Publications by authors named "Cheng Feng"

543 Publications

MoS-Based Photodetectors Powered by Asymmetric Contact Structure with Large Work Function Difference.

Nanomicro Lett 2019 Apr 16;11(1):34. Epub 2019 Apr 16.

Center for Nanoscale Characterization and Devices (CNCD) Wuhan National Laboratory for Optoelectronics (WNLO) and School of Physics and School of Materials Science and Engineering, Huazhong University of Science and Technology (HUST), Luoyu Road 1037, Wuhan, 430074, People's Republic of China.

Self-powered devices are widely used in the detection and sensing fields. Asymmetric metal contacts provide an effective way to obtain self-powered devices. Finding two stable metallic electrode materials with large work function differences is the key to obtain highly efficient asymmetric metal contacts structures. However, common metal electrode materials have similar and high work functions, making it difficult to form an asymmetric contacts structure with a large work function difference. Herein, MoC crystals with low work function (3.8 eV) was obtained by chemical vapor deposition (CVD) method. The large work function difference between MoC and Au allowed us to synthesize an efficient MoC/MoS/Au photodetector with asymmetric metal contact structure, which enables light detection without external electric power. We believe that this novel device provides a new direction for the design of miniature self-powered photodetectors. These results also highlight the great potential of ultrathin MoC prepared by CVD in heterojunction device applications.
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http://dx.doi.org/10.1007/s40820-019-0262-4DOI Listing
April 2019

Macula Densa NOS1β Modulates Renal Hemodynamics and Blood Pressure During Pregnancy: Role in Gestational Hypertension.

J Am Soc Nephrol 2021 Jun 14. Epub 2021 Jun 14.

R Liu, Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, United States

Regulation of renal hemodynamics and blood pressure (BP) via tubuloglomerular feedback (TGF) may be an important adaptive mechanism during pregnancy. Because the β-splice variant of nitric oxide synthase 1 (NOS1β) in the macula densa is a primary modulator of TGF, we evaluated its role in normal pregnancy and gestational hypertension in a mouse model. We hypothesized that pregnancy upregulates NOS1β in the macula densa, thus blunting TGF, allowing glomerular filtration rate (GFR) to increase and BP to decrease. We employed sophisticated techniques, including microperfusion of juxtaglomerular apparatus , micropuncture of renal tubules , clearance kinetics of plasma FITC-sinistrin, and radio-telemetry BP monitoring, to determine the effects of normal pregnancy or reduced uterine perfusion pressure (RUPP) on macula densa NOS1β/NO levels, TGF responsiveness, GFR, and BP in wild-type and macula densa-specific NOS1 knockout (MD-NOS1KO) mice. Macula densa NOS1β was upregulated during pregnancy, resulting in blunted TGF, increased GFR, and decreased BP. These pregnancy-induced changes in TGF and GFR were largely diminished, with a significant rise in BP, in MD-NOS1KO mice. In addition, RUPP resulted in a downregulation in macula densa NOS1β, enhanced TGF, decreased GFR, and hypertension. The superimposition of RUPP into MD-NOS1KO mice only caused a modest further alteration in TGF and its associated changes in GFR and BP. Finally, in African green monkeys, renal cortical NOS1β expression increased in normotensive pregnancies but decreased in spontaneous gestational hypertensive pregnancies. Macula densa NOS1β plays a critical role in control of renal hemodynamics and BP during pregnancy.
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http://dx.doi.org/10.1681/ASN.2020070969DOI Listing
June 2021

Fluorescence-based screening for engineered aldo-keto reductase KmAKR with improved catalytic performance and extended substrate scope.

Biotechnol J 2021 Jun 14:e2100130. Epub 2021 Jun 14.

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.

Background: Aldo-keto reductases-catalyzed transformations of ketones to chiral alcohols have become an established biocatalytic process step in the pharmaceutical industry. Previously, we have discovered an aldo-keto reductase (AKR) from Kluyveromyces marxianus that is active to the aliphatic tert-butyl 6-substituted (5R/S)-hydroxy-3-oxohexanoates, but it is inactive to aromatic ketones. In order to acquire an excellent KmAKR mutant for ensuring the simultaneous improvement of activity-thermostability toward tert-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate ((5R)-1) and broadening the universal application prospects toward more substrates covering both aliphatic and aromatic ketones, a fluorescence-based high-throughput (HT) screening technique was established.

Main Methods And Major Results: The directed evolution of KmAKR variant M5 (KmAKR-W297H/Y296W/K29H/Y28A/T63M) produced the "best" variant M5-Q213A/T23V. It exhibited enhanced activity-thermostability toward (5R)-1, improved activity toward all 18 test substrates and strict R-stereoselectivity toward 10 substrates in comparison to M5. The enhancement of enzymatic activity and the extension of substrate scope covering aromatic ketones are proposed to be largely attributed to pushing the binding pocket of M5-Q213A/T23V to the enzyme surface, decreasing the steric hindrance at the entrance and enhancing the flexibility of loops surrounding the active center. In addition, combined with 0.94 g dry cell weight (DCW) L glucose dehydrogenase from Exiguobacterium sibiricum (EsGDH) for NADPH regeneration, 2.81 g DCW L M5-Q213A/T23V completely converted (5R)-1 of up to 450 g L at 120 g g substrates/catalysts (S/C), yielding the corresponding optically pure tert-butyl 6-cyano-(3R,5R)-dihydroxyhexanoate ((3R,5R)-2, > 99.5% d.e. ) with a space-time yield (STY) of 1.08 kg L day .

Conclusions: A fluorescence-based HT screening system was developed to tailor KmAKR's activity, thermostability and substrate scope. The "best" variant M5-Q213A/T23V holds great potential application for the synthesis of aliphatic/aromatic R-configuration alcohols. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/biot.202100130DOI Listing
June 2021

Diastereodivergent Synthesis of Chiral 4-Fluoropyrrolidines ( and ') Based on the Cu(II)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition.

