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1.
J Colloid Interface Sci ; 607(Pt 2): 1280-1286, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34583033

RESUMO

Before completely applying inorganic materials as hole transport materials (HTM) for perovskite solar cells (PSCs), modifying devices with inorganic oxides that have the potential as inorganic hole transporters is an effective way to improve device performance and stability. Co2+ doped CuGaO2 nanocrystals (Co-CuGaO2 NCs) with sizes about 20 nm are synthesized by hydrothermal method and used for surface passivation at the interface of perovskite (PVK)/2,2',7,7'-Tetrakis[N,N-di (4-methoxyphenyl) amino]-9,9'-spirobifluorene (spiroOMeTAD). Co-CuGaO2 NCs have a larger bandgap with lower valance band compared with spiroOMeTAD, which is more beneficial to the conduction of holes and the blocking of electrons. Furthermore, the Co-CuGaO2 has a lower valance band energy compared with the original CuGaO2, which reduces the energy gap between Co-CuGaO2 and PVK. Co-CuGaO2 NCs fully cover the upper surface of PVK, which helps prevent direct contact between PVK and oxygen and moisture. The Co-CuGaO2 NCs surface passivation also gives better hole transport as revealed by the ultraviolet photoelectron spectroscopy (UPS), steady-state photoluminescence (PL), and time-resolved photoluminescence (TRPL) data. When the concentration of Co-CuGaO2 NCs solution is set to 7.5 mg mL-1, the device exhibits a best PCE of 20.39% and maintains 84.34% of the initial power conversion efficiency (PCE) after stored 30 days under air atmosphere with 15 ±â€¯5% humidity.

2.
Neuropharmacology ; 203: 108871, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742928

RESUMO

Ghrelin is a circulating peptide hormone that promotes feeding and regulates metabolism in humans and rodents. The action of ghrelin is mediated by the growth hormone secretagogue receptor type 1a (GHSR-1a) that is widely distributed in the brain, including the hippocampus. Studies have demonstrated the critical role of hippocampal ghrelin/GHS-R1a signaling in synaptic physiology and memory. However, those findings are controversial, and the mechanism underlying ghrelin modulation of learning and memory is uncertain. Here, we report that micro-infusion of ghrelin in the CA1 region of the dorsal hippocampus during training specifically impairs memory acquisition. The activation of GHS-R1a and the subsequent PI3K/Akt/GSK3ß signaling cascades are involved in this process. Moreover, we report that bath application of ghrelin suppresses the intrinsic excitability of dCA1 pyramidal neurons through activating GHS-R1a, and PI3K inhibitor LY294002 blocks ghrelin's effect. However, LY294002 fails to rescue ghrelin-induced LTP impairment. Our findings support an adverse effect of ghrelin-dependent activation of GHS-R1a on memory acquisition, and suggest that PI3K/Akt/GSK3ß signaling-dependent repression of neuronal intrinsic excitability is an important novel mechanism underlying memory inhibition of ghrelin in the hippocampus.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34807564

RESUMO

In addition to thermoelectric (TE) performance tuning through defect or strain engineering, progress in mechanical research is of increasing importance to wearable applications of bismuth telluride (Bi2Te3) TE semiconductors, which are limited by poor deformability. For improving dislocation-controlled deformability, we clarify an order-tuned energy-dissipation strategy that facilitates large deformation through multilayer alternating slippage and stacking fault destabilization. Given that energy dissipation and dislocation motions are governed by van der Waals sacrificial bond (SB) behavior, molecular dynamics simulation is implemented to reveal the relation between the shear deformability and lattice order changes in Bi2Te3 crystals. Using the disorder parameter (D) that is defined according to the configurational energy distribution, the results of strain rates and initial crack effects show how the proper design of the initial structure and external conditions can suppress strain localization that would cause structural failure from the lack of energy dissipation, resulting in large homogeneous deformation of Bi2Te3 nanocrystals. This study uncovers the essence of the tuning mechanism in which highly deformable Bi2Te3 crystals should become disordered as slowly as possible until fracture. This highlights the role of the substructure evolution of SB-defect synergy that facilitates energy dissipation and performance stability during slipping. The disorder parameter D provides a bridge between micro/local mechanics and fracture strain, hinting at the possible mechanical improvement of Bi2Te3 semiconductors for designing flexible TE devices through order tuning and energy dissipation.

