Publications by authors named "Tong Wang"

1,198 Publications

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Vildagliptin, a dipeptidyl peptidase-4 inhibitor, attenuated endothelial dysfunction through miRNAs in diabetic rats.

Arch Med Sci 2021 12;17(5):1378-1387. Epub 2019 Jul 12.

Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether vildagliptin protected endothelial function in diabetic rats and explored the involved mechanism.

Material And Methods: Experimental diabetic rats were obtained by feeding a high-fat diet and administering an intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups: controls (CON), diabetes (DM), diabetes + low dose of vildagliptin (Lvil, 10 mg/kg/day), and diabetes + high dose of vildagliptin (Hvil, 20 mg/kg/day). The metabolic parameters, endothelial function, and whole miRNA expression were measured.

Results: After a 12-week treatment, vildagliptin-treated rats showed a significant reduction in blood glucose and blood lipid levels. Moreover, vildagliptin recovered aortic endothelial function in diabetic rats. We identified 31 miRNAs that were differentially expressed in the Hvil group compared with the diabetic group. Importantly, through miRNA target biological function and pathway analysis, we found that vildagliptin activated miR-190-5p to inhibit expression and inhibited miR-134-5p and miR-375-3p to increase and expression in the aorta.

Conclusions: Our present study indicates that vildagliptin can recover endothelial function in diabetic rats. Anti-inflammatory and anti-apoptosis mechanisms and endothelial moderation may be the intervention targets of vildagliptin to protect the cardiovascular system through miRNA regulation.
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http://dx.doi.org/10.5114/aoms.2019.86609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425228PMC
July 2019

Reactive astrocytes induced by 2-chloroethanol modulate microglia polarization through IL-1β, TNF-α, and iNOS upregulation.

Food Chem Toxicol 2021 Sep 10;157:112550. Epub 2021 Sep 10.

Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, China. Electronic address:

The synthetic organic chemical, 1,2-dichloroethane (1,2-DCE), can cause brain edemas under subacute poisoning. Our previous studies indicated that neuroinflammation could be induced due to astrocytes and microglia activation during brain edemas in 1,2-DCE-intoxicated mice. However, the crosstalk between these two glial cells in 1,2-DCE-induced neuroinflammation remained unclear. In this study, primary cultured rat astrocytes and microglia, as well as an immortalized microglia cell line were employed to study the effects of 2-chloroethanol (2-CE, a 1,2-DCE intermediate metabolite in vivo) treated astrocytes on microglia polarization. Our current results revealed that 2-CE treated rat astrocytes were activated through p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) signaling pathways. Theses pathways were triggered by reactive oxygen species (ROS) produced during 2-CE metabolism. Also, astrocytes were more sensitive to 2-CE effects than microglia. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expressions were upregulated in 2-CE-induced reactive astrocytes, enhancing IL-1β, TNF-α, and nitric oxide (NO) excretions, which stimulated microglia polarization. Therefore, the neuroinflammation induced by 1,2-DCE in mice's brains is probably triggered by reactive astrocytes.
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http://dx.doi.org/10.1016/j.fct.2021.112550DOI Listing
September 2021

Establishment of a simplified dichotomic size-exclusion chromatography for isolating extracellular vesicles toward clinical applications.

J Extracell Vesicles 2021 Sep;10(11):e12145

MOE Key Laboratory of Tumor Molecular Biology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.

Size-exclusion chromatography (SEC) is a widely adopted method for the isolation of extracellular vesicles (EVs) from complex samples. SEC can efficiently remove high-abundant proteins, while often requires multiple fractionation operation using diversified column settings. In this study, we aim to establish a simplified SEC method to acquire high quality EVs. In comparison of all three cross-linked Sepharose resins with the sample types of FBS and human serum (HS), CL-6B and CL-4B showed superior performance in regular SEC to CL-2B in terms of significantly narrower EV and protein peaks, higher resolutions and EV purity. By increasing their bed volumes to 20 ml, the resolutions of CL-6B and CL-4B columns could be significantly improved, while the CL-6B column had the best performance with higher particle yields and tighter EV peaks. With the CL-6B 20 ml column, we further established a simplified dichotomic SEC method that only requires two bulk elutions to acquire EVs in the Eluate 1 and proteins in the Eluate 2. We further justified that such CL-6B columns were reusable for at least 10 consecutive times, and the dichotomic SEC was applicable to EV isolations from HS and FBS-free supernatants of fluorescently labelled and unlabelled SW620 cells. The proteomics analysis implicated that although the two methods had dissimilar abilities in removing different co-isolating contaminant proteins from EVs, the dichotomic SEC and ultracentrifugation could isolate EVs from human plasma with comparable purity. This dichotomic SEC has its intriguing potential to be used for EV preparation toward clinical testing and/or basic research.
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http://dx.doi.org/10.1002/jev2.12145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435528PMC
September 2021

A neural network with encoded visible edge prior for limited-angle computed tomography reconstruction.

Med Phys 2021 Sep 5. Epub 2021 Sep 5.

School of Mathematical Sciences, Capital Normal University, Beijing, China.

Purpose: Limited-angle computed tomography is a challenging but important task in certain medical and industrial applications for nondestructive testing. The limited-angle reconstruction problem is highly ill-posed and conventional reconstruction algorithms would introduce heavy artifacts. Various models and methods have been proposed to improve the quality of reconstructions by introducing different priors regarding to the projection data or ideal images. However, the assumed priors might not be practically applicable to all limited-angle reconstruction problems. Convolutional neural network (CNN) exhibits great promise in the modeling of data coupling and has recently become an important technique in medical imaging applications. Although existing CNN methods have demonstrated promising results, their robustness is still a concern. In this paper, in light of the theory of visible and invisible boundaries, we propose an alternating edge-preserving diffusion and smoothing neural network (AEDSNN) for limited-angle reconstruction that builds the visible boundaries as priors into its structure. The proposed method generalizes the alternating edge-preserving diffusion and smoothing (AEDS) method for limited-angle reconstruction developed in the literature by replacing its regularization terms by CNNs, by which the piecewise constant assumption assumed by AEDS is effectively relaxed.

