Publications by authors named "Xiong Li"

719 Publications

Metal- and Base-Free C(sp)-H Arylsulfonylation of Enamides for Synthesis of ()-β-Amidovinyl Sulfones via the Insertion of Sulfur Dioxide.

Org Lett 2021 Jun 11. Epub 2021 Jun 11.

Department of Dermatology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, P.R. China.

A metal- and base-free C(sp)-H direct arylsulfonylation of secondary and tertiary enamides with aryldiazonium salts and ex situ generated SO (from SOgen) is presented. This method runs smoothly to produce β-amidovinyl sulfones with excellent stereoselectivities in moderate to excellent yields. Moreover, this strategy features good functional group tolerance and environmentally benign reaction conditions. Mechanistic experiments indicate that this sulfonylation may proceed in a radical pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c01419DOI Listing
June 2021

Digestion & fermentation characteristics of sulfated polysaccharides from Gracilaria chouae using two extraction methods in vitro and in vivo.

Food Res Int 2021 Jul 11;145:110406. Epub 2021 May 11.

Faculty of Food Technology & Biotechnology, University of Zagreb, Prolaz Kasandrića 6, 23000 Zadar, Croatia.

The sulfated polysaccharides extracted from Gracilaria chouae using critic acid extraction and water extraction, respectively, and their digestion and fermentation characteristics were compared in vitro and in vivo. The molecular weight of water extracted polysaccharide of G. chouae (WGCP) was 1.73 × 10 kDa while critic acid extracted polysaccharide (CGCP) was 31.5 kDa. During stimulated gastrointestinal digestion in vitro, WGCP and CGCP were lightly degraded. However, the glycemic index (GI) of WGCP and CGCP were 17.7 and 36.12, respectively. After 24 h of fermentation in vitro, the pH values of CGLP in the fecal culture decreased from 6.89 to 4.82, similar to the inulin but significantly (p < 0.05) lower than those of the WGCP and normal control. In addition, CGCP and inulin showed similar microbial fermentation characteristics according to the microbiome compositions and contents of short-chain fatty acids (SCFAs). Nevertheless, CGCP gavage for four weeks could also promote the growth of microbes producing the SCFAs such as Peptococcus, Roseburia and Butyricicoccus in the cecum of KM mice. The present study suggests that polysaccharides prepared by acid-extraction method could potentially be used as a good source of prebiotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodres.2021.110406DOI Listing
July 2021

Comparative transcriptomics analysis reveals differential Cd response processes in roots of two turnip landraces with different Cd accumulation capacities.

Ecotoxicol Environ Saf 2021 Jun 5;220:112392. Epub 2021 Jun 5.

Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Xishuangbanna 666303, China. Electronic address:

Understanding the molecular mechanisms of cadmium (Cd) tolerance and accumulation in plants is important to address Cd pollution. In the present study, we performed comparative transcriptome analysis to identify the Cd response processes in the roots of two turnip landraces, KTRG-B14 (high-Cd accumulation) and KTRG-B36 (low-Cd accumulation). Two common enhanced processes, glutathione metabolism and antioxidant system, were identified in both landraces. However, some differential antioxidant processes are likely employed by two landraces, namely, several genes encoding peptide methionine sulfoxide reductases and thioredoxins were up-regulated in B14, whereas flavonoid synthesis was potentially induced to fight against oxidative stress in B36. In addition to the commonly upregulated ZINC INDUCED FACILITATOR 1-like gene in two landraces, different metal transporter-encoding genes identified in B14 (DETOXIFICATION 1) and B36 (PLANT CADMIUM RESISTANCE 2-like, probable zinc transporter 10, and ABC transporter C family member 3) were responsible for Cd accumulation and distribution in cells. Several genes that encode extensins were specifically upregulated in B14, which may improve Cd accumulation in cell walls or regulate root development to absorb more Cd. Meanwhile, the induced high-affinity nitrate transporter 2.1-like gene was also likely to contribute to the higher Cd accumulation in B14. However, Cd also caused some toxic symptoms in both landraces. Cd stress might inhibit iron uptake in both landraces whereas many apoenzyme-encoding genes were influenced in B36, which may be attributed to the interaction between Cd and other metal ions. This study provides novel insights into the molecular mechanism of plant root response to Cd at an early stage. The transporters and key enzymes identified in this study are helpful for the molecular-assisted breeding of low- or high-Cd-accumulating plant resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112392DOI Listing
June 2021

Diosmetin ameliorate type 2 diabetic mellitus by up-regulating Corynebacterium glutamicum to regulate IRS/PI3K/AKT-mediated glucose metabolism disorder in KK-Ay mice.

Phytomedicine 2021 Jun 3;87:153582. Epub 2021 Jun 3.

College of Pharmaceutical Sciences, Southwest University, No.2 Tiansheng Road, Beibei, Chongqing 400716, PR China. Electronic address:

Background And Purpose: Diosmetin (Dios), a flavonoid compound with multiple pharmacological activities. However, fewer studies have reported its effects on type 2 diabetic mellitus (T2DM). Here, we address the effect of Dios on glucose metabolism and gut microbiota in KK-Ay diabetic mice.