4.
BMJ Open ; 11(11): e047774, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772745

RESUMO

AIMS: To develop a nomogram for incident chronic kidney disease (CKD) risk evaluation among community residents with high cardiovascular disease (CVD) risk. METHODS: In this retrospective cohort study, 5730 non-CKD residents with high CVD risk participating the National Basic Public Health Service between January 2015 and December 2020 in Guangzhou were included. Endpoint was incident CKD defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 during the follow-up period. The entire cohorts were randomly (2:1) assigned to a development cohort and a validation cohort. Predictors of incident CKD were selected by multivariable Cox regression and stepwise approach. A nomogram based on these predictors was developed and evaluated with concordance index (C-index) and area under curve (AUC). RESULTS: During the median follow-up period of 4.22 years, the incidence of CKD was 19.09% (n=1094) in the entire cohort, 19.03% (727 patients) in the development cohort and 19.21% (367 patients) in the validation cohort. Age, body mass index, eGFR 60-89 mL/min/1.73 m2, diabetes and hypertension were selected as predictors. The nomogram demonstrated a good discriminative power with C-index of 0.778 and 0.785 in the development and validation cohort. The 3-year, 4-year and 5-year AUCs were 0.817, 0.814 and 0.834 in the development cohort, and 0.830, 0.847 and 0.839 in the validation cohort. CONCLUSION: Our nomogram based on five readily available predictors is a reliable tool to identify high-CVD risk patients at risk of incident CKD. This prediction model may help improving the healthcare strategies in primary care.

5.
Nanotechnology ; 33(7)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34757948

RESUMO

Phenol is considered as an important platform molecule for synthesizing value-added chemical intermediates and products. To date, various strategies for phenol transformation have been developed, and among them, selective hydrogenation of phenol toward cyclohexanone (K), cyclohexanol (A) or the mixture KA oil has been attracted great interest because they are both the key raw materials for the synthesis of nylon 6 and 66, as well as many other chemical products, including polyamides. However, until now it is still challengeable to realize the industrilized application of phenol hydrogenation toward KA oils. To better understand the selective hydrogenation of phenol and fabricate the enabled nanocatalysts, it is necessary to summarize the recent progress on selective hydrogenation of phenol with different catalysts. In this review, we first summarize the selective hydrogenation of phenol toward cyclohexanone or cyclohexanol by different nanocatalysts, and simultaneously discuss the relationship among the active components, type of supports and their performances. Then, the possible reaction mechanism of phenol hydrogenation with the typical metal nanocatalysts is summarized. Subsequently, the possible ways for scale-up hydrogenation of phenol are discussed. Finally, the potential challenges and future developments of metal nanocatalysts for the selective hydrogenation of phenol are proposed.

6.
Biosens Bioelectron ; : 113829, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34840016

RESUMO

Common reference methods for COVID-19 diagnosis include thermal cycling amplification (e.g. RT-PCR) and isothermal amplification methods (e.g. LAMP and RPA). However, they may not be suitable for direct detection in environmental and biological samples due to background signal interference. Here, we report a rapid and label-free interference reduction nucleic acid amplification strategy (IR-NAAS) that exploits the advantages of luminescent iridium(III) probes, time-resolved emission spectroscopy (TRES) and multi-branch rolling circle amplification (mbRCA). Using IR-NAAS, we established a luminescence approach for diagnosing COVID-19 RNAs sequences RdRp, ORF1ab and N with a linear range of 0.06-6.0 × 105 copies/mL and a detection limit of down to 7.3 × 104 copies/mL. Moreover, the developed method was successfully applied to detect COVID-19 RNA sequences from various environmental and biological samples, such as domestic sewage, and mice urine, blood, feces, lung tissue, throat and nasal secretions. Apart from COVID-19 diagnosis, IR-NAAS was also demonstrated for detecting other RNA viruses, such as H1N1 and CVA10, indicating that this approach has great potential approach for routine preliminary viral detection.

