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1.
J Clin Invest ; 131(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34623322

RESUMO

Triggering receptor expressed on myeloid cells 2 (TREM-2) is a modulator of pattern recognition receptors on innate immune cells that regulates the inflammatory response. However, the role of TREM-2 in in vivo models of infection and inflammation remains controversial. Here, we demonstrated that TREM-2 expression on CD4+ T cells was induced by Mycobacterium tuberculosis infection in both humans and mice and positively associated with T cell activation and an effector memory phenotype. Activation of TREM-2 in CD4+ T cells was dependent on interaction with the putative TREM-2 ligand expressed on DCs. Unlike the observation in myeloid cells that TREM-2 signals through DAP12, in CD4+ T cells, TREM-2 interacted with the CD3ζ-ZAP70 complex as well as with the IFN-γ receptor, leading to STAT1/-4 activation and T-bet transcription. In addition, an infection model using reconstituted Rag2-/- mice (with TREM-2-KO vs. WT cells or TREM-2+ vs. TREM-2-CD4+ T cells) or CD4+ T cell-specific TREM-2 conditional KO mice demonstrated that TREM-2 promoted a Th1-mediated host defense against M. tuberculosis infection. Taken together, these findings reveal a critical role of TREM-2 in evoking proinflammatory Th1 responses that may provide potential therapeutic targets for infectious and inflammatory diseases.

2.
EClinicalMedicine ; 41: 101155, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34693233

RESUMO

Background: This study provides the first systematic review and meta-analysis to identify the predictors of unfavorable prognosis of COVID-19 in children and adolescents. Methods: We searched literature databases until July 2021 for studies that investigated risk factors for unfavorable prognosis of children and adolescents with COVID-19. We used random-effects models to estimate the effect size with 95% confidence interval (CI). Findings: We identified 56 studies comprising 79,104 individuals. Mortality was higher in patients with multisystem inflammatory syndrome (MIS-C) (odds ratio [OR]=58.00, 95% CI 6.39-526.79) and who were admitted to intensive care (OR=12.64, 95% CI 3.42-46.68). Acute respiratry distress syndrme (ARDS) (OR=29.54, 95% CI 12.69-68.78) and acute kidney injury (AKI) (OR=55.02, 95% CI 6.26-483.35) increased the odds to be admitted to intensive care; shortness of breath (OR=16.96, 95% CI 7.66-37.51) increased the need of respiratory support; and neurological diseases (OR=5.16, 95% CI 2.30-11.60), C-reactive protein (CRP) level ≥80 mg/L (OR=11.70, 95% CI 4.37-31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76-236.44) increased the odds of progression to severe or critical disease. Interpretation: Congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, MIS-C, shortness of breath, ARDS, AKI, gastrointestinal symptoms, elevated CRP and D-dimer are associated with unfavourable prognosis in children and adolescents with COVID-19.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34654043

RESUMO

BACKGROUND: Alzheimer disease (AD) is the most common neurodegenerative disease of the central nervous system. The stability of the telomere-telomerase system is closely related to AD. A previous meta-analysis indicated that AD patients had shorter telomere length (TL) than control subjects. However, there are no consistent telomerase activity findings in AD patients, and the published telomerase studies were not meta-analyzed yet. METHODS: We searched all the related studies that probed into TL and/or telomerase activity in AD patients based on PubMed and Embase database from the establishment to September 2020. The Chinese National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database were also utilized. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale. All the statistical analyses of this meta-analysis were performed using Stata version 15.0. RESULTS: Analyzing 30 TL data from 2248 AD patients and 4865 controls, AD patients had a significantly shorter TL than the controls, with a standardized mean difference of -0.70 (confidence interval: -0.95 to -0.46; P<0.05). The meta-analysis included 3 primary studies and did not find a significant difference in the telomerase activity between 233 AD patients and 132 controls, but AD patients had a trend of increased telomerase activity compared with controls (standardized mean difference: 0.47; confidence interval: -0.29 to 1.23; P>0.05). CONCLUSION: Our results showed that compared with the control group, the AD group had a shorter TL and may have higher telomerase activity.