Method: Wild type C57BL/6 J mice or diabetic KK-Ay mice were treated with vehicle or Dios for one month. The ELISA kit and fluorescence microscope system were respectively employed to the evaluation of serum biochemical indicators and histopathological changes. Liver RNA-Seq and western blot were used to reveal the key signaling pathway. The effects of Dios on gut microbiota was investigated by the 16S rRNA gene sequencing, as well as the relationship between Dios and C. glu on glucose metabolism was explored with the C. glu transplantation.

Results: Dios treatment significantly decreased blood glucose and increased serum insulin concentrations. RNA-Seq analysis found that the underlying action mechanism of Dios on T2DM was via modulating glucose metabolism, which was proved by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. Besides, Dios treatment reshaped the unbalanced gut microbiota by suppressing the ratio of Firmicutes/Bacteroidetes and markedly increasing the richness of C. glu. Moreover, treatment with C. glu and Dios together could markedly ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation.

Conclusions: Dios treatment remarkably ameliorated glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu via IRS/PI3K/AKT signaling pathway and reshaped the unbalanced gut microbiota. Our study provided evidence for the application of Dios to the treatment of T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2021.153582DOI Listing
June 2021

Generalized Pancharatnam-Berry Phase in Rotationally Symmetric Meta-Atoms.

Phys Rev Lett 2021 May;126(18):183902

State Key Laboratory of Optical Technologies on Nano-Fabrication and Micro-Engineering, Institute of Optics and Electronics, Chinese Academy of Sciences, Chengdu 610209, China.

Pancharatnam-Berry geometric phase has attracted enormous interest in subwavelength optics and electromagnetics during the past several decades. Traditional theory predicts that the geometric phase is equal to twice the rotation angle of anisotropic elements. Here, we show that high-order geometric phases equal to multiple times the rotation angle could be achieved by meta-atoms with highfold rotational symmetries. As a proof of concept, the broadband angular spin Hall effect of light and optical vortices is experimentally demonstrated by using plasmonic metasurfaces consisting of space-variant nanoapertures with C2, C3, and C5 rotational symmetries. The results provide a fundamentally new understanding of the geometric phase as well as light-matter interaction in nanophotonics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevLett.126.183902DOI Listing
May 2021

Cyr61 from adipose-derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin α β.

Mol Oncol 2021 May 17. Epub 2021 May 17.

Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Adipose-derived stem cells (ADSCs) play a vital role in colorectal cancer (CRC) progression, but the mechanism remains largely unknown. Herein, we found that ADSCs isolated from CRC patients produced more cysteine-rich 61 (Cyr61) than those from healthy donors, and the elevated serum Cyr61 levels were associated with advanced TNM stages. Moreover, serum Cyr61 displayed a better diagnostic value for CRC compared to carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9). Mechanistically, integrin α β was identified as the functional receptor by which Cyr61 promotes CRC cell metastasis in vitro and in vivo by activating the α β /FAK/NF-κB signaling pathway. In addition, Cyr61 promotes vasculogenic mimicry (VM) formation, thereby promoting tumor growth and metastasis through a α β /FAK/HIF-1α/STAT3/MMP2 signaling cascade. Histologically, xenografts and clinical samples of CRC both exhibited VM, which was correlated with HIF-1α and MMP2 activation. Notably, we demonstrated the synergistic effect of combined anti-VM therapy (integrin α β inhibitor) and anti-VEGF therapy (bevacizumab) in patient-derived xenograft models. Further investigation showed that CRC cell-derived exosomal STAT3 promoted Cyr61 transcription in ADSCs. These findings indicate that Cyr61 derived from ADSCs plays a critical role in promoting CRC progression via integrin α β and provides a novel antitumor strategy by targeting Cyr61/α β .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1878-0261.12998DOI Listing
May 2021

KIF11 is upregulated in colorectal cancer and silencing of it impairs tumor growth and sensitizes colorectal cancer cells to oxaliplatin via p53/GSK3β signaling.

J Cancer 2021 3;12(12):3741-3753. Epub 2021 May 3.

Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Colorectal cancer (CRC) is the most frequently diagnosed cancer of the digestive tract. Chemotherapy drugs such as oxaliplatin are frequently administered to CRC patients diagnosed with advanced or metastatic disease. A deep understanding of the molecular mechanism underlying CRC tumorigenesis and identification of optimal biomarkers for estimating chemotherapy sensitivity are essential for the treatment of CRC. Numerous members of the kinesin family are dysregulated in cancers, contributing to tumorigenesis, metastasis and drug resistance. KIF11 is a key component of the bipolar spindle and is highly expressed in several cancer types. We analyzed KIF11 expression in clinical samples by Western blotting and qRT-PCR and explored its role and mechanism in CRC growth and sensitivity to oxaliplatin via detection of the phosphorylation profile of kinases and gain-and-loss-of-function assays. We found that KIF11 was upregulated in CRC tissues and was associated with advanced clinical stage and vessel invasion and that knockdown of KIF11 led to tumor growth arrest and increased sensitivity to oxaliplatin via enhanced DNA damage and apoptosis. Mechanistically, aberrantly activated p53 signaling or possibly deactivated GSK3β signaling was responsible for KIF11 knockdown-mediated effects in CRC cells. Thus, our data firmly demonstrated that KIF11 could serve as a potential oncogene and proper biomarker for assessing oxaliplatin sensitivity in CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.52103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120193PMC
May 2021

