Publications by authors named "Heng Wang"

712 Publications

Large refractive index modulation based on a BDK-doped step-index PMMA optical fiber for highly reflective Bragg grating inscription.

Opt Lett 2021 Jun;46(12):2864-2867

We experimentally report high reflectivity on the poly(methyl methacrylate) (PMMA)-based polymer optical fiber Bragg gratings by means of a 266 nm pulsed laser and phase mask technique. In the first recipe, fiber Bragg gratings (FBGs) were manufactured with a single pulse up to 3.7 mJ. After post-annealing, a stable refractive index change up to 4.2×10 was obtained. In the second recipe, FBGs were inscribed by 22 pulses with a lower pulse energy of 1.4 mJ, showing a stable refractive index change of 6.2×10. Both behaviors may mainly be attributed to the movement of initiating radicals arising from benzyl dimethyl ketal (BDK) under UV irradiation. The high refractive index change in step-index fibers paves the way to tilted FBG manufacturing with large tilt angles potentially for biomedical applications.
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http://dx.doi.org/10.1364/OL.427042DOI Listing
June 2021

Pyruvate kinase deficiency in children.

Pediatr Blood Cancer 2021 Jun 14:e29148. Epub 2021 Jun 14.

Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts, USA.

Background: Pyruvate kinase deficiency (PKD) is a rare, autosomal recessive red blood cell enzyme disorder, which leads to lifelong hemolytic anemia and associated complications from the disease and its management.

Methods: An international, multicenter registry enrolled 124 individuals younger than 18 years old with molecularly confirmed PKD from 29 centers. Retrospective and prospective clinical data were collected.

Results: There was a wide range in the age at diagnosis from 0 to 16 years. Presentation in the newborn period ranged from asymptomatic to neonatal jaundice to fulminant presentations of fetal distress, myocardial depression, and/or liver failure. Children <5 years old were significantly more likely to be transfused than children >12 to <18 years (53% vs. 14%, p = .0006), which correlated with the timing of splenectomy. Regular transfusions were most common in children with two severe PKLR variants. In regularly transfused children, the nadir hemoglobin goal varied considerably. Impact on quality of life was a common reason for treatment with regular blood transfusions and splenectomy. Splenectomy increased the hemoglobin and decreased transfusion burden in most children but was associated with infection or sepsis (12%) and thrombosis (1.3%) even during childhood. Complication rates were high, including iron overload (48%), perinatal complications (31%), and gallstones (20%).

Conclusions: There is a high burden of disease in children with PKD, with wide practice variation in monitoring and treatment. Clinicians must recognize the spectrum of the manifestations of PKD for early diagnostic testing, close monitoring, and management to avoid serious complications in childhood.
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http://dx.doi.org/10.1002/pbc.29148DOI Listing
June 2021

Over one century after discovery: pyrylium salt chemistry emerging as a powerful approach for the construction of complex macrocycles and metallo-supramolecules.

Chem Sci 2020 Oct 14;11(45):12249-12268. Epub 2020 Oct 14.

College of Chemistry and Environmental Engineering, Shenzhen University Shenzhen 518055 China

Over one century after its discovery, pyrylium salt chemistry has been extensively applied in preparing light emitters, photocatalysts, and sensitizers. In most of these studies, pyrylium salts acted as versatile precursors for the preparation of small molecules (such as furan, pyridines, phosphines, pyridinium salts, thiopyryliums and betaine dyes) and poly(pyridinium salt)s. In recent decades, pyrylium salt chemistry has emerged as a powerful approach for constructing complex macrocycles and metallo-supramolecules. In this perspective, we attempt to summarize the representative efforts of synthesizing and self-assembling large, complex architectures using pyrylium salt chemistry. We believe that this perspective not only highlights the recent achievements in pyrylium salt chemistry, but also inspires us to revisit this chemistry to design and construct macrocycles and metallo-supramolecules with increasing complexity and desired function.
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http://dx.doi.org/10.1039/d0sc04585cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163312PMC
October 2020

Particulate matter pollution associated with schizophrenia hospital re-admissions: a time-series study in a coastal Chinese city.

Environ Sci Pollut Res Int 2021 Jun 11. Epub 2021 Jun 11.

Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China.

Schizophrenia (SCZ) hospital re-admissions constitute a serious disease burden worldwide. Some studies have reported an association between air pollutants and hospital admissions for SCZ. However, evidence is scarce regarding the effects of ambient particulate matter (PM) on SCZ hospital re-admissions, especially in coastal cities in China. The purpose of this study was to examine whether PM affects the risk of SCZ hospital re-admission in the coastal Chinese city of Qingdao. Daily SCZ hospital re-admissions, daily air pollutants, and meteorological factors from 2015 to 2019 were collected. A quasi-Poisson generalized linear regression model combined with distributed lag non-linear model (DLNM) was applied to model the exposure-lag-response relationship between PM and SCZ hospital re-admissions. The relative risks (RRs) were estimated for an inter-quartile range (IQR) increase in PM concentrations. Subgroup analyses by age and gender were conducted to identify the vulnerable subgroups. There were 6220 SCZ hospital re-admissions during 2015-2019. The results revealed that PM, including PM (particles with an aerodynamic diameter ≤10 μm), PM (particles >2.5 μm but <10 μm), and PM (particles ≤2.5 μm), was positively correlated with SCZ hospital re-admissions. The strongest single-day effects all occurred on lag3 day, and the corresponding RRs were 1.07 (95% CI: 1.02-1.11) for PM, 1.03 (95% CI: 1.00-1.07) for PM, and 1.05 (95% CI: 1.01-1.09) for PM per IQR increase. Stronger associations were observed in males and younger individuals (<45 years). Our findings suggest that PM exposure is associated with increased risk of SCZ hospital re-admission. Active intervention measures against PM exposure should be taken to reduce the risk of SCZ hospital re-admission, especially for males and younger individuals.
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http://dx.doi.org/10.1007/s11356-021-14816-3DOI Listing
June 2021

Drum-like Metallacages with Size-Dependent Fluorescence: Exploring the Photophysics of Tetraphenylethylene under Locked Conformations.

