Publications by authors named "Ying Du"

278 Publications

N6-methyladenosine demethylase FTO impairs hepatic ischemia-reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation.

Cell Death Dis 2021 May 4;12(5):442. Epub 2021 May 4.

Department of Hepatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia-reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.
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http://dx.doi.org/10.1038/s41419-021-03622-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096847PMC
May 2021

Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease.

Front Neurol 2021 15;12:595984. Epub 2021 Apr 15.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Neuro Behçet's disease (NBD) is a rare but most aggressive manifestation of Behçet's disease (BD) with a poor prognosis, and some patients even present a relapsing and treatment-resistant progressive course. In some relapsing NBD cases, traditional corticosteroids and immunosuppressive drugs show limited efficacy, while benefits of biological agents, such as anti-B-lymphocyte CD20 biological agent rituximab (RTX), gradually represent potential therapeutic advantages with clinical rapid remission and long-time maintenance. However, up to now, the optimal dosage of RTX in NBD is still elucidated. Here, we report two patients with relapsing NBD, despite continuous high dose steroids and sufficient azathioprine treatment, still presenting severe and relapsing meningoencephalitis or brainstem involvement. Repeated low-dose RTX (100 mg × 3/1 week apart, 100 mg repeated every 6 months) is then attempted with rapid recovery and sustained remission. The approach in our cases may expand therapeutic options and provide helpful references for relapsing NBD treatment.
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http://dx.doi.org/10.3389/fneur.2021.595984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081882PMC
April 2021

Design, synthesis and antifungal/anti-oomycete activity of pyrazolyl oxime ethers as novel potential succinate dehydrogenase inhibitors.

Pest Manag Sci 2021 Apr 19. Epub 2021 Apr 19.

Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, China.

Background: Succinate dehydrogenase inhibitors (SDHIs) play an increasingly important role in controlling plant diseases. However, the similar structures of SDHIs result in rapid development of cross-resistance development and a clear bottleneck of poor activity against oomycetes, therefore the need to seek new SDHI fungicides with novel structures is urgent.

Results: Innovative pyrazolyl oxime ethers were designed by replacing amide with oxime ether based on the succinate dehydrogenase (SDH) structure, and 19 pairs of Z- and E-isomers were efficiently prepared for the discovery of SDHI compounds with a novel bridge. Their biological activities against four fungi and two oomycetes were evaluated, and substantial differences were observed between the Z- and E- isomers of the title compounds. Furthermore, most of these compounds exhibited remarkable activities against Rhizoctonia solani with EC values of less than 10 mg L in vitro, and bioassay in vivo further confirmed that E-I-6 exhibited good protective efficacy (76.12%) at 200 mg L . In addition, Z-I-12 provided better activity against the oomycetes Pythium aphanidermatum and Phytophthora capsici (EC  = 1.56 and 0.93 mg L ) than those of boscalid. Moreover, E-I-12 exhibited excellent SDH inhibition (IC  = 0.21 mg L ) thanks to its good binding ability to the SDH by hydrogen-bonding interactions, π-cation interaction and hydrophobic interactions.

Conclusion: Novel pyrazolyl oxime ethers have the potential as SDHI compounds for future development, and the strategy of replacing an amide bond with oxime ether may offer an alternative option in SDHI fungicide discovery.
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http://dx.doi.org/10.1002/ps.6418DOI Listing
April 2021

IGF2 deficiency causes mitochondrial defects in skeletal muscle.

Clin Sci (Lond) 2021 Apr;135(7):979-990

Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Exercise training improves muscle fitness in many aspects, including induction of mitochondrial biogenesis and maintenance of mitochondrial dynamics. The insulin-like growth factors were recently proposed as key regulators of myogenic factors to regulate muscle development. The present study aimed to investigate the physical exercise impact on insulin-like growth factor 2 (IGF2) and analyzed its functions on skeletal muscle cells in vitro. Using online databases, we stated that IGF2 was relatively highly expressed in skeletal muscle cells and increased after exercise training. Then, IGF2 deficiency in myotubes from C2C12 and primary skeletal muscle cells (PMSCs) led to impaired mitochondrial function, reduced mitochondria-related protein content, and decreased mitochondrial biogenesis. Furthermore, we explored the possible regulatory pathway and found that mitochondrial regulation in skeletal muscle cells might occur through IGF2-Sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) signaling pathway. Therefore, the present study first demonstrated the relationship between IGF2 and mitochondria in skeletal muscle.
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http://dx.doi.org/10.1042/CS20210128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055961PMC
April 2021

Current applications of platelet gels in wound healing-A review.

Wound Repair Regen 2021 Mar 22. Epub 2021 Mar 22.

Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Human platelets play important roles in several physiologic and pathologic processes. Platelet concentrates are activated with thrombin or calcium, resulting in a viscous coagulum (platelet gel [PG]), composed of 95% platelets at least. PG is increasingly used for the treatment of a variety of soft and hard tissue defects, most notably in the management of chronic non-healing wounds. During wound healing, platelets not only play a critical role in primary hemostasis and thrombosis, but also release growth factors and cytokines to promote tissue regeneration, enhance collagen synthesis, and trigger an immune response. This review addresses a variety of aspects relevant to the functions of well-known platelet growth factors, animal and clinical studies of PG in the last decade, and different sources of platelets for PG. PG is used for non-healing chronic wounds, such as oral ulcerations related to epidermolysis bullosa and chronic graft-versus-host disease, for those, the traditional treatment effect is poor. PG maybe provide a new therapeutic direction for these diseases. Nevertheless, some uncertainty is present, the number of clinical studies is not enough. Hence, randomized controlled trials are still required to study the potential of the use of PG in the near future.
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http://dx.doi.org/10.1111/wrr.12896DOI Listing
March 2021

Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study.

Diabetologia 2021 May 9;64(5):1066-1078. Epub 2021 Mar 9.

Department of Endocrinology, West China Hospital Sichuan University, Sichuan, China.

Aims/hypothesis: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes.

Methods: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 μg) for 12 weeks. The primary endpoint was the change in HbA from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug.

Results: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 μg, 150 μg and 200 μg groups). At the end of 12 weeks, mean differences in HbA in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 μg, 150 μg and 200 μg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death.

Conclusions/interpretation: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes.

Trial Registration: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.
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http://dx.doi.org/10.1007/s00125-021-05392-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012337PMC
May 2021

A Positive Role of Negative Mood on Creativity: The Opportunity in the Crisis of the COVID-19 Epidemic.

Front Psychol 2020 20;11:600837. Epub 2021 Jan 20.

Ministry of Education Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, China.

The COVID-19 epidemic is associated with negative mood, which has the potential to be a powerful driver of creativity. However, the influence of negative mood on cognitive creativity and emotional creativity remains elusive. Previous research has indicated that self-focused attention is likely to be related to both negative mood and creativity. The current study introduced two self-focused attention variables (i.e., rumination, reflection) to explore how negative mood might contribute to cognitive creativity and emotional creativity. Based on a sample of 351 participants, our study found that (1) negative mood during the outbreak of COVID-19 was associated with cognitive creativity and emotional creativity. Meanwhile, there were significant serial mediation effects of rumination and reflection in the relationship between negative mood and creativity and (2) the psychological impact after exposure to the COVID-19 epidemic was positively correlated with emotional creativity but not with cognitive creativity. These results suggested that individuals, in real life and work, could achieve better creative performance through moderate self-focus. Moreover, individuals with different mood states can be induced to enhance their creativity in times of crisis through intervention training to promote reflection.
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http://dx.doi.org/10.3389/fpsyg.2020.600837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854895PMC
January 2021

Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series.

BMC Neurol 2021 Jan 11;21(1):12. Epub 2021 Jan 11.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an City, 710038, Shaanxi Province, China.

Background: SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described.

Methods: In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients.

Results: By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language.

Conclusions: The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.
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http://dx.doi.org/10.1186/s12883-020-02040-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798194PMC
January 2021

A Review of Biomimetic Nanoparticle Drug Delivery Systems Based on Cell Membranes.

Drug Des Devel Ther 2020 14;14:5495-5503. Epub 2020 Dec 14.

Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province 210009, People's Republic of China.

Cancers have always been an intractable problem because of recurrence and drug resistance. In the past few decades, nanoparticles have been explored intensely to diagnose, prevent and treat malignancy due to their good penetrability and better targeting. However, most nanocarriers have poor biodegradation and can be discharged out of the body quickly or cleared by immune cells while failing to obtain effective drug concentration at the specific sites. The emergence of biological membrane encapsulation technology relieves the fast clearance of antitumor drugs and reduces toxicity in vivo. This review will discuss the advantages and disadvantages of several blood cell membrane-coated nanoparticles and further introduce exosome-carried drugs to evidence the promising prospect of biomimetic nanoparticle drug delivery systems.
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http://dx.doi.org/10.2147/DDDT.S282368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753887PMC
December 2020

The changed functional status of the brain was involved in patients with poststroke aphasia: Coordinate-based (activation likelihood estimation) meta-analysis.

Brain Behav 2020 12 6;10(12):e01867. Epub 2020 Oct 6.

Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Background And Purpose: Although many functional magnetic resonance imaging (fMRI) studies have investigated the language architecture and neurobiological mechanism underlying poststroke aphasia (PSA), the pathophysiological mechanisms of PSA still remain poorly understood. In addition to a limited number of subjects (<20) tested with different methodologies and stimuli, inconsistent reports of the brain regions involved have been a major factor. Thus, we conducted a meta-analysis of 12 peer-reviewed studies of abnormal brain activation regions in PSA patients at rest using activation likelihood estimation (ALE).