Methods: The AEDSNN is derived by unrolling the AEDS algorithm. AEDSNN consists of several blocks, and each block corresponds to one iteration of the AEDS algorithm. In each iteration of the AEDS algorithm, three subproblems are sequentially solved. So, each block of AEDSNN possesses three main layers: data matching layer, -direction regularization layer for visible edges diffusion, and -direction regularization layer for artifacts suppressing. The data matching layer is implemented by conventional ordered-subset simultaneous algebraic reconstruction technique (OS-SART) reconstruction algorithm, while the two regularization layers are modeled by CNNs for more intelligent and better encoding of priors regarding to the reconstructed images. To further strength the visible edge prior, the attention mechanism and the pooling layers are incorporated into AEDSNN to facilitate the procedure of edge-preserving diffusion from visible edges.

Results: We have evaluated the performance of AEDSNN by comparing it with popular algorithms for limited-angle reconstruction. Experiments on the medical dataset show that the proposed AEDSNN effectively breaks through the piecewise constant assumption usually assumed by conventional reconstruction algorithms, and works much better for piecewise smooth images with nonsharp edges. Experiments on the printed circuit board (PCB) dataset show that AEDSNN can better encode and utilize the visible edge prior, and its reconstructions are consistently better compared to the competing algorithms.

Conclusions: A deep-learning approach for limited-angle reconstruction is proposed in this paper, which significantly outperforms existing methods. The superiority of AEDSNN consists of three aspects. First, by the virtue of CNN, AEDSNN is free of parameter-tuning. This is a great facility compared to conventional reconstruction methods; Second, AEDSNN is quite fast. Conventional reconstruction methods usually need hundreds even thousands of iterations, while AEDSNN just needs three to five iterations (i.e., blocks); Third, the learned regularizer by AEDSNN enjoys a broader application capacity, which could work well with piecewise smooth images and surpass the piecewise constant assumption frequently assumed for computed tomography images.
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http://dx.doi.org/10.1002/mp.15205DOI Listing
September 2021

Dual responsive hybrid nanoparticle for tumor chemotherapy combined with photothermal therapy.

J Pharm Sci 2021 Sep 1. Epub 2021 Sep 1.

School of Pharmaceutical Sciences, Zhengzhou University, No.100, Kexue Avenue, Zhengzhou 450001, China.

With the deepening of tumor targeting research, the application of intelligent responsive drug carriers in the field of controlled drug release has become more and more extensive, and multiple responsive nano drug carriers have attracted greater attention. In this paper, nanoparticles with gold nanorods (GNR) as the core, mesoporous silica (mSiO) doped with hydroxyapatite (HAP) as the inorganic hybrid shell and physically loaded with doxorubicin hydrochloride (DOX•HCl) are prepared (DOX/GNR/mSiO/HAP, DNPs). DNPs nanoparticles have a typical core-shell structure. The gold nanorods as the core have extremely high light-to-heat conversion efficiency. Under the irradiation of near-infrared light, light can be converted into heat. The inorganic hybrid shell is a drug reservoir. The excellent photothermal response of gold nanorods combined with the excellent pH response of hydroxyapatite can obtain slow and sustained release of chemotherapeutic drugs. In vivo and in vitro anti-tumor cell activity study show that the DNPs in the laser showed stronger cytotoxicity than the other groups. Compared to chemotherapy and phototherapy alone, DNPs selectively accumulate in the tumor through the enhanced penetration and retention (EPR) effects. and have the unified function of hyperthermia and chemotherapy, and have significant inhibitory effect on tumor growth. Therefore, this study provides a new idea for the study of the combination of multiple therapeutic methods in the treatment of cancer.
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http://dx.doi.org/10.1016/j.xphs.2021.08.034DOI Listing
September 2021

Bifunctional citrate-NiCo(OH) layer coated fluorine-doped hematite for simultaneous hole extraction and injection towards efficient photoelectrochemical water oxidation.

Nanoscale 2021 Sep 12;13(33):14197-14206. Epub 2021 Aug 12.

State Key Laboratory of Applied Organic Chemistry (SKLAOC), The Key Laboratory of Catalytic Engineering of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.

Surface modification by loading a water oxidation co-catalyst (WOC) is generally considered an efficient means to optimize the sluggish surface oxygen evolution reaction (OER) of a hematite photoanode for photoelectrochemical (PEC) water oxidation. However, the surface WOC usually exerts little impact on the bulk charge separation of hematite. Herein, an ultrathin citrate-NiCo(OH) [Cit-NiCo(OH)] is conformally coated on the fluorine-doped hematite (F-FeO) photoanode for PEC water oxidation to simultaneously promote the internal hole extraction and surface hole injection of the target photoanode. Besides, the conformally coated Cit-NiCo(OH) overlayer passivates the redundant surface trap states of F-FeO. These factors result in a superior photocurrent density of 2.52 mA cm at 1.23 V versus a reversible hydrogen electrode (V vs. RHE) for the target photoanode. Detailed investigation manifests that the hole extraction property in Cit-NiCo(OH) is mainly derived from the Ni sites, while Co incorporation endows the overlayer with more catalytic active sites. This synergistic effect between Ni and Co contributes to a rapid and continuous hole migration pathway from the bulk to the interface of the target photoanode, and then to the electrolyte for water oxidation.
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http://dx.doi.org/10.1039/d1nr03257gDOI Listing
September 2021

Effects of NLRP3 inflammasome blockade on postresuscitation cerebral function in a rat model of cardiopulmonary resuscitation.

Biomed Pharmacother 2021 Aug 30;143:112093. Epub 2021 Aug 30.

Department of Emergency, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA; Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond,VA, USA. Electronic address:

