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1.
Sci Adv ; 8(18): eabn3534, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522744

RESUMO

Living systems consist of complex transient cellular networks guiding structural, catalytic, and switchable functions driven by auxiliary triggers, such as chemical or light energy inputs. We introduce two different transient, dissipative, biocatalytic cascades, the coupled glucose oxidase (GOx)/horseradish peroxidase (HRP) glucose-driven oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS2-) to the radical anion (ABTS•-) and the lactate dehydrogenase (LDH)/nicotinamide adenine dinucleotide (NAD+) lactate-driven reduction of NAD+ to NADH. The transient biocatalytic systems are driven by nucleic acid reaction modules using a nucleic acid fuel strand L1' and a nicking enzyme, Nt.BbvCI, as fuel-degrading catalyst, leading to the dynamic spatiotemporal transient formation of structurally proximate biocatalysts activating the biocatalytic cascades and transient coupled processes, including the generation of chemiluminescence and the synthesis of alanine. Subjecting the mixture of biocatalysts to selective inhibitors allows the gated transient operation of the biocatalysts. The kinetics of transient biocatalytic cascades are accompanied by kinetic models and computational simulations.

2.
J Transl Med ; 20(1): 202, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538543

RESUMO

BACKGROUND: Prostatic cancer (PCa) is one of the most common malignant tumors in men worldwide. Emerging evidence indicates significance of hypoxia and immunity in PCa invasion and metastasis. This study aimed to develop a hypoxia- and immune-related gene risk signature and explore the molecular mechanisms to formulate a better prognostic tool for PCa patients. METHODS: The hypoxia and immune scores of all PCa patients in The Cancer Genome Atlas (TCGA) dataset were calculated via the maximally selected rank statistics method and the ESTIMATE algorithm. From common genes identified overlapping hypoxia- and immune-related differentially expressed genes (DE-HRGs and DE-IRGs), a hypoxia- and immune-related gene risk signature was developed utilizing univariate and multivariate Cox regression analyses, and validated in the Memorial Sloan Kettering Cancer Centre (MSKCC) database. The immune cell infiltration level of PCa samples were evaluated with ssGSEA algorithm. Differential expression of prognostic genes was evidenced by immunohistochemistry and western blot (WB) in paired PCa samples. Expression levels of these genes and their variations under regular and hypoxic conditions were examined in cell lines. The functional effects of the prognostic gene on PCa cells were examined by wound healing and transwell assays. RESULTS: A hypoxia- and immune-related gene risk signature constructed by ISG15 and ZFP36 displays significant predictive potency, with higher risk score representing worse survival. A nomogram based on independent prognostic factors including the risk score and Gleason score exhibited excellent clinical value in the survival prediction of PCa. Infiltration levels of eosinophils, neutrophils, Tcm, Tem, TFH, Th1 cells, and Th17 cells were significantly lower in the high-risk group. Conversely, aDC, pDC, T helper cells, and Tregs were significantly higher. Additionally, the two prognostic genes were closely correlated with the tumor-infiltrating immune cell subset in PCa progression. RT-qPCR and WB presented higher and lower expression of ISG15 and ZFP36 in PCa cells, respectively. They were correspondingly increased and decreased in PCa cells under hypoxic conditions. Wound healing and transwell assays showed that over-expression of ISG15 promoted the migration and invasion of PCa cells. CONCLUSION: Our study identified a novel hypoxia- and immune-related gene signature, contributing a new perspective to the treatment of PCa.