Results: A meta-analysis was performed based on 24 experiments with 497 total participants in 12 studies to establish the ALE of regional activation in PSA. Through experiments with PSA patients and healthy controls, we found that hypoactivation in PSA converged on the left superior frontal gyrus and the left parietal postcentral gyrus, whereas there was hyperactivation in the right cerebellar anterior lobe, left fusiform gyrus, left superior parietal lobule, and right subgyral hippocampus.

Conclusion: Our study verified that dominant and nondominant language networks play roles in the recovery of language function.
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http://dx.doi.org/10.1002/brb3.1867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749604PMC
December 2020

Identification of key gene modules and genes in colorectal cancer by co-expression analysis weighted gene co-expression network analysis.

Biosci Rep 2020 09;40(9)

Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Colorectal cancer (CRC) has been one of the most common malignancies worldwide, which tends to get worse for the growth and aging of the population and westernized lifestyle. However, there is no effective treatment due to the complexity of its etiology. Hence, the pathogenic mechanisms remain to be clearly defined. In the present study, we adopted an advanced analytical method-Weighted Gene Co-expression Network Analysis (WGCNA) to identify the key gene modules and hub genes associated with CRC. In total, five gene co-expression modules were highly associated with CRC, of which, one gene module correlated with CRC significantly positive (R = 0.88). Functional enrichment analysis of genes in primary gene module found metabolic pathways, which might be a potentially important pathway involved in CRC. Further, we identified and verified some hub genes positively correlated with CRC by using Cytoscape software and UALCAN databases, including PAICS, ATR, AASDHPPT, DDX18, NUP107 and TOMM6. The present study discovered key gene modules and hub genes associated with CRC, which provide references to understand the pathogenesis of CRC and may be novel candidate target genes of CRC.
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http://dx.doi.org/10.1042/BSR20202044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463304PMC
September 2020

Anti-proliferative effects of diterpenoids from L. tubers on colon cancer cells by targeting the NF-κB pathway.

Food Funct 2020 Sep;11(9):7717-7726

College of Biotechnology, Guilin Medical University, Guilin 541100, China.

A new labdane-type diterpenoid, ent-19-ol-13-epi-manoyl oxide,19-undecane ester, together with ten known diterpenes, were isolated from the ethanolic crude extract of the fresh tubers of Sagittaria trifolia L. The chemical structures of these compounds were determined by extensive 2-D NMR experiments and by comparison with the data reported in the literature. These compounds showed different inhibitory effects on various human cancer cells. Among these, compound 11 exhibited potential inhibition effects against human colon cancer cells. Moreover, flow cytometry demonstrated that compound 11 arrested the cell cycle at the G1 phase and induced cellular apoptosis, accompanied by mitochondrial membrane potential reduction. Mechanistic studies revealed that treatment with compound 11 inhibited IKKα/β phosphorylation and IκBα phosphorylation, which subsequently caused the blockage of NF-κB p65 phosphorylation and nuclear translocation. Compound 11 also inhibited the expression of c-Myc, Cyclin D1, and Bcl-2, the downstream targets of NF-κB. Therefore, our findings provided insight into the anticancer components of Sagittaria trifolia L. tubers, which could facilitate their utilization as functional food ingredients.
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http://dx.doi.org/10.1039/d0fo00228cDOI Listing
September 2020

Preparation and Characterization of Furan-Matrix Composites Blended with Modified Hollow Glass Microsphere.

Polymers (Basel) 2020 Jul 1;12(7). Epub 2020 Jul 1.

School of Material Science and Engineering, Tianjin University, Tianjin 300350, China.

In this study, a new class of thermal insulation composites was prepared by blending a modified hollow glass microsphere (HGM) with furan resin. The particle dispersion between the microparticles and resin matrix was improved using 3-methacryloxypropyltrimethoxy silane (KH-570). Furthermore, the structure and morphology of the modified HGM were characterised by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). In addition, the effects of the modified HGM on the thermal insulation, flame retardancy, and thermal properties of the composites were investigated. The thermal conductivity of the composites was lower than that of the native furan resin. The minimum thermal conductivity of the composites was 0.0274 W/m·K; the flame retardancy of the composites improved, and the limiting oxygen index become a maximum of 31.6%, reaching the refractory material level. Furthermore, the thermal analysis of the composites demonstrated enhanced thermal stability. This study demonstrates that the composite material exhibited good thermal insulation performance and flame retardancy and that it can be applied in the field of thermal insulation.
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http://dx.doi.org/10.3390/polym12071480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407303PMC
July 2020

The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells.

EMBO J 2020 07 25;39(13):e103786. Epub 2020 May 25.

Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Lgr5 intestinal stem cells (ISCs) exhibit self-renewal and differentiation features under homeostatic conditions, but the mechanisms controlling Lgr5 + ISC self-renewal remain elusive. Here, we show that the chromatin remodeler SRCAP is highly expressed in mouse intestinal epithelium and ISCs. Srcap deletion impairs both self-renewal of ISCs and intestinal epithelial regeneration. Mechanistically, SRCAP recruits the transcriptional regulator REST to the Prdm16 promoter and induces expression of this transcription factor. By activating PPARδ expression, Prdm16 in turn initiates PPARδ signaling, which sustains ISC stemness. Rest or Prdm16 deficiency abrogates the self-renewal capacity of ISCs as well as intestinal epithelial regeneration. Collectively, these data show that the SRCAP-REST-Prdm16-PPARδ axis is required for self-renewal maintenance of Lgr5 + ISCs.
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http://dx.doi.org/10.15252/embj.2019103786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327502PMC
July 2020

The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection.

Front Immunol 2020 28;11:669. Epub 2020 Apr 28.

Center for Infectious Disease Research, Seattle, WA, United States.

The RTS,S/AS01 vaccine provides partial protection against infection but determinants of protection and/or disease are unclear. Previously, anti-circumsporozoite protein (CSP) antibody titers and blood RNA signatures were associated with RTS,S/AS01 efficacy against controlled human malaria infection (CHMI). By analyzing host blood transcriptomes from five RTS,S vaccination CHMI studies, we demonstrate that the transcript ratio MX2/GPR183, measured 1 day after third immunization, discriminates protected from non-protected individuals. This ratiometric signature provides information that is complementary to anti-CSP titer levels for identifying RTS,S/AS01 immunized people who developed protective immunity and suggests a role for interferon and oxysterol signaling in the RTS,S mode of action.
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http://dx.doi.org/10.3389/fimmu.2020.00669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199517PMC
March 2021

A Counter Propagating Lens-Mirror System for Ultrahigh Throughput Single Droplet Detection.

Small 2020 05 20;16(20):e1907534. Epub 2020 Apr 20.

Institute for Chemical and Bioengineering, ETH Zürich, Vladimir-Prelog-Weg 1, Zurich, 8093, Switzerland.

Fluorescence-based detection schemes provide for multiparameter analysis in a broad range of applications in the chemical and biological sciences. Toward the realization of fully portable analysis systems, microfluidic devices integrating diverse functional components have been implemented in a range of out-of-lab environments. That said, there still exits an unmet and recognized need for miniaturized, low-cost, and sensitive optical detection systems, which provide not only for efficient molecular excitation, but also enhanced photon collection capabilities. To this end, an optofluidic platform that is adept at enhancing fluorescence light collection from microfluidic channels is presented. The central component of the detection module is a monolithic parabolic mirror located directly above the microfluidic channel, which acts to enhance the number of emitted photons reflected toward the detector. In addition, two-photon polymerization is used to print a microscale-lens below the microfluidic flow channel and directly opposite the mirror, to enhance the delivery of excitation radiation into the channel. Using such an approach, it is demonstrated that fluorescence signals can be enhanced by over two orders of magnitude, with component parallelization enabling the detection of pL-volume droplets at rates up to 40 000 droplets per second.
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http://dx.doi.org/10.1002/smll.201907534DOI Listing
May 2020

Yeast chromatin remodeling complexes and their roles in transcription.

Curr Genet 2020 Aug 1;66(4):657-670. Epub 2020 Apr 1.

Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada.

The nucleosome is a small unit of chromatin, which is dynamic in eukaryotes. Chromatin conformation and post-translational modifications affect nucleosome dynamics under certain conditions, playing an important role in the epigenetic regulation of transcription, replication and reprogramming. The Snf2 remodeling family is one of the crucial remodeling complexes that tightly regulate chromatin structure and affect nucleosome dynamics. This family alters nucleosome positioning, exchanges histone variants, and assembles and disassembles nucleosomes at certain locations. Moreover, the Snf2 family, in conjunction with other co-factors, regulates gene expression in Saccharomyces cerevisiae. Here we first review recent findings on the Snf2 family remodeling complexes and then use some examples to illustrate the cooperation between different members of Snf2 family, and the cooperation between Snf2 family and other co-factors in gene regulation especially during transcription initiation.
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http://dx.doi.org/10.1007/s00294-020-01072-0DOI Listing
August 2020

Long non-coding RNA colon cancer-associated transcript-1 regulates tumor cell proliferation and invasion of non-small-cell lung cancer through suppressing miR-152.

Geriatr Gerontol Int 2020 Jun 30;20(6):629-636. Epub 2020 Mar 30.

Department of Clinical Medicine, College of Medicine, Pingdingshan University, Pingdingshan, China.

Aim: Lung cancer serves as one of the most common cancers in the world, and approximately 50% of non-small-cell lung cancer (NSCLC) patients are found to be aged >70 when diagnosed. In this study, we aimed to explore the effect of long non-coding RNAs colon cancer-associated transcript-1 (CCAT1) in NSCLC.

Methods: A total of 72 clinical samples from older NSCLC patients were collected for analysis. The relative mRNA level of CCAT1 was detected through real-time polymerase chain reaction. Overall survival of NSCLC patients was detected through Kaplan-Meier survival analysis. MTT assays were used to detect cell proliferation. Cell invasion was determined by transwell assay. Protein levels were detected through western blot.

