Publications by authors named "Lin Ding"

321 Publications

Neck Circumference Is Associated With Hyperuricemia in Women With Polycystic Ovary Syndrome.

Front Endocrinol (Lausanne) 2021 6;12:712855. Epub 2021 Sep 6.

Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Objective: To evaluate the association between neck circumference (NC) and hyperuricemia in women with polycystic ovary syndrome (PCOS).

Methods: This is a cross-sectional study that recruited 601 women with PCOS from January 2018 to January 2021. PCOS was diagnosed according to the Rotterdam definition. Hyperuricemia was defined as serum uric acid level of at least 357 μmol/L.

Results: PCOS females with hyperuricemia had significantly greater values of NC, body mass index (BMI), waist circumference (WC) and hip circumference (HC). NC was positively associated with serum uric acid levels, with a standardized regression coefficient of 0.34 after adjusting for confounding factors. Furthermore, logistic regression analysis showed that NC was significantly associated with an increased risk of hyperuricemia, with an adjusted odds ratio of 1.36. The associations between NC and serum uric acid levels were more considerable in those with medium/high BMI (BMI ≥ 21.63 kg/m), all ranges of WC or medium/high HC (HC ≥ 90 cm). The optimal cut-off point of NC in predicting hyperuricemia was 32.0 cm (Youden index = 0.48), with the sensitivity and negative predictive value of 84.81% and 92.08%, respectively.

Conclusions: NC was positively correlated with serum uric acid levels and the prevalence of hyperuricemia in women with PCOS. Therefore, we suggest NC as a simple, novel, and reliable anthropometric measure to be used in the routine clinical assessment of women with PCOS to screen those at high risk of hyperuricemia.
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http://dx.doi.org/10.3389/fendo.2021.712855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450923PMC
September 2021

Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.

Mol Neurodegener 2021 09 15;16(1):64. Epub 2021 Sep 15.

Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 4939 Charles Katz Drive, San Antonio, TX, 78229, USA.

Background: Human genetic association studies point to immune response and lipid metabolism, in addition to amyloid-beta (Aβ) and tau, as major pathways in Alzheimer's disease (AD) etiology. Accumulating evidence suggests that chronic neuroinflammation, mainly mediated by microglia and astrocytes, plays a causative role in neurodegeneration in AD. Our group and others have reported early and dramatic losses of brain sulfatide in AD cases and animal models that are mediated by ApoE in an isoform-dependent manner and accelerated by Aβ accumulation. To date, it remains unclear if changes in specific brain lipids are sufficient to drive AD-related pathology.

Methods: To study the consequences of CNS sulfatide deficiency and gain insights into the underlying mechanisms, we developed a novel mouse model of adult-onset myelin sulfatide deficiency, i.e., tamoxifen-inducible myelinating glia-specific cerebroside sulfotransferase (CST) conditional knockout mice (CST/Plp1-CreERT), took advantage of constitutive CST knockout mice (CST), and generated CST/ApoE double knockout mice (CST/ApoE), and assessed these mice using a broad range of methodologies including lipidomics, RNA profiling, behavioral testing, PLX3397-mediated microglia depletion, mass spectrometry (MS) imaging, immunofluorescence, electron microscopy, and Western blot.

Results: We found that mild central nervous system (CNS) sulfatide losses within myelinating cells are sufficient to activate disease-associated microglia and astrocytes, and to increase the expression of AD risk genes (e.g., Apoe, Trem2, Cd33, and Mmp12), as well as previously established causal regulators of the immune/microglia network in late-onset AD (e.g., Tyrobp, Dock, and Fcerg1), leading to chronic AD-like neuroinflammation and mild cognitive impairment. Notably, neuroinflammation and mild cognitive impairment showed gender differences, being more pronounced in females than males. Subsequent mechanistic studies demonstrated that although CNS sulfatide losses led to ApoE upregulation, genetically-induced myelin sulfatide deficiency led to neuroinflammation independently of ApoE. These results, together with our previous studies (sulfatide deficiency in the context of AD is mediated by ApoE and accelerated by Aβ accumulation) placed both Aβ and ApoE upstream of sulfatide deficiency-induced neuroinflammation, and suggested a positive feedback loop where sulfatide losses may be amplified by increased ApoE expression. We also demonstrated that CNS sulfatide deficiency-induced astrogliosis and ApoE upregulation are not secondary to microgliosis, and that astrogliosis and microgliosis seem to be driven by activation of STAT3 and PU.1/Spi1 transcription factors, respectively.

Conclusion: Our results strongly suggest that sulfatide deficiency is an important contributor and driver of neuroinflammation and mild cognitive impairment in AD pathology.
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http://dx.doi.org/10.1186/s13024-021-00488-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442347PMC
September 2021

High exposure effect of the adsorption site significantly enhanced the adsorption capacity and removal rate: A case of adsorption of hexavalent chromium by quaternary ammonium polymers (QAPs).

J Hazard Mater 2021 08 28;416:125829. Epub 2021 Apr 28.

College of Chemistry, Nanchang University, Nanchang 330031, PR China; Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle, Nanchang Hangkong University, Nanchang 330063, PR China. Electronic address:

Enhancing the performance of adsorbents to the utmost extent is an objective but challenging in applying adsorption technology to wastewater treatment. In this work, novel quaternary ammonium polymers (QAPs) with high density adsorption site (i.e., quaternized N, confirmed by FT-IR results) were designed and prepared for rapid selective removal of Cr(VI) from water. The results of EDS analysis indicated the maximum exposure rate of N on the surface of QAPs was as high as 86.1%, which almost doubled comparing to that of Cr(VI) ions imprinted polymers (Cr(VI)-IIP) (46.2%). Interestingly, the maximum adsorption capacity (211.8 mg/g) and initial adsorption rate (h0, 66.6 mg/ (g·min)) of QAPs (i.e., 5:1(TRIM)) for Cr(VI) are about 3.6 times and 4.9 times those of Cr(VI)-IIP (63.0 mg/g and 13.5 mg/(g·min)), respectively. Impressively, flow-through adsorption experiments demonstrated 5:1(TRIM) can completely remove 5 mg/L of Cr(VI) within five seconds. Additionally, 5:1(TRIM) exhibited a remarkable selectivity for Cr(VI) adsorption, and high purity (100%) of chromium can be readily obtained. The proposed idea of high exposure effect of the adsorption site can provide a valuable guidance for designing rapid selective adsorbents to remove and reclaim Cr(VI) from wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125829DOI Listing
August 2021

Trans-ethnic genome-wide association study of severe COVID-19.

Commun Biol 2021 08 31;4(1):1034. Epub 2021 Aug 31.

