Publications by authors named "Mei Hong"

539 Publications

Associations between KCNQ1 and ITIH4 gene polymorphisms and infant weight gain in early life.

Pediatr Res 2021 Jul 10. Epub 2021 Jul 10.

Department of Woman and Child's Care and Adolescence Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: An earlier meta-analysis of genome-wide association studies in Asian populations detected five novel body mass index-associated single-nucleotide polymorphisms (SNPs), including potassium voltage-gated channel subfamily Q member 1 (KCNQ1) (rs2237892), ALDH2/MYL2 (rs671, rs12229654), ITIH4 (rs2535633), and NT5C2 (rs11191580). Whether these SNPs take effect in early life, for example, affect infant rapid weight gain (RWG), is unclear.

Methods: We obtained genomic DNA from 460 term infants with normal birth weight. RWG was defined as the change of weight-for-age standardized Z-score, calculated according to the Children Growth Standard released by the World Health Organization, from birth to 3 months of age >0.67. Using genetic models, associations between the candidate SNPs and infant RWG were examined, along with the interaction between the SNPs and the potential risk factors.

Results: RWG was presented in 225 of 460 infants. SNP rs2535633 and rs2237892 were associated with the risk of RWG. Both additive and multiplicative interaction effects were found between infant delivery mode and rs2237892. The negative association between the rs2237892 T allele and infant RWG was only observed in vaginally delivered infants.

Conclusions: Obesity-related loci rs2535633 and rs2237892 are associated with infant RWG in the first 3 months of infancy. The relationship between rs2237892 and infant RGW might be moderated by cesarean delivery.

Impact: Genetic predisposition is an essential aspect to understand infant weight gain. Obesity-related SNPs, rs2535633 and rs2237892, are associated with RWG in very early years of life. The negative association between rs2237892 T allele and RWG is only observed in infants delivered vaginally instead of cesarean section.
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http://dx.doi.org/10.1038/s41390-021-01601-8DOI Listing
July 2021

Cellulose-derived polyols as high-capacity adsorbents for rapid boron and organic pollutants removal from water.

J Hazard Mater 2021 Jun 26;419:126503. Epub 2021 Jun 26.

Key Laboratory of New Membrane Materials, Ministry of Industry and Information Technology, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, PR China; Institute of Polymer Ecomaterials, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, PR China. Electronic address:

Excess boron in water could result in a critical hazard to plants and humans. Traditional treatment approaches cannot efficiently remove boron from water, especially during seawater desalination using reverse osmosis technology. Achieving satisfactory adsorption capacity and rate for boron remains an unmet goal for decades. Herein, we report cellulose-derived polyols as high-performance adsorbents that can rapidly remove boron and organic pollutants from water. Cellulose-derived polyols were synthesized from saccharides and cellulose via controlled radical polymerization and click reaction. Remarkably, [email protected] can adsorb boron with an astonishing capacity of ~34 mg g in 10 min, which surpasses all those cellulose-based materials reported thus far, meanwhile, much faster than those of commercial adsorption resin. Moreover, cellulose-derived polyols also showed high removal efficiencies (70-98% in several minutes) toward certain organic pollutants, including Congo red and Reactive Blue 19. The water-insoluble characteristic of cellulose-derived polyols is advantageous to be separated from the treated sewage after adsorption for reuse. This work provides a novel insight into the fabrication of safe, fast, and high-capacity cellulose adsorbents for water purification.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126503DOI Listing
June 2021

Xylan Structure and Dynamics in Native Grass Cell Walls Investigated by Solid-State NMR Spectroscopy.

ACS Omega 2021 Jun 3;6(23):15460-15471. Epub 2021 Jun 3.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

The polysaccharide composition and dynamics of the intact stem and leaf cell walls of the model grass are investigated to understand how developmental stage affects the polysaccharide structure of grass cell walls. C enrichment of the entire plant allowed detailed analysis of the xylan structure, side-chain functionalization, dynamics, and interaction with cellulose using magic-angle-spinning solid-state NMR spectroscopy. Quantitative one-dimensional C NMR spectra and two-dimensional C-C correlation spectra indicate that stem and leaf cell walls contain less pectic polysaccharides compared to previously studied seedling primary cell walls. Between the stem and the leaf, the secondary cell wall-rich stem contains more xylan and more cellulose compared to the leaf. Moreover, the xylan chains are about twofold more acetylated and about 60% more ferulated in the stem. These highly acetylated and ferulated xylan chains adopt a twofold conformation more prevalently and interact more extensively with cellulose. These results support the notion that acetylated xylan is found more in the twofold screw conformation, which preferentially binds cellulose. This in turn promotes cellulose-lignin interactions that are essential for the formation of the secondary cell wall.
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http://dx.doi.org/10.1021/acsomega.1c01978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210444PMC
June 2021

Mangiferin Promotes Bregs Level, Activates Nrf2 Antioxidant Signaling, and Inhibits Proinflammatory Cytokine Expression in Murine Splenic Mononuclear Cells In Vitro.

Curr Med Sci 2021 Jun 15;41(3):454-464. Epub 2021 Jun 15.

Department of Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.

