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1.
Bioact Mater ; 19: 418-428, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35574059

RESUMO

Labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential method for magnetic resonance imaging (MRI) tracking of transplanted cells in tissue repair studies and clinical trials. Labeling of MSCs using clinically approved SPIONs (ferumoxytol) requires the use of transfection reagents or magnetic field, which largely limits their clinical application. To overcome this obstacle, we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol. Unlike conventional methods, ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids. Moreover, the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety. Strikingly, the encapsulated ferumoxytol was localized in the extracellular matrix (ECM) of the spheroids instead of the cytoplasm, minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids. This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.

2.
Front Microbiol ; 13: 840562, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369425

RESUMO

Antibiotic resistance is one of the most important environmental challenges. Microalgae has been considered as a promising green media for environmental purification. In this work, sulfadimethoxine (SDM) biodegradation potential of Chlorella sp. L38 and Phaeodactylum tricornutum MASCC-0025 is investigated. Experimental results indicated that the tested freshwater and marine microalgae strains presented stress response to SDM addition. For Chlorella sp. L38, it has a good adaptability to SDM condition via antioxidant enzyme secretion (SOD, MDA, and CAT up to 23.27 U/mg, 21.99 µmol/g, and 0.31 nmol/min/mg) with removal rate around 88%. P. tricornutum MASCC-0025 exhibited 100% removal of 0.5 mg/L SDM. With increasing salinity (adding a certain amount of NaCl) of cultivation media, the removal rate of SDM by microalgae increased. Although its adaptive process was slower than Chlorella sp. L38, the salinity advantage would facilitate enzyme accumulation. It indicated that microalgae could be used to remove SDM from freshwater and marine environment via suitable microalgae strain screening.

3.
Dev Cell ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35917813

RESUMO

Gut epithelial morphogenesis is maintained by intestinal stem cells. Here, we report that depletion of N6-adenosine methyltransferase subunit Mettl14 from gut epithelial cells in mice impaired colon mucosal morphogenesis, leading to increased mucosal permeability, severe inflammation, growth retardation, and premature death. Mettl14 ablation triggered apoptosis that depleted Lgr5+ stem cells and disrupted colonic organoid growth and differentiation, whereas the inhibition of apoptosis rescued Mettl14-deleted mice and organoids. Mettl14 depletion disrupted N6-adenomethylation on GsdmC transcripts and abolished GsdmC expression. Reconstitution of Mettl14-deleted organoids or mice with GSDMC rescued Lgr5 expression and prevented apoptosis and mouse premature death, whereas GSDMC silence eliminated LGR5 and triggered apoptosis in human colonic organoids and epithelial cells. Mechanistically, Mettl14 depletion eliminated mitochondrial GsdmC, disrupted mitochondrial membrane potential, and triggered cytochrome c release that activates the pro-apoptotic pathway. In conclusion, GsdmC N6-adenomethylation protects mitochondrial homeostasis and is essential for Lgr5+ cell survival to maintain normal colonic epithelial regeneration.

4.
J Asian Nat Prod Res ; : 1-12, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920176

RESUMO

Twenty-two metabolites were isolated from Penicillium sp. CPCC 401423 cultured on rice. The structures of all compounds were elucidated mainly by MS and NMR analysis as well as the necessary CD experimental evidence, of which penicillidione A (1), penicillidione B (2), (E)-4-[(4-acetoxy-3-methyl-2-butenyl)oxy]phenylacetic acid (3), (S)-2-hydroxy-2-{4-[(3-methyl-2-butenyl)oxy]phenyl} (4), (S)-4-(2,3-dihydroxy-3-methyl-butoxy)phenylacetic acid (5), (E)-4-[(3-carboxy-2-butenyl)oxy]benzoic acid (6), (Z)-4-[(4-hydroxy-3-methyl-2-butenyl)oxy]benzoic acid (7), open-cycled N-demethylmelearoride A (12), and penostatin M (16) were identified as new compounds. The cytotoxic activity against human pancreatic carcinoma cell line MIA PaCa-2a was detected. Among them, compounds 13-15 and 22 displayed significant cytotoxicity against MIA-PaCa-2 cells with IC50 values of 8.9, 36.5, 31.8, and 22.3 µM, respectively (positive control gemcitabine IC50 65.0 µM).