Cardiac arrest (CA) remains a major public health issue. Inflammatory responses with overproduction of interleukin-1β regulated by NLRP3 inflammasome activation play a crucial role in cerebral ischemia/reperfusion injury. We investigated the effects of the selective NLRP3-inflammasome inhibitor MCC950 on post-resuscitation cerebral function and neurologic outcome in a rat model of cardiac arrest. Thirty-six male rats were randomized into the MCC950 group, the control group, or the sham group (N = 12 of each group). Each group was divided into a 6 h non-survival subgroup (N = 6) and a 24 h survival subgroup (N = 6). Ventricular fibrillation (VF) was electrically induced and untreated for 6 min, followed by 8 min of precordial compressions and mechanical ventilation. Resuscitation was attempted with a 4J defibrillation. Either MCC950 (10 mg/kg) or vehicle was injected intraperitoneally immediately after the return of spontaneous circulation (ROSC). Rats in the sham group underwent the same surgical procedures without VF and CPR. Brain edema, cerebral microcirculation, plasma interleukin Iβ (IL-1β), and neuron-specific enolase (NSE) concentration were measured at 6 h post-ROSC of non-survival subgroups, while 24 h survival rate, neurological deficits were measured at 24 h post-ROSC of survival subgroups. Post-resuscitation brain edema was significantly reduced in animals treated with MCC950 (p < 0.05). Cerebral perfused vessel density (PVD) and microcirculatory flow index (MFI) values were significantly higher in the MCC950 group compared with the control group (p < 0.05). The plasma concentrations of IL-1β and NSE were significantly decreased in animals treated with MCC950 compared with the control group (p < 0.05). 24 h-survival rate and neurological deficits score (NDS) was also significantly improved in the MCC950 group compared with the control group (p < 0.05). NLRP3 inflammasome blockade with MCC950 at ROSC reduces the circulatory level of IL-1β, preserves cerebral microcirculation, mitigates cerebral edema, improves the 24 h-survival rate, and neurological deficits.
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http://dx.doi.org/10.1016/j.biopha.2021.112093DOI Listing
August 2021

Design of Crystalline Reduction-Oxidation Cluster-Based Catalysts for Artificial Photosynthesis.

JACS Au 2021 Aug 8;1(8):1288-1295. Epub 2021 Jul 8.

School of Chemistry, South China Normal University, Guangzhou 510006, P. R. China.

Metal cluster-based compounds have difficulty finishing the photocatalytic carbon dioxide reduction reaction (CORR) and water oxidation reaction (WOR) simultaneously because of the big challenge in realizing the coexistence of independently and synergistically reductive and oxidative active sites in one compound. Herein, we elaborately designed and synthesized one kind of crystalline reduction-oxidation () cluster-based catalysts connecting reductive { } (M = Zn, Co, and Ni for , , respectively) cluster and oxidative {PMoVO} cluster through a single oxygen atom bridge to achieve artificial photosynthesis successfully. These clusters can all photocatalyze CO-to-CO and HO-to-O reactions simultaneously, of which the CO yield of is 13.8 μmol/g·h, and the selectivity is nearly 100%. Density functional theory calculations reveal that the concomitantly catalytically reductive and oxidative active sites (for CORR and WOR, respectively) and the effective electron transfer between the sites in these photocatalysts are the key factors to complete the overall photosynthesis.
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http://dx.doi.org/10.1021/jacsau.1c00186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397352PMC
August 2021

Simultaneous determination of nine tyrosine kinase inhibitors in three complex biological matrices by using high-performance liquid chromatography-diode array detection combined with a second-order calibration method.

J Sep Sci 2021 Aug 31. Epub 2021 Aug 31.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, P. R. China.

An intelligent chemometric second-order calibration method called alternating trilinear decomposition- assisted multivariate curve resolution combined with high-performance liquid chromatography-diode array detection was used for the simultaneous quantification of nine tyrosine kinase inhibitors in three complex biological systems. The method allows simultaneous quantification of the components in different biological matrices without the need for cumbersome pre-treatment steps, complex elution conditions, and complete peak separation. Even with the varying time shift, severe peak overlap, and various unknown interferences, the proposed method can extract pure chromatographic and spectroscopic information for each analyte, while providing accurate qualitative and quantitative results of nine common tyrosine kinase inhibitors in three different biological matrices. All the drugs were eluted in 7 min. The results showed that the nine drugs in each matrix showed good linearity (r > 0.984) in the calibration range with a root mean square error of calibration less than 0.9 μg/mL. The average spiked recoveries of the target analytes were all in the range of 83.4-110.0%, with standard deviations less than 9.0%. Finally, the classical method was used to validate the proposed method. In comparison to the traditional method, the proposed strategy is accuracy, simultaneous, and interference-free.
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http://dx.doi.org/10.1002/jssc.202100293DOI Listing
August 2021

Whole-genome sequencing of brown-marbled grouper (Epinephelus fuscoguttatus) provides insights into adaptive evolution and growth differences.

Mol Ecol Resour 2021 Aug 28. Epub 2021 Aug 28.

State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, China.

The brown-marbled grouper (Epinephelus fuscoguttatus) is an important species of fish in the coral reef ecosystem and marine aquaculture industry. In this study, a high-quality chromosome-level genome of brown-marbled grouper was assembled using Oxford Nanopore technology and Hi-C technology. The GC content and heterozygosity were approximately 42% and 0.35%, respectively. A total of 230 contigs with a total length of 1047 Mb and contig N50 of 13.8 Mb were assembled, and 228 contigs (99.13%) were anchored into 24 chromosomes. A total of 24,005 protein-coding genes were predicted, among which 23,862 (99.4%) predicted genes were annotated. Phylogenetic analysis showed that brown-marbled grouper and humpback grouper were clustered into one clade that separated approximately 11-23 million years ago. Collinearity analyses showed that there was no obvious duplication of large fragments between chromosomes in the brown-marbled grouper. Genomes of the humpback grouper and giant grouper showed a high collinearity with that of the brown-marbled grouper. A total of 305 expanded gene families were detected in the brown-marbled grouper genome, which is mainly involved in disease resistance. In addition, a genetic linkage map with 3061.88 cM was constructed. Based on the physical and genetic map, one growth-related quantitative trait loci was detected in 32,332,447 bp of chromosome 20, and meox1 and etv4 were considered candidate growth-related genes. This study provides pivotal genetic resources for further evolutionary analyses and artificial breeding of groupers.
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http://dx.doi.org/10.1111/1755-0998.13494DOI Listing
August 2021

Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice.

Pflugers Arch 2021 Aug 29. Epub 2021 Aug 29.

Department of Cellular and Molecular Physiology, Yale School of Medicine University, 333 Cedar Street, P.O. Box 208026, New Haven, CT, 06520-8026, USA.