4.
Sci Total Environ ; 806(Pt 2): 150634, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34597565

RESUMO

Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.

5.
Front Med (Lausanne) ; 8: 723904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540870

RESUMO

The potential relationship among airway Candida spp. de-colonization, nebulized amphotericin B (NAB), and occurrence of ventilator-associated pneumonia (VAP) in patients who are critically ill has not been fully investigated, especially concerning effects on survival. In this observational, retrospective, cohort study in a 22-bed central intensive care unit, we included patients aged >18 years who required mechanical ventilation (MV) for >48 h, with at least two consecutive positive Candida spp. test results. Patients were categorized into NAB and no NAB (control) groups. Propensity matching at 1:1 was performed according to strict standards, and multiple Cox proportional hazard model and multivariate analyses were performed to evaluate the effects of NAB treatment. Throughout an 8-year study period, 526 patients had received MV and had positive respiratory tract Candida spp. cultures. Of these, we included 275 patients and excluded 251 patients. In total, we successfully matched 110 patients from the two groups (each group, n = 55; total population median age, 64 years; Acute Physiology and Chronic Health Evaluation II [APACHE II] score, 25.5; sequential organ failure assessment score, 9). The Candida spp. de-colonization rate was 69.1% in patients treated with NAB. VAP incidence did not differ significantly between the NAB (10.91%) and control (16.36%) groups (P = 0.405). Pseudomonas aeruginosa-related VAP rates differed significantly between the NAB (10.91%) and control (25.45%) groups (P = 0.048). Five (9.1%) patients in the NAB group died during hospitalization compared with 17 (30.9%) controls (P = 0.014). At 28 days, 9 (16.4%) and 16 (29.1%) deaths occurred in the NAB and control groups, respectively, (P = 0.088). The cumulative 90-day mortality rate differed significantly between the two groups (23.6 vs. 43.6%, P = 0.015). Multivariate logistic regression analyses indicated a decreased 90-day mortality in the NAB group (adjusted odds ratio 0.413; 95% confidence interval 0.210-0.812; P = 0.01). In subgroup analyses, the NAB-associated decreased risk of death at 90 days was consistent across subgroups of patients with a Candida score of 2, younger age (<64 years), a higher APACHE II score (≥25), fewer Candida sites (<2), or MV at admission. NAB treatment contributed to Candida spp. airway de-colonization, was associated with a reduced risk of P. aeruginosa-related VAP, and improved 90-day mortality in patients critically ill with Candida spp. tracheobronchial colonization who had received MV for >2 days. NAB may be an alternative treatment option for critically ill patients with VAP.

6.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

7.
Oncogene ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556812

RESUMO

Complete blockade of the HER2 protein itself and HER signaling network is critical to achieving effective HER2-targeted therapies. Despite the success of HER2-targeted therapies, the diseases will relapse in a significant fraction of patients with HER2+ breast cancers. How to improve the therapeutic efficacy of existing HER2-targeted agents remains an unmet clinical need. Here, we uncover a role of Melatonin in diminishing HER2-mediated signaling by destruction of HER2 protein. Mechanistically, Melatonin treatment attenuated the protective effect of the HSP90 chaperone complex on its client protein HER2, triggering ubiquitylation and subsequent endocytic lysosomal degradation of HER2. The inhibitory effect of Melatonin on HER2 signaling substantially enhanced the cytotoxic effects of the pan-HER inhibitor Neratinib in HER2+ breast cancer cells. Lastly, we demonstrate that dual inhibition of HER2 by combined use of Melatonin and Neratinib effectively blocked the growth of HER2+ breast tumor xenografts in vivo. Our findings shed light on the potential use of Melatonin in a novel dual HER2 blockade strategy for HER2+ breast cancer treatment.

