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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35555413

RESUMO

N6-methyladenosine (m6A) modification is the most abundant mRNA modification which plays important roles in the regulation of mRNA stability, splicing, translocation, and translation. Methyltransferase-like 3 (METTL3), a primary RNA methyltransferase that catalyzes RNA m6A modification, is implicated in several human cancers including hepatocellular carcinoma (HCC), although its mechanisms of actions remain to be further defined. In the current study, we aimed to further determine the effect and mechanism of METTL3-derived m6A in HCC. We have analyzed the TCGA database and observed that METTL3 expression is significantly upregulated in HCC patients which is associated with lower survival rate (P < 0.001). In a mouse model of HCC induced by hydrodynamic tail vein injection of hyperactive form of YAP and ß-catenin in conjunction with the sleeping beauty (SB) transposon system, we observed that the expression of METTL3 was notably high in YAP/ß-catenin-induced HCC. In cultured human HCC cell lines (Huh7 and PLC/PRF/5), we observed that stable knockdown of METTL3 by shRNA significantly decreased tumor cell proliferation, colony formation and migration, in vitro. When Huh and PLC/PRF/5 cells with shRNA knockdown of METTL3 were inoculated into the livers of SCID mice, we found that METTL3 knockdown significantly inhibited xenograft tumor growth, in vivo. We next delivered METTL3 and YAP expression plasmids to the livers of wild type mice via hydrodynamic tail vein injection and observed that co-expression of METTL3 plus YAP induced the development of HCC which involves almost the entire livers (20 weeks after tail vein injection). These findings provide important evidence for a tumor-promoting role of METTL3 in HCC development. Through N6-methyladenosine-sequencing (m6A-Seq) and RNA sequencing (RNA-Seq), we identified BMI1 and RNF2, two key components of the polycomb repressive complex 1 (PRC1), as direct downstream targets of METTL3 in HCC. Our further analyses revealed that both BMI1 and RNF2 were significantly elevated in HCC patients and were associated with lower survival rate and that the expression of BMI1 and RNF2 were positively correlated with METTL3 in human HCC tissues. Consistent with the above results, our further data showed that knockdown of METTL3 in Huh7 and PLC/PRF/5 significantly decreased the expression of BMI1 and RNF2. Accordingly, treatment of Huh7 and PLC/PRF/5 cells with the METTL3 inhibitor, STM2457, significantly reduced the expression of BMI1 and RNF2 and decreased tumor cell proliferation and colony formation. Moreover, our data showed that inhibition of the m6A reader YTHDF1 by siRNA significantly decreased the expression of BMI1 and RNF2 in human HCC cells. Collectively, our study provides important evidence that METTL3 promotes HCC development and progression through m6A modification of BMI1 and RNF2 mRNAs which involve a YTHDF1 dependent mechanism. It is conceivable that the METTL3-m6A-BMI1/RNF2 axis may represent a promising target for HCC treatment.

2.
Polymers (Basel) ; 14(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35567051

RESUMO

The development and treatment of some diseases, such as large-area cerebral infarction, cerebral hemorrhage, brain tumor, and craniocerebral trauma, which may involve the injury of the dura mater, elicit the need to repair this membrane by dural grafts. However, common dural grafts tend to result in dural adhesions and scar tissue and have no further neuroprotective effects. In order to reduce or avoid the complications of dural repair, we used PLGA, tetramethylpyrazine, and chitosan as raw materials to prepare a nanofibrous dura mater (NDM) with excellent biocompatibility and adequate mechanical characteristics, which can play a neuroprotective role and have an antifibrotic effect. We fabricated PLGA NDM by electrospinning, and then chitosan was grafted on the nanofibrous dura mater by the EDC-NHS cross-linking method to obtain PLGA/CS NDM. Then, we also prepared PLGA/TMP/CS NDM by coaxial electrospinning. Our study shows that the PLGA/TMP/CS NDM can inhibit the excessive proliferation of fibroblasts, as well as provide a sustained protective effect on the SH-SY5Y cells treated with oxygen-glucose deprivation/reperfusion (OGD/R). In conclusion, our study may provide a new alternative to dural grafts in undesirable cases of dural injuries.

