Publications by authors named "Yi Lin"

1,191 Publications

  • Page 1 of 1

The effect of orthodontic treatment on temporomandibular joint morphology in adult skeletal class II deep overbite patients.

Am J Transl Res 2021 15;13(8):9070-9075. Epub 2021 Aug 15.

Department of Stomatology, Fujian Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital Fuzhou, Fujian Province, China.

Objective: To explore the morphological changes of the temporomandibular joint (TMJ) in adult patients with skeletal class II deep overbite before and after orthodontic treatment, and to analyze the effect of the orthodontic treatment.

Methods: A total of 40 adult skeletal class II deep overbite patients were recruited as the study cohort. For each subject, the morphology and position of the TMJ were determined using cone beam computed tomography.

Results: Compared with before the treatment, the morphology of the condyle changed. The maximum cross-sectional area of the condyle in the axial plane and the condyle neck anteroposterior diameter in the coronal plane were reduced. The condylar apex height in the sagittal plane and the anterior condyle oblique inclination increased with statistically significant differences (all P<0.001). There were more patients who showed their condyles moving forward and their condyles in the middlee after the treatment compared with before the treatment, and with a statistically significant difference (P=0.002). The morphology of the glenoid fossa changed after the treatment. The articular eminence to the FH plane angle in the sagittal plane and the inclination of the posterior glenoid increased. The total height of the fossa increased with statistically significant differences (all P<0.001).

Conclusion: TMJs can be adaptive to reconstruction. Orthodontic treatment shows a favorable efficacy in skeletal class ll deep overbite patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430164PMC
August 2021

Protective effect of 18β-glycyrrhetinic acid against HO-induced injury in Schwann cells based on network pharmacology and experimental validation.

Exp Ther Med 2021 Nov 1;22(5):1241. Epub 2021 Sep 1.

College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.

The aim of the present study was to assess the protective effects of 18β-GA against hydrogen peroxide (HO)-induced injury. First, the SMILES annotation for 18β-GA was used to search PubChem and for reverse molecular docking in Swiss Target Prediction, the Similarity Ensemble Approach Search Server and the TargetNet database to obtain potential targets. Injury-related molecules were obtained from the GeneCards database and the predicted targets of 18β-GA for injury treatment were selected by Wayne diagram analysis. Subsequently, Kyoto Encyclopedia of Genes and Genomes analysis was performed by WebGestalt. The experimental cells were assorted into control, model, 10 µM SB203580-treated, 5 µM 18β-GA-treated and 10 µM 18β-GA-treated groups. Hoechst 33258 staining was performed and intracellular reactive oxygen species (ROS) levels, cell apoptosis, Bcl-xl, Bcl-2, Bad, Bax, cleaved-caspase 3, cleaved-caspase 7, transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) levels, as well as p38 MAPK phosphorylation were measured. The 'Inflammatory mediator regulation of TRP channels' pathway was selected for experimental verification. The results indicated that 10 µM 18β-GA significantly increased cell viability as compared with the HO-treated model group. As suggested by the difference in intracellular ROS fluorescence intensity, 18β-GA inhibited HO-induced ROS production in Schwann cells. Hoechst 33258 staining indicated that 18β-GA reversed chromatin condensation and the increase in apoptotic nuclei following HO treatment. Furthermore, flow cytometry suggested that 18β-GA substantially inhibited HO-induced apoptosis. Pre-treatment with 18β-GA obviously reduced Bad, Bax, cleaved-caspase3, cleaved-caspase 7, TRPA1 and TRPV1 levels and p38 MAPK phosphorylation after HO treatment and increased Bcl-2 and Bcl-xl levels. In conclusion, 18β-GA inhibited Schwann cell injury and apoptosis induced by HO and may be a potential drug to prevent peripheral nerve injury.
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http://dx.doi.org/10.3892/etm.2021.10676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438673PMC
November 2021

Potential markers for sample size estimations in hereditary spastic paraplegia type 5.

Orphanet J Rare Dis 2021 Sep 19;16(1):391. Epub 2021 Sep 19.

Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, Fujian Medical University, Fuzhou, 350005, China.

Background: Aim to identify potential biomarkers to assess therapeutic efficacy for hereditary spastic paraplegias type 5 (SPG5) by investigating the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features.

Methods: We performed a cross-sectional study to compare SPG5 patients with age- and sex-matched healthy controls who underwent conventional and quantitative MRI techniques of spinal cord (C1-T9) and brain. SPG5 patients also underwent assessment for clinical status and CSF biomarkers (27-hydroxycholesterol, neurofilament light). We identified a set of markers with standardized effect sizes (|t|> 0.5) to estimate sample sizes for disease progression (disease duration > 14 years vs. ≤ 14 years).

Results: Seventeen genetically confirmed SPG5 patients (11 men, 6 women; age range, 13-49 years; median disease duration, 14 years) were enrolled. Compared to healthy controls, the total spinal cord area (SCA) of SPG5 patients was reduced particularly at the thoracic levels (cervical levels: 12-27%; thoracic levels 41-60%). Patients did not show significant alterations of brain signal abnormalities or atrophy relative to controls. A total of 10 surrogate markers were selected and a minimum sample size was achieved with the measurement of SCA on T9 (n = 22) much less that what would be required if using clinical disability assessment (n = 124).

