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1.
Crit Rev Biotechnol ; : 1-16, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32166983

RESUMO

Heavy oil accounts for around one-third of total global oil and gas resources. The progressive depletion of conventional energy reserves has led to an increased emphasis on the efficient exploitation of heavy oil and bitumen reserves in order to meet energy demand. Therefore, it is imperative to develop new technologies for heavy oil upgrading and recovery. Biologically-based technology that involves using microorganisms or their metabolites to mobilize heavy oil trapped in reservoir rocks can make a significant contribution to the recovery of heavy oils. Here, the results of laboratory experiments and field trials applying microbial enhanced oil recovery (MEOR) technologies are summarized. This review provides an overview of the basic concepts, mechanisms, advantages, problems, and trends in MEOR, and demonstrates the credibility of MEOR methods for applications in enhanced heavy oil recovery and the petroleum refining processes. This technology is cost-effective and environmentally-friendly. The feasibility of MEOR technologies for heavier oil has not yet been fully realized due to the perceived process complexity and a lack of sufficient laboratory research and field test data. However, novel developments such as enzyme-enhanced oil recovery continues to improve MEOR methods.HighlightsHeavy oil represents the largest known potentially-recoverable petroleum energy resource.Novel biotechnological processes are needed to recover or upgrade heavy oil.Microbial technologies have great potential for heavy oil recovery.Microorganisms can produce metabolic byproducts to mobilize oil trapped in reservoirs.More technological research is needed to develop microbial enhanced oil recovery.

2.
Nanoscale Horiz ; 5(3): 488-494, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32118250

RESUMO

We designed and synthesized a novel nano-thermometer using aggregation-induced-emission (AIE) dye as the reporter and household butter as the matrix. This temperature nanosensor showed decreased fluorescence intensities (∼2%/°C) and shorter fluorescence lifetimes (∼0.11 ns/°C) upon increasing the environmental temperature in the physiological temperature range. Such fluorescence responses were reversible and independent of the environmental pH and ionic strength. The application of these nano-thermometers in temperature sensing in living cells using fluorescence lifetime imaging microscopy (FLIM) was also demonstrated. To the best of our knowledge, this is the first example of AIE-based nano-thermometer for temperature sensing in living cells. This work also provides us with a simple and low-cost method for rapid fabrication of an effective nanosensor based on AIE mechanism.

3.
Chempluschem ; 85(3): 405-410, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32118370

RESUMO

By virtue of an efficient rhodium(III)-catalyzed redox-neutral C-H activation/ring-opening of a strained ring/[4+2] annulation cascade of N-methoxybenzamides with propargyl cycloalkanols, diverse 3-acyl isoquinolin-1(2H)-ones were directly obtained in good yields and with excellent functional group compatibility. Additionally, their antitumor activities against various human cancer cells including HepG2, A549, MCF-7 and SH-SY5Y were evaluated and the action mechanism of the selected compound was also investigated in vitro. The results revealed that these products possessed a potent efficacy, by inhibiting proliferation and inducing apoptosis in a time-dependent and dose-dependent manner, suggesting that such compounds can serve as promising candidates for anti lung cancer drug discovery.

5.
Aging (Albany NY) ; 12(5): 4178-4192, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32139662

RESUMO

Sirtuin 3 (SIRT3) is a type III histone deacetylase that inhibits cardiac hypertrophy. It is mainly localized in the mitochondria and is thus implicated in mitochondrial metabolism. Recent studies have shown that SIRT3 can also accumulate in the nuclear under stressed conditions, and participated in histone deacetylation of target proteins. Poly [ADP-ribose] polymerase 1 (PARP-1) functions as an important PARP isoform that was involved in cardiac hypertrophy. Our experiments showed that SIRT3 accumulated in the nuclear of cardiomyocytes treated with isoproterenol or SIRT3 overexpression. Moreover, overexpression of SIRT3 by adenovirus inhibited the expression of cardiac hypertrophic genes-ANF and BNP, as well as abrogating PARP-1 activation induced by isoproterenol or phenylephrine. In addition, co-immunoprecipitation experiments revealed that SIRT3 could interact with PARP-1, and overexpression of SIRT3 could decrease the acetylation level of PARP-1. Our results indicate that SIRT3 exerts protective effects against cardiac hypertrophy by reducing the level of acetylation and activity of PARP-1, thus providing novel mechanistic insights into SIRT3-mediated cardiprotective actions.