3.
Mol Ther ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35570396

RESUMO

Bispecific T-cell engagers (BiTEs) are bispecific antibodies that redirect T cells to target antigen-expressing tumors. We hypothesized that BiTE-secreting T cells could be a valuable therapy in solid tumors, with distinct properties in mono- or multi-valent strategies incorporating chimeric antigen receptor (CAR) T cells. Glioblastomas represent a good model for solid tumor heterogeneity, representing a significant therapeutic challenge. We detected expression of tumor-associated epidermal growth factor receptor (EGFR), EGFR variant III (EGFRvIII), and interleukin-13 receptor alpha 2 (IL13Rα2) on glioma tissues and cancer stem cells. These antigens formed the basis of a multivalent approach, using a conformation-specific tumor-related EGFR targeting antibody (806) and Hu08, an IL13Rα2-targeting antibody, as the scFvs to generate new BiTE molecules. Compared with CAR T cells, BiTE T cells demonstrated prominent activation, cytokine production, and cytotoxicity in response to target-positive gliomas. Superior response activity was also demonstrated in BiTE secreting bivalent T cells compared with bivalent CAR T cells in a glioma mouse model at early phase, but not in the long-term. In summary, BiTEs secreted by mono- or multi- valent T cells have potent anti-tumor activity in vitro and in vivo with significant sensitivity and specificity, demonstrating a promising strategy in solid tumor therapy.

4.
Ying Yong Sheng Tai Xue Bao ; 33(3): 784-792, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35524532

RESUMO

In this study, we investigated the effects of long-term continuous cucumber cropping on phenolic acids in rhizosphere soil, as well as their link to soil chemical characteristics, enzyme activities, and microbiological activities, using rhizosphere soil from the 2nd, 6th, 10th, 14th, 18th, 20th, 24th, and 26th round of cucumber cultivation in solar greenhouse. The results showed that contents of phenolic acids increased significantly with increasing continuous cropping rounds. The increase amount per round of total phenolic acid was significantly higher in the early stage (0-2 rounds) and late stage (20-26 rounds) than middle stage (10-14 rounds) of continuous cropping. Soil nutrient contents were enriched, while invertase enzyme activity and microbial activities were decreased. Redundancy analysis showed that organic matter, total phosphorus, total nitrogen, available nitrogen, microbial biomass carbon and microbial metabolic entropy were main soil fertility factors correlating with the accumulation of phenolic acids. Results of structural equation model showed that soil phosphorus enrichment directly led to the accumulation of phenolic acids, and that nitrogen enrichment indirectly facilitated the accumulation of phenolic acids by altering the activity of microorganisms. As a result, proper nitrogen and phosphorus fertilizers application would reduce the accumulation of phenolic acids and alleviate the cucumber continuous cropping obstacles.


Assuntos
Cucumis sativus , Solo , Agricultura/métodos , Nitrogênio , Fósforo , Solo/química , Microbiologia do Solo
5.
Adv Healthc Mater ; : e2200546, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35545965

RESUMO

Antimicrobial peptidomimetics (AMPMs) have received widespread attention as potentially powerful weapons against antibiotic resistance. However, AMPMs' membrane disruption mechanism not only brings resistance-resistant nature, but also non-specific binding and disruption toward eukaryotic cell membranes, and consequently, their hemolytic activity has been the primary concern on clinical applications. Here we report the preparation and screening of an AMPM library, through which a best-performing hit, PT-b1, can be obtained. To further improve PT-b1's hemocompatibility, we devised a strategy to mask the amphiphilicity of the AMPM using a charge-free, FDA-approved amphiphilic polymer, Pluronic F-127 (PF127). A PF127 solution containing PT-b1 can form a temperature-sensitive, absorbable hydrogel at higher concentration, but dissolve and complex with PT-b1 through hydrophobic interactions at lower concentration or lower temperature. The complexation from PF127 can mask the amphiphilicity of PT-b1 and render it extremely hemocompatible, yet the reversibility in such nanocomplexation and the existence of a secondary mechanism of action ensured that the AMPM's potency remains unchanged. The in vivo effectiveness of this antimicrobial hydrogel system is demonstrated using a mice wound infection model established with Methicillin-resistant Staphylococcus aureus, and observations indicate the hydrogel can promote wound healing and suppress bacteria-caused inflammation even when resistant pathogens are involved. This article is protected by copyright. All rights reserved.

