Publications by authors named "Wei Zhao"

4,334 Publications

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Preventive Effect of Collagen Peptides from on Acute Kidney Injury through Attenuation of Oxidative Stress and Inflammation.

Oxid Med Cell Longev 2022 10;2022:8186838. Epub 2022 May 10.

Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.

The protective effect of collagen peptide from (Amp) on acute kidney injury (AKI) in mice and its mechanism were explored. The results showed that Amp-fed could effectively improve the renal mass index and histopathological morphology. The levels of serum creatinine and urea nitrogen decreased significantly, while the antioxidant enzyme catalase (CAT) and superoxide dismutase (SOD) increased significantly in Amp-fed groups. Western blot results disclosed that Amp significantly upregulates the levels of heme oxygenase-1 (HO-1), Nrf2, p-PI3K, and p-AKT in the kidney. In addition, Amp could significantly downregulate the levels of nuclear factor NF-kappa-B (NF-B), tumor necrosis factor (TNF-), inflammatory cytokines interleukin 6 (IL-6) and interleukin 1 (IL-1). These findings provide evidence that Amp plays a protective role in AKI via attenuation of oxidative stress and inflammation mediated by PI3K/AKT/Nrf2 and PI3K/AKT/NF-B pathways. This study laid a foundation for the application of Amp in the prevention of AKI.
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http://dx.doi.org/10.1155/2022/8186838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113864PMC
May 2022

Charge Accumulation in the Homo-Crosslinked-Polyethylene Bilayer.

Materials (Basel) 2022 Apr 21;15(9). Epub 2022 Apr 21.

State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an 710049, China.

The homo-crosslinked-polyethylene (H-XLPE) bilayer simplifies the returned insulation structure of the factory joint in submarine cables, and its dielectric property is key to the reliability of the power transmission system. In this paper, we investigated the charge accumulation phenomenon in a secondary thermocompression H-XLPE bilayer using the pulse electro-acoustic method. The charge accumulation reduces its overall breakdown strength when compared with XLPE. According to X-ray diffraction measurement and thermal analysis results, the specimen forms a homo-junction region between the bilayers, which has overlapping spherulites with a thick lamella, high crystallinity, and high surface free energy. The charge accumulation can be ascribed to fused lamellas and the crystal imperfection of the homo-junction region, which restricts the charge transport process and exhibits a higher number of deep traps. This study emphasizes the importance of the homo-junction region in the H-XLPE bilayer, which should be considered in the design and operation of factory joint insulation.
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http://dx.doi.org/10.3390/ma15093024DOI Listing
April 2022

Polystyrene microplastic exposure induces insulin resistance in mice via dysbacteriosis and pro-inflammation.

Sci Total Environ 2022 May 16:155937. Epub 2022 May 16.

Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Institute of Clinical Pharmacy, Beijing 100050, China; Beijing Key Laboratory for Evaluation of Rational Drug Use, Beijing 100038, China. Electronic address:

Microplastics (MPs) as emerging contaminants have become a global environmental problem. However, studies on the effects of MPs on metabolic diseases remain limited. Here, we evaluated the effects of polystyrene (PS), one of the most prominent types of MPs, on insulin sensitivity in mice fed with normal chow diet (NCD) or high-fat diet (HFD), and explained the underlying mechanisms. Mice fed with NCD or HFD both showed insulin resistance (IR) after PS exposure accompanied by increased plasma lipopolysaccharide and pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β. Exposure to PS also resulted in a significant decrease in the richness and diversity of gut microbiota, particularly an increase in the relative abundance of Gram-negative bacteria such as Prevotellaceae and Enterobacteriaceae. Additionally, PS with a small particle size (5 μm) accumulated in the liver, kidneys and blood vessels of mice. Further analyses showed inhibition of the insulin signaling pathway in the liver of PS exposed mice, such as inhibition of IRS1 and decreased expression of PI3K. Hence, the mechanism of PS exposure to induce IR in mice might be mediated through regulating gut microbiota and PS accumulation in tissues, stimulating inflammation and inhibiting the insulin signaling pathway. In conclusion, PS might be a potential environmental contaminant that causes metabolic diseases associated with IR.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155937DOI Listing
May 2022

Aerial-aquatic robots capable of crossing the air-water boundary and hitchhiking on surfaces.

Sci Robot 2022 May 18;7(66):eabm6695. Epub 2022 May 18.

School of Mechanical Engineering and Automation, Beihang University, Beijing, China.

Many real-world applications for robots-such as long-term aerial and underwater observation, cross-medium operations, and marine life surveys-require robots with the ability to move between the air-water boundary. Here, we describe an aerial-aquatic hitchhiking robot that is self-contained for flying, swimming, and attaching to surfaces in both air and water and that can seamlessly move between the two. We describe this robot's redundant, hydrostatically enhanced hitchhiking device, inspired by the morphology of a remora () disc, which works in both air and water. As with the biological remora disc, this device has separate lamellar compartments for redundant sealing, which enables the robot to achieve adhesion and hitchhike with only partial disc attachment. The self-contained, rotor-based aerial-aquatic robot, which has passively morphing propellers that unfold in the air and fold underwater, can cross the air-water boundary in 0.35 second. The robot can perform rapid attachment and detachment on challenging surfaces both in air and under water, including curved, rough, incomplete, and biofouling surfaces, and achieve long-duration adhesion with minimal oscillation. We also show that the robot can attach to and hitchhike on moving surfaces. In field tests, we show that the robot can record video in both media and move objects across the air/water boundary in a mountain stream and the ocean. We envision that this study can pave the way for future robots with autonomous biological detection, monitoring, and tracking capabilities in a wide variety of aerial-aquatic environments.
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http://dx.doi.org/10.1126/scirobotics.abm6695DOI Listing
May 2022

Studying bona fide SARS-CoV-2 biology in a BSL-2 biosafety environment using a split-virus-genome system.

Sci China Life Sci 2022 May 12. Epub 2022 May 12.

Faculty of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

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http://dx.doi.org/10.1007/s11427-022-2114-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116080PMC
May 2022

(+)- and (-)-Xanthostones A-D: Four Pairs of Enantiomeric Cinnamoyl-β-triketone Derivatives from Xanthostemon chrysanthus.

