Publications by authors named "Xiaoling Wang"

483 Publications

Association of Subregional Quantitative Ultra-widefield Fluorescence Angiography Characteristics With the Occurrence of Diabetic Macular Edema and Proliferative Diabetic Retinopathy.

Front Med (Lausanne) 2021 24;8:720564. Epub 2021 Sep 24.

Eye Center, Renmin Hospital of Wuhan University, Wuhan, China.

To explore the relationships of region-specific properties of ultra-widefield fluorescence angiography (UWFFA) images with two adverse outcomes, diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR), and also the severity of diabetic retinopathy (DR). A cross-sectional observational study was performed to retrospectively analyze UWFFA images of patients with DR. All patients underwent UWFFA and optical coherence tomography examination. Leakage index and microaneurysm (MA) count were measured using Trainable Weka Segmentation, a machine learning algorithm, and ischemic index (ISI) was measured manually. The correlation between UWFFA parameters and severity of DR was analyzed, and receiver operating characteristic curves were used to estimate their diagnostic value for DME and PDR. A total of 108 eyes from 108 patients with DR (mean age of 56.04 ± 8.85 years) were analyzed. As the severity of DR increased, the ISI and leakage index of the panretina and all subregions increased. Panretinal MA count and leakage index were significantly higher in eyes with DME than those without DME ( = 0.044 and 0.001, respectively). Leakage index and ISI were significantly higher in eyes with PDR than those without PDR in both panretinal and subregion-specific measurements (all < 0.05). Throughout the retina and specifically in the posterior area (PoA), the leakage index had a higher diagnostic value for DME than ISI or MA count (all < 0.05). The diagnostic value of MA count for PDR was lower than that of ISI and leakage index (all < 0.05). The ISI, leakage index, and MA count in the PoA and panretina correlated with the severity of DR, especially the posterior parameter. The leakage index was more valuable than ISI and MA count in determining the occurrence of DME. ISI and leakage index were better predictors of PDR.
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http://dx.doi.org/10.3389/fmed.2021.720564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497797PMC
September 2021

Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice.

Blood Adv 2021 Oct;5(19):3799-3806

Department of Hematology, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, and.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.
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http://dx.doi.org/10.1182/bloodadvances.2020004110DOI Listing
October 2021

The effectiveness of the problem-based learning in medical cell biology education: A systematic meta-analysis.

Medicine (Baltimore) 2021 Oct;100(39):e27402

School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Problem-based learning (PBL) was widely adopted in medical cell biology education for Chinese student; however, there was no systematic analysis to prove PBL was much more effective than lecture-based learning (LBL). Our aim is to evaluate the effectiveness of PBL on cell biology curriculum compared with LBL.

Method: We systematically searched the publications related to PBL teaching approach in cell biology curriculum for medical education from databases until to February 2021. Pooled standard mean differences (SMDs) and risk ratios with their 95% confidence intervals were used to assess the effectiveness of PBL and the satisfaction of students to PBL compared to LBL in meta-analysis. The heterogeneity of the included studies was assessed by statistical I2 of heterogeneity. Meta-regression and subgroup analysis were performed to analyze the source of heterogeneity. Funnel plots and Egger tests were performed to assess publication bias.

Result: After initial searching and selection, 9 studies were included for meta-analysis. All of these 9 studies were in high quality. The SMDs (95% confidence intervals) of total examination scores and comprehensive examination scores between PBL and LBL curriculum in cell biology teaching was calculated to be 0.89 (0.52, 1.26) and 0.53 (0.29, 0.78). Meanwhile, the risk ratios of the satisfaction of PBL vs LBL were calculated to be 1.18 (0.96, 1.46). However, there was a heterogeneity among the pooled SMDs of 10 studies with I2 = 89.7%, P < .001. The factors including the different teachers, the similar or same examination paper and over 100 student numbers among PBL and LBL groups raised the heterogeneity in the pooled SMDs. There is no publication bias in these 10 publications after Egger and Begg test.

Conclusion: The result indicated PBL was better than LBL in improvement of examination scores and comprehensive examination scores in cell biology curriculum to some extent. However, the satisfaction of students to PBL and LBL had no difference. The factors, including the different teachers, the similar or same examination papers and over 100 student numbers, affected the effectiveness of PBL and raised the heterogeneity of the pooled SMDs.
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http://dx.doi.org/10.1097/MD.0000000000027402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483832PMC
October 2021

An Imported Confirmed Case of COVID-19 Vaccinated in Brazil - Shanghai Municipality, China, March 17, 2021.

China CDC Wkly 2021 Jul;3(30):650-652

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Chinese Center for Tropical Diseases Research; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Ministry of Science and Technology; Key Laboratory of Parasitic and Vector Biology, National Health Commission of China; The School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine; Huangpu, Shanghai, China.