6.
J Am Chem Soc ; 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35605024

RESUMO

Imine-linked covalent organic frameworks (COFs) have received widespread attention because of their structure features such as high crystallinity and tunable pores. However, the intrinsic reversibility of the imine bond leads to the poor stability of imine-linked COFs under strong acid conditions. Also, their thermal stability is significantly lower than that of many other COFs. Herein, we report for the first time that the reversible imine bonds in the skeleton of COFs can be locked through the asymmetric hydrophosphonylation reaction of phosphite. The functionalized COFs not only retain the crystallinity and porous structure but also exhibit evidently improved chemical and thermal stabilities. In addition, the phosphorous acid groups generated by acidic hydrolysis attached to the skeleton endow the COFs with good intrinsic proton conductivity. Due to the diversity of phosphite derivatives and imine-linked COFs, this work may provide an avenue for extending the COF structures and functions through the asymmetric hydrophosphonylation reaction.

7.
PLoS One ; 17(5): e0268376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35551283

RESUMO

We examined multi-level factors related to the longitudinal physical activity trajectories of adolescent girls to determine the important predictors for physical activity. The Trial of Activity in Adolescent Girls (TAAG) Maryland site recruited participants at age 14 (n = 566) and followed up with these girls at age 17 (n = 553) and age 23 (n = 442). Individual, social factors and perceived environmental factors were assessed by questionnaire; body mass index was measured at age 14 and age 17, and self-reported at age 23. Neighborhood factors were assessed by geographic information systems. The outcome, moderate-to-vigorous physical activity (MVPA) minutes in a day, was assessed from accelerometers. A mixture of linear mixed-effects models with double penalization on fixed effects and random effects was used to identify the intrinsic grouping of participants with similar physical activity trajectory patterns and the most relevant predictors within the groups simultaneously. Three clusters of participants were identified. Two hundred and forty participants were clustered as "maintainers" and had consistently low MVPA over time; 289 participants were clustered as "decreasers" who had decreasing MVPA over time; 39 participants were grouped as "increasers" and had increasing MVPA over time. Each of the three clusters has its own cluster-specific factors identified using the clustering method, indicating that each cluster has unique characteristics.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35565057

RESUMO

The eye is a superficial organ directly exposed to the surrounding environment. Thus, the toxicity of nanoparticle (NP) pollutants to the eye may be potentially severer relative to inner organs and needs to be monitored. However, the cytotoxic mechanisms of NPs on the eyes remain rarely reported. This study was to screen crucial genes associated with NPs-induced retinal injuries. The gene expression profiles in the retina induced by NPs [GSE49371: Au20, Au100, Si20, Si100; GSE49048: presumptive therapeutic concentration (PTC) TiO2, 10PTC TiO2] and commonly used retinal cell injury models (optic nerve injury procedure: GSE55228, GSE120257 and GSE131486; hypoxia exposure: GSE173233, GSE151610, GSE135844; H2O2 exposure: GSE122270) were obtained from the Gene Expression Omnibus database. A total of 381 differentially expressed genes (including 372 mRNAs and 9 lncRNAs) were shared between NP exposure and the optic nerve injury model when they were compared with their corresponding controls. Function enrichment analysis of these overlapped genes showed that Tlr2, Crhbp, Ccl2, Cxcl10, Fas, Irf8, Socs3, Stat3, Gbp6, Casp1 and Syk were involved in inflammatory- and apoptotic-related processes. Protein-protein interaction network analysis revealed eight of them (Tlr2, Ccl2, Cxcl10, Irf8, Socs3, Stat3, Casp1 and Syk) were hub genes. Moreover, Socs3 could interact with upstream Stat3 and downstream Fas/Casp1/Ccl2/Cxcl10; Irf8 could interact with upstream Tlr2, Syk and downstream Cxcl10. Competing endogenous RNAs network analysis identified Socs3, Irf8, Gdf6 and Crhbp could be regulated by lncRNAs and miRNAs (9330175E14Rik-mmu-miR-762-Socs3, 6430562O15Rik-mmu-miR-207-Irf8, Gm9866-mmu-miR-669b-5p-Gdf6, 4933406C10Rik-mmu-miR-9-5p-Crhbp). CMap-CTD database analyses indicated the expression levels of Tlr2, Ccl2, Cxcl10, Fas, Irf8, Socs3, Stat3, Gbp6, Casp1 and Syk could be reversed by folic acid. Crhbp and Gdf6 were also verified to be downregulated, while Tlr2, Ccl2, Irf8, Socs3 and Stat3 were upregulated in hypoxia/H2O2-induced retinal injury models. Hereby, our findings suggest that Crhbp, Irf8, Socs3 and Gdf6 as well as their upstream mRNAs, lncRNAs and miRNAs may be potential monitoring biomarkers and therapeutic targets for NP-induced retinal injuries. Folic acid supplementation may be a preventive and therapeutic approach.

