Publications by authors named "Yichen Li"

81 Publications

Is Bariatric Surgery Effective for Chinese Patients with Type 2 Diabetes Mellitus and Body Mass Index < 35 kg/m? A Systematic Review and Meta-analysis.

Obes Surg 2021 Jul 10. Epub 2021 Jul 10.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215123, China.

Background: Bariatric surgery has been applied for weight loss and comorbidity control in China since 2000. Recent studies have shown positive results for bariatric surgery in patients with a body mass index (BMI) of less than 35 kg/m. However, the effect of surgery on Chinese patients with type II diabetes mellitus (T2DM) has not yet been systematically investigated.

Methods: A comprehensive literature search was performed in the Cochrane Library, Embase, PubMed, and Web of Science from January 2014 to March 2020. All studies examined bariatric surgery outcomes on Chinese patients at 12-, 36-, and 60-month follow-up. The research followed the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) recommendations.

Results: Eleven studies containing 611 patients were included in this meta-analysis. Clinical indices at 12-, 36-, and 60-month follow-up were analyzed. Significant decreases were identified in body weight, BMI, waist circumference (WC), blood pressure (BP), fasting plasma glucose (FPG), glycosylated hemoglobin A1c (hemoglobin A1c, or HbA1c), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) postoperatively. An increasing trend in the T2DM remission rate was discovered. The remission group was observed to have significantly lower HbA1c and C-peptide level, a shorter duration of T2DM, and a higher BMI than the nonremission group at 12 months.

Conclusions: Bariatric surgery successfully provided significant BMI control as well as a reduction and normalization of glucose- and lipid-related metabolism at 12, 36, and 60 months postoperatively in Chinese patients with T2DM with a preoperative BMI of less than 35 kg/m. An increasing trend in the T2DM remission rate suggested promising future applications in this population.
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http://dx.doi.org/10.1007/s11695-021-05520-9DOI Listing
July 2021

ORMDL1 is upregulated and associated with favorable outcomes in colorectal cancer.

Transl Oncol 2021 Jul 6;14(10):101171. Epub 2021 Jul 6.

Guangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China. Electronic address:

Background: The ORMDL1 gene is known as a crucial negative regulator of sphingolipid biogenesis. However, the ORMDL1 gene has rarely been studied in a tumor-related context. Therefore, its prognostic value and functional significance in colorectal cancer (CRC) remain to be explored.

Methods: TCGA CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the ORMDL1 expression level. The association between ORMDL1 expression and various clinical characteristics was analyzed by chi-square tests. The overall survival (OS) of CRC patients was analyzed by Kaplan-Meier analysis. In vitro and in vivo cell-based assays were performed to explore the role of ORMDL1 in cell proliferation, invasion and migration. Transcriptional changes in cells with either ORMDL1 knockdown or overexpression were compared and analyzed.

Results: ORMDL1 was upregulated in CRC tissues in both the TCGA and our cohort. Interestingly, its expression was significantly lower in patients with metastasis than in patients without metastasis, and the high expression group had longer OS than the low expression group. Knockdown of ORMDL1 expression can promote proliferation, colony formation and invasion, while attenuating migration in CRC cell lines. In contrast, forced overexpression of ORMDL1 reduced cell proliferation, colony formation and invasion, while enhancing cell migration. Stable knockdown of ORMDL1 can promote cancer cell proliferation in vivo to some extent. Finally, Rho GTPase activity was influenced by ORMDL1, and the expression of ORMDL1 was enhanced by DTT treatment.

Conclusion: ORMDL1 is upregulated and may serve as a biomarker to predict favourable outcomes in colorectal cancer.
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http://dx.doi.org/10.1016/j.tranon.2021.101171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273222PMC
July 2021

Hsp70 chaperones TDP-43 in dynamic, liquid-like phase and prevents it from amyloid aggregation.

Cell Res 2021 Jul 8. Epub 2021 Jul 8.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.

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http://dx.doi.org/10.1038/s41422-021-00526-5DOI Listing
July 2021

Assessment of the necessity of frontal sinostomy in cases of frontal sinusitis associated with fungus ball of the maxillary sinus.

Eur Arch Otorhinolaryngol 2021 Jun 15. Epub 2021 Jun 15.

Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, Anhui, China.

Purpose: This study was conducted to evaluate outcomes in patients presenting with fungus ball of the maxillary sinus (MSFB) and frontal sinusitis who were treated via middle meatal antrostomy alone.

Methods: This was a randomized, controlled study with a parallel group design. Patients with MSFB and frontal sinusitis were randomly assigned to the maxillary middle meatal antrostomy (MMMA) or control (MMMA + frontal sinusotomy) groups. Patient demographics, complaints, imaging findings were analyzed, and surgical outcomes were evaluated using the Lund-Kennedy endoscopic score (LKES) and the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire.

