Publications by authors named "Yong Liang"

724 Publications

Genome-wide meta-analysis identifies ten new psoriasis susceptibility loci in the Chinese population.

J Genet Genomics 2021 Oct 22. Epub 2021 Oct 22.

Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230031, China; Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, 230031, China; Anhui Provincial Institute of Translational Medicine, 230031, China. Electronic address:

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http://dx.doi.org/10.1016/j.jgg.2021.10.001DOI Listing
October 2021

Polychlorinated dibenzo-p-dioxins and dibenzofurans in lotus from a lake historically polluted by the chlor-alkali industry: Occurrence, organ distribution and health risk from dietary intake.

Environ Pollut 2021 Oct 20;292(Pt B):118395. Epub 2021 Oct 20.

Hubei Key Laboratory of Industrial Fume and Dust Pollution Control, School of Environment and Health, Jianghan University, Wuhan, 430056, China. Electronic address:

In this study, the organ distribution and exposure risk from dietary intake of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were investigated for lotus collected from Ya-er Lake, a lake in Hubei Province, Central China that was historically polluted by the chlor-alkali industry. The highest concentrations of PCDD/Fs were found in the main and fibrous lotus roots, with mean values of 48.9 ± 90.1 pg/g and 94.6 ± 143 pg/g, respectively. In all the investigated samples, Octa-CDD (OCDD) and Octa-CDF (OCDF) were the predominant congeners, at 26% and 17% of Σ PCDD/Fs, respectively, followed by 1,2,3,4,6,7,8-HpCDF (9%). The distribution ratios of PCDD/Fs in adjacent lotus organs indicated that PCDD/Fs accumulated easily in edible organs, such as lotus seeds, membrane and leaves. The WHO-TEQ in the edible lotus organs and the probable daily intake (PDI) of lotus products by residents were calculated: the toxic equivalents in the lotus fruit parts reached a mean of 2 pg WHO-TEQ/g dw, and the mean weekly intake of lotus products for adolescents living around Ya-er Lake was 2.3 pg WHO-TEQ/kg bw/week. These results suggested that long-term consumption of lotus products from Ya-er Lake presents a health hazard to residents.
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http://dx.doi.org/10.1016/j.envpol.2021.118395DOI Listing
October 2021

Generation of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy.

Nat Commun 2021 Oct 22;12(1):6145. Epub 2021 Oct 22.

State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.

Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL/FL), but a small PA ratio between 755 and 905 nm (PA/PA). Oxidation of 1-Br-Et by •OH decreases the FL/FL while concurrently increasing the PA/PA, allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy.
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http://dx.doi.org/10.1038/s41467-021-26380-yDOI Listing
October 2021

Insight into the defluorination ability of per- and polyfluoroalkyl substances based on machine learning and quantum chemical computations.

Sci Total Environ 2021 Oct 15:151018. Epub 2021 Oct 15.

Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China. Electronic address:

UV-generated hydrated electrons play a critical role in the defluorination reaction of poly- and perfluoroalkyl substances (PFAS). However, limited experimental data hinder insight into the effects of the structural characteristics of emerging PFAS on their defluorination abilities. Therefore, in this study, we adopted quantity structure-activity relationship models based on machine learning algorithms to develop the predictive models of the relative defluorination ability of PFAS. Five-fold cross-validations were used to perform the hyperparameter tuning of the models, which suggested that the gradient boosting algorithms with PaDEL descriptors as the best model possessed superior predictive performance (R = 0.944 and RMSE = 0.114). The importance of the descriptor indicated that the electrostatic properties and topological structure of the compounds significantly affected the defluorination ability of the PFAS. For the emerging PFAS the best model showed that most compounds, such as potential alternatives of perfluorooctane sulfonic acid, were recalcitrant to reductive defluorination, whereas perfluoroalkyl ether carboxylic acids had relatively stronger defluorination abilities than perfluorooctanoic acid. The theoretical calculations implied that additional electrons on PFAS could cause molecular deconstruction, such as changes in the dihedral angle involved in the carbon chain, as well as C-F bond and ether C-O bond cleavages. In general, the current computational models could be useful for screening emerging PFAS to assess their defluorination ability for the molecular design of fluorochemical structures.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151018DOI Listing
October 2021

Detection of Dengue Fever Nonstructural Protein 1 Antigen by Proteolytic Peptide Imprinting Technology and UHPLC-MS/MS.

Anal Chem 2021 Oct 17;93(42):14106-14112. Epub 2021 Oct 17.

School of Chemistry, South China Normal University, Guangzhou 51006, China.

