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1.
Plant Physiol ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34618093

RESUMO

Salicylic acid (SA) plays an important role for plant immunity, especially resistance against biotrophic pathogens. SA quickly accumulates after pathogen attack to activate downstream immunity events and is normally associated with a tradeoff in plant growth. Therefore, the SA level in plants has to be strictly controlled when pathogens are absent, but how this occurs is not well understood. Previously we found that in Arabidopsis (Arabidopsis thaliana), HISTONE DEACETYLASE 6 (HDA6), a negative regulator of gene expression, plays an essential role in plant immunity since its mutation allele shining 5 (shi5) exhibits autoimmune phenotypes. Here we report that this role is mainly through suppression of SA biosynthesis: first, the autoimmune phenotypes and higher resistance to Pst DC3000 of shi5 mutants depended on SA; second, SA significantly accumulated in shi5 mutants; third, HDA6 repressed SA biosynthesis by directly controlling the expression of CALMODULIN BINDING PROTEIN 60g (CBP60g) and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1). HDA6 bound to the chromatin of CBP60g and SARD1 promoter regions, and histone H3 acetylation was highly enriched within these regions. Furthermore, the transcriptome of shi5 mutants mimicked that of plants treated with exogenous SA or attacked by pathogens. All these data suggest that HDA6 is vital for plants in finely controlling the SA level to regulate plant immunity.

2.
Ecotoxicol Environ Saf ; 227: 112885, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34634601

RESUMO

The coexistence of nanoplastics (NPs) and pollutants such as arsenic (As) has become an unignorable environmental problem. However, there is still a considerable knowledge gap about the impact of NPs and pollutants on human health risks. In this study, the human gastric adenocarcinoma (AGS) cells were used as a model to investigate the toxicity of NPs with different particle sizes and As by MTT assay, western blotting, immunofluorescence and so on. The results showed that 20 nm (8 µg/mL), 50 nm (128 µg/mL), 200 nm (128 µg/mL), 500 nm (128 µg/mL), 1000 nm (128 µg/mL) polystyrene (PS) did not affect cell viability, ROS, intracellular calcium and activate apoptosis pathway in AGS cells. However, noncytotoxic concentration of NPs enhanced the cytotoxicity and intracellular accumulation of As. NPs destroys the fluidity of cell membrane and cytoskeleton, inhibits the activity of ABC transporter, and leads to the accumulation of As in cells. This work highlights that the damage caused by NPs, especially at the level of noncytotoxicity, joint with As cannot be ignored and provides a specific toxicological mechanism of NPs accompanied by exposure to As.

3.
Int Immunopharmacol ; 101(Pt B): 108216, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634689

RESUMO

Herpes zoster (HZ) is a recurrent nerve tissue infection caused by the reactivation of varicella-zoster virus (VZV). At present, two vaccines, the live attenuated vaccine Zostavax™ and AS01B-adjuvanted recombinant subunit vaccine Shingrix™, are commercially available for HZ. The latter is superior to the former in terms of efficacy and duration of immunity in the elderly. In this study, we used glycoprotein E (gE) as an antigen, and investigated the effects of various adjuvants (MF59, MF59/CpG 2006, and MF59/QS-21) on the immune response of C57BL/6J mice to find an alternative adjuvant to AS01B-like adjuvant of liposome/QS-21/MPL. In addition to safety, the gE-specific antibody, IgG antibody subtype, and cytokine secretion by splenocytes, and cell-mediated immune responses were determined using ELISA and ELISPOT assays, respectively. Our results showed no significant effects on the body weight, temperature, or behavior of mice vaccinated with PBS or all adjuvanted vaccines. All adjuvanted vaccine groups showed significantly higher gE-specific IgG antibody levels than the gE-alone group on day 28 after the first vaccine dose. In addition, all adjuvants induced a remarkable increase in both IgG1 and IgG2b levels. However, MF59/QS-21 and MF59/CpG 2006 showed comparable capacities to those of liposome/QS-21/MPL in increasing the IgG2c levels, being superior to MF59. Further investigation revealed that MF59 only induced a limited increase in the levels of Th1 and Th2 cytokines, while MF59/QS-21, MF59/CpG 2006, and liposome/QS-21/MPL led to a significant increase in the secretion of interferon gamma (IFN-γ), IL-2, IL-4, and IL-10 and showed a Th1-biased immune response. Moreover, MF59/QS-21, MF59/CpG 2006, and liposome/QS-21/MPL adjuvanted vaccines resulted in comparable gE-specific IFN-γ + immune cell responses. These results suggest that the combination of MF59 with QS-21 or CpG 2006 may be a promising adjuvant candidate for subunit HZ vaccines. Further investigations are needed to illustrate their durability and efficacy in aged mice.

