Publications by authors named "Lin Huang"

774 Publications

Bay-Region Annulative π-Extension of -Iodobiphenyls with Aliphatic Anhydrides Catalyzed by Pd(OAc).

Org Lett 2021 Sep 23. Epub 2021 Sep 23.

College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610068, P. R. China.

Bay-region annulative π-extension of -iodobiphenyls with aliphatic anhydrides was developed. Many -iodobiphenyls and aliphatic anhydrides can react well under the optimized conditions. A lot of phenanthrol derivatives can be efficiently prepared by this approach. The control experiments support that dibenzopalladacyclopentadienes may be the reaction intermediates.
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http://dx.doi.org/10.1021/acs.orglett.1c02746DOI Listing
September 2021

Norcantharidin ameliorates the development of murine lupus via inhibiting the generation of IL-17 producing cells.

Acta Pharmacol Sin 2021 Sep 22. Epub 2021 Sep 22.

Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Systemic lupus erythematosus (SLE) is a devastating autoimmune disorder associated with severe organ damage. The abnormality of T cell apoptosis is considered as an important pathogenetic mechanism of SLE. Norcantharidin (NCTD), a derivative of Cantharidin, is an efficacious anti-cancer drug by inhibiting cell proliferation and inducing cell apoptosis. Besides, NCTD has also been proved to protect the function of kidneys, while damaged renal function is the most important predictor of morbidity and mortality in SLE. All these suggest the potential effects of NCTD in SLE treatment. In this study we investigated whether NCTD exerted therapeutic effects in a mouse SLE model. Lupus prone female MRL/lpr mice were treated with NCTD (1, 2 mg·kg·d, ip) for 8 weeks. We showed that NCTD administration significantly decreased mortality rate, diminished the expression of anti-dsDNA IgG antibody, a diagnostic marker for SLE, as well as restored renal structure and function in MRL/lpr mice. Moreover, NCTD administration dose-dependently inhibited lymphoproliferation and T cell accumulation in the spleens of MRL/lpr mice. We further revealed that NCTD specifically inhibited DN T cell proliferation and Th17 cell differentiation both via blocking activation of signal transducer and activator of transcription 3 (STAT3) signaling pathway. On the other hand, NCTD did not affect T cell apoptosis in MRL/lpr mice. Taken together, our data suggest that NCTD may be as a promising therapeutic drug through targeting T cells for the treatment of SLE.
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http://dx.doi.org/10.1038/s41401-021-00773-7DOI Listing
September 2021

Pva-miR-252 participates in ammonia nitrogen-induced oxidative stress by modulating autophagy in Penaeus vannamei.

Ecotoxicol Environ Saf 2021 Sep 16;225:112774. Epub 2021 Sep 16.

Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, College of Life Science, South China Normal University, Guangzhou 510631, PR China. Electronic address:

MicroRNAs (miRNAs) are critical post-transcriptional regulators, which play a crucial role in resistance to adverse environmental stress by regulating autophagy. However, the mechanism of miRNA involved in the autophagy regulation of shrimp under ammonia nitrogen stress is still limited. In the present study, ammonia nitrogen could induce hepatopancreas injury and oxidative stress of P. vannamei, and significantly increase the content of ROS in hemocytes by flow cytometry. Simultaneously, it is accompanied by autophagy occurred in the hemocytes and hepatopancreas. Furthermore, the qRT-PCR analysis revealed that the expression of pva-miR-252 in P. vannamei decreased significantly after ammonia nitrogen stress, and pva-miR-252 negatively regulated PvPI3K by binding to 3'UTR of PvPI3K by double-luciferase assay. Pva-miR-252 overexpression could significantly increase the level of autophagy, and restore the autophagy inhibition caused by Chloroquine in vitro , whereas silencing of pva-miR-252 resulted in the opposite effect. More importantly, overexpression of pva-miR-252 could enhance the activity of antioxidant enzymes and reduced the production of ROS of shrimp under ammonia nitrogen stress. In conclusion, pva-miR-252 could positively regulate autophagy through PvPI3K and improve the antioxidant enzyme activity of P. vannamei under ammonia nitrogen stress, and our study provides a novel theoretical molecular mechanism for further understanding the shrimp cope with a high ammonia nitrogen environment.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112774DOI Listing
September 2021

Basic pH reversed-phase liquid chromatography (bRPLC) in combination with tip-based strong cation exchange (SCX-Tip), ReST, an efficient approach for large-scale cross-linked peptide analysis.

Anal Chim Acta 2021 Sep 7;1179:338838. Epub 2021 Jul 7.

State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, 200438, China. Electronic address:

Chemical cross-linking in combination with mass spectrometry (XL-MS) has emerged as a useful method for structural elucidation of proteins and protein complexes. Due to the low stoichiometry of cross-linked peptides, a specific enrichment method is always necessary prior to LC-MS/MS analysis, especially for complex samples. Currently, strong cation exchange chromatography (SCX), size exclusion chromatography (SEC), and affinity tag-based enrichment are among the widely used enrichment strategies. Herein, we present a two-dimensional strategy combining basic pH reversed-phase liquid chromatography (bRPLC) fractionation and tip-based SCX (SCX-Tip) enrichment, termed ReST, for the characterization of cross-linked peptides. We revealed the unbiased separation effects of the bRPLC in the cross-linked peptide fractionation. We optimized the enrichment conditions of SCX-Tip using well-designed cross-linked peptides. Taking advantage of the high resolution of bRPLC separation and the high enrichment efficiency of SCX-Tip, we were able to identify 43.6% more cross-linked peptides than the conventional SCX approach. The presented ReST is a simple and efficient approach for proteome-scale protein-protein interaction studies.
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http://dx.doi.org/10.1016/j.aca.2021.338838DOI Listing
September 2021

Biocompatible, antibacterial and anti-inflammatory zinc ion cross-linked quaternized cellulose‑sodium alginate composite sponges for accelerated wound healing.