Dengue fever is caused by mosquito-transmitted dengue virus infection and continues to increase worldwide, threatening public health in tropical and subtropical regions. The primary difficulties in preventing a reduction of the medical burden of dengue fever lies in the lack of effective mosquito control, preventive dengue vaccines, and clinically effective antiviral drugs to treat dengue infections. Rapid and accurate diagnosis is crucial for proper patient care and effective control of epidemics. The present work proposes an alternative strategy for detecting the dengue virus nonstructural protein 1 (NS1) antigen in clinical serum samples by using ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in combination with the molecularly imprinted polymers. Rather than the whole protein, the NS1 signature peptide is selected as a template for molecular imprinting and quantified as a stoichiometric readout of NS1. Three functional monomers with hydrophobic, positively charged, and negatively charged groups were synthesized by click reactions in terms of the signature peptide. These three functional monomers provide abundant recognition sites for the peptide, allowing the peptide template to be effectively imprinted during polymerization. The imprinting conditions were optimized, and the molecularly imprinted polymers were characterized and used for enriching the signature peptide from digested serum samples by solid-phase extraction and then detected by UHPLC-MS/MS. The proposed method is used to detect the dengue virus NS1 in clinical samples and holds significant promise for early confirmation of dengue virus infection.
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http://dx.doi.org/10.1021/acs.analchem.1c01983DOI Listing
October 2021

Using Caenorhabditis elegans to assess the ecological health risks of heavy metals in soil and sediments around Dabaoshan Mine, China.

Environ Sci Pollut Res Int 2021 Oct 14. Epub 2021 Oct 14.

Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, Institute of Environment and Health, Jianghan University, Wuhan, 430056, China.

Heavy metal pollution is a global environmental problem, and the potential risks associated with heavy metals are increasing. The acid mine drainage (AMD) which is generated by mining activities at Dabaoshan Mine, the largest polymetallic mine in southern China, is harmful to local residents. A detailed regional survey of the ecological and human health risks of this polluted area is urgently needed. In this study, eight sediments and farmland samples were collected along the flow direction of tailing wastewater and Fandong Reservoir; the content of multiple heavy metals in these samples was determined by inductively coupled plasma mass spectrometry. The biological toxicity of water-soluble extracts from the samples was further assessed by referring to different endpoints of Caenorhabditis elegans (C. elegans). The relationship between specific heavy metals and biological toxicity was estimated by partial least squares regression. The results indicated that the risk of heavy metals in Dabaoshan mining area was very high (potential ecological risk index = 721.53) and was related to geographical location. In these samples, the carcinogenic risk (the probability that people are induced carcinogenic diseases or injuries when exposed to carcinogenic pollutants) of arsenic (As) for adults exceeded the standard value 1 × 10 and indicated that As presented a high carcinogenic risk to adults, while the high risk of non-carcinogenic effects (the hazard degree of human exposure to non-carcinogenic pollutants) in children was related to lead exposure (hazard index = 1.24). In addition, the heavy metals at high concentration in the water-soluble fraction of sediment and farmland soil extracts, which might easily distribute within the water cycle, inhibited the survival rate and growth of C. elegans. Gene expression and enzymatic activity related to oxidative stress were increased and genes related to apoptosis and metallothionein were also affected. In conclusion, the results of chemical analysis and biological assays provided evidence on the toxicity of soil and sediment extracts in the Dabaoshan mining area and advocated the control and remediation of heavy metal pollution around Dabaoshan Mine.
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http://dx.doi.org/10.1007/s11356-021-16807-wDOI Listing
October 2021

Decreased bioavailability of both inorganic mercury and methylmercury in anaerobic sediments by sorption on iron sulfide nanoparticles.

J Hazard Mater 2021 Sep 30;424(Pt B):127399. Epub 2021 Sep 30.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Methylmercury (MeHg), derived via inorganic mercury (Hg(II)) methylation by anaerobic microorganisms, is a neurotoxic contaminant causing concern worldwide. Establishing how to reduce Hg(II) methylation and MeHg bioavailability is essential for effective control of Hg pollution. Iron sulfide nanoparticles (FeS) is a promising passivator for Hg(II) methylation. However, its effect on the fate of MeHg in aquatic systems remains poorly understood. This study investigated the effect of FeS on Hg(II) bioavailability, MeHg production and bioavailability in aquatic environments. Results demonstrated that FeS rapidly sorbed Hg(II) and MeHg, with sorption affected by pH, chloride ion and dissolved organic matter. Hg-specific biosensor analysis showed that Hg(II) sorbed onto FeS significantly reduced its bioavailability to microorganisms. Double stable isotope (Hg(II) and MeHg) addition revealed that FeS significantly inhibited MeHg production in anaerobic sediments. Furthermore, synthetic gut juice extraction suggested that FeS decrease concentrations of bioavailable MeHg and Hg(II), reducing their integration into food webs. However, the sorbed MeHg and Hg(II) in sediments can be released after FeS oxidation, potentially enhancing the risk of exposure to aquatic organisms. Overall, these findings increase our understanding of Hg transformation and exposure risks in aquatic systems, providing valuable information for the development of in situ Hg remediation systems.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127399DOI Listing
September 2021

Next generation of tumor-activating type I IFN enhances anti-tumor immune responses to overcome therapy resistance.

