Publications by authors named "Yujia Zhai"

96 Publications

Progress in tumour-targeted drug delivery based on cell-penetrating peptides.

J Drug Target 2021 May 4:1-15. Epub 2021 May 4.

Key Laboratory of Chemical Biology, Department of Pharmaceutics, School of Pharmaceutical Sciences, Ministry of Education, Shandong University, Jinan, China.

Since the discovery of cell-penetrating peptides (CPP) in the 1980s, they have played a unique role in various fields owing to their excellent and unique cell membrane penetration function. In particular, in the treatment of tumours, CPPS have been used to deliver several types of 'cargos' to cancer cells. To address the insufficient targeting ability, non-selectivity, and blood instability, activatable cell-penetrating peptides, which can achieve targeted drug delivery in tumour treatment, enhance curative effects, and reduce toxicity have been developed. This study reviews the application of different cell-penetrating peptides in tumour-targeted delivery, overcoming multidrug resistance, organelle targeting, tumour imaging, and diagnosis, and summarises the different mechanisms of activatable cell-penetrating peptides in detail.
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http://dx.doi.org/10.1080/1061186X.2021.1920026DOI Listing
May 2021

Compositional and functional responses of bacterial community to titanium dioxide nanoparticles varied with soil heterogeneity and exposure duration.

Sci Total Environ 2021 Jun 4;773:144895. Epub 2021 Feb 4.

Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, 2300 RA Leiden, the Netherlands.

Titanium dioxide nanoparticles (TiO NPs) are widely used as nano-agrochemicals. In this study we investigated the influence of soil heterogeneity on bacterial communities exposed to TiO NPs over time. Clay and sandy soils with low- and high-organic matter contents were exposed to environmentally relevant concentration of TiO NPs (1 mg/kg) and soil bacterial communities were sampled after short-term (15 days) and long-term exposure (60 days). After short-term TiO NPs exposure, significant effects regarding the enzyme activity, bacterial community structure and composition, and community functioning were observed in the clay soils with high organic matter (clay-HOM) but not in other soil groups. Response alterations were observed to taxa belonging to Acidobacteria and Verrucomicrobia, and functional pathways related to carbohydrates degradation. These results indicated that soil heterogeneity play more important roles in shaping the bacterial community in soil with low clay fraction and less organic matter, while TiO NPs selection was the main driver in inducing the compositional and functional impacts on the soil bacterial community in the presence of clay soil with high organic matter content. As exposure time increased, the bacterial community recovered after a long-term exposure of 60 days, suggesting that the bacterial evolution and adaptation could overcome the TiO NPs selection after long-term exposure. Our results highlighted the importance of soil heterogeneity including clay fraction and organic matter and exposure duration in assessing the impact of nanoparticle on soil bacterial activity, community and function. By comprehensively evaluating the risks of nanoparticles on soil ecosystem and explicitly and explicitly include spatial and temporal variations, the benefit of nano-agrochemical products has the potential to be promoted in future applications.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144895DOI Listing
June 2021

Pegylated Liposomal Doxorubicin in Vindesine-Based and Bortezomib-Based Regimens for Patients With Newly Diagnosed Multiple Myeloma: A Retrospective Study of Efficacy and Safety.

Front Oncol 2021 25;11:597453. Epub 2021 Mar 25.

Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Purpose: Although pegylated liposomal doxorubicin (PLD) has been approved in combination with bortezomib for relapsed/refractory multiple myeloma (MM), the antitumor efficacy and tolerability of PLD in different regimens for patients with newly diagnosed MM (NDMM) have not been fully defined.

Methods: A total of 249 NDMM patients diagnosed between January 2008 and October 2019 were included in this retrospective study. Among them, 112 patients received vindesine-based chemotherapy (35 vDD and 77 vAD) and 137 received bortezomib-based chemotherapy (58 VDD and 79 VD).

Results: In bortezomib-containing regimens, the complete response rate (48.3 30.4%, p = 0.033) and very good partial response or better rate (74.1 . 57.0%, p = 0.038) of VDD were significantly higher than those of VD subgroup. While no superior survival was found between VDD and VD subgroup. In vindesine-containing regimens, no statistical significance was identified between vDD and vAD in terms of response rate and survival. The occurrence rates of all cardiac AEs were similar between VDD and VD.

Conclusions: The vDD regimen was similar with vAD in the aspect of response rate, survival, and toxicity in NDMM patients. The addition of PLD to VD brought deeper response without increased toxicity, while no superior survival was found.
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http://dx.doi.org/10.3389/fonc.2021.597453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030239PMC
March 2021

First report of Geotrichum candidum causing sour rot of peach in China.

Plant Dis 2021 Apr 6. Epub 2021 Apr 6.