J Org Chem 2021 Jun 14. Epub 2021 Jun 14.

Department of Chemistry, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.

1,3-Dipolar cycloaddition of azomethine ylides and electron deficient alkenes is widely studied for rapid installation of pyrrolidine frameworks. Despite significant advances, the major limitations of this process are creating chiral pyrrolidines bearing a quaternary stereogenic center and controlling the diastereoselectivity. Herein, we present an -selective asymmetric 1,3-dipolar cycloaddition to access chiral pyrrolidines with four contiguous stereogenic centers, including a fluorinated quaternary stereogenic center at C4, wherein a Cu(OAc)/()-tol-BINAP catalyst and α-fluoro-α,β-unsaturated arylketone dipolarophiles are used. Epimerization promoted by 5.0 equiv of DBU at 90 °C results in the formation of chiral 4-fluoropyrrolidines (') while maintaining the optical purity.
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http://dx.doi.org/10.1021/acs.joc.1c00509DOI Listing
June 2021

Metabolite Characteristics in Tongue Coating from Damp Phlegm Pattern in Patients with Gastric Precancerous Lesion.

Evid Based Complement Alternat Med 2021 2;2021:5515325. Epub 2021 Jun 2.

Shanghai Key Laboratory of Health Identification and Assessment/Laboratory of TCM Four Diagnostic Information, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: In this study, we analyzed the metabolite profile of the tongue coating of patients having gastric precancerous lesion (GPL) with damp phlegm pattern and proposed a mechanism of pathological transition.

Methods: The changes in tongue-coating metabolites in patients with GPL damp phlegm pattern were analyzed using GC-TOF-MS and UHPLC-QE-MS metabolomics methods.

Results: When compared with 20 patients who did not exhibit a nondamp phlegm pattern, 12 metabolites were highly expressed and 10 metabolites were under expressed in 40 cases of damp phlegm pattern, of which involved 9 metabolic pathways. Compared with 15 healthy people, 134 metabolites were upregulated and 3 metabolites were downregulated in 40 cases exhibiting a damp phlegm pattern, of which involved 17 metabolic pathways. The patients with damp phlegm pattern were compared with nondamp phlegm pattern patients and healthy people, the main differential metabolites were primarily lipids and lipid-like molecules, and the main differential metabolic pathways were related to glycerophospholipid metabolism. In the glycerophospholipid metabolism, the metabolites with changes were phosphatidylethanolamine and lysoPC(18 : 1 (9z)). Among them, phosphatidylethanolamine exists in the synthesis stage of glycerophospholipid metabolism.

Conclusions: Abnormal expression of lipids and lipid-like molecules, as the major metabolic change, was involved in the formation of GPL patients with damp phlegm pattern.
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http://dx.doi.org/10.1155/2021/5515325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189775PMC
June 2021

Using CRISPRa and CRISPRi Technologies to Study the Biological Functions of ITGB5, TIMP1, and TMEM176B in Prostate Cancer Cells.

Front Mol Biosci 2021 24;8:676021. Epub 2021 May 24.

Deparment of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.

Although ITGB5, TIMP1, and TMEM176B are abnormally expressed in several cancers, their molecular biological mechanisms in prostate cancer cells are still to be investigated. The gene regulation technogies based on CRISPR transcription factors could be used to investigate the biological functions of genes in cancer. In this study, we used CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) technologies to regulate the transcription of ITGB5, TIMP1, and TMEM176B in prostate cancer cells. Through a series of cellualr experiments, we found that inhibition of ITGB5 or activation of TIMP1 and TMEM176B suppress prostate cancer. The three genes synergistically affect the proliferation, invasion and migration capabilities of cancer cells.
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http://dx.doi.org/10.3389/fmolb.2021.676021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180862PMC
May 2021

Phylogenetic and morphological significance of an overlooked flying squirrel (Pteromyini, Rodentia) from the eastern Himalayas with the description of a new genus.

Zool Res 2021 Jul;42(4):389-400

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.

The flying squirrels (Pteromyini, Rodentia) are the most diverse and widely distributed group of gliding mammals. Taxonomic boundaries and relationships within flying squirrels remain an area of active research in mammalogy. The discovery of new specimens of ( ) Thomas, 1921 previously considered a synonym of , in Yunnan Province, China allowed a morphological and genetic reassessment of the status of this taxon. Phylogenetic reconstruction was implemented using sequences of two mitochondrial (12S ribosomal DNA and 16S ribosomal DNA) and one nuclear (interphotoreceptor retinoid-binding protein) gene fragments. Morphological assessments involved examinations of features preserved on skins, skulls, and penises of museum specimens, supplemented with principal component analysis of craniometric data. Together these assessments revealed that this taxon should be recognized not only as a distinct species, and should also be placed within a new genus, described here as .
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.039DOI Listing
July 2021

Myeloid Nrf2 deficiency aggravates non-alcoholic steatohepatitis progression by regulating YAP-mediated NLRP3 inflammasome signaling.

iScience 2021 May 16;24(5):102427. Epub 2021 Apr 16.

Hepatobiliary Center of The First Affiliated Hospital and The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), School of Biomedical Engineering and Informatics, Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, 300 Guang Zhou Road, Nanjing, China.