A layer-by-layer assembled D/L-arginine-calix[4]arene-Si-surface for macroscopic enantio-selective discrimination of ()/()-ibuprofen.

Chem Commun (Camb) 2021 Jun;57(46):5706-5709

Key Laboratory of Pesticide and Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.

Chiral arginine was introduced by layer-by-layer assembly onto a calix[4]arene-diacid modified silica surface to control the adsorption of different kinds of ibuprofen droplets. The droplet of (S)-ibuprofen slid off rapidly, whereas the droplet of (R)-ibuprofen absorbed on the modified surface.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc01307fDOI Listing
June 2021

LINC-PINT impedes DNA repair and enhances radiotherapeutic response by targeting DNA-PKcs in nasopharyngeal cancer.

Cell Death Dis 2021 May 7;12(5):454. Epub 2021 May 7.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008, Changsha, P. R. China.

Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03728-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105365PMC
May 2021

LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy.

Nat Cell Biol 2021 May 6;23(5):526-537. Epub 2021 May 6.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8 T cells and triggers anti-tumour immunity. Humans may have 30,000-60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Here, we identify a lncRNA, lncRNA inducing MHC-I and immunogenicity of tumour (LIMIT), in humans and mice. We found that IFNγ stimulated LIMIT, LIMIT cis-activated the guanylate-binding protein (GBP) gene cluster and GBPs disrupted the association between HSP90 and heat shock factor-1 (HSF1), thereby resulting in HSF1 activation and transcription of MHC-I machinery, but not PD-L1. RNA-guided CRISPR activation of LIMIT boosted GBPs and MHC-I, and potentiated tumour immunogenicity and checkpoint therapy. Silencing LIMIT, GBPs and/or HSF1 diminished MHC-I, impaired antitumour immunity and blunted immunotherapy efficacy. Clinically, LIMIT, GBP- and HSF1-signalling transcripts and proteins correlated with MHC-I, tumour-infiltrating T cells and checkpoint blockade response in patients with cancer. Together, we demonstrate that LIMIT is a cancer immunogenic lncRNA and the LIMIT-GBP-HSF1 axis may be targetable for cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41556-021-00672-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122078PMC
May 2021

Rh(III)-Catalyzed Csp-Csp σ-Bond Enolation of α-Indolyl Alcohols.

Org Lett 2021 May 6;23(10):3965-3969. Epub 2021 May 6.

Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China.

A Rh(III)-catalyzed Csp-Csp σ-bond carbenoid functionalization of α-(2-indolyl)alcohols with acceptor/acceptor diazo compounds has been developed. This transformation provides an efficient strategy to assemble stable C2-enolated indole skeletons via Csp-Csp σ-bond cleavage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c01132DOI Listing
May 2021

Assessment of retroperitoneal lymph node status in locally advanced cervical cancer.

BMC Cancer 2021 May 1;21(1):484. Epub 2021 May 1.

Department of Gynecology, Hunan Maternal and Child Health Hospital, Changsha, Hunan, China.

Background: The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods.

Methods: Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed.

Results: The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD < 1.0 cm group (26.82%). The critical values of MAD and SCC-Ag in determining lymph node metastasis were 1.0 cm and 5.2 ng/mL, respectively. The accuracy, specificity, and Youden index of MAD ≥1.0 cm combined with SCC-Ag ≥ 5.2 ng/mL for evaluating lymph node metastasis were 75.71%, 100%, and 0.59, respectively, and were significantly different from the values for the MAD ≥1.0 cm (72.09%, 80.56%, and 0.47, respectively) and SCC-Ag ≥ 5.2 ng/mL (71.43%, 68.97%, and 0.42, respectively) groups. Correlation analysis showed that non-squamous cell carcinoma, pelvic lymph node (PLN) MAD ≥1.0 cm plus number ≥ 2, and 1 PLN MAD ≥1.0 cm with CILN and/or PALN MAD 0.5-1.0 cm were risk factors for CILN and/or PALN metastasis.

Conclusion: Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD < 1.0 cm and SCC-Ag < 5.2 ng/mL may be treated with chemoradiotherapy directly based on imaging, given the low lymph node metastasis rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08208-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088051PMC
May 2021

Rs2686344 and serum squamous cell carcinoma antigen could predict clinical efficacy of neoadjuvant chemotherapy for cervical cancer.

Curr Probl Cancer 2021 Apr 18:100755. Epub 2021 Apr 18.