9.
Chem Commun (Camb) ; 58(42): 6204-6207, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35506761

RESUMO

Transition metal dichalcogenides (TMDs) have attracted great attention as electrocatalysts for the hydrogen evolution reaction (HER) due to their tunable crystal structures and active sites. However, compared with group VI TMDs (such as MoS2 and WS2), the group V TMDs exhibit poor intrinsic catalytic activity towards the HER because the outermost d orbitals of group V metals have only one electron. Herein, we design a new compound Pt3Nb2Se8 by Pt modulation of NbSe2 with enhanced catalytic activity and structural stability for robust HER in an alkaline medium. The introduction of Pt atoms can not only be used as efficient active sites, but also to transfer electrons to Se to synthetically boost the catalytic activity. The Pt3Nb2Se8 exhibits an overpotential of 44 mV at 10 mA cm-2 and a Tafel slope of 38.4 mV dec-1, superior to those of intrinsic NbSe2 and PtSe2, and even exceeding those of commercial Pt/C. This work aims to provide an approach to design group V-based TMDs with enhanced catalytic activity and stability by electronic regulation, as highly efficient electrocatalysts for the HER.

10.
Biomaterials ; 285: 121509, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35533440

RESUMO

The catastrophic global effects of the SARS-CoV-2 pandemic highlight the need to develop novel therapeutics strategies to prevent and treat viral infections of the respiratory tract. To enable this work, we need scalable, affordable, and physiologically relevant models of the human lung, the primary organ involved in the pathogenesis of COVID-19. To date, most COVID-19 in vitro models rely on platforms such as cell lines and organoids. While 2D and 3D models have provided important insights, human distal lung models that can model epithelial viral uptake have yet to be established. We hypothesized that by leveraging techniques of whole organ engineering and directed differentiation of induced pluripotent stem cells (iPSC) we could model human distal lung epithelium, examine viral infection at the tissue level in real time, and establish a platform for COVID-19 related research ex vivo. In the present study, we used type 2 alveolar epithelial cells (AT2) derived from human iPSCs to repopulate whole rat lung acellular scaffolds and maintained them in extended biomimetic organ culture for 30 days to induce the maturation of distal lung epithelium. We observed emergence of a mixed type 1 and type 2 alveolar epithelial phenotype during tissue formation. When exposing our system to a pseudotyped lentivirus containing the spike of wildtype SARS-CoV-2 and the more virulent D614G, we observed progression of the infection in real time. We then found that the protease inhibitor Camostat Mesyalte significantly reduced viral transfection in distal lung epithelium. In summary, our data show that a mature human distal lung epithelium can serve as a novel moderate throughput research platform to examine viral infection and to evaluate novel therapeutics ex vivo.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Antivirais/farmacologia , Ésteres , Guanidinas , Humanos , Pulmão/patologia , Inibidores de Proteases/farmacologia , Ratos , Internalização do Vírus
11.
J Ethnopharmacol ; 294: 115367, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35562090