Recent studies indicated that regulatory B cells (Bregs) and nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signaling pathway play important roles in the pathogenesis of chronic graft-versus-host disease (cGVHD). Mangiferin (MA), a polyphenol compound, has been reported to activate Nrf2/antioxidant-responsive element (ARE) signaling pathway. This study was aimed to investigate the effects of MA on Bregs and Nrf2 antioxidant signaling in murine splenic mononuclear cells (MNCs) in vitro. Our results revealed that MA could increase the Bregs level in murine splenic MNCs. Moreover, MA up-regulated the expression of Bregs-associated immunosuppressive factor interleukin-10 (IL-10) by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) signaling in murine splenic MNCs. Meanwhile, MA inhibited the proinflammatory cytokines IL-2 and interferon-γ (INF-γ) at both mRNA and protein levels. MA also enhanced the transcription and protein expression of Nrf2 and NADPH quinine oxidoreductase 1 (NQO1), whereas decreased that of Kelch-like ECH-associated protein 1 (Keap1) in murine splenic MNCs. Moreover, MA promoted the proliferation and inhibited the apoptosis of murine splenic MNCs. These results suggested that MA exerts immunosuppressive effects by upregulating the Bregs level, activating the Nrf2 antioxidant pathway, and inhibiting the expression of pro-immunoinflammatory factors. MA, as a natural immunomodulatory and anti-inflammatory agent, may have a potential role in the prophylaxis and treatment of cGVHD.
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http://dx.doi.org/10.1007/s11596-021-2371-9DOI Listing
June 2021

The associations of birth outcome differences in twins with prenatal exposure to bisphenol A and its alternatives.

Environ Res 2021 Jun 11;200:111459. Epub 2021 Jun 11.

Department of Occupational and Environmental Health, School of Basic Medicine and Public Health, Jinan University, Guangzhou, Guangdong, PR China. Electronic address:

Background: Bisphenol A (BPA) and its alternatives, including BPF and BPS, exhibit endocrine disruption activities. However, the effects of bisphenols on fetal growth in twins remain unclear.

Objective: To explore the associations of prenatal BPA, BPF, and BPS exposure with birth outcome differences in twins.

Methods: We recruited 289 twin pregnant women who visited the hospital for prenatal examination during the first trimester from 2013 to 2016. Urinary bisphenol levels were determined during the first, second, and third trimesters. The associations of maternal exposure to bisphenols with birth outcome differences in twins were analyzed after stratification by different trimesters. We applied the multiple informant model to estimate trimester-specific associations between urinary bisphenol concentrations and birth outcome differences in twins.

Results: We found low reproducibility (ICC<0.40) for maternal urinary BPA and moderate reproducibility (0.40 < ICC<0.75) for BPF and BPS. Urinary BPA concentrations were positively associated with within-pair twin birth weight difference when comparing the third vs. the first tertile in each of the three trimesters (i.e., 133.06 g, 95% CI: 68.19, 197.94; 144.5 g, 95%CI: 81.82-207.18 g; and 135.04 g, 95%CI: 71.37-198.71 g for the 1st, 2nd, and 3rd trimester, respectively). The effect of urinary BPA concentration on increased birth length difference within-pair twins were also observed across different trimesters (All P for trends < 0.05). Urinary BPA levels were positively associated with the within-pair birth weight and birth length differences across pregnancy trimesters (All of Type 3 P for values < 0.05).

Conclusion: Maternal BPA exposure appeared to influence birth wight and birth length differences in twins. Our results warrant further confirmation.
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http://dx.doi.org/10.1016/j.envres.2021.111459DOI Listing
June 2021

Structurally Based Design of Glucagon Mutants That Inhibit Fibril Formation.

Biochemistry 2021 Jun 14;60(25):2033-2043. Epub 2021 Jun 14.

Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.

The peptide hormone glucagon is prescribed as a pharmaceutical compound to treat diabetic hypoglycemia. However, at the acidic pH where it is highly soluble, glucagon rapidly aggregates into inactive and cytotoxic amyloid fibrils. The recently determined high-resolution structure of these fibrils revealed various stabilizing molecular interactions. On the basis of this structure, we have now designed four arginine mutants of glucagon that resist fibrillization at pharmaceutical concentrations for weeks. An S2R, T29R double mutant and a T29R single mutant remove a hydrogen-bonding interaction in the wild-type fibril, whereas a Y13R, A19R double mutant and a Y13R mutant remove a cation-π interaction. H solution nuclear magnetic resonance spectra and ultraviolet absorbance data indicate that these mutants remain soluble in pH 2 buffer under quiescent conditions at concentrations of ≤4 mg/mL for weeks. Under stressed conditions with high salt concentrations and agitation, these mutants fibrillize significantly more slowly than the wild type. The S2R, T29R mutant and the T29R mutant exhibit a mixture of random coil and α-helical conformations, while the Y13R mutant is completely random coil. The mutation sites are chosen to be uninvolved in strong interactions with the glucagon receptor in the active structure of the peptide. Therefore, these arginine mutants of glucagon are promising alternative compounds for treating hypoglycemia.
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http://dx.doi.org/10.1021/acs.biochem.1c00214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254510PMC
June 2021

Disruption of endothelial Pfkfb3 ameliorates diet-induced murine insulin resistance.

J Endocrinol 2021 Jul 14;250(3):93-104. Epub 2021 Jul 14.

Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.

Overnutrition-induced endothelial inflammation plays a crucial role in high-fat diet (HFD)-induced insulin resistance in animals. Endothelial glycolysis plays a critical role in endothelial inflammation and proliferation, but its role in diet-induced endothelial inflammation and subsequent insulin resistance has not been elucidated. PFKFB3 is a critical glycolytic regulator, and its increased expression has been observed in adipose vascular endothelium of C57BL/6J mice fed with HFD in vivo, and in palmitate (PA)-treated primary human adipose microvascular endothelial cells (HAMECs) in vitro. We generated mice with Pfkfb3 deficiency selective for endothelial cells to examine the effect of endothelial Pfkfb3 in endothelial inflammation in metabolic organs and in the development of HFD-induced insulin resistance. EC Pfkfb3-deficientmice exhibited mitigated HFD-induced insulin resistance, including decreased body weight and fat mass, improved glucose clearance and insulin sensitivity, and alleviated adiposity and hepatic steatosis. Mechanistically, cultured PFKFB3 knockdown HAMECs showed decreased NF-κB activation induced by PA, and consequent suppressed adhesion molecule expression and monocyte adhesion. Taken together, these results demonstrate that increased endothelial PFKFB3 expression promotes diet-induced inflammatory responses and subsequent insulin resistance, suggesting that endothelial metabolic alteration plays an important role in the development of insulin resistance.
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http://dx.doi.org/10.1530/JOE-20-0524DOI Listing
July 2021

Robotic lateral pancreaticojejunostomy surgery for pancreatic duct stones in children.