Chem Biodivers 2022 May 17. Epub 2022 May 17.

Jinan University, College of Pharmacy, 601 Weat Huangpu Avenue, 510610, Guangzhou, CHINA.

Four pairs of cinnamoyl- β -triketone derivative enantiomers, (+)- and (-)-xanthostones A-D ((+)- and (-)- 1 - 4 ), were isolated from Xanthostemon chrysanthus . Compounds 1 and 2 feature a new rearranged cinnamoyl-phloroglucinol scaffold fused with a cinnamyl- β -triketone framework. Compounds 1 , 3 , and 4 are the first examples of natural products with a peculiar phenethyl-pyranone acid unit. Their structures with absolute configurations were determined by spectroscopic data, X-ray diffraction analysis and electronic circular dichroism (ECD) calculation. Interestingly, these novel compounds showed a tautomeric behaviour in solution, which was revealed by NMR spectroscopy and density functional theory calculation. A plausible biosynthetic pathway toward xanthostones A-D was proposed. Additionally, the anti-inflammatory and antibacterial activities of xanthostones A-D were evaluated.
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http://dx.doi.org/10.1002/cbdv.202200356DOI Listing
May 2022

Effect of lncRNA MALAT1 on the Granulosa Cell Proliferation and Pregnancy Outcome in Patients With PCOS.

Front Endocrinol (Lausanne) 2022 27;13:825431. Epub 2022 Apr 27.

Key Laboratory of Reproductive Genetics, Ministry of Education, Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Follicle arrest is one of the main characteristics of polycystic ovary syndrome (PCOS), the most common endocrinological disorder in reproductive-aged women. Increasing evidence proves that high anti-Mullerian hormone (AMH) levels may play an important role in follicular development. Long noncoding RNA (lncRNA) with a length of more than 200 nt is widely involved in the directional differentiation, growth, and development of cells, whereas whether lncRNA is involved in AMH's role in follicular development is unknown. In this study, we analyzed lncRNA expression in ovarian granulosa cells (GCs) collected from women with and without PCOS high-throughput sequencing. The results showed that a total of 79 noncoding transcripts were differently expressed in GCs of PCOS patients, including upregulated lncRNA MALAT1. The upregulation of MALAT1 was further confirmed by RT-qPCR in GCs from a larger cohort of PCOS patients. Furthermore, knockdown MALAT1 can promote the proliferation of KGN cell . These data suggested a role for MALAT1 in the development of PCOS. Meanwhile, MALAT1 and phosphorylated SMAD 1/5 (Ser463/465) protein were upregulated in KGN cells after exogenous AMH stimulation, which identified AMH perhaps as a regulator for the expression of MALAT1. We also found that MALAT1 can predict clinical pregnancy outcome to a certain extent by ROC curve analysis (area: 0.771,  = 0.007, 95% CI: 0.617-0.925, sensitivity: 57.1%, specificity: 91.7%). Thus, our findings revealed a role of lncRNA MALAT1 in inhibiting granulosa cell proliferation and may be correlated with pregnancy outcome in PCOS.
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http://dx.doi.org/10.3389/fendo.2022.825431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094420PMC
May 2022

Real-time dynamic simulation for highly accurate spatiotemporal brain deformation from impact.

Comput Methods Appl Mech Eng 2022 May 9;394. Epub 2022 Apr 9.

Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, United States of America.

Real-time dynamic simulation remains a significant challenge for spatiotemporal data of high dimension and resolution. In this study, we establish a transformer neural network (TNN) originally developed for natural language processing and a separate convolutional neural network (CNN) to estimate five-dimensional (5D) spatiotemporal brain-skull relative displacement resulting from impact (isotropic spatial resolution of 4 mm with temporal resolution of 1 ms). Sequential training is applied to train (N = 5184 samples) the two neural networks for estimating the complete 5D displacement across a temporal duration of 60 ms. We find that TNN slightly but consistently outperforms CNN in accuracy for both displacement and the resulting voxel-wise four-dimensional (4D) maximum principal strain (e.g., root mean squared error (RMSE) of ~1.0% vs. ~1.6%, with coefficient of determination, >0.99 vs. >0.98, respectively, and normalized RMSE (NRMSE) at peak displacement of 2%-3%, based on an independent testing dataset; N = 314). Their accuracies are similar for a range of real-world impacts drawn from various published sources (dummy, helmet, football, soccer, and car crash; average RMSE/NRMSE of ~0.3 mm/~4%-5% and average of ~0.98 at peak displacement). Sequential training is effective for allowing instantaneous estimation of 5D displacement with high accuracy, although TNN poses a heavier computational burden in training. This work enables efficient characterization of the intrinsically dynamic brain strain in impact critical for downstream multiscale axonal injury model simulation. This is also the first application of TNN in biomechanics, which offers important insight into how real-time dynamic simulations can be achieved across diverse engineering fields.
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http://dx.doi.org/10.1016/j.cma.2022.114913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097909PMC
May 2022

Separation of Sulfate Anion From Aqueous Solution Governed by Recognition Chemistry: A Minireview.

Front Chem 2022 29;10:905563. Epub 2022 Apr 29.

Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China.

The sulfate anion (SO ) is known as an end metabolite of cysteine and methionine, and its proper concentration is associated with the expression of key functions in the physiological system. Thus, maintaining sulfate concentration at a precise level is of great significance for biology, environments, and industrial productions. Fundamental research for sulfate anion chemistry can help understand sulfate-associated physiological processes and related applications, for example, remediation. In this minireview, we summarized recent research progresses in sulfate recognition and separation using crystallization and liquid-liquid extraction. We focused on the studies wherein molecular recognition is the key element and is considered the driving force for selective sulfate separations from aqueous solution.
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http://dx.doi.org/10.3389/fchem.2022.905563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099046PMC
April 2022

Single particle plasmonic and electrochemical dual mode detection of amantadine.

