Publications by authors named "Qi Sun"

1,204 Publications

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Association of anaplastic lymphoma kinase variants and alterations with ensartinib response duration in non-small cell lung cancer.

Thorac Cancer 2021 Jul 20. Epub 2021 Jul 20.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression-free survival (PFS).

Methods: We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan-Meier analysis was conducted to identify risk factors for tumor progression.

Results: Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan-Meier analysis (p = 0.002). Additionally, response duration to crizotinib <1 year and liver metastasis were adversely associated with PFS. The combined model, composed of clinicopathological signature and CT radiomic signature, showed good prediction ability with the area under the receiver operating characteristic curve being 0.85, and 0.89 in the training and validation dataset respectively.

Conclusions: Our study showed that secondary ALK alterations were adversely associated with ensartinib efficacy, and that ALK variants might not correlate with PFS. The quantitative radiomic signature provided added prognostic prediction value to the clinicopathological features.
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http://dx.doi.org/10.1111/1759-7714.14083DOI Listing
July 2021

High Mobility Organic Lasing Semiconductor with Crystallization-Enhanced Emission for Light-Emitting Transistors.

Angew Chem Int Ed Engl 2021 Jul 18. Epub 2021 Jul 18.

Tianjin University, Department of Chemistry, zhongguancun, 100190, Beijing, CHINA.

The development of high mobility organic laser semiconductors with strong emission is of great scientific and technical importance, but challenging. Herein, we present a high mobility organic laser semiconductor, 2,7-diphenyl-9H-fluorene (LD-1) showing unique crystallization-enhanced emission guided by elaborately modulating its crystal growth process. The obtained one-dimensional nanowires of LD-1 show outstanding integrated properties including: high absolute photoluminescence quantum yield (PLQY) approaching 80%, high charge carrier mobility of 0.08 cm 2 V -1 s -1 , Fabry-Perot lasing characters with a low threshold of 86 uJ cm -2 and a high-quality factor of ~ 2400. Furthermore, electrically induced emission was obtained from an individual LD-1 crystal nanowire-based light-emitting transistor due to the recombination of holes and electrons simultaneously injected into the nanowire, which provides a good platform for the study of electrically pumped organic lasers and other related ultrasmall integrated electrical-driven photonic devices.
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http://dx.doi.org/10.1002/anie.202108224DOI Listing
July 2021

Sodium Reduction in Traditional Fermented Foods: Challenges, Strategies, and Perspectives.

J Agric Food Chem 2021 Jul 16. Epub 2021 Jul 16.

College of Biomass Science and Engineering, Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China.

Sodium salt is a pivotal ingredient in traditional fermented foods, but its excessive consumption adversely affects human health, product quality, and production efficiency. Therefore, reducing sodium salt content in traditional fermented foods and developing low-sodium fermented foods have attracted increasing attention. Given the essential role of sodium salt in the safety and quality of fermented foods, appropriate approaches should be applied in the production of low-sodium fermented foods. In this review, the challenges of sodium reduction in traditional fermented foods are presented, including the possible growth of pathogenic bacteria, the formation of hazardous chemicals, flavor deficiency, and texture deterioration. Physical, chemical, and biological strategies are also discussed. This review provides references for improving the quality and safety of low-sodium fermented foods.
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http://dx.doi.org/10.1021/acs.jafc.1c01687DOI Listing
July 2021

Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10.

Elife 2021 Jul 13;10. Epub 2021 Jul 13.

Division of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.

Autophagy acts as a pivotal innate immune response against infection. Some virulence effectors subvert the host autophagic machinery to escape the surveillance of autophagy. The mechanism by which pathogens interact with host autophagy remains mostly unclear. However, traditional strategies often have difficulty identifying host proteins that interact with effectors due to the weak, dynamic and transient nature of these interactions. Here, we found that (EPEC) regulates autophagosome formation in host cells dependent on effector NleE. The 26S Proteasome Regulatory Subunit 10 (PSMD10) was identified as a direct interaction partner of NleE in living cells by employing genetically incorporated crosslinkers. Pairwise chemical crosslinking revealed that NleE interacts with the N-terminus of PSMD10. We demonstrated that PSMD10 homodimerization is necessary for its interaction with ATG7 and promotion of autophagy, but not necessary for PSMD10 interaction with ATG12. Therefore, NleE-mediated PSMD10 in monomeric state attenuates host autophagosome formation. Our study reveals the mechanism through which EPEC attenuates host autophagy activity.
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http://dx.doi.org/10.7554/eLife.69047DOI Listing
July 2021

Estrogen Protects Vasomotor Functions in Rats During Catecholamine Stress.

Front Cardiovasc Med 2021 16;8:679240. Epub 2021 Jun 16.

Department of Physiology, Xuzhou Medical University, Xuzhou, China.