J Pediatr Surg 2021 Apr 28. Epub 2021 Apr 28.

Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.jpedsurg.2021.04.021DOI Listing
April 2021

What Links Maternal Prepregnancy BMI to Early Childhood BMI: A Serial Mediation Analysis.

Obesity (Silver Spring) 2021 Jul 14;29(7):1164-1170. Epub 2021 May 14.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: The aim of this study was to explore the potential impact of maternal gestational weight gain (GWG), infant birth weight, and postnatal weight change (ΔWAZ) on the relationship between maternal prepregnancy BMI (ppBMI) and childhood BMI.

Methods: This retrospective cohort study analyzed a data set from Wuhan, China. The mediation effect of targeted mediators on the association between maternal BMI and childhood BMI at the age of 2 years was analyzed.

Results: In the mediation model comprising maternal GWG, infant birth weight, and the first-6-month ΔWAZ as mediators of the association between ppBMI and children's BMI, the per unit increase in ppBMI resulted in a 0.01-kg/m increase in children's BMI, through all three mediators. For the model comprising infant birth weight and the first-6-month ΔWAZ as mediators but maternal GWG as a moderator, the indirect effects of the first-6-month ΔWAZ on the relationship between ppBMI and childhood BMI was 0.0018 higher when maternal GWG increased from average values to 1 SD above the average values.

Conclusions: Maternal GWG, infant birth weight, and the first-6-month ΔWAZ mediated the effects of maternal ppBMI on children's BMI. Interventions targeting these factors can mitigate the risk of childhood obesity.
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http://dx.doi.org/10.1002/oby.23176DOI Listing
July 2021

Inclusion of the C-Terminal Domain in the β-Sheet Core of Heparin-Fibrillized Three-Repeat Tau Protein Revealed by Solid-State Nuclear Magnetic Resonance Spectroscopy.

J Am Chem Soc 2021 May 13;143(20):7839-7851. Epub 2021 May 13.

Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.

Many neurodegenerative diseases such as Alzheimer's disease are characterized by pathological β-sheet filaments of the tau protein, which spread in a prion-like manner in patient brains. To date, high-resolution structures of tau filaments obtained from patient brains show that the β-sheet core only includes portions of the microtubule-binding repeat domains and excludes the C-terminal residues, indicating that the C-terminus is dynamically disordered. Here, we use solid-state NMR spectroscopy to identify the β-sheet core of full-length 0N3R tau fibrillized using heparin. Assignment of C and N chemical shifts of the rigid core of the protein revealed a single predominant β-sheet conformation, which spans not only the R3, R4, R' repeats but also the entire C-terminal domain (CT) of the protein. This massive β-sheet core qualitatively differs from all other tau fibril structures known to date. Using long-range correlation NMR experiments, we found that the R3 and R4 repeats form a β-arch, similar to that seen in some of the brain-derived tau fibrils, but the R1 and R3 domains additionally stack against the CT, reminiscent of previously reported transient interactions of the CT with the microtubule-binding repeats. This expanded β-sheet core structure suggests that the CT may have a protective effect against the formation of pathological tau fibrils by shielding the amyloidogenic R3 and R4 domains, preventing side-on nucleation. Truncation and post-translational modification of the CT may thus play an important role in the progression of tauopathies.
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http://dx.doi.org/10.1021/jacs.1c03314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283780PMC
May 2021

Deep learning-based multi-modal computing with feature disentanglement for MRI image synthesis.

Med Phys 2021 Jul 7;48(7):3778-3789. Epub 2021 Jun 7.

School of Computer Science, Sichuan University, Chengdu, Sichuan, 610065, China.

Purpose: Different Magnetic resonance imaging (MRI) modalities of the same anatomical structure are required to present different pathological information from the physical level for diagnostic needs. However, it is often difficult to obtain full-sequence MRI images of patients owing to limitations such as time consumption and high cost. The purpose of this work is to develop an algorithm for target MRI sequences prediction with high accuracy, and provide more information for clinical diagnosis.

Methods: We propose a deep learning-based multi-modal computing model for MRI synthesis with feature disentanglement strategy. To take full advantage of the complementary information provided by different modalities, multi-modal MRI sequences are utilized as input. Notably, the proposed approach decomposes each input modality into modality-invariant space with shared information and modality-specific space with specific information, so that features are extracted separately to effectively process the input data. Subsequently, both of them are fused through the adaptive instance normalization (AdaIN) layer in the decoder. In addition, to address the lack of specific information of the target modality in the test phase, a local adaptive fusion (LAF) module is adopted to generate a modality-like pseudo-target with specific information similar to the ground truth.

Results: To evaluate the synthesis performance, we verify our method on the BRATS2015 dataset of 164 subjects. The experimental results demonstrate our approach significantly outperforms the benchmark method and other state-of-the-art medical image synthesis methods in both quantitative and qualitative measures. Compared with the pix2pixGANs method, the PSNR improves from 23.68 to 24.8. Moreover the ablation studies have also verified the effectiveness of important components of the proposed method.

Conclusion: The proposed method could be effective in prediction of target MRI sequences, and useful for clinical diagnosis and treatment.
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http://dx.doi.org/10.1002/mp.14929DOI Listing
July 2021

Cationic Glycopolymers with Aggregation-Induced Emission for the Killing, Imaging, and Detection of Bacteria.

