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1.
Br J Ophthalmol ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027355

RESUMO

BACKGROUND: Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. METHODS: Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤-5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. RESULTS: Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. CONCLUSION: In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

2.
J Phys Chem Lett ; : 792-800, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35044179

RESUMO

Nonspecific binding of crowder proteins with functional proteins is likely prevalent in vivo, yet direct quantitative evidence, let alone residue-specific information, is scarce. Here we present nuclear magnetic resonance (NMR) characterization showing that bovine serum albumin weakly but preferentially interacts with the histidine carrier protein (HPr). Notably, the binding interface overlaps with that for HPr's specific partner protein, EIN, leading to competition. The crowder protein thus decreases the EIN-HPr binding affinity and accelerates the dissociation of the native complex. In contrast, Ficoll-70 stabilizes the native complex and slows its dissociation, as one would expect from excluded-volume and microviscosity effects. Our atomistic modeling of macromolecular crowding rationalizes the experimental data and provides quantitative insights into the energetics of protein-crowder interactions. The integrated NMR and modeling study yields benchmarks for the effects of crowded cellular environments on protein-protein specific interactions, with implications for evolution regarding how nonspecific binding can be minimized or exploited.

3.
Eur Radiol ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020012

RESUMO

OBJECTIVES: To examine the diagnostic accuracy of machine learning-based coronary CT angiography-derived fractional flow reserve (FFRCT) in diabetes mellitus (DM) patients. METHODS: In total, 484 patients with suspected or known coronary artery disease from 11 Chinese medical centers were retrospectively analyzed. All patients underwent CCTA, FFRCT, and invasive FFR. The patients were further grouped into mild (25~49 %), moderate (50~69 %), and severe (≥ 70 %) according to CCTA stenosis degree and Agatston score < 400 and Agatston score ≥ 400 groups according to coronary artery calcium severity. Propensity score matching (PSM) was used to match DM (n  = 112) and non-DM (n  = 214) groups. Sensitivity, specificity, accuracy, and area under the curve (AUC) with 95 % confidence interval (CI) were calculated and compared. RESULTS: Sensitivity, specificity, accuracy, and AUC of FFRCT were 0.79, 0.96, 0.87, and 0.91 in DM patients and 0.82, 0.93, 0.89, and 0.89 in non-DM patients without significant difference (all p > 0.05) on a per-patient level. The accuracies of FFRCT had no significant difference among different coronary stenosis subgroups and between two coronary calcium subgroups (all p > 0.05) in the DM and non-DM groups. After PSM grouping, the accuracies of FFRCT were 0.88 in the DM group and 0.87 in the non-DM group without a statistical difference (p > 0.05). CONCLUSIONS: DM has no negative impact on the diagnostic accuracy of machine learning-based FFRCT. KEY POINTS: • ML-based FFRCT has a high discriminative accuracy of hemodynamic ischemia, which is not affected by DM. • FFRCT was superior to the CCTA alone for the detection of ischemia relevance of coronary artery stenosis in both DM and non-DM patients. • Coronary calcification had no significant effect on the diagnostic accuracy of FFRCT to detect ischemia in DM patients.

4.
Med Oncol ; 39(3): 36, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35059870

RESUMO

SOX2 is related to drug resistance in many types of cancer, including lung cancer. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC). The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR, immunohistochemistry, and luciferase reporter assays were used to investigate the underlying mechanism. Kaplan-Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression and patient survival. A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP was higher than that in A549. Knockdown of SOX2 in A549/CDDP-induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by shAPE1 in A549/CDDP. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP treated with SOX2 siSOX2 alone or combined with CDDP compared with control cells. Meaningfully, patients with low expression of SOX2, and even including its regulating APE1, survived longer than those with high expression of SOX2, and APE1. siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.

