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1.
Food Chem ; 367: 130764, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34384986

RESUMO

The development of food proteins as effective delivery systems is of great significance for the encapsulation of active compounds. Foxtail millet prolamin (FP) has a high level of hydrophobic amino acids and proline, meets the basic characteristics of delivery system, and was described here for the first time as an effective delivery system for the encapsulation of curcumin. The interaction between FP and curcumin was confirmed by fluorescence spectroscopy, showing the joint driving of hydrophobic forces and hydrogen bonds. Curcumin-loaded caseinate-stabilized FP nanodispersions were prepared by anti-solvent/evaporation method. The mean particle size was about 220-235 nm, sharing features of a spherical shape, uniform particle size, and smooth surfaces. High level of curcumin was encapsulated in the FP-based nanoparticles, exhibiting high particle yield (>88.4%) and encouraging encapsulation efficiency (>71.3%). X-ray diffraction and Fourier transform infrared spectroscopy demonstrated that the encapsulated curcumin was amorphous state and interacted with proteins via non-covalent bonds. The nano-sized particles can effectively prevent the degradation of curcumin during heat treatment, and significantly enhance the antioxidant and anti-tumor properties. This study provides a new encapsulant for effective protection and targeted delivery of hydrophobic active biomolecules.

2.
Toxicology ; : 152934, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509579

RESUMO

Acrylamide (ACR) is a recognized toxin that is known to induce neurotoxicity in humans and experimental animals. This study aimed to investigate the toxic effects of subacute exposure of the motor endplate (MEP) of the gastrocnemius in rats to ACR. All rats were randomly divided into control, 9, 18, and 36 mg/kg ACR groups, and ACR was administered by gastric gavage for 21 days. The behavioral tests were performed weekly. On the 22nd day, the wet weight of the gastrocnemius was measured. The changes in muscle fiber structure, nerve endings, and MEP in the gastrocnemius were examined by hematoxylin-eosin (HE) and gold chloride staining. Acetylcholinesterase (AChE) content in the gastrocnemius was detected by AChE staining. The expression of AChE and calcitonin gene-related peptide was detected by immunohistochemistry and western blot. Rats exposed to ACR showed a significant increase in gait scores and hind limb splay distance compared with the control group, and the wet weight of the gastrocnemius was reduced, HE staining showed that the muscle fiber structure of the gastrocnemius became thin and the arrangement was dense with nuclear aggregation, gold chloride staining showed that nerve branches decreased and became thin, nerve fibers became short and light, the number of MEPs was decreased, the staining became light, and the structure was not clear. AChE staining showed that the number of MEPs was significantly reduced after exposure to ACR, the shape became small, and the AChE content decreased in a dose-dependent manner. Immunohistochemistry and western blot analysis results of the expression levels of AchE and CGRP showed a decreasing trend as compared to the control group with increasing ACR exposure dose. The reduction in protein levels may be the mechanism by which ACR has a toxic effect on the MEP in the gastrocnemius of rats.

3.
Mol Ecol ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510615

RESUMO

The evolutionary outcomes of high-elevation adaptation have been extensively described. However, whether widely distributed high-elevation endemic animals adopt uniform mechanisms during adaptation to different elevational environments remains unknown, especially with respect to extreme high elevation environments. To explore this, we analyze phenotypic and genomic data of seven populations of plateau zokor (Myospalax baileyi) along elevations ranging from 2700 to 4300 m. Based on whole-genome sequencing data and demographic reconstruction of the evolutionary history, we show that two populations of plateau zokor living at elevations exceeding 3700 m diverged from other populations nearly ten thousand years ago. Further, phenotypic comparisons reveal stress-dependent adaptation, as two populations living at elevations exceeding 3700 m have elevated ratios of heart mass to body mass relative to other populations, and the highest population (4300 m) displays alterations in erythrocytes. Correspondingly, genomic analysis of selective sweeps indicates that positive selection might contribute to the observed phenotypic alterations in these two extremely high-elevation populations, with the adaptive cardiovascular phenotypes of both populations possibly evolving under the functional constrains of their common ancestral population. Taken together, phenotypic and genomic evidence demonstrates that heterogeneous stressors impact adaptations to extreme elevations and reveals stress-dependent and genetically constrained adaptation to hypoxia, collectively providing new insights into the high-elevation adaptation.

