Publications by authors named "Zhuo Yang"

384 Publications

Cross-Modal Retrieval between C NMR Spectra and Structures for Compound Identification Using Deep Contrastive Learning.

Anal Chem 2021 Nov 29. Epub 2021 Nov 29.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences. Beijing 100050, China.

Library matching using carbon-13 nuclear magnetic resonance (C NMR) spectra has been a popular method adopted in compound identification systems. However, the usability of existing approaches has been restricted as enlarging a library containing both a chemical structure and spectrum is a costly and time-consuming process. Therefore, we propose a fundamentally different, novel approach to match C NMR spectra directly against a molecular structure library. We develop a cross-modal retrieval between spectrum and structure (CReSS) system using deep contrastive learning, which allows us to search a molecular structure library using the C NMR spectrum of a compound. In the test of searching 41,494 C NMR spectra against a reference structure library containing 10.4 million compounds, CReSS reached a [email protected] accuracy of 91.64% and a processing speed of 0.114 s per query spectrum. When further incorporating a filter with a molecular weight tolerance of 5 Da, CReSS achieved a new remarkable [email protected] of 98.39%. Furthermore, CReSS has potential in detecting scaffolds of novel structures and demonstrates great performance for the task of structural revision. CReSS is built and developed to bridge the gap between C NMR spectra and structures and could be generally applicable in compound identification.
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http://dx.doi.org/10.1021/acs.analchem.1c04307DOI Listing
November 2021

Asparagine endopeptidase deletion ameliorates cognitive impairments by inhibiting proinflammatory microglial activation in MPTP mouse model of Parkinson disease.

Brain Res Bull 2021 Nov 25;178:120-130. Epub 2021 Nov 25.

Medical School, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin 300071, China. Electronic address:

In addition to motor dysfunction, cognitive impairments have been reported to occur in patients with early-stage Parkinson's disease (PD). In this study, we examined a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This treatment led to the degeneration of nigrostriatal dopaminergic neurons in mice, a phenomenon that is consistent with previous studies. Besides, spatial memory and object recognition of MPTP-treated mice were impaired, as denoted by the Morris water maze (MWM) and novel object recognition (NOR) tests, respectively. Moreover, hippocampal synaptic plasticity (long-term potentiation and depotentiation) and the levels of synaptic proteins in hippocampus were decreased after MPTP treatment. We also found that MPTP resulted in the microglial activation and an inflammatory response in the striatum and hippocampus. Mammalian asparagine endopeptidase (AEP), a cysteine lysosomal protease, is involved in the cleavage and activation of Toll-like receptors (TLRs). The deletion of AEP can inhibit TLR4 in a mouse model of Alzheimer's disease, and TLR4 is upregulated in PD, inducing microglial activation and inflammation. We found that AEP deletion provided greater resistance to the toxic effects of MPTP. AEP knockout ameliorated the cognition and the synaptic plasticity defects in the hippocampus. Furthermore, AEP deletion decreased the expression of TLR4 and reduced microglial activation and the levels of several proinflammatory cytokines. Thus, we suggest that AEP plays a role in the inflammation induced by MPTP, and TLR4 might also involve in this process. AEP deletion could be a possible treatment strategy for the cognitive deficits of PD.
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http://dx.doi.org/10.1016/j.brainresbull.2021.11.011DOI Listing
November 2021

SOCS proteins and their roles in the development of glioblastoma.

Oncol Lett 2022 Jan 5;23(1). Epub 2021 Nov 5.

Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor in adults. GBM is characterized by a high degree of malignancy and aggressiveness, as well as high morbidity and mortality rates. GBM is currently treatable via surgical resection, chemotherapy and radiotherapy, but the prognosis of patients with GBM is poor. The suppressor of cytokine signaling (SOCS) protein family comprises eight members, including SOCS1-SOCS7 and cytokine-inducible SH2-containing protein. SOCS proteins regulate the biogenesis of GBM via the JAK/STAT and NF-κB signaling pathways. Driven by NF-κB, the expression of SOCS proteins can serve as a negative regulator of the JAK/STAT signaling pathway and exerts a potential inhibitory effect on GBM. In GBM, E3 ubiquitin ligase is involved in the regulation of cellular functions, such as the receptor tyrosine kinase (RTK) survival signal, in which SOCS proteins negatively regulate RTK signaling, and kinase overexpression or mutation can lead to the development of malignancies. Moreover, SOCS proteins affect the proliferation and differentiation of GBM cells by regulating the tumor microenvironment. SOCS proteins also serve specific roles in GBM of different grades and different isocitrate dehydrogenase mutation status. The aim of the present review was to describe the biogenesis and function of the SOCS protein family, the roles of SOCS proteins in the microenvironment of GBM, as well as the role of this protein family and E3 ubiquitin ligases in GBM. Furthermore, the role of SOCS proteins as diagnostic and prognostic markers in GBM and their potential role as GBM therapeutics were explored.
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http://dx.doi.org/10.3892/ol.2021.13123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607235PMC
January 2022

Comments on "The Role of Cold Biopsy in Diminutive and Small Colonic Polyp Removal: A Systematic Review and Meta-Analysis".