6.
Mol Med Rep ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32186753

RESUMO

Periodontitis is a common inflammatory disorder affecting the tissues surrounding the teeth, which can lead to the destruction of periodontal tissue and tooth loss. Resveratrol, a natural phytoalexin, exerts multiple biological effects. For example, its anti­inflammatory activity has been widely studied for the treatment of inflammatory bowel disease for a number of years. However, its effect on bone repair and new bone formation in an inflammatory microenvironment is not well understood. Accordingly, the effect of resveratrol on inflammation­affected human periodontal ligament stem cells (hPDLSCs) requires further investigation. In the present study, the effect of tumor necrosis factor­α (TNF­α), resveratrol, or the combination of both on the osteogenic differentiation of hPDLSCs, as well as the underlying mechanisms involved, were investigated. Cell Counting Kit­8 assay, alkaline phosphatase staining, Alizarin red staining, Oil Red O staining, reverse transcription­quantitative PCR and western blotting were used in the present study. It was demonstrated that resveratrol enhanced hPDLSC osteogenesis and reversed the inhibitory effects of TNF­α on this process. Further mechanistic studies indicated that resveratrol exerted anti­inflammatory activity by activating the ERK1/2 pathway, decreasing the secretion of interleukin (IL)­6 and IL­8 induced by TNF­α, and enhancing hPDLSCs osteogenesis. The present study suggested that resveratrol may be a novel and promising therapeutic choice for periodontitis.

7.
J Phys Chem Lett ; : 2658-2666, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32168454

RESUMO

Transition-metal dichalcogenides (TMDs) such as MoS2 display promising electrical and optical properties in the monolayer limit. Due to strong quantum confinement, TMDs provide an ideal environment for exploring excitonic physics using ultrafast spectroscopy. However, the interplay between collective excitation effects on single excitons such as band gap renormalization/exciton binding energy (BGR/EBE) change and multiexciton effects such biexciton formation remains poorly understood. Using two-dimensional electronic spectroscopy, we observe the dominance of single-exciton BGR/EBE signals over optically induced biexciton formation. We make this determination based on a lack of strong PIA features at T = 0 fs in the cryogenic spectra. By means of nodal line slope analysis, we determine that spectral diffusion occurs faster than BGR/EBE change, indicative of distinct processes. These results indicate that at higher sub-Mott limit fluences, collective effects on single excitons dominate biexciton formation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32210080

RESUMO

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and ozone exposure is a main cause of its disease burden. However, studies on COPD hospitalizations from short-term ambient level ozone exposure have not generated consensus results. To address the knowledge gap, comprehensive and systematic searches in several databases were conducted using specific keywords for publications up to February 14, 2020. Random-effect models were used to derive overall excess risk estimates between short-term ambient-level ozone exposure and COPD hospitalizations. The influence analyses were used to test the robustness of the results. Both meta-regression and subgroup analyses were used to explore the sources of heterogeneity and potential modifying factors. Based on the results from 26 eligible studies, the random-effect model analyses show that a 10 µg/m3 increase in maximum 8-h ozone concentration was associated with 0.84% (95% CI: 0.09%, 1.59%) higher COPD hospitalizations. The estimates were higher for warm season and multiple-day lag but lower for old populations. Results from subgroup analyses also indicate a multiple-day lag trend and bigger significant health effects during longer day intervals. Although characteristics of individual studies added modest heterogeneity to the overall estimates, the results remained robust during further analyses and exhibited no evidence of publication bias. Our systematic review and meta-analysis indicate that short-term ambient level ozone exposure was associated with increased risk of COPD hospitalizations. The significant association with multiple-day lag trend indicates that a multiple-day exposure metric should be considered for establishing ambient ozone quality and exposure standards for improvement of population health. Future investigations and meta-analysis studies should include clinical studies as well as more careful lag selection protocol.