4.
Plant J ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469599

RESUMO

Drought stress severely limits plant growth and production in apple (Malus domestica Borkh.). To breed water-deficit-tolerant apple cultivars that maintain high yields under slight or moderate drought stress, it is important to uncover the mechanisms underlying the transcriptional regulation of chlorophyll metabolism in apple. To explore this mechanism, we generated transgenic 'Gala3' apple plants with overexpression or knockdown of MdWRKY17, which encodes a transcription factor whose expression is significantly induced by water deficit. Under moderate drought stress, we observed significantly higher chlorophyll contents and photosynthesis rates in overexpression transgenic plants than in controls, whereas these were dramatically lower in the knockdown lines. MdWRKY17 directly regulates MdSUFB expression, as demonstrated by in vitro and in vivo experiments. MdSUFB, a key component of the sulfur mobilization (SUF) system that assembles Fe-S clusters, is essential for inhibiting chlorophyll degradation and stabilizing electron transport during photosynthesis, leading to higher chlorophyll levels in transgenic apple plants overexpressing MdWRKY17. The activated MdMEK2-MdMPK6 cascade by water-deficit stress fine-tunes the MdWRKY17-MdSUFB pathway by phosphorylating MdWRKY17 under water-deficit stress. This fine-tuning of the MdWRKY17-MdSUFB regulatory pathway is important for balancing plant survival and yield losses (chlorophyll degradation and reduced photosynthesis) under slight or moderate drought stress. The phosphorylation by MdMEK2-MdMPK6 activates the MdWRKY17-MdSUFB pathway at S66 (identified by LC-MS), as demonstrated by in vitro and in vivo experiments. Our findings reveal that the MdMEK2-MdMPK6-MdWRKY17-MdSUFB pathway stabilizes chlorophyll levels under moderate drought stress, which could facilitate the breeding of apple varieties that maintain high yields under drought stress.

5.
Geroscience ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480713

RESUMO

It has been demonstrated that elamipretide (SS-31) rescues age-related functional deficits in the heart but the full set of mechanisms behind this have yet to be determined. We investigated the hypothesis that elamipretide influences post-translational modifications to heart proteins. The S-glutathionylation and phosphorylation proteomes of mouse hearts were analyzed using shotgun proteomics to assess the effects of aging on these post-translational modifications and the ability of the mitochondria-targeted drug elamipretide to reverse age-related changes. Aging led to an increase in oxidation of protein thiols demonstrated by increased S-glutathionylation of cysteine residues on proteins from Old (24 months old at the start of the study) mouse hearts compared to Young (5-6 months old). This shift in the oxidation state of the proteome was almost completely reversed by 8 weeks of treatment with elamipretide. Many of the significant changes that occurred were in proteins involved in mitochondrial or cardiac function. We also found changes in the mouse heart phosphoproteome that were associated with age, some of which were partially restored with elamipretide treatment. Parallel reaction monitoring of a subset of phosphorylation sites revealed that the unmodified peptide reporting for Myot S231 increased with age, but not its phosphorylated form and that both phosphorylated and unphosphorylated forms of the peptide covering cMyBP-C S307 increased, but that elamipretide treatment did not affect these changes. These results suggest that changes to thiol redox state and phosphorylation status are two ways in which age may affect mouse heart function, which can be restored by treatment with elamipretide.

6.
NanoImpact ; 232021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34514184

RESUMO

Carbon dots (CDs) are a promising material currently being explored in many industrial applications in the biomedical and agri-food areas; however, studies supporting the environmental health risk assessment of CDs are needed. This study focuses on various CD forms including iron (FeCD) and copper (CuCD) doped CDs synthesized using hydrothermal method, their fate in gastrointestinal tract, and their cytotoxicity and potential changes to cellular metabolome in a triculture small intestinal epithelial model. Physicochemical characterization revealed that 75% of Fe in FeCD and 95% of Cu in CuCD were dissolved during digestion. No significant toxic effects were observed for pristine CDs and FeCDs. However, CuCD induced significant dose-dependent toxic effects including decreases in TEER and cell viability, increases in cytotoxicity and ROS production, and alterations in important metabolites, including D-glucose, L-cysteine, uridine, citric acid and multiple fatty acids. These results support the current understanding that pristine CDs are relatively non-toxic and the cytotoxicity is dependent on the doping molecules.