8.
Biochem Biophys Res Commun ; 576: 33-39, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34478917

RESUMO

Dendritic cells (DCs) are antigen-presenting cells of the immune system, which play a key role in antitumor immunity by activating cytotoxic T cells. Here, we report that elevated ferroptosis, a lipid peroxidation-mediated cell death, impairs the maturation of DCs and their function in tumor suppression. Ferroptosis is selectively induced in DCs by the GXP4 inhibitor RSL3, but not the SLC7A11 inhibitor erastin. Ferroptotic DCs lose their ability to secrete pro-inflammatory cytokines (TNF and IL6) and express MHC class I in response to the maturation signal of lipopolysaccharide. Moreover, ferroptotic DCs fail to induce CD8+ T cells to produce IFNG/IFNγ. Mechanistically, PPARG/PPARγ, a nuclear receptor involved in the regulation of lipid metabolism, is responsible for RSL3-induced ferroptosis in DCs. Consequently, the genetic depletion of PPARG restores the maturation and function of DCs. Using immunogenic cell death-based DC vaccine models, we further demonstrate that PPARG-mediated ferroptosis of DCs limits antitumor immunity in mice. Together, these findings demonstrate a novel role of ferroptotic DCs in driving an immunosuppressive tumor microenvironment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34562639

RESUMO

BACKGROUND & AIMS: Pancreatitis is characterized by acinar cell death and persistent inflammation. Ferroptosis is a type of lipid peroxidation-dependent necrosis, which is negatively regulated by glutathione peroxidase 4. We studied how trypsin, a serine protease secreted by pancreatic acinar cells, affects the contribution of ferroptosis to triggering pancreatitis. METHODS: In vitro, the mouse pancreatic acinar cell line 266-6 and mouse primary pancreatic acinar cells were used to investigate the effect of exogenous trypsin on ferroptosis sensitivity. Short hairpin RNAs were designed to silence gene expression, whereas a library of 1080 approved drugs was used to identify new ferroptosis inhibitors in 266-6 cells. In vivo, a Cre/LoxP system was used to generate mice with a pancreas-specific knockout of Gpx4 (Pdx1-Cre;Gpx4flox/flox mice). Acute or chronic pancreatitis was induced in these mice (Gpx4flox/flox mice served as controls) by cerulein injections or a Lieber-DeCarli alcoholic liquid diet. Pancreatic tissues, acinar cells, and serum were collected and analyzed by histology, immunoblot, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, or immunohistochemical analyses. RESULTS: Supraphysiological doses of trypsin (500 or 1000 ng/mL) alone did not trigger significant cell death in 266-6 cells and mouse primary pancreatic acinar cells, but did increase the sensitivity of these cells to ferroptosis upon treatment with cerulein, L-arginine, alcohol, erastin, or RSL3. Proteasome 26S subunit, non-adenosine triphosphatase 4-dependent lipid peroxidation caused ferroptosis in pancreatic acinar cells by promoting the proteasomal degradation of glutathione peroxidase 4. The drug screening campaign identified the antipsychotic drug olanzapine as an antioxidant inhibiting ferroptosis in pancreatic acinar cells. Mice lacking pancreatic Gpx4 developed more severe pancreatitis after cerulein infection or ethanol feeding than control mice. Conversely, olanzapine administration protected against pancreatic ferroptotic damage and experimental pancreatitis in Gpx4-deficient mice. CONCLUSIONS: Trypsin-mediated sensitization to ferroptotic damage increases the severity of pancreatitis in mice, and this process can be reversed by olanzapine.

10.
Ecotoxicol Environ Saf ; 226: 112805, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592526

RESUMO

During the production and application of Bacillus thuringiensis (Bt) transgenic crops, large doses of insecticidal Bt toxic proteins are expressed continuously. The multi-interfacial behaviors of Bt proteins entering the environment in multi-media affects their states of existence transformation, transport and fate as well as biological and ecological impacts. Because both soil matrix and organisms will be exposed to Bt proteins to a certain extent, knowledge of the multi-interfacial behaviors and affecting factors of Bt proteins are vital not only for understanding the source-sink distribution mechanisms, predicting their bio-availability, but also for exploring the soil safety and environmental problems caused by the interaction between Bt proteins and soil matrix. This review summarized and analyzed various internal and external factors that affect the adsorption/ desorption and degradation of Bt proteins in the environment, so as to understand the multi-interfacial behaviors of Bt proteins. In addition, the reasons of concentration changes of Bt proteins in soil are discussed. This review will also discuss the existing knowledge of the combined effects of Bt proteins and other pollutants in environment. Finally, discussing the factors that should be considered when assessing the environmental risk of Bt proteins, thus to further improve the understanding of the environmental fate of Bt proteins.

