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1.
J Chem Phys ; 154(23): 234301, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34241252

RESUMO

Extreme ultraviolet (XUV) transient absorption spectroscopy has emerged as a sensitive tool for mapping the real-time structural and electronic evolution of molecules. Here, attosecond XUV transient absorption is used to track dynamics in the A-band of methyl iodide (CH3I). Gaseous CH3I molecules are excited to the A-band by a UV pump (277 nm, ∼20 fs) and probed by attosecond XUV pulses targeting iodine I(4d) core-to-valence transitions. Owing to the excellent temporal resolution of the technique, passage through a conical intersection is mapped through spectral signatures of nonadiabatic wave packet bifurcation observed to occur at 15 ± 4 fs following UV photoexcitation. The observed XUV signatures and time dynamics are in agreement with previous simulations [H. Wang, M. Odelius, and D. Prendergast, J. Chem. Phys. 151, 124106 (2019)]. Due to the short duration of the UV pump pulse, coherent vibrational motion in the CH3I ground state along the C-I stretch mode (538 ± 7 cm-1) launched by resonant impulsive stimulated Raman scattering and dynamics in multiphoton excited states of CH3I are also detected.

2.
ACS Chem Neurosci ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264648

RESUMO

Neuropathic pain is a chronic condition with little specific treatment. Insulin-like growth factor 1 (IGF1), interacting with its receptor, IGF1R, serves a vital role in neuronal and brain functions such as autophagy and neuroinflammation. Yet, the function of spinal IGF1/IGF1R in neuropathic pain is unclear. Here, we examined whether and how spinal IGF1 signaling affects pain-like behaviors in mice with chronic constriction injury (CCI) of the sciatic nerve. To corroborate the role of IGF1, we injected intrathecally IGF1R inhibitor (nvp-aew541) or anti-IGF1 neutralizing antibodies. We found that IGF1 (derived from astrocytes) in the lumbar cord increased along with the neuropathic pain induced by CCI. IGF1R was predominantly expressed on neurons. IGF1R antagonism or IGF1 neutralization attenuated pain behaviors induced by CCI, relieved mTOR-related suppression of autophagy, and mitigated neuroinflammation in the spinal cord. These findings reveal that the abnormal IGF1/IGF1R signaling contributes to neuropathic pain by exacerbating autophagy dysfunction and neuroinflammation.

3.
Antimicrob Agents Chemother ; : AAC0050621, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252307

RESUMO

Amikacin and kanamycin are second line injectables used in the treatment of multidrug resistant tuberculosis (MDR-TB), based on the clinical utility of streptomycin, another aminoglycoside and first line anti-TB drug. While streptomycin was tested as a single agent in the first controlled TB clinical trial, introduction of amikacin and kanamycin into MDR-TB regimens was not preceded by randomized controlled trials. A recent large retrospective meta-analysis revealed that compared with regimens without any injectable drug, amikacin provided modest benefits, and kanamycin was associated with worse outcomes. Although their long-term use can cause irreversible ototoxicity, they remain part of MDR-TB regimens because they have a role in preventing emergence of resistance to other drugs. To quantify the contribution of amikacin and kanamycin to second-line regimens, we applied 2-dimensional MALDI mass spectrometry imaging in large lung lesions, quantified drug exposure in lung and lesions of rabbits with active TB, and measured the concentrations required to kill or inhibit growth of the resident bacterial populations. Using these metrics, we applied site-of-action pharmacokinetic and pharmacodynamic (PK-PD) concepts and simulated drug coverage in patients' lung lesions. The results provide a pharmacological explanation for the limited clinical utility of both agents and reveal better PK-PD lesion coverage for amikacin than kanamycin, consistent with retrospective data of contribution to treatment success. Together with recent mechanistic studies dissecting antibacterial activity from aminoglycoside ototoxicity, the limited but rapid penetration of streptomycin, amikacin and kanamycin to the sites of TB disease supports the development of analogs with improved efficacy and tolerability.