Department of Gynecology & Obstetrics, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China. Electronic address:

Objective: To evaluate the predictive value of a single nucleotide polymorphism (SNP) rs2686344 and squamous cell carcinoma antigen (SCCAg) levels in the clinical efficacy of neoadjuvant chemotherapy (NACT) for cervical cancer.

Methods: A total of 92 patients with stage IB2-IIIB carcinoma of the uterine cervix who received NACT treatment were enrolled. The relationship between the genotypes of SNP rs2686344 which is located on CAMKK2 on chromosome 12, SCCAg levels and the response to NACT was analyzed. The relationship between the SNP rs2686344 genotypes, SCCAg levels, the response to NACT and the five-year survival rate was evaluated.

Results: The effective group accounted for 84.85% in patients with low level (≤3.5 ng/mL) of post-treatment SCCAg (post-SCCAg), while the ineffective group accounted for 15.15%. The post-SCCAg levels and the genotypes of rs2686344 were significantly correlated with NACT response (P = 0.003, and P = 0.006). In patients with CC or CT genotype of SNP rs2686344, effective group accounted for 81.18%, while ineffective group accounted for 18.82%; For patients with TT genotype, effective response group accounted for 28.57%, ineffective group accounted for 71.43%. Post-SCCAg level >3.5 ng/mL and TT genotype of SNP rs2686344 showed as independent risk factors for NACT response in the multivariate analysis (P = 0.002, and P = 0.048). There was no significant difference in 5-year overall survival and 5-year disease-free survival between patients with different levels of post-SCCAg, or among different rs2686344 genotypes.

Conclusion: The high level of post-SCCAg (>3.5 ng/mL) and TT genotype of rs2686344 may suggest a higher risk of poor response to NACT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.currproblcancer.2021.100755DOI Listing
April 2021

A novel mutation of WFS1 gene leading to increase ER stress and cell apoptosis is associated an autosomal dominant form of Wolfram syndrome type 1.

BMC Endocr Disord 2021 Apr 21;21(1):76. Epub 2021 Apr 21.

Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, P. R. China.

Background: Wolfram syndrome (WS) is a rare autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Mutations in Wolfram syndrome 1 (WFS1) gene may cause dysregulated endoplasmic reticulum (ER)-stress and cell apoptosis, contributing to WS symptoms. The aim of this study was to identify the molecular etiology of a case of WS and to explore the functional consequence of the mutant WFS1 gene in vitro.

Methods: A 27 years-old Chinese man was diagnosed as wolfram syndrome type 1 based on clinical data and laboratory data. DNA sequencing of WFS1 gene and mitochondrial m.3337G > A, m.3243A > G mutations were performed in the patient and his 4 family members. Functional analysis was performed to assessed the in vitro effect of the newly identified mutant. ER stress were evaluated by ER stress response element (ERSE)-luciferase assay. Cell apoptosis were performed by CCK-8, TUNEL staining and flow cytometric analysis.

Results: A novel heterozygous 10-base deletion (c. 2067_2076 del10, p.W690fsX706) was identified in the patient. In vitro studies showed that mutant p.W690fsX706 increased ERSE reporter activity in the presence or absence of thapsigargin instead of wild type WFS1. Knockdown of WFS1 activated the unfolded protein response (UPR) pathway and increased the cell apoptosis, which could not be restored by transfection with WFS1 mutant (p.W690fsX706) comparable to the wild type WFS1.

Conclusions: A novel heterozygous mutation of WFS1 detected in the patient resulted in loss-of-function of wolframin, thereby inducing dysregulated ER stress signaling and cell apoptosis. These findings increase the spectrum of WFS1 gene mutations and broaden our insights into the roles of mutant WFS1 in the pathogenesis of WS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12902-021-00748-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059287PMC
April 2021

Early immune responses and prognostic factors in children with COVID-19: a single-center retrospective analysis.

BMC Pediatr 2021 04 17;21(1):181. Epub 2021 Apr 17.

Department of Hematology, Wuhan Children's Hospital (Wuhan Medical Care Center for Women and Children), Tongji College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: Early diagnostic indicators and the identification of possible progression to severe or critical COVID-19 in children are unknown. To investigate the immune characteristics of early SARS-CoV-2 infection in children and possible key prognostic factors for early identification of critical COVID-19, a retrospective study including 121 children with COVID-19 was conducted. Peripheral blood lymphocyte subset counts, T cell-derived cytokine concentrations, inflammatory factor concentrations, and routine blood counts were analyzed statistically at the initial presentation.

Results: The T lymphocyte subset and natural killer cell counts decreased with increasing disease severity. Group III (critical cases) had a higher Th/Tc ratio than groups I and II (common and severe cases); group I had a higher B cell count than groups II and III. IL-6, IL-10, IFN-γ, SAA, and procalcitonin levels increased with increasing disease severity. Hemoglobin concentration, and RBC and eosinophil counts decreased with increasing disease severity. Groups II and III had significantly lower lymphocyte counts than group I. T, Th, Tc, IL-6, IL-10, RBC, and hemoglobin had relatively high contribution and area under the curve values.