9.
Thorac Cancer ; 11(3): 769-776, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32012474

RESUMO

BACKGROUND: Anastomosis is one of the important factors affecting anastomotic complications after esophagectomy, and multiple reports have compared anastomotic complications among various techniques. However, there is insufficient evidence in the literature to definitively recommend one anastomotic technique over another. METHOD: We retrospectively evaluated 34 consecutive patients who underwent an improved totally mechanical side-to-side: posterior-to-posterior linear stapled (TM-STS) technique for minimally invasive Ivor Lewis esophagogastric anastomosis, performed by a single surgeon between February 2015 to November 2017. The operative techniques and short-term outcomes are analyzed in this study. RESULTS: There were no conversions to an open approach and a complete resection was achieved in all patients undergoing this improved procedure. During the first half of the series, the median operation time was 355 minutes, ranging from 257 to 480 minutes. Over the second half of this series, the median operation time was reduced to 256 minutes. There were no mortalities or serious postoperative complications. Only one patient (2.9%) had an anastomotic leak, which resolved without intervention. Another patient (2.9%) experienced transient, delayed conduit emptying which upper gastrointestinal radiography determined was due to a mechanical obstruction caused by an abnormally long gastric tube in the chest cavity. CONCLUSIONS: The results of our study suggest that this improved TM-STS technique is safe and effective for minimally invasive Ivor Lewis esophagectomy, and can be considered as one of the alternative procedure for patients with lower esophageal as well as Siewert types I/II gastroesophageal junction carcinoma.

10.
J Mater Chem B ; 8(10): 2115-2122, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32073099

RESUMO

Finding out how to overcome multistage biological barriers for nanocarriers in cancer therapy to obtain highly precise drug delivery is still a challenge. Herein, we prepared a multistage and cascaded switchable polymeric nanovehicle, self-assembled from polyethylene glycol grafted amphiphilic copolymer containing hydrophobic poly(ortho ester) and hydrophilic ethylenediamine-modified poly(glycidyl methacrylate) (PEG-g-p(GEDA-co-DMDEA)) for imaging-guided chemo-photothermal combination anticancer therapy. Notably, a novel ATRP initiator containing cyanine dye was designed and attached to the polymer, providing the nanovehicle with NIR-light induced photothermal and fluorescent properties. The PEG shell displayed tumor-microenvironment-induced detachment, resulting in the surface charge change of the nanovehicle from neutral to positive and thus enhancing cellular uptake. Subsequently, the hydrophobic pDMDEA hydrolyzed into a hydrophilic segment in the acidic lysosome, leading to sufficient drug release. Finally, with the aid of the photothermal property, the therapeutic drug DOX successfully escaped from the lysosome to exert chemotherapy. This well-defined polymeric nanoplatform promoted the development of designing novel theranostic polymeric nanovehicles for precise cancer therapy.

11.
Brief Bioinform ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065211

RESUMO

The locations of the initiation of genomic DNA replication are defined as origins of replication sites (ORIs), which regulate the onset of DNA replication and play significant roles in the DNA replication process. The study of ORIs is essential for understanding the cell-division cycle and gene expression regulation. Accurate identification of ORIs will provide important clues for DNA replication research and drug development by developing computational methods. In this paper, the first integrated predictor named iORI-Euk was built to identify ORIs in multiple eukaryotes and multiple cell types. In the predictor, seven eukaryotic (Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana, Pichia pastoris, Schizosaccharomyces pombe and Kluyveromyces lactis) ORI data was collected from public database to construct benchmark datasets. Subsequently, three feature extraction strategies which are k-mer, binary encoding and combination of k-mer and binary were used to formulate DNA sequence samples. We also compared the different classification algorithms' performance. As a result, the best results were obtained by using support vector machine in 5-fold cross-validation test and independent dataset test. Based on the optimal model, an online web server called iORI-Euk (http://lin-group.cn/server/iORI-Euk/) was established for the novel ORI identification.