J Am Chem Soc 2021 Jun 9. Epub 2021 Jun 9.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

Materials with aggregation-induced emission (AIE) properties are of growing interest due to their widespread applications. AIEgens, such as tetraphenylethylene units, display varying emission behaviors during their conformational changes. However, the structure-property relationships of the intermediate conformations have rarely been explored. Herein, we show that the conformational restriction on TPE units can affect the structural relaxation in the excited state and the resulting photophysical behaviors. Specifically, three metallacages of different sizes were prepared via the coordination-driven self-assembly of a TPE-based tetrapyridyl donor with length-increasing Pt(II) acceptors. While the metallacages share similar scaffolds, they exhibit a trend of red-shifted fluorescence and attenuated quantum yield with the increase of their sizes. Furthermore, spectroscopic and computational studies together with a control experiment were conducted, revealing that the degree of cage tension imposed on the excited-state conformational relaxation of TPE moieties resulted in their distinct photophysical properties. The precise control of conformation holds promise as a strategy for understanding the AIE mechanism as well as optimizing the photophysical behaviors of materials on the platform of supramolecular coordination complexes.
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http://dx.doi.org/10.1021/jacs.1c04288DOI Listing
June 2021

From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1.

Front Genet 2021 20;12:652400. Epub 2021 May 20.

DDC Clinic Center for Special Needs Children, Middlefield, OH, United States.

A decade has passed since transmembrane coiled-coil domains 1 (TMCO1) defect syndrome was identified in 11 undiagnosed patients within the Old Order Amish of Northeastern Ohio-a disorder characterized by a distinctive craniofacial dysmorphism, skeletal anomalies and global developmental delay. Twenty seven patients, from diverse ethnic groups, have been reported with pathogenic TMCO1 variants now recognized to cause cerebrofaciothoracic dysplasia (CFTD). The implication of previously uncharacterized TMCO1 within disease has instigated a 10-year journey to understand the function of TMCO1 protein in Ca homeostasis. TMCO1 is an ER Ca leak channel which facilitates Ca leak upon ER "overload" through the novel Ca load activated Ca mechanism. This mini-review brings together the clinical and scientific advances made since the discovery of TMCO1 deficiency in disease, including broadened phenotype, understanding of pathophysiology, and implications to patient management of TMCO1 defect syndrome.
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http://dx.doi.org/10.3389/fgene.2021.652400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172970PMC
May 2021

Narcissistic self-sorting in anion-coordination-driven assemblies.

Chem Commun (Camb) 2021 Jun 26;57(49):6078-6081. Epub 2021 May 26.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069, China.

Three tris-bis(urea) ligands with triphenylamine-based C-symmetric spacers were synthesized, which assembled with sulfate or phosphate to form anionic AL pinwheel helices (A = anion and L = ligand) and AL tetrahedra, respectively. Interestingly, narcissistic self-sorting was observed in both structures from the mixture of the ligands, wherein each assembly contains only one type of ligand with no detectable mixed-ligand product as confirmed by the NMR and MS studies.
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http://dx.doi.org/10.1039/d1cc01652kDOI Listing
June 2021

Chiral Tridentate Ligands in Transition Metal-Catalyzed Asymmetric Hydrogenation.

Chem Rev 2021 May 20. Epub 2021 May 20.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.

Asymmetric hydrogenation (AH) of double bonds has been one of the most effective methods for the preparation of chiral molecules and for the synthesis of important chiral building blocks. In the past 60 years, noble metals with bidentate ligands have shown marvelous reactivity and enantioselectivity in asymmetric hydrogenation of a series of prochiral substrates. In recent years, developing chiral tridentate ligands has played an increasingly important role in AH. With modular frameworks and a variety of functionalities on the side arms, chiral tridentate ligand complexes enable both reactivities and stereoselectivities. Although great achievements have been made for noble metal catalysts with chiral tridentate ligands since the 1990s, the design of chiral tridentate ligands for earth abundant metal catalysts has still been in high demand. This review summarizes the development of chiral tridentate ligands for homogeneous asymmetric hydrogenation. The philosophy of ligand design and the reaction mechanisms are highlighted and discussed as well.
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http://dx.doi.org/10.1021/acs.chemrev.1c00075DOI Listing
May 2021

High Expression of SLC41A3 Correlates with Poor Prognosis in Hepatocellular Carcinoma.

Onco Targets Ther 2021 5;14:2975-2988. Epub 2021 May 5.

Graduate Department, Bengbu Medical College, Bengbu, Anhui, 233000, People's Republic of China.

Purpose: SLC41A3 is a member of the solute carrier family 41 (SLC41) and is involved in many cellular processes as a magnesium ion transporter. Although it plays an important role in cancer formation and development, the correlation between the expression of SLC41A3 and the occurrence and prognosis of hepatocellular carcinoma (HCC) remains unclear. Therefore, this study was focused on the evaluation of the relationship between SLC41A3 and the development and prognosis of HCC.

Patients And Methods: Firstly, we collected the mRNA expression of SLC41A3 in HCC through the platform of Oncomine. Then, the subgroups of HCC were performed by the UALCAN website and the prognosis of HCC was analyzed by Kaplan-Meier Plotter database. Subsequently, immunohistochemistry (IHC) method was used to detect SLC41A3 expression in 323 clinically confirmed HCC samples and 184 non-cancerous liver tissues. Finally, function enrichment analysis was done using the LinkInterpreter module in LinkedOmics, and gene set enrichment analysis (GSEA) was performed using TCGA data set.

Results: The Oncomine database and immunohistochemical (IHC) showed higher SLC41A3 expression in HCC tissue compared to normal tissue. The expression of SLC41A3 was significantly correlated with tumor metastasis, Edmondson grade, microvascular invasion, and AFP level. Kaplan-Meier and Cox regression analyses verified that high SLC41A3 expression is a significant prognostic factor for reduced overall survival in HCC patients.

