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1.
Brain Res ; : 147685, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34637761

RESUMO

The outer mitochondrial membrane protein mitochondrial Rho-GTPase 1 (Miro1) is known to be involved in the regulation of mitochondrial transport required for neuronal protection. Previous reports established that disruption of Miro1-dependent mitochondrial movement could result in nervous system diseases such as Parkinson's disease and Alzheimer's disease. This study was designed to explore the expression and mechanisms of Miro1 in secondary brain injury after traumatic brain injury (TBI). A total of 115 male Sprague Dawley rats were used in the weight-drop TBI rat model, and Miro1 in vivo knockdown was performed 24 h before TBI modeling by treatment with Miro1 short-interfering RNA. Real-time polymerase chain reaction, western blot, immunofluorescence, adenosine triphosphate (ATP) level assay, neuronal apoptosis, brain water content measurement, and neurological score analyses were carried out. Our results showed that the mRNA and protein levels of Miro1 were increased after TBI and co-localized with neurons and astrocytes in the peri-injury cortex. Moreover, Miro1 knockdown further exacerbated neuronal apoptosis, brain edema, and neurological deficits at 48 h after TBI, accompanied by impaired mitochondrial transport, reduction of mitochondria number and energy deficiency. Additionally, the apoptosis-related factors Bax upregulation and Bcl-2 downregulation as Miro1 knockdown after TBI implied that antiapoptotic effects on neuroprotection of Miro1, which were verified by the Fluoro-Jade C (FJC) staining and TUNEL staining. In conclusion, these findings suggest that Miro1 probably plays a neuroprotective role against secondary brain injury through the mitochondria trafficking pathway, suggesting that enhancing Miro1 might be a new strategy for the treatment of TBI.

2.
Biomater Sci ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647942

RESUMO

Multienzyme nanoassemblies (MENAs) that combine the functions of several enzymes into one entity have attracted widespread research interest due to their improved enzymatic performance and great potential for multiple applications. Considerable progress has been made to design and fabricate MENAs in recent years. This review begins with an introduction of the up-to-date strategies in designing MENAs, mainly including substrate channeling, compartmentalization and control of enzyme stoichiometry. The desirable properties that endow MENAs with important applications are also discussed in detail. Then, the recent advances in utilizing MENAs in the biomedical field are reviewed, with a particular focus on biosensing, tumor therapy, antioxidant and drug delivery. Finally, the challenges and perspectives for development of versatile MENAs are summarized.

3.
J Biochem Mol Toxicol ; : e22926, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605098

RESUMO

Globally, doxorubicin (DOX)-induced cardio dysfunction is a serious cause of morbidity and mortality in cancerous patients. An adverse event of cardiotoxicity is the main deem to restrict in the clinical application by oncologists. Corilagin (CN) is well known for its antioxidative, anti-fibrosis, and anticancer effects. Herein, we aimed to evaluate the action of CN on DOX-induced experimental animals and H9c2 cells. The myocardium-specific marker, CK-MB, and the influx of mitochondrial calcium levels were measured by using commercial kits. Biochemical indices reflecting oxidative stress and antioxidant attributes such as malondialdehyde, glutathione peroxidase, reduced glutathione, superoxide dismutase, and catalase were also analyzed in DOX-induced cardiotoxic animals. In addition, mitochondrial ROS were measured by DCFH-DA in H9c2 cells under fluorescence microscopy. DOX induction significantly increased oxidative stress levels and also modulated apoptosis/survival protein expressions in myocardial tissues. Western blots were used to measure the expressional levels of Bax/Bcl-2, caspase-3, PI3-K/AKT, and PPARγ signaling pathways. Histological studies were executed to observe morphological changes in myocardial tissues. All of these DOX-induced effects were attenuated by CN (100 mg/kg bw). These in vitro and in vivo results point towards the fact that CN might be a novel cardioprotective agent against DOX-induced cardiotoxicity through modulating cardio apoptosis and oxidative stress.

