Publications by authors named "Bin Zhou"

1,799 Publications

  • Page 1 of 1

Mutations in RNA Methyltransferase Gene Confer High Risk of Outflow Tract Malformation.

Front Cell Dev Biol 2021 21;9:623394. Epub 2021 Apr 21.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

, encoding a cytosine-5 RNA methyltransferase and located in the 7q11.23 locus, is a candidate gene for tetralogy of Fallot (TOF). Deletion of the 7q11.23 locus in humans is linked to cardiac outflow tract (OFT) disorders including TOF. We identified four potential pathogenic mutations in the coding region of and which were enriched in TOF patients by an association study of 132 TOF patients and 2,000 in-house controls ( = 1.44 × 10). We then generated a null () mouse model to validate the human findings by defining the functions of in OFT morphogenesis. The OFT did not develop properly in the deletion embryonic heart. We found a misalignment of the aorta and septum defects caused by the delayed fusion of the membraneous ventricular spetum as an OFT development delay. This caused OFT development delay in 27 of 64 (42.2%) mice. Moreover, we also found OFT development delay in 8 of 51 (15.7%) mice. Further functional experiments showed that the loss of function impaired the 5-methylcytosine (mC) modification and translation efficiency of essential cardiac genes. is required for normal OFT morphogenesis and it regulates the mC modification of essential cardiac genes. Our findings suggest the involvement of in the pathogenesis of TOF.
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http://dx.doi.org/10.3389/fcell.2021.623394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097101PMC
April 2021

lncRNA NORAD promotes the progression of osteosarcoma via targeting of miR-155-5p.

Exp Ther Med 2021 Jun 18;21(6):645. Epub 2021 Apr 18.

Department of Orthopedics, Ezhou Central Hospital, Ezhou, Hubei 436000, P.R. China.

Osteosarcoma (OS) is the most common malignant bone tumor in teens. Non-coding RNA activated by DNA damage (NORAD), a long non-coding RNA (lncRNA), has been reported to be involved in cancer biology, although its role in OS remains largely unknown. In the present study reverse transcription-quantitative PCR (RT-qPCR) was used to determine the expression levels of NORAD and miR-155-5p in samples from patients with OS. OS cell lines (Saos-2 and U2OS) were used as cell models. The biological influence of NORAD on OS cells was studied using Cell Counting Kit-8 and Transwell assays. The interaction between NORAD and miR-155-5p was clarified by bioinformatics analysis, RT-qPCR, luciferase reporter assay and RNA immunoprecipitation. NORAD was significantly increased in OS samples in comparison with controls, while miR-155-5p was reduced. Knockdown of NORAD and transfection of miR-155-5p mimics markedly inhibited the viability, migration and invasion of OS cells. There was a negative correlation between NORAD and miR-155-5p expression levels in OS samples. Taken together, the results of the present study indicated that the NORAD/miR-155-5p axis played a crucial role in regulating the proliferation, migration and invasion of OS cells. It is hypothesized that NORAD and miR-155-5p may serve as potential novel therapeutic targets for OS management.
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http://dx.doi.org/10.3892/etm.2021.10077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097224PMC
June 2021

Competitive adsorption of Dibutyl phthalate (DBP) and Di(2-ethylhexyl) phthalate (DEHP) onto fresh and oxidized corncob biochar.

Chemosphere 2021 Apr 23;280:130639. Epub 2021 Apr 23.

College of Natural Resources and Environment, South China Agricultural University, Guangzhou, 510642, PR China; College of Resource and Environmental Engineering, Jiangxi University of Science and Technology, Ganzhou Jiangxi, 341000, PR China.

Phthalates (PAEs) often exist simultaneously in contaminated soil and wastewater systems, and their adsorption to biochar might impact their behavior in the environment. So far, the competitive adsorption of PAEs to biochar has not been reported. In this study, the competitive adsorption of Dibutyl phthalate (DBP) and Di(2-ethylhexyl) phthalate (DEHP) on corncob biochar (fresh and oxidized) was investigated, and experiments of kinetics, isotherms, and thermodynamics were conducted. Langmuir and Freundlich models, pseudo-first-order and second-order kinetic models were used to simulate the experimental data. In the mono PAEs component systems, the biochar showed significantly greater adsorption capacity for DEHP (11.8-16.16 mg g) than for DBP (9.86-13.2 mg g). The oxidized biochar has higher adsorption capacities than the fresh one. Moreover, a fast adsorption rate for DBP was observed, which can be attributed to the smaller size and shorter carbon chains in the DBP molecule, resulting in faster diffusion into the biochar pores. In the binary PAEs component systems, competition between DEHP and DBP in their adsorption to the biochars was observed, and DEHP (11.7-15.0 mg g) was preferred over DBP (3.4-7.9 mg g). The stronger adsorption of DEHP can be explained by stronger hydrophobic interaction with biochar. Compared to DBP, DEHP has a high octanol-water partition coefficient (logK) and low water solubility. The positive entropy (ΔS) and enthalpy(ΔH) values for the adsorption of both DEHP and DBP further indicated that hydrophobic interaction played an important role, even though H-bonds and π-π interactions could also be involved.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130639DOI Listing
April 2021

Rapid development of neutralizing and diagnostic SARS-COV-2 mouse monoclonal antibodies.