Nuclear-erythroid-2-related factor 2 (Nrf2) is involved in the pathogenesis of different liver diseases. Herein, we first demonstrated that Nrf2 expression was diminished in nonalcoholic steatohepatitis (NASH) liver macrophages. In myeloid Nrf2-deficiency mice, aggravated liver steatosis and inflammation in high-fat-diet (HFD)-fed mice were observed compared with the chow-diet group. Moreover, the increasing inflammatory cytokines influenced the lipid metabolism in hepatocytes . Further study showed Nrf2 regulated reactive-oxygen-species-mediated Hippo-yes-associated protein (YAP) signaling, which in turn modulated the NLRP3 inflammasome activation. Administration of YAP activator also significantly ablated the lipid accumulation and inhibited the NLRP3 activation in the Nrf2 deletion condition both Overexpression Nrf2 in liver macrophages effectively alleviated steatohepatitis in wild-type mice fed with an HFD . Our data support that by modulating YAP-mediated NLRP3 inflammasome activity, macrophage Nrf2 slows down NASH progression.
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http://dx.doi.org/10.1016/j.isci.2021.102427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141901PMC
May 2021

Urolithin A Inhibits Epithelial-Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway.

Onco Targets Ther 2021 17;14:3199-3208. Epub 2021 May 17.

Research Laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, 241001, People's Republic of China.

Purpose: The epithelial-to-mesenchymal transition (EMT) is a fundamental process in tumor progression that endows cancer cells with migratory and invasive potential. Snail, a zinc finger transcriptional repressor, plays an important role in the induction of EMT by directly repressing the key epithelial marker E-cadherin. Here, we assessed the effect of urolithin A, a major metabolite from pomegranate ellagitannins, on Snail expression and EMT process.

Methods: The role of Snail in urolithin A-induced EMT inhibition in lung cancer cells was explored by wound healing assay and cell invasion assay. The qRT-PCR and CHX assay were performed to investigate how urolithin A regulates Snail expression. Immunoprecipitation assays were established to determine the effects of urolithin A in mdm2-Snail interaction. In addition, the expression of p53 was manipulated to explore its effect on the expression of mdm2 and Snail.

Results: The urolithin A dose-dependently upregulated epithelial marker and decreased mesenchymal markers in lung cancer cells. In addition, exposure to urolithin A decreased cell migratory and invasive capacity. We have further demonstrated that urolithin A inhibits lung cancer cell EMT by decreasing Snail protein expression and activity. Mechanistically, urolithin A disrupts the interaction of p53 and mdm2 which leads Snail ubiquitination and degradation.

Conclusion: We conclude that urolithin A could inhibit EMT process by controlling mainly Snail expression. These results highlighted the role of pomegranate in regulation of EMT program in lung cancer.
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http://dx.doi.org/10.2147/OTT.S305595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139733PMC
May 2021

Freeze-Casting with 3D-Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration.

Adv Healthc Mater 2021 May 24:e2100238. Epub 2021 May 24.

Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

A new approach is described for fabricating 3D poly(ε-caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze-casting with 3D-printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D-printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro-/microchannels within nanofiber aerogels significantly increase preosteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)-mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promotes the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling.
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http://dx.doi.org/10.1002/adhm.202100238DOI Listing
May 2021

Sexual orientation and quality of life of people living with HIV/AIDS in China: evidence from an institutional-based cross-sectional study.

Qual Life Res 2021 May 24. Epub 2021 May 24.

Center for Health Policy Studies, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.

Background: At the end of 2019, there were approximately one million people known to be living with HIV/AIDS (PLWHA) in China. Different sexual orientation groups were observed within the people living with HIV in general, and studies have found that socially marginalized groups exist among this population, such as men who have sex with men (MSM) and bisexual individuals. Correspondingly, sexual orientation may pose challenges to the emotional and psychological development of PLWHA. Under this background, we aim to analyze whether sexual orientation affects the health-related quality of life (HRQOL) of PLWHA in order to provide evidence and suggestions for how wellbeing can be enhanced for sexual minorities living with HIV/AIDS.

Method: An institutional-based cross-sectional study design was used to collect data from PLWHA in Yunnan province and Beijing municipality in China. In our study, sexual orientation was classified as heterosexual, homosexual and bisexual, and HRQOL was measured using the Chinese WHOQOL-HIV-BREF scale. Logistic regression model was used to analyze the relationships of participants' sexual orientation and HRQOL. In addition, multivariable stepwise liner regression model was used to analyze the factors influencing HRQOL of PLWHA.

Results: In total, 2610 PLWHA were included in the study, 36.5% of the participants identified as homosexual and most were males, 13.8% were bisexuals and 49.7% were heterosexuals. For the overall HRQOL, the homosexual PLWHA group scored highest (81.53 ± 12.45) with a high HRQOL score signifying a better health-related quality of life, followed by bisexuals (79.72 ± 12.81) and heterosexuals (78.02 ± 13.06). However, the bisexual group showed a markedly higher level of spiritual health. In addition, there was no statistical difference in the total HRQOL scores and domains by sex roles among the homosexual group (p > 0.01). However, sexual orientation was statistically associated with the physical and spiritual domains of HRQOL (p < 0.05).

Conclusion: In terms of sexual orientation for those living with HIV/AIDS, a better quality of life was found for homosexual individuals, whilst being a heterosexual individual saw a negative impact on quality of life, especially in the physical and spiritual domains. Strengthening the individualized and comprehensive care for heterosexual group as well as other sexual minority populations is imperative. Moreover, heterosexual PLWHA are more likely to be ignored and require more support and care to improve their HRQOL than do those in sexual minorities.
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http://dx.doi.org/10.1007/s11136-021-02877-3DOI Listing
May 2021

Handheld bioprinting strategies for in situ wound dressing.

Essays Biochem 2021 May 24. Epub 2021 May 24.

Division of Engineering in Medicine, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Cambridge, MA 02139, U.S.A.