4.
BMC Musculoskelet Disord ; 22(1): 612, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243728

RESUMO

BACKGROUND: There is mixed evidence for the impact of cigarette smoking on outcomes following anterior cervical surgery. It has been reported to have a negative impact on healing after multilevel anterior cervical discectomy and fusion, however, segmental mobility has been suggested to be superior in smokers who underwent one- or two-level cervical disc replacement. Hybrid surgery, including anterior cervical discectomy and fusion and cervical disc replacement, has emerged as an alternative procedure for multilevel cervical degenerative disc disease. This study aimed to examine the impact of smoking on intermediate-term outcomes following hybrid surgery. METHODS: Radiographical and clinical outcomes of 153 patients who had undergone continuous two- or three-level hybrid surgery were followed-up to a minimum of 2-years post-operatively. The early fusion effect, 1-year fusion rate, the incidence of bone loss and heterotopic ossification, as well as the clinical outcomes were compared across three smoking status groups: (1) current smokers; (2) former smokers; (3) nonsmokers. RESULTS: Clinical outcomes were comparable among the three groups. However, the current smoking group had a poorer early fusion effect and 1-year fusion rate (P < 0.001 and P < 0.035 respectively). Both gender and smoking status were considered as key factors for 1-year fusion rate. Upon multivariable analysis, male gender (OR = 6.664, 95% CI: 1.248-35.581, P = 0.026) and current smoking status (OR = 0.009, 95% CI: 0.020-0.411, P = 0.002) were significantly associated with 1-year fusion rate. A subgroup analysis demonstrated statistically significant differences in both early fusion process (P < 0.001) and the 1-year fusion rate (P = 0.006) across the three smoking status groups in female patients. Finally, non-smoking status appeared to be protective against bone loss (OR = 0.427, 95% CI: 0.192-0.947, P = 0.036), with these patients likely to have at least one grade lower bone loss than current smokers. CONCLUSIONS: Smoking is associated with poor outcomes following hybrid surgery for multilevel cervical disc disease. Current smokers had the poorest fusion rate and most bone loss, but no statistically significant differences were seen in clinical outcomes across the three groups.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Estudos de Coortes , Discotomia/efeitos adversos , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/cirurgia , Masculino , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-34270374

RESUMO

An exaggerated exercise pressor reflex (EPR) causes excessive sympatho-excitation and exercise intolerance during physical activity in the chronic heart failure (CHF) state. Muscle afferent sensitization contributes to the genesis of the exaggerated EPR in CHF. However, the cellular mechanisms underlying muscle afferent sensitization in CHF remain unclear. Considering that voltage-gated potassium (Kv) channels critically regulate afferent neuronal excitability, we examined the potential role of Kv channels in mediating the sensitized EPR in male CHF rats. Real time RT-PCR and western blotting experiments demonstrate that both mRNA and protein expressions of multiple Kv channel isoforms (Kv1.4, Kv3.4, Kv4.2 and Kv4.3) were downregulated in lumbar DRGs of CHF rats compared to sham rats. Immunofluorescence data demonstrates significant decreased Kv channel staining in both NF200-positive and IB4-positive lumbar DRG neurons in CHF rats compared to sham rats. Data from patch clamp experiments demonstrate that the total Kv current, especially IA, was dramatically decreased in medium-sized IB4-negative muscle afferent neurons (a subpopulation containing mostly Aδ neurons) from CHF rats compared to sham rats, indicating a potential functional loss of Kv channels in muscle afferent Aδ neurons. In in vivo experiments, adenoviral overexpression of Kv4.3 in lumbar DRGs for one week attenuated the exaggerated EPR induced by muscle static contraction and the mechanoreflex by passive stretch without affecting the blunted cardiovascular response to hindlimb arterial injection of capsaicin in CHF rats. These data suggest that Kv channel dysfunction in DRGs play a critical role in mediating the exaggerated EPR and muscle afferent sensitization in CHF.

6.
Immunotherapy ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231370

RESUMO

Brain metastases (BM) is common in non-small-cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors (ICIs) have gradually become a routine treatment for NSCLC BM patients. Currently, three PD-1 inhibitors (pembrolizumab, nivolumab and cemiplimab), one PD-L1 inhibitor (atezolizumab) and one CTLA-4 inhibitor (ipilimumab) have been approved for the first-line treatment of metastatic NSCLC. It is still controversial whether PD-L1, tumor infiltrating lymphocytes, and tumor mutation burden can be used as predictive biomarkers for immune checkpoint inhibitors in NSCLC patients with BM. In addition, clinical data on NSCLC BM were inadequate. Here, we review the theoretical basis and clinical data for the application of ICIs in the therapy of NSCLC BM.