5.
Immunol Invest ; : 1-13, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921125

RESUMO

BACKGROUND: The present study was designed to identify and understand the potential effectiveness of therapeutic target in intervertebral disc degeneration (IVDD) and its regulation mechanism. METHODS: The role and mechanism of interleukin-18 (IL-18) in the disease were investigated. The IVDD degenerative nucleus pulposus (NP) tissues from the human and mouse models were used.A total of three groups of Male BALB/c mice were randomly made i.e control, IVDD, and IVDD+Ad-shIL-18 groups. After Ad-shIL-18 transfection, the expression of ECM synthesis related protein Aggrecan (ACAN) and Collagen II, apoptotic effector Caspases (Caspase-3, 8, 9, 12 and Cleaved-Caspase 3, 8, 9, 12), pro-apoptotic gene Bax and anti-apoptotic factors Bcl-2 in NP cells of the human were evaluated. RESULTS: The results of our study revealed that the mRNA and protein expression levels of IL-18 were notably increased in the NP tissues of IVDD patients and mice models. In the IVDD mice model, Ad-sh-IL-18 treatment reversed the IVDD progression. The levels of Aggrecan and Collagen II, contributing to ECM degradation in NP cells, were also significantly increased. Additionally, Ad-sh-IL-18 could inhibit the NP cell's apoptosis via regulating the caspase-3/9 pathway. CONCLUSION: The IL-18 knockdown via the caspase-3/9 pathway, might reduce the NP cell's death as well as the imbalance between catabolism and anabolism of ECM in IVDD.

6.
Arch Physiol Biochem ; : 1-12, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913790

RESUMO

BACKGROUND: HECTD3 (HECT domain E3 ubiquitin protein ligase 3) exerts biological activities in neuroinflammation of distinct diseases, such as autoimmune encephalomyelitis and donations after heart death. However, the effect of HECTD3 on diabetes-associated cognitive decline (DACD) remains unclear. METHODS: Wild-type or HECTD3-knockout rats were administered with streptozotocin to establish diabetic model. Pathological changes in the hippocampus were assessed by NISSL and haematoxylin and eosin staining. Morris water maze test was used to assess cognitive function. Neuronal survival and inflammation were investigated by immunofluorescence staining and ELISA assay. NLRP3 inflammasome and pyroptosis were assessed by western blot, immunofluorescence and flow cytometry assays. RESULTS: HECTD3 was up-regulated in hippocampus of streptozotocin-induced diabetic rats and high glucose-induced PC12 cells. Knockout of HECTD3 increased the number of neurons and improved the learning and memory function. Moreover, knockout of HECTD3 promoted in vivo neuronal survival, and reduced levels of IL-1ß, TNF-α, and IL-6 in the hippocampus. Silencing of HECTD3 increased cell viability, and reduced IL-1ß, TNF-α, and IL-6 in high glucose-induced PC12 cells. Fluorescence intensities of NLRP3, GSDMD-N and caspase-1 were reduced in HECTD3-knockout diabetic rats, and knockdown of HECTD3 down-regulated protein expression of NLRP3, GSDMD-N, caspase-1, IL-1ß, and IL-18 in high glucose-induced PC12 cells to suppress the pyroptosis. HECTD3 promoted the stability of mucosa-associated lymphoid tissue 1 (MALT1) through up-regulation of c-JUN and phospho (p)-JNK in high glucose-induced PC12 cells. Over-expression of MALT1 attenuated neuroprotective effects of HECTD3 silencing on high glucose-induced PC12 cells. CONCLUSION: HECTD3 silencing exerted neuroprotective effect against DACD through MALT1-mediated JNK signalling.HighlightsHECTD3 was up-regulated in hippocampus of streptozotocin-induced diabetic rats and high glucose-induced PC12.Knockout of HECTD3 promoted in vivo neuronal survival, reduced inflammation and pyroptosis, and improved the learning and memory function in diabetic rats.Knockout of HECTD3 suppressed the activation of NLRP3 inflammasome in diabetic rats.Silencing of HECTD3 exerted neuroprotective effects through MALT1-mediated JNK signalling.