College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.
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http://dx.doi.org/10.1038/s42003-021-02549-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408224PMC
August 2021

Phytochemistry, pharmacology, and potential clinical applications of saffron: A review.

J Ethnopharmacol 2021 Aug 23;281:114555. Epub 2021 Aug 23.

Zhejiang Provincial Key Laboratory of Resources Protection and Innovation of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou, 311300, China; State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, 311300, China. Electronic address:

Ethnopharmacological Relevance: Saffron, the dried red stigma of the perennial herb Crocus sativus L. (Iridaceae), is one of the most important and expensive spices in the world. It is used as a traditional Chinese medicine with demonstrated effects in promoting blood circulation and suppressing blood stasis, cooling blood detoxification, and relieving depression. It is mainly used for the treatment of depression, irregular menstruation, postpartum thrombosis, and bruises.

Aim Of The Study: This review aims to provide a systematic and up-to-date overview of the phytochemistry, pharmacology, and clinical applications of saffron. We hope it could provide useful references and guidance for the future directions of research on saffron.

Materials And Methods: The online database, such as Web of Science, Google Scholar, Science Direct, PubMed, SpringerLink, Wiley Online Library, SciFinder and Chemical book, and CNKI were used to collect relevant literature. And the classic books about Chinese herbal medicine were also being referenced.

Results: More than 150 chemical compounds, including carotenoids, flavonoids and flavonoid glycosides, monoterpenes and monoterpenoid derivatives, monocyclic aromatic hydrocarbons, amino acids, alkaloids and others, were revealed. The pharmacological activities study of saffron were focused on the antioxidant, anti-inflammatory, antitumor, antidepressant, hypoglycemic, hypolipidemic, memory-enhancing, and so on. Currently, saffron is mainly used for the treatment of diabetes, Alzheimer's disease, depression, anxiety disorders, cardiovascular diseases, learning and memory disorders, cancer, and other conditions.

Conclusions: Phytochemical and pharmacological analyses of saffron have been revealed in recent studies. However, clinical studies have focused mainly on AD, depression and anxiety disorders. Therefore, a large number of clinical trials are needed to study the efficacy of saffron and its major chemical components against other diseases including hypertension, hyperlipidemia, and cancer. Further studies of the mechanism of action and toxicological properties of saffron are also required, especially research to establish an effective dose of saffron and its long-term toxicity in vivo.
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http://dx.doi.org/10.1016/j.jep.2021.114555DOI Listing
August 2021

Using Combined Methods of Genetic Mapping and Nanopore-Based Sequencing Technology to Analyze the Insertion Positions of -EPSPS and Transgenes in Maize.

Front Plant Sci 2021 29;12:690951. Epub 2021 Jul 29.

State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

The insertion position of the exogenous fragment sequence in a genetically modified organism (GMO) is important for the safety assessment and labeling of GMOs. SK12-5 is a newly developed transgenic maize line transformed with two trait genes [i.e., -5-enolpyrul-shikimate-3-phosphate synthase (EPSPS) and ] that was recently approved for commercial use in China. In this study, we tried to determine the insertion position of the exogenous fragment for SK12-5. The transgene-host left border and right border integration junctions were obtained from SK12-5 genomic DNA by using the thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR) and next-generation Illumina sequencing technology. However, a Basic Local Alignment Search Tool (BLAST) analysis revealed that the flanking sequences in the maize genome are unspecific and that the insertion position is located in a repetitive sequence area in the maize genome. To locate the fine-scale insertion position in SK12-5, we combined the methods of genetic mapping and nanopore-based sequencing technology. From a classical bulked-segregant analysis (BSA), the insertion position in SK12-5 was mapped onto Bin9.03 of chromosome 9 between the simple sequence repeat (SSR) markers and (26,822,048-100,724,531 bp). The nanopore sequencing results uncovered 10 reads for which one end was mapped onto the vector and the other end was mapped onto the maize genome. These observations indicated that the exogenous T-DNA fragments were putatively integrated at the position from 82,329,568 to 82,379,296 bp of chromosome 9 in the transgenic maize SK12-5. This study is helpful for the safety assessment of the novel transgenic maize SK12-5 and shows that the combined method of genetic mapping and the nanopore-based sequencing technology will be a useful approach for identifying the insertion positions of transgenic sequences in other GM plants with relatively large and complex genomes.
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http://dx.doi.org/10.3389/fpls.2021.690951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358107PMC
July 2021

Comparison of IOL Power Calculation Formulas for a Trifocal IOL in Eyes With High Myopia.

J Refract Surg 2021 Aug 1;37(8):538-544. Epub 2021 Aug 1.

Purpose: To analyze the results of new intraocular lens (IOL) formulas (Emmetropia Verifying Optical [EVO], Kane, Olsen, and Barrett Universal II), traditional formulas (Haigis and SRK/T), and modified Wang-Koch axial length adjustment formulas with the SRK/T and Holladay 1 (SRK/T and H1) in Chinese patients with long eyes.

Methods: In this retrospective case series, patients with an axial length of 26 mm or greater having uneventful femtosecond laser-assisted cataract surgery with one trifocal IOL model were enrolled. The actual postoperative spherical equivalent of the manifest refraction was compared with the formula-predicted refraction based on the implanted IOL power. A subgroup analysis was performed based on the axial length.

Results: A total of 113 eyes was enrolled. Using User Group for Laser Interference Biometry constants, the modified Wang-Koch formulas had the lowest percentage of eyes with hyperopic outcomes. The Barrett Universal II, Olsen, Kane, and EVO 2.0 formulas produced a statistically lower median absolute error than the SRK/T and SRK/T formulas ( < .05). The Barrett Universal II formula produced higher percentages of eyes within ±0.50 diopters (D) of the prediction error than the SRK/T formula ( < .05). In eyes with axial lengths of less than 28 mm, there were no significant differences in the prediction accuracy of the eight formulas. In eyes with axial lengths of 28 mm or greater, the new IOL formulas yielded the lowest median absolute error, followed by the H1 and Haigis formulas. The SRK/T formula had the highest mean absolute error and the lowest percentages of eyes within ±0.25 and ±0.50 D of endpoint. The traditional formulas yielded the highest risk of refractive surprise.

Conclusions: All formulas achieved good results in eyes with axial lengths of less than 28 mm with trifocal IOL implanted. The newer formulas tend to produce better outcomes for eyes with high myopia. The SRK/T formula provided improved accuracy only in eyes with axial lengths of 30 mm or greater. .
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http://dx.doi.org/10.3928/1081597X-20210506-01DOI Listing
August 2021

Application of Comprehensive Artificial intelligence Retinal Expert (CARE) system: a national real-world evidence study.