4.
Neuroscience ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626749

RESUMO

With-no-lysine kinase 3 (WNK3) is a key regulator of chloride ion transport and neuronal survival in diverse cell types. WNK3 was previously found to regulate the activity of Na+-K+-2Cl- cotransporter-1 (NKCC1) in ischemia-associated brain damage. However, the role of WNK3 in traumatic brain injury (TBI) has not yet been studied. A weight-drop TBI model was established in Sprague-Dawley rats. Overexpression and specific inhibition were used to investigate the role of WNK3 in TBI via Western blot, immunofluorescence, neuronal apoptosis, brain water content, and neurological score analyses. We found pronounced TBI-induced downregulation of WNK3 expression and upregulation of NKCC1 expression in neurons, especially at 48 h. Overexpression of WNK3 significantly ameliorated neuronal apoptosis, blood-brain barrier (BBB) disruption, brain edema and neurological deficits at 48 h after TBI. These effects were concomitant with reductions in p-NKCC1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) expression. Furthermore, bumetanide administration enhanced the neuroprotective effects of WNK3 overexpression against brain injury. Thus, WNK3 plays a neuroprotective role in TBI, and overexpression of WNK3 may increase cell resistance to apoptotic insults and brain edema, thereby alleviating secondary brain injury.

5.
J Med Chem ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643383

RESUMO

RORγ is a dual-functional drug target, which involves not only induction of inflammation but also promotion of cancer immunity. The development of agonists of RORγ promoting Th17 cell differentiation could provide a novel mechanism of action (MOA) as an immune-activating anticancer agent. Herein, we describe new 2-(ortho-substituted benzyl)-indole derivatives as RORγ agonists by scaffold hopping based on clinical RORγ antagonist VTP-43742. Interestingly, subtle structural differences of the compounds led to the opposite biological MOA. After rational optimization for structure-activity relationship and pharmacokinetic profile, we identified a potent RORγ agonist compound 17 that was able to induce the production of IL-17 and IFNγ in tumor tissues and elicit antitumor efficacy in MC38 syngeneic mouse colorectal tumor model. This is the first comprehensive work to demonstrate the in vivo antitumor efficacy of an RORγ agonist.

6.
Biotechnol Bioeng ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491579

RESUMO

Glycolate is a bulk chemical with wide applications in the textile, food processing, and pharmaceutical industries. Glycolate can be produced from glucose via the glycolysis and glyoxylate shunt pathways, followed by reduction to glycolate. However, two problems limit the productivity and yield of glycolate when using glucose as the sole carbon source. The first is a cofactor imbalance in the production of glycolate from glucose via the glycolysis pathway, since NADPH is required for glycolate production, while glycolysis generates NADH. To rectify this imbalance, the NADP+ -dependent glyceraldehyde 3-phosphate dehydrogenase GapC from Clostridium acetobutylicum was introduced to generate NADPH instead of NADH in the oxidation of glyceraldehyde 3-phosphate during glycolysis. The soluble transhydrogenase SthA was further eliminated to conserve NADPH by blocking its conversion into NADH. The second problem is an unfavorable carbon flux distribution between the tricarboxylic acid cycle and the glyoxylate shunt. To solve this problem, isocitrate dehydrogenase (ICDH) was eliminated to increase the carbon flux of glyoxylate and thereby improve the glycolate titer. After engineering through the integration of gapC, combined with the inactivation of ICDH, SthA, and by-product pathways, as well as the upregulation of the two key enzymes isocitrate lyase (encoding by aceA), and glyoxylate reductase (encoding by ycdW), the glycolate titer increased to 5.3 g/L with a yield of 1.89 mol/mol glucose. Moreover, an optimized fed-batch fermentation reached a titer of 41 g/L with a yield of 1.87 mol/mol glucose after 60 h.

7.
J Med Chem ; 64(18): 13693-13703, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34472840

RESUMO

Disrupting the interaction between HIF1α and p300 is a promising strategy to modulate the hypoxia response of tumor cells. Herein, we designed a constrained peptide inhibitor derived from the CITED2/p300 complex to disturb the HIF1α/p300 interaction. Through truncation/mutation screening and a terminal aspartic acid-stabilized strategy, a constrained peptide was constructed with outstanding biochemical/biophysical properties, especially in binding affinity, cell penetration, and serum stability. To date, our study was the first one to showcase that stabilized peptides derived from CITED2 using helix-stabilizing methods acted as a promising candidate for modulating hypoxia-inducible signaling.