China Agricultural University College of Horticulture, 534806, Beijing, China;

Peach (Prunus persica L. Batsch) is one of the most important fruit crops in China (Wang et al. 2011). Yangshan Town of Jiangsu Province is one of the four major peach producing areas in China, with a growing area of 2,000 ha (Tian et al. 2018). During June 2020, a postharvest disease presenting with brown necrosis and rot occurred on peaches in Yangshan Town. The estimated damage was more than 10% of the total harvest. The symptoms included soft rot, and the lesion appeared sunken, accompanied with sour odor and white mycelia. Twelve peaches with representative symptom were sampled for pathogen isolation. Pieces (about 5 mm × 5 mm) from the lesion edge of symptomatic fruits were dissected and surface disinfected (3% NaClO for 10 s and 75% ethanol for 30 s), then rinsed three times with distilled water, dried on sterile filter paper and transferred to Potato Dextrose Agar (PDA) media plates supplemented with 150 ng/mL streptomycin sulfate. The plates were incubated at 28 ℃ for 3 days. Forty-eight isolations were obtained from the plates and isolates were single-spored. All isolates presented white, flat, milky yeast-like colonies with radial mycelia. Hyphae under microscope were septate, branched, disarticulating into arthroconidia measuring 3.39 to 9.27 × 2.05 to 7.71 μm. The morphological characteristics are consistent with Geotrichum candidum (De Hoog et al. 1986). Internal transcribed spacer (ITS) and 18s nuclear ribosomal small subunit (SSU) of the 48 isolates were amplified and sequenced using the primers ITS5/ITS4, and NS1/NS4 for molecular identification (Schoch et al. 2012). The resulted sequences showed no difference among all the isolates. Alignment by blastn showed the sequence of ITS and SSU were 100% (accession number. GQ376093) and 99.7% identical (accession number. KY977411.1) to Geotrichum candidum, respectively. The sequences of ITS (accession number MW493646) and SSU (accession number MW493648) were submitted to the GenBank. Commercial ripe peaches with the size of about 15 cm × 15 cm × 10 cm was used for pathogenicity test. Peaches were surface disinfected with 75% ethanol, then a wound with 4 mm in diameter and 5 mm in depth was made on the surface of each fruit. Ten peaches were inoculated with 10 μL (1×105 spores /mL) of the isolate suspension. Another ten peaches were inoculated with 10 μL sterile water as the control. Peaches were incubated individually at 28 ℃and a relative humidity of about 85%. After three days, large scale of pits and necrosis appeared on every peach inoculated, and the symptoms were consistent with the diseased peaches in Yangshan Town, while no symptoms non-inoculated on the control peaches were observed. The pathogen was re-isolated from the diseased fruit and was identified again by sequencing of ITS and SSU. All the tests were conducted three times. Considering the evidence, we identified the pathogen as G. candidum. This pathogen has been reported to cause sour rot was reported in kiwifruit, strawberry, melon and other fruits (Alonzo et al. 2020; Cheng et al. 2020; Halfeld-Vieira et al. 2020). To our knowledge, this is the first report of G. candidum causing sour rot of peach in China, which may cause a great loss to peach industry of China.
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http://dx.doi.org/10.1094/PDIS-02-21-0279-PDNDOI Listing
April 2021

Effects of humic substances on the aqueous stability of cerium dioxide nanoparticles and their toxicity to aquatic organisms.

Sci Total Environ 2021 Mar 19;781:146583. Epub 2021 Mar 19.

Institute of Environmental Sciences (CML), Leiden University, Leiden 2300, RA, the Netherlands; Centre for Safety of Substances and Products, National Institute of Public Health and the Environment (RIVM), Bilthoven 3720 BA, the Netherlands.

The impacts of humic substances (HS) on the aquatic stability and toxicity of nano‑cerium dioxide (nCeO) to three organisms with different exposure characteristics were investigated. Addition of HS to suspensions of nCeO lowered the surface zeta potential of the particles, reduced their hydrodynamic size, and increased the energy barrier as indicated by the total potential energy profile. This resulted in a more stable suspension compared to suspensions without HS added. Moreover, a higher concentration of HS further stabilized nCeO in the suspension. Acute toxicity of the suspensions to the unicellular green alga Raphidocelis subcapitata and to the crustacean Chydorus sphaericus was lower as compared to exposure without HS added. The acute toxicity of nCeO suspensions to the zebrafish (Danio rerio) eleutheroembryo was on the other hand significantly enhanced (additive and synergistic) upon increasing HS concentration. Our findings emphasize that HS is important to stabilize the nano-suspensions and that its impact on nCeO toxicity differs across different aquatic organisms. Emphasizing the exposure characteristics of each of the organisms selected from the trophic levels can explain how particle stability impacts particle toxicity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146583DOI Listing
March 2021

Analyzing knowledge entities about COVID-19 using entitymetrics.

Scientometrics 2021 Mar 12:1-19. Epub 2021 Mar 12.

Department of Information Management, Peking University, Beijing, China.

COVID-19 cases have surpassed the 109 + million markers, with deaths tallying up to 2.4 million. Tens of thousands of papers regarding COVID-19 have been published along with countless bibliometric analyses done on COVID-19 literature. Despite this, none of the analyses have focused on domain entities occurring in scientific publications. However, analysis of these bio-entities and the relations among them, a strategy called entity metrics, could offer more insights into knowledge usage and diffusion in specific cases. Thus, this paper presents an entitymetric analysis on COVID-19 literature. We construct an entity-entity co-occurrence network and employ network indicators to analyze the extracted entities. We find that ACE-2 and C-reactive protein are two very important genes and that lopinavir and ritonavir are two very important chemicals, regardless of the results from either ranking.
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http://dx.doi.org/10.1007/s11192-021-03933-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953944PMC
March 2021

Mild to Severe Depressive Symptoms in Elderly Stroke Survivors and Its Associated Factors: Evidence From a Cross-Sectional Study in Zhejiang Province, China.

Front Psychiatry 2020 25;11:551621. Epub 2021 Feb 25.

Director Office, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.