Lancet Digit Health 2021 08;3(8):e486-e495

Guangdong Medical Devices Quality Surveillance and Test Institute, Guangzhou, Guangdong, China.

Background: Medical artificial intelligence (AI) has entered the clinical implementation phase, although real-world performance of deep-learning systems (DLSs) for screening fundus disease remains unsatisfactory. Our study aimed to train a clinically applicable DLS for fundus diseases using data derived from the real world, and externally test the model using fundus photographs collected prospectively from the settings in which the model would most likely be adopted.

Methods: In this national real-world evidence study, we trained a DLS, the Comprehensive AI Retinal Expert (CARE) system, to identify the 14 most common retinal abnormalities using 207 228 colour fundus photographs derived from 16 clinical settings with different disease distributions. CARE was internally validated using 21 867 photographs and externally tested using 18 136 photographs prospectively collected from 35 real-world settings across China where CARE might be adopted, including eight tertiary hospitals, six community hospitals, and 21 physical examination centres. The performance of CARE was further compared with that of 16 ophthalmologists and tested using datasets with non-Chinese ethnicities and previously unused camera types. This study was registered with ClinicalTrials.gov, NCT04213430, and is currently closed.

Findings: The area under the receiver operating characteristic curve (AUC) in the internal validation set was 0·955 (SD 0·046). AUC values in the external test set were 0·965 (0·035) in tertiary hospitals, 0·983 (0·031) in community hospitals, and 0·953 (0·042) in physical examination centres. The performance of CARE was similar to that of ophthalmologists. Large variations in sensitivity were observed among the ophthalmologists in different regions and with varying experience. The system retained strong identification performance when tested using the non-Chinese dataset (AUC 0·960, 95% CI 0·957-0·964 in referable diabetic retinopathy).

Interpretation: Our DLS (CARE) showed satisfactory performance for screening multiple retinal abnormalities in real-world settings using prospectively collected fundus photographs, and so could allow the system to be implemented and adopted for clinical care.

Funding: This study was funded by the National Key R&D Programme of China, the Science and Technology Planning Projects of Guangdong Province, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, and the Fundamental Research Funds for the Central Universities.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2589-7500(21)00086-8DOI Listing
August 2021

Synthesis, molecular docking and mosquitocidal efficacy of lawsone and its derivatives against the dengue vector Aedes aegypti L. (Diptera: Culicidae).

Med Chem 2021 Jul 27. Epub 2021 Jul 27.

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou 311300, China.

Background: Aedes aegypti is the primary dengue vector, a significant public health problem in many countries. Controlling the growth of Ae. aegypti is the biggest challenge in the mosquito control program, and there is a need for finding bioactive molecules to control Ae. aegypti in order to prevent dengue virus transmission.

Objective: To assess the mosquitocidal property of lawsone and its 3-methyl-4H-chromen-3-yl-1-phenylbenzo[6,7]chromeno[2,3,c]pyrazole-dione derivatives (6a-6h) against various life stages of Ae. aegypti. Besides, to study the mode of action of the active compound by molecular docking and histopathological analysis.

Methods: All derivatives were synthesized from the reaction between 2-hydroxy-1,4-naphthoquinone, chromene-3-carbaldehyde, and 1-phenyl-3-methyl-pyrazol-5-one by using one pot sequential multicomponent reaction. The mosquito life stages were subjected to diverse concentrations ranging from 1.25, 2.5, 5.0, and 10 ppm for lawsone and its derivatives. The structure of all synthesized compounds was characterized by spectroscopic analysis. Docking analysis was performed using autodock tools. Midgut sections of Ae. aegypti larvae were analyzed for histopathological effects.

Results: Among the nine compounds screened, derivative 6e showed the highest mortality on Ae. aegypti life stages. The analyzed LC50 and LC90 results of derivative 6e were 3.01, 5.87 ppm, and 3.41, 6.28 ppm on larvae and pupae of Ae. aegypti, respectively. In the ovicidal assay, the derivative 6e recorded 47.2% egg mortality after 96-hour post-exposure to 10 ppm concentration. In molecular docking analysis, the derivative 6e confirmed strong binding interaction (-9.09 kcal/mol and -10.17 kcal/mol) with VAL 60 and HIS 62 of acetylcholinesterase 1 (AChE1) model and LYS 255, LYS 263 of kynurenine aminotransferase of Ae. aegypti, respectively. The histopathological results showed that the derivative 6e affected the columnar epithelial cells (CC) and peritrophic membrane (pM).

Conclusion: The derivative 6e is highly effective in the life stages of Ae. aegypti mosquito and it could be used in the integrated mosquito management programme.
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http://dx.doi.org/10.2174/1573406417666210727121654DOI Listing
July 2021

Preclinical and clinical study on [F]DRKXH1: a novel β-amyloid PET tracer for Alzheimer's disease.

Eur J Nucl Med Mol Imaging 2021 Jul 22. Epub 2021 Jul 22.

Department of Nuclear Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kongjiang Street, Yangpu District, Shanghai, 200092, China.

Background: The deposition of β-amyloid (Aβ) in the brain is a biomarker of Alzheimer's disease (AD). Highly sensitive Aβ positron emission tomography (PET) imaging plays an essential role in diagnosing and evaluating the therapeutic effects of AD.

Aim: To synthesize a new Aβ tracer [F]DRKXH1 (5-(4-(6-(2-[18]fluoroethoxy)ethoxy)imidazo[1,2-alpha]pyridin-2-yl)phenyl) and evaluate the tracer performance by biodistribution analysis, in vivo small-animal PET-CT dynamic scan, ex vivo and in vitro autoradiography, and PET in human subjects.

Methods: [F]DRKXH1 was synthesized automatically by the GE FN module. Log D (pH 7.4) and biodistribution of [F]DRKXH1 were investigated. Small-animal-PET was used for [F]DRKXH1 and [F]AV45 imaging study in AD transgenic mice (APPswe/PSEN1dE9) and age-matched normal mice. The distribution volume ratios (DVR) and standardized uptake value ratios (SUVRs) were calculated with the cerebellum as the reference region. The deposition of Aβ plaques in the brain of AD transgenic mice was determined by ex vivo autoradiography and immunohistochemistry. In vitro autoradiography was performed in the postmortem brain sections of AD patients and healthy controls. Two healthy control subjects and one AD patient was subjected to in vivo PET study using [F]DRKXH1.