Anal Chim Acta 2022 May 19;1209:339838. Epub 2022 Apr 19.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China. Electronic address:

Herein, a facile and sensitive dual mode sensing strategy for amantadine (AMD) level evaluation by coupling the plasmonic Au nanorod (NR) and supramolecular SH-cyclodextrin (CD) through strong Au-S bond is proposed. Methylene blue (MB) molecules can be inserted into the cavity of CD molecules through the hydrophobic interaction, which would cause the plasmon resonance energy transfer (PRET) process as well as electrochemical signal response due to the spectrum overlap between Au NR and MB molecules and the electrochemical conversion activity of MB molecules. Subsequently, AMD would induce the replacement of MB molecules because of the stronger interaction with CD, resulting the recovery of scattering intensity of Au NR and decrease of the electrooxidation current of MB. On one hand, the increase of Au NR scattering intensity is linearly proportional to AMD with the concentration from 0.4 to 3.0 μM, and reaches a limit of detection (LOD) of 0.28 μM. On the other hand, electrochemical measurement method enlarged the detection range of AMD. The variation of electrochemical oxidation peak current of MB is linearly proportional to the logarithm value of AMD concentration from 2.5 to 375.0 μM, with LOD of 1.9 μM. Subsequently, the proposed dual mode response sensing strategy was successfully employed for the detection of AMD in human serum samples with great selectivity and sensitivity, with a recovery percentage ranged from 92.6 to 112.0%. Overall, this Au [email protected] nanoparticle based single particle plasmonic and electrochemical dual mode sensing method provides great potential in the field of clinical drug detection or metabolic process investigation in the future.
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http://dx.doi.org/10.1016/j.aca.2022.339838DOI Listing
May 2022

Effects of NRF-1 and PGC-1α cooperation on HIF-1α and rat cardiomyocyte apoptosis under hypoxia.

Gene 2022 May 12:146565. Epub 2022 May 12.

School of Basic Medicine, Ningxia Medical University, 1160 Shengli South Street, Xingqing District, Yinchuan City, Ningxia Hui Autonomous Region, China. Electronic address:

Background: Hypoxia is a primary inducer of cardiomyocyte injury, its significant marker being hypoxia-induced cardiomyocyte apoptosis. Nuclear respiratory factor-1 (NRF-1) and hypoxia-inducible factor-1α (HIF-1α) are transcriptional regulatory elements implicated in multiple biological functions, including oxidative stress response. However, their roles in hypoxia-induced cardiomyocyte apoptosis remain unknown. The effect HIF-α, together with NRF-1, exerts on cardiomyocyte apoptosis also remains unclear.

Methods: We established a myocardial hypoxia model and investigated the effects of these proteins on the proliferation and apoptosis of rat cardiomyocytes (H9C2) under hypoxia. Further, we examined the association between NRF-1 and HIF-1α to improve the current understanding of NRF-1 anti-apoptotic mechanisms.

Results: The results show that NRF-1 and HIF-1α are important anti-apoptotic molecules in H9C2 cells under hypoxia, although their regulatory mechanisms differ. NRF-1 could bind to the promoter region of Hif1a and negatively regulate its expression. Additionally, HIF-1β exhibited competitive binding with NRF-1 and HIF-1α, demonstrating a synergism between NRF-1 and the peroxisome proliferator-activated receptor-gamma coactivator-1α.

Conclusion: These results indicate that cardiomyocytes can regulate different molecular patterns to tolerate hypoxia, providing a novel methodological framework for studying cardiomyocyte apoptosis under hypoxia.
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http://dx.doi.org/10.1016/j.gene.2022.146565DOI Listing
May 2022

Comparison of machine learning approaches for radioisotope identification using NaI(TI) gamma-ray spectrum.

Appl Radiat Isot 2022 Apr 14;186:110212. Epub 2022 Apr 14.

State Key Laboratory of NBC Protection for Civilian, Beijing, China. Electronic address:

This research aims at comparing the performance of different machine learning algorithms used for NaI(TI) gamma-ray detector based radioisotope identification. Six machine learning algorithms were implemented, including support vector machine (SVM), k-nearest neighbor (KNN), logistic regression (LR), naive Bayes (NB), decision tree (DT), and multilayer perceptron (MLP). The hyper-parameters of each model were elaborately optimized. The effects of data size, statistical fluctuation, and spectrum drift were considered. Results show that for smaller data size (5 types of radioisotopes and 6000 spectra), the support vector machine and the logistic regression classifier exhibit higher identification accuracy with less training/predicting time. Whereas for larger data size (14 types of radioisotopes corresponding to the standard IEC 62327-2017), the multilayer perceptron showed highest accuracy but required the longest time for model training. The naive Bayes classifier and the decision tree were prone to make mistakes when fluctuations and distortions were added to the spectra. The k-nearest neighbor classifier, though showing high accuracy for most data sets, consumed the longest time while making prediction.
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http://dx.doi.org/10.1016/j.apradiso.2022.110212DOI Listing
April 2022

Embryo morphological quality in relation to the metabolic and cognitive development of singletons conceived by in vitro fertilization/intracytoplasmic sperm injection: A matched cohort study.

Am J Obstet Gynecol 2022 May 11. Epub 2022 May 11.

Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Birth Defect Control and Prevention Research Center of Zhejiang Province, Hangzhou, Zhejiang, China; International Science and Technology Cooperation Base of Reproductive Health of Zhejiang Province, Hangzhou, Zhejiang, China.

Background: Embryos with higher morphological quality may have a greater potential to achieve clinical pregnancy leading to live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of offspring.

Objective: This pilot study aimed to examine the associations between embryo morphological quality and the physical, metabolic and cognitive development of singletons conceived by in vitro fertilization/intracytoplasmic sperm injection at their pre-school age.

Study Design: This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of Women's Hospital, School of Medicine, Zhejiang University. A total of 144 4- to 6-year-old children participated in the follow-up assessment from 2020-2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched to singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children's age (±1 year). We measured offspring's height, weight, body mass index, blood pressure, thyroid hormone levels and metabolic indicators. Neurodevelopmental assessments using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition and Adaptive Behavior Assessment System, Second Edition were performed. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphological quality and offspring health outcomes.

Results: A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function and metabolic indicators were comparable in the two groups. After adjustment for potential risk factors by linear regression Model 1 and Model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than did good-quality embryo offspring (beta: 0.22, 95% confidence interval: 0.09 to 0.90; beta: 0.22, 95% confidence interval: 0.09 to 0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessment, there was no difference in the full-scale intelligence quotient of the Wechsler Preschool and Primary Scale of Intelligence (109.96 ± 12.42 versus 109.60 ± 14.46, P = 0.88) or the general adaptive index of the Adaptive Behavior Assessment System (108.26 ± 11.70 versus 108.08 ± 13.44, P = 0.94) between the two groups. The subindices of the two tests were also comparable. These findings remained after linear regression analysis.