Biomacromolecules 2021 05 28;22(5):2224-2232. Epub 2021 Apr 28.

Key Laboratory of New Membrane Materials, Ministry of Industry and Information Technology, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. China.

Cationic glycopolymers with structures similar to those of typical poly(ionic liquid)s (PILs) were synthesized the quaternization reaction of poly(4-vinyl pyridine) with halogen-functionalized d-mannose and tetraphenylethylene units. Such postpolymerization modification provided PILs with aggregation-induced emission effect as well as specific carbohydrate-protein recognition with lectins such as concanavalin A. The interactions between cationic glycopolymers and different microorganisms, including Gram-positive and Gram-negative , were used for the killing, imaging, and detection of bacteria. Besides, these sugar-containing PILs showed a relatively low hemolysis rate due to the presence of saccharide units, which may have potential application in the field of biomaterials.
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http://dx.doi.org/10.1021/acs.biomac.1c00298DOI Listing
May 2021

Clinical features and follow-up of pediatric patients hospitalized for COVID-19.

Pediatr Pulmonol 2021 07 14;56(7):1967-1975. Epub 2021 Apr 14.

Medicine Research Center, Ningbo City First Hospital, Ningbo, Zhejiang Province, China.

Objective: This report summarizes the clinical features and 1-month follow-up observations for pediatric patients who were hospitalized with coronavirus disease 2019 (COVID-19) in Wuhan Women and Children's Hospital.

Methods: The 1-month follow-up data included clinical manifestations and results from serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and IgM tests, reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2, lung computed tomography (CT) scans, and laboratory tests.

Results: Between January 20 and March 15, 2020, 127 patients aged 0-15 years were hospitalized for COVID-19 treatment, including 3 severe cases and 124 mild or moderate cases. The main therapies included inhalation of aerosolized interferon-α (122/127) and additional antiviral drugs (28/127). Among the 81 patients who had pneumonia at admission, 35 with right lobe pneumonia had the longest hospital stay (mean 14.5 ± 7 days); 17 with left lobe pneumonia had the highest creatine kinase (154 ± 106 U/L) and creatine kinase myocardial band  (CK-MB, 43 ± 48 U/L) levels; and 29 with bilateral pneumonia had the highest white blood cell counts (8.3 ± 4 × 10 /L). Among the 46 patients who were successfully followed up 1 month after discharge, two notable findings were right lobe pneumonia in 22% (95% confidence interval [CI]: 11%-37%) of patients and persistently elevated serum creatine kinase and CK-MB levels. The median duration of elevated CK-MB was 45 days. The mean concentrations of serum SARS-CoV-2 IgG and IgM in 41 patients were 8.0 ± 7.5 and 98 ± 40 ng/ml, respectively. At follow-up, four patients retested positive for SARS-CoV-2.

Conclusions: The involvement of different lung lobes in patients with COVID-19 was associated with variations in the persistence of pneumonia and elevation of CK-MB levels and body temperature.
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http://dx.doi.org/10.1002/ppul.25407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250880PMC
July 2021

Comparative analysis of C chemical shifts of β-sheet amyloid proteins and outer membrane proteins.

J Biomol NMR 2021 May 12;75(4-5):151-166. Epub 2021 Apr 12.

Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, MA, 02139, USA.

Cross-β amyloid fibrils and membrane-bound β-barrels are two important classes of β-sheet proteins. To investigate whether there are systematic differences in the backbone and sidechain conformations of these two families of proteins, here we analyze the C chemical shifts of 17 amyloid proteins and 7 β-barrel membrane proteins whose high-resolution structures have been determined by NMR. These 24 proteins contain 373 β-sheet residues in amyloid fibrils and 521 β-sheet residues in β-barrel membrane proteins. The C chemical shifts are shown in 2D C-C correlation maps, and the amino acid residues are categorized by two criteria: (1) whether they occur in β-strand segments or in loops and turns; (2) whether they are water-exposed or dry, facing other residues or lipids. We also examine the abundance of each amino acid in amyloid proteins and β-barrels and compare the sidechain rotameric populations. The C chemical shifts indicate that hydrophobic methyl-rich residues and aromatic residues exhibit larger static sidechain conformational disorder in amyloid fibrils than in β-barrels. In comparison, hydroxyl- and amide-containing polar residues have more ordered sidechains and more ordered backbones in amyloid fibrils than in β-barrels. These trends can be explained by steric zipper interactions between β-sheet planes in cross-β fibrils, and by the interactions of β-barrel residues with lipid and water in the membrane. These conformational trends should be useful for structural analysis of amyloid fibrils and β-barrels based principally on NMR chemical shifts.
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http://dx.doi.org/10.1007/s10858-021-00364-yDOI Listing
May 2021

RNA methylation in hematological malignancies and its interactions with other epigenetic modifications.

Leukemia 2021 05 25;35(5):1243-1257. Epub 2021 Mar 25.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hematological malignancies are a class of malignant neoplasms attributed to abnormal differentiation of hematopoietic stem cells (HSCs). The systemic involvement, poor prognosis, chemotherapy resistance, and recurrence common in hematological malignancies urge researchers to look for novel treatment targets and mechanisms. In recent years, epigenetic abnormalities have been shown to play a vital role in tumorigenesis and progression in hematological malignancies. In addition to DNA methylation and histone modifications, which are most studied, RNA methylation has become increasingly significant. In this review, we elaborate recent advances in the understanding of RNA modification in the pathogenesis, diagnosis and molecular targeted therapies of hematological malignancies and discuss its intricate interactions with other epigenetic modifications, including DNA methylation, histone modifications and noncoding RNAs.
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http://dx.doi.org/10.1038/s41375-021-01225-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102199PMC
May 2021

Concurrent vs sequential chemoradiotherapy for patients with advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials.