7.
Int J Biol Macromol ; 185: 792-803, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34229015

RESUMO

Chitosan/montmorillonite (CTS/MMT) and chitosan­gold nanoparticles/montmorillonite (CTS-Au/MMT) composites were prepared, characterized through Fourier transformed infrared (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM), and utilized as support for immobilization of polyphenol oxidase (PPO). PPO was immobilized on CTS/MMT (IPPO) and CTS-Au/MMT (IPPO-Au) by physical adsorption, respectively. In order to achieve simultaneous maximization of immobilization efficiency and enzyme activity, the immobilization process parameters were optimized by Taguchi-Grey relational analysis (TGRA) approach. Under the optimal immobilization condition, the immobilization efficiency and enzyme activity reached at 50.16% and 1.46 × 104 U/mg for IPPO, and 63.35% and 3.01 × 104 U/mg for IPPO-Au, respectively. The isotherm, kinetic and thermodynamics of PPO adsorption were investigated in detail. The adsorption process was better explained by Toth isotherm and Fractal-like pseudo second order model, respectively. Intra-particle diffusion and film diffusion were involved in the adsorption process and intra-particle diffusion was not the only rate-controlling step. The adsorption of PPO was exothermic, physical and spontaneous at the investigated temperature range. The immobilized PPO were used to oxidize phenolic compounds. All investigated phenolic compounds showed the higher conversion as catalyzed by IPPO-Au. For both IPPO and IPPO-Au, the conversion of substituted phenols was higher than that of phenol.

8.
Ann Palliat Med ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34263624

RESUMO

BACKGROUND: This study aimed to build a radiomics model with deep learning (DL) and human auditing and examine its diagnostic value in differentiating between coronavirus disease 2019 (COVID-19) and community-acquired pneumonia (CAP). METHODS: Forty-three COVID-19 patients, whose diagnoses had been confirmed with reverse-transcriptase polymerase-chain-reaction (RT-PCR) tests, and 60 CAP patients, whose diagnoses had been confirmed with sputum cultures, were enrolled in this retrospective study. The candidate regions of interest (ROIs) on the computed tomography (CT) images of the 103 patients were determined using a DL-based segmentation model powered by transfer learning. These ROIs were manually audited and corrected by 3 radiologists (with an average of 12 years of experience; range 6-17 years) to check the segmentation acceptance for the radiomics analysis. ROI-derived radiomics features were subsequently extracted to build the classification model and processed using 4 different algorithms (L1 regularization, Lasso, Ridge, and Z test) and 4 classifiers, including the logistic regression (LR), multi-layer perceptron (MLP), support vector machine (SVM), and extreme Gradient Boosting (XGboost). A receiver operating characteristic curve (ROC) analysis was conducted to evaluate the performance of the model. RESULTS: Quantitative CT measurements derived from human-audited segmentation results showed that COVID-19 patients had significantly decreased numbers of infected lobes compared to patients in the CAP group {median [interquartile range (IQR)]: 4 (3, 4) and 4 (4, 5); P=0.031}. The infected percentage (%) of the whole lung was significantly more elevated in the CAP group [6.40 (2.77, 11.11)] than the COVID-19 group [1.83 (0.65, 4.42); P<0.001], and the same trend applied to each lobe, except for the superior lobe of the right lung [1.81 (0.09, 5.28) for COVID-19 vs. 1.32 (0.14, 7.02) for CAP; P=0.649]. Additionally, the highest proportion of infected lesions were observed in the CT value range of (-470, -370) Hounsfield units (HU) in the COVID-19 group. Conversely, the CAP group had a value range of (30, 60) HU. Radiomic model using corrected ROIs exhibited the highest area under ROC (AUC) of 0.990 [95% confidence interval (CI): 0.962 -1.000] using Lasso for feature selection and MLP for classification. CONCLUSIONS: The proposed radiomics model based on human-audited segmentation made accurate differential diagnoses of COVID-19 and CAP. The quantification of CT measurements derived from DL could potentially be used as effective biomarkers in current clinical practice.