Conclusion: At 4-6 years of age, singletons born from poor-quality embryo transfer have comparable metabolic and cognitive development to those born from good-quality embryo transfer using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and result in live birth are likely to have developmental potential comparable to that of good-quality embryos.
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http://dx.doi.org/10.1016/j.ajog.2022.05.019DOI Listing
May 2022

Inherent Flame-Retardant, Humid Environment Stable and Blue Luminescent Polyamide Elastomer Regulated by Siloxane Moiety.

Polymers (Basel) 2022 May 9;14(9). Epub 2022 May 9.

Henan Key Laboratory of Advanced Nylon Materials and Application, School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China.

The rapid development of the polymeric materials market has created an urgent demand for the thermoplastic polyamide elastomer (TPAE) owing to its greater functionality, and ability to be synthesized via a facile and industrial route. In this work, a series of novel silicone-containing polyamides (PA1212/Si12) were successfully synthesized from 1,12-dodecarboxylic acid (LA), 1,12-dodecarbondiamine (DMDA), and 1,3-bis (amino-propyl) tetramethyldisiloxane (BATS), via a one-pot melt polycondensation method in the absence of a catalyst. FTIR, H-NMR, GPC and inherent viscosity results cohesively prove that the polymerization of monomers was well conducted, and the chemical structure was in high accordance with the design. As expected, the Si12 unit-content of the copolymers regulate the properties of the series. As the feeding ratio of BATS in the diamines increases from 5 mol% to 40 mol%, the thermal transition temperatures, and , decline steadily before finally stabilizing at ~6 °C and 160 °C, respectively, indicating that the co-polyamides possess improved chain flexibility but restricted crystallization ability. The conspicuous evolution in crystalline morphology of the series was observed by XRD and AFM. The increased PA Si12 phase induces the crystallized PA 1212 phase to transit from a thermally-favorable large and rigid crystal structure (α phase) to a kinetically-favorable small and ductile crystal structure (γ phase). Reflected in their stress-strain behavior, PA1212/Si12 copolymers are successfully tailored from rigid plastic to ductile elastomer. The tensile strength mildly drops from above 40 MPa to ~30 MPa while the reversible elongation increases from ~50% to approximately 350%. Accordingly, the moderate surface tension differences in the monomers facilitate the efficient conduction of the co-polymerization process, and the distributed short siloxane unit in the backbone fulfills the copolymer with desirable elasticity. Interestingly, the novel silicone-containing polyamides also display Si12 unit-content dependent flame retardancy, humidity stability, and unconventional solid-state fluorescence properties. The elastomers exhibit a low bibulous rate and anti-fouling characteristics to dye droplets and mud contamination, pass the V-1 rating (UL 94) with a constantly declining PHRR value, and emit blue luminescence under a 365 nm light source. Herein, we propose a new facile strategy for developing a high-performance and multifunctional silicone-modified polyamide, which bears promising industrialization potential. In addition, this first reported silicone-containing thermoplastic polyamide elastomer, which is self-extinguishing, anti-fouling and blue-luminescent, will further broaden the application potential of thermoplastic polyamide elastomers.
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http://dx.doi.org/10.3390/polym14091919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104639PMC
May 2022

Long-term outcomes of patients with conjunctival extranodal marginal zone lymphoma.

Am J Hematol 2022 May 12. Epub 2022 May 12.

Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida, USA.

Comprehensive information on clinical features and long-term outcomes of primary conjunctival extranodal marginal zone lymphoma (PCEMZL) is scarce. We present a large single-institution retrospective study of 72 patients. The median age was 64 years, and 63.9% were female. Stage I was present in 87.5%. Radiation therapy (RT) alone was the most common treatment (70.8%). Complete response (CR) was 87.5%, and 100% in RT-treated patients. With a median follow-up of 6.7 years, relapse/progression and death occurred in 19.4% each, with one relapse within the RT field. The 10-year progression-free survival (PFS) and overall survival (OS) were 68.4% (95% CI 52.8%-79.8%) and 89.4% (95% CI 77.4%-95.2%), respectively. The 10-year rate for time to progression from diagnosis was 22.5% (95% CI 11.6%-35.7%). The 10-year PFS and OS of MALT-IPI 0 versus 1-2 were 83.3% versus 51.3%, (p = .022) and 97.6% versus 76.6%, (p = .0052), respectively. The following characteristics were associated with shorter survival: age > 60 years (PFS: HR = 2.93, 95% CI 1.08-7.95; p = .035, OS: HR = 9.07, 95% CI 1.17-70.26; p = .035) and MALT-IPI 1-2 (PFS: HR = 2.67, 95% CI 1.12-6.31; p = .027, OS: HR = 6.64, 95% CI 1.45-30.37; p = .015). CR following frontline therapy was associated with longer PFS (HR = 0.13, 95% CI 0.04-0.45; p = .001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR = 0.34, 95% CI 0.12-0.96 p = .041 and SHR = 0.11, 95% CI 0.03-0.36; p < .001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure.
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http://dx.doi.org/10.1002/ajh.26591DOI Listing
May 2022

Effects of Low-Concentration Graphene Oxide Quantum Dots on Improving the Proliferation and Differentiation Ability of Bone Marrow Mesenchymal Stem Cells through the Wnt/β-Catenin Signaling Pathway.

ACS Omega 2022 Apr 18;7(16):13546-13556. Epub 2022 Apr 18.

Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, P. R. China.