Conclusion: Our results demonstrated that high expression of SLC41A3 was the predictor of poor prognosis in HCC patients, suggesting that this protein may be a potential target for HCC therapy.
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http://dx.doi.org/10.2147/OTT.S296187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107057PMC
May 2021

Identification of a methylomics-associated nomogram for predicting overall survival of stage I-II lung adenocarcinoma.

Sci Rep 2021 May 11;11(1):9938. Epub 2021 May 11.

Department of Cardiothoracic Surgery, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450000, China.

The aim of this paper was to identify DNA methylation based biomarkers for predicting overall survival (OS) of stage I-II lung adenocarcinoma (LUAD) patients. Methylation profile data of patients with stage I-II LUAD from The Cancer Genome Atlas (TCGA) database was used to determine methylation sites-based hallmark for stage I-II LUAD patients' OS. The patients were separated into training and validation datasets by using median risk score as cutoff. Univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were employed to develop a DNA methylation signature for OS of patients with stage I-II LUAD. As a result, an 11-DNA methylation signature was determined to be critically associated with the OS of patients with stage I-II LUAD. Analysis of receiver operating characteristics (ROC) suggested a high prognostic effectiveness of the 11-DNA methylation signature in patients with stage I-II LUAD (AUC at 1, 3, 5 years in training set were (0.849, 0.879, 0.831, respectively), validation set (0.742, 0.807, 0.904, respectively), entire TCGA dataset (0.747, 0.818, 0.870, respectively). Kaplan-Meier survival analyses exhibited that survival was significantly longer in the low-risk cohort compared to the high-risk cohort in the training dataset (P = 7e - 07), in the validation dataset (P = 1e - 08), and in the all-cohort dataset (P = 6e - 14). In addition, a nomogram was developed based on molecular factor (methylation risk score) as well as clinical factors (age and cancer status) (AUC at 1, 3, 5 years entire TCGA dataset were 0.770, 0.849, 0.979, respectively). The result verified that our methylomics-associated nomogram had a strong robustness for predicting stage I-II LUAD patients' OS. Furthermore, the nomogram combined clinical and molecular factors to determine an individualized probability of recurrence for patients with stage I-II LUAD, which stood for a major advance in the field of personalized medicine for pulmonary oncology. Collectively, we successfully identified a DNA methylation biomarker and a DNA methylation-based nomogram to predict the OS of patients with stage I-II LUAD.
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http://dx.doi.org/10.1038/s41598-021-89429-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113535PMC
May 2021

GS-441524 inhibits African swine fever virus infection in vitro.

Antiviral Res 2021 Jul 1;191:105081. Epub 2021 May 1.

Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, People's Republic of China; Research Center for African Swine Fever Prevention and Control, South China Agricultural University, Guangzhou, People's Republic of China; National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China. Electronic address:

African swine fever virus (ASFV) is a highly infectious and lethal swine pathogen that causes serious socio-economic consequences in endemic countries for which no safe and effective vaccine is currently available. GS-441524, a 1-cyano-substituted adenine C-nucleoside ribose analogue, inhibits viral RNA transcription by competing with natural nucleosides (ATP, TTP, CTP, and GTP) and effectively inhibits viral RNA-dependent RNA polymerase activity. However, whether GS-441524 can inhibit the replication of DNA viruses is unknown. In this study, we confirmed that GS-441524 inhibits ASFV infection in porcine alveolar macrophages (PAMs) in a dose-dependent manner; GS-441524 significantly inhibited ASFV replication at different time points after ASFV infection, particularly at the early stages of viral replication. Notably, GS-441524 did not increase the levels of antiviral cytokines or ATP in PAMs. However, an increase in the concentration of natural ATP in PAMs promoted the replication of ASFV and attenuated the inhibitory effect of GS-441524 in a dose-dependent manner. Our results suggest that GS-441524 is an effective antiviral against ASFV.
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http://dx.doi.org/10.1016/j.antiviral.2021.105081DOI Listing
July 2021

The Addition of Nature Identical Flavorings Accelerated the Virucidal Effect of Pure Benzoic Acid against African Swine Fever Viral Contamination of Complete Feed.

Animals (Basel) 2021 Apr 14;11(4). Epub 2021 Apr 14.

Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases, South China Agricultural University, Guangzhou 510642, China.

African swine fever virus is one of the most highly contagious and lethal viruses for the global swine industry. Strengthening biosecurity is the only effective measure for preventing the spread of this viral disease. The virus can be transmitted through contaminated feedstuffs and, therefore, research has been conducted to explore corresponding mitigating measures. The purpose of the current study was to test a combination of pure benzoic acid and a blend of nature identical flavorings for their ability to reduce African swine fever viral survival in feed. This virus was inoculated to feed with or without the supplementation of the test compounds, and the viral presence and load were measured by a hemadsorption test and quantitative real time polymerase chain reaction. The main finding was that the combination of pure benzoic acid and nature identical flavorings could expedite the reduction in both viral load and survival in a swine feed. Therefore, this solution could be adopted as a preventive measure for mitigating the risk of contaminated feed by African swine fever virus.
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http://dx.doi.org/10.3390/ani11041124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071002PMC
April 2021

Observer-based finite frequency H∞ state-feedback control for autonomous ground vehicles.

ISA Trans 2021 Apr 13. Epub 2021 Apr 13.

School of Automation and Electrical Engineering, Key Laboratory of Knowledge Automation for Industrial Processes of Ministry of Education, University of Science and Technology Beijing, Beijing, 100083, PR China.

This paper studies the problem of path tracking of Autonomous Ground Vehicles (AGVs) in the presence of sideslip angles. An observer is designed to estimate both the sideslip angle and the vehicle yaw rate, based on which an observer-based controller is established such that the closed-loop system is stable and the vehicle follows a desired path accurately. In particular, the nonlinear vehicle dynamics model is reformulated as a Linear Parameter Varying (LPV) system, and a finite frequency H criteria is satisfied such that the disturbances are attenuated effectively, the parameter-dependent gain matrices are calculated simultaneously by solving a convex optimization problem. Simulation results show the effectiveness of the method proposed.
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http://dx.doi.org/10.1016/j.isatra.2021.03.027DOI Listing
April 2021

Insight into the drug resistance whole genome of Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa, Pakistan.