12.
Phytomedicine ; 68: 153182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32065953

RESUMO

BACKGROUND: Gegen Qinlian decoction (GQ) is a well-known traditional Chinese medicine that has been clinically proven to be effective in treating ulcerative colitis (UC). However, its therapeutic mechanism has not been fully elucidated. Notch signaling plays an essential role in the regeneration of the intestinal epithelium. PURPOSE: This study was designed to ascertain the mechanism by which GQ participates in the recovery of the colonic mucosa by regulating Notch signaling in acute and chronic UC models. METHODS: Acute and chronic UC mice (C57BL/6) were established with 3 and 2% dextran sulfate sodium (DSS), respectively, and treated with oral administration of GQ. The expression of the Notch target gene Hes1 and the Notch-related proteins RBP-J, MAML and Math1 was analyzed by western blotting. PTEN mRNA levels were detected by qRT-PCR. Mucin production that is characteristic of goblet cells was determined by Alcian blue/periodic acid-Schiff staining and verified by examining MUC2 mRNA levels by qRT-PCR. Cell proliferation was assayed by immunohistochemistry analysis of Ki67. HT-29 and FHC cells and Toll-like receptor 4 knockout (TLR4-/-) acute UC mice were also used in this study. RESULTS: GQ restored the injured colonic mucosa in both acute and chronic UC models. We found that Notch signaling was hyperactive in acute UC mice and hypoactive in chronic UC mice. GQ downregulated Hes1, RBP-J and MAML proteins and augmented goblet cells in the acute UC models, whereas GQ upregulated Hes1, RBP-J and MAML proteins in chronic UC mice, reducing goblet cell differentiation and promoting crypt base columnar (CBC) stem cell proliferation. Hes1 mRNA was suppressed in TLR4-/- UC mice, and GQ treatment reversed this effect. In vitro, GQ reduced Hes1 protein in Notch-activated HT29 and FHC cells but increased Hes1 protein in Notch-inhibited cells. CONCLUSIONS: GQ restored the colonic epithelium by maintaining mucosal homeostasis via bidirectional regulation of Notch signaling in acute/chronic UC models.

13.
J Hazard Mater ; 392: 122265, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32078969

RESUMO

Evidence demonstrates that 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) is able to disturb thyroid hormones (THs) homeostasis, yet the mechanisms remain unknown. We sought to investigate the effects of PBDE-47 on endoplasmic reticulum (ER) and lysosomes in thyroids. Using female Sprague-Dawley rats orally administered PBDE-47 at environmentally relevant doses (0.1, 1.0, 10 mg/kg/day) beginning ten days before breeding and ending at weaning, we showed that perinatal PBDE-47 exposure resulted in a reduction in serum THs levels and relative thyroid weight in adult female rats. These were accompanied by thyroid structural abnormalities with cell apoptosis. Mechanistically, PBDE-47 caused ER stress and activation of unfolded protein response (UPR). Moreover, PBDE-47 elicited lysosomal membrane permeabilization and the release of cathepsin. Importantly, the apoptotic cells co-localized with IRE1α, a stress sensor protein of UPR branch that mediates ER stress-induced apoptosis, or cathepsin B, a lysosomal cysteine protease that is involved in thyroglobulin, the precursor of THs, degradation and apoptosis induction. Interestingly, thyroglobulin was accumulated and predominantly presented in cells harboring compromised ER or lysosomal activity. Collectively, our findings suggest that perinatal low-dose PBDE-47 exposure hampers thyroglobulin turnover and induces thyroid cell apoptosis by triggering ER stress and lysosomal destabilization contributing to thyroid toxicity in adult female rats.