Sci Rep 2021 05 6;11(1):9682. Epub 2021 May 6.

Immunodiagnostic Development Team/Reagent Diagnostic Services Branch (RDSB)/DSR/NCEZID/CDC, 1600 Clifton Rd NE., Atlanta, GA, 30333, USA.

The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.
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http://dx.doi.org/10.1038/s41598-021-88809-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102525PMC
May 2021

CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish.

Immunol Lett 2021 May 2. Epub 2021 May 2.

SCU-CUHK Joint Laboratory for Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

The number and function of T cells are abnormal as observed in cystic fibrosis (CF) patients and CF mouse models, and our previous work shows that the CFTR mutant leads to deficiency of primitive and definitive hematopoietic in zebrafish. However, the functions and underlying mechanisms of CFTR in T cell development during early embryogenesis have not been explored. Here, we report that the genetic ablation of CFTR in zebrafish resulted in abrogated embryonic T lymphopoiesis, which was ascribed to impaired thymic homing and expansion of hematopoietic stem cells (HSCs). Transcriptome analysis of isolated HSCs in zebrafish embryos at 48 hpf showed a significant alteration of key factors essential for T cell development and Wnt signaling, consistent with our previous work on CFTR regulating hematopoiesis. In brief, we uncovered the function of CFTR in embryonic T cell development and suggest that the immune deficiency of CF patients may originate from an early embryonic stage.
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http://dx.doi.org/10.1016/j.imlet.2021.04.010DOI Listing
May 2021

Anti-pandemic lessons and altruistic behavior from major world religions at the time of COVID-19.

Brain Behav Immun 2021 May 1. Epub 2021 May 1.

Nutrition and Health Research Group, Department of Population Health (DoPH), Luxembourg Institute of Health (LIH), 1 A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg.

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http://dx.doi.org/10.1016/j.bbi.2021.04.023DOI Listing
May 2021

Convergence analysis of sample average approximation for a class of stochastic nonlinear complementarity problems: from two-stage to multistage.

Numer Algorithms 2021 Apr 27:1-28. Epub 2021 Apr 27.

Jiangsu Key Laboratory for NSLSCS, School of Mathematical Sciences, Nanjing Normal University, Nanjing, 210023 China.

In this paper, we consider the sample average approximation (SAA) approach for a class of stochastic nonlinear complementarity problems (SNCPs) and study the corresponding convergence properties. We first investigate the convergence of the SAA counterparts of two-stage SNCPs when the first-stage problem is continuously differentiable and the second-stage problem is locally Lipschitz continuous. After that, we extend the convergence results to a class of multistage SNCPs whose decision variable of each stage is influenced only by the decision variables of adjacent stages. Finally, some preliminary numerical tests are presented to illustrate the convergence results.
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http://dx.doi.org/10.1007/s11075-021-01110-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076443PMC
April 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

Real-Time and Efficient Traffic Information Acquisition via Pavement Vibration IoT Monitoring System.

Sensors (Basel) 2021 Apr 10;21(8). Epub 2021 Apr 10.

National Center for Materials Service Safety, University of Science and Technology Beijing, Haidian District, Beijing 100083, China.

Traditional road-embedded monitoring systems for traffic monitoring have the disadvantages of a short life, high energy consumption and data redundancy, resulting in insufficient durability and high cost. In order to improve the durability and efficiency of the road-embedded monitoring system, a pavement vibration monitoring system is developed based on the Internet of things (IoT). The system includes multi-acceleration sensing nodes, a gateway, and a cloud platform. The key design principles and technologies of each part of the system are proposed, which provides valuable experience for the application of IoT monitoring technology in road infrastructures. Characterized by low power consumption, distributed computing, and high extensibility properties, the pavement vibration IoT monitoring system can realize the monitoring, transmission, and analysis of pavement vibration signal, and acquires the real-time traffic information. This road-embedded system improves the intellectual capacity of road infrastructure and is conducive to the construction of a new generation of smart roads.
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http://dx.doi.org/10.3390/s21082679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069318PMC
April 2021

Radicicol Inhibits Chikungunya Virus Replication by Targeting Nonstructural Protein-2.