The incidence of dysfunctional vasomotor diseases has mostly occurred in postmenopausal women but not in premenopausal women. Hence, this study sought to investigate the impact of estrogen deficiency during catecholamine stress on vasomotor function. Also, attempts were made to utilize estrogen replacement therapy to mitigate the adverse effects (pathological remodeling) of stress on the aortic vessels to preserve vasomotor functions. To do this, female Sprague-Dawley (SD) rats were ovariectomized (OVX) along with sham operations (Sham). Day 14 after OVX operation, 17-estradiol (E) was subcutaneously implanted (OVX+E). Day 35 after operation, stress was induced by isoproterenol (ISO) subcutaneous injections. Clinically relevant blood pressure indexes (systolic, diastolic, and mean atrial blood pressures) were assessed in the rats. Aortic vascular ring tensions were assessed to ascertain the impact of E on their vasomotor function. Aortic vascular rings (AVRs) from OVX+ISO exhibited a significant increase in contractility in response to phenylephrine than AVRs isolated from Sham+ISO rats. Also, sera levels of nitric oxide (NO) and endothelin-1 (ET-1) and the expression of p-eNOS/eNOS from vascular tissues were ascertained. We demonstrate that, during stress, E prevented excessive weight gain and OVX rats had higher blood pressures than those in the Sham group. Further, we showed that E decreases ET-1 expressions during stress while upregulating NO expressions via enhancing eNOS activities to facilitate vasomotor functions. Finally, histological assessment revealed the E treatments during stress preserved vasomotor functions by preventing excessive intima-media thickening and collagen depositions in the aortic vascular walls.
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http://dx.doi.org/10.3389/fcvm.2021.679240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241912PMC
June 2021

KCNN4-mediated Ca/MET/AKT axis is promising for targeted therapy of pancreatic ductal adenocarcinoma.

Acta Pharmacol Sin 2021 Jun 28. Epub 2021 Jun 28.

Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China.

As a member of the potassium calcium-activated channel subfamily, increasing evidence suggests that KCNN4 was associated with malignancies. However, the roles and regulatory mechanisms of KCNN4 in PDAC have been little explored. In this work, we demonstrated that the level of KCNN4 in PDAC was abnormally elevated, and the overexpression of KCNN4 was induced by transcription factor AP-1. KCNN4 was closely correlated with unfavorable clinicopathologic characteristics and poor survival. Functionally, we found that overexpression of KCNN4 promoted PDAC cell proliferation, migration and invasion. Conversely, the knockdown of KCNN4 attenuated the growth and motility of PDAC cells. In addition to these, knockdown of KCNN4 promoted PDAC cell apoptosis and led to cell cycle arrest in the S phase. In mechanistic investigations, RNA-sequence revealed that the MET-mediated AKT axis was essential for KCNN4, encouraging PDAC cell proliferation and migration. Collectively, these findings reveal a function of KCNN4 in PDAC and suggest it's an attractive therapeutic target and tumor marker. Our studies underscore a better understanding of the biological mechanism of KCNN4 in PDAC and suggest novel strategies for cancer therapy.
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http://dx.doi.org/10.1038/s41401-021-00688-3DOI Listing
June 2021

Carvedilol protects against the H2O2-induced cell damages in rat myoblasts by regulating the circ_NFIX/miR-125b-5p/TLR4 signal axis.

J Cardiovasc Pharmacol 2021 Jun 25. Epub 2021 Jun 25.

Department of Cardiology, The Seventh People's Hospital of Changzhou, Changzhou, 213011, Jiangsu, China.

Abstract: Circular RNAs (circRNAs) have been involved in the regulation of various kinds of cardiovascular diseases, including acute myocardial infarction (AMI). This study was performed to investigate the molecular mechanism associated with circRNA nuclear factor IX (circ_NFIX) in carvedilol-mediated cardioprotection in H2O2-treated H9c2 cells. Flow cytometry was performed for the analysis of cell cycle and apoptosis. Cell proliferation was evaluated using colony formation assay and 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Lactate dehydrogenase (LDH) activity was measured via LDH assay. The relative levels of circ_NFIX, microRNA-125b-5p (miR-125b-5p) and toll-like receptor 4 (TLR4) were determined via quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels were examined by western blot. The target interaction was proved via dual-luciferase reporter assay. H2O2-induced cell cycle arrest, proliferation repression, apoptosis and LDH promotion in H9c2 cells were inhibited by carvedilol. Circ_NFIX level was reduced after carvedilol treatment in H2O2-treated H9c2 cells, and circ_NFIX overexpression inhibited the protective effects of carvedilol on H2O2-induced cell damages. Furthermore, circ_NFIX was validated to serve as a sponge of miR-125b-5p and the inhibitory function of circ_NFIX in carvedilol-induced cardioprotection was achieved by sponging miR-125b-5p. Moreover, TLR4 acted as a target gene of miR-125b-5p and miR-125b-5p inhibitor upregulated the TLR4 expression to suppress the protective effects of carvedilol on H2O2-treated H9c2 cells. In addition, circ_NFIX regulated the TLR4 level by exerting the sponge influence on miR-125b-5p. Rat model also indicated that Carv might suppressed the progression of AMI via regulating the levels of circ_NFIX, miR-125b-5p and TLR4. These findings suggested that carvedilol protected H9c2 cells against the H2O2-induced cell dysfunction through depending on the circ_NFIX/miR-125b-5p/TLR4 axis.
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http://dx.doi.org/10.1097/FJC.0000000000001095DOI Listing
June 2021

Computational strategy for intrinsically disordered protein ligand design leads to the discovery of p53 transactivation domain I binding compounds that activate the p53 pathway.

Chem Sci 2020 Dec 28;12(8):3004-3016. Epub 2020 Dec 28.

BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University Beijing 100871 China +861062757486.