Nat Commun 2021 10 7;12(1):5866. Epub 2021 Oct 7.

Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.

Type I interferon is promising in treating different kinds of tumors, but has been limited by its toxicity, lack of tumor targeting, and very short half-life. To target tumors, reduce systemic toxicity, and increase half-life, here we engineer a masked type I IFN-Fc (ProIFN) with its natural receptor connected by a cleavable linker that can be targeted by tumor-associated proteases. ProIFN has a prolonged serum half-life and shows an improved tumor-targeting effect. Interestingly, ProIFN-treated mice show enhanced DC cross-priming and significant increased CD8 infiltration and effector function in the tumor microenvironment. ProIFN is able to improve checkpoint blockade efficacy in established tumors, as well as radiation efficacy for both primary and metastatic tumors. ProIFN exhibits superior long-term pharmacokinetics with minimal toxicity in monkeys. Therefore, this study demonstrates an effective tumor-activating IFN that can increase targeted immunity against primary tumor or metastasis and reduce periphery toxicity to the host.
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http://dx.doi.org/10.1038/s41467-021-26112-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497482PMC
October 2021

Molecular composition and biotoxicity effects of dissolved organic matters in sludge-based carbon: Effects of pyrolysis temperature.

J Hazard Mater 2021 Sep 26;424(Pt A):127346. Epub 2021 Sep 26.

Hubei Key Laboratory of Yangtze Catchment Environmental Aquatic Science, School of Environmental Studies, China University of Geosciences, Wuhan 430074, Hubei, China; Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Sludge pyrolysis carbonization has shown potential to convert sludge biomass into multifunctional carbon materials. However, ecological risks of dissolved organic matters (DOMs) with obscure molecular characteristics retaining in sludge-based carbons (SBCs) have received little attention. This study investigated the impact of pyrolysis temperatures on the molecular conversion and biotoxicity effects of DOMs in SBCs. The results revealed that DOMs in SBCs were mainly derived from depolymerization of biopolymers and the polycondensation and cyclization of small intermediate molecules, which mainly consisted of aromatic CHON compounds with 1-3 N atoms, featuring high unsaturation and molecular weights. High-temperature pyrolysis (500-800 °C) promoted the decomposition and ring-opening of aromatic CHON compounds into saturated aliphatic CHO compounds with 2-4 O atoms in SBCs. Noteworthily, SBCs-derived DOMs showed relatively strong biotoxicity on the growth and development of wild-type zebrafish embryos, pakchoi seeds, and Vibrio qinghaiensis Q67, which was significantly related to aromatic amines, phenols, and heterocyclic-N compounds in DOMs of SBCs. SBCs-derived DOMs were mainly straight-chain fatty acids and showed no observable acute biotoxicity. This study highlights the negative impact of DOMs in SBCs on the ecological environment, and provides the theoretical basis for controlling toxic byproducts in sludge pyrolysis process.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127346DOI Listing
September 2021

Research on Classification of Fine-Grained Rock Images Based on Deep Learning.

Comput Intell Neurosci 2021 20;2021:5779740. Epub 2021 Sep 20.

College of Mechanical and Control Engineering, Guilin University of Technology, Guilin, Guangxi 541004, China.

Rock classification is a significant branch of geology which can help understand the formation and evolution of the planet, search for mineral resources, and so on. In traditional methods, rock classification is usually done based on the experience of a professional. However, this method has problems such as low efficiency and susceptibility to subjective factors. Therefore, it is of great significance to establish a simple, fast, and accurate rock classification model. This paper proposes a fine-grained image classification network combining image cutting method and SBV algorithm to improve the classification performance of a small number of fine-grained rock samples. The method uses image cutting to achieve data augmentation without adding additional datasets and uses image block voting scoring to obtain richer complementary information, thereby improving the accuracy of image classification. The classification accuracy of 32 images is 75%, 68.75%, and 75%. The results show that the method proposed in this paper has a significant improvement in the accuracy of image classification, which is 34.375%, 18.75%, and 43.75% higher than that of the original algorithm. It verifies the effectiveness of the algorithm in this paper and at the same time proves that deep learning has great application value in the field of geology.
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http://dx.doi.org/10.1155/2021/5779740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478565PMC
October 2021

An NADPH-dependent Ketoreductase Catalyses the Tetracyclic to Pentacyclic Skeletal Rearrangement in Chartreusin Biosynthesis.

