Publications by authors named "Jingjing Chen"

327 Publications

Single-nucleotide-level mapping of DNA regulatory elements that control fetal hemoglobin expression.

Nat Genet 2021 May 6. Epub 2021 May 6.

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Pinpointing functional noncoding DNA sequences and defining their contributions to health-related traits is a major challenge for modern genetics. We developed a high-throughput framework to map noncoding DNA functions with single-nucleotide resolution in four loci that control erythroid fetal hemoglobin (HbF) expression, a genetically determined trait that modifies sickle cell disease (SCD) phenotypes. Specifically, we used the adenine base editor ABEmax to introduce 10,156 separate A•T to G•C conversions in 307 predicted regulatory elements and quantified the effects on erythroid HbF expression. We identified numerous regulatory elements, defined their epigenomic structures and linked them to low-frequency variants associated with HbF expression in an SCD cohort. Targeting a newly discovered γ-globin gene repressor element in SCD donor CD34 hematopoietic progenitors raised HbF levels in the erythroid progeny, inhibiting hypoxia-induced sickling. Our findings reveal previously unappreciated genetic complexities of HbF regulation and provide potentially therapeutic insights into SCD.
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http://dx.doi.org/10.1038/s41588-021-00861-8DOI Listing
May 2021

Association between malnutrition and long-term mortality in older adults with ischemic stroke.

Clin Nutr 2021 Apr 21;40(5):2535-2542. Epub 2021 Apr 21.

Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, China; Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China; Stroke Center & Department of Neurology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, Anhui, China; Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, 210002, China. Electronic address:

Background & Aims: Malnutrition is associated with poor prognosis of different diseases. This study aimed to investigate the association of malnutrition with long-term mortality of older adults with ischemic stroke in China.

Methods: We selected patients aged ≥65 years with first-ever ischemic stroke from the Nanjing Stroke Registry Program. Malnutrition was defined according to the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index score (PNI), respectively. Multivariable Cox proportional hazards regressions and competing risk regressions were performed to explore the relationship between malnutrition and the risk of mortality in older adults with ischemic stroke.

Results: Among 1065 enrolled patients, 60.5%, 46.7%, and 30.6% of patients were malnourished according to CONUT, GNRI, and PNI score. During a median follow-up of 4.74 (3.73-5.82) years, 205 (19.2%) patients died. In multivariate analysis, malnutrition (severe risk versus normal nutrition) was associated with significantly increased risk for mortality by the CONUT (adjusted hazard ratio [HR] 4.615, 95% confidence interval [CI] 1.373-15.514, P = 0.013), GNRI (adjusted HR 3.641, 95% CI 1.924-6.891, P < 0.001), and PNI score (adjusted HR 1.587, 95% CI, 1.096-2.297, P = 0.014). Furthermore, adding the malnutrition indexes to models modestly improved the predictive ability of mortality.

Conclusions: Our study indicated that malnutrition was highly prevalent in older Chinese adults with ischemic stroke and associated with increased mortality. Further research is required to evaluate the efficacy of nutritional management in these patients.
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http://dx.doi.org/10.1016/j.clnu.2021.04.018DOI Listing
April 2021

Improved Performance of D-Psicose 3-Epimerase by Immobilisation on Amino-Epoxide Support with Intense Multipoint Attachment.

Foods 2021 Apr 11;10(4). Epub 2021 Apr 11.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

D-allulose is an epimer of D-fructose at the C-3 position. With similar sweetness to sucrose and a low-calorie profile, D-allulose has been considered a promising functional sweetener. D-psicose 3-epimerase (DPEase; EC 5.1.3.30) catalyses the synthesis of D-allulose from D-fructose. Immobilised enzymes are becoming increasingly popular because of their better stability and reusability. However, immobilised DPEase generally exhibits less activity or poses difficulty in separation. This study aimed to obtain immobilised DPEase with high catalytic activity, stability, and ease of separation from the reaction solution. In this study, DPEase was immobilised on an amino-epoxide support, ReliZyme HFA403/M (HFA), in four steps (ion exchange, covalent binding, glutaraldehyde crosslinking, and blocking). Glycine-blocked (four-step immobilisation) and unblocked (three-step immobilisation) immobilised DPEase exhibited activities of 103.5 and 138.8 U/g support, respectively, but contained equal amounts of protein. After incubation at 60 °C for 2 h, the residual activity of free enzyme decreased to 12.5%, but the activities of unblocked and blocked DPEase remained at 40.9% and 52.3%, respectively. Immobilisation also altered the substrate specificity of the enzyme, catalysing L-sorbose to L-tagatose and D-tagatose to D-sorbose. Overall, the immobilised DPEase with intense multipoint attachment, especially glycine-blocked DPEase, showed better properties than the free form, providing a superior potential for D-allulose biosynthesis.
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http://dx.doi.org/10.3390/foods10040831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069956PMC
April 2021

LINC00184 Promotes Ovarian Cancer Cells Proliferation and Cisplatin Resistance by Elevating CNTN1 Expression via Sponging miR-1305.

Onco Targets Ther 2021 19;14:2711-2726. Epub 2021 Apr 19.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.

Objective: Cisplatin resistance is one of the main reasons for treatment failure in ovarian cancer (OC). Here, the effects of LINC00184 on cisplatin-resistant OC were studied.

Patients And Methods: LINC00184, miR-1305 and CNTN1 expression in tissues from 70 OC patients was determined by qRT-PCR, in situ hybridization and Western blot. OC cell lines and OC cisplatin-resistant cell lines were cultured. Cells were transfected using Lipofectamine 2000 and treated with 100 nM cisplatin. Cell proliferation and apoptosis were researched by the CCK-8 assay and flow cytometry. A dual-luciferase reporter gene assay and RNA pull-down were performed to explore the relationship between two genes. LINC00184, miR-1305 and CNTN1 expression in cells was detected by qRT-PCR and Western blot. An in vivo experiment was conducted using nude mice. Ki67 and CNTN1 expression and apoptosis of xenograft tumors were investigated using immunohistochemistry and a TUNEL assay.