The objective of the study is to explore the prevalence of mild to severe depressive symptoms in elderly stroke survivors and its associated factors. We did data analyses of 335 elders with stroke history. Data were collected in a survey conducted between 2014 and 2015, among permanent residents aged 60 and older in Zhejiang Province, China. Prevalence of mild to severe depressive symptoms among stroke survivors were calculated, and univariate analyses and multilevel logistic regression were used to explore its associated factors. Prevalence of mild to severe depressive symptoms was 22.09% (95% CI: 17.65-26.53%) in elders with stroke history, more than twice compared to their counterparts not suffering stroke (9.77%, < 0.001). In multilevel logistic regression, we found that elderly stroke survivors who were illiterate (OR = 2.33, = 0.008), or had limitation in activities of daily living (OR = 3.04, = 0.001) were more likely to be present with mild to severe depressive symptoms, respectively, while those with more fresh vegetable consumption were at lower odds (OR = 0.82, = 0.047). Prevalence of mild to severe depressive symptoms was high in elderly stroke survivors. Targeted screening might be needed for those being illiterate, disabled in activities of daily living, and having little consumption of fresh vegetable. The association between fresh vegetable consumption and depressive symptom in stroke patients calls for further research.
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http://dx.doi.org/10.3389/fpsyt.2020.551621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947299PMC
February 2021

Does aluminum exposure affect cognitive function? a comparative cross-sectional study.

PLoS One 2021 16;16(2):e0246560. Epub 2021 Feb 16.

Department of Public Health Surveillance and Advisory, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China.

Objectives: This study assessed the cognitive function of aluminum-exposed participants from an alum mining zone, compared them with unexposed subjects, and aimed to elucidate the effect of aluminum exposure on cognition.

Design: This was a comparative cross-sectional study. Univariate analyses were used to assess the differences between the aluminum-exposed and unexposed groups. Binary logistic regression models were applied to analyze the effect of aluminum exposure.

Setting: The aluminum-exposed participants were included from an alum mining zone and the unexposed subjects were residents from another district without alum-mine-related factories.

Participants: We included 539 aluminum-exposed participants (254 men, 285 women) and 1720 unexposed participants (692 men, 1028 women).

Results: The mean cognition score on Mini-Mental State Examination was 21.34 (± 6.81) for aluminum-exposed participants. The exposed group had 6.77 times (95% confidence interval, 5.09-9.00) more risk of cognitive impairment than the unexposed group, after adjusting for age, sex, and educational level. No statistically significant association was found between exposure duration and cognition.

Conclusions: This study demonstrated a significant association between aluminum exposure and lower cognitive function.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246560PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886175PMC
February 2021

Alteration of dominant cyanobacteria in different bloom periods caused by abiotic factors and species interactions.

J Environ Sci (China) 2021 Jan 21;99:1-9. Epub 2020 Jun 21.

College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Freshwater cyanobacterial blooms have drawn public attention because they threaten the safety of water resources and human health worldwide. Heavy cyanobacterial blooms outbreak in Lake Taihu in summer annually and vanish in other months. To find out the factors impacting the cyanobacterial blooms, the present study measured the physicochemical parameters of water and investigated the composition of microbial community using the 16S rRNA gene and internal transcribed spacer amplicon sequencing in the months with or without bloom. The most interesting finding is that two major cyanobacteria, Planktothrix and Microcystis, dramatically alternated during a cyanobacterial bloom in 2016, which is less mentioned in previous studies. When the temperature of the water began increasing in July, Planktothrix appeared first and showed as a superior competitor for M. aeruginosa in NO-rich conditions. Microcystis became the dominant genus when the water temperature increased further in August. Laboratory experiments confirmed the influence of temperature and the total dissolved nitrogen (TDN) form on the growth of Planktothrix and Microcystis in a co-culture system. Besides, species interactions between cyanobacteria and non-cyanobacterial microorganisms, especially the prokaryotes, also played a key role in the alteration of Planktothrix and Microcystis. The present study exhibited the alteration of two dominant cyanobacteria in the different bloom periods caused by the temperature, TDN forms as well as the species interactions. These results helped the better understanding of cyanobacterial blooms and the factors which contribute to them.
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http://dx.doi.org/10.1016/j.jes.2020.06.001DOI Listing
January 2021

Blood pressure and cognitive decline over the course of 2 years in elderly people: a community-based prospective cohort study.

Aging Clin Exp Res 2020 Sep 26. Epub 2020 Sep 26.

Department of Public Health Surveillance and Advisory, Zhejiang Provincial Center for Disease Control and Prevention, No. 3399, Binsheng Rd., Binjiang District, Hangzhou, Zhejiang, People's Republic of China.

Background: Numerous studies have shown a significant association between blood pressure (BP) and cognition, but little is known about the effect of BP on the rate of cognitive decline.

Aims: To investigate the relationship between blood pressure and the subsequent rate of cognitive decline in elderly people.

Methods: Based on a prospective cohort that has been followed since 2014, we collected baseline blood pressures and other covariates in 7874 Chinese individuals aged 60 years or older, and followed their cognitive change using the Mini-Mental State Examination (MMSE) until Dec 31, 2016. Linear mixed-effects models were used to measure changes in MMSE scores over time in relation to blood pressure values, and in addition to the covariates, we included random effects for intercepts and slopes.

Results: In the non-hypertension group, we observed that faster cognitive decline was associated with higher systolic blood pressure, lower diastolic blood pressure, lower mean arterial pressure, and higher pulse pressure. In the hypertension group, lower diastolic blood pressure, lower mean arterial pressure, and higher pulse pressure were associated with faster cognitive decline, but not systolic blood pressure.