Antimicrob Agents Chemother 2021 Apr 26. Epub 2021 Apr 26.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine, City University of Hong Kong, Hong Kong SAR, China

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a debilitating febrile illness characterized by persistent muscle and joint pain. The widespread distribution of transmission-competent vectors, species mosquitoes, indicates the potential risk of large-scale epidemics with high attack rates that can severely impact public health globally. Despite this, currently, there are no antivirals available for the treatment of CHIKV infections. Thus, we aimed to identify potential drug candidates by screening a chemical library using a cytopathic effect-based high-throughput screening assay. As a result, we identified radicicol, a heat-shock protein 90 (Hsp90) inhibitor that effectively suppressed CHIKV replication by blocking the synthesis of both positive- and negative-strand viral RNA as well as expression of viral proteins. Interestingly, selection for viral drug-resistant variants and mutational studies revealed nonstructural protein 2 (nsP2) as a putative molecular target of radicicol. Moreover, co-immunoprecipitation and modeling analyses determined that G641D mutation in the methyltransferase (MT)-like domain of nsP2 is essential for its interaction with cytoplasmic Hsp90β chaperone. Our findings collectively support the potential application of radicicol as an anti-CHIKV agent. The detailed study of the underlying mechanism of action further contributes to understanding virus-host interactions for novel therapeutics against CHIKV infection.
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http://dx.doi.org/10.1128/AAC.00135-21DOI Listing
April 2021

Susceptibility to SARS-CoV-2 of Cell Lines and Substrates Commonly Used to Diagnose and Isolate Influenza and Other Viruses.

Emerg Infect Dis 2021 05;27(5):1380-1392

Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines.
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http://dx.doi.org/10.3201/eid2705.210023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084484PMC
May 2021

Profiling Oncogenic Germline Mutations in Unselected Chinese Lung Cancer Patients.

Front Oncol 2021 7;11:647598. Epub 2021 Apr 7.

Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, China.

Introduction: Emerging evidence has suggested that inherited factors are also involved in lung cancer development. However, most studies focused on well-elucidated cancer predisposition genes, the majority of which are tumor suppressor genes. The profile of germline mutations in oncogenic driver genes remains unrevealed, which might also provide potential clinical implications for lung cancer management.

Methods: Sequencing data from 36,813 unselected lung cancer patients who underwent somatic mutation profiling were retrospectively reviewed. All recruited patients had matched white blood cell samples sequenced in parallel using a capture-based panel including eight key lung cancer driver genes ( (, , and (). Likely pathogenic/pathogenic (LP/P) variants were called according to the classification criteria of the American College of Medical Genetics and Genomics. Variants of uncertain significance (VUS) located in the kinase domains of driver genes and occurring recurrently (n ≥3) were also included for further analyses.

Results: Seven different LP/P variants in , , or were identified in 0.03% of lung cancer patients (n = 14) and 25 different VUS in the kinase domains of seven driver genes (except ) were found with a prevalence of 0.3% (n = 117).Collectively, germline mutations were most frequently seen in (n = 31, 0.084%), followed by (n = 23, 0.062%), (n = 22, 0.06%), (n = 22, 0.06%) and (n = 17, 0.046%). LP/P variants and VUS fell the most commonly in (n = 10, 72%) and (n = 31, 26%), respectively. Of the 10 patients with LP/P germline mutation, 70% also acquired somatic driver mutation exon21 p.L858R or exon19 deletion at baseline; while the three patients with pathogenic germline mutation displayed distinct baseline somatic profiles of rare mutation or exon2 p.G12C. We discovered 11 germline mutations that also occurred somatically, including four LP/P variants and seven VUS.

Conclusion: We present the first study to systemically characterize the germline mutation in oncogenic driver genes in a large cohort of unselected patients with lung cancers.
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http://dx.doi.org/10.3389/fonc.2021.647598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058453PMC
April 2021

Lipid Metabolism Profiles in Rheumatic Diseases.

Front Pharmacol 2021 9;12:643520. Epub 2021 Apr 9.

Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, China.

Rheumatic diseases are a group of chronic autoimmune disorders that involve multiple organs or systems and have high mortality. The mechanisms of these diseases are still ill-defined, and targeted therapeutic strategies are still challenging for physicians. Recent research indicates that cell metabolism plays important roles in the pathogenesis of rheumatic diseases. In this review, we mainly focus on lipid metabolism profiles (dyslipidaemia, fatty acid metabolism) and mechanisms in rheumatic diseases and discuss potential clinical applications based on lipid metabolism profiles.
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http://dx.doi.org/10.3389/fphar.2021.643520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064727PMC
April 2021

Rational Engineering of the DNA Walker Amplification Strategy by Using a Au@TiC@PEI-Ru(dcbpy) Nanocomposite Biosensor for Detection of the SARS-CoV-2 RdRp Gene.

ACS Appl Mater Interfaces 2021 May 23;13(17):19816-19824. Epub 2021 Apr 23.

NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, P.R. China.

The detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for preventing and controlling infectious diseases and disease treatment. In this work, a Au@TiC@PEI-Ru(dcbpy) nanocomposite-based electrochemiluminescence (ECL) biosensor was rationally designed, which realized sensitive detection of the RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2. In addition, a DNA walker was also used to excise the hairpin DNAs under the action of Nb.BbvCI endonuclease. Furthermore, model DNA-Ag nanoclusters (model DNA-AgNCs) were used to quench the initial ECL signal. As a result, the ECL biosensor was used to sensitively detect the SARS-CoV-2 RdRp gene with a detection range of 1 fM to 100 pM and a limit of detection of 0.21 fM. It was indicated that the ECL biosensor had a great application potential for clinical medical detection. Furthermore, the DNA walker amplification also played a reliable candidate strategy for other detection methods.
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http://dx.doi.org/10.1021/acsami.1c04453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084271PMC
May 2021

Effects of cadmium and high-fat diet on essential metal concentration in the mouse testis.

Toxicol Rep 2021 20;8:718-723. Epub 2021 Mar 20.

Department of Pharmacology and Toxicology, University of LouisvilleSchool of Medicine, University of Louisville, USA.

The effects of exposure to the environmental toxicant cadmium, in combination with obesity, on the metal content in mouse testis were evaluated. Starting in utero and continuing through to 10 or 24 weeks post-weaning, male mice were exposed to cadmium (0, 0.5 or 5 ppm), and fed either a low (LFD) or high fat diet (HFD) post-weaning. Testicular levels of cadmium and essential metals were determined 10 and 24 weeks post-weaning by ICP-MS. Similar to what has been previously observed in the liver, kidney, heart and brain, significant levels of cadmium accumulated in the testis under all exposure conditions. Additionally, HFD-fed animals accumulated more cadmium than did their LFD-treated counterparts. Both treatments affected essential metal homeostasis in the testis. These findings suggest that cadmium and obesity may compromise the reproductive potential in the male mouse by disrupting essential metal levels.
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http://dx.doi.org/10.1016/j.toxrep.2021.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047427PMC
March 2021

Development of zein/soluble soybean polysaccharide nanoparticle-stabilized Pickering emulsions.

J Food Sci 2021 Apr 22. Epub 2021 Apr 22.

Key Laboratory of Fermentation Engineering, Ministry of Education, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, School of Biological Engineering and Food, Hubei University of Technology, Wuhan, China.

Pickering emulsions have received wide attention due to their "surfactant-free" character and the ability of delivery bioactive compounds. In the current work, zein and soluble soybean polysaccharide (SSPS) food-grade composite nanoparticles (NPs) were fabricated as Pickering stabilizers. The particle size of the composite NPs varied with the concentration of zein and SSPS, consequently leading to larger hydrodynamic diameters compared with zein nanoparticles (ZPs) in all formulations, also seen from the scanning electron microscopy (SEM) images. At pH 4.0, the dispersions of ZPs exhibited a positive ζ-potential (around at +12 mV); however, zein/SSPS NPs obtained at the same pH had much lower ζ-potential (about -2 mV) further proving that there was electrostatic interaction between SSPS and zein. The composite nanoparticles (NPs) were well dispersed through the results of polydispersity index (PDI). The physical properties and stability of zein/SSPS NPs stabilized Pickering emulsions were evaluated at a fixed oil phase volume (30%, v/v). On the surface of the oil droplets, a densely packed interface layer was observed by confocal laser scanning microscopy (CLSM), which could prevent oil droplets from coalescence and Ostwald ripening. At zein concentration of 6 mg/mL and SSPS concentration of 1 mg/mL, the formed Pickering emulsions had higher stability at 25 °C. PRACTICAL APPLICATION: The findings of this study can be utilized and integrated to further extend the application of zein in foods, medicine, or cosmetics field. This study showed that the food-grade composite colloidal particles formed by electrostatic interaction can significantly improve the emulsification properties of zein and soluble soybean polysaccharides, and stability. The Pickering emulsions have been observed in long-term testing.
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http://dx.doi.org/10.1111/1750-3841.15730DOI Listing
April 2021

Inhibiting BDNF/TrkB.T1 receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia.

J Neuroinflammation 2021 Apr 19;18(1):96. Epub 2021 Apr 19.

Department of Anesthesiology and Pain Management, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu, China.

Background: Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. A truncated isoform of the tropomyosin receptor kinase B (TrkB) receptor TrkB.T1, as a high-affinity receptor of BDNF, is upregulated in multiple nervous system injuries, and such upregulation is associated with pain. Acid-sensitive ion channel 3 (ASIC3) is involved in chronic neuropathic pain, but its relation with BDNF/TrkB.T1 in the peripheral nervous system (PNS) during PHN is unclear. This study aimed to investigate whether BDNF/TrkB.T1 contributes to PHN through regulating ASIC3 signaling in dorsal root ganglia (DRGs).