Conclusions: SPG5 patients showed distinct MRI features of spinal cord atrophy without significant brain alterations. Our finding supports the measurements of spinal cord on T9 level as potential endpoint for SPG5 clinical trials. Trial registration ClinicalTrials.gov, NCT04006418. Registered 05 July 2019, https://clinicaltrials.gov/ct2/show/NCT04006418?term=NCT04006418&draw=2&rank=1 .
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http://dx.doi.org/10.1186/s13023-021-02014-wDOI Listing
September 2021

Periconnection: A novel macroecological effect in snow cover phenology modulating ecosystem productivity over upper Northern Hemisphere.

Authors:
Yi Lin Geoff West

Sci Total Environ 2021 Sep 7;805:150164. Epub 2021 Sep 7.

Department of Spatial Sciences, Curtin University of Technology, Perth 6708, Australia.

Snow cover plays an important role in maintaining ecosystems. However, knowledge on how snow cover phenology (SP) modulates ecosystem productivity (EP), especially for the lower- and higher-productivity ecosystems, is limited yet. The situation becomes more embarrassed when asking a more in-depth question as to the macroecological pattern of SP modulating EP - does this process act with the neighborhood effect common in ecology or any other? To answer this question, we proposed a new concept of "periconnection", by following the way of defining "teleconnection" but also exploring the potential effect from the surrounding sites. In the case study of two published data of plant dynamics (1999-2013) and SP (2001-2014), we made a series of new findings as follows. Over upper Northern Hemisphere, the lower- and higher-productivity ecosystems presented weaker trends of productivity increasing than the entire ecosystems did. But for the ecosystems of all these three types, their productivity was all more sensitive to the snow-onset than -end SP. Further, the interannual variations of their productivity was all more modulated by the SP around - the neighborhood effect, in principle, was detected but also with other novel traits. Such modulations occurred more to north in North America while more to south in North Eurasia - termed directional effect. The first two inferences added the common knowledge of SP modulating EP, while the in-depth question was solved with the last two coherent effects, which compose a new macroecological beyond-neighborhood effect - periconnection. As a creative theoretical term and its principle framework in macroecology, this basic concept is of referencing implication on extensively advancing various sphere-interaction fields at other scales.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150164DOI Listing
September 2021

Design of a FAIR digital data health infrastructure in Africa for COVID-19 reporting and research.

Adv Genet (Hoboken) 2021 Jun 11;2(2):e10050. Epub 2021 Jun 11.

Stanford Center for Biomedical Informatics Research Stanford University Stanford California USA.

The limited volume of COVID-19 data from Africa raises concerns for global genome research, which requires a diversity of genotypes for accurate disease prediction, including on the provenance of the new SARS-CoV-2 mutations. The Virus Outbreak Data Network (VODAN)-Africa studied the possibility of increasing the production of clinical data, finding concerns about data ownership, and the limited use of health data for quality treatment at point of care. To address this, VODAN Africa developed an architecture to record clinical health data and research data collected on the incidence of COVID-19, producing these as human- and machine-readable data objects in a distributed architecture of locally governed, linked, human- and machine-readable data. This architecture supports analytics at the point of care and-through data visiting, across facilities-for generic analytics. An algorithm was run across FAIR Data Points to visit the distributed data and produce aggregate findings. The FAIR data architecture is deployed in Uganda, Ethiopia, Liberia, Nigeria, Kenya, Somalia, Tanzania, Zimbabwe, and Tunisia.
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http://dx.doi.org/10.1002/ggn2.10050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420285PMC
June 2021

Low-dose exposure to black carbon significantly increase lung injury of cadmium by promoting cellular apoptosis.

Ecotoxicol Environ Saf 2021 Nov 31;224:112703. Epub 2021 Aug 31.

Tianjin Medical University General Hospital, Tianjin 300211, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Particulate matter 2.5 (PM) has adverse biological effects on major living organs in the body, including lungs. The complex composition of PM, including carbon black and heavy metals, cause toxic effects to the lung. Nonetheless, there exists considerable knowledge gaps regarding the impact of carbon black (CB) on environmental health and safety (EHS). Thus far, the synergistic effects of CB have not gained much attention in past decades. Here, we showed that combined exposure of CB and Cadmium (Cd) enhance the cytotoxicity by altering the state of cell membrane. Specially, CB caused cell membrane collapse and increased the permeability of cells, and remarkedly enhanced the metal Cd toxicity. Furthermore, upon pre-treatment sublethal-dose CB, the increased intracellular Cd brought about a significantly amount of lactate dehydrogenase (LDH) and high expression of metallothionein-1 (MT-1) in human lung epithelial cell line (BEAS-2B) cells, and ultimately resulted an increased cellular toxicity. The lung of mice exposed CBs and Cd presented remarkably inflammation than Cd alone. Mechanistic exploration deciphered that CB pre-treatment triggered cell damage via apoptosis due to Cd exposure. Collectively, our findings reveal a novel path for understanding the impact of CB on EHS with its synergistic effects, through which nanomaterials might exert detrimental effects on organisms.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112703DOI Listing
November 2021

Comparison of 2-year outcomes with CAR T cells (ZUMA-1) versus salvage chemotherapy in refractory large B-cell lymphoma.