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http://dx.doi.org/10.46234/ccdcw2021.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393173PMC
July 2021

An Investigation of a Confirmed Imported Case of COVID-19 Infected Abroad - Qingpu District, Shanghai Municipality, China, November 15, 2020.

China CDC Wkly 2021 Mar;3(10):207-210

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.

Summary: A passenger who was from the United States was taken to the hotel for the required isolation on November 13, 2020. During the quarantine she was diagnosed as the COVID-19 patient on November 15, 2020. Controlling the importation of COVID-19 remains a major challenge.

In this study, an epidemiological investigation was conducted for a confirmed case of COVID-19, including the treatment records in the hospital and 14-day travel trajectory before the onset of disease.

This study described an epidemiological investigation and management process on an imported case of COVID-19 and analyzed the test results, aiming to provide useful warnings to strengthen the capacity of public health system in response to the importation.
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http://dx.doi.org/10.46234/ccdcw2021.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392976PMC
March 2021

FAK Shutdown: Consequences on Epithelial Morphogenesis and Biomarker Expression Involving an Innovative Biomaterial for Tissue Regeneration.

Int J Mol Sci 2021 Sep 10;22(18). Epub 2021 Sep 10.

Center for Dental Medicine, Division of Oral Biotechnology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany.

By employing an innovative biohybrid membrane, the present study aimed at elucidating the mechanistic role of the focal adhesion kinase (FAK) in epithelial morphogenesis in vitro over 4, 7, and 10 days. The consequences of siRNA-mediated FAK knockdown on epithelial morphogenesis were monitored by quantifying cell layers and detecting the expression of biomarkers of epithelial differentiation and homeostasis. Histologic examination of FAK-depleted samples showed a significant increase in cell layers resembling epithelial hyperplasia. Semiquantitative fluorescence imaging (SQFI) revealed tissue homeostatic disturbances by significantly increased involucrin expression over time, persistence of yes-associated protein (YAP) and an increase of keratin (K) 1 at day 4. The dysbalanced involucrin pattern was underscored by ROCK-II activity at day 7 and 10. SQFI data were confirmed by quantitative PCR and Western blot analysis, thereby corroborating the FAK shutdown-related expression changes. The artificial FAK shutdown was also associated with a significantly higher expression of filaggrin at day 10, sustained keratinocyte proliferation, and the dysregulated expression of K19 and vimentin. These siRNA-induced consequences indicate the mechanistic role of FAK in epithelial morphogenesis by simultaneously considering prospective biomaterial-based epithelial regenerative approaches.
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http://dx.doi.org/10.3390/ijms22189774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470904PMC
September 2021

Transcriptome analysis of host response to porcine epidemic diarrhea virus nsp15 in IPEC-J2 cells.

Microb Pathog 2021 Sep 24:105195. Epub 2021 Sep 24.

Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

Background: Porcine epidemic diarrhea virus (PEDV) is an enveloped positive-sense ssRNA virus which is highly lethal to piglets, causing enormous economic losses to swine industry worldwide. Nsp15 protein is an endoribonuclease of PEDV and plays an indispensable role in the viral proliferation. We reported the transcription files of nsp15 transfected IPEC-J2 cells for the first time to broaden our understanding of PEDV pathogenesis.

Methods: RNA-seq was performed to compare gene expression profiles between pCAGGS-HA-nsp15 transfected IPEC-J2 cells and pCAGGS-HA (empty vector) transfected IPEC-J2 cells. Immune-related genes and pathways were identified and analyzed to deepen our understanding of nsp15 for PEDV pathogenicity. IPEC-J2 cells transfected with pCAGGS-HA-CCL5/CXCL8/CXCL10 were infected with CV777 and the virus load of PEDV was detected by qRT-PCR.

Results: A total of 21,654 genes were obtained by RNA-Seq and 415 differential expressed genes (DEGs) were identified, including 136 up-regulated and 279 down-regulated genes. A number of effect genes involved in immune responses and inflammation were differentially expressed. GO and KEGG enrichment analysis showed that 32 GO terms were significantly enriched and the DEGs were mainly enriched in immune-related pathways such as TNF signaling pathway, RIG-I-like receptor signaling pathway and Cytosolic DNA-sensing pathway. qRT-PCR results indicated the overexpression of selected chemokines, CCL5/CXCL8/CXCL10, can inhibit PEDV proliferation in IPEC-J2 cells.

