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1.
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.

2.
Nano Lett ; 21(18): 7796-7805, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34516141

RESUMO

Immunotherapy holds great promise for patients undergoing tumor treatment. However, the clinical effect of immunotherapy is limited because of tumor immunogenicity and its immunosuppressive microenvironment. Herein, the metal-organic framework (MIL-100) loaded with chemotherapeutic agent mitoxantrone (MTO) was combined with photothermal-chemotherapy for enhancing immunogenic cell death. MIL-100 loaded with MTO and hyaluronic acid as nanoparticles (MMH NPs) yielded an NP with two therapeutic properties (photothermal and chemotherapy) with dual imaging modes (photoacoustic and thermal). When MMH NPs were coinjected with an anti-OX40 antibody in colorectal cancer, the highest antitumor efficacy and a robust immune effect were achieved. This work provides a novel combined therapeutic strategy, which will hold great promise in future tumor therapy.

3.
Mod Pathol ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493823

RESUMO

V-domain Ig-containing suppressor of T-cell activation (VISTA) is a novel immune checkpoint protein and a potential immunotherapeutic target. However, its expression in endometrial cancer has not been clearly defined. This study aimed to investigate VISTA expression and determine its associations with clinicopathological features, molecular subtypes, programmed cell death-ligand 1 (PD-L1) expression, CD8+ T-cell count, and survival in a cohort of 839 patients with endometrial cancer. Using direct sequencing of the polymerase epsilon (POLE) exonuclease domain and immunohistochemistry for mismatch repair (MMR) proteins and p53, we stratified endometrial cancers into four molecular subtypes: POLE ultramutated, MMR-deficient, p53-mutant, and nonspecific molecular profile (NSMP). PD-L1, CD8, and VISTA were detected via immunohistochemistry. VISTA was expressed in the immune cells of 76.6% (643/839) of the samples and in the tumor cells of 6.8% (57/839). VISTA positivity in the immune cells was frequent in tumors staged I-III, those with positive PD-L1 or high CD8+ T-cell density, and those representing POLE ultramutated and MMR-deficient subtypes. Furthermore, VISTA positivity in tumor cells was more frequent in clear cell carcinoma samples. VISTA in immune cells was associated with improved survival in the entire cohort as well as in the endometrioid histology, stage I, PD-L1-negative, MMR-deficient, MMR-proficient, and high and low number of CD8+ T-cell-infiltrated tumor subgroups. VISTA in immune cells was a prognostic factor overall, as well as in patients with endometrioid histology, independent of molecular subtype or CD8+ T-cell density. The data produced by this study, which was the largest to focus on VISTA expression in patients with endometrial cancer to date, suggest that VISTA is a predictor of improved survival.

4.
Orphanet J Rare Dis ; 16(1): 385, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503559

RESUMO

BACKGROUND: Spinal muscular atrophy (SMA) is a rare neurogenetic disease which involves multisystem dysfunctions such as respiratory, digestive, and motor disorders. Anxiety, depression and other psychological disorders often accompany severe chronic physical diseases. The aim of this study was to investigate the prevalence of anxiety and depression along with their influencing factors among school-age patients with SMA. METHODS: We conducted a cross-sectional study on school-age SMA patients in China. Patients aged 8-18 years with a genetic diagnosis of 5qSMA were invited to answer a questionnaire composed of sociodemographic and clinical questions, then to complete the Screen for Child Anxiety-Related Emotional Disorders and Depression Self-Rating Scale for depression and anxiety level evaluation. At the end of the questionnaire, further questions assessed the subjective anxiety and subjective depression of patients' caregivers and their expectations for their child's future. RESULTS: Complete data were available for 155 patients. The sample included 45.8% boys and 54.2% girls; 65.2% were type II, 27.1% were type III, and the remainder were type I SMA. Rates of anxiety and depression in these school-age SMA patients were 40.0% and 25.2%, respectively. Gender, age, and disease type were not associated with anxiety or depression, but respiratory system dysfunction, digestive system dysfunction, skeletal deformity, rehabilitation exercise, academic delay, specialized support from school, household income level, caregivers' subjective anxiety, and caregivers' expectations were significantly related to both anxiety and depression. CONCLUSIONS: There was a high prevalence of anxiety and depression in school-age SMA patients in China. Professional psychological care maybe included in the standard of care. These results also call for possible targets for intervention such as reducing complications, improving drug accessibility, retaining normal schooling, strengthening school support, and enhancing the ability of the caregivers of SMA patients to assist in the diagnosis and treatment of the disease, so improving the mental health of SMA patients.

