Publications by authors named "Wei Xie"

964 Publications

Functional and structural investigation of N-terminal domain of the SpTad2/3 heterodimeric tRNA deaminase.

Comput Struct Biotechnol J 2021 5;19:3384-3393. Epub 2021 Jun 5.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of China.

Editing is a post-transcriptional process that changes the content of nucleic acids occurring on both DNA and RNA levels. Inosine at position 34 in tRNA is one such example, commonly produced via the deamination of A34, catalyzed by adenosine deaminase acting on tRNA (ADAT or Tad). The formation of inosine is essential for cell viability. The eukaryotic deaminases normally consist of the catalytic subunit Tad2 and the structural subunit Tad3, but the catalytic process is poorly understood. Despite the conservation of the (pseudo-) catalytic domains, the heterodimeric enzyme Tad2/3 also possesses additional domains that could exhibit novel functions. Here we present the structure of the N-terminal domain of the Tad2/3 heterodimeric tRNA(A34) deaminase (N-SpTad2), which shares ~30% sequence identities with uridine-cytidine or pantothenate kinases, but lacks the predicted kinase functions. While biochemical assays indicated that the domain is not a nucleic-acid binder, it is able to significantly influence the A34-tRNA deamination activity of the holoenzyme. Through co-expression and purification analyses, we deduce that N-SpTad2 plays a role in mediating protein-protein contacts and enhancing the stability and solubility of SpTad2/3, without which the deaminase is not functional. Taken together, our structural and biochemical studies highlighted the importance of the additional domains to the intrinsic deaminase functions of heterodimeric Tad2/3 enzymes and promoted our understanding on this essential post-transcriptional tRNA modification.
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http://dx.doi.org/10.1016/j.csbj.2021.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217354PMC
June 2021

Surface-Enhanced Raman Spectroscopic Evidences of Key Intermediate Species and Role of NiFe Dual-Catalytic Center in Water Oxidation.

Angew Chem Int Ed Engl 2021 Jun 29. Epub 2021 Jun 29.

Nankai University, College of Chemistry, CHINA.

NiFe-based electrocatalysts have attracted great interests due to the low price and high activity in oxygen evolution reaction (OER). However, the complex reaction mechanism of NiFe-catalyzed OER has not been fully explored yet. Detection of intermediate species can bridge the gap between OER performances and catalyst component/structure properties. Here, we performed label-free surface-enhanced Raman spectroscopic (SERS) monitoring of interfacial OER process on Ni 3 FeO x nanoparticles (NPs) in alkaline medium. By using bifunctional [email protected] 3 FeO x core-satellite superstructures as Raman signal enhancer, we found direct spectroscopic evidences from intermediate O-O - species. According to the SERS results, Fe atoms are the catalytic sites for the initial OH - to O-O - oxidation. The O-O - species adsorbed across neighboring Fe and Ni sites experiences further oxidation caused by electron transfer to Ni(III) and eventually forms O 2 product. This work shows spectroscopic evidence of interfacial intermediates and confirms the dual-metal-centered catalysis in OER on NiFe oxides, which may provide a guidance for rational design of high-performance OER electrocatalysts.
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http://dx.doi.org/10.1002/anie.202103888DOI Listing
June 2021

The relationship between dietary patterns and overweight and obesity among adult in Jiangsu Province of China: a structural equation model.

BMC Public Health 2021 06 25;21(1):1225. Epub 2021 Jun 25.

Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, China.

Aims: This study aimed to analyze the relationship between diet and overweight and obesity in Jiangsu Province by using structural equation modeling (SEM), and to determine dietary differences between genders in the model.

Methods: Data from 1739 individuals (53.8% female, n = 935) were analyzed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to classify dietary patterns. SEM and multivariate logistic regression were used to explore the relationship between dietary patterns and overweight and obesity.

Results: Overweight and obesity was found in 49.1%, and no difference was found in gender (51.2% of men and 47.2% of women, respectively; P = 0.090). Three dietary patterns: the traditional dietary pattern (i.e., poultry, light-colored vegetables, red meat and its products, cereals and tubers products, condiment, oils and dark-colored vegetables), the fruit-egg dietary pattern (i.e., fruit, whole grains, pickled vegetables and eggs and eggs products) and nut-wine dietary pattern (i.e., nut, wine and pastry snacks) were established by using EFA and CFA. It was found that the traditional dietary pattern for adult male was positively associated with the overweight and obesity in Jiangsu Province of China through multivariate logistic regression and SEM (OR = 1.954; 95%CI: 1.258 ~ 3.036; β =0.121, P < 0.05, respectively).

Conclusion: The traditional dietary pattern only have positive association with overweight and obesity in men in Jiangsu Province, China.
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http://dx.doi.org/10.1186/s12889-021-11341-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229268PMC
June 2021

Insights into the Catalytic Mechanism of a Novel XynA and Structure-Based Engineering for Improving Bifunctional Activities.

Biochemistry 2021 Jul 22;60(26):2071-2083. Epub 2021 Jun 22.

Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.