14.
Funct Plant Biol ; 47(3): 263-278, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029065

RESUMO

Leaf senescence is an important factor that affects crop yield traits and is regulated by various factors. Here, we propose the photo-carbon imbalance hypothesis to explain the mechanism of rice leaf senescence. The main idea of this hypothesis is that carbon assimilation decreases faster than the absorption of light energy in photosynthesis during the late stages of rice growth, which ultimately results in leaf senescence. Our results indicate that endogenous ascorbic acid (Asc) plays an important role in leaf senescence by affecting the expression of senescence genes, thereby influencing photosynthetic capacity and consequently grain yield. The effects of exogenous Asc and methyl jasmonate (MeJA) on photosynthetic capability implied that the balance between photoreaction and carbon assimilation is regulated by exogenous antioxidants or accelerators of senescence. The results of the shading treatments indicated that shading will mitigate the photo-carbon imbalance and improve photosynthetic capacity, resulting in increased yields. Increasing antioxidant concentrations can enhance the reactive oxygen species (ROS) scavenging capacity, whereas shading reduces excess light energy, which may help to restore the photo-carbon balance.

15.
Int J Biol Macromol ; 151: 609-617, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32061700

RESUMO

ß-Glucosidases (BGL) are key members of the cellulase enzyme complex that determine efficiency of lignocellulosic biomass degradation, which have shown great functional importance to many biotechnological systems. A previous reported BGL from Neosartorya fischeri (NfBGL) showed much higher activity than other BGLs. Screening the important residues based on sequence alignment, analyzing a homology model, and subsequent alteration of individually screened residues by site-directed mutagenesis were carried out to investigate the molecular determinants of the enzyme's high catalytic efficiency. Tyr320, located in the wild-type NfBGL substrate-binding pocket was identified as crucial to the catalytic function of NfBGL. The replacement of Tyr320 with aromatic amino acids did not significantly alter the catalytic efficiency towards p-nitrophenyl ß-d-glucopyranoside (pNPG). However, mutants with charged and hydrophilic amino acids showed almost no activity towards pNPG. Computational studies suggested that an aromatic acid is required at position 320 in NfBGL to stabilize the enzyme-substrate complex formation. This knowledge on the mechanism of action of the molecular determinants can also help rational protein engineering of BGLs.

16.
Fitoterapia ; 142: 104498, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32058053

RESUMO

Three new triterpenoids, mallomacrostins A-C (1-3), and 11 known ones (4-14) were obtained from the twigs and leaves of Mallotus macrostachyus. Mallomacrostin A possessed a new trinor-D:B-friedobaccharane skeleton. The structures of the new compounds were elucidated on the basis of extensive spectroscopic techniques including HR-ESIMS and NMR and the structure of 1 was confirmed by single crystal X-ray diffraction analysis. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 2 and 10 exhibited significant anti-inflammatory activity by inhibiting LPS-induced release of nitric oxide with IC50 of 70.0 µM and 14.0 µM, respectively.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32015430

RESUMO

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to birth outcomes in a sex-specific manner. These outcomes may be mediated by placental inflammation, which is the proposed biological mechanism. This is the first study to address the relationship between phthalate exposure and gene expression in placental inflammation in a sex-specific manner. We performed quantitative PCR to measure placental inflammatory mRNAs (CRP, TNF-α, IL-1ß, IL-6, IL-10, MCP-1, IL-8, CD68, and CD206) in 2469 placentae that were sampled at birth. We estimated the associations between mRNA and urinary phthalate monoesters using multiple linear regression models. Mono-n-butyl phthalate (MBP) was correlated with higher IL-1ß, IL-6, and CRP expression in placentae of male fetuses and with higher IL-6, CRP, MCP-1, IL-8, IL-10, and CD68 expression in placentae of female fetuses. Mono benzyl phthalate (MBzP) increased the expression of TNF-α, MCP-1, and CD68 only in placentae of male fetuses. Mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with CRP, MCP-1, and CD68 in placentae of female fetuses. Maternal phthalate exposure was associated with inflammatory variations in placental tissues. The associations were stronger in placentae of male than of female fetuses. Compared with the other metabolites, MBP plays a strong role in these associations. The placenta is worth being further investigated as a potential mediator of maternal exposure-induced disease risk in children.

18.
Org Lett ; 22(4): 1295-1300, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32017582

RESUMO

By using a synergistic dual directing group-assisted C-H activation strategy and simply modifying the reaction conditions, we realized a robust and general Cp*Rh(III)-catalyzed C-H cyclopropylation of N-acetoxybenzamides with cyclopropenyl alcohols, providing regio-, chemo-, and diastereoselective access to ortho trans- and cis-1,1-dimethylcyclopropane-functionalized benzamides in a redox-neutral and controllable manner. Experimental and density functional theory studies clarify the roles of the NH-OAc and OH groups and deduce two distinct Rh(III)-Rh(V)-Rh(III) pathways for presenting such selectivity.