Results: LINC00184 was up-regulated in OC clinical tissues and OC cells, especially in cisplatin-resistant OC patients and cells (<0.01 or <0.0001). LINC00184 overexpression significantly enhanced OC cell proliferation and cisplatin resistance, and inhibited OC cell apoptosis (<0.05 or <0.01). LINC00184 elevated CNTN1 expression via sponging miR-1305. LINC00184 overexpression markedly exacerbated the malignant phenotype of OC cells and cisplatin-resistant OC cells via the miR-1305/CNTN1 axis (<0.01). Silencing of LINC00184 significantly suppressed OC cell growth and cisplatin resistance in vivo (<0.01). LINC00184 silencing inhibited Ki67 and CNTN1 expression and promoted apoptosis of xenograft tumors. CNTN1 overexpression promoted proliferation and cisplatin resistance, and reduced apoptosis of OC cells (<0.05 or <0.01).

Conclusion: LINC00184 promoted OC cell proliferation and cisplatin resistance by elevating CNTN1 expression via sponging miR-1305.
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http://dx.doi.org/10.2147/OTT.S280490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064690PMC
April 2021

Reliability and Validity of the Adapted Chinese Version of the Satisfaction of Adolescents with Postoperative Pain Management - Idiopathic Scoliosis (SAP-S) Scale.

J Pain Res 2021 12;14:953-960. Epub 2021 Apr 12.

Department of Orthopedics, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People's Republic of China.

Study Design: A prospective study.

Objective: The aim of this study was to evaluate the internal reliability and structure validity of an adapted simplified Chinese version of the Satisfaction of Adolescents with Postoperative pain management - idiopathic Scoliosis (SAP-S) scale in mainland China.

Summary Of Background Data: Pain management is a major issue for adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusions. There is a lack of valid scales for evaluating patients' satisfaction with postoperative pain management. The SAP-S was proven to be a valid and reliable measure in English and French.

Methods: The SAP-S was translated into Chinese according to the internationally recognized guidelines. A total of 95 AIS patients undergoing posterior fusion surgery completed the CSAP-S, along with other self-reported questionnaires, including the 36-Item Short Form Health Survey (SF-36) and Scoliosis Research Society-22 (SRS-22) questionnaires. The internal consistency, test-retest reliability, and construct validity of the CSAP-S were determined.

Results: The SAP-S was successfully translated into Chinese. All patients completed the CSAP-S twice and the other instruments. The CSAP-S had good internal consistency and test-retest reliability with Cronbach's alpha coefficient measuring 0.895 and intraclass correlation coefficient (ICC) measuring 0.97. Elimination of any one item did not result in a value of Cronbach's alpha of <0.80. A good construct validity was shown by good correlation with bodily pain (r=0.883, p=0.004) and social functioning (r=0.786, p=0.002) domains of SF-36 and pain (r=0.752, p=0.001) and satisfaction with management (r=0.746, p=0.005) domains of SRS-22.

Conclusion: The CSAP-S demonstrated good internal consistency, reliability, and construct validity, and may be used for the evaluation of AIS patients' satisfaction with postoperative pain management in mainland China.
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http://dx.doi.org/10.2147/JPR.S301205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052124PMC
April 2021

Adult onset Still's disease in the elderly: a case-based literature review.

BMC Rheumatol 2021 Apr 20;5(1):12. Epub 2021 Apr 20.

MedStar Health Internal Medicine Residency Program, Baltimore, MD, USA.

Background: Adult onset Still's disease (AOSD) is a rare inflammatory disorder that classically presents with high spiking fevers, evanescent rash, and arthritis. The diagnosis is one of exclusion and can be further complicated by atypical presentations, particularly in elderly patients in whom AOSD is very rare.

Case Presentation: A case of AOSD in a 73-year-old woman with a non-classic presentation, leading to delayed diagnosis and management, is presented along with a review of the English literature for AOSD cases in elderly people over 70 years of age. Thirty nine case reports and series were identified and the current case was added, totaling 42 individual cases. Significant findings included a four-times higher prevalence in females, a higher prevalence of macrophage activation syndrome despite lower mortality, the presence of pruritic rash in almost one fifth of the cases, and high prevalence of delayed diagnosis.

Conclusions: AOSD in the elderly may vary from the classic criteria described in the medical literature and may lead to delayed diagnosis and management. Further evaluation and better characterization of AOSD in the elderly remains an area of interest.
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http://dx.doi.org/10.1186/s41927-021-00183-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056719PMC
April 2021

Effect of Enzymatic Hydrolysis on the Zinc Binding Capacity and Gastrointestinal Stability of Peptides Derived From Pumpkin (.) Seeds.

Front Nutr 2021 31;8:647782. Epub 2021 Mar 31.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

Zinc is a crucial micronutrient for maintaining body immune system and metabolism function. However, insufficient intake from diet may lead to zinc deficiency and impair normal body function. In addition, conventional zinc salts supplementation has the disadvantage of low bioavailability since the zinc ions may be easily chelated by dietary fiber or phytate commonly found in diets rich in plants, and form precipitates that cannot be absorbed. Therefore, the objective of the present study is to prepare pumpkin seed derived peptides and to evaluate the effect of structure and surface properties on the zinc binding behavior of the pumpkin seed protein hydrolysate (PSPH), as well as their gastrointestinal stability. Briefly, different PSPHs were prepared using enzymatic hydrolysis method with bromelain, papain, flavourzyme, alcalase, and pepsin. The particle size, zeta potential, surface hydrophobicity, degree of hydrolysis, ATR-FTIR spectra, and zinc binding capacity were determined. The representative samples were chosen to characterize the binding energy and surface morphology of PSPH-Zn. At last, the gastrointestinal stability of PSPH and PSPH-Zn were evaluated. Our results showed that peptides hydrolyzed by papain had the largest average molecular weight, smallest particle size, highest hydrophobicity, and the greatest zinc binding capacity. Zinc showed better gastrointestinal stability in PSPHs chelates than in its salt. Meanwhile, PSPH-Zn with higher zinc binding capacity showed better stability. The result of this study indicated pumpkin seed hydrolyzed by papain may be used as a potential source for zinc fortification. The findings in this study may provide important implications for developing plant-based zinc chelating peptides.
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http://dx.doi.org/10.3389/fnut.2021.647782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044297PMC
March 2021

Structure characterization and in vitro hypoglycemic effect of partially degraded alginate.