Intrinsically disordered proteins or intrinsically disordered regions (IDPs) have gained much attention in recent years due to their vital roles in biology and prevalence in various human diseases. Although IDPs are perceived as attractive therapeutic targets, rational drug design targeting IDPs remains challenging because of their conformational heterogeneity. Here, we propose a hierarchical computational strategy for IDP drug virtual screening (IDPDVS) and applied it in the discovery of p53 transactivation domain I (TAD1) binding compounds. IDPDVS starts from conformation sampling of the IDP target, then it combines stepwise conformational clustering with druggability evaluation to identify potential ligand binding pockets, followed by multiple docking screening runs and selection of compounds that can bind multi-conformations. p53 is an important tumor suppressor and restoration of its function provides an opportunity to inhibit cancer cell growth. TAD1 locates at the N-terminus of p53 and plays key roles in regulating p53 function. No compounds that directly bind to TAD1 have been reported due to its highly disordered structure. We successfully used IDPDVS to identify two compounds that bind p53 TAD1 and restore wild-type p53 function in cancer cells. Our study demonstrates that IDPDVS is an efficient strategy for IDP drug discovery and p53 TAD1 can be directly targeted by small molecules.
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http://dx.doi.org/10.1039/d0sc04670aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179352PMC
December 2020

Long non-coding RNA CDKN2B-AS1 enhances LPS-induced apoptotic and inflammatory damages in human lung epithelial cells via regulating the miR-140-5p/TGFBR2/Smad3 signal network.

BMC Pulm Med 2021 Jun 14;21(1):200. Epub 2021 Jun 14.

Department of Intensive Care Unit, The Second Clinical Medical College, Jingzhou Central Hospital, Yangtze University, No. 1 Renmin Road, Jingzhou District, Jingzhou, 434000, Hubei, China.

Background: Sepsis is a complicated disease with systemic inflammation or organ dysfunction, and it is the leading cause of acute lung injury (ALI). Long non-coding RNAs (lncRNAs) have played important roles in the pathogenesis of sepsis. This study was designed to explore the biological function and regulatory mechanism of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in lipopolysaccharide (LPS)-induced lung injury.

Methods: ALI model was established after human lung epithelial cell line BEAS-2B was exposed to LPS. CDKN2B-AS1, microRNA-140-5p (miR-140-5p) and transforming Growth Factor Beta Receptor II (TGFBR2) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was measured using Cell Counting Kit-8 (CCK-8). Cell apoptosis was assessed by caspase3 activity and flow cytometry. Inflammatory cytokines were examined via enzyme-linked immunosorbent assay (ELISA). Protein analysis was performed through western blot. Dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays were applied to validate the interaction between targets.

Results: CDKN2B-AS1 and TGFBR2 were abnormally upregulated in sepsis patients. Functionally, CDKN2B-AS1 or TGFBR2 knockdown promoted cell growth but inhibited cell apoptosis and inflammatory response in LPS-treated BEAS-2B cells. Moreover, the regulation of CDKN2B-AS1 in LPS-induced cell injury was achieved by increasing the TGFBR2 expression. CDKN2B-AS1 was identified as a miR-140-5p sponge and TGFBR2 was a target of miR-140-5p. Furthermore, CDKN2B-AS1 could regulate the TGFBR2/Smad3 pathway by sponging miR-140-5p.

Conclusions: These results suggested that CDKN2B-AS1 contributed to the LPS-mediated apoptosis and inflammation in BEAS-2B cells via the miR-140-5p/TGFBR2/Smad3 axis.
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http://dx.doi.org/10.1186/s12890-021-01561-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201744PMC
June 2021

Intermolecular Charge-Transfer-Induced Strong Optical Emission from Herringbone H-Aggregates.

Nano Lett 2021 Jun 14;21(12):5394-5400. Epub 2021 Jun 14.

MOE Key Laboratory of Organic OptoElectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084, P.R. China.

Luminescence in molecular aggregates can be quenched either by intermolecular charge transfer or by forming a dipole-forbidden lower Frenkel exciton in H-aggregate. Taking intermolecular charge transfer and excitonic coupling into a three-state model through localized diabatization, we demonstrate that the low-lying intermolecular charge-transfer state could couple with the upper bright Frenkel exciton to form dipole-allowed S that lies below the dark state, which accounts for the recent experimentally discovered strong luminescence in organic light-emitting transistors (OLETs) system with DPA and dNaAnt herringbone aggregates. The condition of forming such bright state is that the electron and hole transfer integrals, and , are of the same sign, and should be notably larger than the excitonic coupling (), that is , × > 2. This theoretical finding not only rationalizes recent experiments but unravels an exciting scenario where strong luminescence and high charge mobilities become compatible, which is a preferable condition for both OLETs and electrically pumped lasing.
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http://dx.doi.org/10.1021/acs.nanolett.1c01734DOI Listing
June 2021

Catalyst- and Solvent-Free Synthesis of a Chemically Stable Aza-Bridged Bis(phenanthroline) Macrocycle-Linked Covalent Organic Framework.

Angew Chem Int Ed Engl 2021 Jul 26;60(31):17191-17197. Epub 2021 Jun 26.

School of Energy and Chemical Engineering, Center for Dimension Controllable Organic Frameworks, Ulsan National Institute of Science and Technology, South Korea.

Developing new linkage-based covalent organic frameworks (COFs) is one of the major topics in reticular chemistry. Electrically conductive COFs have enabled applications in energy storage and electrochemical catalysis, which are not feasible using insulating COFs. Despite significant advances, the construction of chemically stable conductive COFs by the formation of new linkages remains relatively unexplored and challenging. Here we report the solvent- and catalyst-free synthesis of a two-dimensional aza-bridged bis(phenanthroline) macrocycle-linked COF (ABBPM-COF) from the thermally induced poly-condensation of a tri-topic monomer and ammonia gas. The ABBPM-COF structure was elucidated using multiple techniques, including X-ray diffraction analysis combined with structural simulation, revealing its crystalline nature with an ABC stacking mode. Further experiments demonstrated its excellent chemical stability in acid/base solutions. Electrical-conductivity measurements showed that the insulating ABBPM-COF becomes a semiconducting material after exposure to iodine vapor.
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http://dx.doi.org/10.1002/anie.202106389DOI Listing
July 2021

Plant-Based Diet Index and Metabolic Risk in Men: Exploring the Role of the Gut Microbiome.