Conclusions: Our transcriptome profile illustrated a number of genes involving in immune responses and inflammation were inhibited by nsp15, such as CCL5, CXCL8, CXCL10, OAS, MXs, STAT1 and IRF9. The results suggested that nsp15 can antagonize IFNs and block chemokine system to provide an adequate intracellular environment for viral proliferation.
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http://dx.doi.org/10.1016/j.micpath.2021.105195DOI Listing
September 2021

A KG-enhanced Multi-Graph Neural Network for Attentive Herb Recommendation.

IEEE/ACM Trans Comput Biol Bioinform 2021 Sep 27;PP. Epub 2021 Sep 27.

Traditional Chinese Medicine (TCM) has the longest clinical history in Asia and contributes a lot to health maintenance worldwide. An essential step during the TCM diagnostic process is syndrome induction, which comprehensively analyzes the symptoms and generates an overall summary of the symptoms. Given a set of symptoms, the existing herb recommenders aim to generate the corresponding herbs as a treatment by inducing the implicit syndrome representations based on TCM prescriptions. As different symptoms have various importance during the comprehensive consideration, we argue that treating the co-occurred symptoms equally to do syndrome induction in the previous studies will lead to the coarse-grained syndrome representation. In this paper, we bring the attention mechanism to model the syndrome induction process. Given a set of symptoms, we leverage an attention network to discriminate the symptom importance and adaptively fuse the symptom embeddings. Besides, we introduce a TCM knowledge graph to enrich the input corpus and improve the quality of representation learning. Further, we build a KG-enhanced Multi-Graph Neural Network architecture, which performs the attentive propagation to combine node feature and graph structural information. Extensive experimental results on two TCM data sets show that our proposed model has the outstanding performance over the state-of-the-arts.
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http://dx.doi.org/10.1109/TCBB.2021.3115489DOI Listing
September 2021

Automated Grading of Diabetic Retinopathy with Ultra-Widefield Fluorescein Angiography and Deep Learning.

J Diabetes Res 2021 8;2021:2611250. Epub 2021 Sep 8.

Eye Center, Renmin Hospital of Wuhan University, Wuhan, China.

Purpose: The objective of this study was to establish diagnostic technology to automatically grade the severity of diabetic retinopathy (DR) according to the ischemic index and leakage index with ultra-widefield fluorescein angiography (UWFA) and the Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field (7-SF).

Methods: This is a cross-sectional study. UWFA samples from 280 diabetic patients and 119 normal patients were used to train and test an artificial intelligence model to differentiate PDR and NPDR based on the ischemic index and leakage index with UWFA. A panel of retinal specialists determined the ground truth for our data set before experimentation. A confusion matrix as a metric was used to measure the precision of our algorithm, and a simple linear regression function was implemented to explore the discrimination of indexes on the DR grades. In addition, the model was tested with simulated 7-SF.

Results: The model classification of DR in the original UWFA images achieved 88.50% accuracy and 73.68% accuracy in the simulated 7-SF images. A simple linear regression function demonstrated that there is a significant relationship between the ischemic index and leakage index and the severity of DR. These two thresholds were set to classify the grade of DR, which achieved 76.8% accuracy.

Conclusions: The optimization of the cycle generative adversarial network (CycleGAN) and convolutional neural network (CNN) model classifier achieved DR grading based on the ischemic index and leakage index with UWFA and simulated 7-SF and provided accurate inference results. The classification accuracy with UWFA is slightly higher than that of simulated 7-SF.
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http://dx.doi.org/10.1155/2021/2611250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445732PMC
September 2021

Author Correction: 58-F, a flavanone from Ophiopogon japonicus, prevents hepatocyte death by decreasing lysosomal membrane permeability.

Sci Rep 2021 Sep 13;11(1):18563. Epub 2021 Sep 13.

Department of Biology, School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

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http://dx.doi.org/10.1038/s41598-021-98198-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438086PMC
September 2021

Superstructured mesocrystals through multiple inherent molecular interactions for highly reversible sodium ion batteries.

Sci Adv 2021 Sep 8;7(37):eabh3482. Epub 2021 Sep 8.

BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, College of Materials Science and Engineering, Sichuan University, Chengdu Sichuan 610065, China.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abh3482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442931PMC
September 2021

Targeting thioredoxin reductase by deoxyelephantopin from Elephantopus scaber triggers cancer cell apoptosis.

Arch Biochem Biophys 2021 Oct 10;711:109028. Epub 2021 Sep 10.

