Ni is highly active for CO2 electroreduction.The CO2 electroreduction performance degrades with the increase of Ni doping amount.Various characterization techniques are used to disclose the negative effect.Ni doping decreases the perovskite stability under electroreduction conditions, Fe and Ni cations in the B-site are reduced to metal nanoparticles and SrCO3 forms on the surface of the perovskite.The phase instability results from the weaker Ni–O bond.Although the Fe-Ni nanoparticles are in favor of the CO2 electroreduction, too much SrCO3 and carbon deposition block the charge transfer and diffusion of oxygenous species on the cathode surface.

Overexpressed NEDD8 as a potential therapeutic target in esophageal squamous cell carcinoma

Objective:The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target.We aimed to study whether NEDD8(neural precursor cell expressed,developmentally down-regulated 8)might serve as a therapeutic target in esophageal squamous cell carcinoma(ESCC).Methods:The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas(TCGA)database and tissue arrays.NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms.Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways.The cell cycle and apoptosis were assessed with fluorescence activated cell sorting.A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing in vivo.Results:NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC,and NEDD8 overexpression was associated with poorer overall patient survival(mRNA level:P=0.028,protein level:P=0.026,log-rank test).Downregulation of NEDD8 significantly suppressed tumor growth both in vitro and in vivo.Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest,DNA damage,and apoptosis in ESCC cells.Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases(CRLs)substrates through inactivation of CRLs,thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC.Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown.Conclusions:Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown,and validated NEDD8 as a potential target for ESCC therapy.

Application of Social Support System in the Rehabilitation of Vagrants and Beggars with Mental Illness

Objective:Analyze the specific role of social support in vagrants and beggars with mental illness.Methods:80 patients with vagrant psychosis admitted into our hospital from April 2020 to April 2021 were randomly selected.The patients were treated for more than 6 months.The patients were randomly divided into two groups by drawing lots,with 40 cases in each group.The control group received routine nursing,and the observation group received routine nursing along with social support.The objective support,subjective support,and the utilization of support,which were combined into total social support of the two groups were compared after different nursing interventions.Results:After different nursing interventions,through the comparison of social support scale,the scores of objective support,subjective support,and utilization of support,and the total social support in the observation group were higher than the control group,and the differences were statistically significant(P<0.05).Conclusion:The application of social support system and while providing routine nursing among vagrants and beggars with psychosis can effectively improve their mental status,make them feel more valued and supported,and help improve their mental health and quality of life.

混合导体透氧膜反应器中水分解反应研究进展

混合导体透氧膜反应器可以将供氧反应、氧分离和耗氧反应耦合在一个单元,实现反应和分离一体化,简化化工过程.水分解反应参与的混合导体透氧膜反应器能够实现氢气的制备和分离,近年来受到越来越多的关注.这篇文章综述了混合导体透氧膜反应器中水分解反应领域的研究进展,总结了包括膜材料、催化剂、操作条件等对透氧膜反应器中水分解反应的影响,分析了目前存在的问题,同时展望了该领域在膜材料、膜结构和催化剂开发等方面的未来发展方向,希望有助于促进膜反应器中水分解反应的研究.

Binding between Prion Protein and Aβ Oligomers Contributes to the Pathogenesis of Alzheimer’s Disease

A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential.Although it remains elusive how protein aggregation leads to AD,it is becoming clear that cellular prion protein(PrP^c)plays an important role in AD pathogenesis.Here,we briefly reviewed AD pathogenesis and focused on recent progresses how PrP^c contributed to AD development.In addition,we proposed a potential mechanism to explain why infectious agents,such as viruses,conduce AD pathogenesis.Microbe infections cause AD deposition and upregulation of PrP^c,which lead to high affinity binding between AD oligomers and PrP^c.The interaction between PrP^c and AP oligomers in turn activates the Fyn signaling cascade,resulting in neuron death in the central nervous system(CNS).Thus,silencing PrP^c expression may turn out be an effective treatment for PrP^c dependent AD.

Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis

Unfolded protein response(UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum(ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein(PrP) is a glycosylated cell surface protein that has been shown to be up-regulated in many cancer cells. Since PrP is a protein prone to misfolding, ER stress can result in under-glycosylated PrP, which in turn may activate ER stress. To assess whether ER stress leads to the production of under-glycosylated PrP and whether underglycosylated PrP may contribute to ER stress thus leading to cancer cell apoptosis, we treated different cancer cells with brefeldin A(BFA), thapsigargin(Thps), and tunicamycin(TM). We found that although BFA, Thps, and TM treatment activated UPR, only ATF4 was consistently activated by these reagents, but not other branches of ER stress. However, the canonical PERK-eIF2α-ATF4 did not account for the observed activation of ATF4 in lung cancer cells. In addition, BFA,but neither Thps nor TM, significantly stimulated the expression of cytosolic PrP. Finally, we found that the levels of PrP contributed to anti-apoptosis activity of BFA-induced cancer cell death. Thus, the pathway of BFA-induced persistent ER stress may be targeted for lung and pancreatic cancer treatment.