4.
Mol Cancer ; 20(1): 132, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649567

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive. METHODS: CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology. RESULTS: CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development. CONCLUSION: Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.

5.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2976-2983, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472314

RESUMO

Life sciences are the disciplines most closely related with human beings. As experimental disciplines, life sciences develop rapidly and highly intersect in many scientific fields. Under the "double first-class" initiative, the comprehensive development-oriented talent training system has put forward an urgent need for life sciences literacy and comprehensive ability training of college students. Taking the reform of liberal education curriculum system as an opportunity, we developed a series of eight life sciences practical liberal courses for students with non-biology majors. The courses cover all sub-disciplines or directions of life sciences, and aim to foster interdisciplinary talents with life sciences knowledge and literacy, as well as practical and innovative abilities. These courses could serve as references for experimental teaching centers in colleges and universities to set up practical liberal and experimental courses.


Assuntos
Disciplinas das Ciências Biológicas , Estudantes , Currículo , Humanos , Universidades
6.
Shanghai Kou Qiang Yi Xue ; 30(3): 253-257, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476440

RESUMO

PURPOSE: To investigate the effects of extracellular matrix stiffness on proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) in polydimethylsiloxane (PDMS)-based cell culture substrate model. METHODS: The premolars removed during orthodontic treatment in Changzhou NO.2 People's Hospital were collected for DPSCs culture. PDMS matrix membranes were prepared, and divided into three groups according to the different stiffness degrees, group A (binder/hardener: 10∶1; 135 kPa), group B (binder/hardener: 20∶1; 54 kPa), and group C (binder/hardener: 30∶1; 16 kPa). Group free from PDMS was set as control group. Thereafter, DPSCs cells were cultured on PDMS matrix, and various indexes were detected. The proliferation rate of DPSCs was detected by CCK-8, the osteogenic differentiation of DPSCs was detected by alizarin red staining, and the protein expression levels of osteocalcin(OCN), RUNX2, Wnt1 and ß-catenin were detected by Western blot. The data were processed with SPSS 22.0 software package. RESULTS: Alizarin red staining showed that DPSCs cells in group A had obvious morphological changes, and the cell arrangement showed obvious orientation, its morphology gradually changed from polygon and spindle shape to square shape, and calcified nodules were also observed. The number of calcified nodules among four groups were the most in the group A, followed by group B and group C, which was the lowest in control group, with significant difference (P<0.05). The cell proliferation rate and the expression of OCN, RUNX2, Wnt1 and ß-catenin were the highest in group A, followed by group B and group C, which was the lowest in control group, with significant difference(P<0.05). CONCLUSIONS: The extracellular matrix with high stiffness may promote the proliferation and osteogenic differentiation of DPSCs by activating Wnt/ß-catenin signaling pathway, which may provide a theoretical basis for periodontal tissue engineering.


Assuntos
Polpa Dentária , Osteogênese , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Dimetilpolisiloxanos , Matriz Extracelular , Humanos , Células-Tronco
7.
Artigo em Inglês | MEDLINE | ID: mdl-34488595

RESUMO

BACKGROUND: Carvacrol is a monoterpenic phenol extracted from traditional Chinese herbs, including oregano and thyme. Currently, carvacrol has been widely studied for its therapeutic role in central nervous system diseases, liver diseases and digestive system cancer. OBJECTIVE: However, the role of carvacrol in osteosarcoma and its underlying molecular mechanism remain elusive. Here, we aimed to examine the anticancer effects of carvacrol on osteosarcoma. METHODS: The effects of carvacrol on the osteosarcoma proliferation capacity were revealed by CCK-8 and colony formation assays. Flow cytometry and Hoechst assays were used to determine the effects of carvacrol on osteosarcoma cell apoptosis. The effect of carvacrol on migration and invasion of osteosarcoma cells was determined by wound healing and transwell tests. Protein expression was evaluated by WB assays. The suppressive effects of carvacrol on osteosarcoma in vivo were examined by a xenograft animal model, immunohistochemistry and HE staining. RESULTS: We demonstrated that carvacrol treatment reduced viability and inhibited the colony formation of U2OS and 143B cells in a concentration-dependent manner. Apoptotic cell number increased after exposure to carvacrol. Meanwhile, the expression of Bax increased, and that of Bcl-2 decreased by carvacrol treatment. In addition, the MMP-9 expression and migration and invasion of 143B and U2OS cells were inhibited by carvacrol. We also found that these carvacrol-induced effects on osteosarcoma are associated with the regulation of the Wnt/ß-catenin signaling pathway. CONCLUSION: Our findings suggest that carvacrol suppresses proliferation, migration, invasion and promotes apoptosis in osteosarcoma cells, in part by regulating the Wnt/ß-catenin signaling pathway.