Graphene oxide quantum dots (GOQDs) are considered to be a new method for regulating the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). However, there are few reports on such regulation with different concentrations of GOQDs, and the molecular mechanism has not been fully elucidated. The purposes of this study were, first, to explore the effects of GOQDs on the proliferation and differentiation of BMSCs and , and, second, to provide a theoretical basis for the repair of bone defects. Live/Dead staining, EdU staining, immunofluorescence staining, alkaline phosphatase (ALP), western blotting, and qT-PCR were used for detecting the proliferation and differentiation of BMSCs after coculture with GOQDs of different concentrations. Hematoxylin and eosin (HE) staining and Van Gieson (VG) staining were used to detect new bone regeneration . The results showed that low-concentration GOQDs (0.1 and 1 μg/mL) promoted the proliferation and differentiation of BMSCs. Compared with the 1 μg/mL GOQD group, the 0.1 μg/mL GOQD group had better ability to promote the proliferation and differentiation of BMSCs. HE and VG staining results showed the greatest proportion of new bone area on sandblasted, large-grit, and acid-etched (SLA)/GOQD scaffolds. Furthermore, the ratio of active β-catenin and the phosphorylation level of GSK-3β (p-GSK-3β) increased after BMSCs treatment with 0.1 μg/mL GOQDs. Low concentrations of GOQDs improved the osteogenic differentiation ability of BMSCs by activating the Wnt/β-catenin signaling pathway.
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http://dx.doi.org/10.1021/acsomega.1c06892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088760PMC
April 2022

Development and Validation of a Prediction Model for Cardiovascular Events in Exercise Assessment of Coronary Heart Disease Patients After Percutaneous Coronary Intervention.

Front Cardiovasc Med 2022 26;9:798446. Epub 2022 Apr 26.

Department of Cardiology, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.

Objective: This study aimed to develop a model for predicting cardiovascular events in the exercise assessment of patients with coronary heart disease after percutaneous coronary intervention (PCI) based on multidimensional clinical information.

Methods: A total of 2,455 post-PCI patients who underwent cardiopulmonary exercise testing (CPET) at the Peking University Third Hospital from January 2016 to September 2019 were retrospectively included in this study; 1,449 post-PCI patients from January 2018 to September 2019 were assigned as the development cohort; and 1,006 post-PCI patients from January 2016 to December 2017 were assigned as the validation cohort. Clinical data of patients before testing and various indicators in the exercise assessment were collected. CPET-related cardiovascular events were also collected, including new-onset angina pectoris, frequent premature ventricular contractions, ventricular tachycardia, atrial tachycardia, and bundle branch block during the examination. A nomogram model for predicting CPET-related cardiovascular events was further developed and validated.

Results: In the development cohort, the mean age of 1,449 post-PCI patients was 60.7 ± 10.1 years. CPET-related cardiovascular events occurred in 43 cases (2.9%) without fatal events. CPET-related cardiovascular events were independently associated with age, glycosylated hemoglobin, systolic velocity of mitral annulus, ΔVO/ΔWR slope inflection, and VE/VCO slope > 30. The C-index of the nomogram model for predicting CPET-related cardiovascular events was 0.830, and the area under the ROC curve was 0.830 (95% CI: 0.764-0.896). For the validation cohort of 1,006 patients, the area under the ROC curve was 0.807 (95% CI: 0.737-0.877).

Conclusion: Post-PCI patients with older age, unsatisfactory blood glucose control, impaired left ventricular systolic function, oxygen uptake parameter trajectory inflection, and poor ventilation efficiency have a higher risk of cardiovascular events in exercise assessment. The nomogram prediction model performs well in predicting cardiovascular events in the exercise assessment of post-PCI patients and can provide an individualized plan for exercise risk prediction.
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http://dx.doi.org/10.3389/fcvm.2022.798446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086511PMC
April 2022

A Newly Isolated Strain of GXU-A23 Improves the Growth Performance, Antioxidant and Anti-Inflammatory Status, Metabolic Capacity and Mid-intestine Morphology of Juvenile .

Front Physiol 2022 25;13:882091. Epub 2022 Apr 25.

College of Life Sciences, Sun Yat-sen University, Guangzhou, China.

can be used as a green additive in aquafeeds due to it contains rich astaxanthin and polyunsaturated fatty acid. In the present study, a newly strain of GXU-A23 with high concentration of astaxanthin was firstly isolated by a newly culture strategy in our laboratory. In addition, GXU-A23 was applied in the feed for determining whether it has positive effects on the growth performance, antioxidant and anti-inflammatory status, metabolic capacity and mid-intestine morphology of juvenile . Shrimp with 0.63 g approximately initial body weight were fed diets supplemented with/without 50 g/kg GXU-A23. After 8 weeks feeding intervention, significantly higher growth performance of was obtained in the GXU-A23 treatment group compared to the control group ( < 0.05). At the same time, fed with GXU-A23 acquired significantly better antioxidant and anti-inflammatory status than the control group ( < 0.05). In addition, higher RNA expression level of hepatopancreas digestive enzyme, hepatopancreas lipid and glucose metabolic enzymes as well as better mid-intestine morphology were found in the GXU-A23 treatment group than the control group ( < 0.05). These results indicated that 50 g/kg GXU-A23 was suitable for the feed, which could improve the growth performance, antioxidant and anti-inflammatory status, metabolic capacity and mid-intestine morphology of juvenile
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http://dx.doi.org/10.3389/fphys.2022.882091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081789PMC
April 2022

Two Novel Mutations in Ectodysplasin-A Identified in Syndromic Tooth Agenesis.

J Coll Physicians Surg Pak 2022 May;32(5):570-574

Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People's Republic of China.

Objective: To discover novel ectodysplasin-A (EDA) and wingless-type MMTV integration site family, member 10A (WNT10A) mutations in tooth agenesis (TA) patients.

Study Design: Case series.

Place And Duration Of Study: Guanghua School of Stomatology, Guangzhou, China, from March 2018 to August 2020.

Methodology: EDA and WNT10A were analysed in eleven TA families by PCR and Sanger sequencing. Bioinformatics and structure modelling analyses were performed after identifying different variants, to predict the resulting conformational alterations in WNT10A and EDA.

Results:  Two novel mutations (c.796C>A (p.L266I), c.769G>A (p.G257R)) in EDA and two reported mutations (c.637G>A (p.G213S), c.511C>T (p.R171C))in WNT 10A were detected. Combined with the 3D structural analysis, we discovered a correlation between alterations in hydrogen bond formation and the observed phenotypes, potentially affecting protein binding.

Conclusions: The mutations were predicted to be pathogenic through bioinformatics analyses. In addition, by identifying novel mutations, our knowledge regarding the TA spectrum and tooth development was considerably expanded.