Results: In total, 40 patients were separated into two groups, with similar symptoms including nasal obstruction, mucopurulent rhinorrhea, maxillary or frontal pain, blood stained nasal discharge, nasal cacosmia and orbital pain being observed in both groups. Total LKES and SNOT-22 scores were significantly improved in both groups at 6 months post-treatment, with no significant differences in these scores between groups within a mean 6.8-month follow-up.

Conclusion: These results suggest that frontal sinusotomy is not required to resolve frontal sinusitis associated with MSFB. As such frontal sinusitis appears to be a reactive process caused by fungal ball obstruction, it regresses spontaneously following fungus ball removal, drainage of the maxillary sinus, and middle meatal antrostomy.
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http://dx.doi.org/10.1007/s00405-021-06933-zDOI Listing
June 2021

Preclinical Investigation of Alpinetin in the Treatment of Cancer-Induced Cachexia Activating PPARγ.

Front Pharmacol 2021 21;12:687491. Epub 2021 May 21.

Department of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

The ongoing loss of skeletal muscle is a central event of cancer cachexia, and its consequences include adverse effects on patient's quality of life and survival. Alpinetin (Alp), a natural plant-derived flavonoid obtained from Hayata, has been reported to possess potent anti-inflammatory and antitumor activities. This study aimed to explore the therapeutic effect and underlying mechanism of Alp in the prevention of cancer cachexia. We found that Alp (25-100 μM) dose-dependently attenuated Lewis lung carcinoma-conditioned medium-induced C2C12 myotube atrophy and reduced expression of the E3 ligases Atrogin-1 and MuRF1. Moreover, Alp administration markedly improved vital features of cancer cachexia with visible reduction of the loss of tumor-free body weight and wasting of multiple tissues, including skeletal muscle, epididymal fat, and decreased expression of Atrogin-1 and MuRF1 in cachectic muscle. Alp suppressed the elevated spleen weight and serum concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Further, Alp treatment remained protective against cancer cachexia in the advanced stage of tumor growth. Molecular docking results suggested that Alp was docked into the active site of PPARγ with the docking score of -7.6 kcal/mol, forming a hydrogen bond interaction with PPARγ protein amino acid residue HIS449 with a bond length of 3.3 Å. Mechanism analysis revealed that Alp activated PPARγ, resulting in the downregulated phosphorylation of NF-κB and STAT3 and . PPARγ inhibition induced by GW9662 notably attenuated the improvement of Alp on the above cachexia phenomenon, indicating that PPARγ activation mediated the therapeutic effect of Alp. These findings suggested that Alp might be a potential therapeutic candidate against cancer cachexia.
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http://dx.doi.org/10.3389/fphar.2021.687491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176100PMC
May 2021

Identification of microbial markers across populations in early detection of colorectal cancer.

Nat Commun 2021 05 24;12(1):3063. Epub 2021 May 24.

Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-L-glycero-beta-D-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.
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http://dx.doi.org/10.1038/s41467-021-23265-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144394PMC
May 2021

Protocol for single-molecule fluorescence recovery after photobleaching microscopy to analyze the dynamics and spatial locations of nuclear transmembrane proteins in live cells.

STAR Protoc 2021 Jun 30;2(2):100490. Epub 2021 Apr 30.

Department of Biology Temple University, Philadelphia, PA 19122, USA.

Single-molecule fluorescence recovery after photobleaching (smFRAP) is a newly developed technique that combines single-molecule super-resolution microscopy and traditional FRAP microscopy. smFRAP enables researchers to measure the dynamics, spatial locations, and relative concentrations of proteins. Here, we describe a step-by-step protocol for smFRAP on nuclear envelope transmembrane proteins on the inner nuclear membrane and outer nuclear membrane in live cells. For complete details on the use and execution of this protocol, please refer to Mudumbi et al. (2016a, 2016b, 2020 .
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http://dx.doi.org/10.1016/j.xpro.2021.100490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111821PMC
June 2021

Impact of e-Liquid Composition, Coil Temperature, and Puff Topography on the Aerosol Chemistry of Electronic Cigarettes.

Chem Res Toxicol 2021 Jun 5;34(6):1640-1654. Epub 2021 May 5.

Department of Environmental Toxicology, University of California at Davis, Davis, California 95616, United States.

E-cigarette aerosol is a complex mixture of gases and particles with a composition that is dependent on the e-liquid formulation, puffing regimen, and device operational parameters. This work investigated mainstream aerosols from a third generation device, as a function of coil temperature (315-510 °F, or 157-266 °C), puff duration (2-4 s), and the ratio of propylene glycol (PG) to vegetable glycerin (VG) in e-liquid (100:0-0:100). Targeted and untargeted analyses using liquid chromatography high-resolution mass spectrometry, gas chromatography, in situ chemical ionization mass spectrometry, and gravimetry were used for chemical characterizations. PG and VG were found to be the major constituents (>99%) in both phases of the aerosol. Most e-cigarette components were observed to be volatile or semivolatile under the conditions tested. PG was found almost entirely in the gas phase, while VG had a sizable particle component. Nicotine was only observed in the particle phase. The production of aerosol mass and carbonyl degradation products dramatically increased with higher coil temperature and puff duration, but decreased with increasing VG fraction in the e-liquid. An exception is acrolein, which increased with increasing VG. The formation of carbonyls was dominated by the heat-induced dehydration mechanism in the temperature range studied, yet radical reactions also played an important role. The findings from this study identified open questions regarding both pathways. The vaping process consumed PG significantly faster than VG under all tested conditions, suggesting that e-liquids become more enriched in VG and the exposure to acrolein significantly increases as vaping continues. It can be estimated that a 30:70 initial ratio of PG:VG in the e-liquid becomes almost entirely VG when 60-70% of e-liquid remains during the vaping process at 375 °F (191 °C). This work underscores the need for further research on the puffing lifecycle of e-cigarettes.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00070DOI Listing
June 2021