8.
J Affect Disord ; 295: 422-430, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34507222

RESUMO

BACKGROUND: The prefrontal-limbic-subcortical network has been suggested as an important circuitry in the pathophysiology underlying bipolar disorder during depressive episodes (BDD). However, the relationships between disrupted prefrontal-limbic-subcortical connection and the emotional endophenotypes in BDD patients remain largely unclear. METHODS: Forty-three BDD patients and 63 matched healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging scan. The altered clusters were first identified by using a spatial pairwise clustering method and then were extracted as regions of interest to calculate the functional connectivity (FC). Group comparisons were conducted to identify the abnormal FCs. Classification analysis was employed to examine whether the altered FCs could distinguish BDD from HCs. The relationships between FC alterations and the emotional endophenotypes as measured by the Affective Neuroscience Personality Scales (ANPS) were further detected in BDD. RESULTS: Compared with HCs, BDD patients showed abnormal FCs in the prefrontal-limbic-striatum circuit. Importantly, the altered FCs yielded 84.91% accuracy (p< 1/5000) with 93.65% sensitivity and 72.09% specificity in differentiating between BDD and HCs. Moreover, the decreased FCs in the prefrontal-striatum and prefrontal-limbic systems were positively correlated with negative emotional endophenotypes of Sadness and Fear scores. CONCLUSIONS: The findings demonstrated that prefrontal-limbic-striatum disconnection may be identified as a potential effective biomarker for BDD, which could help further explain the neurobiological mechanisms underlying BDD.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34479169

RESUMO

Banggai cardinalfish, Pterapogon kauderni, is a tropical fish listed as an endangered species by IUCN. Its distribution and survival condition are extremely limited, and the changes of living environment caused by global warming may seriously threaten its geographical distribution. In order to understand the survival temperature range and the potential mechanism of temperature plasticity of P. kauderni, transcriptome analysis was performed under five temperature conditions (18 °C, 22 °C, 26 °C, 30 °C and 34 °C). A total of 432,444,497 clean reads were obtained from the mix tissues of whole head, viscera (except intestine), and muscle. All clean data were spliced into 194,832 unigenes. Compared with 26 °C, 57, 107, 187 and 174 differentially expressed genes (DEGs) were obtained at 18 °C, 22 °C, 30 °C and 34 °C, respectively. Gene Ontology (GO) analysis showed the most highly enriched in the DEGs were cellular processes, binding, metabolic processes and biological regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated circadian rhythm, protein processing in endoplasmic reticulum, influenza A and prion disease were significantly enriched. 47 genes that may be related to temperature stress were identified, such as Per1, MLP, IGFBP1, HSP70, HSP90α, HSPA4, DNAJB1, CALR. This is the first RNA-Seq study of P. kauderni. This information should be valuable for further targeted studies on temperature tolerance, thereby assisting the protection and development of P. kauderni.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34555906

RESUMO

Photocatalytic reduction of CO2 toward eight-electron CH4 product with simultaneously high conversion efficiency and selectivity remains great challenging owing to the sluggish charge separation and transfer kinetics and lack of active sites for the adsorption and activation of reactants. Herein, a defective TiO2 nanosheet photocatalyst simultaneously equipped with AuCu alloy co-catalyst and oxygen vacancies (AuCu-TiO2-x NSs) was rationally designed and fabricated for the selective conversion of CO2 into CH4. The experimental results demonstrated that the AuCu alloy co-catalyst not only effectively promotes the separation of photogenerated electron-hole pairs but also acts as synergistic active sites for the reduction of CO2. The oxygen vacancies in TiO2 contribute to the separation of charge carriers and, more importantly, promote the oxidation of H2O, thus providing rich protons to promote the deep reduction of CO2 to CH4. Consequently, the optimal AuCu-TiO2-x nanosheets (NSs) photocatalyst achieves a CO2 reduction selectivity toward CH4 up to 90.55%, significantly higher than those of TiO2-x NSs (31.82%), Au-TiO2-x NSs (38.74%), and Cu-TiO2-x NSs (66.11%). Furthermore, the CH4 evolution rate over the AuCu-TiO2-x NSs reaches 22.47 µmol·g-1·h-1, which is nearly twice that of AuCu-TiO2 NSs (12.10 µmol·g-1·h-1). This research presents a unique insight into the design and synthesis of photocatalyst with oxygen vacancies and alloy metals as the co-catalyst for the highly selective deep reduction of CO2.