Conclusion: Higher systolic blood pressure, lower diastolic blood pressure, lower mean arterial pressure, and higher pulse pressure accelerate the subsequent rate of cognitive decline in elderly people. The results of this study may help improve blood-pressure control strategies to prevent cognitive decline.
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http://dx.doi.org/10.1007/s40520-020-01717-7DOI Listing
September 2020

The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease.

Nature 2020 10 2;586(7831):735-740. Epub 2020 Sep 2.

Ronald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Innate immunity is associated with Alzheimer's disease, but the influence of immune activation on the production of amyloid-β is unknown. Here we identify interferon-induced transmembrane protein 3 (IFITM3) as a γ-secretase modulatory protein, and establish a mechanism by which inflammation affects the generation of amyloid-β. Inflammatory cytokines induce the expression of IFITM3 in neurons and astrocytes, which binds to γ-secretase and upregulates its activity, thereby increasing the production of amyloid-β. The expression of IFITM3 is increased with ageing and in mouse models that express familial Alzheimer's disease genes. Furthermore, knockout of IFITM3 reduces γ-secretase activity and the formation of amyloid plaques in a transgenic mouse model (5xFAD) of early amyloid deposition. IFITM3 protein is upregulated in tissue samples from a subset of patients with late-onset Alzheimer's disease that exhibit higher γ-secretase activity. The amount of IFITM3 in the γ-secretase complex has a strong and positive correlation with γ-secretase activity in samples from patients with late-onset Alzheimer's disease. These findings reveal a mechanism in which γ-secretase is modulated by neuroinflammation via IFITM3 and the risk of Alzheimer's disease is thereby increased.
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http://dx.doi.org/10.1038/s41586-020-2681-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919141PMC
October 2020

Seniors' Physical Activity in Neighborhood Parks and Park Design Characteristics.

Front Public Health 2020 29;8:322. Epub 2020 Jul 29.

College of Architecture and Urban Planning, Tongji University, Shanghai, China.

Physical activity brings multiple health benefits to seniors. Neighborhood parks provide seniors with accessible spaces and opportunities to engage in physical activity. This study investigated the associations between neighborhood park design characteristics and seniors' total walking step and energy expenditure during the park visit. Seniors' total step was measured by pedometer, and energy expenditure was calculated based on self-reported activities in the park. The study was conducted in 15 neighborhood parks with an area <10 ha, and included 234 senior participants. One-way ANOVA analyses indicated that seniors in parks with larger surface area, longer trail, larger natural area and outdoor fitness equipment had taken more steps. While seniors in parks without water expended more energy. For instance, seniors in parks with surface areas <3 ha walked 507 fewer steps than seniors in parks with areas between 3 and 5 ha, and 691 fewer steps than those in parks larger than 5 ha. When including seniors' demographic attributes, multiple regression analyses suggested that total step was negatively associated with age, but positively associated with total natural area in the park and the presence of outdoor fitness equipment. Seniors energy expenditure was positively associated with BMI and the presence of outdoor fitness equipment. Energy expenditure was also related to income. These findings provide direct implications for neighborhood park design and management. Planners and designers can include more natural areas over paved areas, create longer trails and place more outdoor fitness equipment in parks to encourage seniors to walk and spend more energy.
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http://dx.doi.org/10.3389/fpubh.2020.00322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403175PMC
July 2020

Molecular mechanism of mitochondrial phosphatidate transfer by Ups1.

Commun Biol 2020 Aug 25;3(1):468. Epub 2020 Aug 25.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.

Cardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The α2-loop, L2-loop, and α3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.
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http://dx.doi.org/10.1038/s42003-020-01121-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447767PMC
August 2020

Association of empty nest and group activity with cognitive impairment in Chinese older adults: A cross-sectional study.

Arch Gerontol Geriatr 2020 Sep - Oct;90:104120. Epub 2020 May 21.

Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Binjiang District, Hangzhou 310051, Zhejiang, China. Electronic address:

Objectives: This study explored the associations of empty nest and group activity with cognitive impairment in Chinese older adults.

Materials And Methods: Data were analyzed from 10,349 participants of the second-round survey database of the Zhejiang Ageing and Health Cohort Study aged 60 years and over. Cognitive impairment was assessed by the Mini-Mental State Examination questionnaire. Logistic regression models controlled for an extensive range of potential confounders were generated to examine the associations of empty nest and group activity with cognitive impairment.

Results: No association was found between empty nest and cognitive impairment in total participants. However, when stratified by sex, empty nest women were less likely to have cognitive impairment than non-empty nest women, odds ratio (OR) (95 % confidence interval [CI]) (0.846; 0.721, 0.993). Elders who participated in group activities showed significantly lower odds of cognitive impairment than those who never attended group activities, (0.811; 0.723, 0.910). This association remained significant in the 60-69-years group when further stratified by age, with an OR (95 % CI) of 0.616 (0.514, 0.739).

Conclusions: Empty nesters were not vulnerable to poor cognitive function. Participation in group activities was significantly associated with lower odds of cognitive impairment. Prospective studies are needed to assess the effect of empty nest and group activity on the risk of cognitive impairment.
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http://dx.doi.org/10.1016/j.archger.2020.104120DOI Listing
December 2020

Prognostic Utility of Monocyte to High-Density Lipoprotein Ratio in Patients With Acute Coronary Syndrome: A Meta-Analysis.

Am J Med Sci 2020 05 27;359(5):281-286. Epub 2020 Jan 27.