Shaanxi Key Laboratory of Phytochemistry and College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji, 721013, China. Electronic address:

Elevated expression of thioredoxin reductase (TrxR) is associated with the tumorigenesis and resistance to cancer chemoradiotherapy, highlighting the potential of TrxR inhibitors as anticancer drugs. Deoxyelephantopin (DET) is the major active ingredient of Elephantopus scaber and reveals potent anticancer activity. However, the potential mechanism of action and the cellular target of DET are still unknown. Here, we found that DET primarily targets the Sec residue of TrxR and irreversibly prohibits enzyme activity. Suppression of TrxR by DET leads to accumulation of reactive oxygen species and dysregulation in intracellular redox balance, eventually inducing cancer cell apoptosis mediated by oxidative stress. Noticeably, down-regulation of TrxR1 by shRNA increases cell sensitivity to DET. Collectively, targeting of TrxR1 by DET uncovers a novel mechanism of action in DET and deepens the understanding of developing DET as a potential chemotherapeutic agent for treating cancers.
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http://dx.doi.org/10.1016/j.abb.2021.109028DOI Listing
October 2021

Aberrant expression of miR-483-5p in patients with asymptomatic carotid artery stenosis and its predictive value for cerebrovascular event occurrence.

Exp Ther Med 2021 Oct 2;22(4):1101. Epub 2021 Aug 2.

Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.

MicroRNAs (miRNAs/miRs) may be used as novel promising diagnostic and prognostic biomarkers for various diseases, including asymptomatic carotid artery stenosis (ACAS). The present study aimed to investigate the abnormal expression of microRNA-483-5p (miR-483-5p) in patients with ACAS and to evaluate its diagnostic value for ACAS screening and its predictive value for cerebrovascular events. A total of 128 patients with ACAS and 76 healthy controls were included in the present study. The expression of miR-483-5p in serum was measured by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-483-5p in patients with ACAS. Kaplan-Meier curves were drawn and Cox regression analysis was used to determine the predictive value of miR-483-5p for cerebrovascular events in patients with ACAS. Serum miR-483-5p levels were significantly increased in patients with ACAS as compared with those in healthy controls. The expression of miR-483-5p was significantly associated with diabetes (P=0.011), dyslipidemia (P=0.047) and the degree of carotid stenosis (P=0.006) in patients with ACAS. In addition, the area under the ROC curve was 0.910, with a sensitivity of 80.5% and a specificity of 89.5% at the cutoff value of 0.705, indicating that serum miR-483-5p expression has a certain diagnostic value in patients with ACAS. Furthermore, the patients with high miR-483-5p expression had a higher proportion of cerebrovascular events than patients with low miR-483-5p levels (log-rank P=0.011) and miR-483-5p was an independent prognostic marker for predicting the occurrence of cerebrovascular events in patients with ACAS. The results indicated that miR-483-5p expression is significantly increased in patients with ACAS and that abnormal miR-483-5p expression may be a candidate biomarker for ACAS diagnosis and the prediction of cerebrovascular event occurrence.
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http://dx.doi.org/10.3892/etm.2021.10536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383747PMC
October 2021

The self-healing of Bacillus subtilis biofilms.

Arch Microbiol 2021 Nov 31;203(9):5635-5645. Epub 2021 Aug 31.

State Key Laboratory of Computer Science, Institute of Software, University of Chinese Academy of Sciences, Beijing, 100190, China.

Self-healing is an intrinsic ability that exists widely in every multicellular biological organism. Our recent experiments have shown that bacterial biofilms also have the ability to self-heal after man-make cuts, but the mechanism of biofilm self-healing have not been studied. We find that the healing process of cuts on the biofilm depends on cut geometries like its location or direction, the biofilm itself like the biofilm age, the growing substrate properties like its hardness, and also the environments such as the competitive growth of multiple biofilms. What is more, the healing rate along the cut is heterogeneous, and the maximum healing rate can reach 260 μm/h, which is three times the undestroyed biofilm expansion rate. The cut does not change the rounded shape growth of biofilms. Further study of phenotypic evolution shows that the cut delays bacterial differentiation; motile cells perceive the cut and move to the cut area, while the cut only heals when there are enough matrix-producing cells in the cut area. Our work suggests new ideas for developing self-healing materials.
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http://dx.doi.org/10.1007/s00203-021-02542-wDOI Listing
November 2021

Negative/Zero Thermal Quenching of Luminescence Electronic Structural Transition in Copper-Iodide Cluster-Based Coordination Networks.

J Phys Chem Lett 2021 Sep 23;12(34):8237-8245. Epub 2021 Aug 23.

Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Advanced Catalysis & Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou, Jiangsu 213164, P. R. China.