7.
J Colloid Interface Sci ; 607(Pt 1): 357-366, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34509110

RESUMO

Gas sensors have become increasingly significant because of the rapid development in electronic devices that are applied in detecting noxious gases. Adjusting the crystal phase structure of sensing materials can optimize the band gap and oxygen-adsorptive capacity, which influences the gas sensing characteristics. Therefore, titanium dioxide (TiO2) materials with different crystal phase structures including rutile TiO2 nanorods (R-TiO2 NRs), anatase TiO2 nanoparticles (A-TiO2 NRs) and brookite TiO2 nanorods (B-TiO2 NRs) were synthesized successfully via one-step hydrothermal process, respectively. The gas sensing characteristics were also investigated systematically. The sensors based on R-TiO2 NRs displayed the higher response value (12.3) to 100 ppm acetone vapor at 320 °C compared to A-TiO2 NRs (4.1) and B-TiO2 NRs (2.3). Furthermore, gas sensors based on R-TiO2 NRs exhibited excellent repeatability under six cycles and good selectivity to acetone. The outstanding sensing properties of gas sensors based on R-TiO2 NRs can be ascribed to relatively narrow band gap and more oxygen vacancies of rutile phase, which showed a probable way for design gas sensors based on metal oxide semiconductors with remarkable gas sensing performances by the crystal phase adjustment engineering in the future.

8.
Trans GIS ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34512104

RESUMO

In order to find useful intervention strategies for the novel coronavirus (COVID-19), it is vital to understand how the disease spreads. In this study, we address the modeling of COVID-19 spread across space and time, which facilitates understanding of the pandemic. We propose a hybrid data-driven learning approach to capture the mobility-related spreading mechanism of infectious diseases, utilizing multi-sourced mobility and attributed data. This study develops a visual analytic approach that identifies and depicts the strength of the transmission pathways of COVID-19 between areal units by integrating data-driven deep learning and compartmental epidemic models, thereby engaging stakeholders (e.g., public health officials, managers from transportation agencies) to make informed intervention decisions and enable public messaging. A case study in the state of Colorado, USA was performed to demonstrate the applicability of the proposed transmission modeling approach in understanding the spatio-temporal spread of COVID-19 at the neighborhood level. Transmission path maps are presented and analyzed, demonstrating their utility in evaluating the effects of mitigation measures. In addition, integrated embeddings also support daily prediction of infected cases and role analysis of each area unit during the transmission of the virus.

9.
Nat Commun ; 12(1): 5398, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518545

RESUMO

As one of the largest biotechnological applications, activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses, with 10-1,000-fold higher concentrations than in natural environments. However, the compositional variation and host-connections of AS viruses remain poorly explored. Here, we report a catalogue of ~50,000 prokaryotic viruses from six WWTPs, increasing the number of described viral species of AS by 23-fold, and showing the very high viral diversity which is largely unknown (98.4-99.6% of total viral contigs). Most viral genera are represented in more than one AS system with 53 identified across all. Viral infection widely spans 8 archaeal and 58 bacterial phyla, linking viruses with aerobic/anaerobic heterotrophs, and other functional microorganisms controlling nitrogen/phosphorous removal. Notably, Mycobacterium, notorious for causing AS foaming, is associated with 402 viral genera. Our findings expand the current AS virus catalogue and provide reference for the phage treatment to control undesired microorganisms in WWTPs.

10.
Accid Anal Prev ; 162: 106396, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34547668

RESUMO

This study estimates the effect of gasoline prices on road deaths by vehicle mode using annual data for 62 countries for 2000-2018 and all states of the United States (US) for 1998-2018. Higher gasoline prices are associated with fewer overall road deaths. The proportional effect on motorcyclist deaths tends to be smaller or even have the opposite sign, especially in countries that are not highly dependent on motorcycles. For the US, a positive effect of gasoline prices on motorcyclist deaths is found, with an elasticity of about 0.3. There is also a positive relationship between gasoline prices and motorcycle registrations in the US. The results confirm that additional attention towards motorcyclist safety is warranted in times of high fuel prices.