Food Chem 2021 Sep 30;356:129728. Epub 2021 Mar 30.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.

Alginate is a low-cost polysaccharide found abundantly in seaweeds which consists of mannuronate and guluronate, and it is considered a sustainable gum source for dietary fiber. To solve the high viscosity-related problems while retaining its physiological properties, four partially degraded alginate products (PDA1-4) with molecular weight of 1.05-0.40 × 10 g mol and intrinsic viscosity of 170.9-38.9 mL g were enzymatically prepared and characterized. H Nuclear magnetic resonance analysis showed the used alginate lyase had a preference to degrade guluronate-blocks. PDA1 and PDA2 presented random coil conformation, whereas PDA3 and PDA4 displayed compact spherical-coil conformation over random coil conformation in solution. In vitro assays suggested a glucose-adsorption capacity order of PDA1 < PDA2 < alginate < PDA3 < PDA4 and a glucose-diffusion retardation capacity order of PDA3 < PDA1 ≤ alginate < PDA2 < PDA4, indicating that partially degraded alginate reinforced the hypoglycemic effect, especially mannuronate-rich PDA4. Overall, the study may have important implications for development of PDA as dietary fiber with potential hypoglycemic activity.
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http://dx.doi.org/10.1016/j.foodchem.2021.129728DOI Listing
September 2021

Genetic Variants Are Associated with the Susceptibility to Cervical Cancer in a Chinese Population.

Biomed Res Int 2021 20;2021:6670456. Epub 2021 Mar 20.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082 Shaanxi, China.

Background: Cervical cancer (CC) is the second most common tumor in women worldwide. Studies have been accepted that genetic variations play an important role in the development of CC. The aim of this study was to evaluate the impact of variants on CC risk.

Methods: 508 patients of cervical cancer and 497 healthy subjects were recruited to determine the impact of polymorphisms on CC susceptibility. The associations were investigated by computing odds ratios (ORs) and 95% confidence intervals. The effect of SNP-SNP interactions on CC risk was explored by multifactor dimensionality reduction analysis.

Results: Our study showed that rs11904127 (OR 0.79, = 0.010) and rs62162674 (OR 0.82, = 0.044) of significantly decreased cervical cancer risk. Stratified analysis indicated that rs11904127 and rs62162674 present decreased susceptibility to CC in age > 51 years (OR 0.74, = 0.019; OR 0.72, = 0.014, respectively). Haplotype analyses revealed that GTC has a lower risk to cervical cancer (OR = 0.43, = 0.018). Besides, there is strong interaction of rs11904127 and rs2366264.

Conclusion: Rs11904127 and rs62162674 in are related to cervical cancer. We suggest that these variants can be used as prognostic markers for judging the susceptibility to cervical cancer.
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http://dx.doi.org/10.1155/2021/6670456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007361PMC
March 2021

Effect of Roasting on the Antioxidant Activity, Phenolic Composition, and Nutritional Quality of Pumpkin ( L.) Seeds.

Front Nutr 2021 10;8:647354. Epub 2021 Mar 10.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

In recent years, with the increasing awareness of health concerns and environment protection needs, there is a growing interest for consumers to choose plant-based food diets compared with those made from animal origin. Pumpkin seed is an excellent dietary source for protein, oil, and some essential micronutrients. Raw pumpkin seed may have a compromised flavor, color, as well as digestibility. Therefore, the objective of present study is to study the influence of roasting (120, 160, and 200°C for 10 min) on the phenolics content, flavonoids content, antioxidant property, fatty acids, and volatile matter composition, as well as protein profile of pumpkin seeds. Our results indicated that, total phenolic compounds, total flavonoids content, as a consequence, total antioxidant capacity increased as the roasting temperature increased. Maillard reaction products and lipid peroxidation products were identified, especially from those pumpkin seeds roasted at high temperature. In the meantime, the composition and content of fatty acids did not change significantly after roasting. The results of electrophoresis and particle size analysis showed that the optimum roasting temperature was 160°C to obtain protein with better nutritional quality. The findings of this study may contribute to the utilization of pumpkin seed component in plant-based diets with increased nutritional quality.
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http://dx.doi.org/10.3389/fnut.2021.647354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988230PMC
March 2021

Whole-cell biosynthesis of d-tagatose from maltodextrin by engineered Escherichia coli with multi-enzyme co-expression system.

Enzyme Microb Technol 2021 Apr 28;145:109747. Epub 2021 Jan 28.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, 214122, China.

d-tagatose is a functional sweetener that occurs in small quantity in nature. It is mainly produced through the isomerization of d-galactose by l-arabinose isomerase (l-AI; EC 5.3.1.4). However, the cost of d-galactose is much higher than those commonly used for the production of functional sweeteners such as glucose, maltodextrin, or starch. Here, a multi-enzyme catalytic system consists of five enzymes that utilizes maltodextrin as substrate to synthesize d-tagatose were co-expressed in E. coli, resulting in recombinant cells harboring the plasmids pETDuet-αgp-pgm and pCDFDuet-pgi-gatz-pgp. The activity of this whole-cell catalyst was optimal at 60 °C and pH 7.5, and 1 mM Mg and 50 mM phosphate were the optimal cofactors for activity. Under the optimal reaction conditions, 2.08 and 3.2 g Ld-tagatose were produced by using 10 and 20 g L maltodextrin as substrates with recombinant cells for 24 h. This co-expression system provides a one-pot synthesis approach for the production of d-tagatose using inexpensive substrate, avoiding enzymes purification steps and supplementation of expensive cofactors.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109747DOI Listing
April 2021

Longtime Vision Function Prediction in Childhood Cataract Patients Based on Optical Coherence Tomography Images.

Front Bioeng Biotechnol 2021 5;9:646479. Epub 2021 Mar 5.