High Structural Stability of Photonic Crystals on Textile Substrates, Prepared a Surface-Supported Curing Strategy.

ACS Appl Mater Interfaces 2021 Apr 19;13(16):19221-19229. Epub 2021 Apr 19.

Engineering Research Centre for Eco-Dyeing and Finishing of Textiles, Ministry of Education, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Over the past years, photonic crystals (PCs) with a periodically ordered nanostructure have attracted great attention due to their potential as advanced optical materials for structural coloration of textiles. However, the weak structural stability of PCs on flexible textile substrates makes them vulnerable to strong external forces, hampering their large-scale application. In this work, a waterborne polyurethane (wPU) is chosen for enhancing the structural stability of PCs. The composite PCs (PCs/wPU) show both brilliant structural colors and significantly improved structural stability. The structural color produced by the encapsulated PCs is found to depend on the properties of encapsulating agents. The wPU with high surface tension solidifies mainly on the PC surface in the form of a transparent film, protecting the overall structure of PCs. Meanwhile, a small amount of wPU, infiltrating into the interior of PCs, provides strong adhesion and ensures stability among nanospheres. In turn, polydimethylsiloxane (PDMS) with low surface tension is easy to infiltrate into the interior of PCs, forming fully encapsulated PCs. This reduces the brightness of structural color produced by the final PCs/PDMS composite over the original PCs, due to the replacement of air by PDMS, and thus the decrease in the refractive index contrast of PCs. The supported curing strategy using the encapsulating agent with high surface tension is shown to not only improve the structural stability of PCs but also exert almost no influence on the optical properties of PCs, facilitating the practice application of structural coloration in the textile industry.
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http://dx.doi.org/10.1021/acsami.1c00176DOI Listing
April 2021

The structure of a minimum amyloid fibril core formed by necroptosis-mediating RHIM of human RIPK3.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

University of Chinese Academy of Sciences, 100049 Beijing, China;

Receptor-interacting protein kinases 3 (RIPK3), a central node in necroptosis, polymerizes in response to the upstream signals and then activates its downstream mediator to induce cell death. The active polymeric form of RIPK3 has been indicated as the form of amyloid fibrils assembled via its RIP homotypic interaction motif (RHIM). In this study, we combine cryogenic electron microscopy and solid-state NMR to determine the amyloid fibril structure of RIPK3 RHIM-containing C-terminal domain (CTD). The structure reveals a single protofilament composed of the RHIM domain. RHIM forms three β-strands (referred to as strands 1 through 3) folding into an S shape, a distinct fold from that in complex with RIPK1. The consensus tetrapeptide VQVG of RHIM forms strand 2, which zips up strands 1 and 3 via heterozipper-like interfaces. Notably, the RIPK3-CTD fibril, as a physiological fibril, exhibits distinctive assembly compared with pathological fibrils. It has an exceptionally small fibril core and twists in both handedness with the smallest pitch known so far. These traits may contribute to a favorable spatial arrangement of RIPK3 kinase domain for efficient phosphorylation.
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http://dx.doi.org/10.1073/pnas.2022933118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040640PMC
April 2021

Gastrointestinal sequelae 90 days after discharge for COVID-19.

Lancet Gastroenterol Hepatol 2021 05 10;6(5):344-346. Epub 2021 Mar 10.

Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; School of Medicine, Sun Yat-Sen University, Shenzhen, China. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(21)00076-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943402PMC
May 2021

Adverse Outcomes Associated With Corticosteroid Use in Critical COVID-19: A Retrospective Multicenter Cohort Study.

Front Med (Lausanne) 2021 10;8:604263. Epub 2021 Feb 10.

The Third Clinical Medical College of Yangtze University, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, China.