Department of Physiology, Basic Medical College of Beihua University, Jilin City, China. Electronic address:

Background: The monocyte to high-density lipoprotein ratio (MHR) has been used to predict adverse clinical outcomes in patients with acute coronary syndrome (ACS). This meta-analysis aimed to evaluate the prognostic utility of MHR in patients with ACS.

Materials And Methods: We comprehensively searched for relevant studies in Pubmed, Embase, CNKI, WanFang and VIP databases until March 12, 2019. Epidemiologic studies investigating the association between MHR and major adverse cardiovascular events (MACE) or all-cause mortality in patients with ACS were included. Pooled effect was expressed as risk ratios (RR) with 95% confidence intervals (CI) for the highest versus the reference lower MHR group.

Results: Eight studies involving 6,480 patients with ACS were included and analyzed. Meta-analysis indicated that the highest MHR was significantly associated with higher risk of MACE (RR 1.65; 95%CI 1.36-2.02) and all-cause mortality (RR 2.61; 95%CI 1.29-4.89) after adjusting for the conventional confounders. The prognostic values of MACE with the highest MHR caused no significant changes in the in-hospital follow-up (RR 1.76; 95%CI 1.34-2.32) and >6 months follow-up (RR 1.68; 95%CI 1.08-2.62) subgroups. Furthermore, ST elevation myocardial infarction patients with the highest MHR had a 2.07-fold higher risk of in-hospital MACE (RR 2.07; 95%CI 1.52-2.80).

Conclusions: Elevated MHR is independently associated with an increased risk of MACE and all-cause mortality in patients with ACS. MHR may serve as a potential prognostic indicator for ACS prognosis.
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http://dx.doi.org/10.1016/j.amjms.2020.01.018DOI Listing
May 2020

Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding.

Elife 2020 03 31;9. Epub 2020 Mar 31.

National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Mammalian mitochondrial inner membrane fusion is mediated by optic atrophy 1 (OPA1). Under physiological conditions, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (L-OPA1) and a soluble short isoform (S-OPA1). A combination of L-OPA1 and S-OPA1 is essential for efficient membrane fusion; however, the relevant mechanism is not well understood. In this study, we investigate the cryo-electron microscopic structures of S-OPA1-coated liposomes in nucleotide-free and GTPγS-bound states. S-OPA1 exhibits a general dynamin-like structure and can assemble onto membranes in a helical array with a dimer building block. We reveal that hydrophobic residues in its extended membrane-binding domain are critical for its tubulation activity. The binding of GTPγS triggers a conformational change and results in a rearrangement of the helical lattice and tube expansion similar to that of S-Mgm1. These observations indicate that S-OPA1 adopts a dynamin-like power stroke membrane remodeling mechanism during mitochondrial inner membrane fusion.
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http://dx.doi.org/10.7554/eLife.50294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156267PMC
March 2020

The fate and toxicity of Pb-based perovskite nanoparticles on soil bacterial community: Impacts of pH, humic acid, and divalent cations.

Chemosphere 2020 Jun 19;249:126564. Epub 2020 Mar 19.

Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, 2300, RA, Leiden, the Netherlands.

Pb-based perovskite nanoparticles (PbPNPs) are amongst others used within highly efficient solar cells. PbPNPs can be released into the environment during their production, recycling or waste processing. In this study we investigated the fate and toxicity of PbPNPs on soil bacterial community under simulated natural environmental conditions across a range of pH, humic acid, and divalent cation concentrations. Increasing pH decreased PbPNPs-particle aggregation as well as Pb-ion release. The presence of only humic acid (HA) prevented the aggregation of PbPNPs-particles, whereas the presence of only divalent cations promoted the aggregation of PbPNPs-particles. The amount of Pb-ions released from the PbPNPs-particles was reduced in the presence of either HA or the divalent cations. Results of toxicity testing of PbPNPs by determining the metabolic potential of a bacterial community indicated that increasing pH alleviated particle toxicity. The presence of only HA reduced the toxicity of PbPNPs, while the presence of only divalent cations enhanced the particle toxicity. The coexistence of HA and divalent cations enhanced PbPNPs aggregation and reduced toxicity, with both Pb-ions and the interaction between the PbPNPs-particles and bacterial cells contributing to the toxic effects. Our study emphasized that environmental conditions play important roles that influencing the fate and toxicity of PbPNPs.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126564DOI Listing
June 2020

Passive Smoking Exposure in Living Environments Reduces Cognitive Function: A Prospective Cohort Study in Older Adults.

Int J Environ Res Public Health 2020 02 21;17(4). Epub 2020 Feb 21.

Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032, China.

There is currently no consensus regarding the effects of passive smoking exposure on cognitive function in older adults. We evaluated 7000 permanent residents from six regions within Zhejiang Province, China, aged ≥60 years, without cognitive impairment at baseline and during follow-up examinations for two years. The Chinese version of the Mini-Mental State Examination was used to assess the participants' cognitive function. Multivariate regression analyses were carried out to calculate the adjusted relative risks (RRs) as measures of the association between passive smoking exposure and cognitive impairment after adjusting for potential confounders. The results showed an association between passive smoking exposure in the living environment and increased risk of cognitive impairment (RR: 1.16; 95% confidence interval (CI): 1.01-1.35). No dose-response relationship between the cumulative dose of passive smoking exposure (days) and cognitive impairment was observed. The results of stratified analyses suggested a harmful effect of passive smoking exposure on cognitive function in non-smokers (RR: 1.24; 95% CI: 1.06-1.46), but not in smokers (RR: 1.11; 95% CI: 0.71-1.92). Therefore, passive smoking exposure increased the risk of cognitive impairment in older adults, especially non-smokers. More effective measures to restrict smoking in the living environment should be developed and implemented.
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http://dx.doi.org/10.3390/ijerph17041402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068506PMC
February 2020

Spatial and temporal analysis of severe fever with thrombocytopenia syndrome in Zhejiang Province, China, 2011 - 2015.