Conclusions: Decreased T, Th, Tc, RBC, hemoglobin and increased IL-6 and IL-10 in early SARS-CoV-2 infection in children are valuable indices for early diagnosis of severe disease. The significantly reduced Th and Tc cells and significantly increased IL-6, IL-10, ferritin, procalcitonin, and SAA at this stage in children with critical COVID-19 may be closely associated with the systemic cytokine storm caused by immune dysregulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-021-02561-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052550PMC
April 2021

Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma.

Theranostics 2021 13;11(11):5464-5490. Epub 2021 Mar 13.

Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. Sorafenib is an oral kinase inhibitor that inhibits tumor cell proliferation and angiogenesis and induces cancer cell apoptosis. It also improves the survival rates of patients with advanced liver cancer. However, due to its poor solubility, fast metabolism, and low bioavailability, clinical applications of sorafenib have been substantially restricted. In recent years, various studies have been conducted on the use of nanoparticles to improve drug targeting and therapeutic efficacy in HCC. Moreover, nanoparticles have been extensively explored to improve the therapeutic efficacy of sorafenib, and a variety of nanoparticles, such as polymer, lipid, silica, and metal nanoparticles, have been developed for treating liver cancer. All these new technologies have improved the targeted treatment of HCC by sorafenib and promoted nanomedicines as treatments for HCC. This review provides an overview of hot topics in tumor nanoscience and the latest status of treatments for HCC. It further introduces the current research status of nanoparticle drug delivery systems for treatment of HCC with sorafenib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.54822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039945PMC
March 2021

Super-oscillatory metasurface doublet for sub-diffraction focusing with a large incident angle.

Opt Express 2021 Mar;29(7):9991-9999

Based on the delicate interference behavior of light in the far field, the optical super-oscillatory phenomenon has been successfully applied in non-invasive sub-diffraction focusing and super-resolution imaging in recent years. However, the optical super-oscillatory field is particularly sensitive to the change of incident angle, leading to a limited field of view for super-resolution imaging. In this paper, a super-oscillatory metasurface doublet is proposed to achieve far-field sub-diffraction focusing with an incident angle of up to 25°. The constructed doublet, consisting of high-aspect-ratio rectangular nanopillars with high efficiency, is further demonstrated through a full-wave simulation, and the numerical results indicate that the sub-diffraction foci with about 0.75 times of the diffraction limit is achieved for different incident angles. The proposed super-oscillatory metasurface doublet may find intriguing applications in label-free super-resolution microscopy and optical precise fabrication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.417884DOI Listing
March 2021

Topology-optimized catenary-like metasurface for wide-angle and high-efficiency deflection: from a discrete to continuous geometric phase.

Opt Express 2021 Mar;29(7):10181-10191

We investigate the topology optimization of geometric phase metasurfaces for wide-angle and high-efficiency deflection, where adjoint-based multi-object optimization approach is adopted to improve the absolute efficiency while maintaining the polarization conversion characteristic of geometric phase metasurfaces. We show that, for the initially discrete geometric phase metasurfaces with different materials and working wavelengths, the topology shapes gradually evolve from discrete structures to quasi-continuous arrangements with the increment of optimization iteration operations. More importantly, the finally optimized metasurfaces manifest as catenary-like structure, providing significant improvements of absolute efficiency. Furthermore, for the initial structure with catenary distribution, the corresponding optimized metasurface also has a catenary-like topology shape. Our results on the topology-optimized geometric phase metasurfaces reveal that, from the perspective of numerical optimization, the continuous catenary metasurfaces is superior to the discrete geometric phase metasurfaces.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.422112DOI Listing
March 2021

VEGF/Src signaling mediated pleural barrier damage and increased permeability contributes to subpleural pulmonary fibrosis.

Am J Physiol Lung Cell Mol Physiol 2021 Jun 31;320(6):L990-L1004. Epub 2021 Mar 31.

Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson's and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajplung.00436.2020DOI Listing
June 2021

Sucrose enhanced reactive oxygen species generation promotes cotton fibre initiation and secondary cell wall deposition.

Plant Biotechnol J 2021 Jun 2;19(6):1092-1094. Epub 2021 Jun 2.

Chongqing Key Laboratory of Application and Safety Control of Genetically Modified Crops, Biotechnology Research Center, Southwest University, Chongqing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pbi.13594DOI Listing
June 2021

Six genes involved in prognosis of hepatocellular carcinoma identified by Cox hazard regression.

BMC Bioinformatics 2021 Mar 30;22(1):167. Epub 2021 Mar 30.

Shenzhen Center for Chronic Disease Control, Shenzhen, People's Republic of China.

Background: Hepatocellular carcinoma (HCC), derived from hepatocytes, is the main histological subtype of primary liver cancer and poses a serious threat to human health due to the high incidence and poor prognosis. This study aimed to establish a multigene prognostic model to predict the prognosis of patients with HCC.