11.
Nanomicro Lett ; 13(1): 200, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550499

RESUMO

Electronic skins (e-skins) with an excellent sensing performance have been widely developed over the last few decades. However, wearability, biocompatibility, environmental friendliness and scalability have become new limitations. Self-healing ability can improve the long-term robustness and reliability of e-skins. However, self-healing ability and integration are hardly balanced in classical structures of self-healable devices. Here, cellulose nanofiber/poly(vinyl alcohol) (CNF/PVA), a biocompatible moisture-inspired self-healable composite, was applied both as the binder in functional layers and the substrate. Various functional layers comprising particular carbon materials and CNF/PVA were patterned on the substrate. A planar structure was beneficial for integration, and the active self-healing ability of the functional layers endowed self-healed e-skins with a higher toughness. Water served as both the only solvent throughout the fabrication process and the trigger of the self-healing process, which avoids the pollution and bioincompatibility caused by the application of noxious additives. Our e-skins could achieve real-time monitoring of whole-body physiological signals and environmental temperature and humidity. Cross-interference between different external stimuli was suppressed through reasonable material selection and structural design. Combined with conventional electronics, data could be transmitted to a nearby smartphone for post-processing. This work provides a previously unexplored strategy for multifunctional e-skins with an excellent practicality.

12.
Ecotoxicol Environ Saf ; 224: 112640, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34392154

RESUMO

Hydrogen agriculture is recently recognized as an emerging and promising approach for low-carbon society. Since shorter retention time for hydrogen gas (H2) in conventional electrolytically produced hydrogen-rich water (HRW) limits its application, seeking a more suitable method to produce and maintain H2 level in HRW for longer time remain a challenge for scientific community. To solve above problems, we compared and concluded that the H2 in HRW prepared by ammonia borane (NH3·BH3) could meet above requirement. The biological effects of HRW prepared by NH3·BH3 were further evaluated in seedlings of rapeseed, the most important crop for producing vegetable oil worldwide. Under our experimental conditions, 2 mg/L NH3·BH3-prepared HRW could confer 3-day-old hydroponic seedlings tolerance against 150 mM sodium chloride (NaCl), 20% polyethylene glycol (PEG; w/v), or 100 µM CdCl2 stress, and intensify endogenous nitric oxide (NO) accumulation under above stresses. The alleviation of seedlings growth stunt was confirmed by reducing cell death and reestablishing redox homeostasis. Reconstructing ion homeostasis, increasing proline content, and reducing Cd accumulation were accordingly observed. Above responses were sensitive to the removal of endogenous NO with its scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxyl-3-oxide (cPTIO; 100 µM), reflecting the requirement of NO functioning in the regulation of plant physiology achieved by NH3·BH3-prepared HRW. The application of 1 mM tungstate, an inhibitor of nitrate reductase (NR; an important NO synthetic enzyme), showed the similar blocking responses in the phenotype, suggesting that NR might be the major source of NO involved in above H2 actions. Together, these results revealed that HRW prepared by NH3·BH3 could enhance rapeseed seedlings tolerance against abiotic stress, thus opening a new window for the application of H2 in agricultural production.

13.
BMC Infect Dis ; 21(1): 750, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348692

RESUMO

BACKGROUND: An upper abdominal mass without tenderness often indicates a benign or malignant tumor once liver or spleen hyperplasia has been excluded. A lymphadenopathic mass from Talaromyces marneffei infection is rare. CASE PRESENTATION: We report the case of a 29-year-old human immunodeficiency virus (HIV) infected man who presented with an upper abdominal mass and without any symptoms related with infection. Histopathology and next-generation sequencing (NGS) following biopsy of the mass confirmed T. marneffei-infected lymphadenopathy, and the patient was successfully treated with amphotericin B and itraconazole. CONCLUSIONS: This case report suggests that potential fungal infection should be considered during the diagnostic workup of a mass in clinical practice.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34417144

