Publications by authors named "Nan Wu"

928 Publications

Disruptive Variants Implicated in Congenital Vertebral Malformations.

Genes (Basel) 2021 Oct 14;12(10). Epub 2021 Oct 14.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Genetic perturbations in nicotinamide adenine dinucleotide de novo (NAD) synthesis pathway predispose individuals to congenital birth defects. The encodes the final enzyme in the de novo NAD synthesis pathway and, therefore, plays an important role in NAD metabolism and organ embryogenesis. Biallelic mutations in the gene have been reported to be causative of congenital organ defects known as VCRL syndrome (Vertebral-Cardiac-Renal-Limb syndrome). Here, we analyzed the genetic variants in in an exome-sequenced cohort consisting of patients with congenital vertebral malformations (CVMs). A total number of eight variants in , including two truncating variants and six missense variants, were identified in nine unrelated patients. All enrolled patients presented multiple organ defects, with the involvement of either the heart, kidney, limbs, or liver, as well as intraspinal deformities. An in vitro assay using COS-7 cells demonstrated either significantly reduced protein levels or disrupted enzymatic activity of the identified variants. Our findings demonstrated that functional variants in were involved in the complex genetic etiology of CVMs and provided further evidence for the causative variants in congenital NAD Deficiency Disorder.
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http://dx.doi.org/10.3390/genes12101615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535205PMC
October 2021

Isolation and purification of flavonoids from Euonymus alatus by high speed countercurrent chromatography and neuroprotective effect of rhamnazin-3-O-rutinoside in vitro.

J Sep Sci 2021 Oct 20. Epub 2021 Oct 20.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.

The flavonoids from Euonymus alatus exhibit many biological activities including significant antioxidant, anti-inflammatory, anticancer. In this work, a high speed countercurrent chromatography method for isolation and purification of flavonoids from crude extracts of Euonymus alatus was established. The effects of several solvent systems on the separation efficiency of target compounds in the extract of Euonymus alatus were studied. The solvent system composed of n-hexane-ethyl acetate-methanol-water at a volume ratio of (3:5:3:5, v/v) was chosen, in which the lower phase was used as the mobile phase at the rotation speed of 800 rpm and flow rate of 2.0 mL/min. The three flavonoids were obtained and identified as patuletin-3-O-rutinoside, rhamnazin-3-O-rutinoside and dehydrodicatechin A by MS and NMR, and the quantities of patuletin-3-O-rutinoside, rhamnazin-3-O-rutinoside and dehydrodicatechin A were 2.2 mg, 9.7 mg, and 1.8 mg respectively. The results indicated that high speed countercurrent chromatography was a simple and efficient method for isolation and purification of flavonoids from the crude extracts of Euonymus alatus. The cellular antioxidant activity experimental result indicted that rhamnazin-3-O-rutinoside could alleviate H O -induced oxidative stress. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jssc.202100607DOI Listing
October 2021

Editorial: Gastrointestinal Immunity and Crosstalk With Internal Organs in Fish.

Front Immunol 2021 28;12:734538. Epub 2021 Sep 28.

Animal Nutrition Institute, Sichuan Agricultural University, Ya'an, China.

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http://dx.doi.org/10.3389/fimmu.2021.734538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506000PMC
September 2021

Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis.

Cell Death Dis 2021 Oct 11;12(10):929. Epub 2021 Oct 11.

Key laboratory of preservation of human genetic resources and disease control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, 150081, China.

Cervical adenocarcinoma is an important disease that affects young women and it has a high mortality and poor prognosis. Denticleless E3 ubiquitin protein ligase homolog (DTL) gene with oncogenic function has been evaluated in several cancers. Through this study, we aimed to clarify the clinical and molecular characteristics of cervical adenocarcinoma involving overexpression of DTL and elucidate its molecular mechanism. Bioinformatics analysis was performed through multiple databases. RNA sequencing was used to obtain differentially expressed genes after DTL was overexpressed in cells. The role of DTL in cervical adenocarcinoma was explored through in vitro and in vivo experiments. We found that DTL has an unfavorable prognostic implication for patients with cervical adenocarcinoma. Overexpression of DTL induced the migration and invasion of tumor cells in vitro and promoted intra-pulmonary metastasis in vivo. In addition, DTL activated JNK through RAC1 and upregulated FOXO1 to induce epithelial-mesenchymal transition, and the migration and invasion of tumor cells. Therefore, we conclude that overexpression of DTL enhanced cell motility and promoted tumor metastasis of cervical adenocarcinoma by regulating the RAC1-JNK-FOXO1 axis. These results suggest that DTL may become a potential therapeutic target for antitumor metastasis of cervical adenocarcinoma.
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http://dx.doi.org/10.1038/s41419-021-04179-5DOI Listing
October 2021

Effect of insect feces (Hermetia illucens) on rice growth and heavy metal migration from polluted soil to rice plant.

Environ Sci Pollut Res Int 2021 Oct 6. Epub 2021 Oct 6.

College of Agronomy and Resource and Environment, Tianjin Agricultural University, Tianjin, 300392, China.