8.
ISA Trans ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34493382

RESUMO

This paper proposes a digital twin solution for unsteady flow state estimation in a pumping station. Digital twin is expected to accurately estimate the real-time hydraulic parameters of blind spots of the pumping station system even under some adverse conditions including the interference of observation noise and model parameters drift. To solve these challenges, a digital twin framework integrating the model-driven method, control theory and data-driven method is presented. In this framework, an unsteady flow state estimation method combining frequency domain analysis and generalized predictive control theory is developed for the first time, which is superior to traditional time-domain numerical discrete methods in terms of computational efficiency and anti-noise interference. In the model parameter calibration process, the novelty concerns modeling of the optimization problem considering the dynamic operation control of the station and unsteady flow of pipelines. And this process is accomplished through the comprehensive application of the model-free adaptive control algorithm, the transient flow model and the particle swarm optimization algorithm. This work is applied to a pumping station in a product pipeline to verify its effectiveness in estimating the transient flow state of data blind spots and map the dynamic operation behavior under the interference of colored noise and parameter drift.

9.
J Immunother Cancer ; 9(9)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34489334

RESUMO

BACKGROUND: A better understanding of the molecular mechanisms that manifest in the immunosuppressive tumor microenvironment (TME) is crucial for developing more efficacious immunotherapies for hepatocellular carcinoma (HCC), which has a poor response to current immunotherapies. Regulatory T (Treg) cells are key mediators of HCC-associated immunosuppression. We investigated the selective mechanism exploited by HCC that lead to Treg cells expansion and to find more efficacious immunotherapies. METHODS: We used matched tumor tissues and blood samples from 150 patients with HCC to identify key factors of Treg cells expansion. We used mass cytometry (CyTOF) and orthotopic cancer mouse models to analyze overall immunological changes after growth differentiation factor 15 (GDF15) gene ablation in HCC. We used flow cytometry, coimmunoprecipitation, RNA sequencing, mass spectrum, chromatin immunoprecipitation and Gdf15 -/-, OT-I and GFP transgenic mice to demonstrate the effects of GDF15 on Treg cells and related molecular mechanism. We used hybridoma technology to generate monoclonal antibody to block GDF15 and evaluate its effects on HCC-associated immunosuppression. RESULTS: GDF15 is positively associated with the elevation of Treg cell frequencies in patients wih HCC. Gene ablation of GDF15 in HCC can convert an immunosuppressive TME to an inflammatory state. GDF15 promotes the generation of peripherally derived inducible Treg (iTreg) cells and enhances the suppressive function of natural Treg (nTreg) cells by interacting with a previously unrecognized receptor CD48 on T cells and thus downregulates STUB1, an E3 ligase that mediates forkhead box P3 (FOXP3) protein degradation. GDF15 neutralizing antibody effectively eradicates HCC and augments the antitumor immunity in mouse. CONCLUSIONS: Our results reveal the generation and function enhancement of Treg cells induced by GDF15 is a new mechanism for HCC-related immunosuppression. CD48 is the first discovered receptor of GDF15 in the immune system which provide the possibility to solve the molecular mechanism of the immunomodulatory function of GDF15. The therapeutic GDF15 blockade achieves HCC clearance without obvious adverse events.