5.
Lancet Planet Health ; 5(9): e620-e632, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34508683

RESUMO

BACKGROUND: Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. METHODS: We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. FINDINGS: From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 µg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 µg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 µg/m3 for PM2·5 and 40 µg/m3 for NO2. INTERPRETATION: Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. FUNDING: Health Effects Institute.

6.
BMC Genomics ; 22(1): 641, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481466

RESUMO

BACKGROUND: Stroke can induce cardiac dysfunction in the absence of primary cardiac disease; however, the mechanisms underlying the interaction between the neurological deficits and the heart are poorly understood. The objective of this study was to investigate the effects of stroke on cardiac function and to identify the transcriptome characteristics of the heart. RESULTS: Stroke significantly decreased heart weight/tibia length ratio and cardiomyocyte cross-sectional areas and increased atrogin-1 and the E3 ubiquitin ligase MuRF-1, indicating myocardial atrophy in MCAO-induced mouse hearts. RNA sequencing of mRNA revealed 383 differentially expressed genes (DEGs) in MCAO myocardium, of which 221 were downregulated and 162 upregulated. Grouping of DEGs based on biological function and quantitative PCR validation indicated that suppressed immune response and collagen synthesis and altered activity of oxidoreductase, peptidase, and endopeptidase may be involved in MCAO-induced cardiomyopathy. The DEGs were mainly distributed in the membrane or extracellular region of cardiomyocytes and acted as potential mediators of stroke-induced cardiac dysregulation involved in cardiac atrophy. CONCLUSION: Stroke induced a unique transcriptome response in the myocardium and resulted in immediate cardiac atrophy and dysfunction.


Assuntos
Isquemia Encefálica , Cardiopatias , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/patologia , Cardiopatias/patologia , Camundongos , Atrofia Muscular , Miócitos Cardíacos , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Transcriptoma
7.
Artigo em Inglês | MEDLINE | ID: mdl-34543208

RESUMO

Brain stroke lesion segmentation is of great importance for stroke rehabilitation neuroimaging analysis. Due to the large variance of stroke lesion shapes and similarities of tissue intensity distribution, it remains a challenging task. To help detect abnormalities, the anatomical symmetries of brain magnetic resonance (MR) images have been widely used as visual cues for clinical practices. However, most methods do not fully utilize structural symmetry information in brain images segmentation. This paper presents a novel mirror difference aware network (MDAN) for stroke lesion segmentation in an encoder-decoder architecture, aiming at holistically exploiting the symmetries of image features. Specifically, a differential feature augmentation (DFA) module is developed in the encoding path to highlight the semantically pathological asymmetries of the features in abnormalities. In the DFA module, a Siamese contrastive supervised loss is designed to enhance discriminative features, and a mirror position-based difference augmentation (MDA) module is used to further magnify the discrepancy information. Moreover, mirror feature fusion (MFF) modules are applied to fuse and transfer the information both of the original input and the horizontally flipped features to the decoding path. Extensive experiments on the Anatomical Tracings of Lesions After Stroke (ATLAS) dataset show the proposed MDAN outperforms the state-of-the-art methods.