Insect feces are a new kind of biological organic fertilizer. Little is known about the influences of insect feces on rice growth and heavy metal migration from soil to rice plant. In this study, the effects of different amounts (CK (0%), T1 (2%), T2 (4%), T3 (6%), and T4 (8%)) of black soldier fly larvae (BSFL) feces on the rice growth and the migration/accumulation of heavy metals (Cd and Pb) were investigated by pot experiments within 2 years. The application of insect feces remarkably increased the contents of soil pH, organic matter, ammonium nitrogen, available phosphorus, and potassium. Meanwhile, the insect feces application reduced the weak acid-soluble contents of soil Cd and Pb by 8.3-56.8%, but increased those in the oxidizable (by 22.4-165.7%) and residual (by 1.8-225.6%) states. Except for the T4 treatment in the first year, all fertilization treatments increased the rice yield (up to 43.7% and 195.5% higher than those of CK within 2 years). Moreover, the insect feces application reduced the contents of Cd (8.3-66.7%) and Pb (6.4-61.8%) in different parts of rice. Under the same treatment, the metal contents in each part of rice in the second year were lower than those in the first year. The insect feces application decreased the absorption coefficients (24.4-57.5%) and secondary transport coefficients (3.6-44.1%) of Cd and Pb by rice plant. The findings implied that the insect feces might act as effective organic fertilizers for rice plants as well as reducing heavy metal accumulation in rice plants growing in polluted soil.
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http://dx.doi.org/10.1007/s11356-021-16803-0DOI Listing
October 2021

Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients.

Front Endocrinol (Lausanne) 2021 13;12:711991. Epub 2021 Sep 13.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Purpose: Congenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying mechanisms a candidate gene-based mutational burden analysis.

Methods: We retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis.

Results: In 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD ( [c.2329T>A, c.7131C>G], [c.731G>A], [c.1102delC], [c.187_207dup]). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that ( = 0.005), ( = 0.006), ( = 0.021) and ( = 0.040) represented top genes enriched in GHD patients.

Conclusion: Our study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.
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http://dx.doi.org/10.3389/fendo.2021.711991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475633PMC
September 2021

Bachmann bundle impairment following linear ablation of left anterior wall: impact on left atrial function.

Int J Cardiovasc Imaging 2021 Sep 27. Epub 2021 Sep 27.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.

We aimed to evaluate the effect of Bachmann bundle (BB) impairment on electrical and mechanical function of the left atrium (LA), as well as the long-term clinical impact of such impairment. We measured activation time in the five LA walls in 56 patients with atrial fibrillation. LA reservoir, conduit, and contractile function were also evaluated. Patients were divided into two groups based on ablation strategy: the circumferential pulmonary vein isolation (CPVI) group and CPVI with LA anterior wall linear ablation (LAAW) group. Patients in the CPVI + LAAW group were divided into two sub-groups based on ECG differences following ablation: the BB impairment group and intact BB group. LA activation time and function were then compared between the ablation strategy groups and the CPVI + LAAW subgroups. Patients in the CPVI + LAAW group exhibited longer activation times in the anterior and lateral walls of the LA, poorer LA synchrony, and reduced LA contractile and reservoir function when compared with those in the CPVI group. In the BB impairment subgroup, we observed a discrepancy between electrical/mechanical remodeling. Among five walls, activation time was longest in this region. BB impairment was also associated with reduced LA function. Significant changes in LA function and conductibility were observed in patients with anterior wall ablation, especially those with iatrogenic BB impairment.
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http://dx.doi.org/10.1007/s10554-021-02362-5DOI Listing
September 2021

Heavily Tungsten Doped Sodium Thioantimonate Solid State Electrolytes with Exceptionally Low Activation Energy for Ionic Diffusion.

Angew Chem Int Ed Engl 2021 Sep 26. Epub 2021 Sep 26.

The University of Texas at Austin, Department of Mechanical Engineering, 2501 Speedway, 78712-1591, Austin, UNITED STATES.

This study puts forward a powerful strategy based on multiple synergistic design rules for modifying the structure of solid-state electrolytes (SSEs) to reduce the cation diffusion activation energy. Two heavily W-doped sodium thioantimonate SSEs, Na 2.895 W 0.3 Sb 0.7 S 4 and Na 2.7 W 0.3 Sb 0.7 S 4 are designed, both exhibiting exceptionally low activation energy and enhanced room temperature (RT) ionic conductivity; 0.09 eV, 24.2 mS/cm and 0.12 eV, 14.5 mS/cm. At -15 ℃ the Na 2.895 W 0.3 Sb 0.7 S 4 displays a total ionic conductivity of 5.5 mS/cm. The 30% W content goes far beyond the 10-12% reported in the prior studies, and results in novel pseudo-cubic or orthorhombic structures. Theoretical studies based on density functional theory (DFT) calculations reveal that these properties result from a combination of multiple diffusion mechanisms, including vacancy defects, strongly correlated modes and excessive Na-ions. An all-solid-state battery (ASSB) using Na 2.895 W 0.3 Sb 0.7 S 4 as the primary SSE and a sodium sulfide (Na 2 S) cathode achieves a reversible capacity of 400 mAh/g.
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http://dx.doi.org/10.1002/anie.202110699DOI Listing
September 2021

Freeze-thaw cycles change the physiological sensitivity of Syntrichia caninervis to snow cover.

J Plant Physiol 2021 Nov 21;266:153528. Epub 2021 Sep 21.

State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, 830011, Urumqi, China. Electronic address:

Spring, especially the freeze-thaw season, is considered the key period for the growth and carbon sequestration of desert mosses. It is not clear how the change in environment water and temperature affects the physiological characteristics of desert mosses in freeze-thaw season. In this study, the effects of water and freeze-thaw cycles on the physiological characteristics of Syntrichia caninervis were assessed by manipulating the increase or removal of 65% snow and changes in the freeze-thaw cycles. The results showed that the changes in snow depth, freeze-thaw cycles, and their interaction significantly affected the plant water content, osmoregulatory substances content, antioxidant substance, and antioxidant enzyme activities. The contents of free proline, soluble sugar, ascorbic acid (AsA), reduced glutathione (GSH), and malondialdehyde (MDA), and superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities increased significantly with the decrease in snow depth and freeze-thaw cycles. POD and free proline were the most sensitive to the snow depth and freeze-thaw cycles, while SOD and CAT were the least sensitive. Therefore, compared with the increase in freeze-thaw cycles, the reduction in freeze-thaw cycles weakened the physiological sensitivity of S. caninervis to snow depth changes.
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http://dx.doi.org/10.1016/j.jplph.2021.153528DOI Listing
November 2021

Artificial intelligence system reduces false-positive findings in the interpretation of breast ultrasound exams.