Handheld bioprinting has recently attracted considerable attention as a technology to deliver biomaterials and/or cells to injury sites by using freeform, user-instructed deposition approaches, specifically targeted towards in situ wound dressing and healing. In this review, we present a concise introduction of handheld bioprinting, and a thorough discussion on design and manufacture of handheld bioprinters and choice over bioinks. Finally, the advantages, challenges, and prospective of the said technologies are elaborated. It is believed that handheld bioprinting will play an essential role in the field of in situ wound healing mainly due to its excellent portability, user-friendliness, cost-effectiveness, and amenability to various wound needs.
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http://dx.doi.org/10.1042/EBC20200098DOI Listing
May 2021

CEBPA-AS1 knockdown alleviates OGD/R-induced neuron cell damage by the miR-24-3p/BOK axis.

Mol Cell Biol 2021 May 17. Epub 2021 May 17.

Department of Neurosurgery, Traditional Chinese Medicine Hospital of Kunshan, Kunshan 215300, China

Cerebral ischemia/reperfusion (I/R) can lead to serious brain function impairments. Long noncoding RNA (lncRNA) CCAAT enhancer binding protein α antisense RNA 1 () was shown to be upregulated in human ischemic stroke. This work investigated the function and mechanism of in I/R. An oxygen-glucose deprivation/reperfusion (OGD/R) model was used to induce I/R injury in SH-SY5Y cells in vitro. RT-qPCR examined the expression of , microRNA-24-3p (miR-24-3p), and Bcl-2-related ovarian killer (Bok). The cell viability, apoptosis, oxidative stress in OGD/R-treated cells were detected using CCK-8, flow cytometry, western blot, ELISA assays. The relationship among genes was tested by RNA pulldown and luciferase reporter assays. We found that OGD/R upregulated expression in SH-SY5Y cells. Functionally, depletion ameliorated OGD/R-induced apoptosis and oxidative stress in SH-SY5Y cells by reducing ROS production and superoxide dismutase (SOD) and glutathione (GSH). Mechanistic investigations indicated that acts as a sponge for miR-24-3p, and miR-24-3p binds to the BOK. Moreover, miR-24-3p upregulation or BOK downregulation antagonized the protective role of depletion in SH-SY5Y cells exposed to OGD/R. Overall, downregulation of exerts protective functions against OGD/R-induced injury by targeting the miR-24-3p/BOK axis.
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http://dx.doi.org/10.1128/MCB.00065-21DOI Listing
May 2021

Forensic nanopore sequencing of STRs and SNPs using Verogen's ForenSeq DNA Signature Prep Kit and MinION.

Int J Legal Med 2021 May 5. Epub 2021 May 5.

School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, People's Republic of China.

The MinION nanopore sequencing device (Oxford Nanopore Technologies, Oxford, UK) is the smallest commercially available sequencer and can be used outside of conventional laboratories. The use of the MinION for forensic applications, however, is hindered by the high error rate of nanopore sequencing. One approach to solving this problem is to identify forensic genetic markers that can consistently be typed correctly based on nanopore sequencing. In this pilot study, we explored the use of nanopore sequencing for single nucleotide polymorphism (SNP) and short tandem repeat (STR) profiling using Verogen's (San Diego, CA, USA) ForenSeq DNA Signature Prep Kit. Thirty single-contributor samples and DNA standard material 2800 M were genotyped using the Illumina (San Diego, CA, USA) MiSeq FGx and MinION (with R9.4.1 flow cells) devices. With an optimized cutoff for allelic imbalance, all 94 identity-informative SNP loci could be genotyped reliably using the MinION device, with an overall accuracy of 99.958% (1 error among 2926 genotypes). STR typing was notably error prone, and its accuracy was locus dependent. We developed a custom-made bioinformatics workflow, and finally selected 13 autosomal STRs, 14 Y-STRs, and 4 X-STRs showing high consistency between nanopore and Illumina sequencing among the tested samples. These SNP and STR loci could be candidates for panel design for forensic analysis based on nanopore sequencing.
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http://dx.doi.org/10.1007/s00414-021-02604-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098014PMC
May 2021

Therapeutic effect of SP-8356 on pulmonary embolism-associated cardiac injury is mediated by its ability to suppress apoptosis and inflammation.

J Cell Mol Med 2021 Jun 4;25(11):5260-5268. Epub 2021 May 4.

Department of Cardiovascular Medicine, The First Affiliated Hospital of South China University, Hengyang, China.

The cyclophilin A-CD147 interaction has been reported to be one of the most potential therapeutic targets for the treatment of acute pulmonary embolism. The signalling of extracellular signal-regulated kinase 1/2 (ERK1/2) was also reported in the pathogenesis of cardiac injury. Since SP-8356 is regarded as a novel Inhibitor of CD147-Cyclophilin, the study aimed to evaluate potential therapeutic effects of SP-8356 for pulmonary embolism-associated cardiac injury. Western blot and immunohistochemistry were carried out to analyse the expression of MMP-9, ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), P65, p-P65, and CyA protein in PE cell and rat models under distinct conditions. Flow cytometry and TUNEL were carried out to examine the apoptosis of primary rat myocardiocytes and PE rat models under distinct conditions. CyA treatment on primary rat myocardiocytes remarkably raised the expression of MMP-9, p-ERK1/2 and p-P65 protein expression; SP8536 treatment effectively restored the CyA-induced up-regulation of MMP-9, p-ERK1/2 and p-P65 protein expression in primary rat myocardiocytes. Besides, flow cytometry analysis showed that SP8536 remarkably suppressed the CyA-induced elevation of cell apoptosis rate of primary rat myocardiocytes. Moreover, SP8536 notably diminished the abnormal elevation of right ventricular systolic pressure (RVSP), Troponin I and Myeloperoxidase activity in PE rat models. Furthermore, SP-8536 significantly restored the up-regulation of MMP-9, p-ERK1/2, p-P65, CyA protein and the cellular apoptosis in the PE rat model. Our study validated that SP-8356 could suppress cell apoptosis and inflammatory response via down-regulating the highly expressed MMP-9, p-ERK1/2, and p-P65 and MMP-9 in PE-associated cardiac injury in a dose-dependent manner.
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http://dx.doi.org/10.1111/jcmm.16535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178275PMC
June 2021

Total parathyroidectomy with forearm autotransplantation in secondary hyperparathyroidism patients: analysis of muscle, subcutaneous and muscle + subcutaneous method.