7.
Polymers (Basel) ; 13(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34833293

RESUMO

This paper presents an innovative pumpable standing support designed for underground mines located in the arid and semi-arid deserts of the Gobi region with a shortage of water resources. The exterior shell of this pumpable standing support is made of carbon fiber-reinforced polymer (CFRP), while the infill material is a sand-based material (SBM). As the novel backfill material, SBM is the combination of high-water cementing material and desert sand. A series of experimental tests were conducted to obtain the mechanical response mechanism of this novel pumpable standing support under uniaxial compression. Test variables investigated in this research covered the water-to-powder ratio of the cementing material, the mixing amount of sand, and the thickness of the CFRP tube. Test results confirmed that the CFRP-confined SBM columns exhibited typical strain hardening behavior with the acceptable axial deformation. It was also demonstrated that using high-strength cementing material, a thicker CFRP tube, and a high mixing amount of sand effectively increased the bearing capacity of the CFRP-confined SBM column. Except for the exemplary structural behavior, the consumption of high-water cementing materials of the novel pumpable standing support is smaller than that of its counterparts made of pure cementing material, when specimens with the same mechanical performance are compared.

8.
J Colloid Interface Sci ; 608(Pt 1): 40-47, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34624764

RESUMO

High efficiency and stability have long been the key issues faced by perovskite solar cells (PSCs). It is found that the CsPbIBr2 all-inorganic perovskite has a suitable band gap and satisfactory stability, so it has attracted much attention. However, the many defects in the CsPbIBr2 film are one of the main problems hindering the improvement of power conversion efficiency (PCE) of the CsPbIBr2 PSCs. The substitution of trace impurities is undoubtedly a simple, cost-effective and efficient strategy. In this work, an appropriate amount of Cd2+ (1.0% mol of Pb2+) is added into the CsPbIBr2 precursor solution to fabricate high quality CsPbIBr2 film with improved crystallinity, reduced trap density, suppressed photo-generated carrier recombination, displayed n-type doping and optimized energy level alignment. The corresponding carbon-based all-inorganic Cd2+-doped CsPbIBr2 PSCs achieve a maximum PCE of 10.63% with a high open circuit voltage (VOC) of 1.324 V, which are much higher than those of the control one with a PCE of 8.48% and an VOC of 1.235 V. The unencapsulated device can still retain more than 92% of the initial PCE when stored at ambient atmosphere (25 °C, relative humidity about 30%) for 40 days.

9.
Small ; : e2101518, 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34658130

RESUMO

Conductive hydrogels can be prepared by incorporating various conductive materials into polymeric network hydrogels. In recent years, conductive hydrogels have been developed and applied in the field of strain sensors owing to their unique properties, such as electrical conductivity, mechanical properties, self-healing, and anti-freezing properties. These remarkable properties allow conductive hydrogel-based strain sensors to show excellent performance for identifying external stimuli and detecting human body movement, even at subzero temperatures. This review summarizes the properties of conductive hydrogels and their application in the fabrication of strain sensors working in different modes. Finally, a brief prospectus for the development of conductive hydrogels in the future is provided.

10.
Ann Palliat Med ; 10(9): 9848-9858, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628911

RESUMO

BACKGROUND: Minimally invasive transforaminal interbody fusion (MI-TLIF) can minimize surgical incision, tissue damage, and intraoperative blood loss in the treatment of spondylolisthesis. However, there is a lack of evidence-based research to confirm its clinical efficacy. METHODS: Chinese and English databases were searched with "open", "minimally invasive transforaminal interbody fusion", "MIS-TLIF", "spondylolisthesis", and "open transforaminal interbody fusion" as search terms. Rev Man 5.3 provided by the Cochrane system was used to assess the quality of the literature. RESULTS: Of the 12 randomized controlled trials (RCTs), 7 references were level A (58.34%), 4 were B level (33.33%), and 1 reference was C level (8.33%). There was a statistically significant difference in intraoperative blood loss between MI-TLIF and open transforaminal interbody fusion (O-TLIF) in the treatment of spondylolisthesis [mean difference (MD) =-349.35, 95% confidence interval (CI): (-410.66, -288.03), P<0.00001]. There was also a statistically significant difference in visual analogue scale (VAS) scores before and after MI-TLIF at the last follow-up [MD =5.72, 95% CI: (4.83, 6.62), P<0.00001], and in the complication rate between MI-TLIF and O-TLIF [odds ratio (OR) =0.48, 95% CI: (0.30, 0.76), P<0.00001]. DISCUSSION: This meta-analysis confirmed that MI-TLIF could significantly reduce intraoperative blood loss, mitigate patient pain, and reduce the incidence of complications without increasing the operation time in the treatment of spondylolisthesis.