Gastrointest Endosc 2021 Dec;94(6):1153

Department of Digestive Endoscopy, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China.

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http://dx.doi.org/10.1016/j.gie.2021.07.007DOI Listing
December 2021

MDM2 is involved in the regulation of p53 expression in the immune response of oyster Crassostrea hongkongensis.

Dev Comp Immunol 2021 Nov 16;128:104321. Epub 2021 Nov 16.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou, 510301, China; Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), Chinese Academy of Sciences, China. Electronic address:

MDM2 (mouse double-minute) and p53 form a negative feedback loop and play a prominent role in preventing the induction of uncontrolled apoptosis. To better understand their potential roles in oyster Crassostrea hongkongensis, MDM2 and p53 homologs were first isolated and cloned in C. hongkongensis (named ChMDM2 and Chp53), and their mRNA expression patterns in tissues and developmental stages were analyzed. Multiple sequence alignment analysis and phylogenetic analysis of ChMDM2 and Chp53 displayed a high degree of homology and conservation. In addition, exposure to Vibrio coralliilyticus resulted in DNA damage and apoptosis in the hemocytes of C. hongkongensis, and found that the mRNA expression level of ChMDM2 was decreased, while the relative expression of Chp53 was significantly increased in the hemocytes and gills. Furthermore, fluorescence from ChMDM2-EGFP and Chp53-Red were found to be distributed in the nucleus of HEK293T cells. Besides, dual-luciferase reporter assays showed that ChMDM2 antagonized with Chp53 and participates in p53 signaling pathway. In addition, the interaction between ChMDM2 and Chp53 was confirmed strongly by Co-immunoprecipitation assays. Furthermore, the results of RNAi showed that ChMDM2 and Chp53 participated in apoptosis which induced infection of V. coralliilyticus. Taken together, our results characterized the features of ChMDM2 and Chp53, which played a critical role in apoptosis of C. hongkongensis.
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http://dx.doi.org/10.1016/j.dci.2021.104321DOI Listing
November 2021

Regulation of the Development in Physcomitrium (Physcomitrella) patens implicates the functional differentiation of plant RNase H1s.

Plant Sci 2021 Dec 29;313:111070. Epub 2021 Sep 29.

Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, 430062, China. Electronic address:

R-loops, consisting of a DNA:RNA hybrid and a single-stranded DNA (ssDNA), form naturally as functional chromosome structures and are crucial in many vital biological processes. However, disrupted R-loop homeostasis will threat to the integrity and stability of genome. As the endonuclease, RNase H1 can efficiently recognize and remove excess R-loops to protect organisms from DNA damage induced by R-loop over-accumulation. Here, we investigated the function of RNase H1 in Physcomitrium (Physcomitrella) patens to illustrate its important role in the evolution of plants. We found that PpRNH1A dysfunction seriously affected shoot growth and branch formation in P. patens, revealing a noticeable functional difference between PpRNH1A and AtRNH1A of Arabidopsis. Furthermore, auxin signaling was significantly affected at the transcriptional level in PpRNH1A mutant plants, as a result of the accumulation of R-loops at several auxin-related genes. This study provides evidence that PpRNH1A regulates the development of P. patens by controlling R-loop formation at specific loci to modulate the transcription of auxin-related genes. It also highlights the interspecific functional differences between early land plants and vascular plants, despite crucial and conserved role of RNase H1 played in maintaining R-loop homeostasis.
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http://dx.doi.org/10.1016/j.plantsci.2021.111070DOI Listing
December 2021

Circulating ANGPTL3 and ANGPTL4 levels predict coronary artery atherosclerosis severity.

Lipids Health Dis 2021 Nov 6;20(1):154. Epub 2021 Nov 6.

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis.

Methods: A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits.

Results: According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively.

Conclusions: Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.
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http://dx.doi.org/10.1186/s12944-021-01580-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571829PMC
November 2021

Loss of FBXW7 correlates with increased IDH1 expression in glioma and enhances IDH1-mutant cancer cell sensitivity to radiation.

Cancer Res 2021 Nov 4. Epub 2021 Nov 4.