3.
Front Bioeng Biotechnol ; 10: 872088, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464728

RESUMO

Surface modification of titanium has been a hot topic to promote bone integration between implants and bone tissue. Titanium dioxide nanotubes fabricated on the surface of titanium by anodic oxidation have been a mature scheme that has shown to promote osteogenesis in vitro. However, mechanisms behind such a phenomenon remain elusive. In this study, we verified the enhanced osteogenesis of BMSCs on nanotopographic titanium in vitro and proved its effect in vivo by constructing a bone defect model in rats. In addition, the role of the mechanosensitive molecule Yap is studied in this research by the application of the Yap inhibitor verteporfin and knockdown/overexpression of Yap in MC3T3-E1 cells. Piezo1 is a mechanosensitive ion channel discovered in recent years and found to be elemental in bone metabolism. In our study, we preliminarily figured out the regulatory relationship between Yap and Piezo1 and proved Piezo1 as a downstream effector of Yap and nanotube-stimulated osteogenesis. In conclusion, this research proved that nanotopography promoted osteogenesis by increasing nuclear localization of Yap and activating the expression of Piezo1 downstream.

4.
Rev Sci Instrum ; 93(4): 044705, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489880

RESUMO

In this paper, a high-power ultra-wideband radiation system, composed of multiply radiation modules, is developed based on the space-synthesis method. The radiation module mainly consists of a transistorized pulser, a 2 × 2 combined antenna array, and a power divider. To improve the out parameters [the amplitude, the pulse repetition frequency (PRF), and the rise time] of the transistorized pulser based on the Marx circuit, the influence of the traveling wave process on the output pulse must be concerned. Based on the theoretical analysis, the printed circuit board circuit parameters and the circuit structure of the pulser are optimized. To improve the power synthesis efficiency, the pulse jitter characteristic of the pulser is improved by replacing the conventional base triggering mode with the collector voltage ramp triggering mode for the first-stage avalanche transistor in the pulser. The previous optimized antenna array is utilized in this radiation system, which has a better radiation performance in the prescribed aperture area. In addition, based on the gradient microstrip structure, the power divider integrated with the pulser is designed, which has the advantages of wide bandwidth, low loss, and light weight. Experimental results show that the peak effective potential rEp of the radiation system of 20 radiation modules is 221.8 kV, the maximum PRF could reach 10 kHz, and the half-power radiation angles of its radiation field are about 5° in both the E plane and the H plane. More radiation modules could be integrated into the system to achieve a higher electric field in the future.

5.
Shock ; 57(4): 565-575, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35271545

RESUMO

ABSTRACT: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by increased permeability of the alveolar-capillary barrier and impaired alveolar fluid clearance. Resolvin E1 (RvE1) is a specialized pro-resolving mediator derived endogenously from omega-3-polyunsaturated fatty acids. RvE1 (10 µg/kg i.v.) was injected to rats 6 h post-lipopolysaccharide (LPS) (14 mg/kg) induction. After another 3 h, alveolar fluid clearance was measured in live rats (n = 8-9). The primary Type II alveolar epithelial cell was isolated and treated by LPS (1 µg/mL) with or without RvE1 (250 nM). The expression of epithelial sodium channel (ENaC), Na+/K+-ATPase (NKA), AKT, serum- and glucocorticoid-induced kinase 1 (SGK1), and Nedd4-2 were detected. RvE1 improved survival rate (30% vs. 70%, P = 0.048), increased the clearance of alveolar fluid (13.34% vs. 18.73%, P  < 0.001), reduced lung wet-dry weight ratio (5.01 vs. 4.63, P  < 0.001), mitigated lung injury scores (13.38 vs. 7.0, P  < 0.05) and inflammation in LPS-induced ARDS in rats. RvE1 upregulated alveolar ENaC and NKA expression in vivo and in vitro. In addition, RvE1 significantly increased the expression of phosphorylated AKT, SGK1, and phosphorylated Nedd4-2 in LPS-stimulated primary alveolar type II cells. The effects of RvE1 were abrogated by blocking phosphatidylinositide3'-kinase (PI3K) and SGK1 with LY294002 and GSK650394, respectively. In summary, RvE1 upregulated ENaC and NKA expression by activating PI3K/AKT/SGK1 pathway to promote alveolar fluid clearance, suggesting that RvE1 may be a potentially effective drug for ARDS treatment.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/metabolismo , Animais , Ácido Eicosapentaenoico/análogos & derivados , Canais Epiteliais de Sódio/metabolismo , Canais Epiteliais de Sódio/uso terapêutico , Lipopolissacarídeos/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Síndrome do Desconforto Respiratório/tratamento farmacológico , ATPase Trocadora de Sódio-Potássio/efeitos adversos , ATPase Trocadora de Sódio-Potássio/metabolismo
6.
Adv Healthc Mater ; : e2200121, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35182457