8.
Ann Palliat Med ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34498477

RESUMO

BACKGROUND: This study aimed to compare the tip location of peripherally inserted central catheter (PICC) under two forward P-wave amplitudes (P-wave amplitude is the autonomous peak or P-wave amplitude is 50-80% of the QRS main wave) by intracavitary electrocardiogram (IC-EKG) to determine the PICC tip in optimal location thus avoiding catheter-related complications. METHODS: The data of 300 cancer patients with PICC insertion were collected retrospectively. For the observation group, the position of the catheter tip was left at the level when P wave amplitude was its autonomous peak (168 patients catheterized in 2018). While for the control group, the catheter tip was left at the level when the P wave amplitude was 50-80% of the QRS main wave (132 patients catheterized in 2017). Both groups of patients underwent the chest X-ray examination (CXR) after catheterization. The total compliance rate [PICC tip was located in the lower third of the Superior Vena Cava (SVC) and the Cavo-Atrial Junction (CAJ)], the optimal position compliance rate (PICC tip was located in the CAJ), and the incidence of the catheter tip malposition were compared between the two groups. The complications after catheterization including arrhythmia after catheterization within 24 hours, catheter-related thrombosis, catheter dysfunction, and catheter infection within 90 days were also compared. RESULTS: There was no difference in the total compliance rate of PICC tip position and the incidence of the catheter malposition in the two groups (P>0.05). But the optimal position compliance rate of the observation group was higher than that of the control group (P<0.05). There was no difference in the incidence of arrhythmia after catheterization within 24 hours of the two groups (P>0.05). The incidence of catheterrelated thrombosis, catheter dysfunction, and catheter infection within 90 days in the observation group was lower than those in the control group (P<0.05). CONCLUSIONS: The PICC tip position at the autonomous peak of the P wave is significantly better than that at the P wave amplitude being 50-80% of the QRS main wave under the IC-EKG guidance for PICC insertion.

9.
Brain Imaging Behav ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499294

RESUMO

Sleep spindles have been implicated in sleep protection, depression and anxiety. However, spindle-related brain imaging mechanism underpinning the deficient sleep protection and emotional regulation in insomnia disorder (ID) remains elusive. The aim of the current study is to investigate the relationship between spindle-related brain activations and sleep quality, symptoms of depression and anxiety in patients with ID. Participants (n = 46, 28 females, 18-60 years) were recruited through advertisements including 16 with ID, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and 30 matched controls. Group differences in spindle-related brain activations were analyzed using multimodality data acquired with simultaneous electroencephalography and functional magnetic resonance imaging during sleep. Compared with controls, patients with ID showed significantly decreased bilateral spindle-related brain activations in the cingulate gyrus (familywise error corrected p ˂ 0.05, cluster size 4401 mm3). Activations in the cingulate gyrus were negatively correlated with Pittsburgh Sleep Quality Index scores (r = -0.404, p = 0.005) and Self-Rating Anxiety Scale scores (r = -0.364, p = 0.013), in the pooled sample. These findings underscore the key role of spindle-related brain activations in the cingulate gyrus in subjective sleep quality and emotional regulation in ID.

10.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3846-3852, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472258

RESUMO

The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-ß-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-ß-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-ß-D-glucopyranoside(trans-urticol-7-O-ß-D-glucopyranoside, 7), cycloolivil-4-O-ß-D-glucopyranoside(8), isolariciresinol-4'-O-ß-D-glucopyranoside(9), and olivil-4'-O-ß-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.


Assuntos
Colestenona 5 alfa-Redutase/farmacologia , Lignanas , Urticaceae , Inibidores de 5-alfa Redutase , Cromatografia Líquida de Alta Pressão , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Urticaceae/efeitos dos fármacos , Urticaceae/enzimologia
11.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4139-4144, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467725

RESUMO

The purpose of the research is to study the bioactive constituents of Callicarpa nudiflora. From the 65% ethanol extract of C. nudiflora leaves, ten compounds were isolated by macroporous adsorption resin, Sephadex LH-20, ODS, silica gel, and preparative HPLC. These compounds were identified as callicapene M6(1), sterebin A(2), isomartynoside(3), crenatoside(4), luteolin-7-O-neohesperidoside(5), apigenin-7-O-ß-D-neohesperidoside(6), isoacteoside(7), acteoside(8),(7R)-campneoside I(9), and(7S)-campneoside I(10) on the basis of NMR, HR-ESI-MS, and optical rotation data. Compound 1 was obtained as a new compound. Compounds 2 and 4 were isolated from the genus Callicarpa for the first time. Compounds 9 and 10 were isolated from C. nudiflora for the first time.