Neurosurgery, Fifth Affiliated Hospital of Zhengzhou University

F-box and WD repeat domain containing 7 (FBXW7) is a substrate receptor of the ubiquitin ligase SKP1-Cullin1-F-box complex and a potent tumor suppressor that prevents unregulated cell growth and tumorigenesis. However, little is known about FBXW7-mediated control of cell metabolism and related functions in cancer therapy. Here, we report that FBXW7 expression inversely correlates with the expression levels of the key metabolic enzyme isocitrate dehydrogenase 1 (IDH1) in glioma patients and public glioma datasets. Deletion of FBXW7 significantly increased both wild type (WT) and mutant IDH1 expression, which was mediated by blocking degradation of sterol regulatory element binding protein 1 (SREBP1). The upregulation of neomorphic mutant IDH1 by FBXW7 deletion stimulated production of the oncometabolite 2-hydroxyglutarate (2-HG) at the expense of increasing pentose phosphate pathway (PPP) activity and NADPH consumption, limiting the buffering ability against radiation-induced oxidative stress. Additionally, FBXW7 knockout and IDH1 mutations induced non-homologous end joining (NHEJ) and homologous recombination (HR) defects, respectively. In vitro and in vivo, loss of FBXW7 dramatically enhanced the efficacy of radiation treatment in IDH1 mutant cancer cells. Taken together, this work identifies FBXW7 deficiency as a potential biomarker representing both DNA repair and metabolic vulnerabilities that sensitizes IDH1 mutant cancers to radiotherapy.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0384DOI Listing
November 2021

Binders for sodium-ion batteries: progress, challenges and strategies.

Chem Commun (Camb) 2021 Nov 23;57(93):12406-12416. Epub 2021 Nov 23.

Institute for Carbon Neutralization, College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, 325035, P. R. China.

Binders as a bridge in electrodes can bring various components together thus guaranteeing the integrity of electrodes and electronic contact during battery cycling. In this review, we summarize the recent progress of traditional binders and novel binders in the different electrodes of SIBs. The challenges faced by binders in terms of bond strength, wettability, thermal stability, conductivity, cost, and environment are also discussed in details. Correspondingly, the designing principle and advanced strategies of future research on SIB binders are also provided. Moreover, a general conclusion and perspective on the development of binder design for SIBs in the future are presented.
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http://dx.doi.org/10.1039/d1cc04563fDOI Listing
November 2021

Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants.

Genome Med 2021 10 14;13(1):164. Epub 2021 Oct 14.

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

Background: The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed.

Methods: Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses.

Results: Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect.

Conclusions: Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.
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http://dx.doi.org/10.1186/s13073-021-00985-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515915PMC
October 2021

Common bile duct morphology is associated with recurrence of common bile duct stones in Billroth II anatomy patients.

World J Clin Cases 2021 Sep;9(26):7671-7681

Department of Digestive Endoscopy, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the primary choice for removing common bile duct (CBD) stones in Billroth II anatomy patients. The recurrence of CBD stones is still a challenging problem.

Aim: To evaluate CBD morphology and other predictors affecting CBD stone recurrence.

Methods: A retrospective case-control analysis was performed on 138 CBD stones patients with a history of Billroth II gastrectomy, who underwent therapeutic ERCP for stone extraction at our center from January 2011 to October 2020. CBD morphology and other predictors affecting CBD stone recurrence were examined by univariate analysis and multivariate logistic regression analysis.

Results: CBD morphology ( < 0.01) and CBD diameter ≥ 1.5 cm (odds ratio [OR] = 6.15, 95% confidence interval [CI]: 1.87-20.24, < 0.01) were the two independent risk factors. In multivariate analysis, the recurrence rate of patients with S type was 16.79 times that of patients with straight type (OR = 16.79, 95%CI: 4.26-66.09, < 0.01), the recurrence rate of patients with polyline type was 4.97 times that of patients with straight type (OR = 4.97, 95%CI: 1.42-17.38, = 0.01), and the recurrence rate of S type patients was 3.38 times that of patients with polyline type (OR = 3.38, 95%CI: 1.07-10.72, = 0.04).

Conclusion: CBD morphology, especially S type and polyline type, is associated with increased recurrence of CBD stones in Billroth II anatomy patients.
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http://dx.doi.org/10.12998/wjcc.v9.i26.7671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462226PMC
September 2021

Fire-Retardant, Stable-Cycling and High-Safety Sodium Ion Battery.

Angew Chem Int Ed Engl 2021 Oct 1. Epub 2021 Oct 1.

Institute for Carbon Neutralization, College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325035, China.

The safety of energy storage equipment has always been a stumbling block to the development of battery, and sodium ion battery is no exception. However, as an ultimate solution, the use of non-flammable electrolyte is susceptible to the side effects, and its poor compatibility with electrode, causing failure of batteries. Here, we report a non-flammable electrolyte design to achieve high-performance sodium ion battery, which resolves the dilemma via regulating the solvation structure of electrolyte by hydrogen bonds and optimizing the electrode-electrolyte interphase. The reported non-flammable electrolyte allows stable charge-discharge cycling of both sodium vanadium [email protected] carbon and Prussian [email protected] carbon full pouch cell for more than 120 cycles with a capacity retention of >85 % and high cycling Coulombic efficiency (99.7 %).
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http://dx.doi.org/10.1002/anie.202112382DOI Listing
October 2021

Improved Sensitivity of Surface-Enhanced Raman Scattering with Gold Nanoparticles-Insulator-Metal Sandwich Layers on Flat Sapphire Substrate.