We compared the regulation of the NaCl cotransporter (NCC) in adaptation to a low-K (LK) diet in male and female mice. We measured hydrochlorothiazide (HCTZ)-induced changes in urine volume (UV), glomerular filtration rate (GFR), absolute (ENa, EK), and fractional (FENa, FEK) excretion in male and female mice on control-K (CK, 1% KCl) and LK (0.1% KCl) diets for 7 days. With CK, NCC-dependent ENa and FENa were larger in females than males as observed previously. However, with LK, HCTZ-induced ENa and FENa increased in males but not in females, abolishing the sex differences in NCC function as observed in CK group. Despite large diuretic and natriuretic responses to HCTZ, EK was only slightly increased in response to the drug when animals were on LK. This suggests that the K-secretory apparatus in the distal nephron is strongly suppressed under these conditions. We also examined LK-induced changes in Na transport protein expression by Western blotting. Under CK conditions females expressed more NCC protein, as previously reported. LK doubled both total (tNCC) and phosphorylated NCC (pNCC) abundance in males but had more modest effects in females. The larger effect in males abolished the sex-dependence of NCC expression, consistent with the measurements of function by renal clearance. LK intake did not change NHE3, NHE2, or NKCC2 expression, but reduced the amount of the cleaved (presumably active) form of γENaC. LK reduced plasma K to lower levels in females than males. These results indicated that males had a stronger NCC-mediated adaptation to LK intake than females.
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http://dx.doi.org/10.1007/s00424-021-02611-5DOI Listing
August 2021

Gate-Defined Quantum Confinement in CVD 2D WS.

Adv Mater 2021 Aug 26:e2103907. Epub 2021 Aug 26.

Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Singapore, 138634, Singapore.

Temperature-dependent transport measurements are performed on the same set of chemical vapor deposition (CVD)-grown WS single- and bilayer devices before and after atomic layer deposition (ALD) of HfO . This isolates the influence of HfO deposition on low-temperature carrier transport and shows that carrier mobility is not charge impurity limited as commonly thought, but due to another important but commonly overlooked factor: interface roughness. This finding is corroborated by circular dichroic photoluminescence spectroscopy, X-ray photoemission spectroscopy, cross-sectional scanning transmission electron microscopy, carrier-transport modeling, and density functional modeling. Finally, electrostatic gate-defined quantum confinement is demonstrated using a scalable approach of large-area CVD-grown bilayer WS and ALD-grown HfO . The high dielectric constant and low leakage current enabled by HfO allows an estimated quantum dot size as small as 58 nm. The ability to lithographically define increasingly smaller devices is especially important for transition metal dichalcogenides due to their large effective masses, and should pave the way toward their use in quantum information processing applications.
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http://dx.doi.org/10.1002/adma.202103907DOI Listing
August 2021

Further Results on Optimal Tracking Control for Nonlinear Systems With Nonzero Equilibrium via Adaptive Dynamic Programming.

IEEE Trans Neural Netw Learn Syst 2021 Aug 24;PP. Epub 2021 Aug 24.

This article develops a novel cost function (performance index function) to overcome the obstacles in solving the optimal tracking control problem for a class of nonlinear systems with known system dynamics via adaptive dynamic programming (ADP) technique. For the traditional optimal control problems, the assumption that the controlled system has zero equilibrium is generally required to guarantee the finiteness of an infinite horizon cost function and a unique solution. In order to solve the optimal tracking control problem of nonlinear systems with nonzero equilibrium, a specific cost function related to tracking errors and their derivatives is designed in this article, in which the aforementioned assumption and related obstacles are removed and the controller design process is simplified. Finally, comparative simulations are conducted on an inverted pendulum system to illustrate the effectiveness and advantages of the proposed optimal tracking control strategy.
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http://dx.doi.org/10.1109/TNNLS.2021.3105646DOI Listing
August 2021

Quantitative analysis of carbaryl and thiabendazole in complex matrices using excitation-emission fluorescence matrices with second-order calibration methods.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Aug 6;264:120267. Epub 2021 Aug 6.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.

In this paper, a fast and efficient analytical strategy was proposed that chemometrics assisted with excitation-emission fluorescence matrices was used to quantify carbaryl (CAR) and thiabendazole (TBZ) in peach, soil and sewage. Even if there are serious overlapped peaks and unknown interferences in fluorescence analysis, the second-order calibration method based on alternating trilinear decomposition (ATLD) algorithm can be used to analyze CAR and TBZ in peach, soil and sewage. The recoveries of CAR and TBZ in peach are 110.4% and 99.7% and their standard deviations are lower than 2.1% and 0.3%, respectively. In addition, the accuracy of the method was assessed with figures of merit as well as intra-day and inter-day precision. The limit of detection, the limit of quantitation of CAR and TBZ in peach are 1.2 ng mL and 0.3 ng mL, 3.5 ng mL and 0.8 ng mL, respectively. And their root-mean-square error of prediction are 17.0 ng mL and 5.0 ng mL and there are high sensitivity and selectivity in this method. Meanwhile, the results obtained by ATLD algorithm were compared with those obtained by the self-weighted alternate trilinear decomposition algorithm (SWATLD) and the parallel factor analysis (PARAFAC) algorithm, and statistical methods such as the t-test, F-test and the elliptic joint confidence region were used to evaluate for analysis. There were no significant differences among these methods. At last, high performance liquid chromatography-fluorescence detector (HPLC-FLD) was used to evaluate the accuracy and reliability of the proposed method. These results are satisfactory and indicate that the proposed method can be used for accurate and rapid determination of pesticides in complex systems.
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http://dx.doi.org/10.1016/j.saa.2021.120267DOI Listing
August 2021

Gait Kinematic and Kinetic Characteristics of Older Adults With Mild Cognitive Impairment and Subjective Cognitive Decline: A Cross-Sectional Study.

Front Aging Neurosci 2021 3;13:664558. Epub 2021 Aug 3.

Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Older adults with mild cognitive impairment (MCI) have slower gait speed and poor gait performance under dual-task conditions. However, gait kinematic and kinetic characteristics in older adults with MCI or subjective cognitive decline (SCD) remain unknown. This study was designed to explore the difference in gait kinematics and kinetics during level walking among older people with MCI, SCD, and normal cognition (NC).

Methods: This cross-sectional study recruited 181 participants from July to December 2019; only 82 met the inclusion criteria and consented to participate and only 79 completed gait analysis. Kinematic and kinetic data were obtained using three-dimensional motion capture system during level walking, and joint movements of the lower limbs in the sagittal plane were analyzed by Visual 3D software. Differences in gait kinematics and kinetics among the groups were analyzed using multivariate analysis of covariance (MANCOVA) with Bonferroni analysis. After adjusting for multiple comparisons, the significance level was < 0.002 for MANCOVA and < 0.0008 for analysis.