Int J Biol Macromol 2021 Sep 14;191:27-39. Epub 2021 Sep 14.

College of Chemistry and Molecular Sciences, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan University, Wuhan 430072, China. Electronic address:

Bacterial infection has become one of the most challenges for wound healing, which causes serious inflammatory response and delays the healing process. Herein, a novel sponge with excellent biocompatible, antibacterial and anti-inflammatory properties based on quaternized cellulose (QC), sodium alginate (SA) and Zn was reported. The existence of physical interactions, such as electrostatic interaction, chelation and hydrogen bonding endowed the sponges with enhanced mechanical property. The composite sponges exhibited outstanding biocompatibility and hemostatic efficiency due to the compatible nature of the component and physical cross-linking, as well as superior antibacterial property benefited from the synergistic effects of steady Zn release and quaternary ammonium group. In vivo investigation validated that the enhanced antibacterial and anti-inflammatory effect of the sponges, which significantly promoted wound closure and the reconstruction of skin tissue through epithelial regeneration, collagen deposition and mitigating inflammatory cell infiltration. Overall, the novel sponge demonstrated great potentials in bacteria-associated wound management.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.047DOI Listing
September 2021

Rapid and sensitive leukemia-derived exosome quantification nicking endonuclease-assisted target recycling.

Anal Methods 2021 Sep 16;13(35):4001-4007. Epub 2021 Sep 16.

School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China.

Exosomes as fluid biomarkers hold great promise for noninvasive cancer diagnosis. However, a method for the rapid and convenient detection of exosomes is still a challenge because current analysis processes involve multiple steps and yield low sensitivity. Here, we developed a wash-free fluorescent biosensor for the rapid and sensitive quantification of exosomes by combining aptamer and nicking endonuclease (Nb·BbvCI). In this system, an aptamer-trigger complex was used as the recognition element; the trigger probe could be released, and it hybridized with gold nanoparticles (GNPs)-DNA-FAM conjugates, thereby resulting in Nb·BbvCI-assisted target recycling. As a result, our method allowed the quantification of exosomes with lower analysis time by using a cocktail containing an aptamer-trigger complex, Nb·BbvCI, and GNPs-DNA-FAM. A high sensitivity with a limit of detection (LOD) of 1.0 × 10 particles per μL could be achieved. Besides, this biosensor exhibited potential application for the quantification of exosomes in human plasma, facilitating the development of exosome-based noninvasive cancer diagnosis.
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http://dx.doi.org/10.1039/d1ay00854dDOI Listing
September 2021

Urban-Rural Differences in Patterns and Associated Factors of Multimorbidity Among Older Adults in China: A Cross-Sectional Study Based on Apriori Algorithm and Multinomial Logistic Regression.

Front Public Health 2021 30;9:707062. Epub 2021 Aug 30.

Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Multimorbidity has become one of the key issues in the public health sector. This study aimed to explore the urban-rural differences in patterns and associated factors of multimorbidity in China and to provide scientific reference for the development of health management strategies to reduce health inequality between urban and rural areas. A cross-sectional study, which used a multi-stage random sampling method, was conducted effectively among 3,250 participants in the Shanxi province of China. The chi-square test was used to compare the prevalence of chronic diseases among older adults with different demographic characteristics. The Apriori algorithm and multinomial logistic regression were used to explore the patterns and associated factors of multimorbidity among older adults, respectively. The findings showed that 30.3% of older adults reported multimorbidity, with significantly higher proportions in rural areas. Among urban older adults, 10 binary chronic disease combinations with strong association strength were obtained. In addition, 11 binary chronic disease combinations and three ternary chronic disease combinations with strong association strength were obtained among rural older adults. In rural and urban areas, there is a large gap in patterns and factors associated with multimorbidity. Multimorbidity was prevalent among older adults, which patterns mainly consisted of two or three chronic diseases. The patterns and associated factors of multimorbidity varied from urban to rural regions. Expanding the study of urban-rural differences in multimorbidity will help the country formulate more reasonable public health policies to maximize the benefits of medical services for all.
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http://dx.doi.org/10.3389/fpubh.2021.707062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437131PMC
August 2021

A New Minimally Invasive Method of Transverse Aortic Constriction in Mice.

J Cardiovasc Transl Res 2021 Sep 8. Epub 2021 Sep 8.

Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, Guangdong Province, China.

Transverse aortic constriction (TAC) in mice is the most popular model to mimic pressure overload heart disease. In this study, we developed a convenient, quick, and less invasive new TAC mice model. Briefly, after anesthetization, endotracheal intubation was then performed, and the endotracheal tube was connected to a ventilator. The second intercostal space was opened and then the home-made retractors were used to push aside the thymus gently. A tunnel under the aortic arch was made and a segment of 6-0 monofilament polypropylene suture which had been threaded through a specifically modified blunted 26-gauge syringe needle was passed through the tunnel. A blunted 27-gauge needle was placed parallel to the transverse aorta and then three knots were tied quickly. After ligation, the spacer was removed promptly and gently to achieve a constriction of 0.4 mm in diameter. Five weeks after TAC, cardiac hypertrophy, fibrosis, and left ventricular dysfunction were observed. The mouse was anesthetized with pentobarbital (50 mg/kg) via intraperitoneal injection. Endotracheal intubation under direct vision was then performed and the endotracheal tube was connected to a ventilator. The second intercostal space was opened and then the home-made retractors were used to push aside the thymus gently. A tunnel under the aortic arch was made and a segment of 6-0 monofilament polypropylene suture which had been threaded through a specifically modified blunted 26-gauge syringe needle was passed through the tunnel.
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http://dx.doi.org/10.1007/s12265-021-10170-4DOI Listing
September 2021

Porous Inorganic Materials for Bioanalysis and Diagnostic Applications.