Assuntos
Callicarpa , Diterpenos , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Folhas de Planta
12.
Inorg Chem ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34474565

RESUMO

Discovering high-performance near-room-temperature thermoelectric materials is extremely imperative to widen the practical application in thermoelectric power generation and refrigeration. Here, ternary Ag2Se1-xTex (x = 0.1, 0.2, 0.3, 0.4, and 0.5) materials are prepared via the wet-mechanical alloying and spark plasma sintering process to investigate their near-room-temperature thermoelectric properties. From density functional theory calculation and single-parabolic-band modeling study, we found that the reduced contribution of Se 4p orbitals to the total density of states decreases the carrier effective mass with increasing Te content, which should enhance the theoretically maximum zT. These calculation results are also verified by the experimental results. Meanwhile, complex microstructures including dislocations, nanograins, high-density boundaries, TeSe substitution, lattice distortions, and localized strain have been observed in ternary Ag2Se1-xTex. These complex microstructures strengthen phonon scattering and in turn lead to ultralow lattice thermal conductivity in the range of 0.21-0.31 W m-1 K-1 in ternary Ag2Se1-xTex at 300 K. Although the increased deformation potential suppresses the carrier mobility, benefiting from the engineered band structures and ultralow lattice thermal conductivity, a high zT of >1 can be potentially obtained in the ternary Ag2Se1-xTex with appropriate carrier concentration. This study indicates that ternary Ag2Se1-xTex is a promising candidate for near-room-temperature thermoelectric applications.

13.
Environ Toxicol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477289

RESUMO

Inflammation has been known to be involved in the pathogenesis of mastitis. And anti-inflammatory agent is proposed to be a possible efficient therapeutic strategy for mastitis. Corynoline, a bioactive compound extracted from Corydalis bungeana Turcz., has been reported to have anti-inflammatory effect. However, whether corynoline has protective effect against mastitis remains unclear. The aim of this study was to evaluate the protective effect of corynoline on LPS-induced mastitis in mice. Inflammatory cytokine production was measured by ELISA. The proteins of signaling pathways were detected by western blot analysis. The results showed that treatment of corynoline at the doses of 15, 30, and 60 mg/kg significantly attenuated LPS-induced pathological damage of mammary tissues. Corynoline also ameliorated LPS-induced MPO activity, MDA content, and inflammatory cytokine TNF-α and IL-1ß production in mammary tissues. LPS-induced NF-κB activation was inhibited by corynoline. Furthermore, our results showed corynoline significantly increased the expression of Nrf2 and the phosphorylation levels of AKT and GSK3ß. In conclusion, our results indicated that corynoline protected against LPS-induced mastitis through regulating AKT/GSK3ß/Nrf2 signaling pathway, which subsequently led to the inhibition of NF-κB and inflammatory response.

14.
Anal Methods ; 13(35): 3947-3953, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528948

RESUMO

Exponential amplification reaction (EXPAR) has attracted much attention due to its simple primers and high amplification efficiency, but its applications are hindered by severe non-specificity amplification. Convenient exogenous chemical modification methods modified the entire template while inhibiting both non-specific and specific amplification. In this paper, we proposed a new self-passivating template with the phosphorothioate strategy to effectively improve the detection limit and applicability of EXPAR. We phosphorothioated several bases where the sequence was prone to form transient intermolecular 3'-end hybridization, thereby inhibiting the non-specific interactions and preventing the extension of templates by DNA polymerase. The melting temperature (Tm) curve and density functional theory (DFT) proved that the stability of hydrogen bonds between phosphorothioated bases did decrease. Benefitting from this strategy, the detection limit had been improved by 3 orders of magnitude. Moreover, due to the antioxidation property of phosphorothioate, this strategy showed good stability in serum, reflecting its excellent prospects in clinical sampling and detection.