Results: Twenty-two participants were MCI [mean ± standard deviation (SD) age, 71.23 ± 6.65 years], 33 were SCD (age, 72.73 ± 5.25 years), and 24 were NC (age, 71.96 ± 5.30 years). MANCOVA adjusted for age, gender, body mass index (BMI), gait speed, years of education, diabetes mellitus, and Geriatric Depression Scale (GDS) revealed a significant multivariate effect of group in knee peak extension angle ( = 8.77, < 0.0001) and knee heel strike angle ( = 8.07, = 0.001) on the right side. comparisons with Bonferroni correction showed a significant increase of 5.91° in knee peak extension angle ( < 0.0001) and a noticeable decrease of 6.21°in knee heel strike angle ( = 0.001) in MCI compared with NC on the right side. However, no significant intergroup difference was found in gait kinetics, including dorsiflexion, plantar flexion, knee flexion, knee extension, hip flexion, and hip extension( > 0.002).

Conclusion: An increase of right knee peak extension angle and a decrease of right knee heel strike angle during level walking were found among older adults with MCI compared to those with NC.
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http://dx.doi.org/10.3389/fnagi.2021.664558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368728PMC
August 2021

Template Instrumentation for "Accurate Constant via Transient Incomplete Separation".

Anal Chem 2021 08 19;93(34):11654-11659. Epub 2021 Aug 19.

Department of Chemistry and Centre for Research on Biomolecular Interactions, York University, Toronto, Ontario M3J 1P3, Canada.

Accurate Constant via Transient Incomplete Separation (ACTIS) is a new method for finding the equilibrium dissociation constant of a protein-small molecule complex based on transient incomplete separation of the complex from the unbound small molecule in a capillary. This separation is caused by differential transverse diffusion of the complex and the small molecule in a pressure-driven flow. The advection-diffusion processes underlying ACTIS can be described by a system of partial differential equations allowing for a virtual ACTIS instrument to be built and ACTIS to be studied in silico. The previous in silico studies show that large variations in the fluidic system geometry do not affect the accuracy of determination, thus, proving that ACTIS is conceptually accurate. The conceptual accuracy does not preclude, however, instrumental inaccuracy caused by run-to-run signal drifts. Here we report on assembling a physical ACTIS instrument with a fluidic system that mimics the virtual one and proving the absence of signal drifts. Furthermore, we confirmed method ruggedness by assembling a second ACTIS instrument and comparing the results of experiments performed with both instruments in parallel. Despite some unintentional differences between the instruments (caused by tolerances in sizes, positions, etc.) and noticeable differences in their respective separagrams, we found that the values determined for identical samples with these instruments were equal. Conclusively, the fluidic system presented here can serve as a template for reliable ACTIS instrumentation.
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http://dx.doi.org/10.1021/acs.analchem.1c02007DOI Listing
August 2021

High-dimensional generalized propensity score with application to omics data.

Brief Bioinform 2021 Aug 19. Epub 2021 Aug 19.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China.

Propensity score (PS) methods are popular when estimating causal effects in non-randomized studies. Drawing causal conclusion relies on the unconfoundedness assumption. This assumption is untestable and is considered more plausible if a large number of pre-treatment covariates are included in the analysis. However, previous studies have shown that including unnecessary covariates into PS models can lead to bias and efficiency loss. With the ever-increasing amounts of available data, such as the omics data, there is often little prior knowledge of the exact set of important covariates. Therefore, variable selection for causal inference in high-dimensional settings has received considerable attention in recent years. However, recent studies have focused mainly on binary treatments. In this study, we considered continuous treatments and proposed the generalized outcome-adaptive LASSO (GOAL) to select covariates that can provide an unbiased and statistically efficient estimation. Simulation studies showed that when the outcome model was linear, the GOAL selected almost all true confounders and predictors of outcome and excluded other covariates. The accuracy and precision of the estimates were close to ideal. Furthermore, the GOAL is robust to model misspecification. We applied the GOAL to seven DNA methylation datasets from the Gene Expression Omnibus database, which covered four brain regions, to estimate the causal effects of epigenetic aging acceleration on the incidence of Alzheimer's disease.
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http://dx.doi.org/10.1093/bib/bbab331DOI Listing
August 2021

Insomnia and other sleep-related problems during the remission period of the COVID-19 pandemic: A large-scale survey among college students in China.

Psychiatry Res 2021 10 3;304:114153. Epub 2021 Aug 3.

Center for Public Health Initiatives, University of Pennsylvania, Philadelphia, PA, USA.

This study aimed to evaluate the sleep-related problems and predictors of probable clinical insomnia among college students during the COVID-19 remission period in China. 146,102 college students from 22 colleges/universities in Guangdong province participated in this study from 1th to 15th June, 2020. Self-administered questionnaires were used to assess demographic characteristics. Sleep-related problems, depression and anxiety symptoms were measured by Youth Self-Rating Insomnia Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7, respectively. The prevalence of difficulty in initiating sleep, difficulty in maintaining sleep, early morning awakening, sleep insufficiency, unrefreshing sleep and daytime functioning impairment were 7.2%, 3.4%, 3.5%, 9.6%, 14.6%, and 7.6%, respectively. 16.9% students had varying degrees of insomnia and 6.3% were considered as displaying probable clinical insomnia. Moreover, being urban residents, having a history of physical or mental illness, and probable clinical depression or anxiety were significant risk factors of probable clinical insomnia, while college senior degree and 7-8 hours' sleep duration per day was the protective factor for probable clinical insomnia. Unrefreshing sleep was the most prominent sleep problem among college students during COVID-19 remission in China. Good sleep hygiene practices are strongly suggested to develop in the time of prolonged home isolation.
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http://dx.doi.org/10.1016/j.psychres.2021.114153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424256PMC
October 2021

The Impact of Gamification-Induced Users' Feelings on the Continued Use of mHealth Apps: A Structural Equation Model With the Self-Determination Theory Approach.

J Med Internet Res 2021 Aug 12;23(8):e24546. Epub 2021 Aug 12.

Institute of Medical Technology, Health Science Center, Peking University, Beijing, China.

Background: Continued use of mHealth apps can achieve better effects in health management. Gamification is an important factor in promoting users' intention to continue using mHealth apps. Past research has rarely explored the factors underlying the continued use of mobile health (mHealth) apps and gamification's impact mechanism or path on continued use.