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

The results of visual prediction reflect the tendency and speed of visual development during a future period, based on which ophthalmologists and guardians can know the potential visual prognosis in advance, decide on an intervention plan, and contribute to visual development. In our study, we developed an intelligent system based on the features of optical coherence tomography images for long-term prediction of best corrected visual acuity (BCVA) 3 and 5 years in advance. Two hundred eyes of 132 patients were included. Six machine learning algorithms were applied. In the BCVA predictions, small errors within two lines of the visual chart were achieved. The mean absolute errors (MAEs) between the prediction results and ground truth were 0.1482-0.2117 logMAR for 3-year predictions and 0.1198-0.1845 logMAR for 5-year predictions; the root mean square errors (RMSEs) were 0.1916-0.2942 logMAR for 3-year predictions and 0.1692-0.2537 logMAR for 5-year predictions. This is the first study to predict post-therapeutic BCVAs in young children. This work establishes a reliable method to predict prognosis 5 years in advance. The application of our research contributes to the design of visual intervention plans and visual prognosis.
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http://dx.doi.org/10.3389/fbioe.2021.646479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973224PMC
March 2021

MicroRNA-23b prevents aortic aneurysm formation by inhibiting smooth muscle cell phenotypic switching via FoxO4 suppression.

Life Sci 2021 Mar 15:119092. Epub 2021 Mar 15.

Department of Cardiology, Zhuhai People's Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai 519000, China. Electronic address:

Aims: Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for the formation of abdominal aortic aneurysms (AAAs). MicroRNA-23b (miR-23b) has recently been shown to play a vital role in maintaining the VSMC contractile phenotype; however, little is known about the role of miR-23b in the formation of AAAs. Here, we investigated whether miR-23b prevents AAA formation by inhibiting VSMC phenotypic switching.

Materials And Methods: We administered angiotensin II (Ang II, 1000 ng/kg/min) or vehicle to 10-12-week-old male apolipoprotein E knockout (ApoE) or C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks.

Key Findings: The expression of miR-23b was significantly reduced in the aorta during the early onset of AAA in angiotensin II-treated ApoE mice and in human AAA samples. In vitro experiments showed that the suppression of SMC contractile marker gene expression induced by Ang II was accelerated by miR-23b inhibitors but inhibited by mimics. In vivo studies revealed that miR-23b deficiency in Ang II-treated C57BL/6J mice aggravated the formation of AAAs in these mice compared with control mice; the opposite results were observed in miR-23b-overexpressing mice. Mechanistically, miR-23b knockdown significantly increased the expression of the transcription factor forkhead box O4 (FoxO4) during VSMC phenotypic switching induced by Ang II. In addition, a luciferase reporter assay showed that FoxO4 is a target of miR-23b in VSMCs.

Significance: Our study revealed a pivotal role for miR-23b in protecting against aortic aneurysm formation by maintaining the VSMC contractile phenotype.
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http://dx.doi.org/10.1016/j.lfs.2021.119092DOI Listing
March 2021

Super-resolution Microscopy-based Bimolecular Fluorescence Complementation to Study Protein Complex Assembly and Co-localization.

Bio Protoc 2020 Feb 20;10(4):e3524. Epub 2020 Feb 20.

Stowers Institute for Medical Research, Kansas City, MO 64110, USA.

Numerous experimental approaches exist to study interactions between two subunits of a large macromolecular complex. However, most methods do not provide spatial and temporal information about binding, which are critical for dissecting the mechanism of assembly of nanosized complexes . While recent advances in super-resolution microscopy techniques have provided insights into biological structures beyond the diffraction limit, most require extensive expertise and/or special sample preparation, and it is a challenge to extend beyond binary, two color experiments. Using HyVolution, a super-resolution technique that combines confocal microscopy at sub-airy unit pinhole sizes with computational deconvolution, we achieved 140 nm resolution in both live and fixed samples with three colors, including two fluorescent proteins (mTurquoise2 and GFP) with significant spectral overlap that were distinguished by means of shifting the excitation wavelength away from common wavelengths. By combining HyVolution super-resolution fluorescence microscopy with bimolecular fluorescence complementation (SRM-BiFC), we describe a new assay capable of visualizing protein-protein interactions at sub-diffraction resolution. This method was used to improve our understanding of the ordered assembly of the spindle pole body (SPB), a ~1 giga-Dalton heteromeric protein complex formed from 18 structural components present in multiple copies. We propose that SRM-BiFC is a powerful tool for examination of direct interactions between protein complex subunits at sub-diffraction resolution in live cells.
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http://dx.doi.org/10.21769/BioProtoc.3524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842369PMC
February 2020

Characterization and enhanced extracellular overexpression of a new salt-activated alginate lyase.

J Sci Food Agric 2021 Feb 19. Epub 2021 Feb 19.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

Background: Alginate lyases (EC 4.4.2.3/4.4.2.11) have been applied to produce alginate oligosaccharides, which have physiological advantages such as prebiotic and antidiabetic effects, and are of benefit in the food and pharmaceutical industries. Extracellular production of recombinant proteins in Escherichia coli presents advantages including simplified downstream processing and high productivity; however, the presence of certain signal peptides does not always ensure successful secretion, which make the extracellular production of alginate lyase in E. coli rarely reported but of great significance.

Results: A PL7 family alginate lyase, Aly01, with its native signal peptide from Vibrio natriegens SK42.001, was identified, characterized, and extracellularly expressed in E. coli. The enzyme specifically released trisaccharide from alginate and was strictly NaCl activated. Green fluorescent protein (GFP) was fused with the Aly01 signal peptide and successfully secreted in E. coli to expand the feasibility of using this signal peptide to produce other heterologous proteins extracellularly. Through a synergistic strategy of utilizing Terrific Broth (TB) medium supplemented with 120 mmol L glycine and 10 mmol L calcium, the lag phase of protein secretion was reduced to 3 h from 12 h; meanwhile calcium remedied glycine-related cell growth impairment, leading to further enhancement of overall enzyme productivity, reaching a maximum of 4.55 U mL .