Key Words:  Anodontia, EDA, WNT 10A, Whole exome sequencing, Odontogenesis.
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http://dx.doi.org/10.29271/jcpsp.2022.05.570DOI Listing
May 2022

Maximizing the peroxidase-like activity of [email protected] nanocubes by precisely controlling the shell thickness and their application in colorimetric biosensors.

Nanoscale 2022 May 11. Epub 2022 May 11.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China.

Although the application of nanoscale artificial enzymes in various industries is an attractive way to circumvent the intrinsic drawbacks of natural enzymes, their catalytic constant () as a critical reaction parameter is far from satisfactory. Presented here is the rational design and fabrication of a unique peroxidase mimic catalyst based upon [email protected] (1 ≤ ≤ 3) prepared by coating PtRu alloy as conformal, ultrathin shells on Pd nanocrystals. Benefiting from an optimal Pt/Ru ratio and well-defined {100} facets, together with confining the Pt-Ru alloy to a shell of averagely 3.3-atomic-layer thick ( [email protected]), the nanocrystals exhibit the highest catalytic activity and kinetics (1.2 × 10 s), resulting in a significant increase of catalytic activity compared with the classical PtRu nanozyme (3.6 × 10 s) and horseradish peroxidase (4.0 × 10 s), respectively. The following density functional theory calculations demonstrate that the origin of the superior catalytic performance could be attributed to the modulation of the adsorption behavior of the key reaction intermediates on the surface. As a proof of concept, its peroxidase mimicking ability is adopted for sensing glucose and glutathione molecules in human serum, with a long linear range and high selectivity. This work opens new horizons for the future development of advanced catalysts based upon alloy nanocrystals for various applications.
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http://dx.doi.org/10.1039/d2nr01375dDOI Listing
May 2022

Variation in biogenic calcite production by coccolithophores across mesoscale eddies in the Bay of Bengal.

Mar Pollut Bull 2022 May 7;179:113728. Epub 2022 May 7.

Research Centre for Indian Ocean Ecosystem, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Marine Resources and Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China; College of Marine Science and Technology, China University of Geosciences (Wuhan), Wuhan 430074, China. Electronic address:

Coccolithophore calcite production (CP) was investigated for the first time in the Bay of Bengal. Against expectation, calcite production was not fueled by the nutrient-enriched cold eddy because of the reduced light penetration. CP rate was observed to be higher at the anticyclonic eddy possibly benefited from rare species production. The adjoining river-induced shallow mixed-layer depth and eddy activity co-influenced CP rate. On average, the integrated CP rates were 0.04, 0.15, and 0.07 mmol C m h for the cyclonic eddy, anticyclonic eddy, and outer area, respectively. In the upper photic waters, CP rates showed a strong correlation with primary productivity (PP). However, a decoupling of CP and PP was observed in the lower photic zone due to differential light and nitrogen preferences in calcification and carbon fixation. Our findings could help to understand the biogenic response of eddy and inorganic-organic carbon association in the pelagic biogeochemical cycles.
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http://dx.doi.org/10.1016/j.marpolbul.2022.113728DOI Listing
May 2022

Effect of esophageal muscle fibrosis on prognosis of per-oral endoscopic myotomy (POEM) in achalasia patients.

Surg Endosc 2022 May 9. Epub 2022 May 9.

Department of Gastroenterology and Hepatology, General Hospital of Tianjin Medical University, Tianjin, China.

Background And Aims: Although esophageal smooth muscle fibrosis of achalasia (AC) patients has been described, the role and mechanism remain unclear. The aim of this study was to evaluate the fibrosis in the distal esophageal muscle in patients with AC and explore its relationship with prognosis of per-oral endoscopic myotomy (POEM).

Methods: Lower esophageal sphincter (LES) muscle from forty patients undergoing POEM for AC were obtained at the time of surgery. Control specimens consisted of similar muscle taken from distal esophagectomy for gastric tumors. The muscle fibrosis were assessed by Masson staining and confirmed by immunohistochemistry for collagen I and III. The total number of eosinophil within the myenteric propria were counted. In addition, clinical data were obtained through electronic medical records. Statistical comparison between groups were made.

Results: A significantly higher proportion of fibrosis in AC as compared with controls (P = 0.000). Eosinophil count, TGF-β1, collagen I, and III were higher than those of control (P = 0.000, P = 0.001, P = 0.011, and P = 0.002, respectively). TGF-β1, collagen I, and III were positively correlated with eosinophil count (all P < 0.05). Furthermore, the proportion of severe LES fibrosis in patients who failed to respond to POEM two years after operation was higher than that in responders (P = 0.028). And, Eckardt score two years after POEM was also positively correlated with degree of fibrosis-related cytokines (all P < 0.05).

Conclusion: Smooth muscle fibrosis was prominent in lower part of esophagus of AC and positively correlated with severity of symptoms two years after POEM. The fibrosis might be relevant to eosinophil infiltration and TGF-β1. Further studies are required to more clearly delineate the mechanism of muscle fibrosis and its correlation with prognosis of therapy for this idiopathic disease.
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http://dx.doi.org/10.1007/s00464-022-09172-3DOI Listing
May 2022

The emerging roles of N6-methyladenosine (m6A)-modified long non-coding RNAs in human cancers.

Cell Death Discov 2022 May 9;8(1):255. Epub 2022 May 9.

The School and Hospital of Stomatology, Tianjin Medical University, Qixiangtai Road, No. 12, Tianjin, 300070, P.R. China.

N-methyladenosine (mA) epitranscriptional modifications widely exist in RNA, which play critical roles in RNA metabolism and biogenesis processes. Long non-coding RNAs (lncRNAs) are class of non-coding RNAs longer than 200 nucleotides without protein-coding ability. LncRNAs participate in a large number of vital biological progressions. With the great improvement of molecular biology, mA and lncRNAs are attracting more attention from researchers and scholars. In this review, we overview the current status of mA and lncRNAs based on the latest research, and propose some viewpoints for future research perspectives.
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http://dx.doi.org/10.1038/s41420-022-01050-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9085772PMC
May 2022

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.

Cell Genom 2022 Jan 13;2(1). Epub 2022 Jan 13.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at indicated the independent signals colocalized with cell-type specific eQTLs for (). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, () and . In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.
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http://dx.doi.org/10.1016/j.xgen.2021.100084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075703PMC
January 2022

Early COPD Risk Decision for Adults Aged From 40 to 79 Years Based on Lung Radiomics Features.