Nanomaterials (Basel) 2021 Sep 16;11(9). Epub 2021 Sep 16.

Smart Display Lab, Department of Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Surface-enhanced Raman scattering (SERS) as a high sensitivity analytical method for molecule detection has attracted much attention in recent research. In this work, we demonstrated an improved SERS substrate, which has the gold nanoparticles randomly distributed on a SiO interception layer over a gold thin film layer on the flat sapphire substrate (AuNP/SiO/Au/Sapphire), over the dispersed gold nanoparticles on a silicon substrate (AuNP/Si), for detection of R6G (1 × 10 M) in a Raman microscope. The fabrication of sandwich layers on top of the sapphire substrate involves evaporation of a gold mirror as thick as 100 nm, plasma enhanced chemical vapor deposition of the silica insulator layer 10 nm thick, and evaporation of a thin gold layer 10 nm thick for forming gold nanoparticles. For comparison, a gold thin film with a thickness of 5 nm and 10 nm was evaporated on a silicon substrate, respectively (AuNP/Si), as the reference SERS substrates in the experiment. The AuNP/SiO/Au/Sapphire substrate demonstrated improved sensitivity in detection of molecules in Raman microscopy, which can enable the molecules to be recognizable at a low laser power as 8.5 × 10 mW, 0.017 mW, 0.085 mW, and 0.17 mW for ultrashort exposure time. The simulation of AuNP/SiO/Au/Sapphire substrate and AuNP/Si substrate, based on the finite-difference time-domain (FDTD) method, explained the improved sensitivity for detection of R6G molecules from the view of classical electromagnetics, and it suggested the optimized size for the gold nanoparticles and the optimized laser wavelength for Raman microscopy for further research.
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http://dx.doi.org/10.3390/nano11092416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468857PMC
September 2021

Development of a long noncoding RNA -dependent gold nanoparticle molecular beacon for the detection of gastric cancer cells.

Nanomedicine (Lond) 2021 10 27;16(25):2255-2267. Epub 2021 Sep 27.

Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No. 83, Xinqiao Street, Shapingba District, Chongqing, 400037, China.

 Long noncoding RNA (lncRNA) -dependent gold nanoparticle molecular beacons (AuNP-MB) were constructed for the detection of gastric cancer cells. The AuNP-MBs were prepared according to well-established procedures based on the Au-S interaction between the gold lattice and thiol functionalized oligonucleotides. More importantly, the stability and targeting ability of AuNP-MB were verified by a series of and experiments. The lncRNA-dependent probes were successfully utilized for AuNP-MB-based intracellular imaging, with fluorescence effectively emitted in GC cells, but not in normal cells. Notably, such fluorescent emission was positively correlated with lncRNA BC032469 expression. The authors developed an effective fluorescent imaging probe for the recognition of gastric cancer cells.
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http://dx.doi.org/10.2217/nnm-2021-0249DOI Listing
October 2021

Cost-effectiveness of field trauma triage among injured children transported by emergency medical services.

Am J Emerg Med 2021 Aug 20;50:492-500. Epub 2021 Aug 20.

Center for Policy and Research in Emergency Medicine, Department of Emergency Medicine, Oregon Health and Science University, Portland, OR, United States of America.

Background: A pediatric field triage strategy that meets the national policy benchmark of ≥95% sensitivity would likely improve health outcomes but increase heath care costs. Our objective was to compare the cost-effectiveness of current pediatric field triage practices to an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity.

Study Design: We developed a decision-analysis Markov model to compare the outcomes and costs of the two strategies. We used a prospectively collected cohort of 3507 (probability weighted, unweighted n = 2832) injured children transported by 44 emergency medical services (EMS) agencies to 28 trauma and non-trauma centers in the Northwestern United States from 1/1/2011 to 12/31/2011 to derive the alternative field triage strategy and to populate model probability and cost inputs for both strategies. We compared the two strategies by calculating quality adjusted life years (QALYs) and health care costs over a time horizon from the time of injury until death. We set an incremental cost-effectiveness ratio threshold of less than $100,000 per QALY for the alternative field triage to be a cost-effective strategy.

Results: Current pediatric field triage practices had a sensitivity of 87.4% (95% confidence interval [CI] 71.9 to 95.0%) and a specificity of 82.3% (95% CI 81.0 to 83.5%) and the alternative field triage strategy had a sensitivity of 97.3% (95% CI 82.6 to 99.6%) and a specificity of 46.1% (95% CI 43.8 to 48.4%). The alternative field triage strategy would cost $476,396 per QALY gained compared to current pediatric field triage practices and thus would not be a cost-effective strategy. Sensitivity analyses demonstrated similar findings.

Conclusion: Current field triage practices do not meet national policy benchmarks for sensitivity. However, an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity is not a cost-effective strategy.
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http://dx.doi.org/10.1016/j.ajem.2021.08.037DOI Listing
August 2021

Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice.