Angew Chem Int Ed Engl 2021 Sep 30. Epub 2021 Sep 30.

Nanjing University, school of life science, CHINA.

Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early 13 C-labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin-dependent monooxygenase ChaZ catalyses a Baeyer-Villiger oxidation on resomycin C to form a seven-membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and afford the α-pyrone containing pentacyclic intermediate in an NADPH-dependent manner, presumably via a cascade reactions including the reduction of the lactone carbonyl group, Aldol-type reaction, followed by a spontaneous γ-lactone ring formation, and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide.
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http://dx.doi.org/10.1002/anie.202112047DOI Listing
September 2021

Minocycline attenuates oxidative and inflammatory injury in a intestinal perforation induced septic lung injury model via down-regulating lncRNA MALAT1 expression.

Int Immunopharmacol 2021 Sep 22;100:108115. Epub 2021 Sep 22.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430070, China. Electronic address:

Background: Oxidative stress and inflammatory responses play an important role in acute lung injury (ALI). Although minocycline (MINO) has anti-inflammatory effects and is a promising candidate in treating inflammatory diseases, the effect of MINO on ALI during sepsis is still unclear.

Methods: In the present study, a mouse model with intestinal perforation was established. C57BL/6 mice received cecal ligation and puncture (CLP) to induce sepsis-associated ALI. MINO was used to treat the mice via intraperitoneal injection at different doses (negative control, 20 mg/kg, 50 mg/kg and 100 mg/kg, respectively) 24 h after CLP. The severity of lung injury was evaluated by pathological examination, and lung wet / dry weight ratio was calculated to evaluate the severity of pulmonary edema. The changes of TNF-α, IL-1β, IL-6, PGE2, MDA, NF-κB, Nrf2, Keap1 and lncRNA MALAT1 levels in lung tissues of the mice were detected with ELISA, chemical colorimetry, Western blot or qRT-PCR.

Results: MINO ameliorated the lung edema and lung injury of the mice induced by CLP in a dose-dependent manner. MINO administration could significantly down-regulate expressions of TNF-α, IL-6, IL-1β, PGE2 and MDA in lung tissues of the mice. Mechanistically, MINO exerted the effects of anti-inflammation and anti-oxidative stress through down-regulating the expression of MALAT1 and regulating Nrf2/Keap1 and NF-κB signaling pathways.

Conclusion: MINO represses oxidative stress and inflammatory response during sepsis-induced ALI via down-regulating MALAT1 expression, and it has the potential to treat septic ALI.
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http://dx.doi.org/10.1016/j.intimp.2021.108115DOI Listing
September 2021

Synthesis of 6-phenylbenzo[]quinolines photoinduced dehydrogenative annulation of ()-2-phenyl-3-styrylpyridines.

Org Biomol Chem 2021 Oct 14;19(39):8554-8558. Epub 2021 Oct 14.

School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.

A concise and environmentally friendly protocol was developed for the synthesis of 6-phenylbenzo[]quinolines. 6-Phenylbenzo[]quinolines were obtained in good yields irradiation of ()-2-phenyl-3-styrylpyridines with a 254 nm UV light (64 W) in EtOH under an argon atmosphere in the presence of TFA. The reaction is a dehydrogenative annulation reaction that proceeds through 6π-electrocyclization, a [1,5]-H shift, 1,3-enamine tautomerization, and elimination of a hydrogen molecule to afford 6-phenylbenzo[]quinolines. The described protocol not only avoids the usage of a transition metal catalyst and an oxidant but also has the advantages of high atom efficiency and mild reaction conditions.
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http://dx.doi.org/10.1039/d1ob01674aDOI Listing
October 2021

Screening and verification of CYP3A4 inhibitors from Bushen-Yizhi formula to enhance the bioavailability of osthole in rat plasma.

J Ethnopharmacol 2022 Jan 14;282:114643. Epub 2021 Sep 14.

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address:

Ethnopharmacological Relevance: With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated.

Aim Of The Study: The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported.

Materials And Methods: Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance.

Results: 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro, we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid, 1,2,3,4,6-O-Pentagalloylglucose, Rutin, and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC = 0.339 μM), and even better than the clinically used drug (Ket) at the concentration of 5 μM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01).