Infect Genet Evol 2021 Aug 20;92:104861. Epub 2021 Apr 20.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, and Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nanshan District, Shenzhen, Guangdong 518055, China. Electronic address:

Whole genome sequencing (WGS) is one of the most reliable methods for detection of drug resistance, genetic diversity in other virulence factor and also evolutionary dynamics of Mycobacterium tuberculosis complex (MTBC). First-line anti-tuberculosis drugs are the major weapons against Mycobacterium tuberculosis (MTB). However, the emergence of drug resistance remained a major obstacle towards global tuberculosis (TB) control program 2030, especially in high burden countries including Pakistan. To overcome the resistance and design potent drugs, genomic variations in drugs targets as well as in the virulence and evolutionary factors might be useful for better understanding and designing potential inhibitors. Here we aimed to find genomic variations in the first-line drugs targets, along with other virulence and evolutionary factors among the circulating isolates in Khyber Pakhtunkhwa, Pakistan. Samples were collected and drug susceptibility testing (DST) was performed as per WHO standard. The resistance samples were subjected to WGS. Among the five whole genome sequences, three samples (NCBI BioProject Accession: PRJNA629298, PRJNA629388) harbored 1997, 1162, and 2053 mutations. Some novel mutations have been detected in drugs targets. Similarly, numerous novel variants have also been detected in virulency and evolutionary factors, PE, PPE, and secretory system of MTB isolates. Exploring the genomic variations among the circulating isolates in geographical specific locations might be useful for future drug designing. To the best of our knowledge, this is the first study that provides useful data regarding the insight genomic variations in virulency, evolutionary factors including ESX and PE/PPE as well as drug targets, for better understanding and management of TB in a WHO declared high burden country.
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http://dx.doi.org/10.1016/j.meegid.2021.104861DOI Listing
August 2021

Hierarchical Self-Assembly of Nanowires on the Surface by Metallo-Supramolecular Truncated Cuboctahedra.

J Am Chem Soc 2021 Apr 13;143(15):5826-5835. Epub 2021 Apr 13.

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.

Parastichy, the spiral arrangement of plant organs, is an example of the long-range apparent order seen in biological systems. These ordered arrangements provide scientists with both an aesthetic challenge and a mathematical inspiration. Synthetic efforts to replicate the regularity of parastichy may allow for molecular-scale control over particle arrangement processes. Here we report the packing of a supramolecular truncated cuboctahedron (TCO) into double-helical (DH) nanowires on a graphite surface with a non-natural parastichy pattern ascribed to the symmetry of the TCOs and interactions between TCOs. Such a study is expected to advance our understanding of the design inputs needed to create complex, but precisely controlled, hierarchical materials. It is also one of the few reported helical packing structures based on Platonic or Archimedean solids since the discovery of the Boerdijk-Coxeter helix. As such, it may provide experimental support for studies of packing theory at the molecular level.
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http://dx.doi.org/10.1021/jacs.1c00625DOI Listing
April 2021

Rediscovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis.

J Biol Chem 2021 Jan 8;296:100257. Epub 2021 Jan 8.

Global Health Drug Discovery Institute, Haidian, Beijing, China. Electronic address:

Mycobacterium tuberculosis (Mtb) remains the deadliest pathogenic bacteria worldwide. The search for new antibiotics to treat drug-sensitive as well as drug-resistant tuberculosis has become a priority. The essential enzyme phenylalanyl-tRNA synthetase (PheRS) is an antibacterial drug target because of the large differences between bacterial and human PheRS counterparts. In a high-throughput screening of 2148 bioactive compounds, PF-3845, which is a known inhibitor of human fatty acid amide hydrolase, was identified inhibiting Mtb PheRS at K ∼ 0.73 ± 0.06 μM. The inhibition mechanism was studied with enzyme kinetics, protein structural modeling, and crystallography, in comparison to a PheRS inhibitor of the noted phenyl-thiazolylurea-sulfonamide class. The 2.3-Å crystal structure of Mtb PheRS in complex with PF-3845 revealed its novel binding mode, in which a trifluoromethyl-pyridinylphenyl group occupies the phenylalanine pocket, whereas a piperidine-piperazine urea group binds into the ATP pocket through an interaction network enforced by a sulfate ion. It represents the first non-nucleoside bisubstrate competitive inhibitor of bacterial PheRS. PF-3845 inhibits the in vitro growth of Mtb H37Rv at ∼24 μM, and the potency of PF-3845 increased against an engineered strain Mtb pheS-FDAS, suggesting on target activity in mycobacterial whole cells. PF-3845 does not inhibit human cytoplasmic or mitochondrial PheRS in biochemical assay, which can be explained from the crystal structures. Further medicinal chemistry efforts focused on the piperidine-piperazine urea moiety may result in the identification of a selective antibacterial lead compound.
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http://dx.doi.org/10.1016/j.jbc.2021.100257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948948PMC
January 2021

Tracing the Origins of Blueberries by Their Mineral Element Contents and Sr/Sr Ratios.

Biol Trace Elem Res 2021 Apr 6. Epub 2021 Apr 6.

College of Agriculture, Guizhou University, Guiyang, 550025, Guizhou, China.