Corticosteroid is commonly used to reduce damage from inflammatory reactions in coronavirus disease 2019 (COVID-19). We aim to determine the outcomes of corticosteroid use in critically ill COVID-19 patients. Ninety six critically ill patients, hospitalized in 14 hospitals outside Wuhan from January 16 to March 30, 2020 were enrolled in this study. Among 96 critical patients, 68 were treated with corticosteroid (CS group), while 28 were not treated with corticosteroids (non-CS group). Multivariable logistic regression were performed to determine the possible correlation between corticosteroid use and the treatment outcomes. Forty-six (68%) patients in the CS group died compared to six (21%) of the non-CS group. Corticosteroid use was also associated with the development of ARDS, exacerbation of pulmonary fibrosis, longer hospital stay and virus clearance time. On admission, no difference in laboratory findings between the CS and the non-CS group was observed. After corticosteroid treatment, patients treated with corticosteroids were associated with higher counts of white blood cells, neutrophils, neutrophil-to-lymphocyte ratio, alanine aminotransferase level and Sequential Organ Failure Assessment score. In conclusion, corticosteroid use in critically ill COVID-19 patients was associated with a much higher case fatality rate. Frequent incidence of liver injury and multi-organ failure in corticosteroid treated patients may have contributed to the adverse outcomes. The multi-organ failure is likely caused by more persistent SARS-CoV-2 infection and higher viral load, due to the inhibition of immune surveillance by corticosteroid.
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http://dx.doi.org/10.3389/fmed.2021.604263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900536PMC
February 2021

Enhancing cancer-associated fibroblast fatty acid catabolism within a metabolically challenging tumor microenvironment drives colon cancer peritoneal metastasis.

Mol Oncol 2021 May 16;15(5):1391-1411. Epub 2021 Feb 16.

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-sen University, Guangzhou, China.

Most cancer-related deaths result from the progressive growth of metastases. Patients with peritoneal metastatic (PM) colorectal cancer have reduced overall survival. Currently, it is still unclear why colorectal cancer (CRC) cells home to and proliferate inside the peritoneal cavity, and there is no effective consolidation therapy for improved survival. Using a proteomic approach, we found that key enzymes of fatty acid oxidation (FAO) were decreased in patients with PM colorectal cancer. Furthermore, we confirmed that carnitine palmitoyltransferase IA (CPT1A), a rate-limiting enzyme of FAO, was expressed at significantly low levels in patients with PM colorectal cancer, as determined by RT-qPCR, IHC, and GEO dataset analysis. However, lipidomics revealed no difference in FFA levels between PM and non-PM primary tumors. Here, we showed that cancer-associated fibroblasts (CAFs) promote the proliferation, migration, and invasion of colon cancer cells via upregulating CPT1A to actively oxidize FAs and conduct minimal glycolysis. In addition, coculture-induced glycolysis increased in cancer cells while fatty acid catabolism decreased with lower adiponectin levels. Importantly, inhibition of glycolysis significantly reduced the survival of CRC cells after incubation with conditioned medium from CAFs in vitro and impaired the survival and growth of organoids derived from CRC-PM. Finally, we found that directly blocking FAO in CAFs with etomoxir inhibits migration and invasion in vitro and decreases tumor growth and intraperitoneal dissemination in vivo, revealing a role for CAF CPT1A in promoting tumor growth and invasion. In conclusion, our results suggest the possibility of testing FAO inhibition as a novel approach and clinical strategy against CAF-induced colorectal cancer with peritoneal dissemination/metastases.
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http://dx.doi.org/10.1002/1878-0261.12917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096782PMC
May 2021

Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy.

Pharmaceutics 2021 Jan 14;13(1). Epub 2021 Jan 14.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Multiple drug resistance (MDR) in bacterial infections is developed with the abuse of antibiotics, posing a severe threat to global health. Tedizolid phosphate (TR-701) is an efficient prodrug of tedizolid (TR-700) against gram-positive bacteria, including methicillin-sensitive staphylococcus aureus (MSSA) and methicillin-resistant staphylococcus aureus (MRSA). Herein, a novel drug delivery system: Red blood cell membrane (RBCM) coated TR-701-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles (RBCM-PLGA-TR-701NPs, RPTR-701Ns) was proposed. The RPTR-701Ns possessed a double-layer core-shell structure with 192.50 ± 5.85 nm in size, an average encapsulation efficiency of 36.63% and a 48 h-sustained release in vitro. Superior bio-compatibility was confirmed with red blood cells (RBCs) and HEK 293 cells. Due to the RBCM coating, RPTR-701Ns on one hand significantly reduced phagocytosis by RAW 264.7 cells as compared to PTR-701Ns, showing an immune escape effect. On the other hand, RPTR-701Ns had an advanced exotoxins neutralization ability, which helped reduce the damage of MRSA exotoxins to RBCs by 17.13%. Furthermore, excellent in vivo bacteria elimination and promoted wound healing were observed of RPTR-701Ns with a MRSA-infected mice model without causing toxicity. In summary, the novel delivery system provides a synergistic antibacterial treatment of both sustained release and bacterial toxins absorption, facilitating the incorporation of TR-701 into modern nanotechnology.
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http://dx.doi.org/10.3390/pharmaceutics13010099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828826PMC
January 2021

High-speed super-resolution imaging of rotationally symmetric structures using SPEED microscopy and 2D-to-3D transformation.

Nat Protoc 2021 01 14;16(1):532-560. Epub 2020 Dec 14.