5.
Neural Regen Res ; 17(6): 1310-1317, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782576

RESUMO

Acupuncture at acupoints Baihui (GV20) and Dazhui (GV14) has been shown to promote functional recovery after stroke. However, the contribution of the contralateral primary sensory cortex (S1) to recovery remains unclear. In this study, unilateral local ischemic infarction of the primary motor cortex (M1) was induced by photothrombosis in a mouse model. Electroacupuncture (EA) was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques. Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction. Intrinsic neuronal excitability and activity were also disturbed, which was rescued by EA. Furthermore, the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1. We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction. Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction. The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine (approval No. 20200407009) April 7, 2020.

6.
Int J Numer Method Biomed Eng ; : e3561, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34865323

RESUMO

A series of three-dimensional (3D) numerical simulations are conducted to investigate the gradual failure process of molars in this study. The real morphology and internal mesoscopic structure of a whole tooth are implemented into the numerical simulations through computerized tomography (CT) scanning, digital image processing and 3D matrix mapping. The failure process of the whole tooth subject to compressions including crack initiation, crack propagation, and final failure pattern is reproduced using 3D realistic failure process analysis (RFPA3D) method. It is concluded that a series of micro-cracks are gradually initiated, nucleated, and subsequently interconnect to form macroscopic cracks when the teeth are under over-compressions. The propagation of the macroscopic cracks results in the formation of fracture surfaces and penetrating cracks, which are essential signs and manifestations of the tooth failure. Moreover, the simulations reveal that, the material heterogeneity is a critical factor that affects the mechanical properties and fracture modes of the teeth, which vary from crown fractures to crown-root fractures and root fractures depending on different homogeneity indices. This article is protected by copyright. All rights reserved.

7.
Abdom Radiol (NY) ; 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910237

RESUMO

PURPOSE: To explore the diagnostic value of American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADS) for hepatocellular carcinoma (HCC) in patients with cirrhosis and chronic hepatitis B. METHODS: A total of 205 patients at high risk of HCC with solitary hepatic nodule were enrolled and retrospectively analyzed. All patients were over 18 years old and had a single lesion with a diameter < 50 mm. Lesions were categorized according to size and contrast enhancement patterns in the arterial, portal venous and late phases. Diagnostic efficacy of CEUS LI-RADS for HCC, and the rate of non-HCC malignancies in the LR-M class were compared between patients with cirrhosis and chronic hepatitis B. RESULTS: Of all 205 nodules (median nodule size was 34 mm), 142 (69.3%) were HCC. Of the 127 (61.9%) LR-5 category nodules, 95.8% (92/96) nodules were corresponded to HCC in cirrhosis, while 61.3% (19/31) nodules were corresponded to HCC in chronic hepatitis B (P = 0.000). Positive predictive value (PPV) of LR-5 category for HCC was 95.8% in cirrhosis and 61.3% in chronic hepatitis B (P = 0.000). More category of LR-4 nodules were proved to be HCC in patients with cirrhosis than chronic hepatitis B (80.0% vs 8.3%, P = 0.000). Of 41 LR-M category nodules, more non-HCC malignancies were found in chronic hepatitis B (76.0%) than that in cirrhosis (25.0%, P = 0.001). CONCLUSIONS: The LR-5 category is highly specific for the diagnosis of HCC in patients with cirrhosis. However, LR-5 category nodules require further CT or MRI examination or histological confirmation in patients with chronic hepatitis B for its unsatisfactory PPV for HCC.

8.
Clin Case Rep ; 9(12): e05220, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34938567

RESUMO

Alternating therapeutic plasma exchange with double plasma molecular adsorption system can rapidly remove bilirubin and ammonia and supplement the essential substance from the blood, which could be used as an effective treatment for fulminant hepatic failure.

9.
Small ; : e2107220, 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34927352

RESUMO

The electronic noise characterization of single-molecule devices provides insights into the mechanisms of charge transport. In this work, it is reported that flicker noise can serve as an indicator of the time-dependent evolution of charge transport mechanisms in the single-molecule break junction process. By introducing time-frequency analysis, the authors find that flicker noise components of the molecule junction show time evolution behavior in the dynamic break junction process. A further investigation of the power-law dependence of flicker with conductance during the dynamic break junction process reveals that the mechanism of charge transport transits from the through-space transport to the through-bond transport, and is dominated by through-space transport again when the junction is about to rupture. The authors' results provide a flicker noise-based way to characterize the time-dependent evolution of charge transport mechanisms in single-molecule break junctions.