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Post stroke depression (PSD), which happens in 40%-60% stroke patients, is one of the most common complications after cerebrovascular accident. Shugan Jieyu Capsule (SGJYC), a traditional Chinese medicine, has been widely prescribed for PSD in China. AIM OF THE STUDY: This study designed and conducted a PRISMA compliant meta-analysis to evaluate the efficacy of SGJYC in treating adults with PSD of randomized controlled trials (RCTs) under the condition that none PRISMA-compliant systematic evaluation or meta-analysis was conducted to fully evaluate the efficacy of SGJYC. METHODS: The study protocol has been registered in PROSPERO with registration number CRD42021250162. PubMed, ScienceDirect, CNKI, and Wanfang Databases were systematically searched to include eligible RCTs which used SGJYC and other antidepressants or placebo for the treatment of PSD adults with the Hamilton Depression Scale (HAMD). The Cochrane Risk of Bias 2 (RoB2) tool was used to evaluate the quality of included RCTs. Outcome measures including HAMD continuous data, efficacy data, and remission data were extracted for meta-analysis on a random-effects model. Adequate essential analyses including subgroup analysis, sensitivity analysis, and meta-regression analysis were performed according to the characteristics of RCTs to test the reliability and robustness of the overall effect sizes. Publication bias was detected with funnel plot, Egger's test, and Begg's test. The evidence strength of this meta-analysis was assessed with the GRADE method. RESULTS: A total of 63 eligible RCTs and 6036 participants were included. The RoB2 found that the overall risk of included RCTs was high. The MD of continuous data was 3.59 (95% CI: [2.63, 4.55]) with statistical significance (P < 0.00001) and significant heterogeneity (Chi2 = 2083.77, I2 = 97%, p < 0.00001). The OR of efficacy data was 2.12 (95% CI: [1.82, 2.47]) with statistical significance (P < 0.00001) and insignificant heterogeneity (Chi2 = 60.52, I2 = 22%, P = 0.09). The OR of remission data was 1.66 (95% CI: [1.45, 1.91]) with statistical significance (P < 0.00001) and insignificant heterogeneity (Chi2 = 26.45, I2 = 0%, P = 0.96). Adequate essential analyses found consistent results of overall effect sizes and most publication bias analyses found insignificant results. The overall evidence strength was assessed as moderate. CONCLUSION: The moderate evidence strength from this PRISMA-compliant meta-analysis found that SGJYC has notable efficacy in treating adults with PSD, although the quality of included RCT was low. The high-quality RCTs with large-sample, multi-centers, and long follow-up periods are still warranted to improve the evidence quality of SGJYC for PSD in further study.

12.
J Ethnopharmacol ; 293: 115280, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405252

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xie Bai San is a Chinese medicine prescription that has been used to treat lung cancer in China for a long time. It has been proven to alleviate the symptoms and extend the survival time of lung cancer patients. Xie Bai San comprises Cortex Lycii, Cortex Mori, and Radix Glycyrrhizae Preparata. The effects and mechanisms of Cortex Mori and Glycyrrhizae on lung cancer have been reported, whereas the underlying mechanism of Cortex Lycii remains unknown. MATERIAL AND METHODS: Network pharmacology was used to explore the unknown mechanisms underlying the effect of Cortex Lycii on lung cancer. Molecular docking was used to predict the binding of a compound to the protein. The fingerprint of Cortex Lycii was obtained by HPLC. Cell counting Kit-8 assay was used to determine the appropriate concentration of Cortex Lycii extract for human lung adenocarcinoma cells, A549 and H1299. Wound healing assay and Matrigel invasion assay were used to detect the influence of Cortex Lycii extract on the migration and invasion ability of A549 and H1299. The protein expression level was detected by western blot and immunohistochemical staining. RESULTS: Using network pharmacology, 38 components of Cortex Lycii and 79 possible lung cancer-related target genes of Cortex Lycii were obtained. The targets were assigned to 35 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and the PI3K-AKT signaling pathway contained the most targets and had the second-lowest P-value. The molecular docking showed the components of Cortex Lycii bound to HSP90AB1. Among them, 6 components bound to HSP90AB1 in which HSP90AB1 binds to and phosphorylates AKT. The functional experiments showed that Cortex Lycii suppressed the migration and invasion of human lung cancer cells in a dose-dependent manner. Cortex Lycii up-regulated E-Cadherin and down-regulated N-Cadherin, Vimentin, and MMP2. Furthermore, Cortex Lycii made no change in the total AKT and mTOR protein levels, but caused the down-regulation of p-AKT and p-mTOR in human lung cancer cells, which was reversed by Terazosin, an agonist of HSP90. Moreover, acacetin and apigenin, two components of Cortex Lycii, reduced the protein level of p-AKT and p-mTOR, and the reduction was also inhibited by Terazosin. CONCLUSION: Cortex Lycii suppressed epithelial-mesenchymal transition (EMT) in lung cancer cells through the PI3K-AKT-mTOR signaling pathway, possibly by targeting HSP90AB1 and inhibiting HSP90AB1-AKT binding.