RESUMO

Multidrug-resistant (MDR) pathogenic bacterial infections have become a major danger to public health. Synergetic therapy through multiple approaches is more powerful than the respective one alone, but has been rarely achieved in defeating MDR bacterial infections so far. Herein, indocyanine green-functionalized Mn3 O4 nanosheets are engineered as an efficient and safe antibacterial agent with photothermal, photodynamic, and oxidase-like activities, which display powerful ability in treating MDR bacterial infections. Therein, photothermal and photodynamic activities can be triggered by a single low-powered near-infrared laser (808 nm, 0.33 W cm-2 ), resulting in the generation of localized hyperthermia (photothermal conversion efficiency, 67.5%) and singlet oxygen. Meanwhile, oxidase-like activity of this material further leads to the generation of hydroxyl radical as well as superoxide radical. Sheet-like structure with rough surfaces make them tends to adhere on bacterial surface and thus damage membrane system as well as influence bacterial metabolism. As a result, Gram-positive and Gram-negative bacteria can both be eradicated. Animal experiments further indicate that the functionalized Mn3 O4 nanosheets can effectively treat methicillin-resistant Staphylococcus aureus-infected wounds through the triple synergetic therapy. Moreover, toxicity evaluation in vitro and in vivo has proved the superior biosafety of this material, which is promising to apply in clinical anti-infective therapy.

7.
Environ Sci Pollut Res Int ; 29(24): 36951-36966, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35066841

RESUMO

Reference evapotranspiration ([Formula: see text]) is an important indicator for hydrometeorological change, which integrates atmospheric and surface conditions, and its downward trends have been reported in many regions over the past several decades. Cold regions constitute an important ecological barrier in China; however, few studies focus on change in [Formula: see text] in cold regions. Especially in the cold region of northeast China (CRNEC), as one of the national strategic grain bases, understanding spatial-temporal variations of [Formula: see text] is important for agriculture water management and ecological protection. This study selected the observations at 113 national meteorological stations located in CRNEC and evaluated the trends of [Formula: see text] and their driving factors from 1961 to 2017. Results indicate that annual [Formula: see text] increases from the northeast to the southwest of CRNEC and has an insignificant decreasing trend in the whole study period, in which 33 stations (29.2%) show significant decreasing trends and only 19 stations (16.8%) show significant increasing trends at the 95% confidence level. An abrupt change in [Formula: see text] data is detected from 1994. Reasons for this abrupt change in [Formula: see text] vary largely over the study areas. Analysis shows that wind speed and minimum air temperature are the two major factors that control the change of [Formula: see text] before 1994. It also shows that wind speed and actual vapor pressure are the two major controlling factors after 1994. We also found that [Formula: see text] shows a certain correlation with Pacific Decadal Oscillation and Western Pacific Index, but there is a significant correlation between meteorological factors and teleconnection factors related to [Formula: see text]. These findings will promote agricultural water management and improve water ecological protection in the CRNEC. We investigated changes in reference evapotranspiration relationships with atmospheric circulation and its attributions over the cold regions in northeast China during 1961 ~ 2017. The results indicate that the wind speed and minimum air temperature are the two major factors that control the change of ET0 before 1994, and wind speed and actual vapor pressure are the two major controlling factors after 1994. We also found that ET0 shows a certain correlation with Western Pacific Index in the whole period.