9.
Antimicrob Agents Chemother ; : AAC0002421, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34228540

RESUMO

SQ109 is a novel well-tolerated drug candidate in clinical development for the treatment of drug resistant tuberculosis (TB). It is the only inhibitor of the MmpL3 mycolic acid transporter in clinical development. No SQ109 resistant mutant has been directly isolated thus far, in vitro, in mice or in patients, tentatively attributed to its multiple targets. It is considered as a potential replacement for poorly tolerated components of multidrug-resistant TB regimens. To prioritize SQ109-containing combinations with best potential for cure and treatment shortening, one must understand its contribution against different bacterial populations in pulmonary lesions. Here we have characterized the pharmacokinetics of SQ109 in the rabbit model of active TB and its penetration at the sites of disease: lung tissue, cellular and necrotic lesions, and caseum. A two-compartment model with first-order absorption and elimination described the plasma pharmacokinetics. At the human-equivalent dose, parameter estimates fell within the ranges published for preclinical species. Tissue concentrations were modelled using an "effect" compartment, showing high accumulation in lung and cellular lesion areas with penetration coefficients in excess of 1,000, and lower passive diffusion in caseum after 7 daily doses. These results, together with the hydrophobic nature and high non-specific caseum binding of SQ109, suggest that multi-week dosing would be required to reach steady state in caseum and poorly vascularized compartments, similar to bedaquiline. Linking lesion pharmacokinetics to SQ109 potency in assays against replicating, non-replicating, and intracellular M. tuberculosis showed SQ109 concentrations markedly above pharmacokinetic-pharmacodynamic targets in lung and cellular lesions throughout the dosing interval. IMPORTANCE Drug-resistant tuberculosis (TB) accounts for over 20% of all fatalities due to drug-resistant pathogens. With recently approved drugs and a promising drug candidate pipeline, the challenge faced by clinical developers is prioritization of drug combinations with the best potential to improve cure rates and shorten treatment duration. To this end, one must understand the contribution of each partner drug against different bacterial populations in pulmonary TB lesions. SQ109 is a safe drug candidate in clinical development for the treatment of multidrug resistant TB. It is active against replicating and non-replicating Mycobacterium tuberculosis persisters in vitro, in mouse models and in patients. SQ109 exhibits extremely low frequency of resistance, unprecedented among all TB drugs so far. Here we characterize the pharmacokinetics and activity of SQ109 at the site of TB disease to inform the selection of drug regimens that account for its lesion-centric pharmacokinetic-pharmacodynamic parameters and best leverage its contribution to efficient disease cure.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34208238

RESUMO

The aim of this study was to evaluate the associations of rotating night shift work with body fat percentage (BF%) and fat mass index (FMI). A cross-sectional study was conducted among 435 female steelworkers, aged 26-57 years in Tangshan, China. BF% was assessed via bioelectrical impedance analysis and FMI was calculated. Different exposure metrics of night shift work were used to examine the effects of night shift work on BF% and FMI. The duration (years), cumulative number (nights), and cumulative length of night shifts (hours) were positively correlated with FMI and BF%, and these relationships were independent of body mass index (BMI). Compared with day workers, night shift workers with an average frequency of night shifts >7 nights/month (odds ratio (OR) 2.50, 95% confidence interval (CI) 1.17 to 5.35) and percentage of hours on night shifts >30% (OR 2.55, 95% CI 1.21 to 5.39) had elevated odds of obesity (BF% ≥ 35.0%). Nonobese night shift workers by the BMI criterion should also be alert to the risk of the excess accumulation of body fat, which is actually responsible for most obesity-associated adverse health consequences. Health interventions for related populations need to be improved, which is currently more focused on overall weight control.

11.
Hum Mutat ; 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245634

RESUMO

HLA-I LOH may facilitate immune evasion. However, large population studies on the prevalence of HLA-I LOH across different cancer types and in relation to mutational profiles are lacking, in particular, in the Chinese population. In this study, analysis was performed in 1504 advanced pan-cancer patients and 134 early-stage non-small-cell lung cancer patients using a 1021-gene panel. The consistency between the 1021-gene panel and whole-exome sequencing was evaluated in 45 samples, where concordant results were obtained in 95.6% (43/45) of the samples. Analytical results revealed that the prevalence of HLA-I LOH in tumor tissue presents considerable differences across cancer types. HLA-I LOH was relevant to genomic instability, reflected in higher tumor mutation burden level. HLA-I LOH occurs more frequently in MSS samples than in MSI-H samples. The alteration frequencies of p53 pathway, RTK/RAS pathway, Notch pathway, Hippo pathway, and Nrf2 pathway in HLA-I LOH group were significantly higher than that in HLA-I stable group (p < .0001, p < .0001, p = .032, p = .013, p = .003, respectively). In DNA damage response pathways, alterations in the checkpoint factor pathway and Fanconi anemia pathway are enriched in HLA-I LOH group (p < .0001, p = .023, respectively). Besides, HLA-I LOH was accompanied by higher mutation rates of several tumor suppressors, including TP53 and LRP1B. These results may shed light on follow-up tumor immunology research.