13.
Phys Rev Lett ; 128(13): 137201, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426702

RESUMO

The antiferromagnet is considered to be a promising hosting material for the next generation of magnetic storage due to its high stability and stray-field-free property. Understanding the switching properties of the antiferromagnetic (AFM) domain state is critical for developing AFM spintronics. By utilizing the magneto-optical birefringence effect, we experimentally demonstrate the switching rate of the AFM domain can be enhanced by more than 2 orders of magnitude through applying an alternating square-wave field on a single crystalline Fe/CoO bilayer. The observed extraordinary speed can be much faster than that triggered by a constant field with the same amplitude. The effect can be understood as the efficient suppression of the pinning of AFM domain walls by the strong exchange torque triggered by the reversal of the Fe magnetization, as revealed by spin dynamics simulations. Our finding opens up new opportunities to design the antiferromagnet-based spintronic devices utilizing the ferromagnet-antiferromagnet heterostructure.

14.
World J Stem Cells ; 14(2): 146-162, 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35432735

RESUMO

Cancer stem cells (CSCs) comprise a subpopulation of cancer cells with stem cell properties, which exhibit the characteristics of high tumorigenicity, self-renewal, and tumor initiation and are associated with the occurrence, metastasis, therapy resistance, and relapse of cancer. Compared with differentiated cells, CSCs have unique metabolic characteristics, and metabolic reprogramming contributes to the self-renewal and maintenance of stem cells. It has been reported that CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism. In this review, we demonstrate that lipid anabolism alterations promote the survival of CSCs, including de novo lipogenesis, lipid desaturation, and cholesterol synthesis. In addition, we also emphasize the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival, the signal trans-duction pathways involved, and the application prospect of lipid synthesis reprogramming in CSC therapy. It is demonstrated that the dependence on lipid synthesis makes targeting of lipid synthesis metabolism a promising therapeutic strategy for eliminating CSCs. Targeting key molecules in lipid synthesis will play an important role in anti-CSC therapy.

15.
J Dent Educ ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442534

RESUMO

BACKGROUND: During the past decades, the rapid development of modern teaching tools and methods has been observed, and the new teaching module constructed through digitization or networking has been widely used in the field of medical education. This study aimed to investigate the effectiveness and acceptability of the online learning combined with case-based discussion (CBD) approach in oral medicine education. METHODS: Sixty senior students majoring in stomatology were randomly divided into two groups. One group (new module-based teaching group [NG], n = 30) watched an online teaching video and discussed clinical cases in groups. The control group (traditional lecture-based group [TG], n = 30) was assigned to the traditional lecture-based teaching. Subsequently, a theory assessment was conducted on the topics taught, and the scores of both groups were compared. Feedback about this teaching model was obtained from the NG. RESULTS: The results showed that students in the NG had significantly better performance in terms of mastering professional knowledge than did students in the TG. Moreover, most students in the NG had a high degree of satisfaction with this new teaching method, as they agreed that it can mobilize their learning enthusiasm and promote their engagement, interaction, and cooperation in the learning of oral medicine. CONCLUSIONS: Our findings indicate the effectiveness and high satisfaction of CBD combined with online learning in the teaching of oral medicine. This study is expected to provide new ideas for improving the dental teaching quality.