ACS Biomater Sci Eng 2021 Sep 8. Epub 2021 Sep 8.

School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, P. R. China.

Porous inorganic materials play an important role in adsorbing targeted analytes and supporting efficient reactions in analytical science. The detection performance relies on the structural properties of porous materials, considering the tunable pore size, shape, connectivity, etc. Herein, we first clarify the enhancement mechanisms of porous materials for bioanalysis, concerning the detection sensitivity and selectivity. The diagnostic applications of porous material-assisted platforms by coupling with various analytical techniques, including electrochemical sensing, optical spectrometry, and mass spectrometry, etc., are then reviewed. We foresee that advanced porous materials will bring far-reaching implications in bioanalysis toward real-case applications, especially as diagnostic assays in clinical settings.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00733DOI Listing
September 2021

Betulinic acid attenuates cyclophosphamide-induced intestinal mucosa injury by inhibiting the NF-κB/MAPK signalling pathways and activating the Nrf2 signalling pathway.

Ecotoxicol Environ Saf 2021 Sep 2;225:112746. Epub 2021 Sep 2.

Hunan Engineering Research Center of Livestock and Poultry Health Care, Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China. Electronic address:

Betulinic acid (BA), a pentacyclic triterpenoid, has been associated with several biological effects, such as antioxidant, anti-inflammatory and antiviral activities. Previous studies have demonstrated that BA has the ability to alleviate intestinal mucosal damage, however, the potential mechanism associated with the effect has not been reported. This study aimed to investigate the possible protective mechanism of BA against cyclophosphamide (CYP)-induced intestinal mucosal damage. Here, we found that BA pretreatment prevented intestinal mucosal barrier dysfuction from CYP-challenged mice by repairing the intestinal physical, chemical, and immune barriers. Moreover, BA treatment suppressed the CYP-induced oxidative stress by activating the nuclear factor erythroid 2 [NF-E2]-related factor (Nrf2) pathway blocked reactive oxygen species (ROS) accumulation. In addition, BA inhibited CYP-triggered intestinal inflammation through down-regulating the nuclear transcription factor kappa B (NF-κB)/mitogen-activating protein kinase (MAPK) pathways. Furthermore, BA pretreatment reduced intestinal apoptosis by blocking ROS-activated mitochondrial apoptotic pathway. Overall, the current study demonstrated the protective effect of BA against CYP-caused intestinal mucosal damage by regulating the Nrf2 and NF-κB/MAPK signalling pathways, which may provide new therapeutic targets to attenuate intestinal impairment and maintain intestinal health.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112746DOI Listing
September 2021

Correction to: Biomimetic Biphasic Electrospun Scaffold for Anterior Cruciate Ligament Tissue Engineering.

Tissue Eng Regen Med 2021 Oct;18(5):915

College of Materials and Metallurgy, Guizhou University, Guiyang, Guizhou, China.

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http://dx.doi.org/10.1007/s13770-021-00386-5DOI Listing
October 2021

Efficacy and safety of standardized Ginkgo biloba L. leaves extract as an adjuvant therapy for sudden sensorineural hearing loss: A systematic review and meta-analysis.

J Ethnopharmacol 2021 Aug 30;282:114587. Epub 2021 Aug 30.

Department of pharmacy, Peking University People's Hospital, Beijing, 100044, China. Electronic address:

Ethnopharmacological Relevance: Ginkgo biloba L. has been used for medical purposes in China for centuries. Standardized Ginkgo biloba L. leaves extract (GBE) is a widely used botanical drug which displays a variety of pharmacological effects against sudden sensorineural hearing loss (SSNHL).

Aim Of The Study: To evaluate the efficacy and safety of GBE as an adjuvant therapy, administered with corticosteroids, for the initial management of patients with SSNHL.

Materials And Methods: We searched seven databases for randomized clinical trials (RCTs) comparing GBE plus corticosteroids with corticosteroids alone for SSNHL treatment. Data analysis was carried out by Review Manager 5.4 and Stata 16.0 software. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. We subsequently evaluated the certainty of evidence using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach.

Results: A total of 11 RCTs involving 1069 patients were included. Meta-analysis indicated that the clinical cure rate (RR = 1.33, 95% CI = 1.12 to 1.58, P = 0.001) and total effective rate (RR = 1.24, 95%CI = 1.17 to 1.31, P < 0.001) in SSNHL patients receiving GBE plus corticosteroids was superior to patients receiving corticosteroids alone. After treatment, pure tone average (PTA) improvement of observation group was better than that in the control group (WMD = 10.33, 95%CI = 6.46 to 14.21, P < 0.001). The levels of whole blood high shear viscosity (WMD = 0.93, 95%CI = 0.28 to 1.59, P = 0.005), whole blood medium shear viscosity (WMD = 0.53, 95%CI = 0.11 to 0.95, P = 0.01), whole blood low shear viscosity (WMD = 1.26, 95%CI = 0.80 to 1.72, P < 0.001), plasma viscosity (WMD = 0.19, 95%CI = 0.09 to 0.30, P < 0.001) and fibrinogen (WMD = 0.80, 95%CI = 0.25 to 1.35, P = 0.004) were lower than those in the control group. There was no significant difference in the change of hematokrit between two groups (WMD = 4.23, 95%CI = -0.54 to 8.99, P = 0.08). GBE was generally well tolerated, and there was no significant difference in the incidence of adverse reactions between two groups (RR = 1.01, 95%CI = 0.57 to 1.79, P = 0.97).