J Nutr 2021 Jun 10. Epub 2021 Jun 10.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabolic conditions, but its association as well as interactions with microbiome have not been elucidated.

Objectives: We aimed to investigate the interrelations between hPDI, gut microbiome, and cardiometabolic risk markers.

Methods: hPDI was derived from dietary assessments by a validated FFQ and was examined in relation to metagenomic profiles of 911 fecal samples collected from 303 men aged 71 ± 4 y with an average BMI (in kg/m2) of 25.2 ± 3.6 in the Men's Lifestyle Validation Study. Principal coordinate (PCo) analysis based on Bray-Curtis dissimilarity was conducted, and interactions between hPDI and PCo were examined by using a metabolic risk score composed of blood lipids, BMI, and glycated hemoglobin.

Results: After multivariable adjustment, hPDI was significantly associated with the relative abundance of 7 species and 9 pathways. In particular, higher hPDI was significantly associated with a higher relative abundance of Bacteroides cellulosilyticus and Eubacterium eligens, amino acid biosynthesis pathways (l-isoleucine biosynthesis I and III and l-valine biosynthesis), and the pathway of pyruvate fermentation to isobutanol. A favorable association between hPDI and the metabolic risk score was more pronounced among men with a higher PCo characterized by higher abundance of Bacteroides uniformis and lower abundance of Prevotella copri. At the individual species level, a similar interaction was also observed between hPDI and P. copri, as well as with Clostridium clostridioforme or Blautia hydrogenotrophica (all P-interaction < 0.01).

Conclusion: A greater adherence to a healthy plant-based diet by older men was associated with a microbial profile characterized by a higher abundance of multiple species, including B. cellulosilyticus and E. eligens, as well as pathways in amino acid metabolism and pyruvate fermentation. In addition, inverse associations between healthy plant-based diet and human metabolic risk may partially depend on microbial compositions.
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http://dx.doi.org/10.1093/jn/nxab175DOI Listing
June 2021

An Efficient Sharing Grouped Convolution via Bayesian Learning.

IEEE Trans Neural Netw Learn Syst 2021 Jun 10;PP. Epub 2021 Jun 10.

Compared with traditional convolutions, grouped convolutional neural networks are promising for both model performance and network parameters. However, existing models with the grouped convolution still have parameter redundancy. In this article, concerning the grouped convolution, we propose a sharing grouped convolution structure to reduce parameters. To efficiently eliminate parameter redundancy and improve model performance, we propose a Bayesian sharing framework to transfer the vanilla grouped convolution to be the sharing structure. Intragroup correlation and intergroup importance are introduced into the prior of the parameters. We handle the Maximum Type II likelihood estimation problem of the intragroup correlation and intergroup importance by a group LASSO-type algorithm. The prior mean of the sharing kernels is iteratively updated. Extensive experiments are conducted to demonstrate that on different grouped convolutional neural networks, the proposed sharing grouped convolution structure with the Bayesian sharing framework can reduce parameters and improve prediction accuracy. The proposed sharing framework can reduce parameters up to 64.17%. For ResNeXt-50 with the sharing grouped convolution on ImageNet dataset, network parameters can be reduced by 96.875% in all grouped convolutional layers, and accuracies are improved to 78.86% and 94.54% for top-1 and top-5, respectively.
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http://dx.doi.org/10.1109/TNNLS.2021.3084900DOI Listing
June 2021

Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats.

J Orthop Surg Res 2021 Jun 9;16(1):368. Epub 2021 Jun 9.

Department of Orthopedic Surgery, Hebei Medical University, 361 Zhongshan E Rd, Shijiazhuang, Hebei, 050000, People's Republic of China.

Background: Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis.

Methods: An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4-5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated.

Results: RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group.

Conclusions: RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.
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http://dx.doi.org/10.1186/s13018-021-02504-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188785PMC
June 2021

Distributional Soft Actor-Critic: Off-Policy Reinforcement Learning for Addressing Value Estimation Errors.

IEEE Trans Neural Netw Learn Syst 2021 Jun 8;PP. Epub 2021 Jun 8.

In reinforcement learning (RL), function approximation errors are known to easily lead to the Q-value overestimations, thus greatly reducing policy performance. This article presents a distributional soft actor-critic (DSAC) algorithm, which is an off-policy RL method for continuous control setting, to improve the policy performance by mitigating Q-value overestimations. We first discover in theory that learning a distribution function of state-action returns can effectively mitigate Q-value overestimations because it is capable of adaptively adjusting the update step size of the Q-value function. Then, a distributional soft policy iteration (DSPI) framework is developed by embedding the return distribution function into maximum entropy RL. Finally, we present a deep off-policy actor-critic variant of DSPI, called DSAC, which directly learns a continuous return distribution by keeping the variance of the state-action returns within a reasonable range to address exploding and vanishing gradient problems. We evaluate DSAC on the suite of MuJoCo continuous control tasks, achieving the state-of-the-art performance.
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http://dx.doi.org/10.1109/TNNLS.2021.3082568DOI Listing
June 2021

Dexmedetomidine Protects Human Cardiomyocytes Against Ischemia-Reperfusion Injury Through α2-Adrenergic Receptor/AMPK-Dependent Autophagy.