Results: The yield of [F]DRKXH1 was 40%, and the specific activity was 156.64 ± 11.55 GBq/μmol. [F]DRKXH1 was mainly excreted through the liver and kidney. The small-animal PET study showed high initial brain uptake and rapid washout of [F]DRKXH1. The concentration of [F]DRKXH1 was detected in the cortex and hippocampus of AD transgenic mice brain. The cortex DVR of AD transgenic mice was higher than that of WT mice (P < 0.0001). Moreover, the SUVRs of AD transgenic mice were higher than those of WT mice based on the 0-60-min dynamic scanning. In vitro autoradiography showed a significant concentration of tracer in the Aβ plaque-rich areas in the brain of AD transgenic mice. The DVR value of [F]-DRKXH1 is higher than that of [F]-AV45 (1.29 ± 0.05 vs. 1.05 ± 0.08; t = 5.33, P = 0.0003). Autoradiography of postmortem human brain sections showed [F]DRKXH1-labeled Aβ plaques in the AD brain. The AD patients had high retention in cortical regions, while healthy control subjects had uniformly low radioactivity uptake.

Conclusions: [F]DRKXH1 is an Aβ tracer with high sensitivity in preclinical study and has the potential for in vivo detection of the human brain.
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http://dx.doi.org/10.1007/s00259-021-05421-0DOI Listing
July 2021

Perioperative Nursing Care of Vascular Decompression for Trigeminal Neuralgia under AR Medical Technology.

J Healthc Eng 2021 19;2021:9921094. Epub 2021 Jun 19.

The First Department of Neurosurgery, People's Hospital of Rizhao, Rizhao 276800, Shandong, China.

AR technology, also known as AR or virtual reality, refers to a technology that combines and allows interaction of the virtual world on the display system with the real world through the position and angle of the camera video and image analysis technology. This technology is different from VR technology, and its characteristics can be easily explained as follows: when using AR technology, the user's eyes can see not only the real world but also the virtual world derived from the computer through things in the real world. At present, AR has been widely used in education, engineering, entertainment, and medical fields. In order to provide better perioperative care and bring patients a good nursing experience, this article mainly introduces the perioperative care of vascular decompression in the treatment of trigeminal neuralgia by augmented reality medical technology, in order to provide better care for patients with trigeminal neuralgia. This article proposes the perioperative nursing research method of vascular decompression for the treatment of trigeminal neuralgia under AR medical technology, including an overview of trigeminal neuralgia, perioperative related research, and AR medical technology algorithms, and designs related experiments to study whether AR medical technology can bring good news to nursing. Experimental results show that 96% of patients believe that with the enhancement of realistic medical technology, perioperative vascular decompression care for trigeminal neuralgia can help them recover faster and can be gradually popularized.
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http://dx.doi.org/10.1155/2021/9921094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238585PMC
June 2021

Urotensin II induces activation of NLRP3 and pyroptosis through calcineurin in cardiomyocytes.

Peptides 2021 Oct 6;144:170609. Epub 2021 Jul 6.

Department of International Medical Care Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China. Electronic address:

Cell pyroptosis, a new type of programmed cell death, has been recently reported to play important roles in the development of cardiac remodeling. How cardiomyocyte pyroptosis is induced remains to be elucidated. Urotensin II (UII) has been known closely related to cardiac remodeling and the development of heart failure. Inhibition of UII receptors has been shown to be effective in the treatment of cardiac hypertrophy and remodeling. However, it is not clear whether UII might induce cardiomyocyte pyroptosis. We here examined the effect of UII treatment on pyroptosis in cultured cardiomyocytes. Treatment of cardiomyocyes of neonatal rats with UII (500 nmol/l) for 48 hours induced a significant pyroptosis as evidenced by not only increased cell death but also upregulated expression levels of NLR family pyrin domain containing 3 (NLRP3), caspase-1, IL-1β, IL-18 and gasdermin D (GMDSD)-N which are important markers for the identification of cell pyroptosis. All these pyroptosis responses induced by UII were abrogated by an inhibitor of NLRP3. Moreover, the antagonist of UII receptor, Urantide abolished UII- induced cardiomyocyte pyroptosis. Additionally, inhibition of calcineurin by cyclosporin A rather than that of CaMKII by KN93 suppressed the UII-upregulated expression levels of those pyroptosis markers. We therefore demonstrate that UII might induce cardiomyocyte pyroptosis through calcineurin.
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http://dx.doi.org/10.1016/j.peptides.2021.170609DOI Listing
October 2021

An easy-to-operate method for single-cell isolation and retrieval using a microfluidic static droplet array.

Mikrochim Acta 2021 07 6;188(8):242. Epub 2021 Jul 6.

School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia.

In-depth study of cellular heterogeneity of rare cells (e.g. circulating tumour cells (CTCs) and circulating foetal cells (CFCs)) is greatly needed in disease management but has never been completely explored due to the current technological limitations. We have developed a retrieval method for single-cell detection using a static droplet array (SDA) device through liquid segmentation with almost no sample loss. We explored the potential of using SDA for low sample input and retrieving the cells of interest using everyday laboratory equipment for downstream molecular analysis. This single-cell isolation and retrieval method is low-cost, rapid and provides a solution to the remaining challenge for single rare cell detection. The entire process takes less than 15 min, is easy to fabricate and allows for on-chip analysis of cells in nanolitre droplets and retrieval of desired droplets. To validate the applicability of our device and method, we mimicked detection of single CTCs by isolating and retrieving single cells and perform real-time PCR on their mRNA contents.
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http://dx.doi.org/10.1007/s00604-021-04897-9DOI Listing
July 2021

Dietary EPA-Enriched Phospholipids Alleviate Chronic Stress and LPS-Induced Depression- and Anxiety-Like Behavior by Regulating Immunity and Neuroinflammation.

Mol Nutr Food Res 2021 Sep 22;65(17):e2100009. Epub 2021 Jul 22.

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao, 266003, P. R. China.

Scope: A growing number of studies have reported the effects of eicosapentaenoic acid (EPA) and terrestrial phospholipids on ameliorating mood disorders. Marine-derived EPA-enriched phospholipids (EPA-PL) exhibit the structural characteristics of EPA and phospholipids. However, the effect of dietary EPA-PL, and the differences between amphiphilic EPA-PL and lyophobic EPA on mood disorders had not been studied.