11.
Biochimie ; 191: 78-86, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492335

RESUMO

SPIN1 is a histone methylation reader, which can epigenetically control multiple tumorigenesis-associated signaling pathways, including the Wnt, PI3K/AKT, and RET pathways. Considerable evidence has shown that SPIN1 is overexpressed in many cancers, which can promote cell proliferation, transformation, metastasis, and chemical or radiation resistance. With the growing understanding of the SPIN1 protein structure, some inhibitors have been developed to interfere with the recognition between SPIN1 and histone H3K4me3 and H3R8me2a methylation and block the oncogenic functions of SPIN1. Therefore, SPIN1 is a potential target of cancer therapy. However, the mechanism by which SPIN1-transformed cells overcome the significant mitotic spindle defects and the factors promoting SPIN1 overexpression in cancers remain unclear. In this review, we described the current understanding of the SPIN1 protein structure and its expression, functions, and regulatory mechanisms in carcinogenesis, and discussed the challenges faced in the mechanisms of SPIN1 overexpression and oncogenic functions, and the potential application of anti-SPIN1 treatment in human cancers.

12.
Exp Cell Res ; 406(2): 112767, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364882

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the world, with a high mortality rate. RAN is a member of the Ras GTPase family and is overexpressed in a range of cancers, however, the relationship between RAN and OSCC is rarely reported. In this study, we found that RAN is overexpressed in OSCC tissues. RAN inhibition retarded OSCC cell proliferation and led to apoptosis and cell cycle arrest. Knockdown of RAN inhibited tumor growth in vivo. Strikingly, we found that RAN and oncogene Y-box binding protein-1 (YBX1) are positively associated with the immune infiltrates of CD4+ Th2 cells in multiple types of cancer, and can promote IL-4 expression. IL-4 treatment can partially rescue RAN knockdown-induced cell apoptosis in OSCC cells. Moreover, overexpression of RAN could rescue cell growth inhibition caused by knockdown of YBX1. Furthermore, patients with low expression of both RAN and YBX1 had better overall survival than others. Collectively, these findings indicate that RAN is a target of YBX1. RAN and YBX1 are required for cell proliferation and IL-4 expression. RAN and YBX1 are co-expressed and can serve as potential co-biomarkers for poor prognosis in OSCC.

13.
Nat Commun ; 12(1): 4902, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385461

RESUMO

Efficient and precise base editors (BEs) for C-to-G transversion are highly desirable. However, the sequence context affecting editing outcome largely remains unclear. Here we report engineered C-to-G BEs of high efficiency and fidelity, with the sequence context predictable via machine-learning methods. By changing the species origin and relative position of uracil-DNA glycosylase and deaminase, together with codon optimization, we obtain optimized C-to-G BEs (OPTI-CGBEs) for efficient C-to-G transversion. The motif preference of OPTI-CGBEs for editing 100 endogenous sites is determined in HEK293T cells. Using a sgRNA library comprising 41,388 sequences, we develop a deep-learning model that accurately predicts the OPTI-CGBE editing outcome for targeted sites with specific sequence context. These OPTI-CGBEs are further shown to be capable of efficient base editing in mouse embryos for generating Tyr-edited offspring. Thus, these engineered CGBEs are useful for efficient and precise base editing, with outcome predictable based on sequence context of targeted sites.


Assuntos
Sistemas CRISPR-Cas , Citidina Desaminase/metabolismo , Edição de Genes/métodos , Aprendizado de Máquina , Uracila-DNA Glicosidase/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Caenorhabditis elegans/genética , Códon/genética , Citidina Desaminase/genética , Escherichia coli/genética , Feminino , Biblioteca Gênica , Células HEK293 , Humanos , Camundongos , Reprodutibilidade dos Testes , Uracila-DNA Glicosidase/genética
14.
Clin Lab ; 67(8)2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34383408

RESUMO

BACKGROUND: The coagulation cascade and inflammatory processes target damage in endothelial cells in sepsis-induced disseminated intravascular coagulation (DIC). This study aimed to measure levels of the molecular marker of endothelial injury, thrombomodulin, in patients with sepsis-induced DIC and to investigate potential relationships with poor clinical outcomes. METHODS: From October 2017 to October 2018, 45 patients with sepsis-induced DIC were recruited at Renmin Hospital of Wuhan University, in China. Concentrations of thrombomodulin and other routine coagulation and inflammatory factors were quantified. RESULTS: Thrombomodulin was present in the plasma of non-survivors at significantly higher levels than in the plasma of survivors (9.30 ± 1.56 vs. 5.54 ± 0.29 TU/mL, p < 0.05). Thrombomodulin showed an area under the curve of 0.87 for predicting mortality. The hazard function curve showed significantly higher mortality risk in patients with high thrombomodulin. Multiple linear regression demonstrated a positive correlation of plasma thrombomodulin with the Sequential Organ Failure Assessment (SOFA) score (ß-coefficient = 0.610, p = 0.042). Logistic regression showed that thrombomodulin level was an independent risk factor for poor prognosis (OR 1.963, 95% CI 1.006 - 3.829). The nomogram based on thrombomodulin level and SOFA score revealed that an initial death risk probability can be established for patients with sepsis-induced DIC without further testing. CONCLUSIONS: Elevated plasma thrombomodulin is associated with poor clinical outcomes in sepsis-induced DIC; therefore, a high plasma thrombomodulin level may be a useful prognostic factor.