J Infect Dev Ctries 2019 01 31;13(1):35-43. Epub 2019 Jan 31.

Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Binjiang District, Hangzhou 310051, Zhejiang, China.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease first discovered in northeast and central China in 2009, and SFTS cases increased year by year in China. This study aimed to identify the spatial and temporal clusters of SFTS in Zhejiang Province, China.

Methodology: We analyzed the surveillance data of SFTS in Zhejiang Province during 2011 - 2015. Descriptive statistics were used to analyze the general characteristics and overall trend of SFTS. Circular statistic method was utilized to identify the seasonality. Space-time scan analysis was performed to explore the high risk spatio-temporal clusters of SFTS cases at county level.

Results: A total of 194 confirmed SFTS cases were reported in Zhejiang Province during 2011 - 2015. We found a significant increase in overall time trend since 2011. The seasonality was statistically significant (P < 0.001), with a mean date (95% CI) of 21st June (12th ~ 30th in June). Totally 21 (23%) counties reported the occurrence of SFTS, which gradually spread throughout Zhejiang. Three spatio-temporal clusters were detected, with one principle cluster (Daishan County, RR 234.48, June 2013 - November 2015) and two secondary clusters (6 counties, RR 30.73, April - October in 2015; Anji County, RR 373.26, May 2014).

Conclusions: Our results suggested that SFTS has increased and spatially expanded over the past years, with a remarkable seasonality. Three spatio-temporal clusters were identified. These findings are important for the improvement of SFTS surveillance and control strategies.
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http://dx.doi.org/10.3855/jidc.10373DOI Listing
January 2019

An across-species comparison of the sensitivity of different organisms to Pb-based perovskites used in solar cells.

Sci Total Environ 2020 Mar 21;708:135134. Epub 2019 Nov 21.

Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, 2300 RA, Leiden, the Netherlands; National Institute of Public Health and the Environment (RIVM), P.O. Box 1, Bilthoven, the Netherlands.

Organic-inorganic perovskite solar cells (PSCs) are promising candidates as photovoltaic cells. Recently, they have attracted significant attention due to certified power conversion efficiencies exceeding 23%, low-cost engineering, and superior electrical/optical characteristics. These PSCs extensively utilize a perovskite-structured composite with a hybrid of Pb-based nanomaterials. Operation of them may cause the release of Pb-based nanoparticles. However, limited information is available regarding the potential toxicity of Pb-based PSCs on various organisms. This study conducted a battery of in vitro and in vivo toxicity bioassays for three quintessential Pb-based PSCs (CHNHPbI, NHCHNHPbBr, and CHNHPbBr) using progressively more complex forms of life. For all species tested, the three different perovskites had comparable toxicities. The viability of Caco-2/TC7 cells was lower than that of A549 cells in response to Pb-based PSC exposure. Concentration-dependent toxicity was observed for the bioluminescent bacterium Vibrio fischeri, for soil bacterial communities, and for the nematode Caenorhabditis elegans. Neither of the tested Pb-based PSCs particles had apparent toxicity to Pseudomonas putida. Among all tested organisms, V. fischeri showed the highest sensitivity with EC values (30 min of exposure) ranging from 1.45 to 2.91 mg L. Therefore, this study recommends that V. fischeri should be preferably utilized to assess. PSC toxicity due to its increased sensitivity, low costs, and relatively high throughput in a 96-well format, compared with the other tested organisms. These results highlight that the developed assay can easily predict the toxic potency of PSCs. Consequently, this approach has the potential to promote the implementation of the 3Rs (Replacement, Reduction, and Refinement) principle in toxicology and decrease the dependence on animal testing when determining the safety of novel PSCs.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135134DOI Listing
March 2020

Risk Factors for Depression in Empty Nesters: A Cross-Sectional Study in a Coastal City of Zhejiang Province and China.

Int J Environ Res Public Health 2019 10 24;16(21). Epub 2019 Oct 24.

Wenling Center for Disease Control and Prevention, Wenling 317500, China.

The elderly are susceptible to depression, especially empty nesters. This study investigated the risk factors associated with depression in empty nesters. The participants were selected via multi-stage random cluster sampling. Depression symptoms were assessed using the Geriatric Depression Scale. The questionnaire surveyed demographic characteristics, underlying diseases, behaviors and lifestyles, negative life experiences, social support, self-care ability, etc. Chronic health conditions, such as being overweight/obese, smoking cessation, cancer, and chronic pain, as well as negative life experiences, such as the death of a loved one and financial loss, increased the risk of depression in empty nesters. In addition, the incapability of performing self-care also increased the risk of depression in empty nesters. The prevalence of depression in empty nesters was high. Being overweight/obese, cancer, chronic pain, smoking cessation, the death of a loved one, financial loss, and the incapability to deliver self-care were risk factors for depression in empty nesters. It is recommended that comprehensive measures be taken to enhance health interventions for this population, including encouraging a proper diet and physical activity for weight control, providing psychological counseling after negative life experiences, and teaching correct methods of smoking cessation.
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http://dx.doi.org/10.3390/ijerph16214106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862174PMC
October 2019

Compositional alterations in soil bacterial communities exposed to TiO nanoparticles are not reflected in functional impacts.