Conclusion: The results of the current study suggested that GBE might be effective and promising as an adjuvant to corticosteroids in the initial treatment of moderate to profound SSNHL. However, the GRADE assessment indicated that the overall strength of evidence was not high. Further studies with high methodological quality and low risk of bias are needed to confirm the positive results. PROSPERO registration No. CRD 42020190113.
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http://dx.doi.org/10.1016/j.jep.2021.114587DOI Listing
August 2021

Effect of posture on pulmonary function and oxygenation after fast-tracking video-assisted thoracoscopic surgery (VATS) lobectomy: a prospective pilot study.

Perioper Med (Lond) 2021 Sep 2;10(1):26. Epub 2021 Sep 2.

Department of Cardiothoracic Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Minimally invasive surgery combined with enhanced recovery programmes has improved outcomes after lung cancer surgery and where early mobilisation may be an important factor. However, little is known about pulmonary function and oxygenation during mobilisation after video-assisted pulmonary lobectomy. The aim of this prospective pilot cohort study was to explore the effect of postural changes (from supine to sitting to standing) on pulmonary function and oxygen saturation in a well-defined enhanced recovery programmes setting after video-assisted thoracoscopic surgery lobectomy.

Methods: A total of 24 patients were evaluated daily for postoperative pain score, pulmonary function (forced expiratory volume 1 s) and oxygen saturation in supine, sitting and standing position from 6 h after surgery to 6 h after chest drain removal.

Results: Mobilisation from supine to standing position showed a significant 7.9% increase (p = 0.04) in forced expiratory volume in 1 s percentage and oxygen saturation about 1.8% (p< 0.001) without increasing pain (p = 0.809).

Conclusions: Early mobilisation should be encouraged to enhance recovery after video-assisted thoracoscopic surgery lobectomy by increasing lung function and oxygen delivery.

Trial Registration: • Name of the registry: clinicaltrials.gov • Trial registration number: NCT04508270 • Date of registration: August 11, 2020.
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http://dx.doi.org/10.1186/s13741-021-00199-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411530PMC
September 2021

Retraction notice to "The effect of LncRNA SNHG16 on vascular smooth muscle cells in CHD by targeting miRNA-218-5p"[Experimental and Molecular Pathology 118C (2021) 104595].

Exp Mol Pathol 2021 Aug 28:104677. Epub 2021 Aug 28.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of NanChang University, Nanchang 330006, Jiangxi Province, China.

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http://dx.doi.org/10.1016/j.yexmp.2021.104677DOI Listing
August 2021

Metabolic disturbance in lettuce (Lactuca sativa) plants triggered by imidacloprid and fenvalerate.

Sci Total Environ 2021 Aug 21;802:149764. Epub 2021 Aug 21.

MOE Key Laboratory of Environment Remediation and Ecological Health, College of Natural Resource & Environmental Sciences, Zhejiang University, Hangzhou 310058, China.

Intensive and indiscriminate use of insecticides in agroecosystems causes phytotoxic disturbances in non-target crops. However, the mechanisms by which plants reprogram cellular metabolites to resist and tolerate such agrochemicals remain unclear. Here, the interaction between lettuce plants with imidacloprid and fenvalerate was investigated by the complementary use of physiological and metabolomic analyses. Neither imidacloprid nor fenvalerate induced overt phytotoxicity in lettuce seedlings. The plant biomass, chlorophyll fluorescence, lipid peroxidation, and membrane integrity were not significantly affected by the selected insecticides. Flavonoid content decreased by 25% in lettuce leaves under fenvalerate exposure, whereas polyphenol and flavonoid contents were not significantly altered by imidacloprid. Although the content of most of the nutrient element in the leaves remained the same following pesticide treatment, iron content decreased by 28.1% under imidacloprid exposure but increased by 22.8% under fenvalerate exposure. Metabolomic analysis revealed that the selected insecticides induced extensive metabolic reprogramming in lettuce roots and shoots. Imidacloprid dramatically increased the metabolism of several amino acids (arginine, cysteine, homoserine, and 4-hydroxyisoleucine), whereas markedly decreased the metabolism of various carbohydrates (glucose, raffinose, maltotetraose, maltopentaose, and stachyose). Fenvalerate did not significantly alter amino acid metabolism but decreased carbohydrate metabolism. Additionally, the relative abundance of most organic acids and polyphenolic compounds decreased significantly after pesticide exposure. These results suggest that plants might program their primary and secondary metabolism to resist and tolerate insecticides. The findings of this study provide important information on how neonicotinoid and pyrethroid insecticides affect the health and physiological state of plants, which are ultimately associated with crop yield and quality.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149764DOI Listing
August 2021

Cross-Talk between Hydrogen Peroxide and Nitric Oxide during Plant Development and Responses to Stress.

J Agric Food Chem 2021 Aug 17;69(33):9485-9497. Epub 2021 Aug 17.