Department of Biology, Temple University, Philadelphia, PA, USA.

Various super-resolution imaging techniques have been developed to break the diffraction-limited resolution of light microscopy. However, it still remains challenging to obtain three-dimensional (3D) super-resolution information of structures and dynamic processes in live cells at high speed. We recently developed high-speed single-point edge-excitation sub-diffraction (SPEED) microscopy and its two-dimensional (2D)-to-3D transformation algorithm to provide an effective approach to achieving 3D sub-diffraction-limit information in subcellular structures and organelles that have rotational symmetry. In contrast to most other 3D super-resolution microscopy or 3D particle-tracking microscopy approaches, SPEED microscopy does not depend on complex optical components and can be implemented onto a standard inverted epifluorescence microscope. SPEED microscopy is specifically designed to obtain 2D spatial locations of individual immobile or moving fluorescent molecules inside sub-micrometer biological channels or cavities at high spatiotemporal resolution. After data collection, post-localization 2D-to-3D transformation is applied to obtain 3D super-resolution structural and dynamic information. The complete protocol, including cell culture and sample preparation (6-7 d), SPEED imaging (4-5 h), data analysis and validation through simulation (5-13 h), takes ~9 d to complete.
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http://dx.doi.org/10.1038/s41596-020-00440-xDOI Listing
January 2021

Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles.

Proc Natl Acad Sci U S A 2020 12 23;117(49):31123-31133. Epub 2020 Nov 23.

Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China;

Membraneless organelles contain a wide spectrum of molecular chaperones, indicating their important roles in modulating the metastable conformation and biological function of membraneless organelles. Here we report that class I and II Hsp40 (DNAJ) proteins possess a high ability of phase separation rendered by the flexible G/F-rich region. Different Hsp40 proteins localize in different membraneless organelles. Specifically, human Hdj1 (DNAJB1), a class II Hsp40 protein, condenses in ubiquitin (Ub)-rich nuclear bodies, while Hdj2 (DNAJA1), a class I Hsp40 protein, condenses in nucleoli. Upon stress, both Hsp40 proteins incorporate into stress granules (SGs). Mutations of the G/F-rich region not only markedly impaired Hdj1 phase separation and SG involvement and disrupted the synergistic phase separation and colocalization of Hdj1 and fused in sarcoma (FUS) in cells. Being cophase separated with FUS, Hdj1 stabilized the liquid phase of FUS against proceeding into amyloid aggregation in vitro and alleviated abnormal FUS aggregation in cells. Moreover, Hdj1 uses different domains to chaperone FUS phase separation and amyloid aggregation. This paper suggests that phase separation is an intrinsic property of Hsp40 proteins, which enables efficient incorporation and function of Hsp40 in membraneless organelles and may further mediate the buildup of chaperone network in membraneless organelles.
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http://dx.doi.org/10.1073/pnas.2002437117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733851PMC
December 2020

The Effects of Combined Social Cognition and Interaction Training and Paliperidone on Early-Onset Schizophrenia.

Front Psychiatry 2020 30;11:525492. Epub 2020 Sep 30.

Department of Psychiatry, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

Background: The limitations associated with antipsychotics in early-onset schizophrenia patients have stimulated more interest in psychological interventions in this population. Nevertheless, the isolated psychosocial interventions are unrealistic in a treatment success covering the complex array of symptoms, and the psychosocial interventions could be an adjunct treatment to the pharmacological treatment. It is necessary to find the benefits of psychological interventions with limited and targeted use of antipsychotics. Social cognition and interaction training (SCIT) was a program for social cognitive rehabilitation in adult schizophrenia. However, it is unclear how generalizable this is to early-onset patients.

Methods: The current study tested this hypothesis that combined SCIT and paliperidone was superior to paliperidone alone in treating early-onset schizophrenia patients on cognitive, functional, and symptom outcomes. Two hundred eight inpatients with schizophrenia aged 13 to 17 years old participated in a 24-week work intervention program. Patients completed a battery of measures administered at a pre-SCIT intervention baseline, 4, 8, 12, and 24 weeks post-SCIT, respectively.

Results: SCIT had significant added benefits above paliperidone for the speed of processing, attention/vigilance, and social cognition of the Chinese version of MATRICS consensus cognitive battery (MCCB) domains (p<0.05). The following logistic regression analysis on the exploration of the influential factors also confirmed the effects of SCIT. However, combined SCIT and paliperidone intervention had a null impact on social functioning and symptomatology.

Conclusions: The present study provides the first evidence that combined SCIT and paliperidone intervention has the potential to improve cognitive functions for the early-onset schizophrenia patients. The findings in the current study are suggestive of the extreme importance of SCIT as an adjunctive treatment in early-onset schizophrenia patients.
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http://dx.doi.org/10.3389/fpsyt.2020.525492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556232PMC
September 2020

Risk factors for the critical illness in SARS-CoV-2 infection: a multicenter retrospective cohort study.