Photoluminescence (PL) intensity in organic or metal-organic emitters usually suffers from thermal quenching (TQ), which severely hinders their industrial applications. The development of negative thermal quenching (NTQ) and/or zero thermal quenching (ZTQ) materials depends on a better understanding of the mechanisms underpinning TQ in luminescent solids. In this work, we investigated the temperature dependence of thermally activated delayed fluorescence (TADF) in copper(I)-organic coordination polymers (CP) ligated with an imidazole or triazole derivative over a broad temperature range. The efficient PL emission of is heavily quenched as the crystalline samples are cooled to 77 K; the PL intensity shows the NTQ effect in the region of 77-238 K followed by a ZTQ effect in the temperature range of 238-318 K. No NTQ or ZTQ effect is observed for reference coordination polymer , where the 1,2,4-triazole group was used instead of the imidazole one. Our work highlights the important role of the ligand's electronic structure in optimizing photophysical properties of coordination polymer emitters and may stimulate new efforts to design luminescent materials exhibiting NTQ and ZTQ effect at higher temperature.
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http://dx.doi.org/10.1021/acs.jpclett.1c02426DOI Listing
September 2021

The Role of Macrophages in Kidney Fibrosis.

Front Physiol 2021 6;12:705838. Epub 2021 Aug 6.

Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.

The phenotypic heterogeneity and functional diversity of macrophages confer on them complexed roles in the development and progression of kidney diseases. After kidney injury, bone marrow-derived monocytes are rapidly recruited to the glomerulus and tubulointerstitium. They are activated and differentiated on site into pro-inflammatory M1 macrophages, which initiate Th1-type adaptive immune responses and damage normal tissues. In contrast, anti-inflammatory M2 macrophages induce Th2-type immune responses, secrete large amounts of TGF-β and anti-inflammatory cytokines, transform into αSMA+ myofibroblasts in injured kidney, inhibit immune responses, and promote wound healing and tissue fibrosis. Previous studies on the role of macrophages in kidney fibrosis were mainly focused on inflammation-associated injury and injury repair. Apart from macrophage-secreted profibrotic cytokines, such as TGF-β, evidence for a direct contribution of macrophages to kidney fibrosis is lacking. However, under inflammatory conditions, Wnt ligands are derived mainly from macrophages and Wnt signaling is central in the network of multiple profibrotic pathways. Largely underinvestigated are the direct contribution of macrophages to profibrotic signaling pathways, macrophage phenotypic heterogeneity and functional diversity in relation to kidney fibrosis, and on their cross-talk with other cells in profibrotic signaling networks that cause fibrosis. Here we aim to provide an overview on the roles of macrophage phenotypic and functional diversity in their contribution to pro-fibrotic signaling pathways, and on the therapeutic potential of targeting macrophages for the treatment of kidney fibrosis.
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http://dx.doi.org/10.3389/fphys.2021.705838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378534PMC
August 2021

CBDPS 1.0: A Python GUI Application for Machine Learning Models to Predict Bitter-Tasting Children's Oral Medicines.

Chem Pharm Bull (Tokyo) 2021 Oct 21;69(10):989-994. Epub 2021 Aug 21.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health.

Bitter tastes are innately aversive and are thought to help protect animals from consuming poisons. Children are extremely sensitive to drug tastes, and their compliance is especially poor with bitter medicine. Therefore, judging whether a drug is bitter and adopting flavor correction and taste-masking strategies are key to solving the problem of drug compliance in children. Although various machine learning models for bitterness and sweetness prediction have been reported in the literature, no learning model or bitterness database for children's medication has yet been reported. In this study, we trained four different machine learning models to predict bitterness. The goal of this study was to develop and validate a machine learning model called the "Children's Bitter Drug Prediction System" (CBDPS) based on Tkinter, which predicts the bitterness of a medicine based on its chemical structure. Users can enter the Simplified Molecular-Input Line-Entry System (SMILES) formula for a single compound or multiple compounds, and CBDPS will predict the bitterness of children's medicines made from those XGBoost-Molecular ACCess System (XgBoost-MACCS) model yielded an accuracy of 88% under cross-validation.
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http://dx.doi.org/10.1248/cpb.c20-00866DOI Listing
October 2021

GW10, a member of P450 subfamily regulates grain size and grain number in rice.

Theor Appl Genet 2021 Aug 21. Epub 2021 Aug 21.

Guangdong Provincial Key Laboratory of Plant Molecular Breeding, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou, 510642, China.