MOE Key Laboratory of Environment Remediation and Ecological Health, College of Natural Resource & Environmental Sciences, Zhejiang University, Hangzhou 310058, China.

Nitric oxide (NO) and hydrogen peroxide (HO) are gradually becoming established as critical regulators in plants under physiological and stressful conditions. Strong spatiotemporal correlations in their production and distribution have been identified in various plant biological processes. In this context, NO and HO act synergistically or antagonistically as signals or stress promoters depending on their respective concentrations, engaging in processes such as the hypersensitive response, stomatal movement, and abiotic stress responses. Moreover, proteins identified as potential targets of NO-based modifications include a number of enzymes related to HO metabolism, reinforcing their cross-talk. In this review, several processes of well-characterized functional interplay between HO and NO are discussed with respect to the most recent reported evidence on hypersensitive response-induced programmed cell death, stomatal movement, and plant responses to adverse conditions and, where known, the molecular mechanisms and factors underpinning their cross-talk.
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http://dx.doi.org/10.1021/acs.jafc.1c01605DOI Listing
August 2021

Macrophage migration inhibitory factor of Thelazia callipaeda induces M2-like macrophage polarization through TLR4-mediated activation of the PI3K-Akt pathway.

FASEB J 2021 09;35(9):e21866

Department of Parasitology, Zunyi Medical University, Zunyi, China.

Macrophage migration inhibitory factor (MIF), an immunoregulatory cytokine plays an important role in inflammation and the immune response, and has been described as having a potential role in immune evasion by parasites. Thelazia callipaeda, a vector-borne zoonotic eye worm with a broad host range, has been documented as an agent of ocular infection of thelaziosis. The ability of T. callipaeda to persist in an immunologically competent host has led to the suggestion that it has evolved specific measures to counter immune defenses. To date, whether the immune evasion of T. callipaeda is related to MIF and the possible related signaling pathway and molecular mechanism have remained unclear. In the present study, we examined the effect of T. callipaeda MIF (T. cp-MIF) on macrophages. We analyzed the antigenic epitopes of the candidate T. cp-MIF and found that it exhibited an ideal antigenic index. Morphology, Flow cytometry, and cytokine analysis showed that T. cp-MIF induced the dynamic polarization of THP-1 macrophages from the M1-like phenotype to the M2-like phenotype. The chemotaxis assay revealed an inhibitory effect of T. cp-MIF on THP-1 macrophages. Western blotting suggested that, compared to the control, THP-1 macrophages exposed to T. cp-MIF had higher TLR4 protein expression and the phosphatidylinositol 3'-kinase (PI3K) -Akt pathway activation. In conclusion, T. cp-MIF induces M2-like macrophage polarization through TLR4-mediated activation of the PI3K-Akt pathway, which might provide a basis for future research on how it affects the immune system of the host.
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http://dx.doi.org/10.1096/fj.202100676RDOI Listing
September 2021

Inhibition of immunoproteasome subunit low molecular mass polypeptide 7 with ONX-0914 improves hypoxic-ischemic brain damage via PI3K/Akt signaling.

Neuroreport 2021 Oct;32(14):1206-1215

Department of Pediatrics, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.

The immunoproteasome subunit low molecular mass polypeptide 7 (LMP7) leads to brain injuries, such as autoimmune neuritis and ischemic stroke, by activating inflammation. However, the roles and mechanisms of LMP7 in hypoxic-ischemic brain damage (HIBD) remain unclear. This study explored these issues in a rat model of HIBD. Pathology was evaluated using hematoxylin-eosin staining. LMP7 expression was detected using western blot analysis, reverse transcription-quantitative PCR (RT-qPCR), and immunohistochemical staining. The presence of proinflammatory cytokines, including tumor necrosis factor-a, interleukin-6, and interleukin-1β, was tested using ELISA and RT-qPCR. Behavioral performance was evaluated using a short-term neurological function score and the Morris water maze test. Compared to those in the Sham group, the HIBD group exhibited obvious upregulated LMP7 and pro-inflammatory cytokine levels. HIBD rats exhibited severe pathological and behavioral damage. LMP7 inhibition with ONX-0914 reduced proinflammatory cytokine expression, attenuated pathological damage, and enhanced behavioral performance of rats with HIBD. Inhibition of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling with LY29400 increased LMP7 expression and abolished the protective effects of ONX-0914 in HIBD rats. Our findings indicate that LMP7 aggravates brain injury by triggering inflammatory responses in HIBD rats. LMP7 inhibition with ONX-0914 exerts protective effects on HIBD rats, possibly via PI3K/Akt signaling.
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http://dx.doi.org/10.1097/WNR.0000000000001715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389355PMC
October 2021

Cell-based assays and molecular simulation reveal that the anti-cancer harmine is a specific matrix metalloproteinase-3 (MMP-3) inhibitor.

Comput Biol Chem 2021 Oct 6;94:107556. Epub 2021 Aug 6.