Front Pharmacol 2021 21;12:615424. Epub 2021 May 21.

Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Ischemia-reperfusion injury (I/R) strongly affects the prognosis of children with complicated congenital heart diseases (CHDs) who undergo long-term cardiac surgical processes. Recently, the α2-adrenergic receptor agonist (Dex) has been reported to protect cardiomyocytes (CMs) from I/R in cellular models and adult rodent models. However, whether and how Dex may protect human CMs in young children remains largely unknown. Human ventricular tissue from tetralogy of Fallot (TOF) patients and CMs derived from human-induced pluripotent stem cells (iPSC-CMs) were used to assess whether and how Dex protects human CMs from I/R. The results showed that when pretreated with Dex, the apoptosis marker-TUNEL and cleaved caspase 3 in the ventricular tissue were significantly reduced. In addition, the autophagy marker LC3II was significantly increased compared with that of the control group. When exposed to the hypoxia/reoxygenation process, iPSC-CMs pretreated with Dex also showed reduced TUNEL and cleaved caspase 3 and increased LC3II. When the autophagy inhibitor (3-methyladenine, 3-MA) was applied to the iPSC-CMs, the protective effect of Dex on the CMs was largely blocked. In addition, when the fusion of autophagosomes with lysosomes was blocked by Bafilomycin A1, the degradation of p62 induced by Dex during the autophagy process was suspended. Moreover, when pretreated with Dex, both the human ventricle and the iPSC-CMs expressed more AMP-activated protein kinase (AMPK) and phospho AMPK (pAMPK) during the I/R process. After AMPK knockout or the use of an α2-adrenergic receptor antagonist-yohimbine, the protection of Dex and its enhancement of autophagy were inhibited. Dex protects young human CMs from I/R injury, and α2-adrenergic receptor/AMPK-dependent autophagy plays an important role during this process. Dex may have a therapeutic effect for children with CHD who undergo long-term cardiac surgical processes.
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http://dx.doi.org/10.3389/fphar.2021.615424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176440PMC
May 2021

A transferable deep learning approach to fast screen potential antiviral drugs against SARS-CoV-2.

Brief Bioinform 2021 Jun 3. Epub 2021 Jun 3.

College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China.

The COVID-19 pandemic calls for rapid development of effective treatments. Although various drug repurpose approaches have been used to screen the FDA-approved drugs and drug candidates in clinical phases against SARS-CoV-2, the coronavirus that causes this disease, no magic bullets have been found until now. In this study, we used directed message passing neural network to first build a broad-spectrum anti-beta-coronavirus compound prediction model, which gave satisfactory predictions on newly reported active compounds against SARS-CoV-2. Then, we applied transfer learning to fine-tune the model with the recently reported anti-SARS-CoV-2 compounds and derived a SARS-CoV-2 specific prediction model COVIDVS-3. We used COVIDVS-3 to screen a large compound library with 4.9 million drug-like molecules from ZINC15 database and recommended a list of potential anti-SARS-CoV-2 compounds for further experimental testing. As a proof-of-concept, we experimentally tested seven high-scored compounds that also demonstrated good binding strength in docking studies against the 3C-like protease of SARS-CoV-2 and found one novel compound that can inhibit the enzyme. Our model is highly efficient and can be used to screen large compound databases with millions or more compounds to accelerate the drug discovery process for the treatment of COVID-19.
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http://dx.doi.org/10.1093/bib/bbab211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195169PMC
June 2021

The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols.

Nutrients 2021 May 30;13(6). Epub 2021 May 30.

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.

Background: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of 'Mankai', a novel cultivated strain of a polyphenol-rich aquatic plant, on the metabolomic-gut clinical axis in vitro, in-vivo and in a clinical trial.

Methods: We used mass-spectrometry-based metabolomics methods from three laboratories to detect Mankai phenolic metabolites and examined predicted functional pathways in a Mankai artificial-gut bioreactor. Plasma and urine polyphenols were assessed among the 294 DIRECT-PLUS 18-month trial participants, comparing the effect of a polyphenol-rich green-Mediterranean diet (+1240 mg/polyphenols/day, provided by Mankai, green tea and walnuts) to a walnuts-enriched (+440 mg/polyphenols/day) Mediterranean diet and a healthy controlled diet.

Results: Approximately 200 different phenolic compounds were specifically detected in the Mankai plant. The Mankai-supplemented bioreactor artificial gut displayed a significantly higher relative-abundance of 16S-rRNA bacterial gene sequences encoding for enzymes involved in phenolic compound degradation. In humans, several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups ( < 0.05) after six and 18 months of intervention (e.g., urine hydroxy-phenyl-acetic-acid and urolithin-A; plasma Naringenin and 2,5-diOH-benzoic-acid). Specific polyphenols, such as urolithin-A and 4-ethylphenol, were directly involved with clinical weight-related changes.

Conclusions: The Mankai new plant is rich in various unique potent polyphenols, potentially affecting the metabolomic-gut-clinical axis.
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http://dx.doi.org/10.3390/nu13061866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229908PMC
May 2021

Protective effect of alpha-lipoic acid on bisphenol A-induced learning and memory impairment in developing mice: nNOS and keap1/Nrf2 pathway.

Food Chem Toxicol 2021 Aug 29;154:112307. Epub 2021 May 29.

Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang, 110122, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, Shenyang, 110122, China. Electronic address:

The adverse effects of bisphenol A (BPA) on learning and memory may be related with oxidative stress, but the mechanisms are unclear. This study aimed to investigate the mechanism of damaged learning and memory caused by BPA through inducing oxidative stress, as well as to explore whether alpha-lipoic acid (ALA) show a protective action. Female mice were exposed to 0.1 μg/mL BPA, 0.2 μg/mL BPA, 0.6 mg/mL ALA, and 0.2 BPA + ALA through drinking water for 8 weeks. The results showed that ALA protected against the impairment of spatial, recognition, and avoidance memory caused by BPA. ALA replenished the reduce of hippocampus coefficient, serum estradiol (E2) level, and hippocampal neurotransmitters levels induced by BPA. ALA alleviated BPA-induced oxidative stress and hippocampal histological changes. BPA exposure reduced the levels of synaptic structural proteins and PKC/ERK/CREB pathway proteins, and ALA improved these reductions. ALA altered the protein levels of nNOS and keap1/Nrf2 pathway affected by BPA. Our results suggested that impairments of learning and memory caused by BPA was related to the damage of hippocampal synapses mediated by oxidative stress, and ALA protected learning and memory by reducing the oxidative stress induced by BPA through regulating the nNOS and keap1/Nrf2 pathway.
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http://dx.doi.org/10.1016/j.fct.2021.112307DOI Listing
August 2021

Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease.

Signal Transduct Target Ther 2021 05 29;6(1):212. Epub 2021 May 29.

BNLMS, Peking-Tsinghua Center for Life Sciences at College of Chemistry and Molecular Engineering, Peking University, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00628-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164054PMC
May 2021

Denosumab alleviates intervertebral disc degeneration adjacent to lumbar fusion by inhibiting endplate osteochondral remodeling and vertebral osteoporosis in ovariectomized rats.

Arthritis Res Ther 2021 05 28;23(1):152. Epub 2021 May 28.

Department of Orthopedic Surgery, Hebei Medical University, 361 Zhongshan ERoad, Hebei, 050000, Shijiazhuang, People's Republic of China.

Background: Although adjacent segmental intervertebral disc degeneration (ASDD) is one of the most common complications after lumbar fusion, its exact mechanism remains unclear. As an antibody to RANKL, denosumab (Dmab) effectively reduces bone resorption and stimulates bone formation, which can increase bone mineral density (BMD) and improve osteoporosis. However, it has not been confirmed whether Dmab has a reversing or retarding effect on ASDD.

Methods: Three-month-old female Sprague-Dawley rats that underwent L4-L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after bilateral ovariectomy (OVX) surgery were given Dmab 4 weeks after PLF surgery (OVX+PLF+Dmab group). In addition, the following control groups were defined: Sham, OVX, PLF, and OVX+PLF (n=12 each). Next, manual palpation and X-ray were used to evaluate the state of lumbar fusion. The bone microstructure in the lumbar vertebra and endplate as well as the disc height index (DHI) of L5/6 was evaluated by microcomputed tomography (μCT). The characteristic alterations of ASDD were identified via Safranin-O green staining. Osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining, and the biomechanical properties of vertebrae were evaluated. Aggrecan (Agg), metalloproteinase-13 (MMP-13), and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) expression in the intervertebral disc were detected by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analysis. In addition, the expression of CD24 and Sox-9 was assessed by immunohistochemistry.

Results: Manual palpation showed clear evidence of the fused segment's immobility. Compared to the OVX+PLF group, more new bone formation was observed by X-ray examination in the OVX+PLF+Dmab group. Dmab significantly alleviated ASDD by retaining disc height index (DHI), decreasing endplate porosity, and increasing vertebral biomechanical properties and BMD. TRAP staining results showed a significantly decreased number of active osteoclasts after Dmab treatment, especially in subchondral bone and cartilaginous endplates. Moreover, the protein and mRNA expression results in discs (IVDs) showed that Dmab not only inhibited matrix degradation by decreasing MMP-13 and ADAMTS-4 but also promoted matrix synthesis by increasing Agg. Dmab maintained the number of notochord cells by increasing CD24 but reducing Sox-9.

Conclusions: These results suggest that Dmab may be a novel therapeutic target for ASDD treatment.
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http://dx.doi.org/10.1186/s13075-021-02525-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161944PMC
May 2021

The severe toxicity of CuO nanoparticles to the photosynthesis of the prokaryotic algae Arthrospira sp.

Environ Sci Pollut Res Int 2021 May 27. Epub 2021 May 27.

State Key Laboratory of Crop Biology, Shandong Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, Shandong, 271018, People's Republic of China.

This research first verified that prokaryotic algae are more sensitive to toxicity of CuO nanoparticles (CuO NPs) than eukaryotic algae and that CuO NPs damaged photosynthesis of prokaryotic algae (Arthrospira sp.) but had no effect on respiration. The Cu released by CuO NPs caused a bending deformation of the thylakoid, which was an important cause of the decline in photosynthetic capacity. In addition, the D1 protein was the most susceptible site to CuO NPs. The degradation of D1 protein reduced photosynthetic electron transport, which enhanced the excess excitation energy to cause the accumulation of reactive oxygen species (ROS) to further result in oxidative stress on algae. Dissolved organic matter (DOM) increased the toxicity of CuO NPs to photosynthesis of Arthrospira sp. The damage of photosynthesis caused by CuO NPs is an important reason why CuO NPs have a serious toxicity to algae.
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http://dx.doi.org/10.1007/s11356-021-14341-3DOI Listing
May 2021

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents.

Neuromodulation 2021 May 26. Epub 2021 May 26.