Respir Res 2020 Oct 21;21(1):277. Epub 2020 Oct 21.

Putuo People's Hospital, Department of Bioinformatics, Tongji University, Shanghai, 200092, China.

Background: Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection.

Methods: Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness.

Results: Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 10/L, neutrophilia > 6.3 × 10/L, lymphopenia < 1.1 × 10/L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 μg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 μM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors.

Conclusions: Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 10/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.
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http://dx.doi.org/10.1186/s12931-020-01492-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576549PMC
October 2020

Magnetically Tunable Plasmon Coupling of Au Nanoshells Enabled by Space-Free Confined Growth.

Nano Lett 2020 Nov 15;20(11):8242-8249. Epub 2020 Oct 15.

Department of Chemistry, University of California, Riverside, California 92521, United States.

We report the unconventional space-free confined growth of Au nanoshells with well-defined plasmonic properties and active tuning of their plasmon coupling by the nanoscale magnetic assembly. The seeded growth of Au exclusively occurred at the hard-soft interfaces between the FeO core and phenolic resin without the need of creating a limiting space, which represents a general and elegant approach to various core-shell nanostructures. The deformability of permeable phenolic layers plays an essential role in regulating the interfacial growth of Au nanoshells. While the polymer elasticity suppresses the radial deposition of Au atoms, their high deformability can afford enough spaces for the formation of conformal metallic shells. The coupled magnetic-plasmonic properties allow active tuning of the plasmon coupling and the resonant scattering of Au nanoshells by the magnetic assembly of the hybrid nanoparticles into plasmonic chains, whose potentials in applications have been demonstrated in designing transparent displays and anticounterfeiting devices.
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http://dx.doi.org/10.1021/acs.nanolett.0c03350DOI Listing
November 2020

Revisiting Image-Language Networks for Open-ended Phrase Detection.

IEEE Trans Pattern Anal Mach Intell 2020 Oct 6;PP. Epub 2020 Oct 6.

Most existing work that grounds natural language phrases in images starts with the assumption that the phrase in question is relevant to the image. In this paper we address a more realistic version of the natural language grounding task where we must both identify whether the phrase is relevant to an image \textbf{and} localize the phrase. This can also be viewed as a generalization of object detection to an open-ended vocabulary, introducing elements of few- and zero-shot detection. We propose an approach for this task that extends Faster R-CNN to relate image regions and phrases. By carefully initializing the classification layers of our network using canonical correlation analysis (CCA), we encourage a solution that is more discerning when reasoning between similar phrases, resulting in over double the performance compared to a naive adaptation on three popular phrase grounding datasets, Flickr30K Entities, ReferIt Game, and Visual Genome, with test-time phrase vocabulary sizes of 5K, 32K, and 159K, respectively.
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http://dx.doi.org/10.1109/TPAMI.2020.3029008DOI Listing
October 2020

Adiantic acid, a new unsaturated fatty acid with a cyclopropane moiety from L.

Nat Prod Res 2020 Oct 5:1-7. Epub 2020 Oct 5.

College of Life Sciences, Shanghai Normal University, Shanghai, China.

Phytochemical investigation of L. led to the isolation of four natural compounds, including a novel unsaturated fatty acid with a cyclopropane moiety, i.e. (,)-7-(2-octylcyclopropylidene)heptanoic acid (), together with three known compounds, isoadiantol B (), stigmast-4-en-6-ol-3-one (), -sitosterol (). Compound was isolated from the A. L. for the first time. The structure of was elucidated following a comprehensive analysis of spectroscopic analyses including MS, 1 D and 2 D NMR, and by a mass spectrometry experiment of the dimethyl disulfide (DMDS) adduct, while the known compounds were identified by comparisons with those reported in the literature. Enzyme evaluation of indicated this compound possesses anti- protein tyrosine phosphatase (PTP1B) activity with an IC value of 6.99 ± 0.41 μM .
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http://dx.doi.org/10.1080/14786419.2020.1827405DOI Listing
October 2020

Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation.

Cell 2020 10 30;183(2):490-502.e18. Epub 2020 Sep 30.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China; Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:

The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants. SHP2 LLPS is mediated by the conserved well-folded PTP domain through multivalent electrostatic interactions and regulated by an intrinsic autoinhibitory mechanism through conformational changes. SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity. Moreover, disease-associated SHP2 mutants can recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation. These results not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis of SHP2-associated human diseases but also provide evidence that PTP may be regulated by LLPS that can be therapeutically targeted.
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http://dx.doi.org/10.1016/j.cell.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572904PMC
October 2020

Insight into the effect of nitrogen-rich substrates on the community structure and the co-occurrence network of thermophiles during lignocellulose-based composting.

Bioresour Technol 2021 Jan 10;319:124111. Epub 2020 Sep 10.