Blood Adv 2021 Sep 3. Epub 2021 Sep 3.

Hopital Saint-Louis, Paris, France.

The SCHOLAR-1 international retrospective study highlighted poor clinical outcomes and survival among patients with refractory large B-cell lymphoma (LBCL) treated with conventional chemotherapy. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, demonstrated durable responses in patients with refractory LBCL in the pivotal phase 1/2 ZUMA-1 study (NCT02348216). Here, we compared SCHOLAR-1 with the 2 year outcomes of ZUMA-1. Prior to comparison of clinical outcomes, propensity scoring (based on a broad set of prognostic covariates) was used to create balance between ZUMA-1 and SCHOLAR-1 patients. In the pivotal phase 2 portion of ZUMA-1, 101 patients received axi-cel and were evaluable for response and survival. In SCHOLAR-1, 434 and 424 patients were evaluable for response and survival, respectively. ZUMA-1 patients were more heavily pretreated than SCHOLAR-1 patients. The median follow-up was 27.1 months in ZUMA-1. The objective response rate and complete response rate were 83% and 54% in ZUMA 1 vs 34% and 12% in SCHOLAR-1, respectively. The 2-year survival rate was 54% in ZUMA-1 and 20% in SCHOLAR-1, and a 73% reduction in the risk of death was observed in ZUMA-1 vs SCHOLAR-1. These results were consistent with those of an additional standardization analysis in which strata were limited to 2 prognostic factors (refractory categorization and presence/absence of stem cell transplant after refractoriness to chemotherapy) to conserve sample size. Despite the limitations of a nonrandomized analysis, these results indicate that axi-cel produces durable responses and a substantial survival benefit versus non-CAR T-cell salvage regimens for patients with refractory LBCL.
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http://dx.doi.org/10.1182/bloodadvances.2020003848DOI Listing
September 2021

Unisensory and Multisensory Stroop Effects Modulate Gender Differences in Verbal and Nonverbal Emotion Perception.

J Speech Lang Hear Res 2021 Sep 22:1-19. Epub 2021 Sep 22.

Department of Speech-Language-Hearing Sciences & Center for Neurobehavioral Development, University of Minnesota, Minneapolis.

Purpose This study aimed to examine the Stroop effects of verbal and nonverbal cues and their relative impacts on gender differences in unisensory and multisensory emotion perception. Method Experiment 1 investigated how well 88 normal Chinese adults (43 women and 45 men) could identify emotions conveyed through face, prosody and semantics as three independent channels. Experiments 2 and 3 further explored gender differences during multisensory integration of emotion through a cross-channel (prosody-semantics) and a cross-modal (face-prosody-semantics) Stroop task, respectively, in which 78 participants (41 women and 37 men) were asked to selectively attend to one of the two or three communication channels. Results The integration of accuracy and reaction time data indicated that paralinguistic cues (i.e., face and prosody) of emotions were consistently more salient than linguistic ones (i.e., semantics) throughout the study. Additionally, women demonstrated advantages in processing all three types of emotional signals in the unisensory task, but only preserved their strengths in paralinguistic processing and showed greater Stroop effects of nonverbal cues on verbal ones during multisensory perception. Conclusions These findings demonstrate clear gender differences in verbal and nonverbal emotion perception that are modulated by sensory channels, which have important theoretical and practical implications. Supplemental Material https://doi.org/10.23641/asha.16435599.
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http://dx.doi.org/10.1044/2021_JSLHR-20-00338DOI Listing
September 2021

Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis.

J Inflamm Res 2021 24;14:4079-4088. Epub 2021 Aug 24.

Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Introduction: Post-traumatic osteoarthritis (PTOA) is an inflammatory condition that occurs following mechanical joint trauma and that results in joint degeneration. This study sought to evaluate the regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in a murine model of anterior cruciate ligament transection (ACLT)-induced PTOA and in an in vitro model of synoviocyte inflammation induced by LPS treatment with the goal of exploring the role of chitinase 3-like-1 (CHI3L1) in this pathogenic context.

Methods: PTOA model mice were intra-articularly injected with Nrf2 overexpression lentiviral vector, and safranin O-fast green staining as well as the Osteoarthritis Research Society International (OARSI) Scoring System were used to evaluate the severity of cartilage damage. Protein expression in the synovial tissue was evaluated by Western blotting, immunohistochemical staining, and ELISA. Additionally, murine synoviocytes were infected with Nrf2 overexpression lentivirus and stimulated with LPS. The levels of inflammatory cytokines were detected by ELISA. ROS levels were measured using dihydroethidium (DHE) dye.

Results: We determined that the overexpression of Nrf2 was sufficient to reduce cartilage degradation in the context of PTOA in vivo, and we observed a significant decrease in the expression of matrix metalloproteinase 13 (MMP13) in the articular cartilage of samples from mice overexpressing Nrf2 relative to control mice. Synovial CHI3L1 expression and serum TNF-α, IL-1β, and IL-6 levels were reduced in animals overexpressing this transcription factor relative to PTOA model controls. Consistent with these findings, murine synoviocytes treated with LPS exhibited dose-dependent increases in ROS, TNF-α, IL-1β, IL-6, Nrf2, and CHI3L1 levels, whereas Nrf2 overexpression was sufficient to suppress these increases.