Conclusions: Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.
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http://dx.doi.org/10.1016/j.jep.2021.114643DOI Listing
January 2022

Origin of Site Selectivity in Toluene Hydroxylation by Cytochrome P450 Enzymes.

J Org Chem 2021 10 17;86(19):13768-13773. Epub 2021 Sep 17.

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023,China.

Computational studies are utilized to reveal factors that determine the site selectivity in toluene hydroxylation by cytochrome P450 enzymes (CYPs). The DFT-computed inherent barriers suggest that the priority of product formation is in the order of benzyl alcohol > - ≈ - > -cresol. However, the specific size and shape of the cavities at the active sites of different CYPs dramatically affect the binding orientation of toluene, and thus, the site selectivity can be reordered.
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http://dx.doi.org/10.1021/acs.joc.1c01295DOI Listing
October 2021

Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury.

World J Emerg Med 2021 ;12(4):303-308

Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Background: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury.

Methods: Sixteen male swine were randomized to CCPR (CCPR; =8; CCPR alone) and ECPR (ECPR; =8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint.

Results: For the two groups, the survival rates between the two groups were not statistically significant (>0.05), the blood and lung biomarkers were statistically significant (<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group.

Conclusions: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390345PMC
January 2021

Percutaneous penetration and dermal exposure risk assessment of chlorinated paraffins.

J Hazard Mater 2021 08 23;416:126178. Epub 2021 May 23.

Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

The widespread occurrence of chlorinated paraffins (CPs) in environmental matrices has resulted in a high frequency exposure to CPs via dermal contact. To quantitatively estimate percutaneous penetration of CPs, Episkin® human skin equivalents (HSE) was applied as an in vitro model to evaluate the mechanism of percutaneous penetration of CPs. The co-exposure of CPs mixtures to HSE showed that about 11.7% and 10.2% of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) could penetrate the HSE and enter the receptor fluid, while no long-chain CPs (LCCPs) (C>17) were able to penetrate the HSE during the 36-h assay period. The experimentally obtained permeability coefficient (K) values for CPs were significantly (p < 0.01) negatively correlated with their log octanol-water partition coefficient (log K). Furthermore, 24 participants were recruited to assess direct human dermal exposure to CPs in China with the total CPs collected onto hand wipes and forehead wipes being 96,600 and 30,400 ng/person, respectively. The proportion of total SCCPs and MCCPs intake via dermal penetration (skin area investigated in this study) accounting for 2.0% of the total intake of CPs. Considering the total skin surface of human body is around 20 times of the area studied, the total intake of CPs through dermal penetration could be a significant exposure pathway.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126178DOI Listing
August 2021

Kinetic Resolution of Spiroindolines through Ir-Catalyzed Asymmetric Allylative Ring-Opening Reaction.

Org Lett 2021 09 16;23(17):6664-6668. Epub 2021 Aug 16.

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Kinetic resolution of racemic spiroindolines with factors of ≤15200 has been developed to access enantiomerically enriched indole-annulated medium-sized lactams and spiroindolines through Ir-catalyzed asymmetric allylative ring-opening reaction. Density functional theory calculations support the idea that the accurate discrimination of two spiroindoline enantiomers by (η-allyl)-iridium(III) species and the perfect central-to-axial chirality conversion during C-C bond fragmentation ensure the stereoselective formation of two contiguous stereogenic centers and one axis in the medium-sized lactams.
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http://dx.doi.org/10.1021/acs.orglett.1c02232DOI Listing
September 2021

Resurgence of Sandstorms Complicates China's Air Pollution Situation.

Environ Sci Technol 2021 09 26;55(17):11467-11469. Epub 2021 Aug 26.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

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http://dx.doi.org/10.1021/acs.est.1c03724DOI Listing
September 2021

In silico identification of novel inhibitors targeting the DNA-binding domain of the human estrogen receptor alpha.

J Steroid Biochem Mol Biol 2021 Oct 17;213:105966. Epub 2021 Aug 17.

Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, Institute of Environment and Health, Jianghan University, Wuhan, 430056, China. Electronic address:

The human estrogen receptor alpha (ERα) is an important regulator in breast cancer development and progression. The frequent ERα mutations in the ligand-binding domain (LBD) can increase the resistance of antiestrogen drugs, highlighting the need to develop new drugs to target ERα-positive breast cancer. In this study, we combined molecular docking, molecular dynamics simulations and binding free energy calculations to develop a structure-based virtual screening workflow to identify hit compounds capable of interfering with the recognition of ERα by the specific response element of DNA. A druggable pocket on the DNA binding domain (DBD) of ERα was identified as the potential binding site. The hits binding modes were further analyzed to reveal the structural characteristics of the DBD-inhibitor complexes. The core structure of the lead molecules was synthesized and was found to inhibit the E2-induced cell proliferation in MCF-7 cell lines. These findings provide an insight into the structural basis of ligand-ERα for alternate sites beyond the LBD-based pocket. The core structure proposed in this study could potentially be used as the lead molecule for further rational optimization of the antiestrogen drug structure with stronger binding of DBD and higher activity.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105966DOI Listing
October 2021

Perfluorooctane sulfonate (PFOS) disturbs fatty acid metabolism in Caenorhabditis elegans: Evidence from chemical analysis and molecular mechanism exploration.

Chemosphere 2021 Aug 24;277:130359. Epub 2021 Mar 24.

College of Resources and Environment, Huazhong Agricultural University, Wuhan, 430070, China.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that might induce disorders in fatty acid (FA) metabolism, but the underlying mechanisms remain unresolved. Caenorhabditis elegans (C. elegans) as a model organism can synthesize polyunsaturated FAs de novo via the polyunsaturated FA synthesis pathway. In this study, synchronized L1 C. elegans were exposed to 0, 0.01, 0.1, 0.5 and 1 μM PFOS for 72 h. Gas chromatography-mass spectrometry (GC-MS) was used to establish a sensitive and reliable analysis method for PFASs in exposed nematode, the instrument detection limits of nine fatty acid methyl esters examined ranged between 1.11 and 27.6 ng/mL, with satisfactory reproducibility (RSD < 10%) observed. Methyl pentadecanoate (C15:0) was used as an internal standard, the linearity of the calibration (0.1-10 μg/mL) nine FAs from the nematode were quantitatively analyzed. Comparing with the control group, PFOS exposure caused significantly decreased levels of C18:0 while significantly increased levels of C18:3n6. A decrease in the C18:3n6: C18:2n6 ratio was observed. Consistently, expression of the FA desaturation gene fat-3 was significantly down-regulated. These findings suggest that the FA disorder is associated with decrease in mRNA expression of Δ6-desaturase genes in C. elegans. Simultaneously, the disorders in FA metabolism were found to disrupt mitochondrial function with a reduction in ATP synthesis, as determined by the luciferase method. In summary, the results of the study provide insights into the adverse effects of PFOS on FA metabolism in living organisms.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130359DOI Listing
August 2021

Tumor-conditional IL-15 pro-cytokine reactivates anti-tumor immunity with limited toxicity.

Cell Res 2021 Aug 10. Epub 2021 Aug 10.

Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

IL-15 is a promising cytokine to expand NK and CD8 T cells for cancer immunotherapy, but its application is limited by dose-limiting, on-target off-tumor toxicity. Here, we have developed a next-generation IL-15 that is activated inside the tumor microenvironment (TME). This pro-IL-15 has the extracellular domain of IL-15Rβ fused to the N-terminus of sIL-15-Fc through a tumor-enriched Matrix Metalloproteinase (MMP) cleavable peptide linker to block its activity. Unlike sIL-15-Fc, pro-IL-15 does not activate the peripheral expansion of NK cells and T cells, thus reducing systemic toxicity, but it still preserves efficient anti-tumor abilities. In various mouse tumors, the anti-tumor effect of pro-IL-15 depends on intratumoral CD8 T cells and IFN-γ. Pro-IL-15 increases the stem-like TCF1Tim-3CD8 T cells within tumor tissue and helps overcome immune checkpoint blockade (ICB) resistance. Moreover, pro-IL-15 synergizes with current tyrosine kinase inhibitor (TKI) targeted-therapy in a poorly inflamed TUBO tumor model, suggesting that pro-IL-15 helps overcome targeted-therapy resistance. Our results demonstrate a next-generation IL-15 cytokine that can stimulate potent anti-tumor activity without severe toxicity.
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http://dx.doi.org/10.1038/s41422-021-00543-4DOI Listing
August 2021

Synthesis of cis/trans-dihydrochromenones via a photoinduced rearrangement of 4-phenyl-3-aryl/cyclohexenylcoumarins.

Org Biomol Chem 2021 Sep 10;19(33):7176-7180. Epub 2021 Aug 10.

Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China and School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.