Assuntos
Produtos Agrícolas , Transpiração Vegetal , China , Meteorologia , Temperatura , Água
8.
Cell Death Dis ; 13(1): 46, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013120

RESUMO

The survival of cancer cells after detaching from the extracellular matrix (ECM) is essential for the metastatic cascade. The programmed cell death after detachment is known as anoikis, acting as a metastasis barrier. However, the most aggressive cancer cells escape anoikis and other cell death patterns to initiate the metastatic cascade. This study revealed the role of cell migration-inducing protein (CEMIP) in autophagy modulation and anoikis resistance during ECM detachment. CEMIP amplification during ECM detachment resulted in protective autophagy induction via a mechanism dependent on the dissociation of the B-cell lymphoma-2 (Bcl-2)/Beclin1 complex. Additional investigation revealed that acting transcription factor 4 (ATF4) triggered CEMIP transcription and enhanced protein kinase C alpha (PKCα) membrane translocation, which regulated the serine70 phosphorylation of Bcl-2, while the subsequent dissociation of the Bcl-2/Beclin1 complex led to autophagy. Therefore, CEMIP antagonization attenuated metastasis formation in vivo. In conclusion, inhibiting CEMIP-mediated protective autophagy may provide a therapeutic strategy for metastatic prostate cancer (PCa). This study delineates a novel role of CEMIP in anoikis resistance and provides new insight into seeking therapeutic strategies for metastatic PCa.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Anoikis , Autofagia , Hialuronoglucosaminidase/metabolismo , Neoplasias da Próstata/patologia , Proteína Quinase C-alfa/metabolismo , Idoso , Animais , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/genética , Masculino , Camundongos , Fosforilação , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
9.
Materials (Basel) ; 15(2)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35057155

RESUMO

Lightweight parts manufactured by metal selective laser melting (SLM) are widely applied in machinery industries because of their high specific strength, good energy absorption effect, and complex shape that are difficult to form by mechanical machining. These samples often serve in three-dimensional stress states. However, previous publications mainly focused on the unidirectional tensile/compressive properties of the samples. In this paper, AlMgSc samples with different geometric parameters were prepared by the SLM process, and the variation of force and microstructure during three-point bending were systematically investigated. The results demonstrate that the deformation resistance of these samples has good continuity without mutation in bending, even for brittle materials; the bending force-displacement curves exhibit representative variation stages during the entire bending process; the equivalent bending strength deduced from free bending formula is not applicable when compactability is less than 67%. The variations of grain orientation and size of the three representative bending layers also show regularity.

10.
ACS Nano ; 16(2): 1791-1801, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35020370

RESUMO

An analytical platform for the selective miRNA-21-guided imaging of breast cancer cells and miRNA-221-guided imaging of ovarian cancer cells and the selective photodynamic therapy (PDT) of these cancer cells is introduced. The method is based on Zn(II)-protoporphyrin IX, Zn(II)-PPIX-loaded UiO-66 metal-organic framework nanoparticles, NMOFs, gated by two hairpins Hi/Hj through ligation of their phosphate residues to the vacant Zr4+-ions associated with the NMOFs. The hairpins are engineered to include the miRNA recognition sequence in the stem domain of Hi, and in the Hi and Hj, partial locked stem regions of G-quadruplex subunits. Intracellular phosphate-ions displace the hairpins, resulting in the release of the Zn(II)-PPIX and intracellular miRNAs open Hi, and this triggers the autonomous cross-opening of Hi and Hj. This activates the interhairpin hybridization chain reaction and leads to the assembly of highly fluorescent Zn(II)-PPIX-loaded G-quadruplex chains. The miRNA-guided fluorescent chains allow selective imaging of cancer cells. Moreover, PDT with visible light selectively kills cancer cells and tumor cells through the formation of toxic reactive oxygen species.