7.
Org Lett ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35925684

RESUMO

Hypersampones A-C (1-3), three unprecedented nor-polycyclic polyprenylated acylphloroglucinols (PPAPs), were isolated from Hypericum sampsonii. These compounds represent the first nor-PPAPs with an unexpected tetracyclic 6/5/5/6 ring system. Their structures were assigned through the analysis of detailed spectroscopic data, X-ray crystallography, and electronic circular dichroism calculations. Compound 1 significantly inhibited the accumulation of lipid in an oleic acid-treated HepG2 cell model by suppressing the protein expression of FAS and ACACA at 5 µM.

8.
Brain ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35925685

RESUMO

The temporal evolutions and relative orderings of Alzheimer disease biomarkers, including CSF amyloid-ß42 (Aß42), Aß40, total tau (Tau) and phosphorylated tau181 (pTau181), standardized uptake value ratio (SUVR) from the molecular imaging of cerebral fibrillar amyloid-ß with PET using the 11C-Pittsburgh Compound-B (PiB), MRI-based hippocampal volume and cortical thickness and cognition have been hypothesized but not yet fully tested with longitudinal data for all major biomarker modalities among cognitively normal individuals across the adult lifespan starting from 18 years. By leveraging a large harmonized database from 8 biomarker studies with longitudinal data from 2609 participants in cognition, 873 in MRI biomarkers, 519 in PET PiB imaging and 475 in CSF biomarkers for a median follow-up of 5-6 years, we estimated the longitudinal trajectories of all major Alzheimer disease biomarkers as functions of baseline age that spanned from 18 to 103 years, located the baseline age window at which the longitudinal rates of change accelerated and further examined possible modifying effects of apolipoprotein E (APOE) genotype. We observed that participants 18-45 years at baseline exhibited learning effects on cognition and unexpected directions of change on CSF and PiB biomarkers. The earliest acceleration of longitudinal change occurred for CSF Aß42 and Aß42/Aß40 ratio (with an increase) and for Tau, and pTau181 (with a decrease) at the next baseline age interval of 45-50 years, followed by an accelerated increase for PiB SUVR at the baseline age of 50-55 years and an accelerated decrease for hippocampal volume at the baseline age of 55-60 years and finally by an accelerated decline for cortical thickness and cognition at the baseline age of 65-70 years. Another acceleration in the rate of change occurred at the baseline age of 65-70 years for Aß42/Aß40 ratio, Tau, pTau181, PiB SUVR and hippocampal volume. Accelerated declines in hippocampal volume and cognition continued after 70 years. For participants 18-45 years at baseline, significant increases in Aß42 and Aß42/Aß40 ratio and decreases in PiB SUVR occurred in APOE ɛ4 non-carriers but not carriers. After age 45 years, APOE ɛ4 carriers had greater magnitudes than non-carriers in the rates of change for all CSF biomarkers, PiB SUVR and cognition. Our results characterize the temporal evolutions and relative orderings of Alzheimer disease biomarkers across the adult lifespan and the modification effect of APOE ɛ4. These findings may better inform the design of prevention trials on Alzheimer disease.