Results: Gene expression datasets (GSE121248, GSE40873, GSE62232) were used to identify differentially expressed genes (DEGs) between tumor and adjacent or normal tissues, and then hub genes were screened by protein-protein interaction (PPI) network and Cytoscape software. Seventeen genes among hub genes were significantly associated with prognosis and used to construct a prognostic model through COX hazard regression analysis. The predictive performance of this model was evaluated with TCGA data and was further validated with independent dataset GSE14520. Six genes (CDKN3, ZWINT, KIF20A, NUSAP1, HMMR, DLGAP5) were involved in the prognostic model, which separated HCC patients from TCGA dataset into high- and low-risk groups. Kaplan-Meier (KM) survival analysis and risk score analysis demonstrated that low-risk group represented a survival advantage. Univariate and multivariate regression analysis showed risk score could be an independent prognostic factor. The receiver operating characteristic (ROC) curve showed there was a better predictive power of the risk score than that of other clinical indicators. At last, the results from GSE14520 demonstrated the reliability of this prognostic model in some extent.

Conclusion: This prognostic model represented significance for prognosis of HCC, and the risk score according to this model may be a better prognostic factor than other traditional clinical indicators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12859-021-04095-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011138PMC
March 2021

Next-Generation Sequencing Is More Efficient at Detecting Mosaic Embryos and Improving Pregnancy Outcomes than Single-Nucleotide Polymorphism Array Analysis.

J Mol Diagn 2021 06 26;23(6):710-718. Epub 2021 Mar 26.

Shanghai Ji Ai Genetics and In Vitro Fertilization Institute, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Berry Genomics Corp., Beijing, China; Key Laboratory of Female Reproductive Endocrine-Related Diseases, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. Electronic address:

We compared chromosomal mosaicism, detected by next-generation sequencing (NGS), during preimplantation genetic testing (PGT) with that detected by single-nucleotide polymorphism (SNP) array-based PGT to assess the pregnancy outcomes associated with both platforms in a retrospective cohort study of patients undergoing in vitro fertilization in a single university-based assisted reproduction center. In total, 6427 blastocysts biopsied from 1513 patients who underwent 2833 oocyte retrievals from January 2017 to February 2019 were identified. The incidence of mosaicism was significantly higher in the NGS-based PGT group than in the SNP array-based PGT group. Furthermore, some aneuploid specimens were affected by mosaicism. The total mosaicism detection rate with NGS-based PGT (23.3%) was significantly higher than that with SNP array-based PGT (7.7%). Mosaicism rates were similar when stratified by maternal age or PGT type. The SNP array cohort showed a significantly higher spontaneous abortion rate than the NGS cohort (10.07% versus 6.33%; P = 0.0403). The ongoing pregnancy/live birth rate was higher in the NGS cohort (44.1%) than in the SNP array cohort (42.28%). Our results confirm that NGS-based PGT can detect mosaicism more frequently than SNP array-based PGT in trophectoderm specimens. Therefore, clinical application of NGS for PGT may improve pregnancy outcomes compared with that of SNP array-based PGT. More detailed blastocyst detection and classification is necessary to prioritize embryo transfers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmoldx.2021.02.011DOI Listing
June 2021

The ubiquitin ligase MDM2 sustains STAT5 stability to control T cell-mediated antitumor immunity.

Nat Immunol 2021 Apr 25;22(4):460-470. Epub 2021 Mar 25.

Department of Surgery, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.

Targeting the p53-MDM2 pathway to reactivate tumor p53 is a chemotherapeutic approach. However, the involvement of this pathway in CD8 T cell-mediated antitumor immunity is unknown. Here, we report that mice with MDM2 deficiency in T cells exhibit accelerated tumor progression and a decrease in tumor-infiltrating CD8 T cell survival and function. Mechanistically, MDM2 competes with c-Cbl for STAT5 binding, reduces c-Cbl-mediated STAT5 degradation and enhances STAT5 stability in tumor-infiltrating CD8 T cells. Targeting the p53-MDM2 interaction with a pharmacological agent, APG-115, augmented MDM2 in T cells, thereby stabilizing STAT5, boosting T cell immunity and synergizing with cancer immunotherapy. Unexpectedly, these effects of APG-115 were dependent on p53 and MDM2 in T cells. Clinically, MDM2 abundance correlated with T cell function and interferon-γ signature in patients with cancer. Thus, the p53-MDM2 pathway controls T cell immunity, and targeting this pathway may treat patients with cancer regardless of tumor p53 status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41590-021-00888-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026726PMC
April 2021

Boosted multi-polarization from [email protected] doped with modifier cations for superior microwave absorption.

J Colloid Interface Sci 2021 Jul 10;593:96-104. Epub 2021 Mar 10.

School of Materials Science and Engineering, Shandong University of Technology, Zibo 255000, China.