11.
Front Cell Dev Biol ; 9: 725933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589489

RESUMO

Male infertility is a widespread health problem affecting approximately 6%-8% of the male population, and hypoxia may be a causative factor. In mammals, two types of hypoxia are known, including environmental and pathological hypoxia. Studies looking at the effects of hypoxia on male infertility have linked both types of hypoxia to poor sperm quality and pregnancy outcomes. Hypoxia damages testicular seminiferous tubule directly, leading to the disorder of seminiferous epithelium and shedding of spermatogenic cells. Hypoxia can also disrupt the balance between oxidative phosphorylation and glycolysis of spermatogenic cells, resulting in impaired self-renewal and differentiation of spermatogonia, and failure of meiosis. In addition, hypoxia disrupts the secretion of reproductive hormones, causing spermatogenic arrest and erectile dysfunction. The possible mechanisms involved in hypoxia on male reproductive toxicity mainly include excessive ROS mediated oxidative stress, HIF-1α mediated germ cell apoptosis and proliferation inhibition, systematic inflammation and epigenetic changes. In this review, we discuss the correlations between hypoxia and male infertility based on epidemiological, clinical and animal studies and enumerate the hypoxic factors causing male infertility in detail. Demonstration of the causal association between hypoxia and male infertility will provide more options for the treatment of male infertility.

12.
Endocrinol Diabetes Metab ; : e00301, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585841

RESUMO

AIMS: Type 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID-19). The effect of T2DM medications on COVID-19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. The current study aims to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin and sulfonylureas, on the mortality of COVID-19 patients with T2DM during hospitalization. METHODS: We continue to carry out a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 and treated with different combinations of diabetes medications. RESULTS: We found that patients using metformin (p = .02) and acarbose (p = .04), alone or both together (p = .03), after admission were significantly more likely to survive than those who did not use either metformin or acarbose. 37 patients continued to take metformin after admission and 35 (94.6%) survived. Among the 57 patients who used acarbose after admission, 52 survived (91.2%). A total of 20 patients used both metformin and acarbose, while 57 used neither. Of the 20 dual-use patients, 19 (95.0%) survived. CONCLUSION: Our analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials.

13.
Cancer Gene Ther ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471232

RESUMO

Although it has long been deemed "undruggable", with the development of drugs specifically binding the KRAS-G12C mutant protein, clinical trials that directly inhibit oncogenic RAS have recently made promising improvements. In particular, the covalent KRAS-G12C inhibitors sotorasib and adagrasib are used to treat patients with advanced non-small cell lung cancer (NSCLC) carrying KRAS-G12C mutations. Unfortunately, the vast majority of patients do not respond to KRAS-G12C inhibitor therapy, mainly due to intrinsic or acquired resistance caused by cellular, molecular, and genetic mechanisms. Improving the understanding of drug response in the tumor microenvironment may continue to promote the design, testing, and clinical application of KRAS-G12C inhibitors.

14.
J Hazard Mater ; 416: 125896, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492834

RESUMO

Cork, a porous biomass material, is consist of thin-walled hollow prismatic cells arranged into a compact and orderly honeycomb-like structure and could be applied as an adsorption material. Here, cork-activated carbons (CACs) with a fluffy honeycomb-like structure were synthesized by two-step pyrolysis with solid KOH chemical activation to rapidly and efficiently adsorb methylene blue (MB) (maximum wavelength: 664 nm). The structure, morphology and surface functional groups of the CACs were characterized using BET, SEM, and FTIR analysis. The results show that the CACs have a well-developed hierarchical porous structure and an ultra-high specific surface area of 2864.9 m2/g, which would facilitate the efficient diffusion and adsorption of MB molecules onto CACs. MB adsorption performance results show that the CACs have an outstanding maximum MB adsorption capacity (1103.68 mg/g) and fast adsorption kinetics (800 mg/L, 99.8% in 10 min), indicating that CACs possess significant advantages compared with most other adsorbents previously reported. The adsorption mechanism was studied by various kinetic models, isothermal models and thermodynamic models. Langmuir model is the most adapted to describe the adsorption process, indicating that the MB molecules are uniformly adsorbed on CAC's surface in a single layer. Moreover, MB adsorption by the CACs was an endothermic, spontaneous and randomly increasing adsorption. The regeneration test showed that the uptake of MB onto CACs can still reached 580 mg/g after three adsorption-desorption cycles, demonstrating the excellent reusability of CACs. The continuous adsorption performance of MB onto CACs was evaluated by a packed column test, which further confirmed its potential as an adsorbent for dye wastewater purification.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Biomassa , Carvão Vegetal , Cinética , Azul de Metileno
15.
IEEE Trans Cybern ; PP2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520383