Results: CCAT1 expression levels significantly increased in NSCLC tumor tissues and were associated with poor overall survival of NSCLC patients. CCAT1 promotes cell proliferation, cell invasion and epithelial-mesenchymal transition of NSCLC cell lines. CCAT1 binds with miR-152, and the effect of si-CCAT1 in NSCLC cell proliferation, cell invasion and epithelial-mesenchymal transition was partially reversed by anti-miR-152.

Conclusions: Long non-coding RNA CCAT1 regulates tumor cell proliferation and invasion in NSCLC through suppressing miR-152. Geriatr Gerontol Int 2020; ••: ••-••.
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http://dx.doi.org/10.1111/ggi.13914DOI Listing
June 2020

Rapid Recognition of Field-Grown Wheat Spikes Based on a Superpixel Segmentation Algorithm Using Digital Images.

Front Plant Sci 2020 6;11:259. Epub 2020 Mar 6.

Jiangsu Key Laboratory of Crop Genetics and Physiology/Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops/Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, China.

Wheat spike number, which could be rapidly and accurately estimated by the image processing technology, serves as the basis for crop growth monitoring and yield prediction. In this research, simple linear iterative clustering (SLIC) was performed for superpixel segmentation of the digital images of field-grown wheat. Firstly, certain characteristic color parameters were extracted and analyzed from the digital images, and the classifiers with the highest accuracy were chosen for subsequent image classification. Next, the main body of wheat spike was extracted through a series of morphological transformation and estimate was performed for each region. Backbone of the head was extracted, and the number of inflection points of backbone was detected. Then the wheat spike number was determined by combining the estimate of inflection points of backbone and the estimate for each region. Finally, the wheat spike number estimate was verified under four nitrogen fertilizer levels. The results were as follows: (1) Super green value (Eg) and normalized red green index (Dgr) were used as classification features to recognize wheat spikes, soil and leaves; (2) compared with pixel-based image processing, wheat spike recognition effect was much better after superpixel segmentation, as the main body of wheat spike extracted was more clear and morphology more intact; and (3) wheat plants had better growth under high nitrogen fertilizer level, and the accuracy of wheat spike number estimation was also the highest, which was 94.01%. The growth status was the worst under no nitrogen fertilizer application, and the accuracy of wheat spikes number estimation was also the lowest, which was only 80.8%. After excluding the no nitrogen condition, the accuracy of wheat spikes number estimation among mixed samples with more uniform growth status was up to 93.8%, which was an increase by 10.1% than before the exclusion. Wheat spikes number estimate based on superpixel segmentation and color features was a rapid and accurate method that was applicable to the field environment. However, this method was not recommended for use when the growth status of wheat was poor or of high heterogeneity. The findings provided reference for field-grown wheat yield estimate.
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http://dx.doi.org/10.3389/fpls.2020.00259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069027PMC
March 2020

Evaluation of the efficacy of optimal pulsed technology treatment in patients with cataract and Meibomian gland dysfunction in the perioperative period.

BMC Ophthalmol 2020 Mar 18;20(1):111. Epub 2020 Mar 18.

Department of Ophthalmology, Provincial Hospital, Shandong University, NO. 324 Jingwuweiqi Road, Jinan, Shandong Province, China.

Background: The aim of this study was to evaluate the efficacy and safety of M22 Optimal Pulsed Technology (OPT) applied in patients with age-related cataract and Meibomian gland dysfunction (MGD) in perioperative period.

Methods: This prospective observational study was carried out in the Jinan Mingshui Eye Hospital (Zhangqiu, China). We studied 60 patients (30 in the OPT treatment group and 30 in the conventional surgery group) with age-related cataract and MGD who underwent phacoemulsification and evaluated the efficacy of OPT treatment before and 1 month and 3 months after surgery. Ocular Surface Disease Index (OSDI) questionnaire, biomicroscopic examination of lid margins, Meibomian gland yielding secretion score (MGYSS), corneal fluorescein staining scores (CFS), tear film break-up time (TBUT), tear meniscus height (TMH) and the morphology of the MG (meibography) followed by Keratograph 5 M (K5M) were used to assess the patients' conditions.

Results: There were significant differences in the scores of OSDI, MGYSS, TBUT, and CFS between the preoperative and postoperative outcomes (p < 0.05). In the OPT treatment group, the postoperative ocular surface condition was obviously better and the patient satisfaction rate was higher than those before surgery. There were significant differences in the scores of OSDI, EMAS, MGYSS and CFS before and 1 month after surgery (p < 0.05). In addition, there were also significant differences in the scores of OSDI, EMAS, MGYSS and MGLS before and 3 months after surgery (p < 0.05). No complications appeared during OPT treatment.