Key Message: A quantitative trait locus GW10 is located on Chromosome 10 by map-based cloning, which encodes a P450 Subfamily protein. The GW10 regulates grain size and grain number in rice involved in the BR pathway. Grain size and grain number play extremely important roles in rice grain yield. Here, we identify GW10, which encodes a P450 subfamily protein and controls grain size and grain number by using Lemont (tropical japonica) as donor parent and HJX74 (indica) as recipient parent. The GW10 locus was mapped into a 14.6 kb region in HJX74 genomic on the long arm of chromosome 10. Lower expression of the gw10 in panicle is contributed to the shorter and narrower rice grain, and the increased number of grains per panicle. In contrast, overexpression of GW10 is contributed to longer and wider rice grain. Furthermore, the higher expression levels of some of the brassinosteroid (BR) biosynthesis and response genes are associated with the NIL-GW10. The sensitivity of the leaf angle to exogenous BR in NIL-GW10 is lower than that in NIL-gw10 and in the KO-GW10, which implied that the GW10 should involve in the brassinosteroid-mediated regulation of rice grain size and grain number.
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http://dx.doi.org/10.1007/s00122-021-03939-3DOI Listing
August 2021

The trans-omics landscape of COVID-19.

Nat Commun 2021 07 27;12(1):4543. Epub 2021 Jul 27.

BGI-Shenzhen, Shenzhen, China.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.
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http://dx.doi.org/10.1038/s41467-021-24482-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316550PMC
July 2021

'Chain and running' induced by mechanical interactions among cells of different phenotypes in the Bacillus subtilis biofilm.

Eur Biophys J 2021 Oct 25;50(7):1013-1023. Epub 2021 Jul 25.

State Key Laboratory of Computer Science, Institute of Software, University of Chinese Academy of Sciences, Beijing, 100190, China.

In either a living system or a non-living system, the interaction among its constituent cells or particles is a fundamental aspect at all scales. For example, during the Bacillus subtilis biofilm formation, cells differentiate into multiple phenotypes to adapt to the environments; few hours after the initial inoculation, we find the phenotype of matrix-producing cells form "chain" structure surrounding the phenotype of the "running" motile cells. We use "chain" to characterize the structure of matrix-producing cells, and "running" to characterize the proliferation and growth of motile cells. Due to a large number of cells in the biofilm, it is impossible to construct a traditional kinetic model to describe the causal link between the single-cell movement and the colony behavior. Here, we obtain cell state information and cell group shape information through experiments; after the image analysis, we get the key interaction rules between cells, and then, we simulate the comparable movement of two cell types and the resulting colony geometry using the multi-agent model. Our work makes a better understanding of the relationship between the macroscopic shape of colonies and microscopic mechanical interactions among cells in the early stage of biofilm growth.
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http://dx.doi.org/10.1007/s00249-021-01562-0DOI Listing
October 2021

Testing of Worn Face Masks for Timely Diagnosis of SARS-CoV-2 in Hemodialysis Patients.

J Am Soc Nephrol 2021 Jul 19. Epub 2021 Jul 19.

Research Division, Renal Research Institute, New York, New York.

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http://dx.doi.org/10.1681/ASN.2021060812DOI Listing
July 2021

Immediate and Delayed Effects of Cupping Therapy on Reducing Neuromuscular Fatigue.

Front Bioeng Biotechnol 2021 1;9:678153. Epub 2021 Jul 1.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, IL, United States.

Cupping therapy has been popular in elite athletes in recent years. However, the effect of cupping therapy on reducing muscle fatigue has not been investigated. The purpose of this study was to investigate the immediate and delayed effects of cupping therapy on reducing biceps brachii fatigue during biceps curls. Twelve healthy untrained participants were recruited for this repeated-measures study. Cupping therapy (-300 mmHg pressure for 5 min) and sham control (no negative pressure for 5 min) were applied after biceps fatigue induced by performing repeated biceps curls at 75% of the 10 repetitions of maximum of the non-dominant hand. Surface electromyography (EMG) with spectral analyses [mean frequency (MNF), median frequency (MDF), and spectral moments ratio (SMR)] were used to assess muscle fatigue during the fatigue task. EMG signals during the first 10 repetitions and the last 10 repetitions of biceps curls were used to assess neuromuscular fatigue. There were significant decreases in MNF and MDF and a significant increase in SMR immediately and 24 h after the sham control (no intervention). When comparing the MNF, MDF, and SMR after cupping therapy to the sham control, there was no significant immediate effect on reducing muscle fatigue. However, there was a significant delayed effect on improving recovery following fatigue for the cupping therapy compared to the sham control (MNF changes: sham 0.87 ± 0.02 vs. cupping 0.91 ± 0.02, 0.05; MDF changes sham: 0.85 ± 0.03 vs. cupping: 0.91 ± 0.02, 0.05; SMR changes: sham 1.89 ± 0.15 vs. cupping 1.58 ± 0.13, 0.05). The findings of this study demonstrate that there is a time effect of cupping therapy for reducing muscle fatigue. Cupping therapy is effective on reducing biceps brachii muscle fatigue after 24 h.
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http://dx.doi.org/10.3389/fbioe.2021.678153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280458PMC
July 2021

Model-Based Meta-Analysis in Psoriasis: A Quantitative Comparison of Biologics and Small Targeted Molecules.