Life Sci 2021 Nov 10;285:119944. Epub 2021 Sep 10.

Medical School, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin 300071, China. Electronic address:

Aims: Chronic cerebral hypoperfusion (CCH) is a state of chronic cerebral blood flow reduction, and it is the main cause of cognitive impairment and neurodegenerative diseases. The abnormal upregulation of legumain, a lysosomal cysteine protease, trigger synaptic plasticity impairment and neuroinflammation, which are involved in the underlying pathophysiology of CCH. At present, few studies have reported the role of legumain in cognitive impairment caused by CCH. In our study, we aimed to investigate the involvement of legumain knockout in cognitive function and neuroinflammation in a CCH mouse model.

Main Methods: In this study, right unilateral common carotid artery occlusion (rUCCAO) was used to simulate the pathological state of cerebral ischemic injury. Various behavioural tests were executed to assess cognitive performance. In vivo electrophysiological recordings were used to measure synaptic functions. Western blotting, Golgi staining, haematoxylin/eosin staining, and immunofluorescence assays were conducted to examine pathological changes and molecular mechanisms.

Key Findings: The data showed that the level of legumain was significantly increased in the hippocampus of mice subjected to rUCCAO. Legumain knockout significantly improved cognitive function and synaptic plasticity induced by rUCCAO, suggesting that legumain knockout-regulation effectively protected against CCH-induced behavioural dysfunctions. Moreover, legumain knockout suppressed rUCCAO-induced microglial activation, reduced the abnormal expression of inflammatory cytokines and the inflammasome complex, and impeded the activation of P65 and pyroptosis.

Significance: These findings suggest that legumain is an effective regulator of CCH, and may be an ideal target for the development of cerebral ischemia treatments in the future.
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http://dx.doi.org/10.1016/j.lfs.2021.119944DOI Listing
November 2021

Soft-Carbon-Coated, Free-Standing, Low-Defect, Hard-Carbon Anode To Achieve a 94% Initial Coulombic Efficiency for Sodium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Sep 10;13(37):44358-44368. Epub 2021 Sep 10.

School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, P. R. China.

Developing hard carbon with a high initial Coulombic efficiency (ICE) and very good cycling stability is of great importance for practical sodium-ion batteries (SIBs). Defects and oxygen-containing groups grown along either the carbon edges or the layers, however, are inevitable in hard carbon and can cause a tremendous density of irreversible Na sites, decreasing the efficiency and therefore causing failure of the battery. Thus, eliminating these unexpected defect structures is significant for enhancing the battery performance. Herein, we develop a strategy of applying a soft-carbon coating onto free-standing hard-carbon electrodes, which greatly hinders the formation of defects and oxygen-containing groups on hard carbon. The electrochemical results show that the soft-carbon-coated, free-standing hard-carbon electrodes can achieve an ultrahigh ICE of 94.1% and long cycling performance (99% capacity retention after 100 cycles at a current density of 20 mA g), demonstrating their great potential in practical sodium storage systems. The sodium storage mechanism was also investigated by operando Raman spectroscopy. Our sodium storage mechanism extends the "adsorption-intercalation-pore filling-deposition" model. We propose that the pore filling in the plateau area might be divided into two parts: (1) sodium could fill in the pores near the inner wall of the carbon layer; (2) when the sodium in the inner wall pores is close to saturation, the sodium could be further deposited onto the existing sodium.
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http://dx.doi.org/10.1021/acsami.1c12171DOI Listing
September 2021

Interaction of tau with HNRNPA2B1 and N-methyladenosine RNA mediates the progression of tauopathy.

Mol Cell 2021 Oct 27;81(20):4209-4227.e12. Epub 2021 Aug 27.

Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; Center for Neurophotonics, Boston University, Boston, MA 02215, USA; Center for Systems Neuroscience, Boston University, Boston, MA 02215, USA. Electronic address:

The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau phosphorylation, aggregation, and a translational stress response that includes stress granules and reduced protein synthesis. Proteomic analysis identifies HNRNPA2B1 as a principle target of oTau-c. The association of HNRNPA2B1 with endogenous oTau was verified in neurons, animal models, and human Alzheimer brain tissues. Mechanistic studies demonstrate that HNRNPA2B1 functions as a linker, connecting oTau with N-methyladenosine (mA) modified RNA transcripts. Knockdown of HNRNPA2B1 prevents oTau or oTau-c from associating with mA or from reducing protein synthesis and reduces oTau-induced neurodegeneration. Levels of mA and the mA-oTau-HNRNPA2B1 complex are increased up to 5-fold in the brains of Alzheimer subjects and P301S tau mice. These results reveal a complex containing oTau, HNRNPA2B1, and mA that contributes to the integrated stress response of oTau.
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http://dx.doi.org/10.1016/j.molcel.2021.07.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541906PMC
October 2021

Large-Scale Plasma Peptidomic Profiling Reveals a Novel, Nontoxic, -Derived Antimicrobial Peptide against Foodborne Pathogens.