9.
BMC Ophthalmol ; 22(1): 332, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932001

RESUMO

BACKGROUND: Prostaglandin analogs (PGAs) are the first-line treatment for primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study aimed to confirm the effectiveness and safety of Tapros® (0.0015% tafluprost eye drops) in Chinese patients with POAG and OH. METHODS: This phase IV, multicenter, non-comparative, prospective study enrolled patients with POAG and OH in China between 12/27/2017 and 04/15/2020. Patients who were treatment-naïve or untreated within one month (group A) or with unreached intraocular pressure (IOP) target after previous monotherapy of other PGAs (group B) or non-PGA IOP-lowering drugs (group C) were treated with 0.0015% tafluprost for three months. The IOP reduction, response rate, and safety were observed. RESULTS: There were 165, 89, and 31 patients in groups A, B, and C, with baseline IOPs of 22.4 ± 4.7, 21.0 ± 3.5, and 22.5 ± 3.2 mmHg, respectively. The least-square means and percentages of IOP reduction at 3 months for groups A, B, and C were 4.7 (19.8%), 1.6 (6.1%), and 4.6 mmHg (20.3%), respectively. A significant reduction in IOP was observed at each visit compared with baseline (all P < 0.05). At the final visit, 57.0% of the participants in group A achieved an IOP reduction of ≥ 20%, while 40.4% and 77.4% in groups B and C achieved an IOP reduction of ≥ 10%. Fifty-eight treatment-related adverse events occurred in 46 participants (15.7%), of which the most common one was conjunctival hyperemia (34/293, 11.6%). CONCLUSIONS: Tafluprost showed a sustained and significant effect with tolerable adverse events in Chinese patients with POAG and OH who were treatment-naïve or untreated within one month or received prior treatments with unsatisfying outcomes.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Hipotensão Ocular , Anti-Hipertensivos/efeitos adversos , Glaucoma/tratamento farmacológico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular , Marketing , Hipotensão Ocular/tratamento farmacológico , Estudos Prospectivos , Prostaglandinas F , Prostaglandinas Sintéticas , Resultado do Tratamento
10.
Spat Spatiotemporal Epidemiol ; 42: 100522, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35934328

RESUMO

Preventive measures, health behaviors, environmental exposures, and sociodemographic characteristics affect individual-level cancer risks. It is unclear how they influence neighborhood-level cancer risks. We developed a large-scale neighborhood health dataset for 72,337 census tracts in the United States by combining data from three publicly available sources. We used Bayesian additive regression trees to identify the most important predictors of tract-level cancer prevalence among adults (age ≥18 years), and examined their impact on cancer prevalence using partial dependence plots. The five most important census tract-level correlates of cancer prevalence were the proportion of population who were aged 65 years and older, had routine checkup and were non-Hispanic White, the proportion of houses built before 1960, and the proportion of population living below the poverty line. The identified predictors of neighborhood-level cancer prevalence may inform public health practitioners and policymakers to prioritize the improvement of environmental and neighborhood factors in reducing the cancer burden.


Assuntos
Setor Censitário , Neoplasias , Adulto , Teorema de Bayes , Humanos , Aprendizado de Máquina , Neoplasias/epidemiologia , Prevalência , Características de Residência , Fatores Socioeconômicos , Estados Unidos/epidemiologia
11.
Front Pediatr ; 10: 865057, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935354

RESUMO

Objective: To investigate the clinical outcomes of preterm infants who received non-invasive high-frequency oscillatory ventilation following extubation in a neonatal intensive care unit. Methods: Infants born between 25 and 34 weeks of gestation with a birth weight of <1,500 g, who were admitted into the neonatal intensive care unit of Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, China, requiring mechanical ventilation on admission were randomized to the non-invasive high-frequency ventilation group, nasal intermittent positive pressure ventilation group, or nasal continuous positive airway pressure group following extubation. Their respiratory and neurodevelopmental outcomes were assessed at 12 and 24 months of corrected age. Results: Among 149 preterm infants who underwent randomization, 139 completed their treatment in the neonatal intensive care unit (45, 47, 47 in the non-invasive high-frequency ventilation group, nasal intermittent positive pressure ventilation group, or nasal continuous positive airway pressure group, respectively), 113 were assessed at 12-month corrected age, and 110 of 113 were assessed again at 24-month corrected age. There were no differences in the number of times bronchitis, pneumonia, wheezing episodes, and re-hospitalization rates appeared due to respiratory diseases among the three groups (P > 0.05); the pulmonary function tests at 12-month corrected age showed respiratory rate, tidal volume, inspiratory time/expiratory time, time to peak expiratory flow/expiratory time, volume at peak expiratory flow/expiratory volume, expiratory flow at 25, 50, and 75% tidal volume were all similar among infants from the 3 groups (P > 0.05). There were no differences in the rates of neurodevelopmental impairment among the three groups at 24-month corrected age (P > 0.05). Conclusion: As post-extubation respiratory support in preterm infants, non-invasive high-frequency ventilation did not increase the rates of long-term respiratory morbidities and neurodevelopmental impairment compared with nasal intermittent positive pressure ventilation and nasal continuous positive airway pressure.