This study investigated the feasibility of using the mineral element contents and Sr/Sr ratios of blueberries to trace their origins. The contents of 28 mineral elements, including K, Al, and Mg, were determined in 104 blueberry samples from three blueberry-producing areas in Guizhou Province, China. Also determined were both the Sr/Sr ratios in 48 blueberry samples as well as the type of soil in which the blueberries were grown. Cluster analysis of Sr/Sr ratios, stepwise discriminant analysis of mineral element contents, and combined discriminant analyses of Sr/Sr ratios and mineral element contents were done. The results show that ten elements (Ca, Cr, Cs, Mg, Mn, P, Rb, Sb, Th, and Y) were selected by linear discriminant analysis, which could be used to establish the provenance traceability model of blueberries in Guizhou. The original accuracy of linear discriminant analysis was 89.4%, and the accuracy of cross-validation was 83.6%. When Sr/Sr ratios were used for tracing, the accuracies of both the original discrimination and the cross-validation were 81.3% as determined by linear discriminant analysis, and the accuracy rate of origin discrimination was 81.25% by cluster analysis. The results of combined discrimination were the best: the accuracy of the original discrimination was 95.8%, and the accuracy of cross-validation was 93.8%. Mineral element contents and Sr/Sr ratios can be used to trace the origins of blueberries, and combining them can significantly improve the discrimination accuracy. Fisher linear discriminant analysis had the greatest accuracy followed by cluster analysis, while principal component analysis was relatively poor in the research of Guizhou blueberry origin traceability.
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http://dx.doi.org/10.1007/s12011-021-02701-6DOI Listing
April 2021

Zearalenone Induces Apoptosis and Cytoprotective Autophagy in Chicken Granulosa Cells by PI3K-AKT-mTOR and MAPK Signaling Pathways.

Toxins (Basel) 2021 03 10;13(3). Epub 2021 Mar 10.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin found in several food commodities worldwide. ZEA causes reproductive disorders, genotoxicity, and testicular toxicity in animals. However, little is known about the functions of apoptosis and autophagy after exposure to ZEA in granulosa cells. This study investigated the effects of ZEA on chicken granulosa cells. The results show that ZEA at different doses significantly inhibited the growth of chicken granulosa cells by inducing apoptosis. ZEA treatment up-regulated Bax and downregulated Bcl-2 expression, promoted cytochrome c release into the cytosol, and triggered mitochondria-mediated apoptosis. Consequently, caspase-9 and downstream effector caspase-3 were activated, resulting in chicken granulosa cells apoptosis. ZEA treatment also upregulated LC3-II and Beclin-1 expression, suggesting that ZEA induced a high level of autophagy. Pretreatment with chloroquine (an autophagy inhibitor) and rapamycin (an autophagy inducer) increased and decreased the rate of apoptosis, respectively, in contrast with other ZEA-treated groups. Autophagy delayed apoptosis in the ZEA-treated cells. Therefore, autophagy may prevent cells from undergoing apoptosis by reducing ZEA-induced cytotoxicity. In addition, our results further show that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in chicken granulosa cells.
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http://dx.doi.org/10.3390/toxins13030199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999718PMC
March 2021

Cost-effectiveness of CYP2C19 genotyping to guide antiplatelet therapy for acute minor stroke and high-risk transient ischemic attack.

Sci Rep 2021 Apr 1;11(1):7383. Epub 2021 Apr 1.

Department of Pharmacy, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou, 515041, Guangdong, China.

Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin within 48 h of acute minor strokes and transient ischemic attacks (TIAs) has been indicated to effectively reduce the rate of recurrent strokes. However, the efficacy of clopidogrel has been shown to be affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. Patients carrying loss-of-function alleles (LoFAs) at a low risk of recurrence (ESRS < 3) cannot benefit from clopidogrel plus aspirin at all and may have an increased bleeding risk. In order to optimize antiplatelet therapy for these patients and avoid the waste of medical resources, it is important to identify the subgroups that genuinely benefit from DAPT with clopidogrel plus aspirin through CYP2C19 genotyping. This study sought to assess the cost-effectiveness of CYP2C19 genotyping to guide drug therapy for acute minor strokes or high-risk TIAs in China. A decision tree and Markov model were constructed to evaluate the cost-effectiveness of CYP2C19 genotyping. We used a healthcare payer perspective, and the primary outcomes included quality-adjusted life years (QALYs), costs and the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to evaluate the robustness of the results. CYP2C19 genotyping resulted in a lifetime gain of 0.031 QALYs at an additional cost of CNY 420.13 (US$ 59.85), yielding an ICER of CNY 13,552.74 (US$ 1930.59) per QALY gained. Probabilistic sensitivity analysis showed that genetic testing was more cost-effective in 95.7% of the simulations at the willingness-to-pay threshold of CNY 72,100 (GDP per capita, US$ 10,300) per QALY. Therefore, CYP2C19 genotyping to guide antiplatelet therapy for acute minor strokes and high-risk TIAs is highly cost-effective in China.
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http://dx.doi.org/10.1038/s41598-021-86824-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016871PMC
April 2021

Beta-endorphin inhibits the inflammatory response of bovine endometrial cells through δ opioid receptor in vitro.

Dev Comp Immunol 2021 Aug 26;121:104074. Epub 2021 Mar 26.

College of Veterinary Medicine, Yangzhou University, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, 225009, China; Joint International Research Laboratory of Agriculture and Agriproduct Safety of the Ministry of Education, Yangzhou, Jiangsu, 225009, China. Electronic address:

Postpartum uterine infections are common reproductive diseases in postpartum cows. Evidence has shown that plasma β-endorphins increase during bovine uterine inflammation. However, the effect of β-endorphins on the inflammatory response in bovine endometrium has not been clarified. The aim of this study was to investigate the effect of β-endorphins on the inflammatory response of bovine endometrial epithelial and stromal cells, and to explore the possible mechanism. The cells were treated with E. coli lipopolysaccharide (LPS) to simulate inflammation, which was characterized by the significant activation of NF-κB signaling pathway and the increased gene expression of the downstream proinflammatory cytokines (approximately 1.2- to 15-fold increase, P < 0.05). By using Western blot and qPCR techniques, we found that β-endorphins inhibited the key protein expression of NF-κB pathway, and the gene expressions of TNF, IL1B, IL6, CXCL8, nitric oxide synthase 2, and prostaglandin-endoperoxide synthase 2 (P < 0.05). The co-treatment of β-endorphins and opioid antagonists showed that the anti-inflammatory effect of β-endorphins could be blocked (P < 0.05) by non-selective opioid antagonist naloxone or δ opioid receptor antagonist ICI 154129, but not the μ opioid receptor antagonist CTAP (P > 0.05). In conclusion, β-endorphins may inhibit the inflammatory response of bovine endometrial epithelial and stromal cells through δ opioid receptor.
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http://dx.doi.org/10.1016/j.dci.2021.104074DOI Listing
August 2021

Discovery of a novel, potent and selective small-molecule inhibitor of PD-1/PD-L1 interaction with robust in vivo anti-tumour efficacy.