Synergy Biomedical Corp., Hsinchu City, 30054, Taiwan, ROC. Electronic address:

The biological activities of harmine have been a much clearer picture in recent years, which include anti-tumor, anti-inflammation and cytotoxic properties. Numerous in vitro and in vivo animal models have confirmed its activities, but its mode of action remains a relative unsolved issue. We therefore investigated harmine for its effects on MMP-3 and the molecular interaction was also simulated. The human glioma cancer cell line, U-87 MG cells, was subjected to different concentrations (1-10 μM) of harmine for 24 h. Methylthiazol tetrazolium (MTT) test, half maximal inhibitory concentration (IC50), western blot analysis, enzyme-linked immunosorbent assay and molecular docking through BIOVIA DiscoveryStudio™ were performed. These results showed that although harmine stimulation in vitro has very little or no effects on MMP-3 expression by U-87 MG cells, the treatment of harmine decreases MMP-3 activity in a dose dependent manner. It was further calculated that 7.9 μM is the IC50 towards MMP-3. Using a molecular dynamic simulation approach, we identified the N2, methyl of C1 and benzene ring of harmine interact with Zn (2.4 Å), His205 (2.4 Å) and His211 (2.4 Å) as well as Val163 (2.7 Å) at the active site of MMP-3, respectively, and thus conferred a striking specific binding advantage. Taken altogether, the present study evidences that harmine acts as an MMP-3 inhibitor specially targeting the enzymatic active site and possibly efficiently ameliorates MMP-3-driven malignant and inflammatory diseases.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107556DOI Listing
October 2021

Plant uptake of CO outpaces losses from permafrost and plant respiration on the Tibetan Plateau.

Proc Natl Acad Sci U S A 2021 Aug;118(33)

Institute of Mountain Hazards and Environment, Chinese Academy of Sciences, Chengdu 610041, China;

High-latitude and high-altitude regions contain vast stores of permafrost carbon. Climate warming may result in the release of CO from both the thawing of permafrost and accelerated autotrophic respiration, but it may also increase the fixation of CO by plants, which could relieve or even offset the CO losses. The Tibetan Plateau contains the largest area of alpine permafrost on Earth. However, the current status of the net CO balance and feedbacks to warming remain unclear, given that the region has recently experienced an atmospheric warming rate of over 0.3 °C decade We examined 32 eddy covariance sites and found an unexpected net CO sink during 2002 to 2020 (26 of the sites yielded a net CO sink) that was four times the amount previously estimated. The CO sink peaked at an altitude of roughly 4,000 m, with the sink at lower and higher altitudes limited by a low carbon use efficiency and a cold, dry climate, respectively. The fixation of CO in summer is more dependent on temperature than the loss of CO than it is in the winter months, especially at higher altitudes. Consistently, 16 manipulative experiments and 18 model simulations showed that the fixation of CO by plants will outpace the loss of CO under a wetting-warming climate until the 2090s (178 to 318 Tg C y). We therefore suggest that there is a plant-dominated negative feedback to climate warming on the Tibetan Plateau.
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http://dx.doi.org/10.1073/pnas.2015283118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379928PMC
August 2021

Biomimetic Biphasic Electrospun Scaffold for Anterior Cruciate Ligament Tissue Engineering.

Tissue Eng Regen Med 2021 Oct 5;18(5):819-830. Epub 2021 Aug 5.

College of Materials and Metallurgy, Guizhou University, Guiyang, Guizhou, China.

Background: Replacing damaged anterior cruciate ligaments (ACLs) with tissue-engineered artificial ligaments is challenging because ligament scaffolds must have a multiregional structure that can guide stem cell differentiation. Here, we designed a biphasic scaffold and evaluated its effect on human marrow mesenchymal stem cells (MSCs) under dynamic culture conditions as well as rat ACL reconstruction model in vivo.

Methods: We designed a novel dual-phase electrospinning strategy wherein the scaffolds comprised randomly arranged phases at the two ends and an aligned phase in the middle. The morphological, mechanical properties and scaffold degradation were investigated. MSCs proliferation, adhesion, morphology and fibroblast markers were evaluated under dynamic culturing. This scaffold were tested if they could induce ligament formation using a rodent model in vivo.

Results: Compared with other materials, poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone) (PLGA/PCL) with mass ratio of 1:5 showed appropriate mechanical properties and biodegradability that matched ACLs. After 28 days of dynamic culturing, MSCs were fusiform oriented in the aligned phase and randomly arranged in a paving-stone-like morphology in the random phase. The increased expression of fibroblastic markers demonstrated that only the alignment of nanofibers worked with mechanical stimulation to promote effective fibroblast differentiation. This scaffold was a dense collagenous structure, and there was minimal difference in collagen direction in the orientation phase.

Conclusion: Dual-phase electrospun scaffolds had mechanical properties and degradability similar to those of ACLs. They promoted differences in the morphology of MSCs and induced fibroblast differentiation under dynamic culture conditions. Animal experiments showed that ligamentous tissue regenerated well and supported joint stability.
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http://dx.doi.org/10.1007/s13770-021-00376-7DOI Listing
October 2021

Why did a Hemodialysis Patient Escape from COVID-19 Familial Cluster Infection?

Disaster Med Public Health Prep 2021 Aug 4:1-2. Epub 2021 Aug 4.

School of Basic Medicine, Zhejiang Chinese Medicine University, Hangzhou, China.

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http://dx.doi.org/10.1017/dmp.2021.247DOI Listing
August 2021

Ultra-Fast Label-Free Serum Metabolic Diagnosis of Coronary Heart Disease via a Deep Stabilizer.

Adv Sci (Weinh) 2021 Sep 29;8(18):e2101333. Epub 2021 Jul 29.

State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.