Environ Res 2019 11 2;178:108713. Epub 2019 Sep 2.

Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, 2300, RA, Leiden, the Netherlands.

Titanium dioxide nanoparticles (TiONP) are increasingly released in soil ecosystems, while there is limited understanding of the impacts of TiONP on soil bacterial communities. Here we investigated the effects of TiONP on the taxonomic composition and functional profile of a soil bacterial community over a 60-day exposure period. In short-term exposure (1-day), contradictory effects on the taxonomic composition of soil bacterial communities were found after exposure to a low realistic environmental concentration of TiONP at 1 mg/kg as compared to the effects induced by medium and high concentrations of TiONP at 500 and 2000 mg/kg. After long-term exposure (60-day), the negative effects of TiONP at the low concentration disappeared, and the inhibition by TiONP of the abundance of core taxa was enhanced along with increasing exposure concentrations. However, although significant alterations were observed in the taxonomic composition over time and exposure concentrations, no significant change was observed in the community functional profile as well as enzyme activity after 60-day exposure, indicating that functional redundancy likely contributed to the bacterial community tolerance after the exposure to TiONP. Our study highlighted the importance of assessing bacterial community compositional and functional responses in assessing the environmental risk of nanoparticles on soil ecosystems.
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http://dx.doi.org/10.1016/j.envres.2019.108713DOI Listing
November 2019

Subtypes of Park Use and Self-Reported Psychological Benefits Among Older Adults: A Multilevel Latent Class Analysis Approach.

Landsc Urban Plan 2019 Oct 3;190. Epub 2019 Jul 3.

College of Architecture and Urban Planning, Big Data and Urban Spatial Analytics Lab, Tongji University, China.

Healthy aging is a global health priority. Urban parks and green space have been demonstrated to provide mental health benefits to older adults. Despite growing interest in prescribing nature and park visits by physicians, we do not know what type of park visit is most effective for the psychological benefits. This lack of knowledge prevents planners and designers from making informed decisions to promote mental health. We collected field data from 200 visitors from 15 different parks in Shanghai, China. The participants completed pre-visit and post-visit surveys, wearing a GPS and a pedometer while visiting the park. A multilevel latent class analysis (LCA) yielded a three-class structure of park use patterns: the active park lingerer, the active walker, and the passive scanner. Paired-sample t-test and ANCOVA tests showed that affective states (i.e., anxiety, depression, relaxation, contention) were enhanced after park visits for all subtypes. However, the active park lingerer displayed significantly higher levels of relaxation and contention, compared to the active walker and the passive scanner. The findings offer insights into park design characteristics that could promote the mental health of older adults.
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http://dx.doi.org/10.1016/j.landurbplan.2019.103605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656528PMC
October 2019

Pluronic F127-functionalized molybdenum oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy.

J Colloid Interface Sci 2019 Oct 20;553:567-580. Epub 2019 Jun 20.

Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China. Electronic address:

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W/[W + W]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.
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http://dx.doi.org/10.1016/j.jcis.2019.06.066DOI Listing
October 2019

The progresses in curcuminoids-based metal complexes: especially in cancer therapy.

Future Med Chem 2019 05 29;11(9):1035-1056. Epub 2019 May 29.

College of Pharmacy, Department of Pharmaceutics, Shandong University, Jinan 250012, PR China.

Curcuminoids (CURs), a series of derivatives in turmeric (), are commonly discovered to control the deterioration of cancers. However, the physiochemical properties and the original side effects of many CURs complexes put barriers in their medical applications. To address them, the investigation of metal-based complexes with CURs is in progress. The complexes were summarized according to articles in recent years. The results showed that the complexes improved the physicochemical properties or therapeutic performances compared with pure CURs. Further, it is possible for the novel complexes to be applied in chemical detecting, paramagnetic-luminescent and bio-imaging fields. Therefore, the formation of the metal-based CURs complexes (MBCCs) is beneficial for the development of CURs especially in medical fields.
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http://dx.doi.org/10.4155/fmc-2018-0190DOI Listing
May 2019

Preparation and Properties of Polyvinylidene Fluoride Nanocomposited Membranes based on Poly(-Isopropylacrylamide) Modified Graphene Oxide Nanosheets.

Polymers (Basel) 2019 Mar 12;11(3). Epub 2019 Mar 12.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.

The nanomaterial of graphene oxide grafting poly (-isopropylacrylamide) (GO-g-PNIPAAm) was synthesized and PVDF/GO-g-PNIPAAm blended membranes were fabricated by wet phase inversion. In this work, a hydrophilic nanomaterial GO-g-PNIPAAm with poly(-isopropylacrylamide) (PNIPAAm) grafted on GO, was synthesized by the atom transfer radical polymerization (ATRP) method. The resulting nanomaterial was confirmed by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectrum, and X-ray photoelectron spectroscopy (XPS) analysis. The synthesized GO-g-PNIPAAm was incorporated with polyvinylidene fluoride (PVDF) via phase inversion, and investigated for its temperature sensitivity, porosity, contact angle, scanning electron microscopy, and permeate properties. The water contact angle measurements confirmed that GO-g-PNIPAAm nanomaterial-endowed PVDF membranes with better hydrophilicity and thermo-responsive properties compared with those of the pristine PVDF membranes. Bovine serum albumin (BSA) adsorption experiments suggested that excellent antifouling properties of membranes were acquired after adding GO-g-PNIPAAm. The modified membranes showed good performance when the doping amount of GO-g-PNIPAAm was 0.2 wt %.
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http://dx.doi.org/10.3390/polym11030473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474125PMC
March 2019

Salidroside attenuates oxidized low‑density lipoprotein‑induced endothelial cell injury via promotion of the AMPK/SIRT1 pathway.