Assuntos
Estruturas Metalorgânicas , MicroRNAs , Nanopartículas , Neoplasias , Fotoquimioterapia , Linhagem Celular Tumoral , MicroRNAs/genética , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Ácidos Ftálicos , Protoporfirinas/química , Zinco
11.
J Asian Nat Prod Res ; : 1-7, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037543

RESUMO

Three new cassane-type diterpenoids, namely, (4S)-6ß,12α,19-trihydroxy-cass-13(15)-en-16,12-olide (1), cass-13(15)-en-​16,12-olide (2), and 12α-hydroxy-cass-13(15)-en-16,12-olide (3), were isolated from the seeds of Caesalpinia sinensis. The structures of 1-3 were established by extensive spectroscopic analysis, and their absolute configurations were assigned by electronic circular dichroism (ECD) calculations. The inhibitory activities against PTP1B of the isolated compounds were evaluated. The results showed that compound 2 possessed PTP1B inhibitory activity with an IC50 value of 217.45 ± 36.4 µM.

12.
IEEE Trans Pattern Anal Mach Intell ; 44(5): 2742-2759, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33196437

RESUMO

In the task of pedestrian trajectory prediction, social interaction could be one of the most complicated factors since it is difficult to be interpreted through simple rules. Recent studies have shown a great ability of LSTM networks in learning social behaviors from datasets, e.g., introducing LSTM hidden states of the neighbors at the last time step into LSTM recursion. However, those methods depend on previous neighboring features which lead to a delayed observation. In this paper, we propose a data-driven states refinement LSTM network (SR-LSTM) to enable the utilization of the current intention of neighbors through a message passing framework. Moreover, the model performs in the form of self-updating by jointly refining the current states of all participants, rather than an input-output mechanism served by feature concatenation. In the process of states refinement, a social-aware information selection module consisting of an element-wise motion gate and a pedestrian-wise attention is designed to serve as the guidance of the message passing process. Considering the pedestrian walking space as a graph where each pedestrian is a node and each pedestrian pair with an edge, spatial-edge LSTMs are further exploited to enhance the model capacity, where two kinds of LSTMs interact with each other so that states of them are interactively refined. Experimental results on four widely used pedestrian trajectory datasets, ETH, UCY, PWPD, and NYGC demonstrate the effectiveness of the proposed model.


Assuntos
Pedestres , Algoritmos , Humanos , Movimento (Física) , Redes Neurais de Computação , Caminhada
13.
Sci Total Environ ; 808: 152069, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34863734

RESUMO

Nitrogen discharged from urban areas greatly deteriorates the water quality of downstream surface water. In this study, sub-hourly high-frequency samples of urban runoff during six rainfall events were collected at the outfall of the stormwater network in an urban watershed in Beijing to explore nitrate export and transportation. Isotopic values of local road dust, soil, and network sediment were measured and used as the sources of nitrate to better elucidate the sources of the urban watershed. The contributions of various sources over and during three rainfall events with different grades were quantified and compared. The results showed that the contribution of sources changed dramatically over and during rainfall events. Along with the increase in the total rainfall amount and the going on of rainfall events, the wash-off effect in the atmosphere and on land surfaces played a more important role in nitrate output. Atmospheric deposition was the dominant contributor of nitrate in heavy and storm events (mean 59.3% and 64.8%, respectively). Network sediment contributed large proportions of nitrate in moderate and heavy events (mean 35.6% and 15.9%, respectively). The contribution of soil increased substantially in the storm event (mean 26.1%). Road dust and network sediment contributed greatly in the early stage of the heavy event. The contribution of fertilizer in heavy events was mainly because of the wash-off of road dust. The changing pattern of sources from atmospheric deposition to inorganic N fertilizer existed during the process of the storm event. The contribution of NO3- fertilizer from soil surfaces increased substantially in the later stage of the storm event. These results provide valuable references for urban nutrient management and mitigation measures implementation.