BMC Surg 2021 May 1;21(1):226. Epub 2021 May 1.

Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.

Background: Forearm autotransplantation after parathyroidectomy has turned into the standard method for secondary hyperparathyroidism (SHPT) treatment in chronic kidney disease patients. Our study aimed to explore the effects of three methods including muscle, subcutaneous and muscle + subcutaneous transplant methods on SHPT.

Methods: Seventy five SHPT patients were enrolled and assigned into the muscle + subcutaneous (M + S) (n = 26), muscle (M) (n = 35), and subcutaneous (S) (n = 14) groups. The operation efficacy evaluation included preoperative and postoperative biological characteristics such as parathyroid hormone (PTH), serum phosphorus, serum calcium and alkaline phosphatase (ALP). The data were recorded from pre-operation time point to 1, 2, 3, 6, 12, 18, 24 month (mo) postoperation periods. After operation, short-form health survey (SF-36) scores was made for life quality identification at 1, 2, 3, 6, 12, 24 time points. Symptoms about SHPT including bone pain, fracture, pruritus, and coronary artery calcification were followed-up based on the scale.

Results: Compared with the preoperative record, all the M + S, M, and S groups showed postoperative decreased levels of PTH, serum phosphorus, serum calcium, calcium-phosphorus. In M + S group, the PTH and serum calcium level kept more steady compared with the M and S groups during a 24 mo duration observation. After this, a SF-36 score scale which represents the life quality show M + S group got more scores at 3, 6, 12, 18 and 24 mo points. At last, the incidence of SHPT associated symptoms including Bone pain, Fracture, Pruritus, and Coronary artery calcification in M + S group were decreased compared with M and S groups at 1, 3, 6, 12 and 24 mo post-operation time points.

Conclusion: M + S seems to be an efficient method for medical treatment of SHPT patients in the control of PTH and serum calcium. This mixed transplant strategy improves the biochemical characterizes compared with M and S groups in SHPT patients. Furthermore, the M + S method make beneficial on clinical outcomes and life quality of patients.
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http://dx.doi.org/10.1186/s12893-021-01222-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088620PMC
May 2021

Women's Perception of Male Involvement in Antenatal, Childbirth and Postnatal Care in Urban Slum Areas in Bangladesh: A Community-Based Cross-Sectional Study.

Healthcare (Basel) 2021 Apr 16;9(4). Epub 2021 Apr 16.

Center for Health Policy Studies, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China.

Male participation in reproductive health issues has been considered to be an effective and promising strategy to address the women's reproductive health problems since the 1990s. Under this background, we aim to explore the women's perception of men's involvement in antenatal care (ANC), delivery and postnatal care (PNC) in the slum community of Bangladesh where various sexual and reproductive health problems exist. A community-based cross-sectional study was conducted among women and their husbands living in 12 slums of Chattogram city. Cross-tabulation with chi-square tests and multivariate logistic regression analyses were performed to examine the predictors of husbands' support in wives' antenatal, delivery and postnatal care. The study demonstrates that the education and economic level of most women and their husbands were very low although husbands seemed to have a better status than wives in these aspects. Almost all men (~90%) had never accessed services related to reproductive and maternal health. Only 10% of respondents gave birth to their last baby in government hospitals or private clinics. In addition, 60% of the husbands took care of their wives during pregnancy with 44% during childbirth and about 30% providing help in receiving postpartum care. Moreover, husbands' discussions with a health worker regarding maternal and reproductive health were the most important predictors for support of their wives during pregnancy, childbirth and postpartum care ( < 0.05). Study participants' perception of a satisfying spousal relationship also appeared to be a significant factor for husbands' responsible role regarding wives' antenatal care, delivery and postnatal care ( < 0.05). This study found that pregnant women living in slums received poorer health-related services when there was a low involvement of men; specifically, the husbands of pregnant women. In addition, men's involvement was influenced by many aspects, particularly awareness-related factors (e.g., knowledge, communication and access to reproductive health services). Therefore, awareness creation is important for active involvement in antenatal, delivery and postnatal care. Strategies should be designed to provide men living in the slums with adequate information, education and communication to gain their interest and support about reproductive and maternal health.
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http://dx.doi.org/10.3390/healthcare9040473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073583PMC
April 2021

NB-UVB Induces Melanocytic Differentiation of Human Hair Follicle Neural Crest Stem Cells.

Ann Dermatol 2020 Aug 30;32(4):289-297. Epub 2020 Jun 30.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Phototherapy is an important method to treat vitiligo. However, it is unclear how phototherapy affects melanocyte precursors and skin neural crest stem cells.

Objective: To investigate the underlying mechanisms of narrow-band ultraviolet B (NB-UVB) induced melanocyte lineage differentiated from human scalp-derived neural crest stem cells (HS-NCSCs).

Methods: HS-NCSCs were expanded from scalp hair follicles. The c-Kit/CD57 HS-NCSCs were isolated by cell sorting. Different doses of NB-UVB were used to irradiate these HS-NCSCs. Cell ultrastructure was examined by transmission electron microscope. Melanocyte marker expression was analyzed by Quantitative RT-PCR and Western blot. Cell proliferation and migration were also evaluated.

Results: The c-Kit/CD57 HS-NCSCs expressed embryonic NCSC biomarkers. NB-UVB at a dose of 100 mJ of NB-UVB had little effect on the cell proliferation of differentiated melanocytes from c-Kit/CD57 HS-NCSCs, while 700 mJ inhibited cell proliferation significantly. The dendritic processes of differentiated melanocytes increased after radiation. The and Melanocortin 1 receptor () expression of differentiated melanocytes increased after NB-UVB exposure. The effect of NB-UVB on expression was modulated by signaling inhibitors H89 and PD98059 as well as level in the cells. The migration ability of differentiated melanocytes was enhanced under 100 mJ exposure.