Authors:
Wei Xiao Mei Hong

Medicine (Baltimore) 2021 Mar;100(11):e21455

Nanjing Chest Hospital, Nanjing, Jiangsu Province, China.

Background: Chemotherapy in combination with thoracic radiotherapy yields significant results in patients with advanced non-small-cell lung cancer (NSCLC) compared with thoracic radiotherapy alone. However, whether concurrent or sequential delivery of chemotherapy combined with thoracic radiotherapy is optimal remains unclear. Herein, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of concurrent vs sequential chemoradiotherapy in patients with NSCLC.

Methods: PubMed, EmBase, and Cochrane Library were systematically searched for RCTs focusing on concurrent and sequential chemoradiotherapy for patients with NSCLC. The pooled-effect estimate was calculated using the random-effects model. Sensitivity, subgroup, and publication biases were also evaluated. A total of 14 RCTs (2634 patients with NSCLC) were selected for the final meta-analysis.

Results: Compared with sequential chemoradiotherapy, concurrent chemoradiotherapy did not increase the 1-year survival rates; however, concurrent chemoradiotherapy significantly increased the 2-, 3-, 4-, and 5-year survival rates. Moreover, although there were no significant differences between concurrent and sequential chemoradiotherapy in terms of distant relapse and locoregional plus distant relapse, concurrent chemoradiotherapy significantly reduced the risk of locoregional relapse. Furthermore, concurrent chemoradiotherapy yielded positive results with respect to overall response rates. Unfortunately, concurrent chemoradiotherapy could result in esophagitis, nausea/vomiting, and reduced leukocyte and platelet counts in patients with NSCLC.

Conclusion: Compared with sequential chemoradiotherapy, concurrent chemoradiotherapy may be significantly beneficial in terms of long-term survival and locoregional relapse, although it increases the risk of grade 3 (or greater) adverse events.
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http://dx.doi.org/10.1097/MD.0000000000021455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982214PMC
March 2021

Water orientation and dynamics in the closed and open influenza B virus M2 proton channels.

Commun Biol 2021 03 12;4(1):338. Epub 2021 Mar 12.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.

The influenza B M2 protein forms a water-filled tetrameric channel to conduct protons across the lipid membrane. To understand how channel water mediates proton transport, we have investigated the water orientation and dynamics using solid-state NMR spectroscopy and molecular dynamics (MD) simulations. C-detected water H NMR relaxation times indicate that water has faster rotational motion in the low-pH open channel than in the high-pH closed channel. Despite this faster dynamics, the open-channel water shows higher orientational order, as manifested by larger motionally-averaged H chemical shift anisotropies. MD simulations indicate that this order is induced by the cationic proton-selective histidine at low pH. Furthermore, the water network has fewer hydrogen-bonding bottlenecks in the open state than in the closed state. Thus, faster dynamics and higher orientational order of water molecules in the open channel establish the water network structure that is necessary for proton hopping.
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http://dx.doi.org/10.1038/s42003-021-01847-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955094PMC
March 2021

Mapping the Worldwide Trends on Energy Poverty Research: A Bibliometric Analysis (1999-2019).

Int J Environ Res Public Health 2021 02 11;18(4). Epub 2021 Feb 11.

College of Public Administration, Huazhong University of Science and Technology, Wuhan 430074, China.

Energy poverty is one of the main challenges facing humanity in the 21st century. Research on energy poverty is becoming a common focus of scholars in many areas. Bibliometrics can help researchers dig deep into the information of specific research fields from a quantitative perspective. In this study, we collected 1018 research papers in the field of energy poverty published in the period 1999-2019 from the Web of Science databases and conducted a bibliometric analysis on them. Cleaning and screening of sample papers, matrix construction, and visualization were performed using Bibliometrix, VOSviewer, and HistCite, summarizing the internal and external characteristics of the papers. With regard to external characteristics, a total of 982 research institutions in 80 regions conducted research in this field. There is extensive cooperation between the countries, and the UK, the USA, Australia, and Italy play the most active role in the cooperation network. With regard to internal characteristics, we found the two most representative citation paths: one path starts from the concerns of energy-poor groups and stops at an ethical discussion on energy poverty; the second path is based on the existing technological path, continuously developing coping policies, evaluation methods, and a conceptual framework for dealing with energy poverty. Furthermore, through coupling analysis, we discovered four focuses of energy poverty research: improvement of definition, improvement of evaluation methods, effects of coping policy, and energy justice. Through a comprehensive analysis of existing papers, this paper reveals some limitations of previous studies and recommends some promising directions for future research on energy poverty.
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http://dx.doi.org/10.3390/ijerph18041764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918555PMC
February 2021

MRF-RFS: A Modified Random Forest Recursive Feature Selection Algorithm for Nasopharyngeal Carcinoma Segmentation.

Methods Inf Med 2020 08 22;59(4-05):151-161. Epub 2021 Feb 22.

School of Computer Science, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Background: An accurate and reproducible method to delineate tumor margins is of great importance in clinical diagnosis and treatment. In nasopharyngeal carcinoma (NPC), due to limitations such as high variability, low contrast, and discontinuous boundaries in presenting soft tissues, tumor margin can be extremely difficult to identify in magnetic resonance imaging (MRI), increasing the challenge of NPC segmentation task.

Objectives: The purpose of this work is to develop a semiautomatic algorithm for NPC image segmentation with minimal human intervention, while it is also capable of delineating tumor margins with high accuracy and reproducibility.