12.
Biomater Adv ; 136: 212773, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35929312

RESUMO

Delayed or non-healing skin wounds causing gangrene or even amputation, greatly threats diabetic patients lives. Herein, a bioactive, in-situ formable hydrogel based wound dressing was designed through simple Schiff base reaction. Oxidized dextran (OD) and carboxyethyl chitosan (CEC) were crosslinked together and applied as the main porous framework of hydrogel. To improve the mechanical strength and biocompatibility, collagen (Col) and EGF (Epidermal Growth Factor) were introduced into OD-CEC precursors: (1) after addition of only Col, the mechanical strength of hydrogels was improved by participating the functional -NH2 group of Col into the crosslinking process. Moreover, swelling ratio was as high as 750% on 3%OD-3%CEC-Col (water retention rate was 65 wt% after 7 days). (2) Once we introduced both Col and EGF into the OD-CEC hydrogel, the proliferation of mouse embryonic fibroblast (NIH 3T3) cells was promoted using 3%OD-3%CEC-Col/EGF, an accelerated wound healing was observed with 86% wound closure after only 14 operative days. Hematoxylin and eosin (H&E) staining and Masson staining indicated the synergy of Col and EGF might promote new tissue's formation, well collagen distributions and thus accelerate skin regeneration, presenting great potentials in wound healing of diabetic patients.


Assuntos
Quitosana , Diabetes Mellitus , Animais , Quitosana/farmacologia , Colágeno/farmacologia , Dextranos/farmacologia , Diabetes Mellitus/tratamento farmacológico , Fator de Crescimento Epidérmico/farmacologia , Fibroblastos , Hidrogéis/farmacologia , Camundongos , Cicatrização
13.
Alzheimers Dement ; 2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-35934777

RESUMO

INTRODUCTION: Screening potential participants in Alzheimer's disease (AD) clinical trials with amyloid positron emission tomography (PET) is often time consuming and expensive. METHODS: A web-based application was developed to model the time and financial cost of screening for AD clinical trials. Four screening approaches were compared; three approaches included an AD blood test at different stages of the screening process. RESULTS: The traditional screening approach using only amyloid PET was the most time consuming and expensive. Incorporating an AD blood test at any point in the screening process decreased both the time and financial cost of trial enrollment. Improvements in AD blood test accuracy over currently available tests only marginally increased savings. Use of a high specificity cut-off may improve the feasibility of screening with only an AD blood test. DISCUSSION: Incorporating AD blood tests into screening for AD clinical trials may reduce the time and financial cost of enrollment. HIGHLIGHTS: The time and cost of enrolling participants in Alzheimer's disease (AD) clinical trials were modeled. A web-based application was developed to enable evaluation of key parameters. AD blood tests may decrease the time and financial cost of clinical trial enrollment. Improvements in AD blood test accuracy only marginally increased savings. Use of a high specificity cut-off may enable screening with only an AD blood test.

14.
Mol Cell Biol ; : e0010722, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35938797

RESUMO

HAS2 antisense RNA 1 (HAS2-AS1) is a long noncoding RNA that has increased expression in mature granulosa cells (GCs) and contributes to cumulus expansion by regulating HAS2 expression. However, the roles of HAS2-AS1 during the pathological process of polycystic ovary syndrome (PCOS) are still unclear. This study investigated the roles of HAS2-AS1 in patients with PCOS. Here, a significant upregulation of HAS2-AS1 was found in the primary GCs from patients with PCOS, which was positively correlated with the level of the protein HAS2. The knockdown of HAS2 restored the upregulation of HAS2-AS1 in promoting migration but could not restore the effects of HAS2-AS1 overexpression in promoting proliferation and repressing apoptosis. Transforming growth factor ß (TGF-ß) upregulated HAS2-AS1 levels, while HAS2-AS1 functioned as a feedback inhibition factor repressing TGF-ß signaling by inhibiting TGF-ß receptor type 2 (TGFBR2) expression. HAS2-AS1 bonded with EZH2 and guided the polycomb complex 2 to the TGFBR2 promoter region. HAS2-AS1 overexpression induced H3K27 hypermethylation in the TGFBR2 promoter region and then repressed TGFBR2 transcription in KGN cells and primary GCs. In conclusion, we identified for the first time that HAS2-AS1 is upregulated in patients with PCOS and represses TGF-ß signaling via inducing TGFBR2 promoter region hypermethylation, which allowed us to explore the pathological processes of PCOS.