Conclusion: These data demonstrate that NB-UVB facilitates melanocytic differentiation of the HS-NCSCs and enhances migration of these cells. and cAMP pathway play a critical role in NB-UVB induced melanocytic differentiation.
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http://dx.doi.org/10.5021/ad.2020.32.4.289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992648PMC
August 2020

Usefulness of New Shear Wave Elastography Technique for Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study.

Ultraschall Med 2021 Apr 28. Epub 2021 Apr 28.

Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Purpose:  To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis.

Methods:  This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated.

Results:  Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05).

Conclusion:  STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients.
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http://dx.doi.org/10.1055/a-1376-6734DOI Listing
April 2021

Soliton-Mediated Magnetic Reversal in an All-Oxide-Based Synthetic Antiferromagnetic Superlattice.

ACS Appl Mater Interfaces 2021 May 20;13(17):20788-20795. Epub 2021 Apr 20.

Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, China.

All-oxide-based synthetic antiferromagnets (SAFs) are attracting intense research interest due to their superior tunability and great potentials for antiferromagnetic spintronic devices. In this work, using the LaCaMnO/CaRuTiO (LCMO/CRTO) superlattice as a model SAF, we investigated the layer-resolved magnetic reversal mechanism by polarized neutron reflectivity. We found that the reversal of LCMO layer moments is mediated by nucleation, expansion, and shrinkage of a magnetic soliton. This unique magnetic reversal process creates a reversed magnetic configuration of the SAF after a simple field cycling. Therefore, it can enable vertical data transfer from the bottom to the top of the superlattice. The physical origin of this intriguing magnetic reversal process could be attributed to the cooperation of the surface spin-flop effect and enhanced uniaxial magnetic anisotropy of the bottom LCMO layer. This work may pave a way to utilize all-oxide-based SAFs for three-dimensional spintronic devices with vertical data transfer and high-density data storage.
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http://dx.doi.org/10.1021/acsami.1c02506DOI Listing
May 2021

Realizing Colorful Holographic Mimicry by Metasurfaces.

Adv Mater 2021 May 18;33(21):e2005864. Epub 2021 Apr 18.

Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, 02115, USA.

Mimicry is a biological camouflage phenomenon whereby an organism can change its shape and color to resemble another object. Herein, the idea of biological mimicry and rich degrees of freedom in metasurface designs are combined to realize holographic mimicry devices. A general mathematical method, called phase matrix transformation, to accomplish the holographic mimicry process is proposed. Based on this method, a dynamic metasurface hologram is designed, which shows an image of a "bird" in the air, and a distinct image of a "fish" when the environment is changed to oil. Furthermore, to make the mimicry behavior more generic, holographic mimicry operating at dual wavelengths is also designed and experimentally demonstrated. Moreover, the fully independent phase modulation realized by phase matrix transformation makes the working efficiency of the device relatively higher than the conventional multiwavelength holographic devices with off-axis illumination or interleaved subarrays. The work potentially opens a new research paradigm interfacing bionics with nanophotonics, which may produce novel applications for optical information encryption, virtual/augmented reality (VR/AR), and military camouflage systems.
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http://dx.doi.org/10.1002/adma.202005864DOI Listing
May 2021

Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1.

J Immunol Res 2021 29;2021:6670495. Epub 2021 Mar 29.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

At present, liver ischemia-reperfusion (IR) injury is still a great challenge for clinical liver partial resection and liver transplantation. The innate immunity regulated by liver macrophages orchestrates the cascade of IR inflammation and acts as a bridge. As a specific macrophage subunit of vacuolar ATPase, ATP6V0D2 (V-ATPase D2 subunit) has been shown to promote the formation of autophagolysosome in vitro. Our research fills a gap which has existed in the study of inflammatory stress about the V-ATPase subunit ATP6V0D2 in liver macrophages. We first found that the expression of specific ATP6V0D2 in liver macrophages was upregulated with the induction of inflammatory cascade after liver IR surgery, and knockdown of ATP6V0D2 resulted in increased secretion of proinflammatory factors and chemokines, which enhanced activation of NLRP3 and aggravation of liver injury. Further studies found that the exacerbated activation of NLRP3 was related to the autophagic flux regulated by ATP6V0D2. Knocking down ATP6V0D2 impaired the formation of autophagolysosome and aggravated liver IR injury through nonspecific V-ATPase activation independent of V-ATPase-Notchl-Hesl signal axis. In general, we illustrated that the expression of ATP6V0D2 in liver macrophages was upregulated after liver IR, and by gradually promoting the formation of autophagolysosomes to increase autophagy flux to limit the activation of liver inflammation, this regulation is independent of the Notch1-Hes1 signal axis.
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http://dx.doi.org/10.1155/2021/6670495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024071PMC
March 2021

Novel Compound Heterozygous Pathogenic Mutations of in a Chinese Patient With Congenital Hypothyroidism.

Front Endocrinol (Lausanne) 2021 19;12:620117. Epub 2021 Mar 19.

The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background And Objectives: Defects in the human sodium/iodide symporter () gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify mutations in Chinese patients with CH and to evaluate the function of the mutation.

Methods: Two hundred and seventy-three patients with primary CH were screened for mutations in using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in . The functional activity of the mutants was further examined .

Results: In 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired.

Conclusion: The undescribed compound heterozygous mutation of was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of in CH pathogenesis.
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http://dx.doi.org/10.3389/fendo.2021.620117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018529PMC
March 2021

Antibacterial, hemostasis, adhesive, self-healing polysaccharides-based composite hydrogel wound dressing for the prevention and treatment of postoperative adhesion.