10.
J Sci Food Agric ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468988

RESUMO

BACKGROUND: The Xinjiang Uygur Autonomous Region is an arid and semi-arid region with low rainfall and strong sunlight; thus, grape berries in this region accumulate sugar content rapidly, and the ripening process is shorter than that in other regions. Although previous studies illustrated that altered sunlight conditions could influence the aroma profiles of grape berries, less attention has been paid to the effect of vine top shading on volatile compounds under a dry-hot climate. RESULT: We focused on the effects of vine top shading on the concentrations of linolenic and linoleic acids, as well as their metabolites, the C6/C9 compounds, in grape berries. Four vine top shading treatments at veraison (ripening onset) and post-veraison (skin full coloration) were performed by reducing solar exposure to the grapevines by 20% and 50% respectively. Apart from (E)-2-hexenal in the 20% shading treatment of 2016, (E)-2-hexenal were not promoted by the 50% shading and 20% shading treatments during veraison to harvest in both of the vintages. By contrast, the influence of vine top shading from post-veraison till harvest was different between the two vintages; these C6 compounds were decreased in both of the shading treatments in 2016, whereas most of them were promoted in 2017, possibly related to daily sunshine hours in this period. In addition, the C9 compound nonanal with very low concentration exhibits a significant difference among various treatments by two-factor analysis of variance. As for linolenic acid and linoleic acid, two types of C6 compound biosynthetic precursors, four shading treatments all reduced their concentration, except for linolenic acid in the 50% shading treatment of 2016. Moreover, it appeared to have no apparent correlation between the variations of two precursors and their volatile metabolites, indicating that there is a complex impact of vine shading on C6 compound biosynthesis. CONCLUSION: Vine top shading at veraison can reduce the accumulation of some C6 compounds in grape berries, but no consistent consequence was attained for the vine shading at pre-veraison. The findings indicate the significance of grapevine solar exposure management at veraison in controlling the level of C6 compounds in a dry-hot region like Xinjiang. © 2021 Society of Chemical Industry.

11.
Chemosphere ; : 132362, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592208

RESUMO

To improve the electrocatalytic activity, carbon nanotubes (CNTs) were used to modify a titanium-supported tin-antimony anode (Ti/SnO2-Sb). Compared to a Ti/SnO2-Sb anode, the Ti/SnO2-Sb-CNTs anode exhibited a higher oxygen evolution potential (1.62 V), smaller crystalline volume (71.23 Å3), larger active surface area (0.371 mC cm-2), lower charge transfer resistance (8.24 Ω), and longer service life (291 h). The CNTs provided the Ti/SnO2-Sb anode with effective electrocatalytic activity, conductivity and stability. To evaluate its performance, the Ti/SnO2-Sb-CNTs anode was utilized for the treatment of coking wastewater. The chemical oxygen demand (COD) and total organic carbon (TOC) removal yields of the coking wastewater reached 83.05% and 74.56% under the optimal current density of 25 mA m-2, Na2SO4 concentration of 35 mM, and plate spacing of 10 mm. UV254, ultraviolet-visible absorption spectroscopy, excitation-emission matrix spectra spectroscopy, and Fourier-transform infrared spectroscopy analyses showed that the aromatic and nitrogenous compounds in the coking wastewater were degraded. Furthermore, the electrochemical treatment could effectively reduce the toxicity of the coking wastewater. The energy consumption of the coking wastewater treatment was reduced to 396.56 kWh (kg COD)-1. This study provides a basis engineering application of the electrochemical oxidation of coking wastewater.

12.
J BUON ; 26(4): 1623-1627, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34565027

RESUMO

PURPOSE: To explore the expression level and prognostic value of ADAMTS9-AS2 in prostate cancer (PCa). METHODS: ADAMTS9-AS2 levels in 110 paired PCa tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between ADAMTS9-AS2 level and clinical parameters of PCa was analyzed. ROC (receiver operating characteristics) curves were depicted for assessing the diagnostic value of ADAMTS9-AS2 in PCa. Through collecting 5-year follow-up data of PCa patients, survival analysis was performed by Kaplan-Meier method. Finally, Cox regression model was used to analyze factors affecting outcomes of PCa patients. RESULTS: ADAMTS9-AS2 was downregulated in PCa tissues than in adjacent normal ones. Its level was lower in PCa tissues with clinical stage III+IV or tumor size ≥3cm compared to those with stage I+II or tumor size <3cm. ROC curves verified the diagnostic value of ADAMTS9-AS2 in PCa (AUC=0.902, cut-off value=0.40, sensitivity=90.00%, specificity=79.09%, Youden index=0.6909). Kaplan-Meier method and log-rank test uncovered worse prognosis in PCa patients expressing low level of ADAMTS9-AS2. Clinical stage, tumor size and ADAMTS9-AS2 level were independent factors influencing prognosis of PCa. CONCLUSIONS: ADAMTS9-AS2 is downregulated in PCa and its low level is unfavorable to the disease prognosis. ADAMTS9-AS2 may be utilized as a potential diagnostic and prognostic hallmark of PCa.