Nat Commun 2021 09 24;12(1):5645. Epub 2021 Sep 24.

Center for Data Science, New York University, New York, NY, USA.

Though consistently shown to detect mammographically occult cancers, breast ultrasound has been noted to have high false-positive rates. In this work, we present an AI system that achieves radiologist-level accuracy in identifying breast cancer in ultrasound images. Developed on 288,767 exams, consisting of 5,442,907 B-mode and Color Doppler images, the AI achieves an area under the receiver operating characteristic curve (AUROC) of 0.976 on a test set consisting of 44,755 exams. In a retrospective reader study, the AI achieves a higher AUROC than the average of ten board-certified breast radiologists (AUROC: 0.962 AI, 0.924 ± 0.02 radiologists). With the help of the AI, radiologists decrease their false positive rates by 37.3% and reduce requested biopsies by 27.8%, while maintaining the same level of sensitivity. This highlights the potential of AI in improving the accuracy, consistency, and efficiency of breast ultrasound diagnosis.
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http://dx.doi.org/10.1038/s41467-021-26023-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463596PMC
September 2021

Assessment of prediction methods for protein structures determined by NMR in CASP14: Impact of AlphaFold2.

Proteins 2021 Sep 24. Epub 2021 Sep 24.

Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Sciences, Rensselaer Polytechnic Institute, Troy, New York, USA.

NMR studies can provide unique information about protein conformations in solution. In CASP14, three reference structures provided by solution NMR methods were available (T1027, T1029, and T1055), as well as a fourth data set of NMR-derived contacts for an integral membrane protein (T1088). For the three targets with NMR-based structures, the best prediction results ranged from very good (GDT_TS = 0.90, for T1055) to poor (GDT_TS = 0.47, for T1029). We explored the basis of these results by comparing all CASP14 prediction models against experimental NMR data. For T1027, NMR data reveal extensive internal dynamics, presenting a unique challenge for protein structure prediction methods. The analysis of T1029 motivated exploration of a novel method of "inverse structure determination," in which an AlphaFold2 model was used to guide NMR data analysis. NMR data provided to CASP predictor groups for target T1088, a 238-residue integral membrane porin, was also used to assess several NMR-assisted prediction methods. Most groups involved in this exercise generated similar beta-barrel models, with good agreement with the experimental data. However, as was also observed in CASP13, some pure prediction groups that did not use any NMR data generated models for T1088 that better fit the NMR data than the models generated using these experimental data. These results demonstrate the remarkable power of modern methods to predict structures of proteins with accuracies rivaling solution NMR structures, and that it is now possible to reliably use prediction models to guide and complement experimental NMR data analysis.
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http://dx.doi.org/10.1002/prot.26246DOI Listing
September 2021

Pediatric ocular trauma with pars plana vitrectomy in Southwest of China: clinical characteristics and outcomes.

Int J Ophthalmol 2021 18;14(9):1321-1326. Epub 2021 Sep 18.

Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Aim: To investigate the clinical characteristics and predictive factors of pediatric ocular trauma patients with vitrectomy.

Methods: Pediatric ocular trauma patients (aged 14y or younger) who received vitrectomy in Southwest Hospital between January 2007 and December 2017 were reviewed retrospectively. Age, gender, mechanism of injury, final visual acuity (VA), and prognostic factors were analyzed.

Results: A total of 139 eyes in 139 pediatric patients were included in the study. The mean age was 7.4±3.7 years old and the male-to-female ratio was 5:1. There were 104 (74.8%) open globe injuries and 35 (25.2%) closed globe injuries. The top one traumatic eye injuries were penetrating injuries occur through sharp metal objects (43.9%). After vitrectomy, 116 patients had favorable anatomic outcome at the last follow-up, and 30 eyes (21.6%) achieved VA of 20/200 or better. Following univariate analysis, we found zone III injuries (=0.021), poor initial VA (=0.005), endophthalmitis (=0.024), and recurrent retinal detachment (<0.001) were poor prognostic factors for pediatric ocular trauma. After Logistic regression analysis, the poor initial VA (odds ratio: 8.276, 95%CI: 1.597-42.897, =0.012) and recurrent retinal detachment (odds ratio: 6.455, 95%CI: 2.372-17.562, <0.001) were significantly correlated with unfavorable vision outcome in pediatric ocular trauma.

Conclusion: The treatment of vitrectomy for severe ocular trauma results in favorable anatomic outcomes, but VA improvement is not as good as anatomic outcomes. Initial VA and recurrent retinal detachment are the independent prognostic indicators for unfavorable visual outcome of severe pediatric ocular trauma.
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http://dx.doi.org/10.18240/ijo.2021.09.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403860PMC
September 2021

Association of CDH11 with Autism Spectrum Disorder Revealed by Matched-gene Co-expression Analysis and Mouse Behavioral Studies.

Neurosci Bull 2021 Sep 14. Epub 2021 Sep 14.

Key Laboratory of Brain Functional Genomics of Shanghai and the Ministry of Education, Institute of Brain Functional Genomics, School of Life Science and the Collaborative Innovation Center for Brain Science, East China Normal University, Shanghai, 200062, China.