10.
Zhonghua Nan Ke Xue ; 27(6): 535-541, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34914295

RESUMO

Objective: To review and analyze the trend of researches on prostatitis in China in the past two decades. METHODS: We searched the core collection of China National Knowledge Infrastructure (CNKI) for studies on prostatitis, and analyzed the data obtained using Excel, Citespace and VOSviewer. RESULTS: Totally, 1 216 original articles were identified, with 3 271 keywords, ≥3-time high-frequency keywords accounting for 12.9%, with "", "", "chronic prostatitis", "prostatitis", and "" as the top 5 ones, each with a centrality higher than 300. Major prostatitis-related studies focused on the 8 keywords, namely, prostatitis, prostatic fluid, rats, prostate, syndromes, efficacy observation, compound (in traditional Chinese medicine, TCM), and therapeutic application. The included literature involved 2 808 authors, with 402 involved more than twice and most of them in a scattered manner. The major topics of prostatitis studies varied in the past two decades, focusing on TCM therapies, promotion of blood circulation and stasis and comprehensive nursing in 2000-2001, on animal models, CD4+ lymphocytes and other experimental molecules in 2007-2010, on urodynamics, risk factors and specific antigens in 2013-2016, and on literature information resources in 2016. CONCLUSIONS: The immune mechanism remains a hot topic in the future researches on prostatitis. In terms of treatment of the disease, TCM has a potential value, and more practice and studies are required for an optimal combination of TCM and Western medicine. Strengthened collaborative efforts are needed to establish an authoritative source channel for the keywords, and incorporate it into the national standard system, and above all, to integrate the prostatitis study into multi-disciplinary researches, eliminate academic barriers, encourage collaborative innovation with multiple parties, and promote the exchanges and development in this field.


Assuntos
Prostatite , Animais , China/epidemiologia , Masculino , Prostatite/tratamento farmacológico , Ratos
12.
Sci Rep ; 11(1): 21814, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750476

RESUMO

The instability of slope has already threatened life and property safety of the people, and improving the monitoring method of slope stability has important theoretical and practical significance for disaster prevention and reduction. According to the idea of "Newton force sudden drop and catastrophic occurrence" proposed by M.C. He in the landslide monitoring, a numerical model with constant resistance bolt has been established. Through numerical simulation research, it is found that the maximum principal stress, minimum principal stress and shear stress of the intersection point P of landslide surface and constant resistance bolt are sudden growth and sudden decrease, the vertical displacement and lateral displacement of this point P appear rise and fall before three kinds of stress. When loading to the next step of the step where three stress have reduced to a minimum value the slope is unstable and destroyed. At this time, the constant resistance bolt has undergone larger plastic deformation and damaged. Finally, comparing the stress curves and the acoustic emission (AE) curves, it can be seen that stress decreases from the maximum value and the AE curves begin to show a significant rise, the two curves display opposite law. It can be seen from the AE diagram that the failure mode of the slope is a combined tension and shear failure. The numerical test results provide a new idea for real-time monitoring and forecasting of slope.

14.
Chin J Nat Med ; 19(11): 868-873, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34844725

RESUMO

Dicarabrols B and C (1 and 2), two new carabrane sesquiterpenoid dimers, along with one new carabrane sesquiterpenoid (3) were isolated from the whole plant of Carpesium abrotanoides L. Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Dicarabrol B possesses a novel C30 skeleton featuring a methylene-tethered bridge between two sesquiterpene moieties, while dicarabrol C presents the unique linkage of a cyclopentane ring in the molecule. Dicarabrol C exhibited potent inhibitory effects on HL-60 cells with an IC50 value of 3.7 µmol·L-1.