12.
Adv Colloid Interface Sci ; 294: 102486, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34274724

RESUMO

To develop efficient catalysts is one of the major ways to solve the energy and environmental problems. Spinel ferrites, with the general chemical formula of MFe2O4 (where M = Mg2+, Co2+, Ni2+, Zn2+, Fe2+, Mn2+, etc.), have attracted considerable attention in catalytic research. The flexible position and valence variability of metal cations endow spinel ferrites with diverse physicochemical properties, such as abundant surface active sites, high catalytic activity and easy to be modified. Meanwhile, their unique advantages in regenerating and recycling on account of the magnetic performances facilitate their practical application potential. Herein, the conventional as well as green chemistry synthesis of spinel ferrites is reviewed. Most importantly, the critical pathways to improve the catalytic performance are discussed in detail, mainly covering selective doping, site substitution, structure reversal, defect introduction and coupled composites. Furthermore, the catalytic applications of spinel ferrites and their derivative composites are exclusively reviewed, including Fenton-type catalysis, photocatalysis, electrocatalysis and photoelectro-chemical catalysis. In addition, some vital remarks, including toxicity, recovery and reuse, are also covered. Future applications of spinel ferrites are envisioned focusing on environmental and energy issues, which will be pushed by the development of precise synthesis, skilled modification and advanced characterization along with emerging theoretical calculation.

13.
Cancer Sci ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251713

RESUMO

Programmed cell death ligand 1 (PD-L1) is a major immunosuppressive checkpoint protein expressed by tumor cells in order to subvert anticancer immunity. Recent studies have shown that ionizing radiation (IR) upregulates the expression of PD-L1 in tumor cells. However, whether an IR-induced DNA damage response (DDR) directly regulates PD-L1 expression and the functional significance of its upregulation are not fully understood. Herein, we show that IR-induced upregulation of PD-L1 expression proceeds through both transcriptional and post-translational mechanisms. The upregulated PD-L1 was predominantly present on the cell membrane, resulting in T-cell apoptosis in a co-culture system. Using mass spectrometry, we identified PD-L1 interacting proteins and found that BCLAF1 (Bcl2 associated transcription factor 1) is an important regulator of PD-L1 in response to IR. BCLAF1 depletion decreased PD-L1 expression by promoting the ubiquitination of PD-L1. In addition, we show that CMTM6 is upregulated in response to IR and participates in BCLAF1-dependent PD-L1 upregulation. Finally, we demonstrated that the ATM/BCLAF1/PD-L1 axis regulated PD-L1 stabilization in response to IR. Together, our findings reveal a novel regulatory mechanism of PD-L1 expression in the DDR.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34200518

RESUMO

Large-scale vegetation restoration greatly changed the soil erosion environment in the Loess Plateau since the implementation of the "Grain for Green Project" (GGP) in 1999. Evaluating the effects of vegetation restoration on soil erosion is significant to local soil and water conservation and vegetation construction. Taking the Ansai Watershed as the case area, this study calculated the soil erosion modulus from 2000 to 2015 under the initial and current scenarios of vegetation restoration, using the Chinese Soil Loess Equation (CSLE), based on rainfall and soil data, remote sensing images and socio-economic data. The effect of vegetation restoration on soil erosion was evaluated by comparing the average annual soil erosion modulus under two scenarios among 16 years. The results showed: (1) vegetation restoration significantly changed the local land use, characterized by the conversion of farmland to grassland, arboreal land, and shrub land. From 2000 to 2015, the area of arboreal land, shrub land, and grassland increased from 19.46 km2, 19.43 km2, and 719.49 km2 to 99.26 km2, 75.97 km2, and 1084.24 km2; while the farmland area decreased from 547.90 km2 to 34.35 km2; (2) the average annual soil erosion modulus from 2000 to 2015 under the initial and current scenarios of vegetation restoration was 114.44 t/(hm²·a) and 78.42 t/(hm²·a), respectively, with an average annual reduction of 4.81 × 106 t of soil erosion amount thanks to the vegetation restoration; (3) the dominant soil erosion intensity changed from "severe and light erosion" to "moderate and light erosion", vegetation restoration greatly improved the soil erosion environment in the study area; (4) areas with increased erosion and decreased erosion were alternately distributed, accounting for 48% and 52% of the total land area, and mainly distributed in the northwest and southeast of the watershed, respectively. Irrational land use changes in local areas (such as the conversion of farmland and grassland into construction land, etc.) and the ineffective implementation of vegetation restoration are the main reasons leading to the existence of areas with increased erosion.