Front Med (Lausanne) 2022 21;9:845286. Epub 2022 Apr 21.

College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China.

Background: Chronic obstructive pulmonary disease (COPD), a preventable lung disease, has the highest prevalence in the elderly and deserves special consideration regarding earlier warnings in this fragile population. The impact of age on COPD is well known, but the COPD risk of the aging process in the lungs remains unclear. Therefore, it is necessary to understand the COPD risk of the aging process in the lungs, providing an early COPD risk decision for adults.

Methods: COPD risk is evaluated for adults to make an early COPD risk decision from the perspective of lung radiomics features. First, the subjects are divided into four groups according to the COPD stages. Their ages are divided into eight equal age intervals in each group. Second, four survival Cox models are established based on the lung radiomics features to evaluate the risk probability from COPD stage 0 to suffering COPD and COPD stages. Finally, four risk ranks are defined by equally dividing the COPD risk probability from 0 to 1. Subsequently, the COPD risk at different stages is evaluated with varying age intervals to provide an early COPD risk decision.

Results: The evaluation metrics area under the curve (AUC)/C index of four survival Cox models are 0.87/0.94, 0.84/0.83, 0.94/0.89, and 0.97/0.86, respectively, showing the effectiveness of the models. The risk rank levels up every 5 years for the subjects who had suffered COPD after 60. For the subjects with COPD stage 0, the risk rank of suffering COPD stage I levels up every 5 years after the age of 65 years, and the risk rank of suffering COPD stages II and III & IV levels up every 5 years after the age of 70 years.

Conclusion: Once the age is above 60 years, the patients with COPD need to take action to prevent the progress and deterioration of COPD. Once the age is above 65 years, the patients with COPD stage 0 need to take precautions against COPD.
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http://dx.doi.org/10.3389/fmed.2022.845286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069013PMC
April 2022

Engineering the Entrance of a Flavonoid Glycosyltransferase Promotes the Glycosylation of Etoposide Aglycone.

ACS Synth Biol 2022 May 6;11(5):1874-1880. Epub 2022 May 6.

Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei University of Technology, Wuhan 430068, China.

Enzyme entrances, which function as the first molecular filters, influence substrate selectivity and enzymatic activity. Because of low binding affinities, engineering enzyme entrances that recognize non-natural substrates is a major challenge for artificial biocatalyst design. Here, the entrance of flavonoid glycosyltransferase UGT78D2 was engineered to promote the recognition of the aglycone of etoposide, a chemotherapeutic agent. We found that Q258, S446, R444, and R450, the key residues surrounding the substrate entrance, specifically guide the flux of etoposide aglycone, which has a high steric hindrance, into the active site; this activity was inferred to be determined by the entrance size and hydrophobic and electrostatic interactions. Engineering the coordination of Q258 and S446 to increase the entrance size and hydrophobic interaction between UGT78D2 and etoposide aglycone increased the affinity by 10.10-fold and the conversion by 10%. The entrance-engineering strategy applied in this study can improve the design of artificial biocatalysts.
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http://dx.doi.org/10.1021/acssynbio.2c00032DOI Listing
May 2022

Efficacy and safety of vibrating capsule for functional constipation (VICONS): A randomised, double-blind, placebo-controlled, multicenter trial.

EClinicalMedicine 2022 May 25;47:101407. Epub 2022 Apr 25.

Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, 168 Changhai Road, Shanghai 200433, China.

Background: Functional constipation (FC) is an intractable disease that carries large financial burden as well as emotional and physical stress. We aimed to assess the efficacy and safety of the newly developed smartphone-controlled vibrating capsule (VC) in patients with FC.

Methods: From December 2018 to February 2020, we did a multicenter, blinded, placebo-controlled randomised trial in six top general hospitals in China focusing on patients aged 18 to 80 with FC. Patients were randomly assigned in a 1:1 ratio to receive VCs or placebo treatment for six weeks (two capsules per week) after a two-week baseline period. The primary outcome was the responder rate, defined as the proportion of patients with an increase of at least one complete spontaneous bowel movement (CSBM) per week during treatment compared to baseline in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT04671264, and is completed.

Findings: 107 patients aged from 18 to 74 were randomly assigned to receive VC ( = 53) or placebo treatment ( = 54). The responder rate in the VC group was significantly higher than that in the placebo group (64·2% vs. 35·8%; difference, 27·7% [95% CI, 10·4-45·1];  = 0·005). More patients in the VC group reported weekly CSBMs ≥ 1 for at least four weeks during treatment (difference, 22·7% [95% CI, 8-46];  = 0·022) and follow-up period (difference, 17.3% [95% CI, 0-35];  = 0·048). The mean Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life score differed significantly from the baseline in both groups (all  < 0·0001). The most common adverse event associated with VC was abdominal discomfort (3·7%).

Interpretation: VCs can promote defecation, as well as ameliorating symptoms and improving the quality of life in patients with FC with sustained efficacy. VC appears to be a potential alternative physical treatment for FC with the exact mechanism and parameters warranting further investigation.

Funding: The study was supported by "One hundred leading scientists for 21st century" of Health Department of Shanghai Municipal Government (to ZL, No.2017BR005).
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http://dx.doi.org/10.1016/j.eclinm.2022.101407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062239PMC
May 2022

Baseline T-lymphocyte and cytokine indices in sheep peripheral blood.

BMC Vet Res 2022 May 5;18(1):165. Epub 2022 May 5.

Ningxia Key Laboratory of Prevention and Treatment of Common Infectious Diseases, Yinchuan, China.

Background: Sheep are an important livestock species worldwide and an essential large-animal model for animal husbandry and veterinary research. Understanding fundamental immune indicators, especially T-lymphocyte parameters, is necessary for research on sheep diseases and vaccines, to better understand the immune response to bacteria and viruses for reducing the use of antibiotics and improving the welfare of sheep. We randomly selected 36 sheep of similar ages to analyze cell-related immune indicators in peripheral blood mononuclear cells (PBMCs). The proportions of CD4 and CD8 T cells in PBMCs were detected by flow cytometry. We used Concanavalin A (Con A) and Phorbol-12-myristate-13-acetate (PMA)/Ionomycin to stimulate PBMCs, and measured the expression of IFN-γ, IL-4, and IL-17A using enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISpot). Simultaneously, PMA/Ionomycin/brefeldin A (BFA) was added to PBMCs, then the expression of IFN-γ, IL-4, and IL-17A was detected by flow cytometry after 4 h of culturing. In addition, we observed the proliferation of PBMCs stimulated with Con A for 3, 4, and 5 days.