15.
Anal Chem ; 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35938925

RESUMO

FcγRIIIa-binding affinity is one of the key factors to ensure the efficacy of many antitumor therapeutic antibodies, which should be monitored along with the titer, protein aggregation, and other critical quality attributes. The conventional workflow for the quality assessment of therapeutic antibodies in harvested cell culture fluid (HCCF) is time-consuming and costly nevertheless. In this study, a tractable method was established for rapid quality assessment of a HCCF sample through differentially extracting IgG with different FcγRIIIa affinity levels using FcγRIIIa-immobilized magnetic microspheres, followed by size exclusion chromatography (SEC) to determine the amount and monomer percentage of IgGs in the preceding eluate. FcγRIIIa-immobilized magnetic microspheres with polydopamine (PDA) and hydrophilic dendrimer (PAMAM) coating (denoted as Fe3O4@PDA@PAMAM-FcγRIIIa) were synthesized for the first time as magnetic adsorbents. The PDA cladding endowed the composites with good chemical stability in acidic elution buffer, and the PAMAM dendrimer empowered the composites of high ligand immobilization capacity and hydrophilic surface. The labile FcγRIIIa was immobilized under mild conditions. By directly applying a simple magnetic solid phase extraction procedure to treat HCCF, favored IgG species with high FcγRIIIa affinity would be selectively captured by Fe3O4@PDA@PAMAM-FcγRIIIa composites for subsequent SEC analysis. The monomer peak area value in SEC, which was set as the read-out of the proposed method, correlated directly with the theoretical overall quality of standard-spiked HCCF samples.

16.
Amino Acids ; 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939077

RESUMO

The post-translational modifications (PTMs), which are crucial in the regulation of protein functions, have great potential as biomarkers of cancer status. Fascin (Fascin actin-bundling protein 1, FSCN1), a key protein in the formation of filopodia that is structurally based on actin filaments (F-actin), is significantly associated with tumor invasion and metastasis. Studies have revealed various regulatory mechanisms of human Fascin, including PTMs. Although a number of Fascin PTM sites have been identified, their exact functions and clinical significance are much less explored. This review explores studies on the functions of Fascin and briefly discusses the regulatory mechanisms of Fascin. Next, to review the role of Fascin PTMs in cell biology and their associations with metastatic disease, we discuss the advances in the characterization of Fascin PTMs, including phosphorylation, ubiquitination, sumoylation, and acetylation, and the main regulatory mechanisms are discussed. Fascin PTMs may be potential targets for therapy for metastatic disease.

17.
Interdiscip Sci ; 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939233

RESUMO

A surge in research has occurred because of current developments in single-cell technologies. Above all, single-cell Assay for Transposase-Accessible Chromatin with high throughput sequencing (scATAC-seq) is a popular approach of analyzing chromatin accessibility differences at the level of single cell, either within or between groups. As a result, it is critical to examine cell heterogeneity at a previously unseen level and to identify both recognized and unknown cell types. However, with the ever-increasing number of cells engendered by technological development and the characteristics of the data, such as high noise, sparsity and dimension, challenges in distinguishing cell types have emerged. We propose scVAEBGM, which integrates a Variational Autoencoder (VAE) with a Bayesian Gaussian-mixture model (BGM) to process and analyze scATAC-seq data. This method combines and takes benefits of a Bayesian Gaussian mixture model to estimate the number of cell types without determining the cluster number in a beforehand. In other words, the size of the clusters is inferred from the data, thus avoiding biases introduced by subjective assessments when manually determining the size of the clusters. Additionally, the method is more robust to noise and can better represent single-cell data in lower dimensions. We also create a further clustering strategy. It is indicated by experiments that further clustering based on the already completed clustering can improve the clustering accuracy again. We test on six public datasets, and scVAEBGM outperforms various dimension reduction baselines. In downstream applications, scVAEBGM can reveal biological cell types.