Methods: Resiniferatoxin (RTX) was used to induce rat PHN models. Mechanical allodynia was assessed by measuring the paw withdrawal thresholds (PWTs). Thermal hyperalgesia was determined by detecting the paw withdrawal latencies (PWLs). We evaluated the effects of TrkB.T1-ASIC3 signaling inhibition on the behavior, neuronal excitability, and inflammatory response during RTX-induced PHN. ASIC3 short hairpin RNA (shRNA) transfection was used to investigate the effect of exogenous BDNF on inflammatory response in cultured PC-12 cells.

Results: RTX injection induced mechanical allodynia and upregulated the protein expression of BDNF, TrkB.T1, ASIC3, TRAF6, nNOS, and c-Fos, as well as increased neuronal excitability in DRGs. Inhibition of ASIC3 reversed the abovementioned effects of RTX, except for BDNF and TrkB.T1 protein expression. In addition, inhibition of TrkB.T1 blocked RTX-induced mechanical allodynia, activation of ASIC3 signaling, and hyperexcitability of neurons. RTX-induced BDNF upregulation was found in both neurons and satellite glia cells in DRGs. Furthermore, exogenous BDNF activated ASIC3 signaling, increased NO level, and enhanced IL-6, IL-1β, and TNF-α levels in PC-12 cells, which was blocked by shRNA-ASIC3 transfection.

Conclusion: These findings demonstrate that inhibiting BDNF/TrkB.T1 reduced inflammation, decreased neuronal hyperexcitability, and improved mechanical allodynia through regulating the ASIC3 signaling pathway in DRGs, which may provide a novel therapeutic target for patients with PHN.
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http://dx.doi.org/10.1186/s12974-021-02148-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054387PMC
April 2021

PMEPA1 stimulates the proliferation, colony formation of pancreatic cancer cells via the MAPK signaling pathway.

Am J Med Sci 2021 Apr 12. Epub 2021 Apr 12.

Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266003, China. Electronic address:

Background: Prostate transmembrane protein androgen-induced 1 (PMEPA1) is reportedly highly expressed in pancreatic cancer (PC). However, its biological role and associated mechanisms have not been addressed in PC progression.

Methods: PMEPA1 mRNA expression and survival outcome of PC patients were evaluated via the GEPIA website. Lentiviral-mediated shRNA knockdown and ectopic expression of PMEPA1 were implemented in the pancreatic cancer cell line PANC1 cells. CCK-8 and colony formation assays were carried out to assess the biological function of PMEPA1 in PANC1 proliferation and viability. Dual-luciferase reporter assays and RT-qPCR were used to assess the interactive relationship between PMEPA1 and the MAPK signaling pathway.

Results: By analyzing the data from GEPIA, we found that PMEPA1 mRNA expression is overexpressed in PC tissues compared with matched nontumor tissues. PMEPA1-high PC patients are predicted to have a worse prognosis than PMEPA1-low PC patients. We found that PMEPA1 shRNA suppressed PANC1 proliferation and colony formation capacity, while enforced expression of PMEPA1 yielded the opposite results. Mechanical investigations showed that PMEPA1 exerts its tumor-promoting function in pancreatic cancer via activation of the MAPK signaling pathway.

Conclusion: PMEPA1 promotes the progression of PC at least partially by activating the MAPK signaling pathway; thus, the PMEPA1/MAPK axis may be a potential therapeutic target in pancreatic cancer.
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http://dx.doi.org/10.1016/j.amjms.2021.04.002DOI Listing
April 2021

Dual recombinases-based genetic lineage tracing for stem cell research with enhanced precision.

Sci China Life Sci 2021 Apr 9. Epub 2021 Apr 9.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Stem cell research has become a hot topic in biology, as the understanding of stem cell biology can provide new insights for both regenerative medicine and clinical treatment of diseases. Accurately deciphering the fate of stem cells is the basis for understanding the mechanism and function of stem cells during tissue repair and regeneration. Cre-loxP-mediated recombination has been widely applied in fate mapping of stem cells for many years. However, nonspecific labeling by conventional cell lineage tracing strategies has led to discrepancies or even controversies in multiple fields. Recently, dual recombinase-mediated lineage tracing strategies have been developed to improve both the resolution and precision of stem cell fate mapping. These new genetic strategies also expand the application of lineage tracing in studying cell origin and fate. Here, we review cell lineage tracing methods, especially dual genetic approaches, and then provide examples to describe how they are used to study stem cell fate plasticity and function in vivo.
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http://dx.doi.org/10.1007/s11427-020-1889-9DOI Listing
April 2021

Epidemiologic characteristics associated with SARS-CoV-2 antigen-based test results, rRT-PCR cycle threshold values, subgenomic RNA, and viral culture results from university testing.

Clin Infect Dis 2021 Apr 13. Epub 2021 Apr 13.

COVID-19 Response Team, CDC.

Background: Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for SARS-CoV-2. Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited.

Methods: Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture.

Results: Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (OR 4.6, CI:1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, CI:0.03-0.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, CI:0.4-0.8) were less likely, and specimens positive for sgRNA (OR 10.2, CI:1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values <29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%).