Methods And Results: A comparative investigation to determine the effects of dietary EPA-enriched ethyl ester (EPA-EE) and EPA-PL on improving depression- and anxiety-like behavior in a mouse model is performed, induced by 4 week chronic unpredictable mild stress (CUMS) coupled with lipopolysaccharide (LPS) challenge. It is found that dietary 4 week 0.6% (w/w) EPA-PL rescued depression- and anxiety-like behavior to a greater extent than did EPA-EE. Moreover, dietary EPA-PL significantly reduced the immobility time by 56.6%, close to the normal level, in forced swimming test, which revealed a reversal of depression-like behavior. Further studies revealed that dietary EPA-PL regulated immunity, monoamine systems, and the hypothalamic-pituitary-adrenal (HPA) axis by multi-target interactions, including inhibition of neuroinflammation and apoptosis.

Conclusion: EPA-PL exerted superior effects to EPA-EE in alleviating depression- and anxiety-like behavior. The data suggest potential novel candidate or targeted dietary patterns to prevent and treat mood disorder.
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http://dx.doi.org/10.1002/mnfr.202100009DOI Listing
September 2021

Comparative evaluation of phosphatidylcholine and phosphatidylserine with different fatty acids on nephrotoxicity in vancomycin-induced mice.

Biosci Biotechnol Biochem 2021 Jul;85(8):1873-1884

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong, China.

Phospholipids reportedly alleviate drug-induced acute kidney injury. However, no study has compared the effect of phospholipids with different fatty acids and polar heads on drug-induced nephrotoxicity. In the present study, we aimed to compare the possible nephroprotection afforded by phosphatidylcholine and phosphatidylserine with different fatty acids in a mouse model of vancomycin-induced nephrotoxicity. Pretreatment with phospholipids rich in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) doubled the survival time when compared with the model group. Moreover, phospholipids rich in DHA/EPA significantly reduced the serum levels of renal function biomarkers and ameliorated kidney pathologies. In terms of alleviating renal damage, no significant differences were observed between different polar heads in DHA-enriched phospholipids, while phosphatidylserine from soybean was better than phosphatidylcholine in mitigating renal injury. Furthermore, DHA/EPA-enriched phospholipids inhibited vancomycin-induced nephrotoxicity mainly by inhibiting apoptosis and oxidative stress. These results provide a scientific basis for phospholipids as potential ingredients to prevent acute kidney injury.
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http://dx.doi.org/10.1093/bbb/zbab105DOI Listing
July 2021

Traditional versus mirror three-dimensional printing technology for isolated acetabular fractures: a retrospective study with a median follow-up of 25 months.

J Int Med Res 2021 Jun;49(6):3000605211028554

Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Yuexiu District, Guangzhou, China.

Objective: To assess the outcomes of traditional three-dimensional (3D) printing technology (TPT) versus mirror 3D printing technology (MTT) in treating isolated acetabular fractures (IAFs).

Methods: Consecutive patients with an IAF treated by either TPT or MTT at our tertiary medical centre from 2012 to 2018 were retrospectively reviewed. Follow-up was performed 1, 3, 6, and 12 months postoperatively and annually thereafter. The primary outcome was the Harris hip score (HHS), and the secondary outcomes were major intraoperative variables and key orthopaedic complications.

Results: One hundred fourteen eligible patients (114 hips) with an IAF (TPT, n = 56; MTT, n = 58) were evaluated. The median follow-up was 25 months (range, 21-28 months). At the last follow-up, the mean HHS was 82.46 ±14.70 for TPT and 86.30 ± 13.26 for MTT with a statistically significant difference. Significant differences were also detected in the major intraoperative variables (operation time, intraoperative blood loss, number of fluoroscopic screenings, and anatomical reduction number) and the major orthopaedic complications (loosening, implant failure, and heterotopic ossification).

Conclusion: Compared with TPT, MTT tends to produce accurate IAF reduction and may result in better intraoperative variables and a lower rate of major orthopaedic complications.
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http://dx.doi.org/10.1177/03000605211028554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258767PMC
June 2021

Liver and Kidney Function Biomarkers, Blood Cell Traits and Risk of Severe COVID-19: A Mendelian Randomization Study.

Front Genet 2021 27;12:647303. Epub 2021 May 27.

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The pandemic of Coronavirus disease 2019 (COVID-19) has posed an enormous threat to human health. According to observational studies, abnormal liver and kidney functions and blood cell traits were associated with severe COVID-19, yet the causal risk factors for COVID-19 severity and the underlying mechanism remained elusive. We performed Mendelian randomization analyses to assess the potential causal role of eight liver function biomarkers, one kidney function biomarker, and 14 hematological traits on COVID-19 severity using genetic association summary statistics from Europeans. Our findings showed that albumin, direct bilirubin, white blood cell count, neutrophil count, lymphocyte count, and mean corpuscular hemoglobin are casually associated with the risk of severe COVID-19. Notably, lymphocyte count and mean corpuscular hemoglobin had an independent effect on severe COVID-19 risk. These causal evidences provide insights into directions for the risk stratification of individuals with abnormal liver function or blood cell indices and motivate more studies to unveil the roles of these abnormalities in COVID-19 pathogenesis.
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http://dx.doi.org/10.3389/fgene.2021.647303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191502PMC
May 2021

Biotechnology for secure biocontainment designs in an emerging bioeconomy.

Curr Opin Biotechnol 2021 Jun 3;71:25-31. Epub 2021 Jun 3.

National Renewable Energy Laboratory, Golden, CO, United States. Electronic address:

Genetically modified organisms (GMOs) have emerged as an integral component of a sustainable bioeconomy, with an array of applications in agriculture, bioenergy, and biomedicine. However, the rapid development of GMOs and associated synthetic biology approaches raises a number of biosecurity concerns related to environmental escape of GMOs, detection thereof, and impact upon native ecosystems. A myriad of genetic safeguards have been deployed in diverse microbial hosts, ranging from classical auxotrophies to global genome recoding. However, to realize the full potential of microbes as biocatalytic platforms in the bioeconomy, a deeper understanding of the fundamental principles governing microbial responsiveness to biocontainment constraints, and interactivity of GMOs with the environment, is required. Herein, we review recent analytical biotechnological advances and strategies to assess biocontainment and microbial bioproductivity, as well as opportunities for predictive systems biodesigns towards securing a viable bioeconomy.
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http://dx.doi.org/10.1016/j.copbio.2021.05.004DOI Listing
June 2021

AAV-mediated expression of NFAT decoy oligonucleotides protects from cardiac hypertrophy and heart failure.

Basic Res Cardiol 2021 06 4;116(1):38. Epub 2021 Jun 4.

Department of Internal Medicine III, University Hospital Schleswig-Holstein and University of Kiel , Arnold-Heller-Str. 3 , Kiel, Germany.