Mater Sci Eng C Mater Biol Appl 2021 Apr 19;123:111978. Epub 2021 Feb 19.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, PR China. Electronic address:

Herein, we fabricated novel self-healing, in situ injectable, biodegradable, and non-toxic hydrogels anti-adhesion barrier materials composed of N, O-carboxymethyl chitosan (N,O-CS) and oxidized dextran (ODA) without requiring any chemical cross-linking agent or external stimuli triggers for the prevention and treatment of post-operative peritoneal adhesions. The N,O-CS/ODA hydrogels have a good suitable gelation time, good cytocompatibility and hemocompatibility, good antibacterial activity, excellent biodegradable and biocompatible, and can effectively inhibit the adhesion of fibroblasts to the wound, thereby suggesting that N,O-CS/ODA hydrogels are suitable for preventing post-operative adhesion. Meanwhile, a rat injury sidewall-cecum abrasion model is developed to investigate the efficacy of these hydrogels in achieving post-operative anti-adhesion. A significant reduction of peritoneal adhesions (10% rat with lower score adhesion) is observed in the N,O-CS/ODA-hydrogel-treated group compared with the commercial hydrogel and control groups. These results demonstrated that N,O-CS/ODA hydrogel could effectively prevent post-operative peritoneal adhesion without side effects. Therefore, the N,O-CS/ODA hydrogels with multi-functional properties exhibit great potential for the prevention and treatment of postoperative adhesion.
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http://dx.doi.org/10.1016/j.msec.2021.111978DOI Listing
April 2021

Signaling Pathways Regulated by Silica Nanoparticles.

Molecules 2021 Mar 5;26(5). Epub 2021 Mar 5.

Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.

Silica nanoparticles are a class of molecules commonly used in drug or gene delivery systems that either facilitate the delivery of therapeutics to specific drug targets or enable the efficient delivery of constructed gene products into biological systems. Some in vivo or in vitro studies have demonstrated the toxic effects of silica nanoparticles. Despite the availability of risk management tools in response to the growing use of synthetic silica in commercial products, the molecular mechanism of toxicity induced by silica nanoparticles is not well characterized. The purpose of this study was to elucidate the effects of silica nanoparticle exposure in three types of cells including human aortic endothelial cells, mouse-derived macrophages, and A549 non-small cell lung cancer cells using toxicogenomic analysis. The results indicated that among all three cell types, the TNF and MAPK signaling pathways were the common pathways upregulated by silica nanoparticles. These findings may provide insight into the effects of silica nanoparticle exposure in the human body and the possible mechanism of toxicity.
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http://dx.doi.org/10.3390/molecules26051398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961477PMC
March 2021

Deletion of Kvβ2 (AKR6) Attenuates Isoproterenol Induced Cardiac Injury with Links to Solute Carrier Transporter SLC41a3 and Circadian Clock Genes.

Metabolites 2021 Mar 29;11(4). Epub 2021 Mar 29.

Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.

Kvβ subunits belong to the aldo-keto reductase superfamily, which plays a significant role in ion channel regulation and modulates the physiological responses. However, the role of Kvβ2 in cardiac pathophysiology was not studied, and therefore, in the present study, we hypothesized that Kvβ2 plays a significant role in cardiovascular pathophysiology by modulating the cardiac excitability and gene responses. We utilized an isoproterenol-infused mouse model to investigate the role of Kvβ2 and the cardiac function, biochemical changes, and molecular responses. The deletion of Kvβ2 attenuated the QTc (corrected QT interval) prolongation at the electrocardiographic (ECG) level after a 14-day isoproterenol infusion, whereas the QTc was significantly prolonged in the littermate wildtype group. Monophasic action potentials verified the ECG changes, suggesting that cardiac changes and responses due to isoproterenol infusion are mediated similarly at both the in vivo and ex vivo levels. Moreover, the echocardiographic function showed no further decrease in the ejection fraction in the isoproterenol-stimulated Kvβ2 knockout (KO) group, whereas the wildtype mice showed significantly decreased function. These experiments revealed that Kvβ2 plays a significant role in cardiovascular pathophysiology. Furthermore, the present study revealed SLC41a3, a major solute carrier transporter affected with a significantly decreased expression in KO vs. wildtype hearts. The electrical function showed that the decreased expression of SLC41a3 in Kvβ2 KO hearts led to decreased Mg responses, whereas, in the wildtype hearts, Mg caused action potential duration (APD) shortening. Based on the in vivo, ex vivo, and molecular evaluations, we identified that the deletion of Kvβ2 altered the cardiac pathophysiology mediated by SLC41a3 and altered the NAD (nicotinamide adenine dinucleotide)-dependent gene responses.
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http://dx.doi.org/10.3390/metabo11040201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066990PMC
March 2021

Benefits of Spectral Property Engineering in Distributed Brillouin Fiber Sensing.

Sensors (Basel) 2021 Mar 8;21(5). Epub 2021 Mar 8.

THz Photonics Group, Institut für Hochfrequenztechnik, Technische Universität Braunschweig, Schleinitzstr. 22, 38106 Braunschweig, Germany.

As one of the most consolidated distributed fiber sensors based on stimulated Brillouin scattering, the Brillouin optical time-domain analyzer (BOTDA) has been developed for decades. Despite the commercial availability and outstanding progresses which has been achieved, the intrinsic Lorentzian gain spectrum restricts the sensing performance from possible further enhancements and hence limits the field of validity of the technique. In this paper, the novel method of engineering the gain spectral properties of the Brillouin scattering and its application on static and dynamic BOTDA sensors will be reviewed. Such a spectral property engineering has not only provided improvements to BOTDA, but also might open a new way to enhance the performance of all kinds of distributed Brillouin fiber sensors.
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http://dx.doi.org/10.3390/s21051881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962463PMC
March 2021

Divergence of three BRX homoeologs in Brassica rapa and its effect on leaf morphology.