13.
Front Public Health ; 9: 687937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395365

RESUMO

To prevent the spread of coronavirus disease 2019 (COVID-19), stringent quarantine measures have been implemented so that healthy people and virus carriers have isolated themselves in the same community owing to the limit capacity of healthcare facilities. With the exponential growth of the infected population, the residential environment is contaminated by fomites from the infected residents and consequently threating the health of susceptible residents. Till now, little has been acknowledged on this indirect transmission route and its role on community transmission. Here we address the impact of self-isolated virus carriers on the residential environment and elucidate the potential transmission pathways via contaminated environment in communities. We urge further investigation on the superspreading cases in communities and hope to arouse the attention to evaluate the potential risk of indirect transmission route as well as the corresponding control measures.


Assuntos
COVID-19 , Fômites , Humanos , Quarentena , SARS-CoV-2
14.
Stem Cell Res Ther ; 12(1): 467, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419165

RESUMO

BACKGROUND: Hypertrophy is a critical process for chondrocyte differentiation and maturation during endochondral ossification, which is responsible for the formation of long bone and postnatal longitudinal growth. Increasing evidence suggests that melatonin, an indole hormone, plays a pivotal role in chondrogenesis. However, little is known about the effects of melatonin on the terminal differentiation of chondrocytes. METHODS: Mesenchymal stem cell (MSC)-derived chondrocytes generated by a high-density micromass culture system were induced to undergo hypertrophic differentiation. Melatonin-mediated hypertrophic differentiation was examined by reverse transcription polymerase chain reaction analysis (RT-PCR) analysis, histological staining and immunohistochemistry. Activation of the Wnt signaling pathway was evaluated by PCR array, RT-PCR, western blotting and immunofluorescence. XAV-939, a Wnt signaling pathway antagonist, was further used to determine whether the effect of melatonin on chondrocyte hypertrophic differentiation was mediated occurred by activation of Wnt signaling pathway. RESULTS: Histological staining showed melatonin increased chondrocyte cell volume and the expression of type X collagen but decreased the expression of type II collagen compared with the control group. RT-PCR showed that melatonin significantly up-regulated the gene expressions of biomarkers of hypertrophic chondrocytes, including type X collagen, alkaline phosphatase, runt-related transcription factor 2, Indian hedgehog and parathyroid hormone-related protein receptor, and melatonin down-regulated the mRNA expression of hallmarks of chondrocytes, including parathyroid hormone-related protein. PCR array showed that the effect of melatonin on chondrocyte hypertrophic differentiation was accompanied by the up-regulation of multiple target genes of the canonical Wnt signaling pathway, and this effect was blocked by XAV-939. CONCLUSIONS: The current findings demonstrate that melatonin enhances the hypertrophic differentiation of MSC-derived chondrocytes through the Wnt signaling pathway. Our findings add evidence to the role of melatonin in promoting bone development and highlight the positive effects of melatonin on terminal differentiation of chondrocytes.


Assuntos
Melatonina , Células-Tronco Mesenquimais , Diferenciação Celular , Células Cultivadas , Condrócitos , Condrogênese/genética , Proteínas Hedgehog/genética , Humanos , Hipertrofia , Melatonina/farmacologia , Proteínas Wnt/genética , Via de Sinalização Wnt
15.
Membranes (Basel) ; 11(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34436350

RESUMO

Studying the influence of grain characteristics on fluid flow in complex porous rock is one of the most important premises to reveal the permeability mechanism. Previous studies have mainly investigated the fluid flow laws in complex rock structures using an uncontrollable one single parameter of natural rock models or oversimplified control group models. In order to solve these problems, this paper proposes a novel method to reconstruct models that can independently control one single parameter of rock grain membranes based on mapping and reverse-mapping ideas. The lattice Boltzmann method is used to analyze the influence of grain parameters (grain radius, space, roundness, orientation, and model resolution) on the permeability characteristics (porosity, connectivity, permeability, flow path, and flow velocity). Results show that the grain radius and space have highly positive and negative correlations with permeability properties. The effect of grain roundness and resolution on permeability properties shows a strong regularity, while grain orientation on permeability properties shows strong randomness. This study is of great significance to reveal the fluid flow laws of natural rock structures.