Conclusion: A new salt-activated alginate lyase, Aly01, was identified and characterized. E. coli employed its signal peptide and extracellularly expressed both Aly01 and a GFP, which indicated the signal peptide of Aly01 could be a powerful tool for extracellular production of other heterologous proteins in E. coli. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11161DOI Listing
February 2021

International snapshot of new psychoactive substance use: Case study of eight countries over the 2019/2020 new year period.

Water Res 2021 Apr 3;193:116891. Epub 2021 Feb 3.

Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide 5001, South Australia, Australia. Electronic address:

There is considerable concern around the use of new psychoactive substances (NPS), but still little is known about how much they are really consumed. Analysis by forensics laboratories of seized drugs and post-mortem samples as well as hospital emergency rooms are the first line of identifying both 'new' NPS and those that are most dangerous to the community. However, NPS are not necessarily all seized by law enforcement agencies and only substances that contribute to fatalities or serious afflictions are recorded in post-mortem and emergency room samples. To gain a better insight into which NPS are most prevalent within a community, complementary data sources are required. In this work, influent wastewater was analysed from 14 sites in eight countries for a variety of NPS. All samples were collected over the 2019/2020 New Year period, a time which is characterized by celebrations and parties and therefore a time when more NPS may be consumed. Samples were extracted in the country of origin following a validated protocol and shipped to Australia for final analysis using two different mass spectrometric strategies. In total, more than 200 were monitored of which 16 substances were found, with geographical differences seen. This case study is the most comprehensive wastewater analysis study ever carried out for the identification of NPS and provides a starting point for future, ongoing monitoring of these substances.
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http://dx.doi.org/10.1016/j.watres.2021.116891DOI Listing
April 2021

Vedolizumab Concentrations in Breast Milk: Results from a Prospective, Postmarketing, Milk-Only Lactation Study in Nursing Mothers with Inflammatory Bowel Disease.

Clin Pharmacokinet 2021 Feb 5. Epub 2021 Feb 5.

Takeda Development Center Americas, 40 Landsdowne St, Cambridge, MA, 02139, USA.

Background And Objectives: The safety of inflammatory bowel disease medications during lactation is of significant relevance to women of childbearing potential. Available data regarding the transfer of biologic agents for inflammatory bowel disease via breast milk are limited to case reports. The objective of this prospective postmarketing lactation study was to assess vedolizumab concentrations in breast milk from lactating vedolizumab-treated women with inflammatory bowel disease.

Methods: Breast milk was serially collected throughout the dosing interval from 11 patients receiving established intravenous vedolizumab 300-mg maintenance therapy every 8, 6, or 4 weeks. Maternal safety was also assessed.

Results: Vedolizumab was detectable in ~90% of milk samples collected from all patients. Following the day 1 dose, vedolizumab milk concentrations increased with a median of 3-4 days to peak concentration, and subsequently decreased exponentially. For the nine patients receiving vedolizumab every 8 weeks, the average relative infant dose was 20.9%. Using a mean trough serum concentration of 11.2 µg/mL from historical studies, the ratio of mean vedolizumab milk-to-serum concentration was ~ 0.4 to 2.2%, consistent with published data on vedolizumab and other monoclonal antibody therapeutics for inflammatory bowel disease. The maternal safety profile was similar to that observed in previous vedolizumab studies. Published vedolizumab studies also showed no adverse findings for infants breastfed by vedolizumab-treated mothers.

Conclusions: Vedolizumab was present in human breast milk at a low level. The decision to use vedolizumab should balance the benefit of therapy to the mother and the potential risks to the infant.

Trial Registration: ClinicalTrials.gov, NCT02559713; registered 24 September, 2015.
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http://dx.doi.org/10.1007/s40262-021-00985-4DOI Listing
February 2021

Determination and Pharmacokinetic Profiles of Four Active Components From in Rats.

Front Pharmacol 2020 13;11:612534. Epub 2021 Jan 13.

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Acteoside, angoroside C, harpagoside, and cinnamic acid, which are the main bioactive ingredients of , have wide clinical use with various biological effects. A new and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established with taxifolin as the internal standard (IS) in this study and was successfully used to study the pharmacokinetic profiles of four active components from in rats after sublingual intravenous administration. After protein precipitation with acetonitrile, the mobile phase (consisting of acetonitrile and 0.1% formic acid) was used to separate the analytes on an Acquity UPLC BEH C18 chromatography column (2.1 × 50 mm, 1.7 μm) under gradient elution. The precursor-to-product ion transitions of 623.4 → 161.3 m/z for acteoside, 783.5 → 175.0 m/z for angoroside C, 493.3 → 345.2 m/z for harpagoside and 147.2 → 103.4 m/z for cinnamic acid were monitored by mass spectrometry with negative electrospray ionization in the multiple reaction monitoring (MRM) mode. The concentration range of 10-1,000 ng/ml could be detected by this method with a lower limit of quantification (LLOQ) of 10 ng/ml for each analyte. The intra- and inter-day precision (RSD%) of the method ranged from 2.6 to 9.9% and 2.7-11.5%, respectively. Meanwhile, the accuracy (RE%) was -9.6-10.7% in this developed method. The mean recoveries of four active components from were more than 76.7% with negligible matrix effects. The four active components from were stable under multiple storage and process conditions. A new, sensitive and simple analytical method had been established and was successfully applied to the pharmacokinetic profiles of four active components from in rats after sublingual intravenous administration.
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http://dx.doi.org/10.3389/fphar.2020.612534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838596PMC
January 2021

Filamentous growth is a general feature of Candida auris clinical isolates.

Med Mycol 2021 Jan 23. Epub 2021 Jan 23.

Department of Infectious Diseases, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

A striking feature of pathogenic Candida species is morphological plasticity that facilitates environmental adaptation and host infection. Candida auris is an emerging multidrug-resistant fungal pathogen first described in Japan in 2009. In this study, we demonstrate that clinical isolates of C. auris have multiple colony and cellular morphologies including the yeast, filamentous, aggregated, and elongated forms. This phenotypic diversity has been observed in eight clinical isolates of C. auris representing four major genetic clades, suggesting that it could be a general characteristic. We further demonstrate that different cell types of C. auris exhibit distinct antifungal resistance and virulence properties in a Galleria mellonella infection model. Our findings imply that morphological diversity is an important biological feature of C. auris and could be a contributor to its emergence and rapid prevalence worldwide.