Assuntos
Nitratos , Poluentes Químicos da Água , Monitoramento Ambiental , Nitratos/análise , Nitrogênio/análise , Chuva , Movimentos da Água , Poluentes Químicos da Água/análise
14.
Eur J Nucl Med Mol Imaging ; 49(6): 1985-1996, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34746969

RESUMO

INTRODUCTION: Radiopharmaceuticals that target cancer-associated fibroblasts (CAFs) have become an increasingly attractive strategy for cancer theranostics. Recently, a series of fibroblast activation protein inhibitor (FAPI)-based radiopharmaceuticals have been successfully applied to the diagnosis of a variety of cancers and exhibited excellent tumor selectivity. Nevertheless, CAF-targeted radionuclide therapy encounters difficulties in cancer treatment, as the tumor uptake and retention of FAPIs are insufficient. To meet this challenge, we tried to conjugate albumin-binding moiety to FAPI molecule for prolonged circulation that may increase the accumulation and retention of radiopharmaceuticals in tumor. METHODS: Two fatty acids, lauric acid (C12) and palmitic acid (C16), were conjugated to FAPI-04 to give two albumin-binding FAPI radiopharmaceuticals, denoted as FAPI-C12 and FAPI-C16, respectively. They had been radiolabeled with gallium-68, yttrium-86, and lutecium-177 for stability study, binding affinity assay, PET and SPECT imaging, biodistribution, and radionuclide therapy study to systematically evaluate their potential for CAF-targeted radionuclide therapy. RESULTS: FAPI-C12 and FAPI-C16 showed high binding affinity to FAP with the IC50 of 6.80 ± 0.58 nM and 5.06 ± 0.69 nM, respectively. They were stable in both saline and plasma. The tumor uptake of [68Ga]Ga-FAPI-04 decreased by 56.9% until 30 h after treated with FAPI-C16 before, and the uptakes of [86Y]Y-FAPI-C12 and [86Y]Y-FAPI-C16 in HT-1080-FAP tumor were both much higher than that of HT-1080-Vehicle tumor which identified the high FAP specific of these two radiopharmaceuticals. Both FAPI-C12 and FAPI-C16 showed notably longer circulation and significantly enhanced tumor uptake than those of FAPI-04. [177Lu]Lu-FAPI-C16 had the higher tumor uptake at both 24 h (11.22 ± 1.18%IA/g) and 72 h (6.50 ± 1.19%IA/g) than that of [177Lu]Lu-FAPI-C12 (24 h, 7.54 ± 0.97%IA/g; 72 h, 2.62 ± 0.65%IA/g); both of them were much higher than [177Lu]Lu-FAPI-04 with the value of 1.24 ± 0.54%IA/g at 24 h after injection. Significant tumor volume inhibition of [177Lu]Lu-FAPI-C16 at the high activity of 29.6 MBq was observed, and the median survival was 28 days which was much longer than that of the [177Lu]Lu-FAPI-04 treated group of which the median survival was only 10 days. CONCLUSION: This proof-of-concept study validates the hypothesis that conjugation of albumin binders may shift the pharmacokinetics and enhance the tumor uptake of FAPI-based radiopharmaceuticals. This could be a general strategy to transform the diagnostic FAP-targeted radiopharmaceuticals into their therapeutic pairs.


Assuntos
Ácidos Graxos , Compostos Radiofarmacêuticos , Albuminas , Linhagem Celular Tumoral , Endopeptidases/metabolismo , Fibroblastos/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
15.
Biol Trace Elem Res ; 200(3): 1312-1320, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33851329