15.
Eur J Appl Physiol ; 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34148146

RESUMO

PURPOSE: To compare the effects of 12-week high-intensity interval training (HIIT) and vigorous-intensity continuous training (VICT) on cognitive function, physical fitness, VO2max, serum neurotransmitters and neurotrophic factors in overweight and obese elderly individuals. METHODS: Twenty-nine physically inactive older adults (18 males and 11 females) with a mean age of 64.8 ± 3.9 years were randomly divided into a control group (CON, n = 9), an HIIT group (4 × 3 min at 90% VO2max interspersed with 3 min at 60% VO2max, n = 10) and a VICT group (25 min at 70% VO2max, n = 10) and submitted to 12 weeks of training. Cognitive function questionnaires, physical fitness, VO2max, serum neurotransmitters and neurotrophic factors were determined at baseline and post training. RESULTS: Twelve weeks of HIIT and VICT improved the VO2max (4.19 ± 2.21 and 1.84 ± 1.63 mL/kg/min, respectively, p = 0.005), sit-and-reach distance (8.7 ± 3.0 and 7.8 ± 3.8 cm, p = 0.033), choice reaction time (- 0.115 ± 0.15 and - 0.09 ± 0.15 s, p = 0.004) and one-leg stand time (4.4 ± 3.4 and 4.2 ± 4.0 s, p < 0.001) of the elderly participants. The serum concentrations of brain-derived neurotrophic factor (375.5 ± 247.9 and 227.0 ± 137.1 pg/ml, p = 0.006), nerve growth factor (33.9 ± 16.7 and 23.3 ± 14.5 pg/ml, p = 0.037), neurotrophin-3 (24.2 ± 9.33 and 16.3 ± 5.91 pg/ml, p = 0.006) and neurotrophin-4 (10.4 ± 3.8 and 7.8 ± 5.0 pg/ml, p = 0.029) increased significantly in the HIIT and VICT groups after training. In addition, compared to VICT, HIIT significantly increased VO2max and the serum neurotrophin-3 concentration. Serum concentrations of the neurotransmitters acetylcholine, dopamine and serotonin trended upward with training. No significant change was observed in the cognitive function questionnaire scores (p > 0.05). CONCLUSION: HIIT is suitable for elderly adults and is more effective than VICT for improving VO2max and serum neurotrophin-3 concentrations. CHINESE CLINICAL TRIAL REGISTRY NUMBER: No. ChiCTR1900022315, date of registration: 4 April 2019.

16.
World J Gastroenterol ; 27(21): 2834-2849, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34135557

RESUMO

BACKGROUND: Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear. AIM: To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice. METHODS: Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry. RESULTS: Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1. CONCLUSION: FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Linfócitos T CD8-Positivos , Colite/induzido quimicamente , Colite/terapia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/terapia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Humanos , Camundongos
17.
Artigo em Inglês | MEDLINE | ID: mdl-34138532

RESUMO

Electrolyte additives have been extensively used as an economical approach to improve Li-ion battery (LIB) performances; however, their selection has been conducted on an Edisonian trial-and-error basis, with little knowledge about the relationship between their molecular structure and reactivity as well as the electrochemical performance. In this work, a series of phosphate additives with systematic structural variation were introduced with the purpose of revealing the significance of additive structure in building a robust interphase and electrochemical property in LIBs. By comparing the interphases formed by tripropyl phosphate (TPPC1), triallyl phosphate (TPPC2), and tripropargyl phosphate (TPPC3) containing alkane, alkene, and alkyne functionalities, respectively, theoretical calculations and comprehensive characterizations reveal that TPPC3 and TPPC2 exhibit more reactivity than TPPC1, and both can preferentially decompose both reductively and oxidatively, forming dense and protective interphases on both the cathode and anode, but they lead to different long-term cycling behaviors at 55 °C. We herein correlate the electrochemical performance of the high energy Li-ion cells to the molecular structure of these additives, and it is found that the effectiveness of TPPC1, TPPC2, and TPPC3 in preventing gas generation, suppressing interfacial resistance growth, and improving cycling stability can be described as TPPC3 > TPPC2 > TPPC1, i.e., the most unsaturated additive TPPC3 is the most effective additive among them. The established correlation between structure-reactivity and interphase-performance will doubtlessly construct the principle foundation for the rational design of new electrolyte components for future battery chemistry.