Institute of Ecology and Biodiversity, School of Life Sciences, Shandong University, Qingdao 266237, PR China. Electronic address:

Thermophilic microorganisms play vital roles in the composting process. To elucidate how raw materials affect thermophilic microbial community composition and their interactions, the succession of thermophilic bacterial and fungal communities were monitored in reed straw co-composting with four common nitrogen-rich substrates. The results of high-throughput sequencing showed that raw materials and composting process significantly changed bacterial and fungal community composition. Firmicutes and Actinobacteria drove the assembly of bacterial communities, while Ascomycetes drove the assembly of fungal communities. Network analysis indicated that during the composting process, the addition of nitrogen-rich sources abundant in easily degradable substances promoted the complexity of thermophilic microbial network. Moreover, microorganisms mainly exhibited synergistic effects, and inter-kingdom competition was more intense than intra-kingdom competition. Notably, rare species play essential roles in maintaining the network construction. Our findings provided novel insights into thermophilic microbial community assembly and their co-occurrence networks during the composting process.
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http://dx.doi.org/10.1016/j.biortech.2020.124111DOI Listing
January 2021

Biomimetic synthesis of chondroitin sulfate-analogue hydrogels for regulating osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells.

Mater Sci Eng C Mater Biol Appl 2020 Dec 11;117:111368. Epub 2020 Aug 11.

College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China; State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. Electronic address:

As a typical representative of crucial glycosaminoglycans (GAGs), chondroitin sulfate (CS) with sulfonated polysaccharide in structures extensively exists in the extracellular matrix (ECM) and exhibits peculiar bioactivity on the regulation of cells behaviors and fates (e.g. proliferation and differentiation) in organisms. Nevertheless, some intrinsic disadvantages of natural CS mainly ascribe to the intricate structure and inhomogeneous composition (especially the uncontrollable sulfonate degrees), resulting in overt restrictions on its physiological functions and applications. Although recent bionic synthesis of artificial GAGs analogues at the molecular level have already provides an efficient strategy to reconstruct GAG for regulating the cellular behaviors and fates, it still remains great challenges to rationally design and synthesize GAGs analogues with special composition and structure for precisely mimicking ECM. Simultaneously, the relevant regulation process of GAG analogues on cell fate needs to be further studied as well. Herein, chondroitin sulfate-analogue (CS-analogue) hydrogels with diverse contents of saccharide and sulfonate units in the networks were fabricated through photo-polymerization and then characterized by Fourier transform infrared (FT-IR) spectroscopy, zeta potential and scanning electron microscope (SEM). Additionally, CS-analogue hydrogels with proper mechanical properties exhibited favorable swelling, degradation performance and prominent cytocompatibility. According to cell cultivation results, CS-analogue hydrogel with a certain proportion of saccharide and sulfonate units presented preferable promotion on the adhesion, spreading, proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), shedding light on the significance of saccharide and sulfonate units in regulating cell behaviors. Furthermore, BMSCs cultivated with CS-analogue hydrogels under different culture conditions were also systematically investigated, revealing that with the help of cultivation environment CS-analogue hydrogels owned the remarkable capacity of directing either chondrogenic or osteogenic differentiation of BMSCs. Therefore, it is envisioned that versatile CS-analogue hydrogels would have promising application prospects in the biomedical and clinical fields.
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http://dx.doi.org/10.1016/j.msec.2020.111368DOI Listing
December 2020

Mini-Scheimpflug lidar system for all-day atmospheric remote sensing in the boundary layer.

Appl Opt 2020 Aug;59(22):6729-6736

Development of a lightweight, low-cost, easy-to-use and low-maintenance lidar technique has been of great interest for atmospheric aerosol remote sensing in recent years and remains a great challenge. In this work, an 808 nm mini-Scheimpflug lidar (SLidar) system with about 450 mm separation between the transmitter and the receiver has been developed by employing a 114 mm aperture Newtonian telescope (F4). System performances, such as the beam characteristic, the range resolution, and the signal-to-noise ratio of the lidar signal, have been carefully investigated. Despite employing a small receiving aperture, all-day measurements were still feasible with about a one-minute signal averaging for both the horizontal urban area monitoring and the slant atmospheric sounding in the boundary layer. The lidar signal in the region of 29-50 m with a scattering angle less than 179.5° could be slightly underestimated due to the variation of the phase function. The extinction coefficient evaluated in the region between 29 and 2000 m according to the Klett method agreed well with the concentrations of particulate matters for both horizontal and slant measurements. The promising result demonstrated in this work has shown great potential to employ the robust mini-SLidar system for atmospheric monitoring in the boundary layer.
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http://dx.doi.org/10.1364/AO.396057DOI Listing
August 2020

Lipid-Bilayer-Supported 3D Printing of Human Cerebral Cortex Cells Reveals Developmental Interactions.

Adv Mater 2020 Aug 14;32(31):e2002183. Epub 2020 Jun 14.

Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK.