Lay Summary: Candida auris is an emerging multidrug-resistant fungal pathogen. Morphological analyses indicate that filamentation is a general feature of clinical isolates of C. auris. This ability is associated with antifungal resistance and virulence.
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http://dx.doi.org/10.1093/mmy/myaa116DOI Listing
January 2021

Purification and Characterization of Resistant Dextrin.

Foods 2021 Jan 18;10(1). Epub 2021 Jan 18.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

In this study, an efficient method for the purification of resistant dextrin (RD) using membrane filtration and anion exchange resin decolorization was developed, then the purified RD was characterized. In the membrane filtration stage, suspended solids in RD were completely removed, and the resulting product had a negligible turbidity of 2.70 ± 0.18 NTU. Furthermore, approximately half of the pigments were removed. Static decolorization experiments revealed that the D285 anion exchange resin exhibited the best decolorization ratio (D%), 84.5 ± 2.03%, and recovery ratio (R%), 82.8 ± 1.41%, among all the tested resins. Under optimal dynamic decolorization conditions, the D% and R% of RD were 86.26 ± 0.63% and 85.23 ± 0.42%, respectively. The decolorization efficiency of the D285 resin was superior to those of activated carbon and HO. Moreover, the chemical characteristics and molecular weight of RD did not change significantly after purification. The nuclear magnetic resonance spectroscopy of RD showed the formation of new glycosidic linkages that are resistant to digestive enzymes. The superior water solubility (99.14%), thermal stability (up to 200 °C), and rheological properties of RD make it possible to be widely used in food industry.
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http://dx.doi.org/10.3390/foods10010185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831330PMC
January 2021

Exogenous NO induces apoptosis of hepatocellular carcinoma cells via positive p38/JNK signaling pathway and negative ERK signaling pathways.

Mol Cell Biochem 2021 Apr 9;476(4):1651-1661. Epub 2021 Jan 9.

Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, 471023, China.

JS-K as an exogenous NO donor could release NO after activation by glutathione S-transferases (GSTs). The present study explores the effects of JS-K on MAPK pathway in HepG2 and Bel-7402 cells. JS-K significantly prompted apoptosis and SB203580 (a p38 inhibitor) and SP600125 (a JNK inhibitor) prior to JS-K could partly reverse apoptosis and activation of cleaved-caspase-3 and cleaved PARP. However, U0126 (a MEK inhibitor) strengthened the cell apoptosis and the expressions of cleaved-caspase-3 and cleaved PARP. JS-K caused phosphorylation of p38 MAPK and JNK but attenuated phosphorylation of ERK, which were reversed by Carboxy-PTIO (a NO scavenger). Meanwhile, the phosphorylation of HSP27, c-JUN and ATF-2 were activated in JS-K-treated cells. SB203580 and SP600125 could attenuate phosphorylation of p38 MAPK and JNK, respectively. The phosphorylation in downstream substrates of p38 MAPK and JNK was also abolished by SB203580 and SP600125 in JS-K-treated cells. Additionally, JS-K decreased phosphorylation of c-Raf, which subsequently caused a decrease of MEK1/2 phosphorylation. Several downstream targets of ERK1/2 including p90RSK and transcription factors (e.g., Elk-1, c-Myc and c-Fos) were inhibited. U0126 potentiated JS-K-induced inhibitory effect of Raf/MEK/ERK pathway. The same results were also observed in the downstream substrates of ERK1/2 including p90RSK, Elk-1, c-Myc and c-Fos. Moreover, Carboxy-PTIO abolished the inhibitory effect of Raf/MEK/ERK pathway triggered by JS-K. Finally, JS-K significantly suppressed the growth of rat primary hepatic carcinoma via MAPK pathway in vivo. Taken together, JS-K can induce hepatocellular carcinoma cells apoptosis through its activation of JNK and p38 MAPK and inactivation of Raf/MEK/ERK signaling pathways.
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http://dx.doi.org/10.1007/s11010-020-04032-xDOI Listing
April 2021

A Study of Multi-Task and Region-Wise Deep Learning for Food Ingredient Recognition.

IEEE Trans Image Process 2021 31;30:1514-1526. Epub 2020 Dec 31.

Food recognition has captured numerous research attention for its importance for health-related applications. The existing approaches mostly focus on the categorization of food according to dish names, while ignoring the underlying ingredient composition. In reality, two dishes with the same name do not necessarily share the exact list of ingredients. Therefore, the dishes under the same food category are not mandatorily equal in nutrition content. Nevertheless, due to limited datasets available with ingredient labels, the problem of ingredient recognition is often overlooked. Furthermore, as the number of ingredients is expected to be much less than the number of food categories, ingredient recognition is more tractable in the real-world scenario. This paper provides an insightful analysis of three compelling issues in ingredient recognition. These issues involve recognition in either image-level or region level, pooling in either single or multiple image scales, learning in either single or multi-task manner. The analysis is conducted on a large food dataset, Vireo Food-251, contributed by this paper. The dataset is composed of 169,673 images with 251 popular Chinese food and 406 ingredients. The dataset includes adequate challenges in scale and complexity to reveal the limit of the current approaches in ingredient recognition.
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http://dx.doi.org/10.1109/TIP.2020.3045639DOI Listing
December 2020

The role of gene dosage in budding yeast centrosome scaling and spontaneous diploidization.

PLoS Genet 2020 12 17;16(12):e1008911. Epub 2020 Dec 17.

Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.