Assuntos
Coagulação Intravascular Disseminada , Sepse , Trombomodulina/metabolismo , Coagulação Intravascular Disseminada/diagnóstico , Células Endoteliais , Humanos , Escores de Disfunção Orgânica , Sepse/complicações , Sepse/diagnóstico , Trombomodulina/sangue
15.
Artigo em Inglês | MEDLINE | ID: mdl-34432420

RESUMO

Photoassisted electrocatalysis (P-EC) emerges as a rising star for hydrogen production by embedding photoactive species in electrocatalysts, for which the interfacial structure design and charge transfer kinetics of the multifunctional catalysts remain a great challenge. Herein, Zn-AgIn5S8 quantum dots (ZAIS QDs) were embedded into 2D NiFe layered double hydroxide nanosheets through a simple hydrothermal treatment to form 0D/2D composite catalysts for P-EC. With evidence from transient photovoltage spectroscopy, we acquired a clear and fundamental understanding on the kinetics of charge extraction time and extraction amount in the 0D/2D heterojunctions that was proved to play a key role in P-EC. Upon light illumination, for HER, the optimized NiFe-ZAIS exhibits obviously reduced overpotentials of 129 and 242 mV at current densities of 10 and 50 mA cm-2, which are 22 and 33 mV lower than those of dark electrocatalysis, respectively. For OER, the NiFe-ZAIS electrode also shows low overpotentials of 220 and 268 mV at current densities of 10 and 50 mA cm-2, respectively, under light illumination, which were able to almost double the intrinsic activity. Finally, with NF@NiFe-ZAIS as both the cathode and the anode, the assembled electrolyzer only requires 1.62 V to reach the overall water splitting current density of 10 mA cm-2 under P-EC. This work provides a useful example for the profound understanding of the design and the kinetics study of multifunctional P-EC catalysts.

16.
Am J Emerg Med ; 50: 242-250, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34416515

RESUMO

BACKGROUND: The role of vitamin C in sepsis is still controversial, we aimed to systematically review the efficacy of intravenous vitamin C supplementation in the treatment of sepsis. METHODS: MEDLINE, EmBase, Web of Science, WanFang Data and CNKI were comprehensively searched to collect randomized controlled trails (RCTs) of vitamin C supplementation for patients with sepsis or sepsis shock from January 2000 to March 2021. Two researchers independently screened the literature, extracted the data and accessed the risk of bias in the included studies; meta-analysis was then performed by using Revman 5.4 software. RESULTS: A total of 10 RCTs involving 1400 participants were included. The results of meta-analysis showed that intravenous vitamin C supplementation can improve SOFA (ΔSOFA) within 72 h [RR = 1.32,95% CI(0.80,1.85), P < 0.0001] of septic patients. There were no difference on short term mortality (28-30d)[RR = 0.83,95% CI(0.65,1.05), P = 0.11], long term mortality (90d) [RR = 1.16,95% CI(0.82,1.66), P = 0.40], hospital LOS[RR = 0.15,95% CI(-0.73,1.03), P = 0.55], ventilator-free days[RR = 0.09,95% CI(-0.24,0.42), P = 0.60], ICU-LOS[RR = 0.22,95% CI(-0.13,0.57), P = 0.22], between two groups. The results of Subgroup analysis showed that intravenous vitamin C alone can reduce the risk of short term mortality (28-30d) [RR = 0.61,95% CI(0.47,0.79), P = 0.0002]of sepsis patients. CONCLUSION: Based on current RCTs, our work indicated that mono-intravenous vitamin C therapy may reduce short-term mortality of sepsis patients, and it may protect organ functions. Due to the limitation of the quantity and quality of included studies, the above conclusions need to be verified by more large scale and high quality randomized control trials.