Br J Pharmacol 2021 Jul 4;178(13):2651-2670. Epub 2021 May 4.

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.

Background And Purpose: PD-1/PD-L1 antibodies have achieved great success in clinical treatment. However, monoclonal antibody drugs also have challenges, such as high manufacturing costs, poor diffusion, low oral bioavailability and limited penetration into tumour tissue. The development of small-molecule inhibitors of PD-1/PD-L1 interaction represents a promising perspective to overcome the above challenges in cancer immunotherapy.

Experimental Approach: We explored structural activity relationships and used biochemical assays to generate a lead compound (ZE132). CD8+ T-cells killing assay and Ifng expression assay were used to verify the in vitro cellular activity of ZE132. Off-target study was performed to verify the selectivity. Syngeneic mouse models were used to verify the in vivo activity of ZE132 in tumour immune microenvironment (TIME). We also performed pharmacokinetics profiling in mice and The Cancer Genome Atlas database analysis.

Key Results: ZE132 can effectively inhibit the PD-1/PD-L1 interactions in vitro, and it has a potent affinity to PD-L1. ZE132 shows robust anti-tumour effects in vivo, better than anti-PD-1 antibody. In the analysis of TIME, we found that ZE132 treatment promotes cytotoxic T-cell tumour infiltration and induces IL-2 expression. In addition, ZE132 elicits strong inhibitory effects on the mRNA expression of TGF-β, which may serve as a potential biomarker to predict responsiveness to PD-1/PD-L1 immunotherapies.

Conclusion And Implications: We identified a new lead compound ZE132 targeting PD-1/PD-L1 interactions, not only showing favourable drug-like properties in vitro and in vivo but also showing the advantage of overcoming the barrier of TIME compared to anti-PD-1 antibody.
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http://dx.doi.org/10.1111/bph.15457DOI Listing
July 2021

Emodin Suppresses the Migration and Invasion of Melanoma Cells.

Biol Pharm Bull 2021 Jun 17;44(6):771-779. Epub 2021 Mar 17.

Department of Plastic and Reconstructive Surgery, Hua Dong Hospital Affiliated to Fu Dan University.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), as an active ingredient in rhubarb roots and rhizomes, has been reported to possess various pharmacological properties including anti-tumor effects. Recent studies have confirmed that emodin inhibited cell proliferation and induced apoptosis of cancer cells. However, the inhibitory effect of emodin on the migration and invasion of melanoma cells and its underlying mechanism are still unclear. In the study, we observed the impercipient effects of emodin in B16F10 and A375 melanoma cells with strong metastatic abilities, focusing on the functions and mechanisms of migration and invasion of B16F10 and A375 melanoma cells. Cell counting kit-8 (CCK-8), colony formation test and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining tests confirmed that emodin possessed anti-proliferative and pro-apoptotic activities in B16F10 and A375 cells. The inhibitory effects on the migration and invasion of B16F10 and A375 cells were proved by wound healing assay and Transwell methods. Moreover, immunofluorescence assay approved the decrease in protein expression of matrix metalloproteinas (MMP)-2/-9 by emodin, and Western blot analyses revealed that emodin could increase the Bax/Bcl-2 ratio and inhibit the MMP-2/-9 protein expression and Wnt/β-catenin pathway in a dose-depended manner. BML-284, as an agonist of Wnt/β-catenin signaling pathway, reversed the effects of emodin on cell growth, migration and invasion in B16F10 cells. These findings may suggest that emodin treatment can be a promising therapeutic strategy for melanoma with highly metastatic abilities.
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http://dx.doi.org/10.1248/bpb.b20-00807DOI Listing
June 2021

Regression patterns of uveal melanoma after iodine-125 plaque brachytherapy.

BMC Ophthalmol 2021 Mar 16;21(1):137. Epub 2021 Mar 16.

Beijing Tongren Hospital, Beijing, 100730, China.

Background: Tumor regression of uveal melanomas (UMs) after radiotherapy has been reported as a valuable prognostic factor for metastasis and metastatic death. But its effect on prognosis is questionable. The purpose of this study was to summarize the regression features of uveal melanoma after iodine-125 plaque brachytherapy and the relationship with prognosis.

Methods: Adult uveal melanoma patients who only received iodine-125 plaque brachytherapy between December 2009 and March 2018 at the Beijing Tongren Hospital, Capital Medical University were enrolled in this study. The regression rate was calculated as the percent change in tumor height, and each eye was classified for four main regression patterns: Decrease (D), Stable (S), Others (O), and Increase (I), according to the trend of height change. Statistical analysis was performed using one-way ANOVA and chi-square test, univariate and multivariate logistic regression, and Kaplan-Meier analysis.

Results: A total of 139 patients was included in the study. The median follow-up was 35 months. Regression patterns status was pattern D in 65 tumors (46.8%), pattern S in 50 tumors (36.0%), pattern O in 6 tumors (4.3%), and pattern I in 18 tumors (12.9%). Reductions of tumor mean height for each follow-up visit were 5.26% (3 months), 10.66% (6 months), 9.37% (12 months), and 14.68% (18 months). A comparison (D vs. S vs. O vs. I) revealed the preoperative height of pattern I was significantly lower than the pattern D, S and O (mean: 7.24 vs. 7.30 vs. 6.77 vs. 5.09 mm, respectively; P = 0.037). LBD (largest basal diameter) was strongly associated with the metastasis (P = 0.03). However, an association between the tumor regression and subsequent melanoma-related metastasis and mortality could not be confirmed (P = 0.66 and P = 0.27, respectively). The tumor regression rate increased with increasing tumor height (P = 0.04) and decreased with increasing of LBD (P = 0.01).