Methods: In this paper, we propose a novel feature selection algorithm for the identification of the margin of NPC image, named as modified random forest recursive feature selection (MRF-RFS). Specifically, to obtain a more discriminative feature subset for segmentation, a modified recursive feature selection method is applied to the original handcrafted feature set. Moreover, we combine the proposed feature selection method with the classical random forest (RF) in the training stage to take full advantage of its intrinsic property (i.e., feature importance measure).

Results: To evaluate the segmentation performance, we verify our method on the T1-weighted MRI images of 18 NPC patients. The experimental results demonstrate that the proposed MRF-RFS method outperforms the baseline methods and deep learning methods on the task of segmenting NPC images.

Conclusion: The proposed method could be effective in NPC diagnosis and useful for guiding radiation therapy.
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http://dx.doi.org/10.1055/s-0040-1721791DOI Listing
August 2020

Association and potential mediators between socioeconomic status and childhood overweight/obesity.

Prev Med 2021 05 20;146:106451. Epub 2021 Feb 20.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

The associations between socioeconomic status and childhood overweight/obesity are inconsistent, and potential underlying factors are unclear. In China, Hukou status is an important attribute of individual's socioeconomic circumstances, but previously received less consideration as a socioeconomic indicator. This study aimed to investigate the association between comprehensive socioeconomic status and childhood overweight/obesity. Using data from Wuhan Maternal and Child Health Management Information System (2009-2018, N = 209,500), clustering analysis was used to create comprehensive socioeconomic groups with indicator components such as parental education level, occupation, and maternal Hukou. The associations between the determined socioeconomic status and childhood overweight/obesity at age 1 and 2 were examined by log-binomial model. Parallel and serial mediation analyses were performed to test the indirect effects of potential mediators, including maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight, in the association between socioeconomic status and childhood overweight/obesity. Four clusters, defined as low, low-medium, medium-high, and high socioeconomic groups, were identified through clustering analysis. Hukou, among five socioeconomic components, contributed the most to the development of childhood overweight/obesity. Children in the low-medium socioeconomic group have a greater risk of overweight/obesity than the low socioeconomic group. Indirect effects of maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight were identified for the association. In conclusion, socioeconomic status may impact childhood obesity through maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight. Hukou should be considered in the evaluation of socioeconomic status in China.
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http://dx.doi.org/10.1016/j.ypmed.2021.106451DOI Listing
May 2021

Development of a Broadly Applicable Cas12a-Linked Beam Unlocking Reaction for Sensitive and Specific Detection of Respiratory Pathogens Including SARS-CoV-2.

ACS Chem Biol 2021 03 15;16(3):491-500. Epub 2021 Feb 15.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.

The outbreak of novel coronavirus SARS-CoV-2 has caused a worldwide threat to public health. COVID-19 patients with SARS-CoV-2 infection can develop clinical symptoms that are often confused with the infections of other respiratory pathogens. Sensitive and specific detection of SARS-CoV-2 with the ability to discriminate from other viruses is urgently needed for COVID-19 diagnosis. Herein, we streamlined a highly efficient CRISPR-Cas12a-based nucleic acid detection platform, termed s12a-nked eam nlocking eactio (CALIBURN). We show that CALIBURN could detect SARS-CoV-2 and other coronaviruses and influenza viruses with little cross-reactivity. Importantly, CALIBURN allowed accurate diagnosis of clinical samples with extremely low viral loads, which is a major obstacle for the clinical applications of existing CRISPR diagnostic platforms. When tested on the specimens from SARS-CoV-2-positive and negative donors, CALIBURN exhibited 73.0% positive and 19.0% presumptive positive rates and 100% specificity. Moreover, unlike existing CRISPR detection methods that were mainly restricted to respiratory specimens, CALIBURN displayed consistent performance across both respiratory and nonrespiratory specimens, suggesting its broad specimen compatibility. Finally, using a mouse model of SARS-CoV-2 infection, we demonstrated that CALIBURN allowed detection of coexisting pathogens without cross-reactivity from a single tissue specimen. Our results suggest that CALIBURN can serve as a versatile platform for the diagnosis of COVID-19 and other respiratory infectious diseases.
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http://dx.doi.org/10.1021/acschembio.0c00840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901234PMC
March 2021

Molecular Epidemiological, Serological, and Pathogenic Analysis of EV-B75 Associated With Acute Flaccid Paralysis Cases in Tibet, China.

Front Microbiol 2020 13;11:632552. Epub 2021 Jan 13.

WHO WPRO Regional Polio Reference Laboratory, NHC Key Laboratory for Biosafety, NHC Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Enterovirus B75 (EV-B75) is a newly identified serotype of the enterovirus B species. To date, only 112 cases related to EV-B75 have been reported worldwide, and research on EV-B75 is still limited with only two full-length genome sequences available in GenBank. The present study reported seven EV-B75 sequences from a child with acute flaccid paralysis and six asymptomatic close contacts in Shigatse, Tibet. Phylogenetic analysis revealed that the Tibetan strain was possibly imported from neighboring India. Seroepidemiological analyses indicated that EV-B75 has not yet caused a large-scale epidemic in Tibet. Similarity plots and boot scanning analyses revealed frequent intertypic recombination in the non-structural region of all seven Tibet EV-B75 strains. All seven Tibetan strains were temperature-sensitive, suggesting their poor transmissibility in the environment. Overall, though the seven Tibetan strains did not cause large-scale infection, prevention and control of the novel enterovirus cannot be underestimated.
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http://dx.doi.org/10.3389/fmicb.2020.632552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873985PMC
January 2021

Antinociceptive and Anti-Inflammatory Properties of Cannabidiol Alone and in Combination with Standardized Bioflavonoid Composition.

J Med Food 2021 Feb 10. Epub 2021 Feb 10.

Unigen, Inc., Tacoma, Washington, USA.