The CRL3^(BTBD9) E3 ubiquitin ligase complex targets TNFAIP1 for degradation to suppress cancer cell migration

Tumor necrosis factor alpha-induced protein 1(TNFAIP1)modulates a plethora of important biological processes,including tumorigenesis and cancer cell migration.However,the regulatory mechanism of TNFAIP1 degradation remains largely elusive.In the present study,with a label-free quantitative proteomic approach,TNFAIP1 was identified as a novel ubiquitin target of the Cullin-RING E3 ubiquitin ligase(CRL)complex.More importantly,Cul3-ROC1(CRL3),a subfamily of CRLs,was identified to specifically interact with TNFAIP1 and promote its polyubiquitination and degradation.Mechanistically,BTBD9,a specific adaptor component of CRL3 complex,was further defined to bind and promote the ubiquitination and degradation of TNFAIP1 in cells.As such,downregulation of BTBD9 promoted lung cancer cell migration by upregulating the expression of TNFAIP1,whereas TNFAIP1 deletion abrogated this effect.Finally,bioinformatics and clinical sample analyses revealed that BTBD9 was downregulated while TNFAIP1 was overexpressed in human lung cancer,which was associated with poor overall survival of patients.Taken together,these findings reveal a previously unrecognized mechanism by which the CRL3^(BTBD9) ubiquitin ligase controls TNFAIP1 degradation to regulate cancer cell migration.

Pro-senescence neddylation inhibitor combined with a senescence activated β-galactosidase prodrug to selectively target cancer cells

Dear Editor,Targeting senescence therapy is a promising anticancer strategy by arresting the cell-cycle and inducing cellular senescence.However,senescent cells can promote malignancy and drug resistance.1,2 Thus,with the induction of senescence emerged as a viable therapeutic concept,it is important to consider how to eliminate those senescent cancer cells.

Regulation of SKP2 protein stability by heat shock protein 90 chaperone machinery

Dear Editor,S phase kinase-associated protein 2(SKP2),a substrate recognition component of the SCFSKP2 ubiquitin ligase complex,plays an oncogenic role in tumorigenesis by targeting a variety of tumor suppressors(e.g.,p21,p27,and p130)for ubiquitina-tion and subsequent degradation.1 As a well-characterized oncoprotein,the aberrant expression and dysregulation of SKP2 are frequently observed in different human cancers.Given its critical role in governing tumorigenesis and progression,SKP2 has emerged as a potential pharmacological target for anticancer therapy.

NEDD8-conjugating enzyme UBC12 as a novel therapeutic target in esophageal squamous cell carcinoma

Dear Editor,Esophageal squamous cell carcinoma(ESCC)is the major histologic subtype of esophageal cancer with high incidence and mortality.1 However,few achievements have been made in the development of targeted drugs.2 Neddylation,a reversible post-translational modification,attaches ubiquitin-like molecule NEDD8 to substrates in a three-step enzymatic reaction catalyzed by NEDD8-activating enzyme E1(NAE,NAE1 and UBA3 heterodimer),NEDD8-conjugating enzyme E2s(UBE2M/UBC12 or UBE2F)and substrate-specific NEDD8-E3 ligases.3 The best-characterized substrates of neddylation are cullin family proteins,the essential components of multiunit Cullin-RING ubiquitin ligases(CRLs).4 Currently,the inhibition of cullin neddylation by targeting overactivated neddylation pathway has emerged as an attractive approach for anticancer therapy.5,6 Our previous study reported that MLN4924,a specific inhibitor of NAE,significantly inhibited the tumor growth of ESCC by blocking cullin neddylation and inactivating CRLs activity.7 However,recent studies found that MLN4924 treatment-emergent NAE mutations would confer the drug resistance.8,9 Therefore,it is urgent to identify other neddylation enzymes(E2s or E3s)as alternative anticancer targets and develop novel anti-ESCC strategies.

Improved hydrogen separation performance of asymmetric oxygen transport membranes by grooving in the porous support layer

Hydrogen separation through oxygen transport membranes(OTMs)has attracted much attention.Asymmetric membranes with thin dense layers provide low bulk diffusion resistances and high overall hydrogen separation performances.However,the resistance in the porous support layer(PSL)limits the overall separation performance significantly.Engineering the structure of the PSL is an appropriate way to enable fast gas transport and increase the separation performance.There is no relevant research on studying the influence of the PSL on hydrogen separation performance so far.Herein,we prepared Ce0.85Sm0.15O1.925–Sm0.6Sr0.4Cr0.3Fe0.7O3-δ(SDC-SSCF)asymmetric membranes with straight grooves in PSL by tape-casting and laser grooving.A~30%improvement in the hydrogen separation rate was achieved by grooving in the PSLs.It indicates that the grooves may reduce the concentration polarization resistance in PSL for the hydrogen separation process.This work provides a straight evidence on optimizing the structures of PSL for improving the hydrogen separation performance of the membrane reactors.