RESUMO

A mixed-integer programming (MIP) problem contains both constraints and integer restrictions. Integer restrictions divide the feasible region defined by constraints into multiple discontinuous feasible parts. In particular, the number of discontinuous feasible parts will drastically increase with the increase of the number of integer decision variables and/or the size of the candidate set of each integer decision variable. Due to the fact that the optimal solution is located in one of the discontinuous feasible parts, it is a challenging task to solve a MIP problem. This article presents a cutting and repulsion-based evolutionary framework (called CaR) to solve MIP problems. CaR includes two main strategies: 1) the cutting strategy and 2) the repulsion strategy. In the cutting strategy, an additional constraint is constructed based on the objective function value of the best individual found so far, the aim of which is to continuously cut unpromising discontinuous feasible parts. As a result, the probability of the population entering a wrong discontinuous feasible part can be decreased. In addition, in the repulsion strategy, once it has been detected that the population has converged to a discontinuous feasible part, the population will be reinitialized. Moreover, a repulsion function is designed to repulse the previously explored discontinuous feasible parts. Overall, the cutting strategy can significantly reduce the number of discontinuous feasible parts and the repulsion strategy can probe the remaining discontinuous feasible parts. Sixteen test problems developed in this article and two real-world cases are used to verify the effectiveness of CaR. The results demonstrate that CaR performs well in solving MIP problems.

16.
Biofabrication ; 13(4)2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34450602

RESUMO

Fiber constructed yarns are the elementary building blocks for the generation of implantable biotextiles, and there are always needs for designing and developing new types of yarns to improve the properties of biotextile implants. In the present study, we aim to develop novel nanofiber yarns (NYs) by combining nanostructure that more closely mimic the extracellular matrix fibrils of native tissues with biodegradability, strong mechanical properties and great textile processibility. A novel electrospinning system which integrates yarn formation with hot drawing process was developed to fabricate poly(L-lactic acid) (PLLA) NYs. Compared to the PLLA NYs without hot drawing, the thermally drawn PLLA NYs presented superbly-orientated fibrous structure and notably enhanced crystallinity. Importantly, they possessed admirable mechanical performances, which matched and even exceeded the commercial PLLA microfiber yarns (MYs). The thermally drawn PLLA NYs were also demonstrated to notably promote the adhesion, alignment, proliferation, and tenogenic differentiation of human adipose derived mesenchymal stem cells (hADMSCs) compared to the PLLA NYs without hot drawing. The thermally drawn PLLA NYs were further processed into various nanofibrous tissue scaffolds with defined structures and adjustable mechanical and biological properties using textile braiding and weaving technologies, demonstrating the feasibility and versatility of thermally drawn PLLA NYs for textile-forming utilization. The hADMSCs cultured on PLLA NY-based textiles presented enhanced attachment and proliferation capacities than those cultured on PLLA MY-based textiles. This work presents a facile technique to manufacture high performance PLLA NYs, which opens up opportunities to generate advanced nanostructured biotextiles for surgical implant applications.