Assuntos
Fusão Vertebral , Espondilolistese , Humanos , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Espondilolistese/cirurgia , Resultado do Tratamento
11.
J Phys Chem Lett ; 12(43): 10486-10496, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34677985

RESUMO

Selective hydrogenation of carbon dioxide (CO2) into value-added chemicals has aroused great interest. The chemical inertness of CO2 and diverse reaction pathways usually require the construction of enabled catalysts. To date, cobalt (Co) catalysts characteristic of metallic and/or divalent Co components show great potential for CO2 hydrogenation. To better regulate the CO2 hydrogenation, it is necessary to summarize the current progress of cobalt catalysts for selective hydrogenation of CO2. In this Perspective, first, hydrogenation of CO2 into methane over metallic Co sites is introduced. Second, hydrogenation of CO2 into methanol and C2+ alcohols is discussed by constructing mixed-valent cobalt sites. Third, hydrogenation of CO2 into light olefins and C5+ liquid fuels over cobalt-containing hybrid catalysts is introduced. Fourth, the reaction paths for selective hydrogenation of CO2 over cobalt catalysts are illustrated. Finally, the current challenges and prospects of cobalt-based nanocatalysts for hydrogenation of CO2 are proposed.

12.
Nanoscale ; 13(42): 17920-17928, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34679151

RESUMO

The development of cost-effective, high-efficiency bifunctional electrocatalysts as alternatives to the state-of-the-art Pt-based materials toward the hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) is of great significance but still challenging. Herein, an advanced bifunctional electrocatalyst is presented, composed of Fe2P encapsulated in carbon nanowalls decorated with well-dispersed Fe3C nanodots (denoted as Fe2P@Fe3C/CNTs), which is achieved by a novel "inside-out" gas-solid reaction protocol. When functioning as a cathodic catalyst for water splitting, the Fe2P@Fe3C/CNT catalyst needs an ultralow overpotential of 83 mV to deliver a current density of 10 mA cm-2, shows a small Tafel slope of 53 mV dec-1 and ensures long-term stability for over 200 h in an alkaline electrolyte. Notably, the Fe2P@Fe3C/CNT catalyst exhibits an extremely impressive ORR performance with an onset potential (Eonset) of 1.060 V and a half-wave potential (E1/2) of 0.930 V, excellent stability (≈94% activity retention after 36 000 s), and a strong methanol resistance ability, even far outperforming commercial Pt/C (Eonset = 0.955 V, E1/2 = 0.825 V, ≈75% activity retention after less than 3500 s). Such outstanding HER and ORR performances are mainly ascribed to the improved corrosion resistance of the unique Fe2P@C core-shell structures, the abundant catalytically active sites of ultrasmall Fe3C nanodots incorporated in carbon nanowalls, and the good electrical conductivity of 2D graphitic carbon nanotubes used as a support.

13.
ACS Appl Mater Interfaces ; 13(42): 50083-50092, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34648264

RESUMO

The practical applications of perovskite solar cells (PSCs) are limited by further improvement of their stability and performance. Additive engineering and interface engineering are promising medicine to cure this stubborn disease. Herein, an alkali metal fluoride as an additive is introduced into the tin oxide (SnO2) electron transport layer (ETL). The formation of coordination bonds of F- ions with the oxygen vacancy of Sn4+ ions decreases the trap-state density and improves the electron mobility; the hydrogen bond interaction between the F ion and amine group (FA+) of perovskite inhibits the diffusion of organic cations and promotes perovskite (PVK) stability. Meanwhile, the alkali metal ions (K+, Rb+, and Cs+) permeated into PVK fill the organic cation vacancies and ameliorate the crystal quality of PVK films. Consequently, a SnO2-based planar PSC exhibits a power conversion efficiency (PCE) of 20.24%, while the PSC modified by CsF achieves a PCE of 22.51%, accompanied by effective enhancement of stability and negligible hysteresis. The research results provide a typical example for low-cost and multifunctional additives in high-performance PSCs.