Previous studies have underlined the substantial role of nuclear factor of activated T cells (NFAT) in hypertension-induced myocardial hypertrophy ultimately leading to heart failure. Here, we aimed at neutralizing four members of the NFAT family of transcription factors as a therapeutic strategy for myocardial hypertrophy transiting to heart failure through AAV-mediated cardiac expression of a RNA-based decoy oligonucleotide (dON) targeting NFATc1-c4. AAV-mediated dON expression markedly decreased endothelin-1 induced cardiomyocyte hypertrophy in vitro and resulted in efficient expression of these dONs in the heart of adult mice as evidenced by fluorescent in situ hybridization. Cardiomyocyte-specific dON expression both before and after induction of transverse aortic constriction protected mice from development of cardiac hypertrophy, cardiac remodeling, and heart failure. Singular systemic administration of AAVs enabling a cell-specific expression of dONs for selective neutralization of a given transcription factor may thus represent a novel and powerful therapeutic approach.
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http://dx.doi.org/10.1007/s00395-021-00880-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178147PMC
June 2021

Long Non-Coding RNA LINC00467 Correlates to Poor Prognosis and Aggressiveness of Breast Cancer.

Front Oncol 2021 28;11:643394. Epub 2021 Apr 28.

Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

Breast cancer remains the leading cause of female cancer-related mortalities worldwide. Long non-coding RNAs (LncRNAs) have been increasingly reported to play pivotal roles in tumorigenesis and cancer progression. Herein, we focused on LINC00467, which has never been studied in breast cancer. Silence of LINC00467 suppressed proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) of breast cancer cells , whereas forced expression of LINC00467 exhibited the opposite effects. Furthermore, we demonstrated overexpression of LINC00467 promoted tumor growth, while knockdown of LINC00467 inhibited pulmonary metastasis Mechanistically, LINC00467 down-regulated miR-138-5p by acting as a miRNA "sponge". Besides, LINC00467 also up-regulated the protein level of lin-28 homolog B (LIN28B) a direct interaction. A higher expression level of LINC00467 was observed in breast cancer tissues as compared to the adjacent normal counterparts and elevated LINC00467 predicted poor overall survival. Our findings suggest LINC00467 promotes progression of breast cancer through interacting with miR-138-5p and LIN28B directly. LINC00467 may serve as a potential candidate for the diagnosis and treatment of breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.643394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113855PMC
April 2021

Dietary n-3 PUFA Deficiency Increases Vulnerability to Scopolamine-Induced Cognitive Impairment in Male C57BL/6 Mice.

J Nutr 2021 Aug;151(8):2206-2214

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong, China.

Background: DHA (22:6n-3), a long-chain n-3 PUFA, is essential for normal brain development and function. Our previous study demonstrated that DHA significantly improves scopolamine-induced dementia. However, there are no reports on the relation between n-3 PUFA deficiency and scopolamine-induced cognitive impairment.

Objectives: The aim of this study was to evaluate whether n-3 PUFA deficiency increases vulnerability to scopolamine-induced cognitive impairment.

Methods: Male and female C57BL/6 mice were mated and fed an n-3 PUFA-adequate [containing 2.88% α-linolenic acid (ALA; 18:3n-3)] or -deficient (containing 0.09% ALA) diet for 2 consecutive generations. The corresponding second-generation male offspring were kept on the same diet as their mothers after weaning, and were randomly assigned to 2 subgroups at 7 wk of age, in which they were intraperitoneally injected with saline [fed n-3 PUFA-adequate (Con) or -deficient (Def) diet] or scopolamine [5 mg/kg body weight; fed n-3 PUFA-adequate (Sco) or -deficient (Def + Sco) diet] once per day for 7 d before killing. Behavioral performance was analyzed using the Morris Water Maze test. Fatty acid composition, protein expression, and indicators of cholinergic and oxidative stress in the brain were measured.

Results: The Def group showed lower brain DHA (-63.7%, P ≤ 0.01) and higher n-6 PUFA (+65.5%, P ≤ 0.05) concentrations than the Con group. The Def + Sco group and the Sco group showed poorer spatial learning and memory (escape latency on the sixth day: +60.3% and +36.8%; platform crossings: -43.9% and -28.2%, respectively) and more obvious cholinergic dysfunction (acetylcholine: -47.6% and -27.7%, respectively), oxidative stress (glutathione peroxidase: -64.2% and -32.5%, respectively), apoptosis [B-cell lymphoma 2 (BCL2)-associated X protein/BCL2: +230.8% and +153.8%; phosphorylated P38/P38: +232% and +130%, phosphorylated c-Jun N-terminal kinase (JNK)/JNK: +104.5% and +58.8%, respectively], neuroinflammation (IL-1β: +317.6% and +95%, respectively), and neurodevelopmental delay (brain-derived neurotrophic factor: -54.4% and -7.25%, respectively) than their corresponding saline-treated controls.

Conclusions: Dietary n-3 PUFA deficiency significantly decreases brain DHA concentrations and increases vulnerability to scopolamine-induced cognitive impairment in C57BL/6 male mice.
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http://dx.doi.org/10.1093/jn/nxab116DOI Listing
August 2021

Sterol sulfate alleviates atherosclerosis mediating hepatic cholesterol metabolism in ApoE mice.

Food Funct 2021 Jun;12(11):4887-4896

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China.

Compared with terrestrial organisms, the sterols in sea cucumber exhibit a sulfate group at the C-3 position. Our previous study demonstrated that dietary sterol sulfate was superior to phytosterol in alleviating metabolic syndrome by ameliorating inflammation and mediating cholesterol metabolism in high-fat-high-fructose diet mice, which indicated its potential anti-atherosclerosis bioactivity. In the present study, administration with sea cucumber-derived sterol sulfate (SCS) significantly decreased the cholesterol level in oleic acid/palmitic acid-treated HepG2 cells, while no significant changes were observed in the triacylglycerol level. RNA-seq analysis showed that the metabolic changes were mostly attributed to the steroid biosynthesis pathway. ApoE-/- mice were used as an atherosclerosis model to further investigate the regulation of SCS on cholesterol metabolism. The results showed that SCS supplementation dramatically reduced atherosclerotic lesions by 45% and serum low-density lipoprotein cholesterol levels by 59% compared with the model group. Dietary SCS inhibited hepatic cholesterol synthesis via downregulating SREBP-2 and HMGCR. Meanwhile, SCS administration increased cholesterol uptake via enhancing the expression of Vldlr and Ldlr. Noticeably, SCS supplementation altered bile acid profiles in the liver, serum, gallbladder and feces, which might cause the activation of FXR in the liver. These findings provided new evidence about the high bioactivity of sterols with the sulfate group on atherosclerosis.
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http://dx.doi.org/10.1039/d0fo03266bDOI Listing
June 2021

Outcomes After Shortened Skilled Nursing Facility Stays Suggest Potential For Improving Postacute Care Efficiency.