Front Pharmacol 2021 1;12:586827. Epub 2021 Jul 1.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed. Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90). A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71-92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12-92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91-77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8-75.7%). What's more, the risankizumab provided the highest response of PASI90 at week 16 and week 24. This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.
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http://dx.doi.org/10.3389/fphar.2021.586827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281289PMC
July 2021

LncRNA LINC01088 inhibits the function of trophoblast cells, activates the MAPK-signaling pathway and associates with recurrent pregnancy loss.

Mol Hum Reprod 2021 08;27(8)

Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.

Long noncoding RNAs (lncRNAs) have been reported to be involved in various cellular processes and to participate in a variety of human diseases. Recently, increasing studies have reported that lncRNAs are related to many reproductive diseases, such as pathogenesis of recurrent pregnancy loss (RPL), preeclampsia (PE) and gestational diabetes mellitus (GDM). In this study, we aimed to investigate the effect of LINC01088 in trophoblast cells and its potential role in pathogenesis of RPL. LINC01088 was found to be upregulated in first-trimester chorionic villi tissues from RPL patients. Increased LINC01088 repressed proliferation, migration and invasion of trophoblast cells, and promoted apoptosis of trophoblast cells. Further exploration indicated that LINC01088 decreased the production of nitric oxide (NO) by binding and increasing Arginase-1 and decreasing eNOS protein levels. Importantly, JNK and p38 MAPK-signaling pathways were active after overexpression of LINC01088. In conclusion, our studies demonstrated that LINC01088 plays an important role in the pathogenesis of RPL, and is a potential therapeutic target for the treatment of RPL.
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http://dx.doi.org/10.1093/molehr/gaab047DOI Listing
August 2021

Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness.

Nat Commun 2021 07 9;12(1):4230. Epub 2021 Jul 9.

Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXβ2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXβ2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXβ2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXβ2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.
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http://dx.doi.org/10.1038/s41467-021-24315-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270969PMC
July 2021

Presence of SARS-CoV-2 Antibodies in Spent Peritoneal Dialysate.

J Am Soc Nephrol 2021 08 6;32(8):1865-1867. Epub 2021 Jul 6.

Research Division, Renal Research Institute, New York, New York.

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http://dx.doi.org/10.1681/ASN.2021020161DOI Listing
August 2021

NEW INSIGHTS INTO THE ASSOCIATION BETWEEN CHOROIDAL VESSELS AND CHORIOCAPILLARIS IN NORMAL EYES.

Retina 2021 Jun 21. Epub 2021 Jun 21.

Eye Center, Renmin Hospital of Wuhan University, Wuhan, China.

Purpose: To determine the relationship between large and medium-sized choroidal vessels and choriocapillaris (CC) using the three-dimensional choroidal vascularity index (3D CVI) and percentage of flow deficits (FD%).

Methods: Prospective observational study. The main outcome measures included choroidal volume parameters (3D CVI, mean choroidal thickness (MCT), total choroidal volume (TCV), choroidal luminal volume (LV), and choroidal stromal volume (SV)), CC parameters (FD%, average area of FD (FDa), and FD count (FDc)), and age and axial length (AL).

Results: A total of 63 healthy individuals with an average age of 40.60 ± 12.32 years were included in this study. Univariate analysis showed that FD% (R = 0.295, P = 0.019) and FDa (R = 0.276, P = 0.028) were significantly positively associated with 3D CVI and FDc was negatively associated with 3D CVI (R = -0.297, P = 0.018). After adjusting for age and AL, a significant correlation between FD% and 3D CVI (R = 0.264, P = 0.039), and between FDa and 3D CVI remained (R = 0.267, P = 0.037). However, no significant correlation was found between FDc and 3D CVI after adjusting for AL (R = -0.220, P = 0.085).

Conclusion: In healthy individuals, choroidal vessel dilatation as suggested by elevated 3D CVI may lead to decreased CC perfusion, which was correlated with an enlarged FDa in CC.
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http://dx.doi.org/10.1097/IAE.0000000000003238DOI Listing
June 2021

Allergen-Specific Treg Cells Upregulated by Lung-Stage Infection Alleviates Allergic Airway Inflammation.

Front Cell Dev Biol 2021 8;9:678377. Epub 2021 Jun 8.

NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, China.

infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of infection on asthma (infection before allergen sensitization), whereas the protective effects of infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of infection influences its protective effect, the mice were percutaneously infected with cercaria of at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post-lung-stage during AAI). We found that lung-stage infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not. Mechanistically, lung-stage infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells partially counteracted the protective effect of lung-stage infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.
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http://dx.doi.org/10.3389/fcell.2021.678377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217774PMC
June 2021

Selective delignification of poplar wood with a newly isolated white-rot basidiomycete Peniophora incarnata T-7 by submerged fermentation to enhance saccharification.