Conclusions: SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.
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http://dx.doi.org/10.1093/cid/ciab303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083323PMC
April 2021

Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis.

Nat Commun 2021 04 12;12(1):2174. Epub 2021 Apr 12.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610064, China.

Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvβ3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.
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http://dx.doi.org/10.1038/s41467-021-22454-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042091PMC
April 2021

The transcription factor Sox7 modulates endocardiac cushion formation contributed to atrioventricular septal defect through Wnt4/Bmp2 signaling.

Cell Death Dis 2021 Apr 12;12(4):393. Epub 2021 Apr 12.

Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.

Cardiac septum malformations account for the largest proportion in congenital heart defects. The transcription factor Sox7 has critical functions in the vascular development and angiogenesis. It is unclear whether Sox7 also contributes to cardiac septation development. We identified a de novo 8p23.1 deletion with Sox7 haploinsufficiency in an atrioventricular septal defect (AVSD) patient using whole exome sequencing in 100 AVSD patients. Then, multiple Sox7 conditional loss-of-function mice models were generated to explore the role of Sox7 in atrioventricular cushion development. Sox7 deficiency mice embryos exhibited partial AVSD and impaired endothelial to mesenchymal transition (EndMT). Transcriptome analysis revealed BMP signaling pathway was significantly downregulated in Sox7 deficiency atrioventricular cushions. Mechanistically, Sox7 deficiency reduced the expressions of Bmp2 in atrioventricular canal myocardium and Wnt4 in endocardium, and Sox7 binds to Wnt4 and Bmp2 directly. Furthermore, WNT4 or BMP2 protein could partially rescue the impaired EndMT process caused by Sox7 deficiency, and inhibition of BMP2 by Noggin could attenuate the effect of WNT4 protein. In summary, our findings identify Sox7 as a novel AVSD pathogenic candidate gene, and it can regulate the EndMT involved in atrioventricular cushion morphogenesis through Wnt4-Bmp2 signaling. This study contributes new strategies to the diagnosis and treatment of congenital heart defects.
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http://dx.doi.org/10.1038/s41419-021-03658-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041771PMC
April 2021

A comparison of non-intubated video-assisted thoracic surgery with spontaneous ventilation and intubated video-assisted thoracic surgery: a meta-analysis based on 14 randomized controlled trials.

J Thorac Dis 2021 Mar;13(3):1624-1640

Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, China.

Background: Video-assisted thoracic surgery (VATS) generally involves endotracheal intubation under general anesthesia. However, inevitably, this may cause intubation-related complications and prolong the postoperative recovery process. Gradually, non-intubated video-assisted thoracic surgery (NIVATS) is increasingly being utilized. However, its safety and efficacy remain controversial.

Methods: Randomized controlled trials (RCTs) published up to August 2020 were selected from the Cochrane Library, Web of Science, PubMed, Embase, and ClinicalTrials.gov databases and included in this study according to the inclusion criteria. Two reviewers screened these RCTs and independently extracted the relevant data. After assessing the risk of bias in these RCTs, a meta-analysis was performed using Review Manager 5.3. Pooled data were meta-analyzed using a random-effects model.

Results: Meta-analysis data demonstrated that the mean difference (MD) in the length of hospital stay between non-intubated patients and intubated patients was -1.41 days, with a 95% confidence interval (CI) of -2.47 to -0.34 (P=0.01). The visual analogue scale (VAS) score between the two groups showed a MD of -0.34 (95% CI: -0.58 to -0.10; P=0.006). Patients who underwent NIVATS presented with lower rates of overall complications [odds ratio (OR) 0.41; 95% CI: 0.25 to 0.67; P=0.0004], air leak (OR 0.45; 95% CI: 0.24 to 0.87; P=0.02), pharyngeal discomfort (OR 0.08; 95% CI: 0.04 to 0.17; P<0.00001), hoarseness (OR 0.06; 95% CI: 0.02 to 0.21; P<0.00001), and gastrointestinal reactions (OR 0.23; 95% CI: 0.10 to 0.53; P=0.0005) compared to intubated patients. The anesthesia satisfaction scores in the NIVATS group were significantly higher than those of the VATS group (MD 0.50; 95% CI: 0.12 to 0.88; P=0.009). However, there were no statistically significant differences in the length of operation time (MD 0.90 hours; 95% CI: -0.23 to 2.03; P=0.12) and surgical field satisfaction (1 point) (OR 0.73; 95% CI: 0.34 to 1.59; P=0.43) between the two groups.

Conclusions: NIVATS is a safe and feasible form of intervention that can reduce the postoperative pain and complications of various systems and shorten hospital stay duration without prolonging the operation time.
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http://dx.doi.org/10.21037/jtd-20-3039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024812PMC
March 2021

Dual Targeting EGFR and STAT3 With Erlotinib and Alantolactone Co-Loaded PLGA Nanoparticles for Pancreatic Cancer Treatment.