16.
Front Neurosci ; 16: 858404, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478849

RESUMO

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21-78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n = 4) and non-comatose (GCS-M > 4; n = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYMrBF) vs. non-comatose patients over a range of MAP values (29 vs. 11%, p = 0.009). ASYMrBF in comatose patients resolved near a MAP range of 70-80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO2 or pH vs. ASYMrBF were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.

17.
Front Cell Infect Microbiol ; 12: 872012, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392605

RESUMO

Dental caries, an ecological dysbiosis of oral microflora, initiates from the virulent biofilms formed on tooth surfaces where cariogenic microorganisms metabolize dietary carbohydrates, producing acid that demineralizes tooth enamel. Forming cariogenic biofilms, Streptococcus mutans and Candida albicans are well-recognized and emerging pathogens for dental caries. Recently, probiotics have demonstrated their potential in treating biofilm-related diseases, including caries. However, limited studies have assessed their effect on cariogenic bacteria-fungi cross-kingdom biofilm formation and their underlying interactions. Here, we assessed the effect of four probiotic Lactobacillus strains (Lactobacillus rhamnosus ATCC 2836, Lactobacillus plantarum ATCC 8014, Lactobacillus plantarum ATCC 14917, and Lactobacillus salivarius ATCC 11741) on S. mutans and C. albicans using a comprehensive multispecies biofilm model that mimicked high caries risk clinical conditions. Among the tested probiotic species, L. plantarum demonstrated superior inhibition on the growth of C. albicans and S. mutans, disruption of virulent biofilm formation with reduced bacteria and exopolysaccharide (EPS) components, and formation of virulent microcolonies structures. Transcriptome analysis (RNA sequencing) further revealed disruption of S. mutans and C. albicans cross-kingdom interactions with added L. plantarum. Genes of S. mutans and C. albicans involved in metabolic pathways (e.g., EPS formation, carbohydrate metabolism, glycan biosynthesis, and metabolism) were significantly downregulated. More significantly, genes related to C. albicans resistance to antifungal medication (ERG4), fungal cell wall chitin remodeling (CHT2), and resistance to oxidative stress (CAT1) were also significantly downregulated. In contrast, Lactobacillus genes plnD, plnG, and plnN that contribute to antimicrobial peptide plantaricin production were significantly upregulated. Our novel study findings support further assessment of the potential role of probiotic L. plantarum for cariogenic biofilm control.


Assuntos
Cárie Dentária , Lactobacillus plantarum , Biofilmes , Candida albicans/fisiologia , Streptococcus mutans/genética
18.
BMC Cancer ; 22(1): 393, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35410148