Conclusions: Cataract surgery can aggravate MGD and is detrimental to ocular surface health. OPT treatment was a safe and effective intervention for patients with MGD and cataract during perioperative period.
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http://dx.doi.org/10.1186/s12886-020-01357-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081679PMC
March 2020

Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice.

Pharm Biol 2020 Dec;58(1):200-207

Department of Anesthesiology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, China.

Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits. This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice. C57BL/6J mice were pre-treated with either GSP 25-100 mg/kg/d for seven days or GSP 100-400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed. Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway. These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stress-related cognitive decline.
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http://dx.doi.org/10.1080/13880209.2020.1730913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067175PMC
December 2020

Dimeric artesunate phospholipid-conjugated liposomes as promising anti-inflammatory therapy for rheumatoid arthritis.

Int J Pharm 2020 Apr 24;579:119178. Epub 2020 Feb 24.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China. Electronic address:

Objective: The dimeric artesunate phospholipid conjugate (Di-ART-GPC) is a novel amphipathic artemisinin derivative, which can be assembled into liposomes. Di-ART-GPC liposomes were prepared and evaluated as potential anti-inflammatory agents for rheumatic arthritis (RA).

Methods: Di-ART-GPC was assembled into liposomes utilizing thin film dispersion-high pressure homogenization. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and electron cryo microscopy (cryo-EM) were employed to characterize the liposomal size and morphology. The in vitro cytotoxicity of the Di-ART-GPC liposomes was assessed using Cell Counting Kit-8 (CCK8). The anti-inflammatory effects were studied utilizing the inflammatory cell model. Finally, the in vivo efficacy of the Di-ART-GPC-conjugated liposomes was investigated using the arthritis rat model.

Results: The particle size of the Di-ART-GPC liposomes decreased to a narrow range of approximately 70 nm following high-pressure homogenization. The in vitro studies revealed low cytotoxicity and good anti-inflammatory effects of the Di-ART-GPC liposomes, which exhibited significantly higher inhibition of the cell secretion of pro-inflammatory cytokines than ART. The in vivo evaluation confirmed that treatment with Di-ART-GPC resulted in a decline in the ankle swelling rate and a low inflammatory response compared with the model control and ART.

Conclusion: Di-ART-GPC liposomes demonstrate remarkable potential as novel ART-based anti-inflammatory agents for RA.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119178DOI Listing
April 2020

English spoken word segmentation activates the prefrontal cortex and temporo-parietal junction in Chinese ESL learners: A functional near-infrared spectroscopy (fNIRS) study.

Brain Res 2020 04 30;1733:146693. Epub 2020 Jan 30.

MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, China; Shaanxi Normal University Branch, Collaborative Innovation Center of Assessment Toward Basic Education Quality at Beijing Normal University, Xi'an, China. Electronic address:

A direct measure of spoken lexical processing based on neuroimaging technology would provide us useful information to understand the neural mechanisms underlying speech or auditory language processing. The neural mechanisms of spoken word segmentation for English as a second language (ESL) learners remain elusive. The present study, using functional near-infrared spectroscopy (fNIRS), addresses this issue by measuring hemodynamic responses in the temporo-parietal junction (TPJ) and the prefrontal cortex (PFC) in a word-spotting task, designed with two task conditions (easy vs. difficult). Thirty participants, divided into a high listening proficiency group (HLG) and a low listening proficiency group (LLG), were tested. Results revealed significantly less TPJ activation in the HLG than in the LLG. Further analyses supported this result by showing that activation in the TPJ was in a negative correlation with listening proficiency. This association appears to be related to the more efficient use of processing resources in a bottom-up fashion for accurate and efficient sensory representations in high proficient language learners. In contrast, cortical activation in the PFC increased with listening proficiency and was stronger in the difficult task condition than in the easy task condition, implying that recruitment of top-down cognitive control functions might play a role in word segmentation. Our results suggest that the combination of the functions mediated via bottom-up sensory input processing (demonstrated in the TPJ activation) and top-down cognitive processing (demonstrated in the PFC activation) are crucial for ESL listeners' spoken word segmentation.
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http://dx.doi.org/10.1016/j.brainres.2020.146693DOI Listing
April 2020

Insecticidal activity and biochemical composition of Citrullus colocynthis, Cannabis indica and Artemisia argyi extracts against cabbage aphid (Brevicoryne brassicae L.).

Sci Rep 2020 01 16;10(1):522. Epub 2020 Jan 16.

College of Plant Protection, Shenyang Agricultural University, Shenyang, 110866, P.R. China.