Front Pharmacol 2021 19;12:625084. Epub 2021 Mar 19.

Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Pancreatic cancer (PC) is one of the most common malignancies and also a leading cause of cancer-related mortality worldwide. Many studies have shown that epidermal growth factor receptor (EGFR) is highly expressed in PC, which provides a potential target for PC treatment. However, EGFR inhibitors use alone was proven ineffective in clinical trials, due to the persistence of cellular feedback mechanisms which foster therapeutic resistance to single targeting of EGFR. Specifically, the signal transducer and activator of transcription 3 (STAT3) is over-activated when receiving an EGFR inhibitor and is believed to be highly involved in the failure and resistance of EGFR inhibitor treatment. Therein, we hypothesized that dual inhibition of EGFR and STAT3 strategy could address the STAT3 induced resistance during EGFR inhibitor treatment. To this end, we tried to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles to co-load Alantolactone (ALA, a novel STAT3 inhibitor) and Erlotinib (ERL, an EGFR inhibitor) for pancreatic cancer to test our guess. The loading ratio of ALA and ERL was firstly optimized to achieve a combined cancer-killing effect. Then, the ALA- and ERL-co-loaded nanoparticles (AE@NPs) were successfully prepared and characterized, and the related anticancer effects and cellular uptake of AE@NPs were studied. We also further detailly explored the underlying mechanisms. The results suggested that AE@NPs with uniform particle size and high drug load could induce significant pancreatic cancer cell apoptosis and display an ideal anticancer effect. Mechanism studies showed that AE@NPs inhibited the phosphorylation of both EGFR and STAT3, indicating the dual suppression of these two signaling pathways. Additionally, AE@NPs could also activate the ROS-p38 axis, which is not observed in the single drug treatments. Collectively, the AE@NPs prepared in this study possess great potential for pancreatic cancer treatment by dual suppressing of EGFR and STAT3 pathways and activating ROS-responsive p38 MAPK pathway.
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http://dx.doi.org/10.3389/fphar.2021.625084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017486PMC
March 2021

Removal of chlortetracycline and antibiotic resistance genes in soil by earthworms (epigeic Eisenia fetida and endogeic Metaphire guillelmi).

Sci Total Environ 2021 Mar 23;781:146679. Epub 2021 Mar 23.

College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642, China; College of Resource and Environmental Engineering, Jiangxi University of Science and Technology, Ganzhou, Jiangxi 341000, PR China. Electronic address:

The impacts of two ecological earthworms on the removal of chlortetracycline (CTC, 0.5 and 15 mg kg) and antibiotic resistance genes (ARGs) in soil were explored through the soil column experiments. The findings showed that earthworm could significantly accelerate the degradation of CTC and its metabolites (ECTC) in soil (P < 0.05), with epigeic Eisenia fetida promoting degradation rapidly and endogeic Metaphire guillelmi exhibiting a slightly better elimination effect. Earthworms alleviated the abundances of tetR, tetD, tetPB, tetG, tetA, sul1, TnpA, ttgB and intI1 in soil, with the total relative abundances of ARGs decreasing by 35.0-44.2% in earthworm treatments at the 28th day of cultivation. High throughput sequencing results displayed that the structure of soil bacteria community was modified apparently with earthworm added, and some possible CTC degraders, Aeromonas, Flavobacterium and Luteolibacter, were promoted by two kinds of earthworms. Redundancy analysis demonstrated that the reduction of CTC residues, Actinobacteria, Acidobacteria and Gemmatimonadetes owing to earthworm stimulation was responsible for the removal of ARGs and intI1 in soil. Additionally, intI1 declined obviously in earthworm treatments, which could weaken the risk of horizontal transmission of ARGs. Therefore, earthworm could restore the CTC-contaminated soil via enhancing the removal of CTC, its metabolites and ARGs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146679DOI Listing
March 2021

Assessment of CPS + EG, Neo-Bioscore and Modified Neo-Bioscore in Breast Cancer Patients Treated With Preoperative Systemic Therapy: A Multicenter Cohort Study.

Front Oncol 2021 16;11:606477. Epub 2021 Mar 16.

Institute of Mental Health, Peking University, Beijing, China.

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals' databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan-Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 . 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore.

Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03437837.
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http://dx.doi.org/10.3389/fonc.2021.606477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009183PMC
March 2021

Endothelial Wnts control mammary epithelial patterning via fibroblast signaling.