Multi-polarization structural design was proved to be a resultful strategy to achieve superior microwave absorbers but limited by the low dielectric properties. In this work, silicate-glasses (SG) nanoparticles doped with different modifier cations (M) have been synthesized by the sol-gel method. Modified silicate-glasses (M-SG) nanoparticles were loaded on reduce graphene oxide (rGO) nanosheets through hydrothermal possess and high-temperature calcination with adding a silane coupling agent (KH-550). The dielectric loss and impedance matching were improved through the synergistic effect of rGO and M-SG. The microwave absorption (MA) performance of [email protected] has been highly boosted, and the minimum reflection loss (RL) is -69.2 dB with a thickness of 2.8 mm. Meanwhile, the X-band and Ku-band absorption can also be obtained with specific M-SG loading at a particular thickness. The results demonstrate that the effects of dipole polarization and interface polarization all play a vital role in improving the microwave absorption performance of [email protected] absorbers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.03.007DOI Listing
July 2021

[Cadmium Accumulation Characteristics of Four Herbs].

Huan Jing Ke Xue 2021 Feb;42(2):960-966

Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.

A pot-based experiment was conducted to study the Cd tolerance and accumulation characteristics of four invasive herbs (, and ) under exposures of 0 (T0), 5 (T5), 25 (T25), and 50 mg·kg (T50) soil Cd concentrations to screen for potential Cd accumulators for phytoremediation. The results showed that the biomasses of both shoots and roots of had no significant changes compared to the control (T0) samples under all Cd treatments, whereas the biomass of the other three Poaceae species significantly decreased under the T25 or T50 treatment. The results indicate that had stronger Cd tolerance than the other three species. The Cd concentrations in the shoots and roots of the four herbs significantly increased with an increase in soil Cd concentrations, but the shoot bioconcentration factors (SBCF) of the four plant species significantly decreased under T5, T25, and T50 treatment. The SBCF of and were greater than 1 whereas those of and were lower than 1. The translocation factors (TF) of were 0.93, 0.73, and 1.04 under T5, T25, and T50 treatment, respectively, which were significantly higher than those of the other three plants under the same soil Cd concentration. In addition, both the total Cd and shoot Cd contents of were notably higher than in the other three species under the same Cd treatment. Moreover, 90% of the Cd in could be transferred aboveground, which was significantly higher than for the other three plants. Based on our comprehensive comparison of Cd tolerance and accumulation capacity, we suggest that is a high-Cd accumulator with considerable phytoremediation potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13227/j.hjkx.202007034DOI Listing
February 2021

Broadband achromatic metasurfaces for sub-diffraction focusing in the visible.

Opt Express 2021 Feb;29(4):5947-5958

Conventional achromatic optical systems are matured to achieve effective chromatic aberration correction and diffraction-limited resolution by the multiple bulky lenses. The emergence of the super-oscillation phenomenon provides an effective method for non-invasive far-field super-resolution imaging. Nevertheless, most super-oscillatory lenses are significantly restricted by the chromatic aberration due to the reliance on delicate interference; on the other hand, most achromatic lenses cannot break the diffraction limit. In this article, a single-layer broadband achromatic metasurface comprising sub-wavelength anisotropic nanostructures has been proposed to achieve sub-diffraction focusing with a focal length of f=60 µm and a diameter of 20 µm in the visible ranging from 400 nm to 700 nm, which are capable of generating sub-diffraction focal spots under the left-handed circularly polarized incident light with arbitrary wavelength in the working bandwidth at the same focal plane. This method may find promising potentials in various applications such as super-resolution color imaging, light field cameras, and machine vision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.417036DOI Listing
February 2021

Towards the elimination of leprosy in Yunnan, China: A time-series analysis of surveillance data.

PLoS Negl Trop Dis 2021 Mar 16;15(3):e0009201. Epub 2021 Mar 16.

Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Background: This study reviews the progress of leprosy elimination in Yunnan, China, over the past 30 years and identifies the challenges for the next stage of the program.

Methodology/principal Findings: Data were collected from the Leprosy Management Information System in China (LEPMIS). The progress made in the elimination of leprosy between 1990 and 2019 was measured. We defined two time periods, time period 1 (1990-2003) and time period 2 (2004-2019), because multidrug therapy (MDT) was launched for the treatment of leprosy in 1990 and a special fund from the central government was established for leprosy in 2004. During the past 30 years, the number of newly detected leprosy patients in Yunnan has steadily declined. In total, 703 newly detected leprosy patients were reported in 1990, and 353 and 136 cases were reported at the end of 2003 and 2019, respectively. At the end of 1990, 90.7% (117/129) of counties in Yunnan Province were identified as leprosy-endemic counties (>1 case per 100,000 population). By the end of 2003 and 2019, 39.3% (46/117) and 85.5% (100/117) of the leprosy-endemic counties, respectively, had dropped below the elimination threshold. The main challenges are the remaining leprosy-endemic counties, the high rate of cases with a contact history, insufficient early detection, and leprosy cases resulting in physical disability.