Objective: This study aimed to explore the factors influencing mHealth app users' intention to continue using mHealth apps and the impact mechanism and path of users' feelings induced by gamification on continued mHealth app use.

Methods: First, based on the expectation confirmation model of information system continuance, we built a theoretical model for continued use of mHealth apps based on users' feelings toward gamification. We used self-determination theory to analyze gamification's impact on user perceptions and set the resulting feelings (competence, autonomy, and relatedness) as constructs in the model. Second, we used the survey method to validate the research model, and we used partial least squares to analyze the data.

Results: A total of 2988 responses were collected from mHealth app users, and 307 responses were included in the structural equation model after passing the acceptance criteria. The intrinsic motivation for using mHealth apps is significantly affected by autonomy (β=.312; P<.001), competence (β=.346; P<.001), and relatedness (β=.165; P=.004) induced by gamification. The intrinsic motivation for using mHealth apps has a significant impact on satisfaction (β=.311, P<.001) and continuance intention (β=.142; P=.045); furthermore, satisfaction impacts continuance intention significantly (β=.415; P<.001). Confirmation has a significant impact on perceived usefulness (β=.859; P<.001) and satisfaction (β=.391; P<.001), and perceived usefulness has a significant impact on satisfaction (β=.269; P<.001) and continuance intention (β=.273; P=.001). The mediating effect analysis showed that in the impact path of the intrinsic motivation for using the mHealth apps on continuance intention, satisfaction plays a partial mediating role (β=.129; P<.001), with a variance accounted for of 0.466.

Conclusions: This study explored the impact path of users' feelings induced by gamification on the intention of continued mHealth app use. We confirmed that perceived usefulness, confirmation, and satisfaction in the classical continued use theory for nonmedical information systems positively affect continuance intention. We also found that the path and mechanism of users' feelings regarding autonomy, competence, and relatedness generated during interactions with different gamification elements promote the continued use of mHealth apps.
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http://dx.doi.org/10.2196/24546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391751PMC
August 2021

The LncRNA MIR503HG/miR-224-5p/TUSC3 Signaling Cascade Suppresses Gastric Cancer Development Modulating ATF6 Branch of Unfolded Protein Response.

Front Oncol 2021 26;11:708501. Epub 2021 Jul 26.

The Second Affiliated Hospital & College of Nursing, Harbin Medical University, Harbin, China.

Background: Unfolded protein response (UPR)-mediated tumor-promoting functions have been identified in multiple cancers, and this study focused on investigating the role and molecular mechanisms of UPR in modulating gastric cancer (GC) pathogenesis.

Methods: The bioinformatics analysis was performed to examine the expression status of cancer associated genes in patients with stomach adenocarcinoma (STAD) and predict the targeting sites of miR-224-5p with LncRNA MIR503HG and TUSC3. Genes expressions were quantified by Real-Time qPCR, Western Blot and immunohistochemistry (IHC). Cell proliferation, viability, apoptosis and mobility were evaluated by MTT assay, trypan blue staining assay, flow cytometer and transwell assay, respectively. The binding sites were validated by dual-luciferase reporter gene system assay.

Results: LncRNA MIR503HG and TUSC3 were downregulated, but miR-224-5p was upregulated in GC tissues and cells, in contrast with their normal counterparts. Further gain- and loss-of-function experiments validated that the malignant phenotypes in GC cells, including cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis, were negatively regulated by LncRNA MIR503HG. Mechanistically, LncRNA MIR503HG upregulated TUSC3 in GC cells through sponging miR-224-5p, resulting in the repression of GC progression. Finally, we validated that knock-down of ATF6, but not other two branches of UPR (PERK1 and IRE1), partially rescued cell proliferation and EMT in the GC cells with LncRNA MIR503HG overexpression.

Conclusions: Targeting the LncRNA MIR503HG/miR-224-5p/TUSC3 signaling cascade suppressed ATF6-mediated UPR, resulting in the blockage of GC development.
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http://dx.doi.org/10.3389/fonc.2021.708501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352579PMC
July 2021

Enzymatic approaches for profiling cytosine methylation and hydroxymethylation.

Mol Metab 2021 Aug 8:101314. Epub 2021 Aug 8.

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: In mammals, modifications to cytosine bases, particularly in cytosine-guanine (CpG) dinucleotide contexts, play a major role in shaping the epigenome. The canonical epigenetic mark is 5-methylcytosine (5mC), but oxidized versions of 5mC, including 5-hydroxymethylcytosine (5hmC), are now known to be important players in epigenomic dynamics. Understanding the functional role of these modifications in gene regulation, normal development, and pathological conditions requires the ability to localize these modifications in genomic DNA. The classical approach for sequencing cytosine modifications has involved differential deamination via the chemical sodium bisulfite; however, bisulfite is destructive, limiting its utility in important biological or clinical settings where detection of low frequency populations is critical. Additionally, bisulfite fails to resolve 5mC from 5hmC.

Scope Of Review: To summarize how enzymatic rather than chemical approaches can be leveraged to localize and resolve different cytosine modifications in a non-destructive manner.

Major Conclusions: Nature offers a suite of enzymes with biological roles in cytosine modification in organisms spanning from bacteriophages to mammals. These enzymatic activities include methylation by DNA methyltransferases, oxidation of 5mC by TET family enzymes, hypermodification of 5hmC by glucosyltransferases, and the generation of transition mutations from cytosine to uracil by DNA deaminases. Here, we describe how insights into the natural reactivities of these DNA-modifying enzymes can be leveraged to convert them into powerful biotechnological tools. Application of these enzymes in sequencing can be accomplished by relying on their natural activity, exploiting their ability to discriminate between cytosine modification states, reacting them with functionalized substrate analogs to introduce chemical handles, or engineering the DNA-modifying enzymes to take on new reactivities. We describe how these enzymatic reactions have been combined and permuted to localize DNA modifications with high specificity and without the destructive limitations posed by chemical methods for epigenetic sequencing.
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http://dx.doi.org/10.1016/j.molmet.2021.101314DOI Listing
August 2021

A review on reducing indoor particulate matter concentrations from personal-level air filtration intervention under real-world exposure situations.

Indoor Air 2021 Aug 10. Epub 2021 Aug 10.