A concise and environmentally friendly protocol has been developed for the synthesis of cis-dihydrochromenones and trans-dihydrochromenones in EtOH at room temperature. Irradiation of 4-phenyl-3-arylcoumarins in EtOH with 313 nm UV light under an argon atmosphere at room temperature gave cis-4b,15c-dihydro-16H-benzofuro[3',2':7,8]phenanthro[9,10-c]chromen-16-ones and cis-8c,14b-dihydro-9H-benzo[11,12]chryseno[5,6-c]chromen-9-ones in good yields. And an analogous treatment of 4-phenyl-3-alkenylcoumarins as 4-phenyl-3-arylcoumarins provided trans-1,2,3,4,4a,14b-hexahydro-5H-phenanthro[9,10-c]chromen-5-ones. The described photorearrangement proceeded smoothly without the addition of any transition metals and additives. The photorearrangement of 4-phenyl-3-arylcoumarins is believed to proceed via 6π-electrocyclization, a [1,3]-hydrogen shift and keto-enol isomerization.
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http://dx.doi.org/10.1039/d1ob01058aDOI Listing
September 2021

Development of chemiluminescence method based on serum type I collagen hydroxyl terminal peptide β special sequence (β-CTX).

Scand J Clin Lab Invest 2021 Oct 30;81(6):494-501. Epub 2021 Jul 30.

Medcial School, Anhui University of Science & Technology, Huainan, China.

The objective of this work is to develop and verify the analytical performance of a chemiluminescence immunoassay for the specific sequence β-carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX) in human serum. Two specific monoclonal antibodies (mAb-8A03 and mAb-3D12) with high affinity for β-CTX were selected, and, under optimized conditions, a chemiluminescence immunoassay method (CLIA) for β-CTX was established. The CLIA of β-CTX detected β-CTX in a wide range of 2.0-6000 ng/L. The recovery rate in serum is 95-105%, the specificity is high, and the cross-reaction rate with common easily interfering substances is low (not more than 0.01%). The CLIA correlates well with Roche electrochemiluminescence immunoassay (ECLIA), with a correlation coefficient of 0.9551, which fully meets the requirements of clinical analysis. The developed β-CTX CLIA kit has high sensitivity and good stability. It has the same performance as the commercial Roche ECLIA kit and can be applied clinically.
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http://dx.doi.org/10.1080/00365513.2021.1952484DOI Listing
October 2021

Clinical course and outcomes of COVID-19 patients with a history of cerebrovascular disease: a retrospective study in Wuhan.

Ann Transl Med 2021 Jun;9(12):988

Department of Gastroenterology, Daping Hospital of Third Military Medical University, Chongqing, China.

Background: Data on patients with coronavirus disease 2019 (COVID-19) who have pre-existing cerebrovascular disease (CVD) are scarce. This study set out to describe the clinical course and outcomes of these patients.

Methods: This single-center retrospective study was performed at Huoshenshan Hospital in Wuhan, China. Patients with confirmed COVID-19 who had pre-existing CVD (N=69) were identified. COVID-19 patients without CVD were randomly selected and matched by age and sex to the patients with CVD. Clinical data were analyzed and compared between the 2 groups. The composite endpoint included intensive care unit admission, use of mechanical ventilation, and death. Multivariable Cox regression analyses with control for medical comorbidities were used to examine the relationship between pre-existing CVD and clinical outcome of COVID-19.

Results: Compared with patients without CVD, patients with pre-existing CVD were more likely to present with unapparent symptoms at first; however, at admission, these patients tended to be in a severer condition than those without CVD, with more underlying hypertension and diabetes. The levels of interleukin-6, creative kinase MB, aspartate transaminase, and creatinine, as well as prothrombin time, were also markedly higher in patients with CVD. Patients with pre-existing CVD were more likely to develop multi-organ dysfunction, deteriorate to critical condition, and yield poorer clinical outcomes than patients without CVD. Concerning therapeutics, greater proportions of patients with pre-existing CVD required mechanical ventilation, higher-order anti-bacterials, and drugs targeting underlying diseases and complications. In the multivariable analysis, pre-existing CVD was significantly associated with a poor clinical outcome.

Conclusions: Patients with a history of CVD are more vulnerable to an over-activated inflammatory response and subsequent multi-organ dysfunction, resulting in a poor clinical outcome. Close monitoring is advisable for these patients.
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http://dx.doi.org/10.21037/atm-21-2237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267260PMC
June 2021

Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study.

J BioX Res 2021 Jun 3;4(2):53-59. Epub 2020 Dec 3.

Anhui Feidong County People's Hospital.

Objective: Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19).

Methods: In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022).

Results: The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.

Conclusion: Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.
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http://dx.doi.org/10.1097/JBR.0000000000000076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237841PMC
June 2021

A mathematical method for calibrating the signal drift in liquid chromatography - mass spectrometry analysis.

Talanta 2021 Oct 13;233:122511. Epub 2021 May 13.