Although mass spectrometry (MS) of metabolites has the potential to provide real-time monitoring of patient status for diagnostic purposes, the diagnostic application of MS is limited due to sample treatment and data quality/reproducibility. Here, the generation of a deep stabilizer for ultra-fast, label-free MS detection and the application of this method for serum metabolic diagnosis of coronary heart disease (CHD) are reported. Nanoparticle-assisted laser desorption/ionization-MS is used to achieve direct metabolic analysis of trace unprocessed serum in seconds. Furthermore, a deep stabilizer is constructed to map native MS results to high-quality results obtained by established methods. Finally, using the newly developed protocol and diagnosis variation characteristic surface to characterize sensitivity/specificity and variation, CHD is diagnosed with advanced accuracy in a high-throughput/speed manner. This work advances design of metabolic analysis tools for disease detection as it provides a direct label-free, ultra-fast, and stabilized platform for future protocol development in clinics.
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http://dx.doi.org/10.1002/advs.202101333DOI Listing
September 2021

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network.

Biomed Res Int 2021 30;2021:6618834. Epub 2021 Jun 30.

Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

Low back pain which resulted from intervertebral disc degeneration (IDD) is a common health problem that afflicts people all over the world. Due to the lack of an overall understanding of the molecular interactions involved in IDD, we hope to better understand the pathogenetic mechanisms that drive the degenerative process. The purpose of this study is to obtain mRNAs, miRNAs, lncRNAs, and circRNAs associated with IDD gained from public databases and to establish an interaction network. According to the results of microarray analysis and bioinformatics analysis from the contrast of IDD and normal nucleus pulposus tissues, a total of 49 mRNAs, 10 miRNAs, 30 lncRNAs, and 4 circRNAs were obtained and a lncRNA/circRNA-miRNA-mRNA interaction network was constructed. NEAT1-miR-5100-COL10A1 and miR663AHG/HEIH/hsa-circ-0003600-miR-4741-HAS2/HYAL1/LYVE1 might be potential interaction axes of the molecular mechanism in IDD. The increased expression of NEAT1 might inhibit miR-5100 and subsequently upregulate the expression of COL10A1, which leads to IDD, while the increased expression of miR663AHG/HEIH/hsa-circ-0003600 might inhibit miR-4741 and indirectly upregulate HAS2/HYAL1/LYVE1, and leads to the protection from IDD. More interaction axes are to be exploited to provide theoretical bases for further study on IDD.
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http://dx.doi.org/10.1155/2021/6618834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263249PMC
September 2021

Determining the function of LvSmad3 on Litopenaeus vannamei in response to acute low temperature stress.

Dev Comp Immunol 2021 Dec 22;125:104209. Epub 2021 Jul 22.

Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, PR China; Key Laboratory of Ecology and Environmental Science in Guangdong Higher Education, College of Life Science, South China Normal University, Guangzhou, 510631, PR China. Electronic address:

Smad3 is a key mediator of the canonical TGF-β signaling pathway and plays an important role in TGF-β1-mediated transcriptional regulation. However, the function of Smad3 in crustaceans such as shrimp, is still poorly understood and needs to be further explored. We characterized Litopenaeus vannamei Smad3 (LvSmad3) and its biological functions were investigated in response low temperature stress. Full-length LvSmad3 cDNA was 2341bp and contained an open reading frame (ORF) of 1326 bp that encoded a 441 amino acid long protein, with a predicted molecular mass of 48.35 kDa. Phylogenetic analysis revealed that LvSmad3 has a high degree of similarity with other known species. LvSmad3 mRNA was detected in all the tested tissues and highest transcription occurred mostly in gills. Further research showed that suppressing the expression of Smad3 could reduce ROS production, DNA damage and the apoptosis rate in shrimp hemocyte under low temperature compared with the dsGFP group. Thus, we speculated that Smad3 could promote the apoptosis of hemocytes. We confirmed that Smad3 could inhibit apoptosis in the hepatopancreas by suppressing the expression of pro-apoptotic genes. Taken together, the silencing of Smad3 can reduce ROS production induced by low temperature stress, weaken the damage to hemocytes and the hepatopancreas by inhibit the apoptosis.
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http://dx.doi.org/10.1016/j.dci.2021.104209DOI Listing
December 2021

Multifunctional chitin-based barrier membrane with antibacterial and osteogenic activities for the treatment of periodontal disease.

Carbohydr Polym 2021 Oct 1;269:118276. Epub 2021 Jun 1.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine Ministry of Education, Department of Dental Implantology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, PR China. Electronic address:

The guided tissue regeneration technique is an effective approach to repair periodontal defect. However, collagen barrier membranes used clinically lose stability easily, leading to soft tissue invasion, surgical site infection, and failure of osteogenesis. An ideal barrier membrane should possess proper antibacterial, osteoconductive activities, and favorable biodegradation. In this study, zinc oxide nanoparticles were homogeneously incorporated into the chitin hydrogel (ChT-1%ZnO) through one-step dissolution and regeneration method from alkaline/urea solution the first time. The remaining weights of ChT-1%ZnO in 150 μg/mL lysozyme solution was 52% after 5 weeks soaking. ChT-1%ZnO showed statistical antibacterial activities for P. gingivalis and S. aureus at 6 h, 12 h, and 24 h. Moreover, ChT-1%ZnO exhibits osteogenesis promotion in vitro, and it was further evaluated with rat periodontal defect model in vivo. The cemento-enamel junction value in ChT-1%ZnO group is 1.608 mm, presenting a statistical difference compared with no-membrane (1.825 mm) and ChT group (1.685 mm) after 8 weeks postoperatively.
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http://dx.doi.org/10.1016/j.carbpol.2021.118276DOI Listing
October 2021

The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer's Disease: Implications for Treatment.