Health Aff (Millwood) 2021 05;40(5):745-753

J. Michael McWilliams is the Warren Alpert Foundation Professor of Health Care Policy in the Department of Health Care Policy at Harvard Medical School and a professor of medicine and general internist at Brigham and Women's Hospital, in Boston, Massachusetts.

Reducing postacute care in skilled nursing facilities (SNFs) in favor of home-based care is a leading cost-saving strategy in new payment models. Yet the extent to which SNF stays can be safely shortened remains unclear. We leveraged the exposure of fee-for-service Medicare beneficiaries without supplemental coverage to cost sharing after SNF benefit day 20 as a cause of shortened stays. Marked reductions in length-of-stay because of cost sharing shifted patients to home more than a week earlier than expected without cost sharing, producing a discharge spike. These reductions were not associated with clear evidence of compromised patient safety as measured by death, hospitalization for fall-related injuries, or all-cause hospitalization within nine days of the spike. Adverse consequences requiring hospitalization could not be excluded for a small proportion of shortened stays. These findings suggest potential for improving postacute care efficiency, as SNF stays may be unnecessarily long to ensure safety.
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http://dx.doi.org/10.1377/hlthaff.2020.00649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130553PMC
May 2021

Rescue of Infectious Sindbis Virus by Yeast Spheroplast-Mammalian Cell Fusion.

Viruses 2021 04 1;13(4). Epub 2021 Apr 1.

J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037, USA.

Sindbis virus (SINV), a positive-sense single stranded RNA virus that causes mild symptoms in humans, is transmitted by mosquito bites. SINV reverse genetics have many implications, not only in understanding alphavirus transmission, replication cycle, and virus-host interactions, but also in biotechnology and biomedical applications. The rescue of SINV infectious particles is usually achieved by transfecting susceptible cells (BHK-21) with SINV-infectious mRNA genomes generated from cDNA constructed via in vitro translation (IVT). That procedure is time consuming, costly, and relies heavily on reagent quality. Here, we constructed a novel infectious SINV cDNA construct that expresses its genomic RNA in yeast cells controlled by galactose induction. Using spheroplasts made from this yeast, we established a robust polyethylene glycol-mediated yeast: BHK-21 fusion protocol to rescue infectious SINV particles. Our approach is timesaving and utilizes common lab reagents for SINV rescue. It could be a useful tool for the rescue of large single strand RNA viruses, such as SARS-CoV-2.
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http://dx.doi.org/10.3390/v13040603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066160PMC
April 2021

MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc influx.

Autophagy 2021 Apr 23:1-22. Epub 2021 Apr 23.

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.

Macroautophagy/autophagy is elevated to ensure the high demand for nutrients for the growth of cancer cells. Here we demonstrated that MCOLN1/TRPML1 is a pharmaceutical target of oncogenic autophagy in cancers such as pancreatic cancer, breast cancer, gastric cancer, malignant melanoma, and glioma. First, we showed that activating MCOLN1, by increasing expression of the channel or using the MCOLN1 agonists, ML-SA5 or MK6-83, arrests autophagic flux by perturbing fusion between autophagosomes and lysosomes. Second, we demonstrated that MCOLN1 regulates autophagy by mediating the release of zinc from the lysosome to the cytosol. Third, we uncovered that zinc influx through MCOLN1 blocks the interaction between STX17 (syntaxin 17) in the autophagosome and VAMP8 in the lysosome and thereby disrupting the fusion process that is determined by the two SNARE proteins. Furthermore, we demonstrated that zinc influx originating from the extracellular fluid arrests autophagy by the same mechanism as lysosomal zinc, confirming the fundamental function of zinc as a participant in membrane trafficking. Last, we revealed that activating MCOLN1 with the agonists, ML-SA5 or MK6-83, triggers cell death of a number of cancer cells by evoking autophagic arrest and subsequent apoptotic response and cell cycle arrest, with little or no effect observed on normal cells. Consistent with the results, administration of ML-SA5 in Patu 8988 t xenograft mice profoundly suppresses tumor growth and improves survival. These results establish that a lysosomal cation channel, MCOLN1, finely controls oncogenic autophagy in cancer by mediating zinc influx into the cytosol.
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http://dx.doi.org/10.1080/15548627.2021.1917132DOI Listing
April 2021

A comparative study of the effects of phosphatidylserine rich in DHA and EPA on Aβ-induced Alzheimer's disease using cell models.

Food Funct 2021 May 20;12(10):4411-4423. Epub 2021 Apr 20.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China.

Alzheimer's disease (AD) is an age-dependent, irreversible neurodegenerative disease, and one of the pathological features is amyloid-β (Aβ) deposition. Previous studies have shown that phosphatidylserine (PS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibited significant effects in preventing and alleviating the progress of AD. However, no studies have focused on the differences in the preventive effects on AD between EPA-PS and DHA-PS. Here, the effects of EPA-PS and DHA-PS on Aβ production, Aβ-induced neurotoxicity and Aβ clearance have been studied. The results show that DHA-PS significantly reduced Aβ production in CHO-APP/PS1 cells compared to EPA-PS. Moreover, both EPA-PS and DHA-PS significantly protected the primary hippocampal neurons against Aβ-induced toxicity by inhibiting the mitochondrial-dependent apoptotic pathway and phosphorylation of JNK and p38. Compared to DHA-PS, EPA-PS administration significantly improved the Aβ phagocytic capacity of BV2 cells. In addition, EPA-PS and DHA-PS significantly promoted the neurite outgrowth of primary hippocampal neurons. These findings might provide dietary guidance for the prevention of AD as well as a reference for the development of related functional foods.
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http://dx.doi.org/10.1039/d1fo00286dDOI Listing
May 2021

A microfluidic approach to rapid sperm recovery from heterogeneous cell suspensions.

Sci Rep 2021 Apr 12;11(1):7917. Epub 2021 Apr 12.

School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia.