15.
Chem Commun (Camb) ; 57(74): 9316-9329, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528952

RESUMO

Although transition metal carbenes have found widespread applications and difluorocarbene has served as a versatile intermediate, it is still quite challenging to make use of transition-metal difluorocarbenes in synthetic chemistry due to their unpredictable reactivities. In this Highlight, we review recent developments in the transition-metal-catalyzed or -mediated transfer of difluorocarbene and the reactivies and conversions of transition-metal difluorocarbene complexes. We start with the MCF2 bonding, then provide the progress in the transfer of difluorocarbene, and finally briefly discuss the conversions of MCF2 into other metal complexes. The understanding of the interesting reactivities of MCF2 may help design the catalytic transfer of difluorocarbene for various reactions.

16.
BMJ Open ; 11(9): e045454, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493502

RESUMO

OBJECTIVES: This phenomenological study aimed to examine intensive care unit (ICU) nurses' experiences of caring for patients with COVID-19, and understand better their everyday experiences of patient' management in the ICU. DESIGN: A descriptive phenomenological research design was used. Individual interviews were conducted. The data were transcribed verbatim and analysed using Colaizzi's seven-step framework. SETTING: An ICU with 16 beds in a tertiary hospital in Wuhan, China. PARTICIPANTS: Nurses who had more than 1 year of experience and had provided care to patients with COVID-19 in ICU for more than 1 week were identified as participants. A total of 13 nurses were interviewed. RESULTS: An analysis of these significant statements yielded four distinct stages of feelings, thereby revealing the essence of this phenomenon. Worry about being infected and infecting family members was present across in all four stages. The themes associated with the four stages were as follows: initial contradictory feelings, quick adaption to the 'new working environment' in the first 1-2 weeks in the ICU, desperation after adaption, holding on and survive. CONCLUSIONS: The nurses reported distinct experiences of providing care to patients with COVID-19 in ICUs. Interventions, such as providing information about the disease, simulation training, emotional support and follow-up care, are needed to help nurses manage patients with COVID-19 and maintain nurses' health.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem no Hospital , Humanos , Unidades de Terapia Intensiva , Pesquisa Qualitativa , SARS-CoV-2
17.
Food Chem ; 369: 130978, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34500209

RESUMO

In this paper, the effects of soybean protein isolate (SPI) on the formations of five heterocyclic aromatic amines (HAAs) in roasted pork were investigated. The levels of all five HAAs improved upon addition of 2.5% of SPI (P < 0.05). With higher SPI dosage, the levels of HAA decreased after seeing an increase. Two HAAs (MeIQx and 4,8-DiMeIQx) were inhibited by 10.0% of SPI, with the inhibitory efficiencies of 7.0 % and 85.7%, respectively. After being heated, the levels of both the free amino acids and carbonyl groups in the SPI were observed significantly increased, from 55.04 µg g·SPI-1 to 91.66 µg g·SPI-1 and from 123.85 ± 13.07 to 931.78 ± 32.56, respectively (P < 0.05). Therefore, the possible promotion mechanism of the SPI was speculated that the heated SPI would provide both the HAA precursors and carbonyls, which significantly promoted the Strecker degradation and generated more HAA intermediates (P < 0.05).