A large number of putative risk genes for autism spectrum disorder (ASD) have been reported. The functions of most of these susceptibility genes in developing brains remain unknown, and causal relationships between their variation and autism traits have not been established. The aim of this study was to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high-confidence ASD risk genes (hcASDs). The results showed that three gene features - gene size, mRNA abundance, and guanine-cytosine content - affect the genome-wide co-expression profiles of hcASDs. To circumvent the interference of these features in gene co-expression analysis, we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched genes. This method is referred to as "matched-gene co-expression analysis" (MGCA). With MGCA, we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene prediction. The results of analysis of two recently-reported ASD candidate genes, CDH11 and CDH9, suggested the involvement of CDH11, but not CDH9, in ASD. Consistent with this prediction, behavioral studies showed that Cdh11-null mice, but not Cdh9-null mice, have multiple autism-like behavioral alterations. This study highlights the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.
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http://dx.doi.org/10.1007/s12264-021-00770-0DOI Listing
September 2021

Correlation of Bulk Degradation and Molecular Release from Enzymatically Degradable Polymeric Hydrogels.

Biomacromolecules 2021 Sep 13. Epub 2021 Sep 13.

Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States.

In this work, we establish a quantitative correlation between molecular release and material degradation. We characterize a radical-initiated photopolymerized hydrogel and base-initiated Michael addition-polymerized hydrogel, which form gels through distinct crosslinking reactions. Both scaffolds use the same degradable peptide crosslinker, which enables them to be degraded through the same enzymatic degradation reaction. A fluorescently labeled poly(ethylene glycol) molecule is chemically conjugated into the scaffold and is released during enzymatic degradation. Real-time changes in scaffold rheological properties during degradation are measured using bulk rheology. Molecular release is measured by quantifying the change in fluorescence in the incubation liquid and the hydrogel scaffold. A complicating factor, previously described in the literature, is that shear may cause increased crosslinking, resulting in an increase in the storage modulus after initiation of degradation, which changes release profiles by limiting the initial release of molecules. Therefore, we also test the hypothesis that shear induces additional crosslinking in degrading hydrogel scaffolds. To determine whether shear changes rheological properties during scaffold degradation, enzymatic degradation is characterized using bulk rheology as materials undergo continuous or minimal shear. To determine the effect of shear on molecular release, shear is induced by shaking the material during incubation. Release is characterized from scaffolds that are incubated with continuous or without shaking. We determine that shear does not make a difference in scaffold degradation or release regardless of the gelation reaction. Instead, we determine that the type of hydrogel crosslinking reaction greatly affects both material degradation and molecular release. A hydrogel crosslinking by base-initiated Michael addition does undergo further crosslinking at the start of degradation. We correlate release with enzymatic degradation for both scaffolds. We determine that the material storage modulus is indirectly correlated with release during degradation. These results indicate that rheological characterization is a useful tool to characterize and predict the release of molecules from degrading hydrogels.
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http://dx.doi.org/10.1021/acs.biomac.1c00719DOI Listing
September 2021

Elastic Properties of High-Symmetry SbO Cage-Molecular Crystal.

J Phys Chem Lett 2021 Sep 13;12(37):9011-9019. Epub 2021 Sep 13.

School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China.

The cubic-phase antimony trioxide (α-SbO) is a room-temperature stable molecular crystal, composed of cage-like tetraantimony hexoxide (SbO) molecules. Despite its versatile functionality, the van der Waals (vdW) bond-dominated nanomechanics is still unclear. Here, the bending plate-like linear behaviors of high-quality α-SbO nanoflakes were observed using the nanoindentation method. It is found that the cage-molecular crystal owns a very low in-plane Young's modulus of 14.9 ± 0.8 GPa and a remarkable maximum tensile strain of 6.0-8.8%, corresponding to a rupture strength of 0.89-1.31 GPa. Elucidated by the atomistic simulations, the compliant elastic modulus and the unexpectedly strong rupture strain are associated with the high-symmetry vdW bonding structure. The vdW nanomechanics is of fundamental and technological relevance to nanoelectronics.
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http://dx.doi.org/10.1021/acs.jpclett.1c02160DOI Listing
September 2021

Safety, Pharmacokinetics, and Pharmacodynamics of a Single Bolus of the γ-aminobutyric Acid (GABA) Receptor Potentiator HSK3486 in Healthy Chinese Elderly and Non-elderly.

Front Pharmacol 2021 27;12:735700. Epub 2021 Aug 27.

Department of Anesthesiology, First Hospital, Jilin University, Jilin, China.

The present clinical trial investigated the potential influences of dosage and age on the pharmacokinetic properties and safety profile of HSK3486, and whether any adjustment in dosing regimen is necessary in elderly patients. Twenty-four elderly participants (65-73 years) were apportioned to three equal cohorts to receive a single IV bolus of 0.2, 0.3, and 0.4 mg/kg HSK3486, respectively. An additional control group comprised eight non-elderly participants (21-44 years), who each received a single IV bolus dose of 0.4 mg/kg. Safety was assessed throughout the study, and the clinical effects were assessed based on modified observer's assessment of alertness/sedation and bispectral index (BIS) monitor. Pharmacokinetic parameters were calculated. The rates of drug-related adverse reactions among the elderly groups were a little higher than that of the non-elderly, and were slightly higher in the elderly receiving 0.4 mg/kg compared with the elderly given lower doses. The pharmacokinetic characteristics of 0.4 mg/kg HSK3486 in the elderly and non-elderly were comparable. The time to recovery was similar in elderly 0.3 mg/kg, elderly 0.4 mg/kg and non-elderly 0.4 mg/kg groups. In the elderly 0.2 mg/kg group, the time to loss of consciousness was a little longer, and the time to recovery was shorter, relative to the other three groups. Administration of 0.3 mg/kg to the elderly and 0.4 mg/kg to the non-elderly were similarly efficacious. A dose of HSK3486 of 0.3 mg/kg may be chosen for clinical use in elderly patients.
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http://dx.doi.org/10.3389/fphar.2021.735700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430033PMC
August 2021

Response to Biesecker et al.