The isolation of sperm cells from background cell populations and debris is an essential step in all assisted reproductive technologies. Conventional techniques for sperm recovery from testicular sperm extractions stagnate at the sample processing stage, where it can take several hours to identify viable sperm from a background of collateral cells such as white bloods cells (WBCs), red blood cells (RBCs), epithelial cells (ECs) and in some cases cancer cells. Manual identification of sperm from contaminating cells and debris is a tedious and time-consuming operation that can be suitably addressed through inertial microfluidics. Microfluidics has proven an effective technology for high-quality sperm selection based on motility. However, motility-based selection methods cannot cater for viable, non-motile sperm often present in testicular or epididymal sperm extractions and aspirations. This study demonstrates the use of a 3D printed inertial microfluidic device for the separation of sperm cells from a mixed suspension of WBCs, RBCs, ECs, and leukemic cancer cells. This technology presents a 36-fold time improvement for the recovery of sperm cells (> 96%) by separating sperm, RBCS, WBCs, ECs and cancer cells into tight bands in less than 5 min. Furthermore, microfluidic processing of sperm has no impact on sperm parameters; vitality, motility, morphology, or DNA fragmentation of sperm. Applying inertial microfluidics for non-motile sperm recovery can greatly improve the current processing procedure of testicular sperm extractions, simplifying the fertility outcomes for severe forms of male infertility that warrant the surgery.
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http://dx.doi.org/10.1038/s41598-021-87046-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042033PMC
April 2021

Primary Gastro-Intestinal Lymphoma and Gastro-Intestinal Adenocarcinoma: An Initial Study of CT Texture Analysis as Quantitative Biomarkers for Differentiation.

Life (Basel) 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.

Background: To explore the potential role of computed tomography (CT) texture analysis and an imaging biomarker in differentiating primary gastro-intestinal lymphoma (PGIL) from gastro-intestinal adenocarcinoma (GIAC).

Methods: A total of 131 patients with surgical pathologically PGIL and GIAC were enrolled in this study. Histogram parameters of arterial and venous phases extracted from contrast enhanced modified discrete cosine transform (MDCT) images were compared between PGIL and GIAC by Mann-Whitney U tests. The optimal parameters for differentiating these two groups were obtained through receiver operating characteristic (ROC) curves and the area under the curve (AUC) was calculated.

Results: Compared with GIAC, in arterial phase, PGIL had statistically higher 5th, 10th percentiles ( = 0.003 and 0.011) and statistically lower entropy ( = 0.001). In the venous phase, PGIL had statistically lower mean, median, 75th, 90th, 95th percentiles, and entropy ( = 0.036, 0.029, 0.007, 0.001 and 0.001, respectively). For differentiating PGIL from GIAC, V-median + A-5th percentile was an optimal parameter for combined diagnosis (AUC = 0.746, < 0.0001), and the corresponding sensitivity and specificity were 81.7 and 64.8%, respectively.

Conclusion: CT texture analysis could be useful for differential diagnosis of PGIL and GIAC.
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http://dx.doi.org/10.3390/life11030264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005065PMC
March 2021

LncRNA XIST Promoted OGD-Induced Neuronal Injury Through Modulating/miR-455-3p/TIPARP Axis.

Neurochem Res 2021 Jun 18;46(6):1447-1456. Epub 2021 Mar 18.

Department of Rehabilitation Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Wuhan, 430014, Hubei, China.

In recent years, the incidence of ischemic stroke has gradually increased, but its pathogenesis has not been fully elucidated. lncRNAs played an important role in the occurrence and regulation of disease, but the research on ischemic stroke is very limited. Therefore, the role of lncRNA in ischemic stroke needs further exploration. The mice model was built to obtain OGD-induced neuronal cells for the following experiments. The protein expression of TCDD inducible poly [ADP-ribose] polymerase (TIPARP), B-cell lymphoma-2 (Bcl-2) and Cleaved Caspase-3 (Cleaved-cas3) were detected with western blot. qRT-PCR was used to analyze expression of XIST, miR-455-3p and TIPARP. CCK-8 assay indicated the capacity of cell proliferation. Flow cytometry was applied to assess cell apoptosis rate. Moreover, dual-luciferase reporter assay and RIP assay were used to determine that the relationship among XIST, miR-455-3p and TIPARP. In this study, we found that oxygen-glucose deprivation (OGD) induced XIST expression, inhibited miR-455-3p expression and promoted TIPARP mRNA and protein expression in neurons. Furthermore, XIST could affect cell growth of OGD-induced neuronal cells. Further analysis showed that XIST could regulate TIPARP by binding to miR-455-3p, and overexpression of miR-455-3p or inhibition of TIPARP could reverse the effects of high XIST expression on OGD-induced neuronal cells. On the contrary, suppression of miR-455-3p or promotion of TIPARP could reverse the effects of low XIST expression on OGD-induced neuronal cells. XIST could affect cell proliferation and apoptosis through miR-455-3p/TIPARP axis in OGD-induced neuronal cells, providing a new regulatory network to understand the pathogenesis of hypoxia-induced neuronal injury.
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http://dx.doi.org/10.1007/s11064-021-03286-1DOI Listing
June 2021

Elongated axial length and myopia-related fundus changes associated with the Arg130Cys mutation in the gene in four Chinese families with congenital cataracts.

Ann Transl Med 2021 Feb;9(3):235

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Congenital cataract (CC) is a congenital abnormality characterized by lens opacity present at birth and is associated with highly heterogeneous clinical manifestations. Lens-specific integral membrane protein () gene expression is localized to tight junctional domains of different lens fiber membranes. To date, only four mutations in have been reported to be associated with congenital or presenile cataracts. Due to the rarity of variants detected in the gene, there is limited progress in understanding the correlation between the genotype and phenotype of patients with mutations in .

Methods: A total of four Chinese families with CCs were recruited for this study, including three families inheriting in an autosomal dominant (AD) pattern and one sporadic case. Genomic DNA was extracted from the leukocytes of peripheral blood collected from all available patients. Whole-exome sequencing (WES) was performed on all probands and at least one of their parents. Bioinformatics analysis was performed to evaluate the pathogenicity of the candidate variants. Exon 4 of was amplified by polymerase chain reaction and directly sequenced. All patients underwent full ocular examinations. This was an observational study to explore the genotype-phenotype relationships in the four families with a common candidate variant.

Results: Various ocular phenotypes were detected in these families, mainly including CCs, elongated axial length, and myopia-related fundus changes. The gene mutation, p.Arg130Cys, was detected in all patients. This was further confirmed by Sanger sequencing. The proportion of probands with this mutation in our CCs database was 3.1% (4/130), which indicated that this mutation appears to be a frequent cause of cataracts in the Han Chinese population. This variation has been reported by other investigators before and was correlated with isolated cataracts.

Conclusions: This is the first study that reports various ocular phenotypes associated with the p.Arg130Cys mutation in the gene, which indicated the phenotypic heterogeneity of this gene. might not only function as an integral membrane protein in lens fiber cells but also be associated with the axial development of the eyeball. Functional studies of the gene are important and should receive more attention.
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http://dx.doi.org/10.21037/atm-20-4275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940952PMC
February 2021
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