18.
Int J Biol Macromol ; 183: 2205-2214, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34087303

RESUMO

Phase inversion induced by water droplets has garnered attention in the field of polymer science as a novel method for preparing porous membranes. This study investigates the effect of the porous structure of poly (lactic acid) (PLA) membranes prepared through phase inversion induced by water droplets at four different temperatures (25, 50, 75, and 100 °C) on the morphology and proliferation of 3T3 cells. The surface properties of the PLA porous membrane, including pore size, pore size distribution, surface roughness, surface hydrophilicity, and cytocompatibility with 3T3 cells, were evaluated. The results indicated that the synthesized PLA membrane had two surfaces with different structures. The upper surface in contact with the water droplets during preparation contained uniformly distributed micropores, whereas the bottom surface was smooth and composed of small particles in contacted with the mold. The upper surface showed high cytocompatibility with 3T3 cells, and the 3T3 cells migrated and grew within the pores at 25 °C. In contrast, the bottom surface exhibited low biocompatibility with the 3T3 cells. Our study has wide-ranging implications and will improve the fabrication and implementation of 3D cultured scaffolds with excellent cytocompatibility.

19.
Anal Methods ; 13(26): 2908-2914, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34156044

RESUMO

Biothiols are widely involved in various important physiological activities and play a significant role in maintaining redox homeostasis in living organisms. Herein, we designed and synthesized three new asymmetric fluorescent probes (BDP-S-Ph, BDP-S-ENE and BDP-S-R) to discriminate Cys from Hcy/GSH. These probes reacted with Cys to form meso-amino-BODIPYs via SNAr substitution-rearrangement, thereby inducing a fluorescence turn-on effect. Moreover, they could selectively and sensitively detect Cys in solution with low detection limits (50 nM, 28 nM and 87 nM, respectively). Through comparing the response rates of the three probes to Cys, we concluded that the increase of conformational restrictions led to a decrease in probe reactivity. Besides, the sensing mechanism was demonstrated by mass spectrometry. Furthermore, cell experiments indicated that the probes were able to image exogenous and endogenous Cys through green or red channels in living cells.

20.
Sci Total Environ ; 788: 147792, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34134368

RESUMO

Zearalenone (ZEN) is a secondary metabolite, which is mainly produced by Fusarium fungi and exists in various feeds and agricultural products. Recently, an increasing amount of data has shown that ZEN, as an estrogen-like hormone, can have harmful effects on the female reproductive system, especially on oogenesis and folliculogenesis. Breast milk is considered to be the ideal form of nutrition for infants; however, there are some records of contaminants in food, such as mycotoxins, which may be transferred from maternal blood to milk. In this study, we investigated the toxic effects of breast milk on folliculogenesis in offspring following maternal ZEN exposure. Our results showed that maternal ZEN exposure significantly inhibited the process of primordial follicle (PF) assembly and reduced the number of PFs in suckled offspring's ovaries. In addition, RNA-seq analysis showed that RIG-I-like receptor (RLRs) signaling pathways were activated after exposed to ZEN, which increased the expression levels of DNA damage (γ-H2AX, RAD51, and PARP1) and apoptosis related protein (BAX/BCL2 and Caspase-3). Finally, ZEN exposure interfered with follicular development, as evidenced by the reduced percentages of oocyte maturation and embryonic development when the offspring grew to adolescence. It is worth noting that maternal ZEN exposure disrupted the tri-methylation levels of H3K4, H3K9, and H3K27 in the offspring's oocytes. Our results indicated that maternal ZEN exposure affected ovarian development in offspring through the breast milk, which may be detrimental to their reproductive capability in adult life.


Assuntos
Zearalenona , Feminino , Humanos , Exposição Materna , Folículo Ovariano , Ovário , Gravidez , Reprodução , Zearalenona/toxicidade
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