Plant extracts contain many active compounds, which are tremendously fruitful for plant defence against several insect pests. The prime objectives of the present study were to calculate the extraction yield and to evaluate the leaf extracts of Citrullus colocynthis (L.), Cannabis indica (L.) and Artemisia argyi (L.) against Brevicoryne brassicae and to conduct biochemical analysis by gas chromatography-mass spectrometry (GC-MS). The results suggested that when using ethanol, C. colocynthis produced a high dry yield (12.45%), followed by that of C. indica and A. argyi, which were 12.37% and 10.95%, respectively. The toxicity results showed that A. argyi was toxic to B. brassicae with an LC of 3.91 mg mL, followed by the toxicity of C. colocynthis and C. indica, exhibiting LC values of 6.26 and 10.04 mg mL, respectively, which were obtained via a residual assay; with a contact assay, the LC values of C. colocynthis, C. indica and A. argyi were 0.22 mg mL, 1.96 and 2.87 mg mL, respectively. The interaction of plant extracts, concentration and time revealed that the maximum mortality based on a concentration of 20 mg L was 55.50%, the time-based mortality was 55% at 72 h of exposure, and the treatment-based mortality was 44.13% for A. argyi via the residual assay. On the other hand, the maximum concentration-based mortality was 74.44% at 20 mg mL, the time-based mortality was 66.38% after 72 h of exposure, and 57.30% treatment-based mortality was afforded by A. argyi via the contact assay. The biochemical analysis presented ten constituents in both the A. argyi and C. colocynthis extracts and twenty in that of C. indica, corresponding to 99.80%, 99.99% and 97% of the total extracts, respectively. Moreover, the detected caryophylleneonides (sesquiterpenes), α-bisabolol and dronabinol (Δ-THC) from C. indica and erucylamide and octasiloxane hexamethyl from C. colocynthis exhibited insecticidal properties, which might be responsible for aphid mortality. However, A. argyi was evaluated for the first time against B. brassicae. It was concluded that all the plant extracts possessed significant insecticidal properties and could be introduced as botanical insecticides after field evaluations.
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http://dx.doi.org/10.1038/s41598-019-57092-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965137PMC
January 2020

IL1R2 Blockade Suppresses Breast Tumorigenesis and Progression by Impairing USP15-Dependent BMI1 Stability.

Adv Sci (Weinh) 2020 Jan 13;7(1):1901728. Epub 2019 Nov 13.

Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Shanghai Medical College Key Laboratory of Breast Cancer in Shanghai Innovation Center for Cell Signaling Network Cancer Institute Fudan University Shanghai 200032 China.

Breast tumor initiating cells (BTICs) with ALDHCD24CD44 phenotype are the most tumorigenic and invasive cell population in breast cancer. However, the molecular mechanisms are still unclear. Here, it is found that a negative immune regulator interleukin-1 receptor type 2 (IL1R2) is upregulated in breast cancer (BC) tissues and especially in BTICs. BC patients with high IL1R2 expression have a poorer overall survival and relapse-free survival. High IL1R2 promotes BTIC self-renewal and BC cell proliferation and invasion. Mechanistically, IL1R2 is activated by IL1β, as demonstrated by the fact that IL1β induces the release of IL1R2 intracellular domain (icd-IL1R2) and icd-IL1R2 then interacts with the deubiquitinase USP15 at the UBL2 domain and promotes its activity, which finally induces BMI1 deubiquitination at lysine 81 and stabilizes BMI1 protein. In addition, IL1R2 neutralizing antibody can suppress the protein expression of both IL1R2 and BMI1, and significantly abrogates the promoting effect of IL1R2 on BTIC self-renewal and BC cell growth both in vitro and in vivo. The current results indicate that blocking IL1R2 with neutralizing antibody provides a therapeutic approach to inhibit BC progression by targeting BTICs.
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http://dx.doi.org/10.1002/advs.201901728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947699PMC
January 2020

Rapid and Sensitive Detection of Hepatitis C Virus in Clinical Blood Samples Using Reverse Transcriptase Polymerase Spiral Reaction.

J Microbiol Biotechnol 2020 Mar;30(3):459-468

Experimental Research Center, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P.R. China.

This study established a new polymerase spiral reaction (PSR) that combines with reverse transcription reactions for HCV detection targeting 5'UTR gene. To avoid cross-contamination of aerosols, an isothermal amplification tube (IAT), as a separate containment control, was used to judge the result. After optimizing the RT-PSR reaction system, its effectiveness and specificity were tested against 15 different virus strains which included 8 that were HCV positive and 7 as non-HCV controls. The results showed that the RT-PSR assay effectively detected all 8 HCV strains, and no false positives were found among the 7 non-HCV strains. The detection limit of our RT-PSR assay is comparable to the real-time RT-PCR, but is more sensitive than the RT-LAMP. The established RT-PSR assay was further evaluated for detection of HCV in clinical blood samples, and the resulting 80.25% detection rate demonstrated better or similar effectiveness compared to the RT-LAMP (79.63%) and real-time RT-PCR (80.25%). Overall, the results showed that the RT-PSR assay offers high specificity and sensitivity for HCV detection with great potential for screening HCV in clinical blood samples.
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http://dx.doi.org/10.4014/jmb.1910.10041DOI Listing
March 2020

A Case Study: Effects of Foot Reflexotherapy in an Infant with Sensorineural Hearing Loss.