17.
Small ; 17(38): e2101671, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34342939

RESUMO

Most transition metal-based catalysts for electrocatalytic oxygen evolution reaction (OER) undergo surface reconstruction to generate real active sites favorable for high OER performance. Herein, how to use self-reconstruction as an efficient strategy to develop novel and robust OER catalysts by designing pre-catalysts with flexible components susceptible to OER conditions is proposed. The NiFe-based layered double hydroxides (LDHs) intercalated with resoluble molybdate (MoO4 2- ) anions in interlayers are constructed and then demonstrated to achieve complete electrochemical self-reconstruction (ECSR) into active NiFe-oxyhydroxides (NiFeOOH) beneficial to alkaline OER. Various ex situ and in situ techniques are used to capture structural evolution process including fast dissolution of MoO4 2- and deep reconstruction to NiFeOOH upon simultaneous hydroxyl invasion and electro-oxidation. The obtained NiFeOOH exhibits an excellent OER performance with an overpotential of only 268 mV at 50 mA cm-1 and robust durability over 45 h, much superior to NiFe-LDH and commercial IrO2 benchmark. This work suggests that the ECSR engineering in component-flexible precursors is a promising strategy to develop highly active OER catalysts for energy conversion.

18.
Angew Chem Int Ed Engl ; 60(41): 22368-22375, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34383376

RESUMO

The salts {[Ln2 Ln*(Hhmq)3 (OAc)3 (hfac)2 ]+ [Ln*(hfac)3 (OAc)(MeOH)]- } (Hhmq=2-methanolquinolin-8-oxide, hfac=hexafluoroacetylacetonate; Ln, Ln*=Er, Gd, Yb) feature a discrete heteronuclear cation consisting of two types of lanthanide atoms. The quinolinoxy O-atom serves as a µ2 -bridge to two Ln atoms and as a µ3 -bridge to all three atoms, with metal⋅⋅⋅metal distances being around 3.7 Å. For 1 ([Yb2 Er]+ ), near-infrared downshifted luminescence is switched to competitive upconversion luminescence upon irradiation by a 980 nm laser under an extremely low excitation power (0.288 W cm-2 ) through introduction of fluoride ions. The stability of 1 after addition of fluoride was confirmed by powder X-ray diffraction and multistage mass spectrometry, associated with the 1 H NMR of 6 ([La2 Eu]+ ). More importantly, the at least 20-fold enhancement of the quantum yield in non-deuterated solvents at room temperature under low power densities (2 W cm-2 ) is the highest among the few molecular examples reported.

20.
Am J Physiol Renal Physiol ; 321(5): F559-F571, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448643

RESUMO

Human kidney organoid technology holds promise for novel kidney disease treatment strategies and utility in pharmacological and basic science. Given the crucial roles of the intrarenal renin-angiotensin system (RAS) and angiotensin II (ANG II) in the progression of kidney development and injury, we investigated the expression of RAS components and effects of ANG II on cell differentiation in human kidney organoids. Human induced pluripotent stem cell-derived kidney organoids were induced using a modified 18-day Takasato protocol. Gene expression analysis by digital PCR and immunostaining demonstrated the formation of renal compartments and expression of RAS components. The ANG II type 1 receptor (AT1R) was strongly expressed in the early phase of organoid development (around day 0), whereas ANG II type 2 receptor (AT2R) expression levels peaked on day 5. Thus, the organoids were treated with 100 nM ANG II in the early phase on days 0-5 (ANG II-E) or during the middle phase on days 5-10 (ANG II-M). ANG II-E was observed to decrease levels of marker genes for renal tubules and proximal tubules, and the downregulation of renal tubules was inhibited by an AT1R antagonist. In contrast, ANG II-M increased levels of markers for podocytes, the ureteric tip, and the nephrogenic mesenchyme, and an AT2R blocker attenuated the ANG II-M-induced augmentation of podocyte formation. These findings demonstrate RAS expression and ANG II exertion of biphasic effects on cell differentiation through distinct mediatory roles of AT1R and AT2R, providing a novel strategy to establish and further characterize the developmental potential of human induced pluripotent stem cell-derived kidney organoids.NEW & NOTEWORTHY This study demonstrates angiotensin II exertion of biphasic effects on cell differentiation through distinct mediatory roles of angiotensin II type 1 receptor and type 2 receptor in human induced pluripotent stem cell-derived kidney organoids, providing a novel strategy to establish and further characterize the developmental potential of the human kidney organoids.

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