Conclusion: Our study showed a lack of association between the prognosis and the regression of uveal melanomas following I-125 plaque radiotherapy. The LBD and original height of the tumor have predictive value in tumor regression rate, and LBD was positively associated with metastasis.
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http://dx.doi.org/10.1186/s12886-021-01898-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968312PMC
March 2021

Positive regulation of Type III secretion effectors and virulence by RyhB paralogs in Salmonella enterica serovar Enteritidis.

Vet Res 2021 Mar 10;52(1):44. Epub 2021 Mar 10.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.

Small non-coding RNA RyhB is a key regulator of iron homeostasis in bacteria by sensing iron availability in the environment. Although RyhB is known to influence bacterial virulence by interacting with iron metabolism related regulators, its interaction with virulence genes, especially the Type III secretion system (T3SS), has not been reported. Here, we demonstrate that two RyhB paralogs of Salmonella enterica serovar Enteritidis upregulate Type III secretion system (T3SS) effectors, and consequently affect Salmonella invasion into intestinal epithelial cells. Specifically, we found that RyhB-1 modulate Salmonella response to stress condition of iron deficiency and hypoxia, and stress in simulated intestinal environment (SIE). Under SIE culture conditions, both RyhB-1 and RyhB-2 are drastically induced and directly upregulate the expression of T3SS effector gene sipA by interacting with its 5' untranslated region (5' UTR) via an incomplete base-pairing mechanism. In addition, the RyhB paralogs upregulate the expression of T3SS effector gene sopE. By regulating the invasion-related genes, RyhBs in turn affect the ability of S. Enteritidis to adhere to and invade into intestinal epithelial cells. Our findings provide evidence that RyhBs function as critical virulence factors by directly regulating virulence-related gene expression. Thus, inhibition of RyhBs may be a potential strategy to attenuate Salmonella.
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http://dx.doi.org/10.1186/s13567-021-00915-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944605PMC
March 2021

The effects of long-term extracurricular scientific research on the medical students: Insight from Jinan University Medical School.

Biochem Mol Biol Educ 2021 Mar 8. Epub 2021 Mar 8.

Division of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.

The benefits and long-term effects of extracurricular scientific research on undergraduate students in many countries have been intensively investigated, but it remains obscure for Chinese medical students. In this study, we investigated the outcome of 60 medical students who have participated in extracurricular scientific research at Jinan University Medical School over a period of 7 years (2011-2018). The results revealed that these students have contributed to 31 biomedical science articles in reputable academic journals, as first- or co-authors. Furthermore, they also independently procured various funding based on their research achievements, and smaller awards for achievements in conferences and competitions. Assessment of the grade point average score of these students revealed that conducting extracurricular scientific research did not affect their routine medical study and exam grades (P>0.05). The students benefited from participating in extracurricular research, by acquiring the ability to think scientifically and enhancing their communication skills. In addition, the medical students were motivated to enlist for postgraduate studies so that they could further embark in scientific research. In sum, Chinese medical students are capable of participating in scientific research and make a significant contribution to science.
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http://dx.doi.org/10.1002/bmb.21499DOI Listing
March 2021

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

Hepatology 2021 Mar 5. Epub 2021 Mar 5.

European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

Mutations in ATP8B1 can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1 (PFIC1). The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide novel insights by using the largest genetically defined cohort of FIC1 deficiency patients to date. This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication); FIC1-A (n=67; no PPTM), FIC1-B (n=29; one PPTM) or FIC1-C (n=34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18y. NLS was comparable between FIC1-A, FIC1-B, and FIC1-C (%NLS at age 10y: 67%, 41%, and 59%, respectively; P=0.12), despite FIC1-C undergoing SBD less often (%SBD at age 10y: 65%, 57%, and 45%, respectively; P=0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10y; sBAs <194 µmol/L: 49% versus sBAs ≥194 µmol/L: 15%; P=0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P=0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P=0.06) and post-SBD sBA concentrations <65μmol/L (P=0.05) tended to be associated with improved NLS. Conclusion: Less than half of FIC1 deficiency patients reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.
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http://dx.doi.org/10.1002/hep.31787DOI Listing
March 2021

Melatonin alleviates Ochratoxin A-induced liver inflammation involved intestinal microbiota homeostasis and microbiota-independent manner.

J Hazard Mater 2021 07 26;413:125239. Epub 2021 Jan 26.

Guangdong Provincial Key Laboratory of Animal Nutrition and Regulation, College of Animal Science, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Melatonin (MEL) shows an anti-inflammatory effect and regulates intestinal microbiota communities in animals and humans; Ochratoxin A (OTA) induces liver inflammation through intestinal microbiota. However, it remains to know whether MEL alleviates the liver inflammation induced by OTA. In this study, MEL reversed various adverse effects induced by OTA. MEL recovered the swarming and motility of intestinal microbiota, decreased the accumulation of lipopolysaccharide (LPS), enhanced the tight junction proteins of jejunum and cecum segments; ultimately alleviated OTA-induced liver inflammation in ducks. However, it is worth noting that MEL still had positive effects on the OTA-exposed ducks after antibiotic treatment. These results suggest that both the maintenance of intestinal microbiota homeostasis and intestinal microbiota-independent manner involved the MEL anti-inflammatory function in OTA-induced liver inflammation. MEL represent a promising protective approach for OTA, even other mycotoxins.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125239DOI Listing
July 2021

Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis.

Parasit Vectors 2021 Jan 29;14(1):87. Epub 2021 Jan 29.

Department of Microbiology and Parasitology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, #5 Dong Dan San Tiao, Beijing, 100005, People's Republic of China.

Background: Small non-coding RNAs play critical regulatory roles in post-transcription. However, their characteristics in Trichomonas vaginalis, the causative agent of human sexually transmitted trichomoniasis, still remain to be determined.