Department of Psychiatry and Psychology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Objectives: Theta burst stimulation (TBS) is often used in clinical practice and research protocols for adults with neuropsychiatric disorders. There are substantial knowledge gaps related to the application of TBS in children and adolescents. This systematic review examined the safety and tolerability of TBS in children and adolescents.

Materials And Methods: A systematic review of human TBS studies in children and adolescents was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following inclusion criteria were applied: 1) articles in English language only; 2) studies that included child and adolescent participants (up to 21 years of age); 3) studies that administered intermittent TBS or continuous TBS or both to participants; 4) studies that had an outcome measure; and 5) availability of full text material. The primary outcome measures were tolerability and safety. When feasible, the clinical effects were reviewed.

Results: Twenty relevant articles met the criteria for inclusion. The reported adverse events were mild and similar to what is noted in adult studies. The most common symptom was headache. One case report described a seizure induced by TBS. Collectively, the studies were heterogeneous but the methodologic quality of randomized trials was high.

Conclusions: TBS interventions in children may have similar safety, tolerability, and feasibility as compared to adults. However, long-term, follow-up studies of TBS are lacking. Future dose-ranging studies with systematic assessment of adverse events will be important in the translation of findings with TBS from adults to youth.
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http://dx.doi.org/10.1111/ner.13455DOI Listing
May 2021

Imparting Ion Selectivity to Covalent Organic Framework Membranes Using Assembly for Blue Energy Harvesting.

J Am Chem Soc 2021 Jun 24;143(25):9415-9422. Epub 2021 May 24.

Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.

It has long been a challenge to fabricate angstrom-sized functional pores for mimicking the function of biological channels to afford selective transmembrane transport. In this study, we describe a facile strategy to incorporate ionic elements into angstrom-sized channels using encapsulation of charged dye molecules during the interface polymerization of a three-dimensional covalent organic framework (3D COF). We demonstrate that this approach is tailorable as it enables control over both the type and content of the guest and thus allows manipulation of the membrane function. The resulting membranes exhibit excellent permselectivity and low membrane resistance, thereby indicating the potential for harvesting salinity gradient (blue) energy. As a proof-of-concept study, the reverse electrodialysis device coupled with positive and negative dye encapsulated COF membranes afforded a power density of up to 51.4 W m by mixing the simulated seawater and river water, which far exceeds the commercialization benchmark (5 W m). We envision that this strategy will pave the way for constructing new multifunctional biomimetic systems.
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http://dx.doi.org/10.1021/jacs.1c02090DOI Listing
June 2021

Long-term Intake of Gluten and Cognitive Function Among US Women.

JAMA Netw Open 2021 May 3;4(5):e2113020. Epub 2021 May 3.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease.

Objective: To examine whether gluten intake is associated with cognitive function in women without celiac disease.

Design, Setting, And Participants: This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were collected from 2014 to 2019. Data analysis was conducted from October 2020 to April 2021.

Exposures: Energy-adjusted gluten intake, cumulatively averaged across questionnaire cycles prior to cognitive assessment.

Main Outcomes And Measures: Three standardized cognitive scores assessed by the validated Cogstate Brief Battery: (1) psychomotor speed and attention score, (2) learning and working memory score, and (3) global cognition score. Higher scores indicated better performance.

Results: The cohort included 13 494 women (mean [SD] age, 60.6 [4.6] years). The mean (SD) gluten intake was 6.3 (1.6) g/d. After controlling for demographic and lifestyle risk factors in linear regression, no significant differences in standardized cognitive scores (mean [SD], 0 [1]) by quintile of gluten intake were found across highest and lowest quintiles of gluten intake (psychomotor speed and attention: -0.02; 95% CI, -0.07 to 0.03; P for trend = .22; learning and working memory: 0.02; 95% CI, -0.03 to 0.07; P for trend = .30; global cognition: -0.002; 95% CI, -0.05 to 0.05; P for trend = .78). The null associations persisted after additional adjustment for major sources of dietary gluten (ie, refined grains or whole grains), comparing decile categories of gluten intake, using gluten intake updated at each previous questionnaire cycle, or modeling changes in gluten intake. Similarly, these associations were not materially altered in sensitivity analyses that excluded women who had reported cancer or dementia diagnosis or had not completed all dietary assessments.

Conclusions And Relevance: In this study, long-term gluten intake was not associated with cognitive scores in middle-aged women without celiac disease. Our results do not support recommendations to restrict dietary gluten to maintain cognitive function in the absence of celiac disease or established gluten sensitivity.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.13020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140370PMC
May 2021

A 3-DNA methylation signature as a novel prognostic biomarker in patients with sarcoma by bioinformatics analysis.

Medicine (Baltimore) 2021 May;100(20):e26040

Department of Nephrology, Huzhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Huzhou, Zhejiang, China.

Background: Tumor-specific DNA methylation can potentially be a useful indicator in cancer diagnostics and monitoring. Sarcomas comprise a heterogeneous group of mesenchymal neoplasms which cause life-threatening tumors occurring throughout the body. Therefore, potential molecular detection and prognostic evaluation is very important for early diagnosis and treatment.

Methods: We performed a retrospective study analyzing DNA methylation of 261 patients with sarcoma from The Cancer Genome Atlas (TCGA) database. Cox regression analyses were conducted to identify a signature associated with the overall survival (OS) of patients with sarcoma, which was validated in a validation dataset.