Current understanding of human brain development is rudimentary due to suboptimal in vitro and animal models. In particular, how initial cell positions impact subsequent human cortical development is unclear because experimental spatial control of cortical cell arrangement is technically challenging. 3D cell printing provides a rapid customized approach for patterning. However, it has relied on materials that do not represent the extracellular matrix (ECM) of brain tissue. Therefore, in the present work, a lipid-bilayer-supported printing technique is developed to 3D print human cortical cells in the soft, biocompatible ECM, Matrigel. Printed human neural stem cells (hNSCs) show high viability, neural differentiation, and the formation of functional, stimulus-responsive neural networks. By using prepatterned arrangements of neurons and astrocytes, it is found that hNSC process outgrowth and migration into cell-free matrix and into astrocyte-containing matrix are similar in extent. However, astrocytes enhance the later developmental event of axon bundling. Both young and mature neurons migrate into compartments containing astrocytes; in contrast, astrocytes do not migrate into neuronal domains signifying nonreciprocal chemorepulsion. Therefore, precise prepatterning by 3D printing allows the construction of natural and unnatural patterns that yield important insights into human cerebral cortex development.
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http://dx.doi.org/10.1002/adma.202002183DOI Listing
August 2020

THE PRESENT AND FUTURE OF THE MASS SPECTROMETRY-BASED INVESTIGATION OF THE EXOSOME LANDSCAPE.

Mass Spectrom Rev 2020 09 29;39(5-6):745-762. Epub 2020 May 29.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, People's Republic of China.

Exosomes are critical intercellular messengers released upon the fusion of multivesicular bodies with the cellular plasma membrane that deliver their cargo in the form of extracellular vesicles. Containing numerous nonrandomly packed functional proteins, lipids, and RNAs, exosomes are vital intercellular messengers that contribute to the physiologic processes of the healthy organism. During the post-genome era, exosome-oriented proteomics have garnered great interest. Since its establishment, mass spectrometry (MS) has been indispensable for the field of proteomics research and has advanced rapidly to interrogate biological samples at a higher resolution and sensitivity. Driven by new methodologies and more advanced instrumentation, MS-based approaches have revolutionized our understanding of protein biology. As the access to online proteomics database platforms has blossomed, experimental data processing occurs with more speed and accuracy. Here, we review recent advances in the technological progress of MS-based proteomics and several new detection strategies for MS-based proteomics research. We also summarize the use of integrated online databases for proteomics research in the era of big data. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.
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http://dx.doi.org/10.1002/mas.21635DOI Listing
September 2020

Development of a Portable SPR Sensor for Nucleic Acid Detection.

Micromachines (Basel) 2020 May 21;11(5). Epub 2020 May 21.

College of Information Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

Nucleic acid detection is of great significance in clinical diagnosis, environmental monitoring and food safety. Compared with the traditional nucleic acid amplification detection method, surface plasmon resonance (SPR) sensing technology has the advantages of being label-free, having simple operation, and providing real-time detection. However, the angle scanning system in many SPR angle modulation detection applications usually requires a high-resolution stepper motor and complex mechanical structure to adjust the angle. In this paper, a portable multi-angle scanning SPR sensor was designed. The sensor only uses one stepping motor to rotate a belt, and the belt pulls the mechanical linkages of incident light and reflected light to move in opposite directions for achieving the SPR angle scanning mode that keeps the incident angle and reflected angle equal. The sensor has an angle scanning accuracy of 0.002°, response sensitivity of 3.72 × 10 RIU (refractive index unit), and an angle scanning range of 30°-74°. The overall size of the system is only 480 mm × 150 mm × 180 mm. The portable SPR sensor was used to detect nucleic acid hybridization on a gold film chip modified with bovine serum albumin (BSA). The result revealed that the sensor had high sensitivity and fast response, and could successfully accomplish the hybridization detection of target DNA solution of 0.01 μmol/mL.
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http://dx.doi.org/10.3390/mi11050526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281666PMC
May 2020

Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores.

Nat Commun 2020 05 4;11(1):2184. Epub 2020 May 4.

Department of Biology, Temple University, Philadelphia, PA, 19122, USA.

Roughly 10% of eukaryotic transmembrane proteins are found on the nuclear membrane, yet how such proteins target and translocate to the nucleus remains in dispute. Most models propose transport through the nuclear pore complexes, but a central outstanding question is whether transit occurs through their central or peripheral channels. Using live-cell high-speed super-resolution single-molecule microscopy we could distinguish protein translocation through the central and peripheral channels, finding that most inner nuclear membrane proteins use only the peripheral channels, but some apparently extend intrinsically disordered domains containing nuclear localization signals into the central channel for directed nuclear transport. These nucleoplasmic signals are critical for central channel transport as their mutation blocks use of the central channels; however, the mutated proteins can still complete their translocation using only the peripheral channels, albeit at a reduced rate. Such proteins can still translocate using only the peripheral channels when central channel is blocked, but blocking the peripheral channels blocks translocation through both channels. This suggests that peripheral channel transport is the default mechanism that was adapted in evolution to include aspects of receptor-mediated central channel transport for directed trafficking of certain membrane proteins.
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http://dx.doi.org/10.1038/s41467-020-16033-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198523PMC
May 2020
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