15.
Free Radic Biol Med ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34767921

RESUMO

Calcium oxalate (CaOx) is the most common component of kidney stones. Oxidative stress, inflammation and autophagy-induced cell death are the major causes of CaOx crystal deposition and CaOx crystal deposition can further lead to kidney injury. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, plays an important role in the pathogenesis of many diseases, such as atherosclerosis, diabetes and chronic kidney disease, but the effect of TMAO on hyperoxaluria-induced CaOx crystal deposition and kidney injury remains unknown. We hypothesize that TMAO aggravates CaOx crystal deposition via promoting CaOx-mediated cell death. C57Bl/6 mice were given high-oxalate diet as a model of hyperoxaluria. TMAO was provided via drinking water. Serum TMAO levels increased 15 days after CaOx treatment (6.30 ± 0.17 µmol/L vs. 34.65 ± 8.95 µmol/L). High-oxalate diet induced inflammation, CaOx deposition and kidney injury, which TMAO aggravated. In accordance, TMAO intensified high-oxalate diet induced oxidative stress, autophagy and apoptosis. Moreover, TMAO enhanced CaOx crystal adhesion to HK-2 cells and reduced cell viability (from 88.9 ± 1.6% to 75.0 ± 2.7%). Protein kinase R-like endoplasmic reticulum kinase (PERK) may mediate these TMAO effects, as TMAO promoted PERK phosphorylation. Consistently, PERK knockdown alleviated TMAO-evoked CaOx-autophagy, apoptosis and oxidative stress in HK-2 cells. In conclusion, TMAO can aggravate hyperoxaluria-induced kidney injury by triggering the PERK/ROS pathway, which enhances autophagy, apoptosis and inflammation, and facilitates CaOx crystal deposition in renal tubular cells.

16.
J Med Chem ; 64(23): 17221-17238, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34809430

RESUMO

Androgen receptor (AR) has proved to be a vital drug target for treating prostate cancer. Here, we reported the discovery of a novel AR antagonist 92 targeting the AR ligand-binding pocket, but distinct from the marketed drug enzalutamide (Enz), 92 demonstrated inhibition on the AR ligand-binding domain (LBD) dimerization, which is a novel mechanism reported for the first time. First, a novel hit (26, IC50 = 5.57 µM) was identified through virtual screening based on a theoretical AR LBD dimer bound with the Enz model. Then, guided by molecular modeling, 92 was discovered with 32.7-fold improved AR antagonistic activity (IC50 = 0.17 µM). Besides showing high bioactivity and safety, 92 can inhibit AR nuclear translocation. Furthermore, 92 inhibited the formation of the AR LBD dimer, possibly through attenuating the hydrogen-bonding network between the two monomers. This interesting finding would pave the way for the discovery of a new class of AR antagonists.

17.
Parasitol Res ; 120(11): 3851-3856, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34626234

RESUMO

This study aimed to explore the effect and mechanism underlying the role of the Schistosoma japonicum antigen of fatty acid-binding protein (SjFABP) on the growth of the schistosomula. SjFABP levels were evaluated by quantitative real-time polymerase chain reaction of samples of mice infected with S. japonicum; SjFABP was expressed and its levels gradually increased during all stages of S. japonicum schistosomula, including on 3, 10, 14, and 21 days of the growth process. Immunohistochemistry results demonstrated that SjFABP was distributed in the parenchyma, especially in the digestive tract of the S. japonicum schistosomula. RNA interference resulted in more than 60% knockdown of SjFABP leading to a reduction in length, volume, width, and area of the schistosomula as compared to control samples, as determined by light microscopy. Terminal deoxynucleotidyl transferase dUTP nick-end labeling detection further suggested that SjFABP knockdown resulted in increased apoptosis of schistosomes. Taken together, these results suggest that SjFABP may be related to the growth and survival of S. japonicum schistosomula, thereby representing a potential target for the treatment of schistosomiasis.


Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Animais , Anticorpos Anti-Helmínticos , Proteínas de Ligação a Ácido Graxo/genética , Marcação In Situ das Extremidades Cortadas , Camundongos , Schistosoma japonicum/genética
18.
Appl Opt ; 60(21): 6331-6336, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613301

RESUMO

In this paper, we demonstrate a high-power, narrow-linewidth, polarization-maintaining fiber amplifier with near-diffraction-limited beam quality. By optimizing the phase modulation signal, a nearly top-hat-shaped spectrum was generated for self-pulsing suppressing. That results in doubling the self-pulsing threshold we got from conventional white noise signal phase modulation with the same optical linewidth. Based on an optimized signal and a high power, polarization-maintaining, counter-pumped fiber amplifier, we obtain a 3.25 kW narrow-linewidth linearly polarized laser output with a linewidth of ∼20GHz, the polarization extinction ratio is about 15 dB, and the M2 is less than 1.22 at the maximum output power. To the best of our knowledge, this is the first demonstration of a narrow-linewidth, linear polarization, all-fiber amplifier with 3.25 kW laser output.

19.
Acta Pharmacol Sin ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654876

RESUMO

Transient receptor potential channel TRPV4 and nicotinamide adenine dinucleotide phosphate oxidase (Nox2) are involved in oxidative stress that increases endothelial permeability. It has been shown that obesity enhances the physical association of TRPV4 and Nox2, but the role of TRPV4-Nox2 association in obesity has not been clarified. In this study we investigated the function of TRPV4-Nox2 complex in reducing oxidative stress and regulating abnormal vascular permeability in obesity. Obesity was induced in mice by feeding a high-fat diet (HFD) for 14 weeks. The physical interaction between TRPV4 and Nox2 was measured using FRET, co-immunoprecipitation and GST pull-down assays. The functional interaction was measured by rhodamine phalloidin, CM-H2DCFDA in vitro, the fluorescent dye dihydroethidium (DHE) staining assay, and the Evans blue permeability assay in vivo. We demonstrated that TRPV4 physically and functionally associated with Nox2, and this physical association was enhanced in aorta of obese mice. Furthermore, we showed that interrupting TRPV4-Nox2 coupling by TRPV4 knockout, or by treatment with a specific Nox2 inhibitor Nox2 dstat or a specific TRPV4 inhibitor HC067046 significantly attenuated obesity-induced ROS overproduction in aortic endothelial cells, and reversed the abnormal endothelial cytoskeletal structure. In order to discover small molecules disrupting the over-coupling of TPRV4 and Nox2 in obesity, we performed molecular docking analysis and found that compound M12 modulated TRPV4-Nox2 association, reduced ROS production, and finally reversed disruption of the vascular barrier in obesity. Together, this study, for the first time, provides evidence for the TRPV4 physically interacting with Nox2. TRPV4-Nox2 complex is a potential drug target in improving oxidative stress and disruption of the vascular barrier in obesity. Compound M12 targeting TRPV4-Nox2 complex can improve vascular barrier function in obesity.

20.
Nanoscale Horiz ; 6(12): 971-978, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34647939

RESUMO

Two-dimensional (2D) van der Waals (vdW) ferroelectrics are core candidates for the development of next-generation non-volatile storage devices, which rely highly on ferroelectric stability and feasible approaches to manipulate the ferroelectric polarization and domain. Here, based on density functional theory calculations, we demonstrate that the bending deformation can not only manipulate the polarization direction and domain size of AgBiP2Se6 monolayers but also significantly improve the ferroelectric stability. The ordered polarization in the bent AgBiP2Se6 monolayers can be well maintained at a temperature of 200 K in molecular dynamics simulations; by contrast, it is broken at only 100 K for their freestanding counterparts. These phenomena can be attributed to synergic effects from the asymmetric strain energy induced by a strain gradient and a reduced migration barrier of Ag ions from convex to concave surfaces. More interestingly, a ferroelectric bubble can be induced in the monolayer under biaxial compression strain. This mechano-ferroelectric coupling represents a new mechanism and feasible route towards stabilization and polarization flip in 2D ferroelectrics.

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