Results: Three DNA methylation signatures were identified to be significantly associated with OS. Kaplan-Meier analysis showed that the 3-DNA methylation signature could significantly distinguish the high- and low-risk patients in both training (first two-thirds) and validation datasets (remaining one-third). Receiver operating characteristic (ROC) analysis confirmed that the 3-DNA methylation signature exhibited high sensitivity and specificity in predicting OS of patients. Also, the Kaplan-Meier analysis and the area under curve (AUC) values indicated that the 3-DNA methylation signature was independent of clinical characteristics, including age at diagnosis, sex, anatomic location, tumor residual classification, and histological subtypes.

Conclusions: The current study showed that the 3-DNA methylation model could efficiently function as a novel and independent prognostic biomarker and therapeutic target for patients with sarcoma.
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http://dx.doi.org/10.1097/MD.0000000000026040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137010PMC
May 2021

Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men.

Gut 2021 Apr 29. Epub 2021 Apr 29.

Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA

Objectives: Gut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals.

Design: We collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men's Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features.

Results: TMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO concentrations (false discovery rate <0.05). Higher habitual intake of red meat and choline was significantly associated with higher TMAO concentrations among participants who were microbial TMAO-producers (p<0.05), as characterised based on four abundant TMAO-predicting species, but not among other participants (for red meat=0.003; for choline, =0.03). Among abundant TMAO-predicting species, significantly strengthened the positive association between red meat intake and HbA1c levels (=0.01). Secondary analyses revealed that some functional features, including choline trimethylamine-lyase activating enzymes, were associated with TMAO concentrations.

Conclusion: We identified microbial taxa that were associated with TMAO concentrations and modified the associations of red meat intake with TMAO concentrations and cardiometabolic risk markers. Our data underscore the interplay between diet and gut microbiome in producing potentially bioactive metabolites that may modulate cardiometabolic health.
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http://dx.doi.org/10.1136/gutjnl-2020-322473DOI Listing
April 2021

Recombinant Pseudorabies Virus with TK/gE Gene Deletion and Flt3L Co-Expression Enhances the Innate and Adaptive Immune Response via Activating Dendritic Cells.

Viruses 2021 04 16;13(4). Epub 2021 Apr 16.

State Key Laboratory of Agricultural Microbiology College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

Owing to viral evolution and recombination, emerging pseudorabies virus (PRV) strains have caused unprecedented outbreaks in swine farms even when the pigs were previously vaccinated, which might indicate that traditional vaccines were unable to provide effective protection. The development of safe and efficacious vaccines presents prospects to minimize the clinical signs and eventually eradicate the infection. In this study, we used an emerging PRV strain, HNX, as the parental strain to construct a recombinant PRV with TK/gE gene deletion and Fms-related tyrosine kinase 3 ligand (Flt3L) expression, named HNX-TK/gE-Flt3L. HNX-TK/gE-Flt3L enhanced the maturation of bone marrow derived dendritic cells (DCs) in vitro. Significantly more activated DCs were detected in HNX-TK/gE-Flt3L-immunized mice compared with those immunized with HNX-TK/gE. Subsequently, a remarkable increase of neutralizing antibodies, gB-specific IgG antibodies, and interferon-gamma (IFN-γ) was observed in mice vaccinated with HNX-TK/gE-Flt3L. In addition, a lower mortality and less histopathological damage were observed in HNX-TK/gE-Flt3L vaccinated mice with upon PRV lethal challenge infection. Taken together, our results revealed the potential of Flt3L as an ideal adjuvant that can activate DCs and enhance protective immune responses and support the further evaluation of HNX-TK/gE-Flt3L as a promising PRV vaccine candidate.
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http://dx.doi.org/10.3390/v13040691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072707PMC
April 2021

Preparation of Cemented Oil Shale Residue-Steel Slag-Ground Granulated Blast Furnace Slag Backfill and Its Environmental Impact.

Materials (Basel) 2021 Apr 19;14(8). Epub 2021 Apr 19.

School of Civil Engineering, Liaoning Technical University, Fuxin 123000, China.

A new environmentally friendly cemented oil shale residue-steel slag-ground granulated blast furnace slag backfill (COSGB) was prepared using oil shale residue (OSR), steel slag (SS) and ground granulated blast furnace slag (GGBS) as constituent materials. Based on univariate analysis and the Box-Behnken design (BBD) response surface method, the three responses of the 28 days unconfined compressive strength (UCS), slump and cost were used to optimize the mix ratio. Using a combination of scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and mercury intrusion porosimetry (MIP), the reaction products, microscopic morphology and pore structure of the specimens with the optimal mix ratio at different curing ages were analyzed. The influence of heavy metal ions from the raw materials and the COSGB mixtures on the groundwater environment was studied by leaching tests. The research demonstrates that the optimal mix ratio is GGBS mixing amount 4.85%, mass ratio of SS to OSR 0.82, and solid mass concentration 67.69%. At shorter curing age, the hydration products are mainly calcium alumino silicate hydrate (C-A-S-H) and calcium silicate hydrate (C-S-H) gels. With the increase of curing age, ettringite (AFt) and C-S-H gels become the main source of the UCS. Meanwhile, the porosity of the filler decreases continuously. The leaching concentration of heavy metal ions from the COSGB mixtures is all lower than the leaching concentration of raw materials and meet the requirements of the Chinese groundwater quality standard (GB/T 14848-2017). Therefore, this new COSGB cannot pollute the groundwater environment and meets backfill requirements. The proposed technology is a reliable and environmentally friendly alternative for recycling OSR and SS while simultaneously supporting cemented paste backfill (CPB).
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http://dx.doi.org/10.3390/ma14082052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073731PMC
April 2021