Department of Occupational and Environmental Health, Peking University School of Public Health, and Peking University Institute of Environmental Medicine, Beijing, China.

Improving air quality in indoor environments where people live is of importance to protect human health. In this systematic review, we assessed the effectiveness of personal-level use of air filtration units in reducing indoor particulate matters (PM) concentrations under real-world situations following systematic review guidelines. A total of 54 articles were included in the review, in which 20 randomized controlled/crossover trials that reported the changes in indoor fine PM (PM ) concentrations were quantitatively assessed in meta-analysis. Standardized mean differences (SMDs) were calculated for changes in indoor PM concentrations following air filtration interventions. Moderate-to-large reductions of 11%-82% in indoor PM  concentrations were observed with SMD of -1.19 (95% CI: -1.50, -0.88). The reductions in indoor PM concentrations varied by geographical locations, filtration technology employed, indoor environmental characteristics, and air pollution sources. Most studies were graded with low-to-moderate risk of bias; however, the overall certainty of evidence for indoor PM concentration reductions was graded at very low level. Considering the effectiveness of indoor air filtration under practical uses, socio-economic disparities across study populations, and costs of air filter replacement over time, our results highlight the importance of reducing air pollution exposure at the sources.
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http://dx.doi.org/10.1111/ina.12922DOI Listing
August 2021

Identifying complex gene-gene interactions: a mixed kernel omnibus testing approach.

Brief Bioinform 2021 Aug 10. Epub 2021 Aug 10.

Department of Statistics and Probability, Michigan State University, East Lansing, MI, USA.

Genes do not function independently; rather, they interact with each other to fulfill their joint tasks. Identification of gene-gene interactions has been critically important in elucidating the molecular mechanisms responsible for the variation of a phenotype. Regression models are commonly used to model the interaction between two genes with a linear product term. The interaction effect of two genes can be linear or nonlinear, depending on the true nature of the data. When nonlinear interactions exist, the linear interaction model may not be able to detect such interactions; hence, it suffers from substantial power loss. While the true interaction mechanism (linear or nonlinear) is generally unknown in practice, it is critical to develop statistical methods that can be flexible to capture the underlying interaction mechanism without assuming a specific model assumption. In this study, we develop a mixed kernel function which combines both linear and Gaussian kernels with different weights to capture the linear or nonlinear interaction of two genes. Instead of optimizing the weight function, we propose a grid search strategy and use a Cauchy transformation of the P-values obtained under different weights to aggregate the P-values. We further extend the two-gene interaction model to a high-dimensional setup using a de-biased LASSO algorithm. Extensive simulation studies are conducted to verify the performance of the proposed method. Application to two case studies further demonstrates the utility of the model. Our method provides a flexible and computationally efficient tool for disentangling complex gene-gene interactions associated with complex traits.
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http://dx.doi.org/10.1093/bib/bbab305DOI Listing
August 2021

Evaluation of the clinical efficacy of nasal surgery in the treatment of obstructive sleep apnoea.

Am J Otolaryngol 2021 Jul 30;43(1):103158. Epub 2021 Jul 30.

Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China. Electronic address:

Study Objectives: The aim of the study was to evaluate the clinical efficacy of nasal surgery in the treatment of obstructive sleep apnoea (OSA) by comparing the improvement of subjective symptoms and objective metrics before surgery and after 6 months of surgery.

Methods: Patients with the main complaint of nasal congestion combined with habitual snoring who were hospitalized and treated were selected. Patients underwent subjective symptom tests and objective indicator monitoring both before surgery and 6 months after surgery. Comparisons between groups were performed using the independent samples t-test.

Results: Subjective scale evaluations demonstrated that nasal congestion, daytime sleepiness, snoring, nose-related symptoms, and sleep symptoms in patients with simple snoring or with OSA were improved after nasal surgery. Additionally, vitality was improved in all groups except for the patients with simple snoring and emotional consequence was improved in patients with simple snoring and mild OSA. Objective evaluations indicated the apnoea-hypopnoea index (AHI), the thickness of the soft palate, and the maximum cross-sectional area of the sagittal plane of the soft palate decreased after surgery in patients with mild OSA. The lowest blood oxygen concentration (LSaO) and anteroposterior diameter of the soft palate increased after surgery in patients with mild OSA. The arousal index also significantly decreased in patients with mild and moderate OSA. The nasal cavity volumes (NCVs) and the nasal minimal cross-sectional areas (NMCAs) of all groups showed significant differences after surgery.

Conclusions: Nasal surgery can effectively improve nose and sleep symptoms in patients with simple snoring or with OSA. It can significantly reduce the nasal resistance and increase the ventilation volume.

Statement Of Significance: Obstructive sleep apnoea (OSA) is becoming a global health problem. OSA is associated with several coexisting conditions, reduced health-related quality of life, and impaired work productivity. This study performed nasal surgery on OSA patients with the main complaint of nasal congestion combined with snoring and patients with simple snoring to compare the improvement of subjective symptoms and objective metrics before and after surgery. We found that: (1) symptoms such as nasal congestion, daytime sleepiness or snoring were improved after nasal surgery; (2) the apnoea-hypopnoea index (AHI) and arousal index decreased after surgery in patients with OSA; (3) the nasal and oropharyngeal cavity volumes increased after surgery. These findings suggest that patients with OSA or with simple snoring could benefit from nasal surgery.
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http://dx.doi.org/10.1016/j.amjoto.2021.103158DOI Listing
July 2021

Effect of ultrasound on the preparation of soy protein isolate-maltodextrin embedded hemp seed oil microcapsules and the establishment of oxidation kinetics models.

Ultrason Sonochem 2021 Sep 30;77:105700. Epub 2021 Jul 30.

School of Computer and Information Engineering, Harbin University of Commerce, Harbin 150028, China.