17.
Small ; : e2102325, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34365728

RESUMO

Carbon dots (CDs) represent a recently emerged class of luminescent materials with a great potential for biomedical theranostics, and there are a lot of efforts to shift their absorption and emission toward deep-red (DR) to near-infrared (NIR) region falling in the biological transparency window. This review offers comprehensive insights into the synthesis strategies aimed to achieve this goal, and the current approaches of modulating the optical properties of CDs over the DR to NIR region. The underlying mechanisms of their absorption, photoluminescence, and chemiluminescence, as well as the related photophysical processes of photothermal conversion and formation of reactive oxygen species are considered. The already available biomedical applications of CDs, such as in the photoacoustic imaging and photothermal therapy, photodynamic therapy, and their use as bioimaging agents and drug carriers are then shortly summarized.

18.
J Colloid Interface Sci ; 604: 680-690, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34280766

RESUMO

Efficient, low-cost, and robust electrocatalysts development for overall water splitting is highly desirable for renewable energy production yet still remains challenging. In this work, Co9S8 nanoneedles arrays are synergistically integrated with NiFe-layered double hydroxide (NiFe-LDH) nanosheets to form Co9S8@NiFe-LDH core-branch hierarchical architectures supported on nickel foam (Co9S8@NiFe-LDH HAs/NF). The Co9S8@NiFe-LDH HAs/NF exhibits high catalytic performances for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) with overpotential of 190 and 145 mV at 10 mA cm-2, respectively. The density functional theory calculations predict that the synergy between Co9S8 and NiFe-LDH contributes to the high catalytic performance by lowering the energy barrier of HER. When used as both anode and cathode electrocatalyst, it can deliver 10 mA cm-2 at a low cell voltage of 1.585 V with excellent long-term durability. This work opens a new avenue toward the exploration of highly efficient and stable electrocatalyst for overall water splitting.

19.
J Ethnopharmacol ; 280: 114434, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274443

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm. f. is a typical traditional Chinese medicine (TCM) collected in the Pharmacopoeia of the People's Republic of China (version 2015). It has been traditionally used for the treatment of constipation, and its potential therapeutic activities have been widely evaluated, including anti-tumor, anti-inflammatory and immune regulatory effects. The wide application of Aloe vera in food and therapy has raised safety issues and there are multiple safety assessments with a diverse toxicity and adverse effects from clinics and animals. AIM OF THE STUDY: This study aimed to investigate the safety of Aloe vera barbadensis extract C (AVBEC) in rats and analyze its anticancer activity in cell lines. MATERIALS AND METHODS: We administrated AVBEC orally in an acute toxicity study and a 6-month chronic toxicity study to observe and confirm its safety in Sprague-Dawley (SD) rats. Additionally, we explored the cytotoxicity of AVBEC in cancer cells and non-cancer cells. We further investigated the anti-tumor activity of AVBEC, and in the meantime, probed the function of component from AVBEC. RESULTS: No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 44.8 g·kg-1 and 4.48 g·kg-1, respectively. In the chronic toxicity study, AVBEC did not cause organ toxicity, including crucial organ structure and chemical function, and peripheral and central immune system damage. Additionally, we found that AVBEC could induce cancer cell apoptosis with a relatively higher apoptotic ratio than in non-cancer cells by decreasing adenosine triphosphate (ATP) concentration and enhancing reactive oxygen species (ROS) production. We also identified components in AVBEC using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) and probed the function of malic acid. This demonstrated that under the same circumstances, malic acid induced cell necrosis in cancer cells and non-cancer cells, while AVBEC did not. CONCLUSIONS: These results reveal a novel mechanism of aloe gel extract in regulating cancer cell apoptosis via modulating the mitochondrial metabolism and imply a possible application of AVBEC for the treatment of malignant cancer with the safety evaluation from rats and anticancer investigation from cancer cells and non-cancer cells.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34279903

RESUMO

Developing n-type materials with high peak and/or average ZT (ZT is the figure of merit) is an urgent need for the lower ZT of the existing n-type BiTeSe materials compared with the p-type BiSbTe materials. Here, we demonstrate that liquid-phase sintering can lead to lowered thermal conductivity and an improved power factor in n-type Ag2Se, which originates from the greatly lowered electronic thermal conductivity attributed to the decreased mobility and improved Seebeck coefficients because of increased effective mass. Benefiting from this, the maximum ZT (ZTmax) of ∼1.21 and the average ZT (ZTave) of 1.06 are successfully achieved in polycrystalline Ag2Se. In this work, ZTave is the highest reported value, being 26% larger than that of Ag2Se reported. Our work shows that liquid-phase sintering to achieve improved thermoelectric (TE) performance opens a great opportunity for designing prospective thermoelectrics.

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