14.
Small ; : e2103336, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34708521

RESUMO

The carrier non-radiative recombination and instability of device caused by the inherent defects are main factors limiting development of perovskite solar cells (PSCs). During the fabrication process of a PSC device, perovskite films often produce Pb0 and I0 defects. This paper reports a strategy for synergistic optimization of perovskite films by defects passivation and surface modification. The doping of phthalide (PT) in the Pb-rich (CH(NH2 )2 )1-x (CH3 NH3 )x PbI3 film can passivate lead cation defects, and the modification of 1-iodooctadecane (1-IO) can reduce halogen anion defects and improve stability of PSCs owing to its hydrophobicity. The PT and 1-IO optimized device achieves a power conversion efficiency (PCE) of 22.27%. The optimized PSCs remain 93.2% of the initial PCE when placed in air environment (relative humidity of 10%, 25 °C) more than 70 days. The PT and 1-IO synergistic optimization provides a novel strategy for improving the performance and stability of PSCs.

15.
Materials (Basel) ; 14(20)2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34683752

RESUMO

This study presented evaluation of a concrete damage process by the acoustic emission (AE) technique under uniaxial multi-step compressive loading procedure combined with digital image correlation (DIC). The results showed that AE elastic wave velocity had good stress dependence in the damage process of concrete specimens with different sizes (cube, prism) and coarse aggregate characteristics (volume fraction, maximum size), and the effects of specimen sizes and coarse aggregate characteristics on the stress dependence can be nearly neglected. The standard deviation of 32 AE elastic wave velocities was used as the criterion to evaluate the relative stress ratio of concrete under different damage states, and the damage process of concrete was divided into three damage stages according to this criterion. When the standard deviation is below 70, in the range of 70 to 1700, and greater than 1700, the concrete damage process is defined as steady damage process, accelerated damage process and buckling damage process, respectively. The accuracy of the presented evaluation methodology was demonstrated by comparative results with digital image correlation. The results indicate that the standard deviation of AE elastic wave velocities can potentially serve as a reliable, convenient, and non-destructive evaluation criterion of concrete damage state under uniaxial compressive loading.

16.
Nanoscale ; 13(38): 16277-16287, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34549748

RESUMO

Developing cost-effective, highly-active and robust electrocatalysts is of vital importance to supersede noble-metal ones for both hydrogen evolution reactions (HERs) and oxygen reduction reactions (ORRs). Herein, a unique vanadium-mediated space confined strategy is reported to construct a composite structure involving Co/Co9S8 nanoparticles anchored on Co-N-doped porous carbon (VCS@NC) as bifunctional electrocatalysts toward HER and ORR. Benefitting from the ultrafine nanostructure, abundant Co-Nx active sites, large specific surface area and defect-rich carbon framework, the resultant VCS@NC exhibits unexceptionable HER catalytic activity, needing extremely low HER overpotentials in pH-universal media (alkaline: 117 mV, acid: 178 mV, neutral: 210 mV) at a current density of 10 mA cm-2, paralleling at least 100 h catalytic durability. Notably, the VCS@NC catalyst delivers high-efficiency ORR performance in alkaline solution, accompanied with a quite high half wave potential of 0.901 V, far overmatching the commercial Pt/C catalyst. Our research opens up novel insight into engineering highly-efficient multifunctional non-precious metal electrocatalysts by a metal-mediated space-confined strategy in energy storage and conversion system.

17.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3116-3122, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467703

RESUMO

Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.