19.
Nanotechnology ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106102

RESUMO

Single-walled carbon nanotubes (SWCNTs) are potential antibacterial material, and their antibacterial activity in aqueous solutions relies on surfactants to create strong interactions with bacterial cells. Here, we designed and synthesized a new family of cationic surfactants by introducing different positively charged hydrophilic heads, i.e., -(CH2)6N+(CH3)3Br-, -(CH2)2N+(CH3)3Br- and -(CH2)2N+PyridineBr-, to cardanol obtained from cashew nut shell liquid. These surfactants can efficiently disperse SWCNTs in aqueous solutions because benzene rings and olefin chains in cardanol enable strong π-stackings on SWCNTs. A much higher fraction of SWCNTs can be dispersed individually as compared to the commonly used surfactants, e.g., dodecylbenzene-sulfonate sodium (SDBS). SWCNTs dispersed in the cardanol-derived surfactants demonstrate significantly improved antibacterial activities. At the concentration of 0.5 wt.%, their minimum inhibitory concentration is 0.33 and 0.02 µg/mL against E. coli and S. aureus, respectively, which is only 0.8-1.5% of that of SDBS dispersed SWCNTs. The intense antibacterial activity can be attributed to better dispersion of SWCNTs and positive charges introduced by hydrophilic heads, which attract to negatively charged bacterial cell surfaces. These cardanol-derived surfactants are promising as sustainable surfactants for enabling various SWCNT applications.

20.
Theranostics ; 10(3): 1245-1261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938063

RESUMO

Polybrominated diphenyl ethers (PBDEs)-induced neurotoxicity is closely associated with mitochondrial abnormalities. Mitochondrial fusion and fission dynamics are required for the maintenance of mitochondrial homeostasis. However, little is known about how PBDEs disrupt this dynamics and whether such disruption contributes to impaired neurodevelopment. Methods: We investigated the effects of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47), the dominant congener in human samples, on mitochondrial fusion and fission dynamics using PC12 cells, a well-defined in vitro neurodevelopmental model. We also evaluated the effects of perinatal low-dose PBDE-47 exposure on hippocampal mitochondrial dynamics and its association with neurobehavioral changes in adult Sprague-Dawley rats. Results: In vitro, PBDE-47 disrupted mitochondrial dynamics by inhibiting mitochondrial fusion and fission simultaneously, accompanied by mitochondrial fragmentation, membrane potential dissipation, ATP loss, and apoptosis activation. Specifically, enhancing mitochondrial fusion by the chemical promoter M1 or adenovirus-mediated mitofusin 2 (Mfn2) overexpression rescued PBDE-47-caused mitochondrial dynamic, morphological and functional impairments, prevented the resultant apoptosis and promoted neuronal survival. Unexpectedly, either stimulating mitochondrial fission by adenovirus-mediated fission protein 1 (Fis1) overexpression or suppressing mitochondrial fission by the mitochondrial division inhibitor-1 (Mdivi-1) failed to reverse whereas aggravated PBDE-47-induced mitochondrial damage and neuronal death. Importantly, promoting mitochondrial fusion by Mfn2 overexpression neutralized the detrimental effects elicited by Fis1 overexpression after PBDE-47 treatment. Finally, perinatal oral administration of PBDE-47 elicited neurobehavioral deficits and hippocampal neuronal loss via apoptosis in adult rats, which were associated with mitochondrial dynamics alterations manifested as a fragmented phenotype. Conclusion: Our results suggest that PBDE-47 disrupts mitochondrial dynamics to induce mitochondrial abnormalities, triggering apoptosis and thus contributing to neuronal loss and subsequent neurobehavioral deficits. Targeting mitochondrial fusion may be a promising therapeutic intervention against PBDE-47 neurotoxicity.

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