Conclusions/significance: A multifaceted strategy for leprosy elimination in Yunnan Province has been successfully implemented, and remarkable progress has been made in the elimination of leprosy in this area. The priorities for leprosy elimination in the next stage are securing sustainable support and investment from the government, establishing an effective surveillance system, ensuring prompt early detection, providing treatment with MDT, preventing transmission of M. leprae, preventing disability, providing health education, and preventing recurrence of the epidemic situation of leprosy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0009201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963107PMC
March 2021

Rational Design of Dual-Emission Lanthanide Metal-Organic Framework for Visual Alkaline Phosphatase Activity Assay.

ACS Appl Mater Interfaces 2021 Mar 8;13(10):11646-11656. Epub 2021 Mar 8.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.

The alkaline phosphatase (ALP) activity assay is very significant for disease diagnosis and biomedical research. Lanthanide metal-organic framework (Ln-MOF) based fluorescence sensors have great application potential in ALP activity assays. However, it is critical but challenging to investigate the emission law of Ln-MOFs for revealing rational design principles and selecting an appropriate MOF. Here, we describe a reasonable design strategy for dual-emission Ln-MOFs based on theoretical calculations. This strategy combines Reinhoudt empirical rule, intramolecular charge transfer theory, and aggregation/coordination-induced emission theory; reveals the luminescence law of Ln-MOFs; and provides theoretical guidance for the rational design of dual-emission Ln-MOFs. On the basis of this strategy, we create a dual-emission Tb-MOF fluorescent probe used for ALP activity assay and investigate the detection mechanism. The probe shows ultrasensitive (limit of detection 0.002 mU mL) and selective response to ALP, and it suits for point-of-care visual detection coupled with a self-designed portable enzyme activity assay kit and smartphone-assisted visual device. The kit-based visual assay method can accurately quantify the activity of ALP in real serum samples (recovery >93%, and relative error is less than 6.8% compared with the results of fluorescence spectrometer-based method) and consumes only 25 μL of serum. In addition, a logical decoder based on the "dual-key unlocking strategy" is designed, providing a feasible solution for the development of intelligent ALP activity detection equipment. As far as we know, this is the first report of a theoretical calculation-guided versatile design strategy for dual-emission Ln-MOFs and a portable enzyme activity assay kit for visual detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c00134DOI Listing
March 2021

Construction of a Cu-Sn Heterojunction Interface Derived from a Schottky Junction in [email protected]/rGO Composites as a Highly Efficient Dielectric Microwave Absorber.

ACS Appl Mater Interfaces 2021 Mar 8;13(10):11911-11919. Epub 2021 Mar 8.

School of Materials Science and Engineering, Shandong University of Technology, Zibo 255000, China.

Developing high-performance dielectric absorbers, low filler loading, and a broad absorption band remains a great challenge for wireless data communication systems, household appliances, local area network, and so on. Herein, we report a facile green method to design and fabricate a copper-coated tin/reduced graphene oxide ([email protected]/rGO) composites with a heterojunction obtained by modifying a Schottky junction. The unique heterojunction can enable an appropriate balance between impedance and strong loss capacity. Meanwhile, it can not only promote the carrier migration but also obtain the rich interfaces. Consequently, a [email protected]/rGO composite with a heterojunction exhibits superior absorption intensity, far surpassing that of other absorbing materials reported. With a weight content of only 5 wt %, the maximum absorptivity reaches -49.19 dB at 6.08 GHz, and an effective absorption bandwidth (RL < -10 dB) of 13.94 GHz is achieved when the absorber's thickness ranges from 1.7 to 5.5 mm. This study provides new insights into the design and synthesis of a novel microwave absorption material with lightweight, smaller filler loading, and strong reflection loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c22049DOI Listing
March 2021

Quasi-Continuous Metasurface Beam Splitters Enabled by Vector Iterative Fourier Transform Algorithm.

Materials (Basel) 2021 Feb 21;14(4). Epub 2021 Feb 21.

State Key Laboratory of Optical Technologies on Nano-Fabrication and Micro-Engineering, Institute of Optics and Electronics, Chinese Academy of Sciences, P.O. Box 350, Chengdu 610209, China.

Quasi-continuous metasurfaces are widely used in various optical systems and their subwavelength structures invalidate traditional design methods based on scalar diffraction theory. Here, a novel vector iterative Fourier transform algorithm (IFTA) is proposed to realize the fast design of quasi-continuous metasurface beam splitters with subwavelength structures. Compared with traditional optimization algorithms that either require extensive numerical simulations or lack accuracy, this method has the advantages of accuracy and low computational cost. As proof-of-concept demonstrations, several beam splitters with custom-tailored diffraction patterns and a 7 × 7 beam splitter are numerically demonstrated, among which the maximal diffraction angle reaches 70° and the best uniformity error reaches 0.0195, showing good consistency with the target energy distribution and these results suggest that the proposed vector IFTA may find wide applications in three-dimensional imaging, lidar techniques, machine vision, and so forth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma14041022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926747PMC
February 2021