16.
Anal Chem ; 93(35): 12122-12130, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34424664

RESUMO

Developing an accurate and reliable detection technique for early embryonic apoptosis is of great significance for real-time monitoring and evaluation of embryonic development in living systems. Herein, we have rationally designed and synthesized a novel near-infrared (NIR) fluorogenic probe CGK(QSY21)DEVD-Cy5.5 for real-time imaging of embryonic apoptosis. This probe is constructed with a NIR dye Cy5.5, a fluorescence quencher QSY21, and a peptide substrate Asp-Glu-Val-Asp (DEVD) of the caspase-3 enzyme that is a key executor of cell apoptosis. The probe was initially nonfluorescent in aqueous solution but emitted strong NIR fluorescence upon specific cleavage by activated caspase-3 in a concentration-dependent manner. Taking advantage of this unique feature, this fluorogenic probe was for the first time used for real-time imaging of caspase-3 activity in apoptotic embryos. More notably, significant fluorescence enhancement was solely determined from the apoptotic embryos with the treatment of the probe both in vitro and in vivo, highly suggesting that this probe has great potential to monitor the apoptosis of embryos. We thus envision that this probe would provide a very useful means for real-time visualization and accurate evaluation of embryonic development in the future.


Assuntos
Apoptose , Corantes Fluorescentes , Caspase 3 , Desenvolvimento Embrionário , Fluorescência , Peptídeos
17.
Sci Rep ; 11(1): 16831, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413332

RESUMO

Routine dental visit is the most common approach to detect the gingivitis. However, such diagnosis can sometimes be unavailable due to the limited medical resources in certain areas and costly for low-income populations. This study proposes to screen the existence of gingivitis and its irritants, i.e., dental calculus and soft deposits, from oral photos with a novel Multi-Task Learning convolutional neural network (CNN) model. The study can be meaningful for promoting the public dental health, since it sheds light on a cost-effective and ubiquitous solution for the early detection of dental issues. With 625 patients included in this study, the classification Area Under the Curve (AUC) for detecting gingivitis, dental calculus and soft deposits were 87.11%, 80.11%, and 78.57%, respectively; Meanwhile, according to our experiments, the model can also localize the three types of findings on oral photos with moderate accuracy, which enables the model to explain the screen results. By comparing to general-purpose CNNs, we showed our model significantly outperformed on both classification and localization tasks, which indicates the effectiveness of Multi-Task Learning on dental disease detection. In all, the study shows the potential of deep learning for enabling the screening of dental diseases among large populations.

18.
Oxid Med Cell Longev ; 2021: 9674809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422211

RESUMO

Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.

19.
J Clin Oncol ; : JCO2003318, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34436928

RESUMO

PURPOSE: Squamous non-small-cell lung cancer (sqNSCLC) is genetically complex with evidence of DNA damage. This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546). PATIENTS AND METHODS: Patients age ≥ 18 years with untreated, advanced sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with veliparib 120 mg twice daily (twice a day) or placebo twice a day for up to six cycles. The primary end point was overall survival (OS) in the veliparib arm versus the control arm in current smokers, based on phase II findings. Archival tumor samples were provided for biomarker analysis using a 52-gene expression histology classifier (LP52). RESULTS: Overall, 970 patients were randomly assigned to carboplatin and paclitaxel plus either veliparib (n = 486) or placebo (n = 484); 57% were current smokers. There was no significant OS benefit with veliparib in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio [HR], 0.905; 95% CI, 0.744 to 1.101; P = .266). In the overall population, OS favored veliparib; median OS was 12.2 versus 11.2 months (HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in progression-free survival (median 5.6 months per arm). In patients with biomarker-evaluable tumor samples (n = 360), OS favored veliparib in the LP52-positive population (median 14.0 v 9.6 months; HR, 0.66; 95% CI, 0.49 to 0.89), but favored placebo in the LP52-negative population (median 11.0 v 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new safety signals were observed in the experimental arm. CONCLUSION: In current smokers with advanced sqNSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy.

20.
Virol Sin ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403037

RESUMO

The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has caused global panic in 2003, and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is available; thus, the development of therapeutic antibodies against SARS-CoV is needed. In this study, a nanobody phage-displayed library was constructed from peripheral blood mononuclear cells of alpacas immunized with the recombinant receptor-binding domain (RBD) of SARS-CoV. Four positive clones were selected after four rounds of bio-panning and subjected to recombinant expression in E. coli. Further biological identification demonstrated that one of the nanobodies, S14, showed high affinity to SARS-CoV RBD and potent neutralization activity at the picomole level against SARS-CoV pseudovirus. A competitive inhibition assay showed that S14 blocked the binding of SARS-CoV RBD to either soluble or cell-expressed angiotensin-converting enzyme 2 (ACE2). In summary, we developed a novel nanobody targeting SARS-CoV RBD, which might be useful for the development of therapeutics against SARS.

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