RESUMO

As a highly toxic heavy metal, chromium has caused a certain threat to public health and livestock breeding in recent years. In poultry, as one of our most commonly consumed meat product, its health issues will seriously threaten the safety of human life. As previous studies have confirmed, when cells are stimulated by the external environment, mitochondria, as an organelle that provides energy to the cells, can cause damage and autophagy. The purpose of this study is to confirm whether Cr(VI) can cause mitophagy in cock heart. We first randomly divided 32 cocks into four groups to explore the mechanism of this effect. The cocks were then separately exposed to four different dose levels, namely, the control level and 10, 30, and 50 mg/kg levels, via daily oral intake into the body through mixed feeding for 45 days. After 45 days, we sampled and detected pathological changes and the levels of inflammatory factors (IL-6, TNF-α, and IFN-γ), mitochondrial membrane potential (MMP), adenosine triphosphatases (ATPases), and mitophagy-related proteins (LC3, p62/SQTM1, TOMM20, and Parkin). We found that IL-6, TNF-α, IFN-γ, and LC3II contents increased with the increase in Cr(VI) concentration. However, MMP, ATPases, p62/SQTM1, and TOMM20 levels decreased with the increase in Cr(VI) concentration. At the same time, Cr(VI) exposure caused heart tissue damages and Parkin translocation. In conclusion, our results proved that inflammatory damage, mitochondrial function damage, and mitophagy in cock heart tissues were dependent on Cr(VI) concentration.


Assuntos
Cromo , Mitofagia , Administração Oral , Animais , Cromo/toxicidade , Mitocôndrias , Aves Domésticas
16.
Urol Int ; 106(2): 109-115, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34515249

RESUMO

Raman spectroscopy is an optical technique that can potentially serve as a molecular diagnosis method. This approach is excellent in many aspects for diagnosing bladder tumors, and over the last 20 years, there has been a rapid increase in the number of related studies. However, no review article has covered the wide use of Raman spectroscopy in bladder tumors. A total of 26 original studies have suggested that Raman spectroscopy shows good performance in diagnosing bladder tumors from 4 aspects, including tissue sections, endoscopic methods, cell screening, and biomarkers. However, Raman spectroscopy needs to be modified by combining it with other techniques, and studies based on a large population are still urgently needed to expand its clinical value.


Assuntos
Análise Espectral Raman , Neoplasias da Bexiga Urinária/diagnóstico , Humanos
17.
Phytochemistry ; 195: 113056, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34953266

RESUMO

Phytochemical investigation of Lycopodium cernuum L. afforded seven undescribed serratene triterpenoids named 3ß, 21ß-dihydroxyserra-14-en-24-oic acid-3ß-(5'-hydroxybenzoate) (1), 3ß, 21ß, 24-trihydroxyserrat-14-en-3ß-(5'-hydroxyl benzoate) (2), 3ß, 14α, 15α, 21ß-tetrahydroxyserratane-24-methyl ester (3), 3ß, 14α, 21ß-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate)-24-methyl ester (4), 3ß, 14α, 21ß-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate) (5), 3ß-hydroxy-21ß-acetate-16-oxoserrat-14-en-24-oic acid (6), 3ß, 21ß-dihydroxy-16α, 29-epoxyserrat-14-en-24-methyl ester (7), together with eleven known compounds (8-18), whose chemical structures were elucidated through spectroscopic analysis of HRESIMS, 1D NMR, 2D NMR and comparison between the literature. All compounds were evaluated for their α-glucosidase inhibitory activity for the first time. The results showed that compounds 1, 2, 4, 5, 6, 10, 13, 15, and 16 were among the most potent α-glucosidase inhibitors, with IC50 values ranging from 23.22 ± 0.64 to 50.65 ± 0.82 µM. Structure-activity relationship (SAR) studies indicated that the combined properties of the 5-hydroxybenzoate moiety at C-3, ß-OH at C-21, COOH- at C-24, and Δ14,15 groups enabled an increase in the α-glucosidase inhibitory effect. In addition, molecular docking studies showed that the potential inhibitors mainly interact with key amino acid residues in the active site of α-glucosidase through hydrogen bonds and hydrophobic forces.