Front Cell Dev Biol 2021 1;9:609908. Epub 2021 Jul 1.

PET Center, Huashan Hospital, Fudan University, Shanghai, China.

Alzheimer's disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found that the expression of SV2A was down-regulated in the hippocampus of AD patients, yet the relation of SV2A to other hallmarks of AD pathology such as amyloid precursor protein (APP), β-amyloid (Aβ), and Tau protein is not thoroughly clear. In addition, SV2A colocalized with APP and was down-regulated at Aβ deposition. Moreover, we found that SV2A deficiency leads to a simultaneous increase in Aβ and Tau hyperphosphorylation, while SV2A overexpression was associated with downregulation of β-site APP cleaving enzyme 1 and apolipoprotein E genes. In addition, evidence gained in the study points to the phosphatidylinositol 3-kinase signaling pathway as a possible mediator in SV2A regulation influencing the incidence and development of AD. With limited effective diagnostic methods for AD, a close interplay between SV2A and AD-related proteins demonstrated in our study may provide novel and innovative diagnostic and therapeutic opportunities.
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http://dx.doi.org/10.3389/fcell.2021.609908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282058PMC
July 2021

The immune checkpoint regulator PD-L1 expression are associated with clinical progression in prostate cancer.

World J Surg Oncol 2021 Jul 16;19(1):215. Epub 2021 Jul 16.

Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Guangxi Zhuang Autonomous Region, Nanning, 530021, China.

Background: The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown positive efficacy in several solid cancers due to their targeted antitumour effects. However, the frequency and clinical implication value in prostate cancer still remain unclear.

Methods: The PD-1/PD-L1 expression was detected by immunohistochemical (IHC) analysis in 96 retrospectively collected cases of prostatic cancer and 44 controls of benign prostatic hyperplasia (BPH). Its correlation with clinicopathological features including age, PSA level, Gleason score, lymph node metastasis, clinical T stage and risk factor grade in prostate cancer was also assessed.

Results: The PD-L1-positive expression was significantly higher in cancer cases compared with benign tissues, whereas no difference in PD-1 positive expression was found. Moreover, the PD-L1 expression in tumour cells or lymphocytes was associated with Gleason score, but not related to age, preoperative PSA level, clinical T-stage, lymph node metastasis and grade of risk factors. In addition, no association between the positive expression of PD-1 and PD-L1 in tumour cells and lymphocytes was found.

Conclusions: The expression of PD-L1 not PD-1 is highly prevalent in prostate cancer. PD-L1 is closely related to Gleason score and may be a co-factor associated with the progression of prostate cancer.
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http://dx.doi.org/10.1186/s12957-021-02325-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285882PMC
July 2021

Advances in chlorin-based photodynamic therapy with nanoparticle delivery system for cancer treatment.

Expert Opin Drug Deliv 2021 Oct 15;18(10):1473-1500. Epub 2021 Jul 15.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China.

: The treatment of tumors is one of the most difficult problems in the medical field at present. Patients often use a comprehensive therapy that combines surgery, radiotherapy, and chemotherapy. Photodynamic therapy (PDT) has prominent potential for eradicating various cancers. Chlorin-based photosensitizers (PSs), as one of the most utilized photosensitizers, have many advantages over conventional photosensitizers; however, a successful chlorin-based PDT needs multi-functional nano-carriers for selective photosensitizer delivery. The number of researches about nanoparticles designed for improved chlorin-based PSs is increasing in the current era. In this article, we give a brief review focused on the recent research progress in design of chlorin-based nanoparticles for the treatment of malignant tumors with photodynamic therapy.: This review focuses on the current nanoparticle platforms for PDT, and describes different strategies to achieve controllable PDT by chlorin-nano-delivery systems. The challenges and prospects of PDT in clinical applications are also discussed.: The requirement for PDT to eradicate cancers has increased exponentially in recent years. The major clinically used photosensitizers are hydrophobic. The main obstacles in effective delivery of PSs are associated with this intrinsic nature. The design of nano-delivery systems to load PSs is pivotal for PSs' widespread use.
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http://dx.doi.org/10.1080/17425247.2021.1950685DOI Listing
October 2021

Case Report: Re-Sensitization to Gefitinib in Lung Adenocarcinoma Harboring EGFR Mutation and High PD-L1 Expression After Immunotherapy Resistance, Which Finally Transform Into Small Cell Carcinoma.

Front Oncol 2021 24;11:661034. Epub 2021 Jun 24.

Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

The treatment sequence of immunotherapy (IO) and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is of great importance for the survival of non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. Here, we reported an advanced lung adenocarcinoma case concurrent with EGFR sensitive mutation and high PD-L1 expression (>50%) that was administrated with gefitinib firstly, and then became resistant to EGFR-TKI. He received the strategy of immunity-combined chemo-radiotherapy and responded significantly. However, the disease re-progressed after 10 months. Surprisingly, the tumor re-sensitized to gefitinib for 13 months. At final, following the treatment pressure of TKI-IO combination therapy-TKI strategy, tumor clone eventually transformed into small cell lung carcinoma (SCLC). For one thing, our study provided novel approach and extended the treatment spectra of overcoming immunotherapy resistance after EGFR resistance in driver oncogene-mutated NSCLC. For another thing, our case is the first time to report that SCLC transformation can be achieved after gefitinib-pembrolizumab-gefitinib resistance in EGFR sensitive mutation NSCLC, providing a new condition for SCLC transformation.
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http://dx.doi.org/10.3389/fonc.2021.661034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264361PMC
June 2021
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