Department of Chemistry, Wuhan University, Wuhan, 430072, PR China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, PR China. Electronic address:

Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) has become the most versatile analytical tool for profiling small-molecule compounds and increasingly been applied in many fields. Nevertheless, LC-MS based quantification still face some challenges, such as signal drift in LC-MS, which may affect the validity of the obtained data and lead to misinterpretation of biological results. Here, we established a calibration method known as "RIM" to compensate the signal drift of LC-MS. To this end, a mixture of d-2-dimethylaminoethylamine (d-DMED)-coded normal fatty acids (C5-C23) was used as calibrants to construct RIM calibration. With the addition of calibrants, not only the MS signal drift, but also the mass accuracy and LC retention time can be calibrated, thereby improving the reliability of quantitative data. The effectiveness of RIM was carefully validated using a human serum extract spiked with 34 standards and then RIM was applied for rat brain untargeted metabolome research. In addition, to expand the functionality and flexibility of RIM for data handling, we generated a MATLAB-based RIM program, which implements the above concepts and allows automatic data process. Taken together, the proposed RIM method has potential application in large-scale quantitative study of complex samples.
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http://dx.doi.org/10.1016/j.talanta.2021.122511DOI Listing
October 2021

[3D printed portable gel electrophoresis device for rapid detection of proteins].

Se Pu 2020 Nov;38(11):1316-1322

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

The growing demand for rapid, portable, and economical detection methods for environmental analysis has resulted in increasing demands on the portability and miniaturization of analytical instruments. The miniaturization of scientific instruments facilitates analysis in the field of medicine, food, and environment, especially for the under-resourced areas. The gel electrophoresis devices currently available for protein separation are primarily used in laboratories. Miniaturized instruments that can be used for on-site and rapid separation of protein have not yet been reported. In this study, a portable gel electrophoresis device for rapid separation and detection of proteins was developed and manufactured by 3D printing in a laboratory, which was economical, convenient, and quick. First, four kinds of portable gel electrophoresis devices that included three kinds of columnar gel and one slab gel electrophoresis device were designed with computer-aided design software SolidWorks 2017 (Dassault Systemes SE, France); the components including gel tubes, gel plates, and gel electrophoresis tanks were then printed using a 3D printer after optimization of the printing parameters. Then, the performance of the four kinds of gel electrophoresis devices was investigated using prestained protein molecular weight standards. The results showed that the single-channel slab gel electrophoresis design can quickly separate proteins with the best separation efficiency. Moreover, the effect of different separation gel lengths (5, 10, 15, and 20 mm) on protein separation was studied and it was found that 10% separation gels with a length of 5 mm could effectively separate prestained protein molecular weight standards (in the range of 15-250 kD) in 20 minutes. Next, the battery was optimized for the portable GE device and a 25 V lithium battery (70 mm×60 mm×40 mm) was used as the power supply, which could provide a constant voltage of 25 V for 100 hours during gel electrophoresis. Then, the One-Step Blue reagent (Biotium, USA) was used to color the separation results of the five standard proteins (carbonic anhydrase, ovalbumin, bovine serum albumin, conalbumin, ribonuclease A), and the results were recorded by mobile phone. Finally, the proposed gel electrophoresis device was compared with the commercial device. The results showed that the two devices are comparable; however, the slab gel electrophoresis was faster, portable, and economical. In summary, this research designed and manufactured a portable gel electrophoresis device using 3D printing technique, which can be used for on-site analysis and detection of proteins. The device presents the following advantages compared with the commercial devices:1) small and portable:the size of the electrophoresis tank of the device is only 15 mm×20 mm×17 mm and the 25 V lithium battery has a working time of approximately 100 hours; 2) low cost:it can be processed in 5 hours using 3D printing technology, with 10 mL of printing material while the total cost is less than 400 RMB; 3) fast separation:this device can quickly achieve protein separation compared with commercial devices and can further use multiple electrophoresis tanks in parallel to analyze more samples at the same time. Besides, this research also highlights the advantages of 3D printing for the development of miniaturized analytical equipment. Though this study has achieved preliminary results for rapid separation of proteins using gel electrophoresis devices, the quantitative analysis of proteins following protein detection and the application of more samples need further research. Meanwhile, the continued application of 3D printing technology will promote the development of miniaturized and portable experimental equipment.
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http://dx.doi.org/10.3724/SP.J.1123.2020.02018DOI Listing
November 2020

Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria.

BMC Med Genomics 2021 06 26;14(1):168. Epub 2021 Jun 26.

Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH.

Methods: Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations.

Results: A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6.

Conclusion: Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.
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http://dx.doi.org/10.1186/s12920-021-01014-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236144PMC
June 2021
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