Ploidy is the number of whole sets of chromosomes in a species. Ploidy is typically a stable cellular feature that is critical for survival. Polyploidization is a route recognized to increase gene dosage, improve fitness under stressful conditions and promote evolutionary diversity. However, the mechanism of regulation and maintenance of ploidy is not well characterized. Here, we examine the spontaneous diploidization associated with mutations in components of the Saccharomyces cerevisiae centrosome, known as the spindle pole body (SPB). Although SPB mutants are associated with defects in spindle formation, we show that two copies of the mutant in a haploid yeast favors diploidization in some cases, leading us to speculate that the increased gene dosage in diploids 'rescues' SPB duplication defects, allowing cells to successfully propagate with a stable diploid karyotype. This copy number-based rescue is linked to SPB scaling: certain SPB subcomplexes do not scale or only minimally scale with ploidy. We hypothesize that lesions in structures with incompatible allometries such as the centrosome may drive changes such as whole genome duplication, which have shaped the evolutionary landscape of many eukaryotes.
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http://dx.doi.org/10.1371/journal.pgen.1008911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775121PMC
December 2020

Redox of Dual-Radical Intermediates in a Methylene-Linked Covalent Triazine Framework for High-Performance Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jan 16;13(1):514-521. Epub 2020 Dec 16.

Department of Materials Science and Engineering, Guangdong-Hong Kong-Macao Joint Laboratory for Photonic-Thermal-Electrical Energy Materials and Devices, Southern University of Science and Technology, Shenzhen, 518055 Guangdong, P. R. China.

Covalent triazine frameworks (CTFs) are promising electrodes for rechargeable batteries due to their adjustable structures, rich redox sites, and tunable porosity. However, the CTFs usually exhibit inferior electrochemical stability because of the inactivation of the unstable radical intermediates. Here, a methylene-linked CTF has been synthesized and evaluated as a cathode for rechargeable lithium-ion batteries. Electron paramagnetic resonance (EPR) and in situ Raman characterizations demonstrated that the redox activity and reversibility of α-C and triazine radical intermediates are essentially important for the charging/discharging process, which have been efficiently stabilized by the synergetic π conjugation and hindrance effect caused by the adjacent rigid triazine rings and benzene rings in the unique CTF-p framework. Additionally, the methylene groups provided extra redox-active sites. As a result, high capacity and cycling stability were achieved. This work inspires the rational modulation of the radical intermediates to enhance the electrochemical performance of organic electrode materials for the next-generation energy storage devices.
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http://dx.doi.org/10.1021/acsami.0c17692DOI Listing
January 2021

Tissue engineering of the larynx: A contemporary review.

J Clin Lab Anal 2021 Feb 15;35(2):e23646. Epub 2020 Dec 15.

Department of Otorhinolaryngology- Head and Neck Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Objective: Tissue engineering has been a topic of extensive research in recent years and has been applied to the regeneration and restoration of many organs including the larynx. Currently, research investigating tissue engineering of the larynx is either ongoing or in the preclinical trial stage.

Methods: A literature search was performed on the Advanced search field of PubMed using the keywords: "(laryncheal tissue engineering) AND (cartilage regeneration OR scaffolds OR stem cells OR biomolecules)." After applying the selection criteria, 65 articles were included in the study.

Results: The present review focuses on the rapidly expanding field of tissue-engineered larynx, which aims to provide stem cell-based scaffolds combined with biological active factors such as growth factors for larynx reconstruction and regeneration. The trend in recent studies is to use new techniques for scaffold construction, such as 3D printing, are developed. All of these strategies have been instrumental in guiding optimization of the tissue-engineered larynx, leading to a level of clinical induction beyond the in vivo animal experimental phase.

Conclusions: This review summarizes the current progress and outlines the necessary basic components of regenerative laryngeal medicine in preclinical fields. Finally, it considers the design of scaffolds, support of growth factors, and cell therapies toward potential clinical application.
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http://dx.doi.org/10.1002/jcla.23646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891509PMC
February 2021

Modified organized ophthalmology pre-internship in China.

Ann Transl Med 2020 Nov;8(21):1426

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

Background: Medical pre-internship plays a crucial role in medical education promoting early involvement of students in clinical setting and helping them explore potential interest of specialty. However, there is currently no specifically designed pre-internship curriculum in China. Using ophthalmology as a pilot field, we have set up a modified organized pre-internship curriculum and evaluated its effectiveness and students' feedback in this study.

Methods: In this prospective noncomparative study, 42 junior undergraduate medical students were enrolled in the organized ophthalmology pre-internship. The effects of organized pre-internship on student performance were evaluated by difference of post- to pre-lecture scores by paired -test. The effects of baseline knowledge level and gender on performance improvement were analyzed by independent -test. Student satisfaction comparing organized pre-internship with traditional pre-internship was measured by questionnaire.

Results: The difference of post- to pre-lecture scores of all participants was 6.21±2.02 (P<0.0001). The improvement in post- to pre-lecture scores of students with low knowledge level (7.08±1.85) was significantly higher than that of students with high knowledge level (4.81±1.42) (P<0.0001). Gender did not influence student performance. The responses to the questionnaire showed that most of students were more satisfied with the organized pre-internship than traditional pre-internship.

Conclusions: The organized pre-internship significantly improved student performance and satisfaction. Performance improvement in students with low knowledge level was more obvious. Compared to traditional pre-internship, the organized pre-internship showed advantages in improving student performance as well as promoting learning enthusiasm. Instructors played an essential role in the organized pre-internship teaching system.
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http://dx.doi.org/10.21037/atm-20-1651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723654PMC
November 2020

LINC00987 Ameliorates COPD by Regulating LPS-Induced Cell Apoptosis, Oxidative Stress, Inflammation and Autophagy Through Let-7b-5p/SIRT1 Axis.

Int J Chron Obstruct Pulmon Dis 2020 4;15:3213-3225. Epub 2020 Dec 4.

Department of Respiratory Medicine, The First Affiliated Hospital of Anhui University of Chinese Medicine, Anhui, Hefei, 230031, People's Republic of China.

Background: Chronic obstructive pulmonary disease (COPD) is the third cause of disease-related death and brings a heavy burden to human health. Long non-coding RNA (lncRNA) was revealed to participate in COPD pathogenesis. This study aims to establish the effects and regulatory mechanism of lncRNA long intergenic non-coding 00987 (LINC00987) in lipopolysaccharide (LPS)-induced apoptosis, oxidative stress, inflammation and autophagy in BEAS-2B cells.