Assuntos
Aconitum , Perfilação da Expressão Gênica , Genes de Plantas/genética , Reação em Cadeia da Polimerase em Tempo Real , Padrões de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Artigo em Inglês | MEDLINE | ID: mdl-34557254

RESUMO

Colorectal cancer (CRC) is one of the most common malignant tumors with high morbidity and mortality. The early symptoms are latent, and most patients are in the middle or late stage when they are diagnosed. The best opportunity for surgery has been lost, and surgical resection has failed to achieve good results. In clinical practice, targeted therapy or chemotherapy is usually the main treatment. The mFOLFOX6 regimen is a standardized regimen for the treatment of advanced CRC. The main drugs in this regimen are oxaliplatin and 5-fluorouracil (5-FU). Patients with advanced CRC combined with standard chemotherapy regimens can achieve a higher resection rate of liver metastases in unresectable patients, which can achieve significant survival improvement. Therefore, in this study, oxaliplatin + calcium folinate + 5-Fu + mFOLFOX6 regimen was combined with cetuximab and simvastatin to treat CRC patients, and the clinical efficacy and prognosis were analyzed, as well as the prognostic factors. The results showed that the addition of simvastatin on the basis of conventional mFOLFOX6 regimen combined with cetuximab chemotherapy could effectively improve the efficacy, reduce the total incidence of adverse reactions, improve the overall survival rate, and prolong the overall survival time of patients. Pathological grade and peritoneal metastasis were the factors affecting the mean survival time of CRC patients.

19.
Redox Biol ; : 102129, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34526248

RESUMO

Hepatotoxicity caused by an overdose of acetaminophen (APAP) is the leading reason for acute drug-related liver failure. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protein that helps to regulate redox homeostasis and coordinate stress responses via binding to the Kelch-like ECH-associated protein 1 (Keap1). Targeting the Keap1-Nrf2 interaction has recently emerged as a potential strategy to alleviate liver injury caused by APAP. Here, we designed and synthesized a number of iridium (III) and rhodium (III) complexes bearing ligands with reported activity against oxidative stress, which is associated with Nrf2 transcriptional activation. The iridium (III) complex 1 bearing a bioactive ligand 2,9-dimethyl-1,10-phenanthroline and 4-chloro-2-phenylquinoline, a derivative of the bioactive ligand 2-phenylquinoline, was identified as a direct small-molecule inhibitor of the Keap1-Nrf2 protein-protein interaction. 1 could stabilize Keap1 protein, upregulate HO-1 and NQO1, and promote Nrf2 nuclear translocation in normal liver cells. Moreover, 1 reversed APAP-induced liver damage by disrupting Keap1-Nrf2 interaction and without inducing organ damage and immunotoxicity in mice. Our study demonstrates the identification of a selective and efficacious antagonist of Keap1-Nrf2 interaction possessed good cellular permeability in cellulo and ideal pharmacokinetic parameters in vivo, and, more importantly, validates the feasibility of conjugating metal complexes with bioactive ligands to generate metal-based drug leads as non-toxic Keap1-Nrf2 interaction inhibitors for treating APAP-induced acute liver injury.

20.
ACS Synth Biol ; 10(8): 1874-1881, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34259519

RESUMO

Tunicosaponins are natural products extracted from Psammosilene tunicoides, which is an important ingredient of Yunnan Baiyao Powder, an ancient and famous Asian herbal medicine. The representative aglycones of tunicosaponins are the oleanane-type triterpenoids of gypsogenin and quillaic acid, which were found to manipulate a broad range of virus-host fusion via wrapping the heptad repeat-2 (HR2) domain prevalent in viral envelopes. However, the unknown biosynthetic pathway and difficulty in chemical synthesis hinder the therapeutic use of tunicosaponins. Here, two novel cytochrome P450-dependent monooxygenases that take part in the biosynthesis of tunicosaponins, CYP716A262 (CYP091) and CYP72A567 (CYP099), were identified from P. tunicoides. In addition, the whole biosynthesis pathway of the tunicosaponin aglycones was reconstituted in yeast by transforming the platform strain BY-bAS with the CYP716A262 and CYP716A567 genes, the resulting strain could produce 146.84 and 314.01 mg/L of gypsogenin and quillaic acid, respectively. This synthetic biology platform for complicated metabolic pathways elucidation and microbial cell factories construction can provide alternative sources of important natural products, helping conserve natural plant resources.

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