Mar Drugs 2021 Jul 26;19(8). Epub 2021 Jul 26.

CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou 510301, China.

Antimicrobial peptides are a fundamental component of mollusks' defense systems, though they remain a thinly investigated subject. Here, infection by triggered a significant increase in antimicrobial activity in oyster plasma. By using PBS-challenged oysters as a control, plasma peptides from immunologically challenged oysters were subjected to peptidomic profiling and in silico data mining to identify bioactive peptides. Thirty-five identified plasma peptides were up-regulated post infection, among which, six up-regulated peptides (URPs) showed a relatively high positive charge. URP20 was validated with significant antibacterial activity. Virtually, URP20 triggered aggregation of bacterial cells, accompanied by their membrane permeabilization. Interestingly, URP20 was found to be active against Gram-positive and Gram-negative foodborne pathogens as well as , with no cytotoxicity to mammalian cells and mice. Our study provides the first large-scale plasma peptidomic dataset that identifies novel bioactive peptides in marine mollusks. Further exploration of peptide diversity in marine invertebrates should prove a fruitful pursuit for designing novel AMPs with broad applications.
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http://dx.doi.org/10.3390/md19080420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399951PMC
July 2021

SLC7A11 negatively associates with mismatch repair gene expression and endows glioblastoma cells sensitive to radiation under low glucose conditions.

Neoplasma 2021 Aug 25. Epub 2021 Aug 25.

Department of Neurosurgery, The Fifth Affiliated Hospital, Zhengzhou University, ZhengZhou, China.

The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.
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http://dx.doi.org/10.4149/neo_2021_210327N410DOI Listing
August 2021

Notch1 participates in the activation of autophagy in the hippocampus of type I diabetic mice.

Neurochem Int 2021 11 11;150:105156. Epub 2021 Aug 11.

School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address:

Notch1 not only plays a key role in the development of the nervous system but also modulates synaptic plasticity and memory. However, the role of Notch1 in the brain of diabetes is still unclear. We hypothesize that Notch1 is involved in type I diabetes-induced cognitive dysfunction. In this study, adult male C57BL/6J mice carrying a heterozygous null mutation in the Notch1 gene (Notch1) and wild-type littermate controls were used in this experiment. They were subjected to streptozocin (55 mg/kg, i.p.) for consecutive five days. After 12 weeks, the cognitive function of all mice was detected by novel object recognition (NOR) test and electrophysiological recording. Our results demonstrated that the levels of Notch1 mRNA and Notch1 receptor were increased in the hippocampus of the wild-type diabetic mice at 12 weeks. It suggested that the Notch1 signal pathway was activated. Compared with the wild-type diabetic mice, the discrimination index and the long-term potentiation was further decreased in the Notch1 diabetic group, the impairment of neuronal ultrastructure was exacerbated in the hippocampus of the Notch1 diabetic mice, and the number of synapses and autophagic vacuoles were significantly reduced in the Notch1 diabetic group. Moreover, some postsynaptic associated protein expressions were down-regulated, as well as the Beclin1 expression and the ratio of LC3II/LC3I were reduced in the hippocampus of the Notch1 diabetic mice. Interestingly, the phosphorylation of mTOR, Akt, and ERK1/2 were all inhibited in the Notch1 diabetic group. Taken together, these results suggest that Notch1 deficiency deteriorates the synaptic plasticity and inhibits the activation of autophagy partly via the mTOR-independent signal pathway in the hippocampus of type I diabetic mice.
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http://dx.doi.org/10.1016/j.neuint.2021.105156DOI Listing
November 2021

Nano-CuO causes cell damage through activation of dose-dependent autophagy and mitochondrial lncCyt b-AS/ND5-AS/ND6-AS in SH-SY5Y cells.

Toxicol Mech Methods 2021 Aug 24:1-12. Epub 2021 Aug 24.

School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin, China.

Metal copper oxide nanoparticles (nano-CuO) are under mass production and have been widely utilized in many fields including catalysis, gas sensors, semiconductor materials, etc. The broad applications of nano-CuO have increased the possibility of risk to incidental exposure to the environment, and therefore, an in-depth investigation of their effects on live cells is required. This study investigated the impact of the nano-CuO on SH-SY5Y cells, and findings showed that the ratio of LC3-II/LC3-I was significantly increased in SH-SY5Y cells when the cells were treated with nano-CuO. However, if the autophagy inhibitor Bafilomycin A1 (Baf A1) was co-treated, the ratio of LC3-II/LC3-I was further improved. These outcomes might indicate that autophagy flux was permanently elevated by adding nano-CuO. Further results found highly activated levels of long noncoding RNAs (lncRNAs) under nano-CuO treatment. The data illustrate a mechanism that nano-CuO can promote autophagy and activate lncCyt b-AS/ND5-AS/ND6-AS in SH-SY5Y cells and have critical implications for nanoparticle biomedical applications.
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http://dx.doi.org/10.1080/15376516.2021.1964665DOI Listing
August 2021

Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders.