Hortic Res 2021 Apr 1;8(1):68. Epub 2021 Apr 1.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Science, Beijing, China.

The leafy head characteristic is a special phenotype of Chinese cabbage resulting from artificial selection during domestication and breeding. BREVIS RADIX (BRX) has been suggested to control root elongation, shoot growth, and tiller angle in Arabidopsis and rice. In Brassica rapa, three BrBRX homoeologs have been identified, but only BrBRX.1 and BrBRX.2 were found to be under selection in leaf-heading accessions, indicating their functional diversification in leafy head formation. Here, we show that these three BrBRX genes belong to a plant-specific BRX gene family but that they have significantly diverged from other BRX-like members on the basis of different phylogenetic classifications, motif compositions and expression patterns. Moreover, although the expression of these three BrBRX genes differed, compared with BrBRX.3, BrBRX.1, and BrBRX.2 displayed similar expression patterns. Arabidopsis mutant complementation studies showed that only BrBRX.1 could rescue the brx root phenotype, whereas BrBRX.2 and BrBRX.3 could not. However, overexpression of each of the three BrBRX genes in Arabidopsis resulted in similar pleiotropic leaf phenotypes, including epinastic leaf morphology, with an increase in leaf number and leaf petiole length and a reduction in leaf angle. These leaf traits are associated with leafy head formation. Further testing of a SNP (T/C) in BrBRX.2 confirmed that this allele in the heading accessions was strongly associated with the leaf-heading trait of B. rapa. Our results revealed that all three BrBRX genes may be involved in the leaf-heading trait, but they may have functionally diverged on the basis of their differential expression.
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http://dx.doi.org/10.1038/s41438-021-00504-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012600PMC
April 2021

APRIL: Anatomical prior-guided reinforcement learning for accurate carotid lumen diameter and intima-media thickness measurement.

Med Image Anal 2021 Jul 18;71:102040. Epub 2021 Mar 18.

Digital Image Group (DIG), London, ON, Canada; School of Biomedical Engineering, Western University, London, ON, Canada. Electronic address:

Carotid artery lumen diameter (CALD) and carotid artery intima-media thickness (CIMT) are essential factors for estimating the risk of many cardiovascular diseases. The automatic measurement of them in ultrasound (US) images is an efficient assisting diagnostic procedure. Despite the advances, existing methods still suffer the issue of low measuring accuracy and poor prediction stability, mainly due to the following disadvantages: (1) ignore anatomical prior and prone to give anatomically inaccurate estimation; (2) require carefully designed post-processing, which may introduce more estimation errors; (3) rely on massive pixel-wise annotations during training; (4) can not estimate the uncertainty of the predictions. In this study, we propose the Anatomical Prior-guided ReInforcement Learning model (APRIL), which innovatively formulate the measurement of CALD & CIMT as an RL problem and dynamically incorporate anatomical prior (AP) into the system through a novel reward. With the guidance of AP, the designed keypoints in APRIL can avoid various anatomy impossible mis-locations, and accurately measure the CALD & CIMT based on their corresponding locations. Moreover, this formulation significantly reduces human annotation effort by only using several keypoints and can help to eliminate the extra post-processing steps. Further, we introduce an uncertainty module for measuring the prediction variance, which can guide us to adaptively rectify the estimation of those frames with considerable uncertainty. Experiments on a challenging carotid US dataset show that APRIL can achieve MAE (in pixel/mm) of 3.02±2.23 / 0.18±0.13 for CALD, and 0.96±0.70 / 0.06±0.04 for CIMT, which significantly surpass popular approaches that use more annotations.
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http://dx.doi.org/10.1016/j.media.2021.102040DOI Listing
July 2021

N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction.

J Heart Lung Transplant 2021 Jun 2;40(6):447-457. Epub 2021 Mar 2.

Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Recent evidence suggests a role for lung microbiome in occurrence of chronic lung allograft dysfunction (CLAD). However, the mechanisms linking the microbiome to CLAD are poorly delineated. We investigated a possible mechanism involved in microbial modulation of mucosal response leading to CLAD with the hypothesis that a Proteobacteria dominant lung microbiome would inhibit N-myc-interactor (NMI) expression and induce epithelial to mesenchymal transition (EMT).

Methods: Explant CLAD, non-CLAD, and healthy nontransplant lung tissue were collected, as well as bronchoalveolar lavage from 14 CLAD and matched non-CLAD subjects, which were followed by 16S rRNA amplicon sequencing and quantitative polymerase chain reaction (PCR) analysis. Pseudomonas aeruginosa (PsA) or PsA-lipopolysaccharide was cocultured with primary human bronchial epithelial cells (PBEC). Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate NMI expression and EMT in explants and in PsA-exposed PBECs. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of EMT regulator NMI.

Results: 16S rRNA amplicon analyses revealed that CLAD patients have a higher abundance of phyla Proteobacteria and reduced abundance of the phyla Bacteroidetes. At the genera level, CLAD subjects had an increased abundance of genera Pseudomonas and reduced Prevotella. Human CLAD airway cells showed a downregulation of the N-myc-interactor gene and presence of EMT. Furthermore, exposure of human primary bronchial epithelial cells to PsA resulted in downregulation of NMI and induction of an EMT phenotype while NMI upregulation resulted in attenuation of this PsA-induced EMT response.

Conclusions: CLAD is associated with increased bacterial biomass and a Proteobacteria enriched airway microbiome and EMT. Proteobacteria such as PsA induces EMT in human bronchial epithelial cells via NMI, demonstrating a newly uncovered mechanism by which the microbiome induces cellular metaplasia.
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http://dx.doi.org/10.1016/j.healun.2021.02.014DOI Listing
June 2021