Conclusion: Our data indicated that Nrf2 negatively regulates CHI3L1, suggesting that this signaling axis may regulate PTOA progression and may thus be a viable therapeutic target in individuals affected by this condition.
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http://dx.doi.org/10.2147/JIR.S310831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403022PMC
August 2021

Outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.

Hematol Oncol 2021 Aug 28. Epub 2021 Aug 28.

Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities. Immunochemotherapy with or without involved-site radiation therapy (ISRT) is considered standard front-line therapy. Over-expression of PD-L1/PD-L2 is seen in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from 1 January 2000 to 31 December 2020. Using the Kaplan-Meier method, we calculated progression-free survival, duration of response, and overall survival in patients who received front-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with and without ISRT, and salvage ICI therapy for relapsed/refractory disease. A total of 28 patients with PCDLBCL, LT were identified. The median PFS in patients treated with R-CHOP plus ISRT was 58 months (95% CI: 18-112) compared to 14 months (95% CI: 5-not reached; p = 0.04) in those treated with R-CHOP without ISRT. The median PFS from salvage ICI therapy was 10 months (95% CI: 4-not reached), and median DOR from salvage ICI therapy was 23 months [95% CI: 4-26]. R-CHOP with ISRT had a significantly longer median PFS compared to R-CHOP without ISRT as front-line therapy for PCDLBCL, LT. ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre-treated patients was observed in this study.
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http://dx.doi.org/10.1002/hon.2919DOI Listing
August 2021

Recombinase-Aided Amplification Coupled with Lateral Flow Dipstick for Efficient and Accurate Detection of Porcine Parvovirus.

Life (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Porcine parvovirus (PPV) infection is the primary cause of SMEDI (stillbirth; mummification; embryonic death; infertility) syndrome, which is a global burden for the swine industry. Thus, it is crucial to establish a rapid and efficient detection method against PPV infection. In the present work, we developed a recombinase-aided amplification (RAA) assay, coupled with a lateral flow dipstick (LFD), to achieve an amplification of PPV DNA at 37 °C within 15 min. The detection limits of PPV RAA-LFD assay were 10 copies/μL recombinant plasmid pMD19-T-VP1, 6.38 × 10 ng/μL PPV DNA, and 10 TCID/mL virus, respectively. This method was highly specific for PPV detection with no cross-reactivity for other swine pathogens. In contrast to polymerase chain reaction (PCR), the PPV RAA-LFD assay is more sensitive and cost-saving. Hence, the established PPV RAA-LFD assay provided an alternative for PPV detection, especially in resource-limited regions.
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http://dx.doi.org/10.3390/life11080762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401844PMC
July 2021

Phloretin Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Regulating the Inflammatory Response, Oxidative Stress and Apoptosis.

Life (Basel) 2021 Jul 26;11(8). Epub 2021 Jul 26.

Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.

The inflammatory process is proposed to be one of the factors to benign prostatic enlargement (BPH), and this is the first study examining the anti-inflammatory ability of phloretin in treating rats with testosterone-induced BPH. BPH would be induced by testosterone (10 mg/kg/day testosterone subcutaneously for 28 days), and the other groups of rats were treated with phloretin 50 mg/kg/day or 100 mg/kg/day orally (phr50 or phr100 group) after induction. Prostate weight and prostate weight to body weight ratio were significantly reduced in the Phr100 group. Reduced dihydrotestosterone without interfering with 5α-reductase was observed in the phr100 group. In inflammatory proteins, reduced IL-6, IL-8, IL-17, NF-κB, and COX-2 were seen in the phr100 group. In reactive oxygen species, malondialdehyde was reduced, and superoxide dismutase and glutathione peroxidase were elevated in the phr100 group. In apoptotic assessment, elevated cleaved caspase-3 was observed in rats of the phr100 group. Enhanced pro-apoptotic Bax and reduced anti-apoptotic Bc1-2 could be seen in the phr100 group. In histological stains, markedly decreased glandular hyperplasia and proliferative cell nuclear antigen were observed with reduced expression in the phr100 group. Meanwhile, positive cells of terminal deoxynucleotidyl transferase dUTP nick end labeling were increased in the phr100 group. In conclusion, the treatment of phloretin 100 mg/kg/day could ameliorate testosterone-induced BPH.
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http://dx.doi.org/10.3390/life11080743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399389PMC
July 2021

Time-resolved ARPES Determination of a Quasi-Particle Band Gap and Hot Electron Dynamics in Monolayer MoS.

Nano Lett 2021 Sep 23;21(17):7363-7370. Epub 2021 Aug 23.

Department of Physics, The University of Texas at Austin, Austin, Texas 78712, United States.