RESUMO

BACKGROUND: For CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) after treatment with murine CD19 (mCD19) CAR-T, the reinfusion of mCD19 CAR-T cells may be ineffective due to anti-mouse single-chain variable fragment (scFv) antibody caused by mCD19 CAR. To overcome this immunogenicity, we applied humanized CD19 (hCD19) CAR-T cells to treat r/r B-ALL patients with prior mCD19 CAR-T therapy. METHODS: Nineteen pediatric and adult patients were included, 16 relapsed after and 3 were primarily resistant to mCD19 CAR-T. All patients presented with more than 5% blasts in bone marrow and/or extramedullary disease, and still showed CD19 antigen expression. Humanized CD19-CARs were lentiviral vectors carrying a second generation CAR with 4-1-BB co-stimulatory and CD3ζ signaling domains. Patient-derived cells were collected for producing CAR-T cells, the median dose of infused hCD19 CAR-T cells was 2.4 × 105/kg (range, 1.0-18.0 × 105/kg). RESULTS: hCD19 CAR-T resulted in a complete remission (CR) rate of 68% (13/19). Among 13 remission patients, 11 underwent allogeneic hematopoietic cell transplantation (allo-HCT) (3 were second HCT) and 10 remained in CR; the event-free survival rates at 12-18 months were 91% in 11 patients received following allo-HCT and 69% in all CR patients. Six cases had no response to hCD19 CAR-T, 3 died of disease progression; another 3 received salvage second transplantation, of them, 2 relapsed again (one died). Cytokine release syndrome (CRS) occurred in 95% (18/19) of patients, most CRS events were grade 1 and grade 2 (n = 17), there was only one grade 4 CRS. Two cases experienced grade 1 neurotoxicity. CONCLUSIONS: Humanized CD19 CAR-T cell therapy could be a treatment option for CD19-positive B-ALL patients who relapsed after or resisted prior murine CD19 CAR-T, hCD19 CAR-T followed by allo-HCT provided a longer remission in CR patients. Nevertheless, the prognosis of non-responders to hCD19 CAR-T remained dismal. TRIAL REGISTRATION: Chinese Clinical Trial Registry/WHO International Clinical Trial Registry ( ChiCTR1900024456 , URL: www.chictr.org.cn ); registered on July 12, 2019.


Assuntos
Linfoma de Burkitt , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Animais , Antígenos CD19 , Linfoma de Burkitt/terapia , Criança , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/genética , Anticorpos de Cadeia Única , Linfócitos T , Organização Mundial da Saúde
19.
Biometrics ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428983

RESUMO

We propose a model-based clustering method for high-dimensional longitudinal data via regularization in this paper. This study was motivated by the Trial of Activity in Adolescent Girls (TAAG), which aimed to examine multilevel factors related to the change of physical activity by following up a cohort of 783 girls over 10 years from adolescence to early adulthood. Our goal is to identify the intrinsic grouping of subjects with similar patterns of physical activity trajectories and the most relevant predictors within each group. The previous analyses conducted clustering and variable selection in two steps, while our new method can perform the tasks simultaneously. Within each cluster, a linear mixed-effects model (LMM) is fitted with a doubly penalized likelihood to induce sparsity for parameter estimation and effect selection. The large-sample joint properties are established, allowing the dimensions of both fixed and random effects to increase at an exponential rate of the sample size, with a general class of penalty functions. Assuming subjects are drawn from a Gaussian mixture distribution, model effects and cluster labels are estimated via a coordinate descent algorithm nested inside the Expectation-Maximization (EM) algorithm. Bayesian Information Criterion (BIC) is used to determine the optimal number of clusters and the values of tuning parameters. Our numerical studies show that the new method has satisfactory performance and is able to accommodate complex data with multilevel and/or longitudinal effects.

20.
Nanomaterials (Basel) ; 12(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458063

RESUMO

A multi-functional broadband absorber based on graphene and strontium titanate (STO) film was designed. Additionally, the frequency, bandwidth, and amplitude of the absorber could be tuned by adjusting temperature and Fermi level of the graphene. By using the finite-difference time-domain (FDTD) method, the numerical calculation result shows that, when keeping the device temperature at 230 K and setting graphene Fermi level to be 1 eV, three absorption peaks at 1.72 THz, 2.08 THz, and 2.59 THz were realized and combined into a broadband absorption from 1.68 to 2.74 THz. As the STO temperature was increased from 230 K to 310 K, the center frequency moved from 2.2 THz to 2.45 THz; correspondingly, the broadband absorption range was widened from 1.06 THz to 1.24 THz. When the temperature was fixed at 230 K and the graphene Fermi level was tuned from 1 eV to 0.7 eV, the absorption bandwidth decreased from 1.06 THz to 0.64 THz. While the Fermi level was tuned continually to be 0.01 eV, only a single absorption peak with an absorption rate of 0.29 existed. The broadband absorption and tuning mechanism of the absorber were analyzed using impedance matching theory. Furthermore, we also studied the effect of incident angle and polarization direction on the properties of the absorber. The multi-functional tunable absorber provides potential applications for the design of more efficient terahertz functional devices in the future.

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