Int J Mol Med 2019 Jun 1;43(6):2279-2290. Epub 2019 Apr 1.

Department of Cardiovascular, Affiliated Hospital of Beihua University, Jilin, Jilin 132011, P.R. China.

Oxidized low‑density lipoprotein (ox‑LDL)‑induced endothelial damage contributes to the initiation and pathogenesis of atherosclerosis. Salidroside can alleviate atherosclerosis and attenuate endothelial cell injury induced by ox‑LDL. However, the mechanisms involved in this process are not fully understood. Therefore, the purpose of the present study was to investigate the role of the adenosine monophosphate‑activated protein kinase (AMPK)/sirtuin (SIRT)1 pathway in the protection of salidroside against ox‑LDL‑induced human umbilical vein endothelial cells (HUVECs) injuries. The results revealed that salidroside reverses ox‑LDL‑induced HUVECs injury as demonstrated by the upregulation of cell viability and downregulation of LDH release. In addition, salidroside increased the expression of the SIRT1 protein in ox‑LDL‑treated HUVECs. Next, it was demonstrated that SIRT1 knockdown induced by transfection with small interfering (si)RNA targeting SIRT1 (siSRT1) abolished the protection of salidroside against ox‑LDL‑induced HUVECs injuries. This was illustrated by a decrease in cell viability and an increase in LDH release, caspase‑3 activity and apoptosis rate. Furthermore, salidroside mitigated ox‑LDL‑induced reactive oxygen species production, upregulated malondialdehyde content and NADPH oxidase 2 expression and decreased superoxide dismutase and glutathione peroxidase activities, while these effects were also reversed by siSIRT1 transfection. In addition, it was demonstrated that salidroside suppressed ox‑LDL‑induced mitochondrial dysfunction as demonstrated by the increase in mitochondrial membrane potential and decreases in cytochrome c expression, and Bax/Bcl‑2 reductions. However, these effects were eliminated by SIRT1 knockdown. Finally, it was demonstrated that salidroside significantly upregulated the phosphorylated‑AMPK expression in ox‑LDL‑treated HUVECs and AMPK knockdown induced by transfection with AMPK siRNA (siAMPK) leads to elimination of the salidroside‑induced increase in cell viability and the decrease in LDH release. Notably, siAMPK transfection further decreased the expression of SIRT1. In conclusion, these results suggested that salidroside protects HUVECs against ox‑LDL injury through inhibiting oxidative stress and improving mitochondrial dysfunction, which were dependent on activating the AMPK/SIRT1 pathway.
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http://dx.doi.org/10.3892/ijmm.2019.4153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488166PMC
June 2019

Repeated restraint stress upregulates rat sulfotransferase 1A1.

J Basic Clin Physiol Pharmacol 2018 Dec 20;30(2):265-273. Epub 2018 Dec 20.

Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74074, USA, Phone: +405-744-2349.

BackgroundSulfotransferases (SULTs) are phase II drug-metabolizing enzymes. SULTs also regulate the biological activities of biological signaling molecules, such as various hormones, bile acids, and monoamine neurotransmitters; therefore, they play critical roles in the endocrine and nervous systems. People are subject to various kinds of physical, chemical, toxicological, physiological, and psychological stresses at one time or another. The study of the effects produced by stress may lead to finding novel remedies for many disease conditions. The effect of repeated restraint stress on rat SULT expression has not been studied. MethodsThis study involves the effect of repeated restraint stress on SULT1A1 expressions. Male Sprague-Dawley rats (n=4) were subjected to repeated restraint stress 2 h/day for 7 days. Protein and RNA expression of SULT1A1 were analyzed by western blot and quantitative real time reverse transcription polymerase chain reaction, respectively, in important tissues. ResultsWe observed that repeated restraint stress increased the expression of SULT1A1 in the liver, adrenal glands, cerebellum, hypothalamus, and cerebral cortex in male rats. Patterns of enhanced expression were observed at both mRNA and protein level, indicating that repeated restraint stress stimulates enzyme expression at the transcriptional level. ConclusionsChanges of SULT1A1 expression in important tissues caused by repeated restraint stress will have a significant effect on drug metabolism and xenobiotics detoxification. The significant changes in endocrine glands and brain sections may also cause disturbances in hormone homeostasis, therefore leading to disease conditions. This report provides clues for the understanding of the effect of stresses on health.
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http://dx.doi.org/10.1515/jbcpp-2016-0038DOI Listing
December 2018

New interfaces on MiD51 for Drp1 recruitment and regulation.

PLoS One 2019 31;14(1):e0211459. Epub 2019 Jan 31.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Mitochondrial fission is facilitated by dynamin-related protein Drp1 and a variety of its receptors. However, the molecular mechanism of how Drp1 is recruited to the mitochondrial surface by receptors MiD49 and MiD51 remains elusive. Here, we showed that the interaction between Drp1 and MiD51 is regulated by GTP binding and depends on the polymerization of Drp1. We identified two regions on MiD51 that directly bind to Drp1, and found that dimerization of MiD51, relevant to residue C452, is required for mitochondrial dynamics regulation. Our Results have suggested a multi-faceted regulatory mechanism for the interaction between Drp1 and MiD51 that illustrates the potentially complicated and tight regulation of mitochondrial fission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211459PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355003PMC
November 2019