Biotechnol Biofuels 2021 Jun 12;14(1):135. Epub 2021 Jun 12.

Hunan Provincial Key Laboratory of Forestry Biotechnology, Central South University of Forestry and Technology, Changsha, 410004, Hunan, P.R. China.

Background: Pretreatment is a critical step required for efficient conversion of woody biomass into biofuels and platform chemicals. Fungal pretreatment is regarded as one of the most promising technology for woody biomass conversion but remains challenging for industrial application. The exploration of potential fungus strain with high efficient delignification and less processing time for woody biomass pretreatment will be valuable for development of biorefinery industry. Here, a newly isolated white-rot basidiomycete Peniophora incarnate T-7 was employed for poplar wood pretreatment.

Results: The chemical component analysis showed that cellulose, hemicellulose and lignin from poplar wood declined by 16%, 48% and 70%, respectively, after 7 days submerged fermentation by P. incarnate T-7. Enzymatic saccharification analysis revealed that the maximum yields of glucose and xylose from 7 days of P. incarnate T-7 treated poplar wood reached 33.4% and 27.6%, respectively, both of which were enhanced by sevenfold relative to the untreated group. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD) and pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) characterization confirmed that lignocellulosic structure of poplar wood was largely broken by P. incarnate T-7, including delignification and de-crystalline of cellulose. Meanwhile, lignin component of poplar wood was selectively degraded by P. incarnate T-7, and G-type unit of lignin was preferentially attacked by the strain. Furthermore, quantitative proteomic analysis revealed that a considerable amount of lignocellulolytic enzymes were detected in the secretory proteins of P. incarnate T-7, especially with high abundance of lignin-degrading enzymes and hemicellulases. Combination of quantitative proteomic with transcriptomic analysis results showed that most of those lignocellulolytic enzymes were highly upregulated on poplar wood substrate compared to glucose substrate.

Conclusions: This study showed that P. incarnate T-7 could selectively delignify poplar wood by submerged fermentation with short time of 7 days, which greatly improved its enzymatic saccharification efficiency. Our results suggested that P. incarnate T-7 might be a promising candidate for industrial woody biomass pretreatment.
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http://dx.doi.org/10.1186/s13068-021-01986-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199694PMC
June 2021

The Whitening Properties of the Mixture Composed of Pomegranate, Osmanthus and Olive and the Protective Effects Against Ultraviolet Deleterious Effects.

Clin Cosmet Investig Dermatol 2021 27;14:561-573. Epub 2021 May 27.

Infinitus Company Ltd, Guangzhou, People's Republic of China.

Background: Ultraviolet (UV) rays are the major environmental factor that damage skin physiology causing deleterious effects such as oxidation, photoaging and pigmentation. There has been considerable interest in using botanicals to prevent skin damages caused by UV irradiation.

Aim: In this study, three plant extracts were tested either individually or combined together (mixture) as well as their corresponding main active compound: pomegranate/punicalagin, osmanthus/verbascoside and olive/hydroxytyrosol. We evaluated the whitening and anti-photoaging properties of the nutritional mixture using 2D human culture model and a 3D full-thickness pigmented skin model exposed to UVB and UVA.

Methods: For exploring skin pigmentation, oxidation and aging, we performed cell viability, tyrosinase activity and melanin content assays as well as histology analysis (Whartin-Starry staining), immunodetection (PMEL, MDA, collagen type I and elastin) and carbonylated proteins analysis by electrophoresis separation.

Results: Results showed that the pomegranate extract and the active molecule punicalagin could reduce the tyrosinase activity and melanin content in melanocytes (P < 0.05). The mixture, pomegranate extract and punicalagin inhibited the melanin production and pre-melanosomal protein (PMEL) expression in the 3D skin pigmented model (P < 0.001). Furthermore, the mixture treatment repaired the expressions of collagen I and elastin decrease by UV exposure (P < 0.01). The mixture also significantly decreased lipid peroxidation (P < 0.001) and carbonylated proteins (P < 0.05) in the skin model compared to the UV-exposed condition.

Conclusion: To conclude, the mixture composed of pomegranate, osmanthus and olive extracts protects human skin from UV rays deleterious effects and exhibits antioxidative, anti-aging and skin whitening properties. Our data suggested pomegranate contributed to the whitening properties of the mixture notably through its main active compound, punicalagin. The mixture might be a good candidates for further development as natural antioxidant and skin care product.
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http://dx.doi.org/10.2147/CCID.S302997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168835PMC
May 2021
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