Nat Commun 2021 08 3;12(1):4408. Epub 2021 Aug 3.

Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS.
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http://dx.doi.org/10.1038/s41467-021-24627-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333096PMC
August 2021

A study on movement characteristics and distribution law of dust particles in open-pit coal mine.

Sci Rep 2021 Jul 19;11(1):14703. Epub 2021 Jul 19.

China Coal Technology & Engineering Group Chongqing Research Institute, Chongqing, China.

Previous simulation studies of dust particles movement behavior in open-pit coal mines only aimed at a single operation link, and the macro simulation is lacking. This study seeks to explore microscopic migration and macroscopic diffusion of dust particles in the mining area by numerical simulation method. The movement characteristics revealed, and the distribution law of the dust particles in a stable state with the corresponding migration paths in the mining area were obtained respectively. The results showed that the increase amplitude of dust particles diffusion velocity was inversely proportional to particle size, which was vital for dust pollution in the mine. And the larger the particle size in the mining pit was, the lower the escape rate of the dust particles was. Dust particles distributed over a wide range that were not limited by space height, and the distribution characteristics of dust particles at different heights were basically the same. Meanwhile, it is found that the dust distribution in the two places is relatively concentrated due to the circulation phenomenon of the mining pit and the west dump. And wind action would accelerate the moving dust particles to reach a stable distribution state.
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http://dx.doi.org/10.1038/s41598-021-94131-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289973PMC
July 2021

Legumain knockout improves repeated corticosterone injection-induced depression-like emotional and cognitive deficits.

Behav Brain Res 2021 09 12;413:113464. Epub 2021 Jul 12.

Medical School, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin 300071, China. Electronic address:

Emotional and cognitive impairment has been recognized as a central feature of depression, which is closely related to hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis caused by down-regulation of glucocorticoid receptor (GR) expression in patients. A decrease in GR expression can cause pathological changes and lead to the impairment of synaptic plasticity. Legumain, a lysosomal cysteine protease, plays an important role in neurological diseases. It is reported that legumain activates the MAPK signaling pathway, which modifies the GR. Therefore, we hypothesize that regulation of the GR by legumain plays a crucial role in the pathological process of depression. The relationships between legumain, GR, synaptic plasticity and emotional and cognitive deficits were explored in this study. The results demonstrated that repeated corticosterone (CORT) injections (3 weeks) induced emotional and cognitive deficits in mice, based on behavioral experiments and the detection of synaptic plasticity. Furthermore, CORT injections decreased the expression of hippocampal synapse-related proteins, cell density and dendritic spine density in the hippocampus, accompanied by increased protein expression in the MAPK signaling pathway and decreased expression of the GR. In conclusion, our results demonstrated that legumain knockout up-regulated expression of the GR by reducing protein expression in the MAPK signaling pathway, thereby improving hippocampal synaptic plasticity as well as the emotional and cognitive impairment of model mice. This suggests that legumain may be an effective therapeutic target for emotional and cognitive deficits.
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http://dx.doi.org/10.1016/j.bbr.2021.113464DOI Listing
September 2021

Application of Absorption and Scattering Properties Obtained through Image Pre-Classification Method Using a Laser Backscattering Imaging System to Detect Kiwifruit Chilling Injury.

Foods 2021 Jun 22;10(7). Epub 2021 Jun 22.

Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB), 14469 Potsdam, Germany.

Kiwifruit chilling injury (CI) damage occurs after long-term exposure to low temperature. A non-destructive approach to detect CI injury was tested in the present study, using a laser backscattering image (LBI) technique calibrated with 56 liquid phantoms for providing absorption coefficient (µ) and reduced scattering coefficient (µ'). Calibration of LBI resulted in a true-positive (TP) classification of 91.5% and 65.6% of predicted µ' and µ, respectively. The optical properties of 'SunGold™'and 'Hayward' kiwifruit were analysed at 520 nm with a two-step protocol capturing pre-classification according to the LBI parameters used in the calibration and estimation with the Farrell equation. Severely injured kiwifruit showed white corky tissue and water soaking, reduced soluble solids content and firmness measured destructively. Non-destructive classification results for 'SunGold™' showed a high percentage of TP for severe CI of 92% and 75% using LBI parameters directly and predicted µ and µ' after pre-classification, respectively. The classification accuracy for severe CI 'Hayward' kiwifruit with LBI parameter was low (58%) and with µ and µ' decreased further (35%), which was assumed to be due to interference caused by the long trichomes on the fruit surface.
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http://dx.doi.org/10.3390/foods10071446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303944PMC
June 2021

Reaction-Diffusion Model-Based Research on Formation Mechanism of Neuron Dendritic Spine Patterns.