The electronic structure and dynamics of 2D transition metal dichalcogenide (TMD) monolayers provide important underpinnings both for understanding the many-body physics of electronic quasi-particles and for applications in advanced optoelectronic devices. However, extensive experimental investigations of semiconducting monolayer TMDs have yielded inconsistent results for a key parameter, the quasi-particle band gap (QBG), even for measurements carried out on the same layer and substrate combination. Here, we employ sensitive time- and angle-resolved photoelectron spectroscopy (trARPES) for a high-quality large-area MoS monolayer to capture its momentum-resolved equilibrium and excited-state electronic structure in the weak-excitation limit. For monolayer MoS on graphite, we obtain QBG values of ≈2.10 eV at 80 K and of ≈2.03 eV at 300 K, results well-corroborated by the scanning tunneling spectroscopy (STS) measurements on the same material.
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http://dx.doi.org/10.1021/acs.nanolett.1c02674DOI Listing
September 2021

Inhibiting miR-129-5p alleviates inflammation and modulates autophagy by targeting ATG14 in fungal keratitis.

Exp Eye Res 2021 Aug 17;211:108731. Epub 2021 Aug 17.

From the Department of Ophthalmology, Fujian Medical University Union Hospital, Fu Zhou, China. Electronic address:

To investigate the role of miR-129-5p in inflammation and autophagy in fungal keratitis, we established a keratitis mouse model infected with Fusarium solani (F. solani) and conducted experiments on corneal stromal cells infected with F. solani. The expression of miR-129-5p was detected via quantitative real-time polymerase chain reaction (PCR). The miR-129-5p antagomir was used to transfect cells and mice to study the regulatory role of miR-129-5p in autophagy and inflammation after fungal infection. The expression of Beclin1 and LC3B and colocalization of LC3B with lysosomes were detected via Western blotting and immunofluorescence. CCK-8 was used to determine the viability of corneal stromal cells. The expression of IL-1β were detected by ELISA. Bioinformatics software was used to predict the potential targets of miR-129-5p, which were verified by a luciferase reporter gene assay. RT-PCR showed that miR-129-5p expression in mouse corneas was significantly increased after infection with F. solani. Subconjunctival injection of the miR-129-5p antagomir significantly enhanced the proteins Beclin-1 and LC3B. At the same time, inhibiting miR-129-5p expression could reduce the inflammatory response in FK and significantly increase the viability of corneal stromal cells infected with F. solan. Moreover, the dual luciferase reporter assay indicated that Atg14 was a direct target of miR-129-5p. Our study shows that miR-129-5p is a novel small molecule that regulates autophagy by targeting Atg14, indicating that it may be a proinflammatory and therapeutic target for fungal keratitis.
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http://dx.doi.org/10.1016/j.exer.2021.108731DOI Listing
August 2021

[Effects of ophiopogonin D on fatty acid metabolic enzymes in cardiomyocytes].

Zhongguo Zhong Yao Za Zhi 2021 Jul;46(14):3672-3677

Institute of Radiation Medicine,Academy of Military Medical Sciences Beijing 100850,China.

To explore the effect of ophiopogonin D on main fatty acid metabolic enzymes in human cardiomyocyte AC-16,so as to provide reference for cardiovascular protection mechanism and safe clinical application of Ophiopogon japonicus.CCK-8 (cell counting kit-8) was used to detect the effect of different concentrations of ophiopogonin D on the viability of cardiomyocytes.Meanwhile,the effect of different concentrations of ophiopogonin D on the morphology and quantity of cardiomyocytes was observed under microscope.The effect of ophiopogonin D on the mRNA expression of CYP2J2,CYP4F3,CYP4A11,CYP4A22 and CYP4F2 in cardiomyocytes was detected by RT-PCR.Western blot was used to detect the protein expression of CYP4F3 in different concentrations of ophiopogonin D.Compared with the control group,low-concentration ophiopogonin D had no effect on the viability of cardiomyocytes.However,ophiopogonin D with a concentration of higher than 20μmol·L~(-1)could promote the viability.Under the microscope,ophiopogonin D with a concentration of below 100μmol·L~(-1)had no significant effect on the morphology and number of cardiomyocytes.RT-PCR results showed that compared with the control group,5μmol·L~(-1)ophiopogonin D could slightly up-regulate mRNA expressions of CYP2J2 and CYP4F3,while high-concentration ophiopogonin D (10 and 20μmol·L~(-1)) could significantly induce mRNA expressions of CYP2J2and CYP4F3 in a dose-dependent manner (P<0.05).The same concentration of ophiopogonin D had a little effect on the mRNA expressions of CYP4A11,CYP4A22 and CYP4F2.Western blot results showed that 20μmol·L~(-1)ophiopogonin D could significantly induce the protein expression of CYP4F3 in a dose-dependent manner (P<0.05).Based on the above results,ophiopogonin D (less than100μmol·L~(-1)) has no effect on the viability of AC-16 cardiomyocytes.Ophiopogonin D (less than 100μmol·L~(-1)) can selectively induce the expressions of CYP2J2 and CYP4F3,regulate the metabolic pathway of fatty acid signaling molecules,and thus protecting the cardiovascular system.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210311.401DOI Listing
July 2021

Atrial Natriuretic Peptide Inhibited ABCA1/G1-dependent Cholesterol Efflux Related to Low HDL-C in Hypertensive Pregnant Patients.

Front Pharmacol 2021 28;12:715302. Epub 2021 Jul 28.

Department of Hypertension, The First Affiliated Hospital of Dalian Medical University, DaLian, China.