Results: The proportions of CD4 T lymphocytes (18.70 ± 4.21%) and CD8 T lymphocytes (8.70 ± 3.65%) were generally consistent among individuals, with a CD4/CD8 ratio of 2.40 ± 0.79. PBMCs produced high levels of IFN-γ, IL-4, and IL-17A after stimulation with PMA/Ionomycin and Con A. Furthermore, PMA/Ionomycin stimulation of PBMC yielded significantly higher cytokine levels than Con A stimulation. Flow cytometry showed that the level of IFN-γ (51.49 ± 11.54%) in CD8 T lymphocytes was significantly (p < 0.001) higher than that in CD4 T lymphocytes (14.29 ± 3.26%); IL-4 (16.13 ± 6.81%) in CD4 T lymphocytes was significantly (p < 0.001) higher than that in CD8 T lymphocytes (1.84 ± 1.33%), There was no difference in IL-17A between CD4 (2.83 ± 0.98%) and CD8 T lymphocytes (1.34 ± 0.67%). The proliferation of total lymphocytes, CD4 T lymphocytes, and CD8 T lymphocytes continued to increase between days 3 and 5; however, there were no significant differences in proliferation between the cell types during the stimulation period.

Conclusions: Evaluating primary sheep immune indicators, especially T lymphocytes, is significant for studying cellular immunity. This study provided valuable data and theoretical support for assessing the immune response of sheep to pathogens and improving sheep welfare.
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http://dx.doi.org/10.1186/s12917-022-03268-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074339PMC
May 2022

Predictive Performance of Pharmacokinetic Model-Based Virtual Trials of Vancomycin in Neonates: Mathematics Matches Clinical Observation.

Clin Pharmacokinet 2022 May 6. Epub 2022 May 6.

Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No.44, Wenhua West Road, Jinan, 250012, Shandong Province, China.

Background And Objective: Vancomycin is frequently used to treat Gram-positive bacterial infections in neonates. However, there is still no consensus on the optimal initial dosing regimen. This study aimed to assess the performance of pharmacokinetic model-based virtual trials to predict the dose-exposure relationship of vancomycin in neonates.

Methods: The PubMed database was searched for clinical trials of vancomycin in neonates that reported the percentage of target attainment. Monte Carlo simulations were performed using nonlinear mixed-effect modeling to predict the dose-exposure relationship, and the differences in outcomes between virtual trials and real-world data in clinical studies were calculated.

Results: A total of 11 studies with 14 dosing groups were identified from the literature to evaluate dose-exposure relationships. For the ten dosing groups where the surrogate marker for exposure was the trough concentration, the mean ± standard deviation (SD) for the target attainment between original studies and virtual trials was 3.0 ± 7.3%. Deviations between - 10 and 10% accounted for 80% of the included dosing groups. For the other four dosing groups where the surrogate marker for exposure was concentration during continuous infusion, all deviations were between - 10 and 10%, and the mean ± SD value was 2.9 ± 4.5%.

Conclusion: The pharmacokinetic model-based virtual trials of vancomycin exhibited good predictive performance for dose-exposure relationships in neonates. These results might be used to assist the optimization of dosing regimens in neonatal practice, avoiding the need for trial and error.
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http://dx.doi.org/10.1007/s40262-022-01128-zDOI Listing
May 2022

Instantaneous Brain Strain Estimation for Automotive Head Impacts via Deep Learning.

Stapp Car Crash J 2021 11;65:139-162

Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01605, USA.

Efficient brain strain estimation is critical for routine application of a head injury model. Lately, a convolutional neural network (CNN) has been successfully developed to estimate spatially detailed brain strains instantly and accurately in contact sports. Here, we extend its application to automotive head impacts, where impact profiles are typically more complex with longer durations. Head impact kinematics (N=458) from two public databases were used to generate augmented impacts (N=2694). They were simulated using the anisotropic Worcester Head Injury Model (WHIM) V1.0, which provided baseline elementwise peak maximum principal strain (MPS). For each augmented impact, rotational velocity () and the corresponding rotational acceleration () profiles were concatenated as static images to serve as CNN input. Three training strategies were evaluated: 1) "baseline", using random initial weights; 2) "transfer learning", using weight transfer from a previous CNN model trained on head impacts drawn from contact sports; and 3) "combined training", combining previous training data from contact sports (N=5661) for training. The combined training achieved the best performances. For peak MPS, the CNN achieved a coefficient of determination (R) of 0.932 and root mean squared error (RMSE) of 0.031 for the real-world testing dataset. It also achieved a success rate of 60.5% and 94.8% for elementwise MPS, where the linear regression slope, k, and correlation coefficient, r, between estimated and simulated MPS did not deviate from 1.0 (when identical) by more than 0.1 and 0.2, respectively. Cumulative strain damage measure (CSDM) from the CNN estimation was also highly accurate compared to those from direct simulation across a range of thresholds (R of 0.899-0.943 with RMSE of 0.054-0.069). Finally, the CNN achieved an average k and r of 0.98±0.12 and 0.90±0.07, respectively, for six reconstructed car crash impacts drawn from two other sources independent of the training dataset. Importantly, the CNN is able to efficiently estimate elementwise MPS with sufficient accuracy while conventional kinematic injury metrics cannot. Therefore, the CNN has the potential to supersede current kinematic injury metrics that can only approximate a global peak MPS or CSDM. The CNN technique developed here may offer enhanced utility in the design and development of head protective countermeasures, including in the automotive industry. This is the first study aimed at instantly estimating spatially detailed brain strains for automotive head impacts, which employs >8.8 thousand impact simulations generated from ~1.5 years of nonstop computations on a high-performance computing platform.
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http://dx.doi.org/10.4271/2021-22-0006DOI Listing
November 2021
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