Am J Hum Genet 2021 09;108(9):1807-1808

Departments of Pediatrics, Obstetrics and Gynecology, and Epidemiology, University of Florida College of Medicine and College of Public Health and Health Professions, Gainesville, FL 32610, USA.

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http://dx.doi.org/10.1016/j.ajhg.2021.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456153PMC
September 2021

Application of silanized melamine sponges in matrix purification for rapid multi-residue analysis of veterinary drugs in eggs by UPLC-MS/MS.

Food Chem 2022 Feb 19;369:130894. Epub 2021 Aug 19.

College of Food and Bioengineering, Zhengzhou University of Light Industry, Zhengzhou, PR China; Henan Key Laboratory of Cold Chain Food Quality and Safety Control, Zhengzhou, PR China; Collaborative Innovation Center of Food Production and Safety, Henan Province, PR China. Electronic address:

Fast and convenient matrix purification is an important prerequisite for high-throughput analysis of drug multiresidues in food. In this study, a silanized melamine sponge was prepared and first applied in the rapid determination of multiclass veterinary drugs in eggs by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Within five seconds, fast, convenient and efficient matrix separation could be achieved through simple soaking and squeezing. Compared to other matrix adsorbents, the developed material demonstrated equivalent or better purification performance. Good validation results were obtained in terms of drug recoveries (61.5%~97.0%, relative standard deviation (RSD) ≤ 10.8%), and linearities (R ≥ 0.999), as well as low limits of quantitation (0.3 ~ 10.9 μg·kg) and detection (0.1 ~ 3.8 μg·kg). By analyzing 52 egg samples, high concentrations of ofloxacin, trimethoprim, metronidazole, and dimetridazole were found at 542.9, 121.2, 66.1 and 58.0 μg·kg, respectively. The silanized melamine sponge has shown its great potential for rapid analysis of multiclass residues in food safety.
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http://dx.doi.org/10.1016/j.foodchem.2021.130894DOI Listing
February 2022

Novel Variants Are Associated with Congenital Scoliosis.

Genes (Basel) 2021 Jul 24;12(8). Epub 2021 Jul 24.

Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

encodes a transmembrane cytokine receptor, which is involved in the early development of the human embryo and plays an important role in gastrulation, organ specification and patterning of various tissues. Pathogenic variants have been associated with Kallmann syndrome and hypogonadotropic hypogonadism. In our congenital scoliosis (CS) patient series of 424 sporadic CS patients under the framework of the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study, we identified four unrelated patients harboring variants, including one frameshift and three missense variants. These variants were predicted to be deleterious by in silico prediction and conservation analysis. Signaling activities and expression levels of the mutated protein were evaluated in vitro and compared to that of the wild type (WT) . As a result, the overall protein expressions of c.2334dupC, c.2339T>C and c.1261A>G were reduced to 43.9%, 63.4% and 77.4%, respectively. By the reporter gene assay, we observed significantly reduced activity for c.2334dupC, c.2339T>C and c.1261A>G, indicating the diminished FGFR1 signaling pathway. In conclusion, variants identified in our patients led to only mild disruption to protein function, caused milder skeletal and cardiac phenotypes than those reported previously.
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http://dx.doi.org/10.3390/genes12081126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393897PMC
July 2021

miR-31-5p Promotes Oxidative Stress and Vascular Smooth Muscle Cell Migration in Spontaneously Hypertensive Rats via Inhibiting FNDC5 Expression.

Biomedicines 2021 Aug 13;9(8). Epub 2021 Aug 13.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing 211166, China.

Oxidative stress and the migration of vascular smooth muscle cells (VSMCs) are important for vascular remodeling in a variety of vascular diseases. miR-31-5p promotes cell migration in colorectal cancer cells but inhibits cell migration in renal cell carcinoma. However, whether miR-31-5p is involved in oxidative stress and VSMC migration remains unknown. This study shows the crucial roles of miR-31-5p in oxidative stress and VSMC migration, as well as underlying mechanisms. Experiments were carried out in primary VSMCs from aortic media of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), as well as the A7r5 cell line. Oxidative stress was assessed by NADPH oxidase (NOX) expression, NOX activity, and reactive oxygen species (ROS) production. Cell migration was evaluated with a Boyden chamber assay and a wound healing assay. The miR-31-5p mimic and inhibitor promoted and attenuated oxidative stress and cell migration in the VSMCs of SHR, respectively. A dual-luciferase reporter assay indicated that miR-31-5p targeted the 3'UTR domain of FNDC5. The miR-31-5p level was raised and FNDC5 expression was reduced in the VSMCs of SHR compared with those of WKY. The miR-31-5p mimic reduced FNDC5 expression in the A7r5 cells and the VSMCs of both WKY and SHR, while the miR-31-5p inhibitor only increased FNDC5 expression in the VSMCs of SHR. Exogenous FNDC5 attenuated not only the oxidative stress and VSMC migration in SHR but also the roles of the miR-31-5p mimic in inducing oxidative stress and VSMC migration. These results indicate that miR-31-5p promotes oxidative stress and VSMC migration in SHR via inhibiting FNDC5 expression. The increased miR-31-5p and reduced FNDC5 in the VSMCs of SHR contribute to enhanced oxidative stress and cell migration.
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http://dx.doi.org/10.3390/biomedicines9081009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393189PMC
August 2021

ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies.

Front Mol Biosci 2021 9;8:703110. Epub 2021 Aug 9.

Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathophysiological and molecular mechanisms underlying articular inflammation and mechanotransduction, as well as chondrocyte hypertrophy were discussed, and the role of ADAMTS5 in each biological process was reviewed, respectively. Senescence, inheritance, inflammation, and mechanical stress are involved in the overactivation of ADAMTS5, contributing to the pathogenesis of OA. Multiple molecular signaling pathways were observed to modulate ADAMTS5 expression, namely, Runx2, Fgf2, Notch, Wnt, NF-κB, YAP/TAZ, and the other inflammatory signaling pathways. Based on the fundamental understanding of ADAMTS5 in OA pathogenesis, monoclonal antibodies and small molecule inhibitors against ADAMTS5 were developed and proved to be beneficial pre-clinically both and . Recent novel RNA therapies demonstrated potentials in OA animal models. To sum up, ADAMTS5 inhibition and its signaling pathway-based modulations showed great potential in future therapeutic strategies for OA.
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http://dx.doi.org/10.3389/fmolb.2021.703110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381022PMC
August 2021

miRNA-27a Transcription Activated by c-Fos Regulates Myocardial Ischemia-Reperfusion Injury by Targeting ATAD3a.

Oxid Med Cell Longev 2021 8;2021:2514947. Epub 2021 Aug 8.

Department of Cardiology, The First Affiliated Hospital of China Medical University, Liaoning, China.

MicroRNA-27a (miR-27a) has been implicated in myocardial ischemia-reperfusion injury (MIRI), but the underlying mechanism is not well understood. This study is aimed at determining the role of miR-27a in MIRI and at investigating upstream molecules that regulate miR-27a expression and its downstream target genes. miR-27a expression was significantly upregulated in myocardia exposed to ischemia/reperfusion (I/R) and cardiomyocytes exposed to hypoxia/reoxygenation (H/R). c-Fos could regulate miR-27a expression by binding to its promoter region. Moreover, overexpression of miR-27a led to a decrease in cell viability, an increase in LDH and CK-MB secretion, and an increase in apoptosis rates. In contrast, suppression of miR-27a expression resulted in the opposite effects. ATPase family AAA-domain-containing protein 3A (ATAD3a) was identified as a target of miR-27a. miR-27a regulated the translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and H/R-induced apoptosis via the regulation of ATAD3a. It was found that inhibiting miR-27a in vivo by injecting a miR-27a sponge could ameliorate MIRI in an isolated rat heart model. In conclusion, our study demonstrated that c-Fos functions as an upstream regulator of miR-27a and that miR-27a regulates the translocation of AIF from the mitochondria to the nucleus by targeting ATAD3a, thereby contributing to MIRI. These findings provide new insight into the role of the c-Fos/miR-27a/ATAD3a axis in MIRI.
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http://dx.doi.org/10.1155/2021/2514947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369174PMC
August 2021

Copper stimulates the incidence of antibiotic resistance, metal resistance and potential pathogens in the gut of black soldier fly larvae.

J Environ Sci (China) 2021 Sep 24;107:150-159. Epub 2021 Feb 24.

College of Agronomy and Resource and Environment, Tianjin Agricultural University, Tianjin 300384, China. Electronic address:

The black soldier fly larvae (BSFL) have been successfully applied to treat various organic wastes. However, the impacts of heavy metals on antibiotic resistance in the BSFL guts are poorly understood. Here, we investigated the effect of copper (exposure concentrations of 0, 100 and 800 mg/kg) on the antibiotic and metal resistance profiles in BSFL guts. A total of 83 antibiotic resistance genes (ARGs), 18 mobile genetic elements (MGEs) and 6 metal resistance genes (MRGs) were observed in larval gut samples. Exposure to Cu remarkably reduced the diversity of ARGs and MGEs, but significantly enhanced the abundances of gut-associated ARGs and MRGs. The levels of MRGs copA, czcA and pbrT were dramatically strengthened after Cu exposure as compared with CK (increased by 2.8-13.5 times). Genera Enterococcus acted as the most predominant potential host of multiple ARG, MGE and MRG subtypes. Meanwhile, high exposure to Cu aggravated the enrichment of potential pathogens in BSFL guts, especially for Escherichia, Enterococcus and Salmonella species. The mantel test and procrustes analysis revealed that the gut microbial communities could be a key determinant for antibiotic and metal resistance. However, no significant positive links were observed between MGEs and ARGs or MRGs, possibly suggesting that MGEs did not play a crucial role in shaping the ARGs or MRGs in BSFL guts under the stress of Cu. These findings extend our understanding on the impact of heavy metals on the gut-associated antibiotic and metal resistome of BSFL.
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http://dx.doi.org/10.1016/j.jes.2021.02.008DOI Listing
September 2021

Safety, satisfaction, and cost savings of accelerated infusions of standard and intensified-dose infliximab for inflammatory bowel disease.

Intern Med J 2021 Aug 18. Epub 2021 Aug 18.

Liverpool Hospital, Liverpool, NSW, Australia.

Introduction: Infliximab remains a mainstay for treatment of inflammatory bowel disease (IBD), but a long infusion duration and subsequent monitoring can be burdensome to patients and health care providers. We assessed the safety of accelerated infusions for standard and dose-intensified infliximab regimens, and the effect on patient satisfaction and potential cost savings.

Methods: Patients with IBD on a stable maintenance dose of infliximab and in clinical remission received one or more accelerated infusions; over 30 min if receiving standard-dose (5 mg/kg), or over 60 min if receiving dose-intensified infliximab (up to 10 mg/kg). Outcomes included incidence of reactions (acute or delayed), patient satisfaction, and potential cost savings. We also explored infliximab trough levels after one and three accelerated infusions.