It has been reported that atrial natriuretic peptide (ANP) regulates lipid metabolism by stimulating adipocyte browning, lipolysis, and lipid oxidation, and by impacting the secretion of adipokines. In our previous study, we found that the plasma ANP concentration of hypertensive disorders of pregnancy (HDP) was significantly increased in comparison to that of normotensive pregnancy patients. Thus, this study's objective was to investigate the lipid profile in patients with HDP and determine the effects of ANP on the cholesterol efflux in THP-1 macrophages. A total of 265 HDP patients and 178 normotensive women as the control group were recruited. Clinical demographic characteristics and laboratory profile data were collected. Plasma total triglycerides (TGs), total cholesterol (TC), low-density cholesterol (LDL-C), and high-density cholesterol (HDL-C) were compared between the two groups. THP-1 monocytes were incubated with different concentrations of ANP. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) mRNA and protein were evaluated. ABCA1- and ABCG1-mediated cholesterol efflux to apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL, respectively, were measured by green fluorescent labeled NBD cholesterol. Natriuretic peptide receptor A (NPR-A) siRNA and specific agonists of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and liver X receptor α (LXRα) were studied to investigate the mechanism involved. Plasma TG, TC, LDL-C, and LDL-C/HDL-C were significantly increased, and HDL-C was significantly decreased in the HDP group in comparison to the control (all < 0.001). ANP inhibited the expression of ABCA1 and ABCG1 at both the mRNA and protein levels in a dose-dependent manner. The functions of ABCA1- and ABCG1-mediated cholesterol efflux to apoA-I and HDL were significantly decreased. NPR-A siRNA further confirmed that ANP binding to its receptor inhibited ABCA1/G1 expression through the PPAR-γ/LXRα pathway. ABCA1/G1 was inhibited by the stimulation of ANP when combined with NPR-A through the PPAR-γ/LXRα pathway in THP-1 macrophages. The ABCA1/G1-mediated cholesterol efflux was also impaired by the stimulation of ANP. This may provide a new explanation for the decreased level of HDL-C in HDP patients.
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http://dx.doi.org/10.3389/fphar.2021.715302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355588PMC
July 2021

Association Between Smoking and Molecular Subtypes of Colorectal Cancer.

JNCI Cancer Spectr 2021 Aug 14;5(4):pkab056. Epub 2021 Jun 14.

Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.

Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking.

Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including mutation, mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction.

Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers ( < .001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and . Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; = 2.1 x 10). The association was also stronger in tumors that were positive, MSI high, or wild type when combined ( < .001).

Conclusion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway.
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http://dx.doi.org/10.1093/jncics/pkab056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346704PMC
August 2021

Phase separation in RNA biology.

J Genet Genomics 2021 Aug 8. Epub 2021 Aug 8.

School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

The ormation of biomolecular condensates via liquid-liquid phase separation (LLPS) is an advantageous strategy for cells to organize subcellular compartments for diverse functions. The involvement of LLPS is more widespread and overrepresented in RNA-related biological processes. This is in part because that RNAs are intrinsically multivalent macromolecules, and the presence of RNAs affects the formation, dissolution, and biophysical properties of biomolecular condensates formed by LLPS. Emerging studies have illustrated how LLPS participates in RNA transcription, splicing, processing, quality control, translation, and function. The interconnected regulation between LLPS and RNAs ensures tight control of RNA-related cellular functions.
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http://dx.doi.org/10.1016/j.jgg.2021.07.012DOI Listing
August 2021

Klotho deficiency-induced arterial calcification involves osteoblastic transition of VSMCs and activation of BMP signaling.

Authors:
Yi Lin Zhongjie Sun

J Cell Physiol 2021 Aug 8. Epub 2021 Aug 8.

Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma, USA.

Klotho is an aging-suppressor gene. The purpose of this study was to investigate whether Klotho deficiency affects arterial structure. We found that Klotho-deficient (kl/kl) mice developed severe arterial calcification and elastin fragmentation. Klotho-deficient mice demonstrated higher levels of bone morphogenetic proteins (BMP2, BMP4) and runt-related transcription factor 2 (RUNX2) in aortas, indicating that Klotho deficiency upregulates expression of BMP2 and RUNX2 (a key transcription factor in osteoblasts). To exclude the potential involvement of hyperphosphatemia in arterial calcification, Klotho-deficient mice were given a low phosphate diet (0.2%). The low phosphate diet normalized blood phosphate levels and abolished calcification in the lungs and kidneys, but it did not prevent calcification in the aortas in Klotho-deficient mice. Thus, Klotho deficiency per se might play a causal role in the pathogenesis of arterial calcification, which is independent of hyperphosphatemia. In cultured mouse aortic smooth muscle cells (ASMCs), Klotho-deficient serum-induced transition of ASMCs to osteoblasts. Klotho-deficient serum promoted BMP2/vitamin D3-induced protein expression of PIT2 and RUNX2, phosphorylation of SMAD1/5/8 and SMAD2/3, and extracellular matrix calcification. Interestingly, treatments with recombinant Klotho protein abolished BMP2/vitamin D3-induced osteoblastic transition and morphogenesis and calcification. Therefore, Klotho is a critical regulator in the maintenance of normal arterial homeostasis. Klotho deficiency-induced arterial calcification is an active process that involves the osteoblastic transition of SMCs and activation of the BMP2-RUNX2 signaling.
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http://dx.doi.org/10.1002/jcp.30541DOI Listing
August 2021

Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs) and Dental Pulp Stem Cells (DPSCs) Display a Similar Profile with Pericytes.