Methods: Small RNA transcriptomes from Trichomonas trophozoites were deep sequenced using the Illumina NextSeq 500 system and comprehensively analyzed to identify Trichomonas microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs). The tsRNA candidates were confirmed by stem-loop quantitative reverse transcription-PCR, and motifs to guide the cleavage of tsRNAs were predicted using the GLAM2 algorithm.

Results: The miRNAs were found to be present in T. vaginalis but at an extremely low abundance (0.0046%). Three categories of endogenous Trichomonas tsRNAs were identified, namely 5'tritsRNAs, mid-tritsRNAs and 3'tritsRNAs, with the 5'tritsRNAs constituting the dominant category (67.63%) of tsRNAs. Interestingly, the cleavage site analysis verified both conventional classes of tRNA-derived fragments (tRFs) and tRNA-halves in tritsRNAs, indicating the expression of tRNA-halves in the non-stress condition. A total of 25 tritsRNAs were experimentally confirmed, accounting for 78.1% of all tested candidates. Three motifs were predicted to guide the production of tritsRNAs. The results prove the expression of tRFs and tRNA-halves in the T. vaginalis transcriptome.

Conclusions: This is the first report of genome-wide investigation of small RNAs, particularly tsRNAs and miRNAs, from Trichomonas parasites. Our findings demonstrate the expression profile of tsRNAs in T. vaginalis, while miRNA was barely detected. These results may promote further research aimed at gaining a better understanding of the evolution of small non-coding RNA in T. vaginalis and their functions in the pathogenesis of trichomoniasis.
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http://dx.doi.org/10.1186/s13071-020-04570-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844918PMC
January 2021

Heavy Metal(loid)s Contamination in Ground Dust and Associated Health Risks at a Former Indigenous Zinc Smelting Area.

Int J Environ Res Public Health 2021 01 21;18(3). Epub 2021 Jan 21.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550081, China.

Indigenous zinc smelting (IZS) is a backward technique that releases a great deal of heavy metal(loid)s into the environment. However, the contamination of heavy metal(loid)s in ground dust and the associated health risks in such areas are poorly known. In this study, a former IZS area in Guizhou, China, was surveyed during 2008-2018 with 15 elements (Ag, As, Bi, Cd, Co, Cr, Cu, Hg, In, Ni, Pb, Sb, Sn, Tl, Zn) being analyzed. The results indicate that most elements (e.g., Ag, As, Cd, Cu, Pb, Sb, Sn, Zn) in ground dust decreased significantly after the cessation of the IZS in 2006; nevertheless, some elements still remained at relatively high levels in 2018, e.g., Pb (average: 762 ± 647 mg/kg), Zn (average: 1287 ± 753 mg/kg), Cd (average: 7.76 ± 5.06 mg/kg), and As (average: 41.9 ± 34.8 mg/kg), indicating they might come from the local contaminated soils, slag residues and smelting potteries. In terms of the impacts on human health, children have both higher non-carcinogenic and carcinogenic risks than that of adults, with the latter subpopulation having a lower risk than the threshold values. Pb and As were the two elements with the highest non-carcinogenic risk for children, the hazard index of local children was still higher than the threshold of 1 (e.g., 1.43 for As, 2.09 for Pb) in 2018. The carcinogenic risk of As exposure to children dropped more than two times to 6.42 × 10 in 2018, which falls below the tolerable range (10-10). This study revealed that although the concentration of heavy metal(loid)s in ground dust and linked health risk in the IZS area has reduced dramatically after the cessation of IZS, continued removal of slag residues and smelting potteries is necessary for further decreasing the human health risk.
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http://dx.doi.org/10.3390/ijerph18030893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864351PMC
January 2021

Investigation of Genetic Relatedness of Strains in Countries Along the Silk Road.

Front Vet Sci 2020 7;7:539444. Epub 2021 Jan 7.

National Institute for Communicable Disease Control and Prevention, Beijing, China.

In this study, MLVA (multiple-locus variable-number tandem repeat analysis) genotype data of strains from 11 countries along the Silk Road were downloaded from the MLVAbank. MLVA data of strains were applied to the constructed Minimum Spanning Tree to explore the species/biovars distribution, geographic origins, and genetic relationships of the strains analyzed. Moreover, whole-genome sequencing-single-nucleotide polymorphism (WGS-SNP) phylogenetic analysis of the genome of strains from GenBank was performed to discriminate the relatedness of strains further and investigate the transmission pattern of brucellosis. A total of 1,503 strains were analyzed in this study: 431 strains (29.8%), 1,009 strains (65.7%), and 63 strains (4.5%). biovar 3 was the dominant species and was shown to be widespread in all of the examined regions, suggesting that the prevention and surveillance of the population are a main challenge in these countries. A wide host spectrum was observed for this population; many animal reservoirs are a potential reason for the continuous brucellosis circulation in these countries. Although the strains from the examined regions had common geographic origins, only a few shared genotypes were observed in different countries. These data revealed that the majority strains were spreading within the national borders. However, the strains from Italy originated from a Western Mediterranean lineage; strains from the other 10 countries originated from Eastern Mediterranean lineage, and this lineage was shared by strains from three to nine different countries, suggesting that the introduction and reintroduction of the disease in the 10 countries might have occurred in the past. Furthermore, the most shared MLVA-16 genotypes were formed in the strains from China, Kazakhstan, and Turkey, suggesting that the introduction and trade in sheep and goats have occurred frequently in these countries. WGS-SNP analysis showed that the in this study originated from the Malta (Italy) region. According to their territorial affiliation between four clade strains from these countries in genotype B, the absence of a clear differentiation suggests that strains continuously expand and spread in countries along with Silk Road. Active exchange and trade of animals (sheep and goats) among these countries are reasonable explanations. strains from different nations showed unique geographic origins and epidemiological characteristics. Therefore, there is an urgent need for the control of transfer and trade of infected sheep (goats) in countries along the Silk Road, namely, the strengthening of the entry-exit quarantine of sheep and goats and improvements in the diagnosis of animal brucellosis.
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http://dx.doi.org/10.3389/fvets.2020.539444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817895PMC
January 2021