Results: 52 patients who received 150 infusions were studied. Incidence of reactions to accelerated infusions was 3.3% (3 out of 89) with standard-dose and 0% (out of 61) with dose-intensified infliximab. Reactions were delayed, mild, and self-limiting. None requiring drug cessation. Patient satisfaction was improved with shortened infusion time as compared to the patients' previous experiences (p = 0.00002). Mean plasma trough level of infliximab reduced from 9.3 mg/L (± 4.9) to 7.9 mg/L (± 4.1) (p = 0.02) with accelerated infusions, but none developed anti-infliximab antibodies. Nursing cost savings were estimated as $123.52 and $247.04 per-patient per-year for standard and dose-intensified infliximab, respectively.

Conclusion: Accelerated infliximab infusions for standard and dose-intensified regimens seems to be safe and improved patient satisfaction. Potential impact on drug trough levels requires further investigations. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15493DOI Listing
August 2021

High-quality genome assembly and resequencing of modern cotton cultivars provide resources for crop improvement.

Nat Genet 2021 09 9;53(9):1385-1391. Epub 2021 Aug 9.

State Key Laboratory of North China Crop Improvement and Regulation, Key Laboratory for Crop Germplasm Resources of Hebei, Hebei Agricultural University, Baoding, China.

Cotton produces natural fiber for the textile industry. The genetic effects of genomic structural variations underlying agronomic traits remain unclear. Here, we generate two high-quality genomes of Gossypium hirsutum cv. NDM8 and Gossypium barbadense acc. Pima90, and identify large-scale structural variations in the two species and 1,081 G. hirsutum accessions. The density of structural variations is higher in the D-subgenome than in the A-subgenome, indicating that the D-subgenome undergoes stronger selection during species formation and variety development. Many structural variations in genes and/or regulatory regions potentially influencing agronomic traits were discovered. Of 446 significantly associated structural variations, those for fiber quality and Verticillium wilt resistance are located mainly in the D-subgenome and those for yield mainly in the A-subgenome. Our research provides insight into the role of structural variations in genotype-to-phenotype relationships and their potential utility in crop improvement.
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http://dx.doi.org/10.1038/s41588-021-00910-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423627PMC
September 2021

Risk Factors for Band Keratopathy in Aphakic Eyes With Silicone Oil Tamponade for Open-Globe Injuries: A Multicenter Case-Control Study.

Front Med (Lausanne) 2021 23;8:713599. Epub 2021 Jul 23.

Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.

Band keratopathy (BK) is a common complication in aphakic eyes with silicone oil tamponade for open-globe injury (OGI), characterized by the grayish-white opacities in the cornea, resulting in a significantly decreased vision when extending to the visual axis. To identify the risk factors for BK in aphakic eyes following vitreoretinal surgical treatment with silicone oil tamponade for OGIs, we performed a multicenter case-control study. The incidence of BK was 28% (28/100 eyes). The multivariate binary logistic regression revealed the silicone oil retention time (SORT) ≥6 months and zone III injury were significant risk factors for BK. From the hierarchical interaction, SORT ≥6 months had a significant risk for BK in eyes with rupture, aniridia, and zone III injury, while zone III injury had a significant risk for BK in eyes with rupture, incomplete/complete iris, and SORT ≥6 months. By using restricted cubic splines with three knots at the 25th, 50th, and 75th centiles to model the association of SORT with BK, we also found a marked increase in the risk for BK at ≥10 months and a slow increase after 6 months, but almost stable within 4-6 months.
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http://dx.doi.org/10.3389/fmed.2021.713599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342885PMC
July 2021

Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial-Mesenchymal Transition in Hypoxic NSCLC Cells the HIF-1α/PFKP Axis.

Front Oncol 2021 21;11:691762. Epub 2021 Jul 21.

Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Background: Tumor cells initiate hypoxia-induced mechanisms to fuel cell proliferation, invasion, and metastasis, largely mediated by low O-responsive Hypoxia-Inducible Factor 1 Alpha (HIF-1α). Therefore, hyperbaric oxygen therapy (HBO) is now being studied in cancer patients, but its impact upon non-small-cell lung cancer (NSCLC) cell metabolism remains uncharacterized.

Methods: We employed the NSCLC cell lines A549 and H1299 for studies. Glucose uptake, pyruvate, lactate, and adenosine triphosphate (ATP) assays were used to assess aerobic glycolysis (Warburg effect). A quantitative glycolytic flux model was used to analyze the flux contributions of HIF-1α-induced glucose metabolism genes. We used a Lewis lung carcinoma (LLC) murine model to measure lung tumorigenesis in C57BL/6J mice.

Results: HBO suppressed hypoxia-induced HIF-1α expression and downstream HIF-1α signaling in NSCLC cells. One HIF-1α-induced glucose metabolism gene-Phosphofructokinase, Platelet (PFKP)-most profoundly enhanced glycolytic flux under both low- and high-glucose conditions. HBO suppressed hypoxia-induced PFKP transactivation and gene expression HIF-1α downregulation. HBO's suppression of the Warburg effect, suppression of hyperproliferation, and suppression of epithelial-to-mesenchymal transition (EMT) in hypoxic NSCLC cell lines is mediated by the HIF-1α/PFKP axis. , HBO therapy inhibited murine LLC lung tumor growth in a Pfkp-dependent manner.

Conclusions: HBO's repression of the Warburg effect, repression of hyperproliferation, and repression of EMT in hypoxic NSCLC cells is dependent upon HIF-1α downregulation. HIF-1α's target gene PFKP functions as a central mediator of HBO's effects in hypoxic NSCLC cells and may represent a metabolic vulnerability in NSCLC tumors.
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http://dx.doi.org/10.3389/fonc.2021.691762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335162PMC
July 2021

RBM10 Deficiency Is Associated With Increased Immune Activity in Lung Adenocarcinoma.