Stem Cells Int 2021 24;2021:8859902. Epub 2021 Jul 24.

Discipline of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.

Background: Pericytes play an important role in forming functional blood vessels and establishing stable and effective microcirculation, which is crucial for vascular tissue engineering. The slow ex vivo expansion rate, limited proliferative capacity, and variability of tissue-specific phenotypes would hinder experimental studies and clinical translation of primary pericytes. In this study, the angiogenic and pericyte functions of stem cells from human exfoliated deciduous teeth (SHEDs) and postnatal human dental pulp stem cells (DPSCs) were investigated.

Methods: Osteogenic and adipogenic induction assays were performed to evaluate the mesenchymal potential of SHEDs, DPSCs, and pericytes. An in vitro Matrigel angiogenesis assay was conducted to reveal the ability of SHEDs, DPSCs, and pericytes to stabilize vascular-like structures. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed to evaluate mRNA expression. Flow cytometry, western blotting, and immunostaining were used to assess the protein expression. Wound healing and transwell assays were performed to evaluate the migration ability of SHEDs, DPSCs, and pericytes.

Results: The osteogenic and adipogenic induction assays showed that SHEDs, DPSCs, and pericytes exhibited similar stem cell characteristics. The mRNA expression levels of PDGFR-, -SMA, NG2, and DEMSIN in SHEDs and DPSCs cultured in EC medium were significantly higher than those in the control groups on day 7 ( < 0.05), but significantly higher than those in the pericytes group on day 14 ( < 0.05). Flow cytometry showed that high proportions of SHEDs and DPSCs were positive for various pericyte markers on day 7. The DPSCs, SHEDs, and pericytes displayed strong migration ability; however, there was no significant difference among the groups ( > 0.05).

Conclusion: The SHEDs and DPSCs display a profile similar to that of pericytes. Our study lays a solid theoretical foundation for the clinical use of dental pulp stem cells as a potential candidate to replace pericytes.
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http://dx.doi.org/10.1155/2021/8859902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328701PMC
July 2021

High glycaemic variability is associated with progression of COVID-19.

Acta Diabetol 2021 Aug 4. Epub 2021 Aug 4.

Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore, 768828, Singapore.

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http://dx.doi.org/10.1007/s00592-021-01779-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335709PMC
August 2021

New function of a well-known promoter: Enhancer activity of minimal CMV promoter enables efficient dual-cassette transgene expression.

J Gene Med 2021 Jul 27:e3380. Epub 2021 Jul 27.

Gene and Cell Therapy Program, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Background: Co-expression of multiple genes in single vectors has achieved varying degrees of success by employing two promoters and/or application of viral 2A-peptide or the internal ribosome entry-site (IRES). However, promoter interference, potential functional-interruption of expressed-proteins by 2A-generated residual peptides or weaker translation of IRES-mediated downstream genes has curtailed their utilization. Thus, there is the need for single vectors that robustly express multiple proteins for enhanced gene therapy applications.

Methods: We engineered lentiviral-vectors for dual-cassette expression of green fluorescent protein and mCherry in uni- or bidirectional architectures using the short-version (Es) of elongation factor 1α (EF) promoter and simian virus 40 promoter (Sv). The regulatory function of a core fragment (cC) from human cytomegalovirus promoter was investigated with cell-lineage specificity in NIH3T3 (fibroblast) and hematopoietic cell lines U937 (monocyte/macrophage), LCL (lymphoid), DAMI (megakaryocyte) and MEL (erythroid).

Results: The cC element in reverse-orientation not only boosted upstream Es promoter to levels comparable to full-length EF in DAMI, U937 and 3T3 cells, but also blocked the suppression of downstream Sv promoter by Es in U937 and 3T3 cells with further improved Sv activity in DAMI cells. Such lineage-restricted up-regulation is likely attributed to two protein-binding domains of cC and diverse expression of related factors in different cell types for enhancer and terminator activities, but not spacing function.

Conclusions: Such a newly developed dual-cassette vector could be advantageous, particularly in hematopoietic cell-mediated gene/cancer therapy, by allowing for independent and robust co-expression of therapeutic gene(s) and/or a selectable gene or imaging marker in the same cells.
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http://dx.doi.org/10.1002/jgm.3380DOI Listing
July 2021

Cortical excitability signatures for the degree of sleepiness in human.

Elife 2021 07 27;10. Epub 2021 Jul 27.

Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Sleep is essential in maintaining physiological homeostasis in the brain. While the underlying mechanism is not fully understood, a 'synaptic homeostasis' theory has been proposed that synapses continue to strengthen during awake and undergo downscaling during sleep. This theory predicts that brain excitability increases with sleepiness. Here, we collected transcranial magnetic stimulation measurements in 38 subjects in a 34 hr program and decoded the relationship between cortical excitability and self-report sleepiness using advanced statistical methods. By utilizing a combination of partial least squares regression and mixed-effect models, we identified a robust pattern of excitability changes, which can quantitatively predict the degree of sleepiness. Moreover, we found that synaptic strengthen occurred in both excitatory and inhibitory connections after sleep deprivation. In sum, our study provides supportive evidence for the synaptic homeostasis theory in human sleep and clarifies the process of synaptic strength modulation during sleepiness.
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http://dx.doi.org/10.7554/eLife.65099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373378PMC
July 2021

Individualism without full individualization? The compressed life trajectories of the Tibetan graduates of an English training program.