Methods: The expression levels of LINC00987 and let-7b-5p were detected by real-time quantitativepolymerase chain reaction (RT-qPCR). The expression of apoptosis-associated proteins, oxidative stress (ROS)-related proteins, autophagy-related proteins and sirtuin1 (SIRT1) protein was determined by Western blot. Cell viability was illustrated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was investigated by caspase3 activity and apoptosis analysis assays. ROS, inflammation and autophagy were demonstrated by detecting reactive ROS level and superoxide dismutase (SOD) activity, enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. The binding sites between let-7b-5p and LINC00987 or SIRT1 were predicted by lncBase or miRWalk online database, and identified by dual-luciferase reporter assay.

Results: LINC00987 expression was strikingly downregulated and let-7b-5p expression was obviously upregulated in COPD tissues and LPS-induced BEAS-2B cells compared with control groups. LINC00987 overexpression promoted BEAS-2B cells against LPS-mediated viability, apoptosis, oxidative stress, inflammation and autophagy, whereas these effects were attenuated by let-7b-5p mimic or SIRT1 knockdown. Furthermore, LINC00987 sponged let-7b-5p and let-7b-5p bound to SIRT1.

Conclusion: LINC00987 ameliorated COPD through modulating LPS-induced cell apoptosis, oxidative stress, inflammation and autophagy via sponging let-7b-5p to associate with SIRT1. This finding will provide a theoretical basis for the research of LncRNA-mediated treatment in COPD.
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http://dx.doi.org/10.2147/COPD.S276429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726835PMC
December 2020

A Blockchain-Driven Supply Chain Finance Application for Auto Retail Industry.

Entropy (Basel) 2020 Jan 13;22(1). Epub 2020 Jan 13.

Department of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310000, China.

In this paper, a Blockchain-driven platform for supply chain finance, BCautoSCF (Zhi-lian-che-rong in Chinese), is introduced. It is successfully established as a reliable and efficient financing platform for the auto retail industry. Due to the Blockchain built-in trust mechanism, participants in the supply chain (SC) networks work extensively and transparently to run a reliable, convenient, and traceable business. Likewise, the traditional supply chain finance (SCF), partial automation of SCF workflows with fewer human errors and disruptions was achieved through smart contract in BCautoSCF. Such open and secure features suggest the feasibility of BCautoSCF in SCF. As the first Blockchain-driven SCF application for the auto retail industry in China, our contribution lies in studying these pain points existing in traditional SCF and proposing a novel Blockchain-driven design to reshape the business logic of SCF to develop an efficient and reliable financing platform for small and medium enterprises (SMEs) in the auto retail industry to decrease the cost of financing and speed up the cash flows. Currently, there are over 600 active enterprise users that adopt BCautoSCF to run their financing business. Up to October 2019, the BCautoSCF provides services to 449 online/offline auto retailors, three B2B asset exchange platforms, nine fund providers, and 78 logistic services across 21 provinces in China. There are 3296 financing transactions successfully completed in BCautoSCF, and the amount of financing is ¥566,784,802.18. In the future, we will work towards supporting a full automation of SCF workflow by smart contracts, so that the efficiency of transaction will be further improved.
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http://dx.doi.org/10.3390/e22010095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516533PMC
January 2020

A hybrid approach of handling missing data under different missing data mechanisms: VISIBLE 1 and VARSITY trials for ulcerative colitis.

Contemp Clin Trials 2021 Jan 22;100:106226. Epub 2020 Nov 22.

Takeda Pharmaceuticals, Cambridge, MA, USA.

Missing data is common in clinical trials. Depending on the volume and nature of missing data, it may reduce statistical power for detecting treatment difference, introduce potential bias and invalidate conclusions. Non-responder imputation (NRI), where patients with missing information to determine endpoint status are considered as treatment failures, is widely used to handle missing data for dichotomous efficacy endpoints in inflammatory bowel disease (IBD) trials. However, it does not consider the mechanisms leading to missing data and can potentially underestimate the treatment effect. We proposed a hybrid imputation approach combining NRI and multiple imputation (MI) as an alternative to NRI to assess the impact of dropouts for different missing data mechanisms (categorized as "missing not at random [MNAR]" and "missing at random [MAR]"). Two phase 3 vedolizumab clinical trials under different study designs in patients with moderate-to-severe ulcerative colitis (UC), VISIBLE 1 and VARSITY, are presented to illustrate how the proposed hybrid approach can be implemented as a pre-specified sensitivity analysis in practice. The proposed hybrid imputation provided consistent efficacy results with those using NRI, and can serve as a useful pre-specified sensitivity analysis to assess the impact of dropouts under different missing data mechanisms and evaluate the robustness of efficacy conclusions.
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http://dx.doi.org/10.1016/j.cct.2020.106226DOI Listing
January 2021

Plant grafting relieves asymmetry of jasmonic acid response induced by wounding between scion and rootstock in tomato hypocotyl.

PLoS One 2020 24;15(11):e0241317. Epub 2020 Nov 24.

Plant and Microbe Interaction Lab, Hei Longjiang Bayi Agricultural University, Daqing, Hei Longjiang, P. R. China.

Plant grafting is a sequential wound healing process. However, whether wounding induces a different jasmonic acid (JA) response within half a day (12 h) after grafting or non-grafting remains unclear. Using the tomato hypocotyl grafting method, we show that grafting alleviates the asymmetrical accumulation of JA and jasmonic acid isoleucine conjugate (JA-Ile) in scion and rootstock caused by wounding, and from 2 h after tomato micrografting, grafting obviously restored the level of JA-Ile in the scion and rootstock. Meanwhile, five JA-related genes, SlLOX11, SlAOS, SlCOI1, SlLAPA and SlJA2L, are detected and show significant changes in transcriptional expression patterns within 12 h of grafting, from asymmetrical to symmetrical, when the expression of 30 JA- and defense-related genes were analyzed. The results indicated that grafting alleviates the asymmetrical JA and defense response between scion and rootstock of the tomato hypocotyl within 12 h as induced by wounding. Moreover, we demonstrate that in the very early hours after grafting, JA-related genes may be involved in a molecular mechanism that changes asymmetrical expression as induced by wounding between scion and rootstock, thereby promoting wound healing and grafting success.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241317PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685457PMC
December 2020