In this study, microcapsules were prepared by spray drying and embedding hemp seed oil (HSO) with soy protein isolate (SPI) and maltodextrin (MD) as wall materials. The effect of ultrasonic power on the microstructure and characteristics of the composite emulsion and microcapsules was studied. Studies have shown that ultrasonic power has a significant impact on the stability of composite emulsions. The particle size of the composite emulsion after 450 W ultrasonic treatment was significantly lower than the particle size of the emulsion without the ultrasonic treatment. Through fluorescence microscopy observation, HSO was found to be successfully embedded in the wall materials to form an oil/water (O/W) composite emulsion. The spray-dried microcapsules showed a smooth spherical structure through scanning electron microscopy (SEM), and the particle size was 10.7 μm at 450 W. Fourier transform infrared (FTIR) spectroscopy analysis found that ultrasonic treatment would increase the degree of covalent bonding of the SPI-MD complex to a certain extent, thereby improving the stability and embedding effect of the microcapsules. Finally, oxidation kinetics models of HSO and HSO microcapsules were constructed and verified. The zero-order model of HSO microcapsules was found to have a higher degree of fit; after verification, the model can better reflect the quality changes of HSO microcapsules during storage.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350418PMC
September 2021

Modified microcoil for preoperative localization of solitary pulmonary nodules: a prospective, single-arm, multicenter clinical study.

J Vasc Interv Radiol 2021 Aug 2. Epub 2021 Aug 2.

Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, China. Electronic address:

Purpose: To evaluate the efficacy and safety of placement of a modified microcoil for precise preoperative localization of solitary pulmonary nodules (SPNs) before video-assisted thoracoscopic surgery(VATS).

Materials And Methods: This prospective single-arm multicenter study included patients who underwent computed tomography (CT)-guided modified microcoil insertion prior to SPN resection by VATS between January 2018 and June 2018. The patient demographics, nodule characteristics and histopathologic findings were recorded. The primary endpoints included efficacy and safety.

Results: A total of 96 patients (41 males and 55 females; mean age: 59.3 ± 8.9 years) with 96 SPNs were eligible for enrolment in the study. The mean maximal transverse diameter of the nodules was 10.3 ± 5.2 mm (range: 8-20 mm). The mean time between CT-guided microcoil insertion and the start of the surgical procedure was 14.6 hours (range: 12-24 hours). The duration of the preoperative CT-guided microcoil localization procedure was 29 ± 9 minutes (range: 10-35 minutes), and the intraoperative fluoroscopy time was 0.7 ± 0.7 minutes (range: 0.5-3 minutes). The clinical success rate was 96.9%(93/96), and all nodules were successfully resected using VATS. One patient experienced asymptomatic pneumothorax, but there were no cases of pulmonary hemorrhage.

Conclusions: SPN localization with the modified microcoil is feasible and safe. The modified microcoil can facilitate the thoracoscopic resection of SPNs.
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http://dx.doi.org/10.1016/j.jvir.2021.06.026DOI Listing
August 2021

Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway.

Evid Based Complement Alternat Med 2021 26;2021:8168657. Epub 2021 Apr 26.

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF- receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.
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http://dx.doi.org/10.1155/2021/8168657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298142PMC
April 2021

study of the drug-drug interaction potential of cetagliptin and clinical study of pharmacokinetic interaction of cetagliptin and metformin in healthy volunteers.

Xenobiotica 2021 Aug 11:1-10. Epub 2021 Aug 11.

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China.

Cetagliptin is an oral, potent, and newly developed selective inhibitor of dipeptidyl peptidase-4 (DPP-4). We evaluated the drug-drug interaction (DDI) potential of cetagliptin, as well as the pharmacokinetics of cetagliptin and metformin and the interaction between cetagliptin and metformin.Cetagliptin did not inhibit CYP1A2, CYP2C8, CYP2B6, CYP2C9, CYP2C19, and CYP3A4, only has a moderate inhibitory effect on CYP2D6, and did not induce CYP1A2, CYP2B6, and CYP3A4. Plasma protein binding of cetagliptin didn't have species differences or concentration dependence. Cetagliptin was a substrate for P-glycoprotein (P-gp).The 34 healthy subjects enrolled were randomly divided into two sequences (A and B) with 17 subjects in each sequence. Coadministration with metformin had no effect on cetagliptin AUC (GMR, 99.25%; 90% CI, 95.96%-102.65%). There was a slightly increase in cetagliptin (GMR, 117.33%; 90% CI, 102.54%-134.25%). Coadministration with cetagliptin did not affect the metformin's AUC (GMR, 108.54%; 90% CI, 101.41%-116.17%) or (GMR, 97.67%; 90% CI, 90.96%-104.89%).Based on study results, cetagliptin is unlikely to cause CYP-mediated, clinically relevant DDI. Although the possibility of transporter-mediated, clinically relevant DDI cannot be ruled out, there is little or no risk of side effects. Coadministration of cetagliptin and metformin had no clinically meaningful effect on the pharmacokinetics of each drug. There was no drug-drug interaction between cetagliptin and metformin. Both monotherapies and combination therapy were well tolerated. No serious AEs and hypoglycaemia was reported.
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http://dx.doi.org/10.1080/00498254.2021.1963010DOI Listing
August 2021

Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues.

Nat Mater 2021 Jul 29. Epub 2021 Jul 29.

Chemistry Life Processes Institute, Northwestern University, Evanston, IL, USA.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.
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http://dx.doi.org/10.1038/s41563-021-01051-xDOI Listing
July 2021

Removal of organic pollutants from aqueous solution using metal organic frameworks (MOFs)-based adsorbents: A review.

Chemosphere 2021 Jun 29;284:131393. Epub 2021 Jun 29.

State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, No. 130 Meilong Road, Shanghai, 200237, China; National Engineering Laboratory for Industrial Wastewater Treatment, East China University of Science and Technology, No. 130 Meilong Road, Shanghai, 200237, China. Electronic address:

The development of metal organic frameworks (MOFs) has recently drawn a lot of scientific interest in water treatment due to the unique properties such as tunable porosities, large pore volumes, hierarchical structures, excellent adsorption and regeneration performances. MOFs represent an eco-friendly alternative to conventional adsorbents especially for the adsorptive removal of noxious organic pollutants from aqueous solution. Advanced MOFs' performances are justified by the introduction of functional groups, magnetic moieties, and specific foreign materials onto MOFs. This however leads to increase in the manufacturing costs of MOFs and consequently possess a huge challenge in large-scale applications. This review hence critically discusses the recent progresses in the development of MOFs-based adsorbents for the removal of selected organic pollutants (e.g., dyes, antibiotics and pesticides) from aqueous solution. Furthermore, major interaction mechanisms between MOFs and organic pollutants in response to numerous experimental conditions, such as pH, temperature, coexisting ions are put forward. Finally, some recommendations in support for designing MOFs with improved adsorption performances are also highlighted.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131393DOI Listing
June 2021
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