RESUMO

INTRODUCTION: MEK inhibition may overcome resistance to EGFR inhibition in patients with RAS wildtype (wt) metastatic colorectal cancer (mCRC). We evaluated antitumor activity of trametinib (MEK1/2 inhibitor) with panitumumab (EGFR monoclonal antibody) in a phase II trial. METHODS: Patients with KRAS, NRAS, and BRAF wt mCRC with prior 5-FU, irinotecan, oxaliplatin, +/- bevacizumab and no prior anti-EGFR therapy were treated with trametinib 1.5 mg oral daily and panitumumab 4.8 mg/kg IV every 2 weeks. Primary endpoint was clinical benefit rate (CB; CR, PR, or SD ≥24 weeks) by RECIST v1.1. A 2-stage minimax design was used. Serial plasma circulating free DNA (cfDNA) was collected and profiled using Oncomine Lung cfDNA assay. RESULTS: Fourteen patients were enrolled from November 2015 to April 2019. CB rate was 38% (5/13) and median progression free survival (PFS) was 4.4 months (95% CI, 2.9-7.1). Confirmed overall response rate was 38% (5/13). Treatment-related AE (trAE) included acneiform rash (85%), diarrhea (62%), maculopapular rash (54%), mucositis (46%), and others. Dose modifications and interruptions of trametinib occurred in 69% and panitumumab in 54% of patients. The trial did not progress to stage II accrual due to tolerability and short duration of response. RAS or BRAF mutations cfDNA were detected in 3/13 patients (23%) before radiographic disease progression. CONCLUSION: The addition of trametinib to panitumumab led to a high rate of tumor shrinkage in RAS/RAF wt metastatic colorectal cancer, with poor tolerability due to a high incidence of skin toxicity. Median PFS was similar to panitumumab alone in historical control data.

15.
Nat Commun ; 12(1): 4765, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362925

RESUMO

Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an 'omics-based' framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as 'current threats' (Rank I; 3%) - already present among pathogens - and 'future threats' (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 'current threat' ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II ('future threats'). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Bactérias/efeitos dos fármacos , Bactérias/genética , Bases de Dados Factuais , Microbioma Gastrointestinal/efeitos dos fármacos , Genes Bacterianos/efeitos dos fármacos , Genoma , Humanos , Metagenoma , Plasmídeos
16.
J Proteome Res ; 20(9): 4452-4461, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34351778

RESUMO

Recent advances in sample preparation enable label-free mass spectrometry (MS)-based proteome profiling of small numbers of mammalian cells. However, specific devices are often required to downscale sample processing volume from the standard 50-200 µL to sub-µL for effective nanoproteomics, which greatly impedes the implementation of current nanoproteomics methods by the proteomics research community. Herein, we report a facile one-pot nanoproteomics method termed SOPs-MS (surfactant-assisted one-pot sample processing at the standard volume coupled with MS) for convenient robust proteome profiling of 50-1000 mammalian cells. Building upon our recent development of SOPs-MS for label-free single-cell proteomics at a low µL volume, we have systematically evaluated its processing volume at 10-200 µL using 100 human cells. The processing volume of 50 µL that is in the range of volume for standard proteomics sample preparation has been selected for easy sample handling with a benchtop micropipette. SOPs-MS allows for reliable label-free quantification of ∼1200-2700 protein groups from 50 to 1000 MCF10A cells. When applied to small subpopulations of mouse colon crypt cells, SOPs-MS has revealed protein signatures between distinct subpopulation cells with identification of ∼1500-2500 protein groups for each subpopulation. SOPs-MS may pave the way for routine deep proteome profiling of small numbers of cells and low-input samples.

17.
Med Sci Monit ; 27: e932545, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34400603

RESUMO

BACKGROUND The type of traumatic temporomandibular joint (TMJ) ankylosis depends on the degree of severity of TMJ trauma. Here, we performed comprehensive differential molecular profiling between TMJ fibrous and bony ankylosis. MATERIAL AND METHODS Six sheep were used and a bilateral different degree of TMJ trauma was performed to induce fibrous ankylosis in one side and bony ankylosis in the other side. The ankylosed calluses were harvested at days 14 and 28 postoperatively and analyzed by Affymetrix OviGene-1_0-ST microarrays. DAVID was used to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Ten DEGs, including 7 hub genes from PPI analysis, were confirmed by real-time PCR. RESULTS We found 90 and 323 DEGs at least 2-fold at days 14 and 28, respectively. At day 14, bony ankylosis showed upregulated DEGs, such as TLR8, SYK, NFKBIA, PTPRC, CD86, ITGAM, and ITGAL, indicating a stronger immune and inflammatory response and cell adhesion, while genes associated with anti-adhesion (PRG4) and inhibition of osteoblast differentiation (SFRP1) had higher expression in fibrous ankylosis. At day 28, bony ankylosis showed increased biological process related to new bone formation, while fibrous ankylosis was characterized by a prolonged immune and inflammatory reaction. CONCLUSIONS This study provides a differential gene expression profile between TMJ fibrous and bony ankylosis. Further study of these key genes may provide new ideas for future treatment of TMJ bony ankylosis.