Symptom-alleviating therapies for osteoarthritis (OA) management are inadequate. Long-term application of first-line treatments, such as nonsteroidal anti-inflammatory drugs, is limited due to associated side effects. We believe that a combination of traditionally used botanical extracts, which have diverse active components that target multiple inflammatory pathways, may provide a safe and efficacious alternative to address the multifactorial nature of OA. Recently, cannabidiol (CBD), the major nonpsychoactive component of the hemp plant, has gained renewed global attention for its pharmacological actions. It has shown promise in reducing pain and inflammation in preclinical models of arthritis. In this study, widely employed inflammatory and noninflammatory animal pain models, such as the hot plate test, visceral pain model (writhing test), and carrageenan-induced rat paw edema model, were utilized to evaluate the antinociceptive and anti-inflammatory activity of CBD alone and in combination with standardized bioflavonoid compositions. CBD was tested at 5, 10, 20, and 40 mg/kg orally and at 5% topically. Administered alone, CBD produced dose-correlated, statistically significant pain inhibition in all the models. Enhanced performance in pain and inflammation reduction was observed when CBD was orally administered in complex with the bioflavonoid compositions. Data from this study show that for clinically meaningful efficacy against OA, CBD may have to be delivered in higher dosage or formulated with other medicinal plants with similar activities.
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http://dx.doi.org/10.1089/jmf.2020.0178DOI Listing
February 2021

Direct Observation of Cholesterol Dimers and Tetramers in Lipid Bilayers.

J Phys Chem B 2021 02 9;125(7):1825-1837. Epub 2021 Feb 9.

Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.

Cholesterol is a ubiquitous component of mammalian cell membranes and affects membrane protein function. Although cholesterol-mediated formation of ordered membrane domains has been extensively studied, molecular-level structural information about cholesterol self-association has been absent. Here, we combine solid-state nuclear magnetic resonance (NMR) spectroscopy with all-atom molecular dynamics simulations to determine the oligomeric structure of cholesterol in phospholipid bilayers. Two-dimensional C-C correlation spectra of differentially labeled cholesterol indicate that cholesterol self-associates in a face-to-face fashion at membrane concentrations from 17 to 44 mol %. 2D C and F spin-counting experiments allowed us to measure the average oligomeric number of these cholesterol clusters. At low cholesterol concentrations of ∼20%, the average cluster size is centered on dimers. At a high cholesterol concentration of 44%, which is representative of virus lipid envelopes and liquid-ordered domains of cell membranes, both dimers and tetramers are observed. The cholesterol dimers are found in both phase-separated membranes that contain sphingomyelin and in disordered and miscible membranes that are free of sphingomyelin. Molecular dynamics simulations support these experimental observations and moreover provide the lifetimes, stabilities, distributions, and structures of these nanoscopic cholesterol clusters. Taken together, these NMR and MD data strongly suggest that dimers are the basic structural unit of cholesterol in phospholipid bilayers. The direct observation of cholesterol dimers and tetramers provides a revised framework for studying cholesterol interactions with membrane proteins to regulate protein functions and for understanding the pathogenic role of cholesterol in diseases.
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http://dx.doi.org/10.1021/acs.jpcb.0c10631DOI Listing
February 2021

Early diagnosis of rabies virus infection by RPA-CRISPR techniques in a rat model.

Arch Virol 2021 Apr 5;166(4):1083-1092. Epub 2021 Feb 5.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.

Rabies, which is caused by rabies virus (RABV), poses an ever-present threat to public health in most countries of the world. Once clinical signs appear, the mortality of rabies approaches 100%. To date, no effective method for early rabies diagnosis has been developed. In this study, an RPA-CRISPR nucleic-acid-based assay was developed for early rabies diagnosis by detecting viral RNA shedding in the cerebrospinal fluid (CSF) of rats. This method can detect a single copy of RABV genomic RNA in 1 μL of liquid. RABV genomic RNA released from viral particles in the CSF could be detected via RPA-CRISPR as early as 3 days postinfection in a rat model. This study provides an RPA-CRISPR technique for early detection of RABV with potential application in the clinical diagnosis of human rabies.
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http://dx.doi.org/10.1007/s00705-021-04970-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862975PMC
April 2021

Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders.

Front Cell Dev Biol 2020 12;8:611354. Epub 2021 Jan 12.

Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, United States.

Myeloid cells, including monocytes/macrophages, primarily rely on glucose and lipid metabolism to provide the energy and metabolites needed for their functions and survival. AMP-activated protein kinase (AMPK, its gene is for human, for rodent) is a key metabolic sensor that regulates many metabolic pathways. We studied recruitment and viability of -deficient myeloid cells in mice and the phenotype of these mice in the context of cardio-metabolic diseases. We found that the deficiency of Prkaa1 in myeloid cells downregulated genes for glucose and lipid metabolism, compromised glucose and lipid metabolism of macrophages, and suppressed their recruitment to adipose, liver and arterial vessel walls. The viability of macrophages in the above tissues/organs was also decreased. These cellular alterations resulted in decreases in body weight, insulin resistance, and lipid accumulation in liver of mice fed with a high fat diet, and reduced the size of atherosclerotic lesions of mice fed with a Western diet. Our results indicate that AMPKα1/PRKAA1-regulated metabolism supports monocyte recruitment and macrophage viability, contributing to the development of diet-induced metabolic disorders including diabetes and atherosclerosis.
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http://dx.doi.org/10.3389/fcell.2020.611354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835533PMC
January 2021

Outcomes of new-onset atrial fibrillation in patients with sepsis: A systematic review and meta-analysis of 225,841 patients.

Am J Emerg Med 2021 04 5;42:23-30. Epub 2021 Jan 5.

Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Geriatrics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Background: The outcomes of new-onset atrial fibrillation (AF) during sepsis are inconsistent and inconclusive. This meta-analysis aims to provide a comprehensive description of the impact of new-onset AF on the prognosis of sepsis.

Methods: Three electronic databases (PubMed, Embase, and the Cochrane Library) were searched for relevant studies. Meta-analysis was performed using odds ratios (OR) and 95% confidence intervals (CI) as effect measures.

Results: A total of 225,841 patients from 13 individual studies were incorporated to the meta-analysis. The summary results revealed that new-onset AF during sepsis was associated with increased odds of in-hospital mortality (pooled OR: 2.09; 95% CI: 1.53-2.86; p < 001), post-discharge mortality (pooled OR: 2.44; 95% CI: 1.81-3.29; p < .001), and stroke (pooled OR:1.88; 95% CI: 1.13-3.14; p < .05). Results also indicated that the incidence of new-onset AF varied from 1.9% for mild sepsis to 46.0% for septic shock. Furthermore, compared to those without AF, people with new-onset AF had longer ICU and hospital stays, as well as a higher recurrence of AF.

Conclusions: New-onset AF is frequently associated with adverse outcomes in patients with sepsis. This is a clinical issue that warrants more attention and should be managed appropriately to prevent poor prognosis.
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http://dx.doi.org/10.1016/j.ajem.2020.12.062DOI Listing
April 2021

Leucine heptad motifs within transmembrane domains affect function and oligomerization of human organic anion transporting polypeptide 1B1.

Biochim Biophys Acta Biomembr 2021 04 8;1863(4):183554. Epub 2021 Jan 8.

College of Life Sciences, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, South China Agricultural University, Guangzhou, China. Electronic address:

Organic anion transporting polypeptides (OATPs) are transmembrane proteins responsible for the uptake of a wide range of endogenous compounds and clinically important drugs. The liver-specific OATP1B1 serves crucial roles in the removal of many orally administered drugs. The proper function of the transporter hence is essential for the pharmacokinetics of various therapeutic agents. Membrane proteins tend to form oligomers that are important for their stability, targeting and/or interactions with the substrates. Previous study in our laboratory revealed that OATP1B1 may form homo-oligomers and that a GXXXG motif localized at transmembrane domain 8 (TM8) may affect its oligomerization. In the current study, three short-form leucine heptad repeats within the transmembrane domains of OATP1B1 were investigated. It was found that the disruption of leucine heptad repeats within TM3 dramatically reduced the uptake function and protein-protein association of OATP1B1; while within TM8, only L378 is essential for the function of OATP1B1 and alanine replacement of L378 exhibited no effect on the oligomerization. The fragmental expression of TM3 interfered with the association of OATP1B1 homo-oligomers as well as its association with OATP1B3, which is also selectively expressed at human hepatocytes, suggesting that the region may be shared by both transporters for their protein-protein interactions.
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http://dx.doi.org/10.1016/j.bbamem.2021.183554DOI Listing
April 2021

Structure and dynamics of the drug-bound bacterial transporter EmrE in lipid bilayers.

Nat Commun 2021 01 8;12(1):172. Epub 2021 Jan 8.

Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, MA, 02139, USA.

The dimeric transporter, EmrE, effluxes polyaromatic cationic drugs in a proton-coupled manner to confer multidrug resistance in bacteria. Although the protein is known to adopt an antiparallel asymmetric topology, its high-resolution drug-bound structure is so far unknown, limiting our understanding of the molecular basis of promiscuous transport. Here we report an experimental structure of drug-bound EmrE in phospholipid bilayers, determined using F and H solid-state NMR and a fluorinated substrate, tetra(4-fluorophenyl) phosphonium (F-TPP). The drug-binding site, constrained by 214 protein-substrate distances, is dominated by aromatic residues such as W63 and Y60, but is sufficiently spacious for the tetrahedral drug to reorient at physiological temperature. F-TPP lies closer to the proton-binding residue E14 in subunit A than in subunit B, explaining the asymmetric protonation of the protein. The structure gives insight into the molecular mechanism of multidrug recognition by EmrE and establishes the basis for future design of substrate inhibitors to combat antibiotic resistance.
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http://dx.doi.org/10.1038/s41467-020-20468-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794478PMC
January 2021

Development of A Super-Sensitive Diagnostic Method for African Swine Fever Using CRISPR Techniques.

Virol Sin 2021 Apr 7;36(2):220-230. Epub 2021 Jan 7.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.

African swine fever (ASF) is an infectious disease caused by African swine fever virus (ASFV) with clinical symptoms of high fever, hemorrhages and high mortality rate, posing a threat to the global swine industry and food security. Quarantine and control of ASFV is crucial for preventing swine industry from ASFV infection. In this study, a recombinase polymerase amplification (RPA)-CRISPR-based nucleic acid detection method was developed for diagnosing ASF. As a highly sensitive method, RPA-CRISPR can detect even a single copy of ASFV plasmid and genomic DNA by determining fluorescence signal induced by collateral cleavage of CRISPR-lwCas13a (previously known as C2c2) through quantitative real-time PCR (qPCR) and has the same or even higher sensitivity than the traditional qPCR method. A lateral flow strip was developed and used in combination with RPA-CRISPR for ASFV detection with the same level of sensitivity of TaqMan qPCR. Likewise, RPA-CRISPR is capable of distinguishing ASFV genomic DNA from viral DNA/RNA of other porcine viruses without any cross-reactivity. This diagnostic method is also available for diagnosing ASFV clinical DNA samples with coincidence rate of 100% for both ASFV positive and negative samples. RPA-CRISPR has great potential for clinical quarantine of ASFV in swine industry and food security.
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http://dx.doi.org/10.1007/s12250-020-00323-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087724PMC
April 2021
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