Front Oncol 2021 21;11:677826. Epub 2021 Jul 21.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China.

Introduction: RBM10 is one of the frequently mutated genes in lung adenocarcinoma (LUAD). Previous studies have confirmed that RBM10 could suppress the disease progression and cell proliferation in LUAD, but its loss-of-function mutations are more frequent in early-stage disease and decrease with the advancement of the clinical stage. This is contradictory to its role of tumor suppressor. Here, we conducted a systematic analysis to elucidate whether there was other potential biological significance of RBM10 deficiency during the progression of LUAD.

Materials And Methods: The whole exome sequencing data of 39 tumor samples from early-stage LUADs (GGN cohort) and genomic and transcriptome data of the Cancer Genome Atlas (TCGA) LUAD cohort (TCGA_LUAD cohort) and a Chinese LUAD cohort (CHOICE_ADC cohort) were first obtained. Systematic bioinformatic analyses were then conducted to determine gene expression signature, immune infiltration levels and predicted immunotherapy response. Immunohistochemistry (IHC) was also conducted to validate the result of immune infiltration.

Results: The mutation rate of RBM10 was significantly higher in the GGN cohort than that in the TCGA_LUAD and CHOICE_ADC cohorts. In both TCGA_LUAD and CHOICE_ADC cohorts, multiple immune related pathways were markedly enriched in RBM10 deficient group. Further analyses showed that tumors with RBM10 mutations displayed higher TMB, and LUADs with RBM10 deficiency also showed higher HLA expression levels, including many HLA class I and II molecules. Additionally, many immune cells, including myeloid dendritic cells, macrophages, neutrophils and CD8+T cells, showed higher infiltration levels in LUADs with RBM10 deficiency. Finally, some immune checkpoint molecules, such as PD-L1 and TIM-3, were highly expressed in RBM10 deficient population and the predicted immunotherapy response was calculated through TIDE algorithm, showing that IFNG expression, MSI score and CD8 expression were higher in RBM10 deficient group, while MDSC and M2 macrophage were lower in RBM10 deficient group.

Conclusion: Our study demonstrates that RBM10 deficient LUADs show higher HLA expression and immune cell infiltration, and some immune checkpoint molecules are also highly expressed. In brief, RBM10 deficiency could enhance anti-tumor immunity in LUAD.
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http://dx.doi.org/10.3389/fonc.2021.677826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336464PMC
July 2021

Exploratory saccades data analysis of video head impulse test in Different Meniere's Disease Stages.

J Vestib Res 2021 Aug 1. Epub 2021 Aug 1.

College of Otolaryngology Head and Neck Sury, Chinese PLA General Hospital, Chinese PLA Medical School, FuxingRoad, Beijing, China.

Background: Unapparent saccades in video head impulse test (vHIT) are usually present in MD patients but tend to be ignored by the clinician. The result of vHIT is constantly questioned in MD patients due to a lack of uniform metrics. A more effective indicator is needed for indicating MD's pathological progress.

Objectives: To get a comprehensive understanding of the nature and usability of saccades in different MD stages.

Methods: 118 patients diagnosed with unilateral MD were recruited in this study. Patient history, audiological examination, caloric test, vHIT were performed. We proposed 'raw saccades' to represent all showed wave peaks behind the head peak and named saccades by their appearance sequence: 1st saccade, 2nd saccade and 3rd saccade. An exploratory saccade analysis was executed to investigate the effectiveness of saccade attributes in identifying MD stages.

Results: MD patients have greater detectable 1st saccade than PR score as well as 2nd saccade. The time and velocity of the 1st saccade show high interaural variability (p = 0.028, p = 0.000 respectively). No statistical difference concerning the vHIT gain, PR score and 2nd saccade among stages could be recognized on both affected and contralateral sides. Multiple comparisons show the affected 1st saccade velocity and affected 1st saccade absolute velocity have stage-difference. At late stages (3&4), the affected 1st saccade is manifested as a speed increase, and this measure shows a relatively high correlation with MD stages compared to other vestibular indicators.

Conclusion: The 1st saccade velocity on the affected side could indicate the MD disease process and severity.
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http://dx.doi.org/10.3233/VES-201642DOI Listing
August 2021

An antisense circular RNA circSCRIB enhances cancer progression by suppressing parental gene splicing and translation.

Mol Ther 2021 Sep 6;29(9):2754-2768. Epub 2021 Aug 6.

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address:

Circular RNAs (circRNAs) represent a large group of non-coding RNAs that are widely detected in mammalian cells. Although most circRNAs are generated in a sense orientation, there is a group of circRNAs that are synthesized in an antisense orientation. High-throughput analysis of breast cancer specimens revealed a significant enrichment of 209 antisense circRNAs. The tumor suppressor SCRIB was shown to potentially produce thirteen circRNAs, three of which are in an antisense orientation. Among these three circRNAs, circSCRIB (hsa_circ_0001831) was the most enriched in the breast cancer panel. This antisense SCRIB circRNA was shown to span one intron and two exons. We hypothesized that this circRNA could decrease pre-mRNA splicing and mRNA translation. To test this, we generated a hsa_circ_0001831 expression construct. We found that there was decreased SCRIB mRNA production but increased cancer cell proliferation, migration, and invasion. In comparison, an exonic sequence construct did not affect mRNA splicing but decreased protein translation, leading to increased E-cadherin expression and decreased expression of N-cadherin and vimentin. Thus, there was increased cell migration, invasion, proliferation, colony formation, and tumorigenesis. Our study suggests a novel modulatory role of antisense circRNAs on their parental transcripts. This may represent a promising approach for developing circRNA-directed therapy.
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http://dx.doi.org/10.1016/j.ymthe.2021.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417507PMC
September 2021
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