18.
Nat Commun ; 12(1): 5113, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433821

RESUMO

SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Δ382 virus genomes fold differently. Proximity ligation sequencing identify hundreds of RNA-RNA interactions within the virus genome and between the virus and host RNAs. SARS-CoV-2 genome binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2'-O-methylated. 2'-O-methylation sites are enriched in viral untranslated regions, associated with increased virus pair-wise interactions, and are decreased in host mRNAs upon virus infection, suggesting that the virus sequesters methylation machinery from host RNAs towards its genome. These studies deepen our understanding of the molecular and cellular basis of SARS-CoV-2 pathogenicity and provide a platform for targeted therapy.


Assuntos
COVID-19/virologia , Interações entre Hospedeiro e Microrganismos , RNA Viral/metabolismo , RNA/metabolismo , SARS-CoV-2/fisiologia , COVID-19/genética , COVID-19/metabolismo , COVID-19/fisiopatologia , Metilação de DNA , Genoma Viral , Humanos , Conformação de Ácido Nucleico , RNA/química , RNA/genética , RNA Viral/química , RNA Viral/genética , SARS-CoV-2/química , SARS-CoV-2/genética
19.
Thorac Cancer ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34423906

RESUMO

BACKGROUND: The aim of the study was to define the clinical significance of circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer (SCLC) patients. METHODS: CTCs/CTECs and their subtypes were determined using SE-iFISH technology in 33 SCLC patients before initial treatment (B1), after two cycles of chemotherapy (B2), at the completion of chemotherapy (B3), and disease progression (B4). The correlations with clinical characteristics, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: CTCs and CTECs were detected in 96.6% and 65.5% of patients, respectively. Patients had higher levels of CTCs compared with CTECs in circulation (p < 0.05). Extensive-stage SCLC patients tended to have higher CTEC counts (p = 0.035), and the detection of CTC-white blood cell (CTC-WBC) clusters was associated with a worse response to treatment (p = 0.030). Patients with CTC-WBC clusters at B1 (17.3 vs. 22.6 months, p = 0.041) and B2 (19.9 vs. 25.2 months, p = 0.018) had significantly shorter OS than those with no detection. Additionally, their presence was revealed as independent predictors for a worse OS in multivariable analyses (B1: HR 9.3, 95% CI: 1.4-48, p = 0.0079; B2: HR 4.4, 95% CI: 1.1-18, p = 0.041). A high CTC level at B4 was an adverse prognostic factor for SCLC patients (PFS: 8.7 vs. 22.5 months, p = 0.0026; OS: 19 months vs. not reached, p = 0.0086). CTC clusters and CTECs also showed prognostic values. CONCLUSIONS: The presence of CTC-WBC clusters at baseline and after two-cycle chemotherapy and the total CTC counts at the completion of chemotherapy are strong predictors for the prognostic survival of SCLC patients receiving first-line treatment.

20.
Proc Natl Acad Sci U S A ; 118(34)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34417312

RESUMO

Interactions of electronic and vibrational degrees of freedom are essential for understanding excited-states relaxation pathways of molecular systems at interfaces and surfaces. Here, we present the development of interface-specific two-dimensional electronic-vibrational sum frequency generation (2D-EVSFG) spectroscopy for electronic-vibrational couplings for excited states at interfaces and surfaces. We demonstrate this 2D-EVSFG technique by investigating photoexcited interface-active (E)-4-((4-(dihexylamino) phenyl)diazinyl)-1-methylpyridin-1- lum (AP3) molecules at the air-water interface as an example. Our 2D-EVSFG experiments show strong vibronic couplings of interfacial AP3 molecules upon photoexcitation and subsequent relaxation of a locally excited (LE) state. Time-dependent 2D-EVSFG experiments indicate that the relaxation of the LE state, S 2, is strongly coupled with two high-frequency modes of 1,529.1 and 1,568.1 cm-1 Quantum chemistry calculations further verify that the strong vibronic couplings of the two vibrations promote the transition from the S 2 state to the lower excited state S 1 We believe that this development of 2D-EVSFG opens up an avenue of understanding excited-state dynamics related to interfaces and surfaces.

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