18.
Se Pu ; 39(10): 1055-1064, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34505427

RESUMO

“Seeing is believing” is the central philosophy of life science research, which runs through the continuous understanding of individual molecules, molecular complexes, molecular dynamic behavior, and the entire molecular network. Living and dynamic molecules are functional in nature; therefore, fluorescence microscopy has emerged as an irreplaceable tool in life science research. However, when fluorescence imaging is performed at the molecular level, some artificial signals may lead to erroneous experimental results. This obstacle is due to the limitation of the optical diffraction limit, and the fluorescence microscope cannot distinguish the target in the diffraction-limited space. Super-resolution fluorescence imaging technology breaks through the diffraction limit, allows visualization of biomolecules at the nanometer scale to the single-molecule level, and allows us to study the structure and dynamic processes of living cells with unprecedented spatial and temporal resolution. It has become a powerful tool for life science research and is gradually being applied to material science, catalytic reaction processes, and photolithography as well. The principle of super-resolution imaging technologies is different; therefore, it has different technical performances, thus limiting their specific technical characteristics and application scope. Current mainstream super-resolution imaging technologies can be classified into three types: structured illumination microscopy (SIM), stimulated emission depletion (STED), and single-molecule localization microscopy (SMLM). These microscopes use different complex technologies, but the strategy is the same and simple, i.e. two adjacent luminous points in a diffraction-limited space can be spatially resolved by time resolution. SIM has been used for three-dimensional real-time imaging in multicellular organisms; however, compared with other technologies, its lower horizontal and vertical resolutions need to be further optimized. STED is limited by its small imaging field of view and high photobleaching; however, the best time resolution can be considered at a high spatial resolution, and it has been proven that three-color STED imaging can be performed. In SMLM super-resolution imaging, the time resolution is affected by the time required to locate all fluorophores, which is closely related to the switching and luminescence properties of the fluorophore. With the improvement in horizontal and vertical resolution of imaging, the image acquisition speed, photobleaching characteristics, and the possibility of multi-color and dynamic imaging have increasingly become the key determinants of super-resolution fluorescence imaging. Thus far, the main use of super-resolution imaging technology has been focused on biological applications for studying structural changes less than 200 nm in dimension. In addition to the combination of structural and morphological characterization with biomolecular detection and identification, super-resolution imaging technology is rapidly expanding into the fields of interaction mapping, multi-target detection, and real-time imaging. In the latter applications, super-resolution imaging technology is particularly advantageous because of more flexible sample staining, higher labeling efficiency, faster and simpler readings, and gentler sample preparation procedures. In this article, we compare the principles of these three technologies and introduce their application progress in biology. We expect the results described herein will help researchers clarify the technical advantages and applicable application directions of different super-resolution imaging technologies, thus facilitating researchers in making reasonable choices in future research.


Assuntos
Imagem Óptica , Imagem Individual de Molécula , Corantes Fluorescentes , Microscopia de Fluorescência
19.
Biomed Chromatogr ; : e5242, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34519061

RESUMO

The following method describes a novel workflow that eliminates the need of authentic reference standards for the quantitation of drug metabolites in biological samples using a single multi-isotopically labeled compound bearing both radio and stable isotopes. The resulting radio and stable bifunctionalized isotopologue (RADSTIL) of parent drug is employed as a substrate for in vitro biotransformation to targeted RADSTILs of metabolites as calibrants. Inclusion of a radio label enables both radiometric and mass spectrometric detection. Addition of stable labels ensures subsequent isotopic interference-free quantitation of unlabeled metabolites in preclinical and clinical samples. This affords a more accurate quantitation workflow compared to current semi-quantitation method, which utilizes isotopic interfering radio isotopologues of metabolites alone as calibrants. The proof-of-concept is illustrated with (14 C,13 C2 )-acetaminophen where in vitro biotransformation produced (14 C,13 C2 )-sulfate and (14 C,13 C2 )-glucuronide calibrants. Absolute quantitation of the acetaminophen metabolites was then achieved by liquid chromatography coupled with radiometry and mass spectrometry (LC-RAD/MS). Quantitative data obtained by this method fell within 82-86% of the values from conventional LC-MS/MS method.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34519394

RESUMO

Although super-resolution imaging offers an opportunity to visualize cellular structures and organelles at the nanoscale level, cellular heterogeneity and unpredictability still pose a significant challenge in the dynamic imaging of live cells. It is thus vital to develop better performing and more photostable probes for long-term super-resolution imaging. Herein, we report a probe LD-FG for imaging lipid droplet (LD) dynamics using structured illumination microscopy (SIM). LD-FG allows wash-free imaging of LDs, owing to hydrogen-bond sensitive fluorogenicity. The replenishment of photobleached LD-FG by intact ones outside LDs further ensure the long-time stability of the fluorescence imaging. With this buffering fluorogenic probe, fast and unpredictable dynamic processes of LDs can be visualized. Two LD coalescence modes (as well as heterogeneity in different regions of the cells and even in between different cells) were discovered for the first time. Notably, the dynamic imaging also allowed us to propose a new model of LD maturation during adipocyte differentiation, i.e. , a fast LD coalescence followed by a slow ripening step. The excellent performance of LD-FG makes the buffer strategy an effective method for designing fluorescent probes for cell dynamic imaging.

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