Front Neurorobot 2021 14;15:563682. Epub 2021 Jun 14.

Institute of Robotics and Automatic Information Systems, College of Artificial Intelligence, Nankai University, Tianjin, China.

The pattern abnormalities of dendritic spine, tiny protrusions on neuron dendrites, have been found related to multiple nervous system diseases, such as Parkinson's disease and schizophrenia. The determination of the factors affecting spine patterns is of vital importance to explore the pathogenesis of these diseases, and further, search the treatment method for them. Although the study of dendritic spines is a hot topic in neuroscience in recent years, there is still a lack of systematic study on the formation mechanism of its pattern. This paper provided a reinterpretation of reaction-diffusion model to simulate the formation process of dendritic spine, and further, study the factors affecting spine patterns. First, all four classic shapes of spines, mushroom-type, stubby-type, thin-type, and branched-type were reproduced using the model. We found that the consumption rate of substrates by the cytoskeleton is a key factor to regulate spine shape. Moreover, we found that the density of spines can be regulated by the amount of an exogenous activator and inhibitor, which is in accordance with the anatomical results found in hippocampal CA1 in SD rats with glioma. Further, we analyzed the inner mechanism of the above model parameters regulating the dendritic spine pattern through Turing instability analysis and drew a conclusion that an exogenous inhibitor and activator changes Turing wavelength through which to regulate spine densities. Finally, we discussed the deep regulation mechanisms of several reported regulators of dendritic spine shape and densities based on our simulation results. Our work might evoke attention to the mathematic model-based pathogenesis research for neuron diseases which are related to the dendritic spine pattern abnormalities and spark inspiration in the treatment research for these diseases.
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http://dx.doi.org/10.3389/fnbot.2021.563682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236519PMC
June 2021

TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.

Life Sci Alliance 2021 08 28;4(8). Epub 2021 Jun 28.

Department of Pharmacy, Ludwig-Maximilians-Universität München, München, Germany

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1β levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1β levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.
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http://dx.doi.org/10.26508/lsa.202101047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321671PMC
August 2021

RNase H1C collaborates with ssDNA binding proteins WHY1/3 and recombinase RecA1 to fulfill the DNA damage repair in Arabidopsis chloroplasts.

Nucleic Acids Res 2021 07;49(12):6771-6787

Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Proper repair of damaged DNA is crucial for genetic integrity and organismal survival. As semi-autonomous organelles, plastids have their own genomes whose integrity must be preserved. Several factors have been shown to participate in plastid DNA damage repair; however, the underlying mechanism remains unclear. Here, we elucidate a mechanism of homologous recombination (HR) repair in chloroplasts that involves R-loops. We find that the recombinase RecA1 forms filaments in chloroplasts during HR repair, but aggregates as puncta when RNA:DNA hybrids accumulate. ssDNA-binding proteins WHY1/3 and chloroplast RNase H1 AtRNH1C are recruited to the same genomic sites to promote HR repair. Depletion of AtRNH1C or WHY1/3 significantly suppresses the binding of RNA polymerase to the damaged DNA, thus reducing HR repair and modulating microhomology-mediated double-strand break repair. Furthermore, we show that DNA polymerase IB works with AtRNH1C genetically to complete the DNA damage repair process. This study reveals the positive role of R-loops in facilitating the activities of WHY1/3 and RecA1, which in turn secures HR repair and organellar development.
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http://dx.doi.org/10.1093/nar/gkab479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266629PMC
July 2021

Heavy Metal Pollution Analysis and Health Risk Assessment of Two Medicinal Insects of Mylabris.

Biol Trace Elem Res 2021 Jun 16. Epub 2021 Jun 16.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.

Mylabris is the dried body of the Chinese blister beetle (Mylabris sp.), which has been used in traditional Chinese medicine and achieved significant positive effects in the treatment of cancer including liver cancer, lung cancer, and rectal cancer. However, heavy metal pollution and accumulation of Mylabris insects could pose threat to human health. This study was carried out to assess levels of different heavy metals like Cu, As, Cd, Hg, and Pb, along with soil-plant-insect system and health risks using two representative Mylabris insects from the Hasi Mountains of Gansu Province, China. The results showed that the heavy metal concentration of plants and insects followed the order Cu > Pb > As > Hg > Cd. Compared with soil and plants, the content of Cu in insects was the highest, reaching 45.65 mg/kg. Cu was the main element that caused insects to absorb and accumulate. The quantitative risk analysis implied the two Mylabris insects had carcinogenic risks, with the contribution of As providing 63% and 60.7%, respectively. This kind of carcinogenic risk that the human body could bear was not easy to cause side effects to normal people, but it was difficult and dangerous for cancer patients. Thus, the evaluation of health risk lays the foundation for pollutant risk monitoring.
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http://dx.doi.org/10.1007/s12011-021-02775-2DOI Listing
June 2021
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