18.
Neurotoxicology ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35944761

RESUMO

BACKGROUND: Prenatal and infant daily exposures to pyrethroid pesticides (PYRs), used in the elimination of harmful organisms in the family environment and agricultural activities, may have an impact on children's language development. OBJECTIVES: To determine the impacts of prenatal and infant PYRs exposure on 2-year-old toddlers' language development. METHODS: From January 2016 to December 2018, women in the third trimester of pregnancy, in Yunnan rural area, China, were recruited, and the development of their newborns was observed from birth till the age of two. We examined three PYRs metabolites: 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-2,2dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) in urine samples collected from women in the third trimester of pregnancy and their infants of 6-8 months after birth, and assessed language development of 2-year-old toddlers by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Generalized linear models were used to analyze the impacts of exposure to PYRs on 2-year-old toddlers' language development. RESULTS: The median concentrations of 3PBA, 4F3PBA and DBCA creatinine-adjusted were 0.21, 0.19, and 0.15µg/g in pregnancy, and 0.25, 0.72, and

19.
Front Immunol ; 13: 916915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936000

RESUMO

Myxofibrosarcoma (MFS) is a highly malignant subtype of soft tissue sarcoma, accounting for 5% of cases. Immunotherapy guided by immune cell infiltration (ICI) is reportedly a promising treatment strategy. Here, MFS samples (n = 104) from two independent databases were classified as ICI clusters A/B/C and gene clusters A/B/C. Then, a close relationship between ICI and gene clusters was established. We found that the features of these clusters were consistent with the characteristics of immune-inflamed tumors (cluster C), immune-desert tumors (cluster B), and immune-excluded tumors (cluster A). Moreover, cluster C was sensitive to immunotherapy. Finally, an independent ICI score was established to predict the therapeutic effect, which has prospects for application in guiding immunotherapy during clinical practice.


Assuntos
Fibrossarcoma , Microambiente Tumoral , Biomarcadores Tumorais/genética , Fibrossarcoma/genética , Fibrossarcoma/terapia , Humanos , Imunoterapia , Prognóstico
20.
ACS Omega ; 7(30): 26165-26173, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35936432

RESUMO

With the outbreak of COVID-19 around the world, rapid and accurate detection of new coronaviruses is the key to stop the transmission of the disease and prevent and control the novel coronavirus, among which polymerase chain reaction (PCR) is the mainstream nucleic acid detection method. A temperature cycling device is the core of the PCR amplification micro-device. The precision of the temperature control and temperature change rate directly affect the efficiency of PCR amplification. This study proposes a new PCR method based on rapid PCR chip optimization of a liquid metal bath, which realizes precise and rapid temperature rise and fall control. We systematically explored the feasibility of using liquid metals with different melting points in the system and proposed a 47 °C bismuth-based liquid metal bath as the heat conduction medium of the system to optimize the system. The heat conduction properties of the thermally conductive silicone oil bath were compared. Compared with the thermally conductive silicone oil bath, thermal cycle efficiency is improved nearly 3 times. The average heating rate of the liquid metal bath is fast, and the temperature control stability is good, which can significantly reduce the hysteresis, and the temperature change curve is more gentle, which can greatly improve the efficiency of PCR amplification. The results of gene amplification using rat DNA as the template and SEC61A as the target also indicate that the system can be successfully used in PCR devices, and the types of PCR containers can be not limited to PCR tubes. Based on the experiment, we proved that the PCR method optimized by the liquid metal bath multi-gene rapid PCR chip can further improve the temperature response speed. It has the advantages of accurate data, fast response speed, low price, safety, and environmental protection and can effectively reduce the time of PCR and improve the application efficiency. As far as we know, this is the first international report on using a liquid metal bath to do rapid-cooling PCR.

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