Assuntos
Lycopodium , Triterpenos , Inibidores de Glicosídeo Hidrolases/farmacologia , Imidazóis , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas , Tiofenos , Triterpenos/farmacologia
18.
Opt Lett ; 46(23): 5986-5989, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851940

RESUMO

Electro-optic (EO) modulators, which convert signals from the electrical to optical domain plays a key role in modern optical communication systems. Lithium niobate on insulator (LNOI) technology has emerged as a competitive solution to realize high-performance integrated EO modulators. In this Letter, we design and experimentally demonstrate a Mach-Zehnder interferometer-based modulator on a silicon nitride loaded LNOI platform, which not only takes full advantage of the excellent EO effect of LiNbO3, but also avoids the direct etching of LiNbO3 thin film. The measured half-wave voltage length product of the fabricated modulator is 2.24 V·cm, and the extinction ratio is ∼20dB. Moreover, the 3 dB EO bandwidth is ∼30GHz, while the modulated data rate for on-off key signals can reach up to 80 Gbps.

19.
Chem Sci ; 12(43): 14473-14483, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34880998

RESUMO

UiO-66 metal-organic framework nanoparticles (NMOFs) gated by aptamer-functionalized DNA tetrahedra provide superior biomarker-responsive hybrid nano-carriers for biomedical applications. Hybrid nano-carriers consisting of ATP-aptamer or VEGF-aptamer functionalized tetrahedra-gated NMOFs are loaded with the chemotherapeutic drug, doxorubicin (DOX). In the presence of ATP or VEGF, both abundant in cancer cells, the tetrahedra-gated NMOFs are unlocked to release the drug. Enhanced and selective permeation of the DOX-loaded ATP/VEGF-responsive tetrahedra-gated NMOFs into MDA-MB-231 breast cancer cells as compared to the reference ATP/VEGF-responsive duplex-gated NMOFs or non-malignant MCF-10A epithelial breast cells is observed. This results in enhanced and selective cytotoxicity of the tetrahedra-gated DOX-loaded NMOFs toward the malignant cells. Additional nano-carriers, consisting of photosensitizer Zn(ii) protoporphyrin IX (Zn(ii)-PPIX)-loaded VEGF-responsive tetrahedra-gated NMOFs, are introduced. The VEGF-triggered unlocking of the NMOFs yields separated G-quadruplex-VEGF aptamer complexes conjugated to the tetrahedra, resulting in the release of loaded Zn(ii)-PPIX. Association of the released Zn(ii)-PPIX to the G-quadruplex structures generates highly fluorescent supramolecular Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra structures. The efficient and selective generation of the highly fluorescent Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra nanostructures in malignant cells allows the light-induced photosensitized generation of reactive oxygen species (ROS), leading to high-efficacy PDT treatment of the malignant cells.

20.
Cancers (Basel) ; 13(23)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34885178

RESUMO

Ferroptosis has been reported to regulate tumorigenesis, metastasis, drug resistance and the immune response. However, the potential roles of ferroptosis regulators in the advancement of bladder cancer remain to be explored. We systematically evaluated the multidimensional alteration landscape of ferroptosis regulators in bladder cancer and checked if their expression correlated with the ferroptosis index. We used least absolute shrinkage and selection operator regression to form a signature consisting of seven ferroptosis regulator. We confirmed the signature's prognostic and predictive accuracy with five independent datasets. A nomogram was built to predict the overall survival and risk of death of patients. The relative expression of the genes involved in the signature was also clarified by real-time quantitative PCR. We found the risk score was related to tumor progression and antitumor immunity-related pathways. Moreover, there existed negative association between the relative antitumor immune cell infiltration level and the risk score, and higher tumor mutation burden was found in the group of lower risk score. We used The Tumor Immune Dysfunction and Exclusion database and IMvigor210 cohort having immunotherapy efficacy results to confirm the prediction function of the risk score. Furthermore, the ferroptosis regulator signature could also reflect the chemotherapy sensitivity of bladder cancer.

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