J Acupunct Meridian Stud 2020 Apr 17;13(2):61-65. Epub 2019 Dec 17.

Nursing Department of North Sichuan Medical College, China. Electronic address:

Sensoryneuronal hearing loss (SNHL) is one type of hearing impairment. The incidence of hearing loss (HL) is 1-3 per 1000 births. Complementary therapies may be effective in addressing the maladies of infants with HL. The aim of this study was to assess the efficacy of foot reflexotherapy in an infant with SNHL. The patient was a 3-month-old infant with SNHL. Pretest and post-test for HL were conducted using an audiologic method (auditory brainstem responses) combined with behavioral audiometry. The subject was treated with foot reflexotherapy for 30 min per session four times per week for a period of 24 weeks. Foot reflexotherapy was effective in auditory recuperation of an infant with SNHL. The results of this novel study suggest that foot reflexotherapy can be an effective complementary treatment for infants with SNHL, especially for those 3 to 9 months of age.
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http://dx.doi.org/10.1016/j.jams.2019.12.001DOI Listing
April 2020

Synergistic Effects of Inorganic-Organic Protective Layer for Robust Cycling Dendrite-Free Lithium Metal Batteries.

ACS Appl Mater Interfaces 2020 Jan 24;12(1):844-850. Epub 2019 Dec 24.

Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, Key Laboratory of Cluster Science, Ministry of Education, School of Chemistry and Chemical Engineering , Beijing Institute of Technology , Beijing 100081 , P. R. China.

The advantages in high theoretical capacity and low electrochemical potential have made Li metal one of the most promising anode materials satisfying the surging requirement of high energy density for the next-generation batteries. However, safety issues caused by the Li dendrite growth during cycling have greatly thwarted its application. Herein, a hybrid artificial protective layer, constructed by the one-step method through chemical reactions between Li metal and 1,1,1,2-perfluorodecyltrimethoxysilane, is demonstrated to guide Li deposition and protect lithium batteries from the destruction of Li dendrites. A synergistic effect of the inorganic and organic components in the protective layer significantly enhances the electrochemical performance of symmetric Li|Li and Li|LiFePO cells. This work provides a facile, simple, and scalable method to design a hybrid artificial protective layer for long-lifespan Li metal batteries.
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http://dx.doi.org/10.1021/acsami.9b18703DOI Listing
January 2020

Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance.

Neural Regen Res 2020 Jun;15(6):1094-1101

Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu Province, China.

Sleep-wake rhythm disturbances, which are characterized by abnormal sleep timing or duration, are associated with cognitive dysfunction. Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments. In this study, we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model. We established a model of sleep rhythm disturbance in C57BL/6J mice via a sleep deprivation method involving manual cage tapping, cage jostling, and nest disturbance. We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function. Our results indicated that an intervention in which the mice were exposed to blue light (40-Hz flickering frequency) for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation. However, interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points, as well as 2 Hz-blue light at 3 intervention time points (subjective day time, subjective night time, and offset time points), had no positive effects on circadian rhythm shift or memory deficits. Additionally, a 2000-Hz sound intervention during subjective day time attenuated the 24-hour-acrophase shift and memory decline, while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms. Overall, these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm. All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University, China (approval No. 20171102) on November 20, 2017.
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http://dx.doi.org/10.4103/1673-5374.270415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034272PMC
June 2020

Early Treatment in Acute Severe Encephalopathy Caused by ATP1A2 Mutation of Familial Hemiplegic Migraine Type 2: Case Report and Literature Review.

Neuropediatrics 2020 06 25;51(3):215-220. Epub 2019 Nov 25.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an City, Shaanxi Province, China.

Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant inheritance disorder caused by mutation, and the clinical spectrum is heterogeneous even with acute severe encephalopathy. However, up to now, early treatments against acute and severe attacks in FHM2 are still insufficient. Here, we report a 15-year-old female with intellectual disability due to FHM2 caused by a pathogenic gene mutation, presenting mild-to-moderate headache at the onset, followed by confusion, complete right hemiparalysis, epileptic partial seizures, and conscious disturbance with rapid progression in acute attack. Brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy have revealed left extensive cerebral cortex edema, slightly decreased N-acetylaspartate for neuronal damage, and mildly increased lactate acid for mitochondrial dysfunction throughout the hemispheric swollen cortex. The patient is diagnosed as severe encephalopathy caused by FHM2. Based on literature review about pathophysiologic mechanism described in FHM2 recently, we use early treatments including prevention of glutamatergic excitotoxicity and protection of mitochondria function, as well as traditional antimigraine drug. The symptoms are all greatly improved and recovered within a short time, and follow-up MRI also shows complete disappearance of edema throughout the left hemispheric cortex. Altogether, the approach in our case may reduce the severity and duration of encephalopathy effectively, expend therapeutic options, and provide helpful references for acute severe encephalopathy in FHM2.
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http://dx.doi.org/10.1055/s-0039-3400986DOI Listing
June 2020