Authors:
Lin Yi Zhuoma Gadou

Br J Sociol 2021 Sep 27;72(4):1113-1126. Epub 2021 Jul 27.

Independent Researcher.

Drawing upon fieldwork data collected among a group of Tibetan graduates who attended an internationally linked English training program that dramatically and fundamentally altered their life trajectories, this study argues that these Tibetans acquired individualism prior to individualization practice. Their pathway is in contrast with the tendency found among Korean women "toward individualization without individualism, a region-wide phenomenon in East Asia'. Different scenarios exactly reveal complicatedness and complexity in compressed modernity of East Asia. However, the study also finds that their exercise of individualization did not turn them into an ontological or radical-that is, egoistic-individualist on account of multiple factors. Toward the end of the article, we also recommend replacing the controversial concept of individualization (individualism) with the notion of individuation-a project of the individual that may be geared toward collective action and shared ideals-to avoid conceptual ambiguity in the future. This individuation project is more likely to contribute to both the integrity and identity of the individual in her search for a legitimate status and a settled life in the wider society, as well as a prosperous society in the future.
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http://dx.doi.org/10.1111/1468-4446.12879DOI Listing
September 2021

Gender Differences in Identifying Facial, Prosodic, and Semantic Emotions Show Category- and Channel-Specific Effects Mediated by Encoder's Gender.

J Speech Lang Hear Res 2021 08 26;64(8):2941-2955. Epub 2021 Jul 26.

Department of Speech-Language-Hearing Sciences & Center for Neurobehavioral Development, University of Minnesota Twin Cities, Minneapolis.

Purpose The nature of gender differences in emotion processing has remained unclear due to the discrepancies in existing literature. This study examined the modulatory effects of emotion categories and communication channels on gender differences in verbal and nonverbal emotion perception. Method Eighty-eight participants (43 females and 45 males) were asked to identify three basic emotions (i.e., happiness, sadness, and anger) and neutrality encoded by female or male actors from verbal (i.e., semantic) or nonverbal (i.e., facial and prosodic) channels. Results While women showed an overall advantage in performance, their superiority was dependent on specific types of emotion and channel. Specifically, women outperformed men in regard to two basic emotions (happiness and sadness) in the nonverbal channels and only the anger category with verbal content. Conversely, men did better for the anger category in the nonverbal channels and for the other two emotions (happiness and sadness) in verbal content. There was an emotion- and channel-specific interaction effect between the two types of gender differences, with male subjects showing higher sensitivity to sad faces and prosody portrayed by the female encoders. Conclusion These findings reveal explicit emotion processing as a highly dynamic complex process with significant gender differences tied to specific emotion categories and communication channels. Supplemental Material https://doi.org/10.23641/asha.15032583.
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http://dx.doi.org/10.1044/2021_JSLHR-20-00553DOI Listing
August 2021

Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study.

Ann Hematol 2021 Oct 24;100(10):2529-2539. Epub 2021 Jul 24.

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, TX, USA.

We conducted a phase II clinical trial to develop an autologous EBV-specific T cell product (baltaleucel T) for advanced, relapsed ENKTL. Among 47 patients who provided whole blood starting material for manufacturing the product, 15 patients received a median of 4 doses of baltaleucel T. Thirty-two (68%) patients did not receive baltaleucel-T due to manufacturing failure, rapid disease progression, and death. Of the 15 patients, 10 patients had measurable disease at baseline (salvage cohort), and 5 patients had no disease at baseline assessment (adjuvant cohort). In the 15 patients, the median follow-up duration was 10.2 months (range 2.0-23.5 months), median progression-free survival (PFS) was 3.9 months, and the median overall survival (OS) was not reached. Patients in the salvage cohort achieved a 30% complete response (CR) and a 50% overall response rate (ORR). In the adjuvant cohort, disease progression was reported in three patients and two patients did not relapse during study follow-up. When we compared survival outcomes of seven responders and eight non-responders, the PFS (P = 0.001) and OS (P = 0.014) of responders proved statistically superior to that of non-responders. Baltaleucel-T was well tolerated. We have performed a phase II clinical trial of autologous EBV-specific T cell treatment (baltaleucel-T) in R/R ENKTL. Autologous EBV-specific T cells were well tolerated and demonstrated single-agent activity in R/R ENTKL.
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http://dx.doi.org/10.1007/s00277-021-04558-0DOI Listing
October 2021

Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma.

Br J Haematol 2021 Aug 22;194(4):690-700. Epub 2021 Jul 22.

University Medical Center Groningen, Groningen, Netherlands, on behalf of HOVON/PPLC.

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 10  CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.
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http://dx.doi.org/10.1111/bjh.17527DOI Listing
August 2021

Beyond the bubble: neighbours helping neighbours.

Intern Med J 2021 07;51(7):1013-1015

Tuberculosis Elimination and Implementation Science Group, Burnet Institute, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/imj.15416DOI Listing
July 2021
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