Cell Rep 2021 Mar;34(13):108897

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address:

Endothelial and fibroblast niches are crucial for epithelial organs. How these heterotypic cells interact is of great interest. In this study, we reveal an axis of signaling in which fibroblasts relay Wnt signals from the endothelial niche to organize epithelial patterning. We generate an Axin2-membrane GFP (mGFP) reporter mouse and observe robust Wnt/β-catenin signaling activities in fibroblasts surrounding the mammary epithelium. To enable cell-type-specific gene manipulation in vitro, we establish an organoid system via coculture of endothelial cells (ECs), fibroblasts, and mammary epithelial cells. Deletion of β-catenin in fibroblasts impedes epithelium branching, and ECs are responsible for the activation of Wnt/β-catenin signaling in fibroblasts. In vivo, EC deletion of Wntless inhibits Wnt/β-catenin signaling activity in fibroblasts, rendering a reduction in epithelial branches. These findings highlight the significance of the endothelial niche in tissue patterning, shedding light on the interactive mechanisms in which distinct niche components orchestrate epithelial organogenesis and tissue homeostasis.
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http://dx.doi.org/10.1016/j.celrep.2021.108897DOI Listing
March 2021

An integrated migration and transformation model to evaluate the occurrence characteristics and environmental risks of Nitrogen and phosphorus in constructed wetland.

Chemosphere 2021 Mar 13;277:130219. Epub 2021 Mar 13.

Tianjin Lingang Construction Development Co., Ltd, Tianjin, 300450, China.

In this study, an integrated migration and transformation (IMT) model based on microbial action, plant absorption, sediment release and substrate adsorption was firstly established to evaluate the temporal-spatial distribution of N and P in Lingang hybrid constructed wetland (CW), Tianjin. Compared to the conventional transformation model that only considers the microbial action, the IMT model could accurately predict the occurrence characteristics of N and P. In Lingang CW, NO-N (0.56-3.63 mg/L) was the most important form of N, and the TP was at a relatively low concentration level (0.04-0.07 mg/L). The spatial distribution results showed that a certain amount of N and P could be removed by CW. Form the temporal perspective, the N and P concentrations were greatly affected by the dissolved oxygen (DO). The simulated values obtained by IMT model indicated that the distribution of N and P was more affected by the temporality compared with the spatiality, which was consistent with measured values. Besides, the PCA indicated that TN, NO-N and DO were important factors, which affected the water quality of CW. The Nemerow pollution index method based on the simulated values indicated that Lingang CW was overall moderately polluted, and the subsurface area was the main functional unit of pollutants removal in CW. This work provides a new model for accurately predicting the occurrence characteristics of N and P pollutants in CW, which is of great significance for identifying its environmental risks and optimizing the construction of wetlands.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130219DOI Listing
March 2021

Pattern recognition in distributed fiber-optic acoustic sensor using an intensity and phase stacked convolutional neural network with data augmentation.

Opt Express 2021 Feb;29(3):3269-3283

Distributed acoustic sensors (DASs) have the capability of registering faint vibrations with high spatial resolution along the sensing fiber. Advanced algorithms are important for DAS in many applications since they can help extract and classify the unique signatures of different types of vibration events. Deep convolutional neural networks (CNNs), which have powerful spectro-temporal feature learning capability, are well suited for event classification in DAS. Generally, these data-driven methods are highly dependent on the availability of large quantities of training data for learning a mapping from input to output. In this work, to fully utilize the collected information and maximize the power of CNNs, we propose a method to enlarge the useful dataset for CNNs from two aspects. First, we propose an intensity and phase stacked CNN (IP-CNN) to utilize both the intensity and phase information from a DAS with coherent detection. Second, we propose to use data augmentation to further increase the training dataset size. The influence of different data augmentation methods on the performance of the proposed CNN architecture is thoroughly investigated. The experimental results show that the proposed IP-CNN with data augmentation produces a classification accuracy of 88.2% on our DAS dataset with 1km sensing length. This indicates that the usage of both intensity and phase information together with the enlarged training dataset after data augmentation can greatly improve the classification accuracy, which is useful for DAS pattern recognition in real applications.
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http://dx.doi.org/10.1364/OE.416537DOI Listing
February 2021

Robust integration of multiple single-cell RNA sequencing datasets using a single reference space.

Nat Biotechnol 2021 Mar 25. Epub 2021 Mar 25.

Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.

In many biological applications of single-cell RNA sequencing (scRNA-seq), an integrated analysis of data from multiple batches or studies is necessary. Current methods typically achieve integration using shared cell types or covariance correlation between datasets, which can distort biological signals. Here we introduce an algorithm that uses the gene eigenvectors from a reference dataset to establish a global frame for integration. Using simulated and real datasets, we demonstrate that this approach, called Reference Principal Component Integration (RPCI), consistently outperforms other methods by multiple metrics, with clear advantages in preserving genuine cross-sample gene expression differences in matching cell types, such as those present in cells at distinct developmental stages or in perturbated versus control studies. Moreover, RPCI maintains this robust performance when multiple datasets are integrated. Finally, we applied RPCI to scRNA-seq data for mouse gut endoderm development and revealed temporal emergence of genetic programs helping establish the anterior-posterior axis in visceral endoderm.
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http://dx.doi.org/10.1038/s41587-021-00859-xDOI Listing
March 2021