Xylan and cellulose are the two major constituents of numerous types of lignocellulose. The bifunctional enzyme that exhibits xylanase/cellulase activity has attracted a great deal of attention in biofuel production. Previously, a thermostable GH10 family enzyme (XynA) from sp. KW1 was found to degrade both xylan and cellulose. To improve bifunctional activity on the basis of structure, we first determined the crystal structure of XynA at 2.3 Å. Via molecular docking and activity assays, we revealed that Gln250 and His252 were indispensable to bifunctionality, because they could interact with two conserved catalytic residues, Glu182 and Glu280, while bringing the substrate close to the activity pocket. Then we used a structure-based engineering strategy to improve xylanase/cellulase activity. Although no mutants with increased bifunctional activity were obtained after much screening, we found the answer in the N-terminal 36-amino acid truncation of XynA. The activities of XynA_ΔN36 toward beechwood xylan, wheat arabinoxylan, filter paper, and barley β-glucan were significantly increased by 0.47-, 0.53-, 2.46-, and 1.04-fold, respectively. Furthermore, upon application, this truncation released more reducing sugars than the wild type in the degradation of pretreated corn stover and sugar cane bagasse. These results showed the detailed molecular mechanism of the GH10 family bifunctional endoxylanase/cellulase. The basis of these catalytic performances and the screened XynA_ΔN36 provide clues for the further use of XynA in industrial applications.
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http://dx.doi.org/10.1021/acs.biochem.1c00134DOI Listing
July 2021

An Insight into the Effects of SnF Assisting the Performance of Lead-Free Perovskite of FASnI: A First-Principles Calculations.

ACS Omega 2021 Jun 3;6(23):14938-14951. Epub 2021 Jun 3.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, P.R. China.

It is an effective method to use SnF and SnF molecules to assist in enhancing the performance of FASnI perovskite. However, the mechanism in this case is not clear as it lacks a certain explanation to specify the phenomenon. Through first-principles calculations, this paper constructed several modes of SnF and SnF adsorbed on the surfaces of FASnI and explored adsorption energies, band structures, photoelectric properties, absorption spectra, and dielectric functions. The SnF molecule adsorbed at the I5 position on the FAI-T surface has the lowest adsorption energy for the F atom, which is 0.5376 eV. The Sn-I bond and Sn-F bond mainly affect the photoelectric properties of FASnI perovskite solar cells, and the SnF adsorption on the FAI-T surface can effectively strengthen the bond energies, which shortens the bond lengths of the Sn-I and Sn-F bond, and eliminate surface unsaturated bonds to passivate the surface defects. Furthermore, the probability of energy transfer was lower between the SnF molecule and the ion around it than between SnF and its ion. Especially, in the aspect of optical properties, we found that the intensity of the absorption peak of SnF adsorption increase was larger than that of SnF adsorption. Additionally, the static dielectric constants of SnF adsorption on the two surfaces, denoted SnF, made the perovskite respond more slowly to the external electric field. Based on this work, we found that SnF had a greater positive effect on the optical property of perovskite than SnF. We consider that our results can help to deeply understand the essence of SnF assistance in the performance of FASnI and help researchers strive for lead-free perovskite solar cells.
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http://dx.doi.org/10.1021/acsomega.1c00767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209804PMC
June 2021

MiR-206 regulates the Th17/Treg ratio during osteoarthritis.

Mol Med 2021 Jun 19;27(1):64. Epub 2021 Jun 19.

Department of Orthopedics, Hubei Provincial Hospital of Traditional Chinese Medicine, No.4, Hua-Yuan-Shan, Yanzhi Road, Wuchang District, Wuhan, 430061, Hubei, China.

Background: The present study aimed to determine the functional role of miR-206 in T helper 17 (Th17)/regulatory T (Treg) cell differentiation during the development of osteoarthritis (OA).

Methods: Patients with OA and healthy controls were recruited for investigating the association between miR-206 and Th17/Treg ratio. Transfection experiments were conducted in CD4 T cells to verify the mechanism of miR-206 on the balance of Treg/Th17. OA model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. OA model was induced in rats to verify the effect of miR-206 inhibition on Th17/Treg immunoregulation.

Results: High expression of miR-206 was positively correlated with peripheral Th17/Treg imbalance in patients with OA. The interactions between miR-206 and the 3' untranslated regions (3'-UTR) of suppressor of cytokine signaling-3 (SOCS3) and fork head transcriptional factor 3 (Foxp3) were confirmed by luciferase reporter assays. MiR-206 disturbed the Th17/Treg balance by targeting SOCS3 and Foxp3. In vivo assay demonstrated that antagomiR directed against miR-206 restored Th17/Treg balance during the development of OA.

Conclusion: MiR-206 contributed to the progression of OA by modulating Th17/Treg imbalance, suggesting that miR-206 inhibition might be a promising therapeutic strategy for the treatment of OA.
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http://dx.doi.org/10.1186/s10020-021-00315-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214293PMC
June 2021

The loss of heterochromatin is associated with multiscale three-dimensional genome reorganization and aberrant transcription during cellular senescence.

Genome Res 2021 Jun 17. Epub 2021 Jun 17.

MOE Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Department of Automation, Tsinghua University, Beijing 100084, China.

Heterochromatin remodeling is critical for various cell processes. In particular, the "loss of heterochromatin" phenotype in cellular senescence is associated with the process of aging and age-related disorders. Although biological processes of senescent cells, including senescence-associated heterochromatin foci (SAHF) formation, chromosome compaction, and redistribution of key proteins, have been closely associated with high-order chromatin structure, the relationship between the high-order chromatin reorganization and the loss of heterochromatin phenotype during senescence has not been fully understood. By using senescent and deep senescent fibroblasts induced by DNA damage harboring the "loss of heterochromatin" phenotype, we observed progressive 3D reorganization of heterochromatin during senescence. Facultative and constitutive heterochromatin marked by H3K27me3 and H3K9me3, respectively, show different alterations. Facultative heterochromatin tends to switch from the repressive B-compartment to the active A-compartment, whereas constitutive heterochromatin shows no significant changes at the compartment level but enhanced interactions between themselves. Both types of heterochromatin show increased chromatin accessibility and gene expression leakage during senescence. Furthermore, increased chromatin accessibility in potential CTCF binding sites accompanies the establishment of novel loops in constitutive heterochromatin. Finally, we also observed aberrant expression of repetitive elements, including LTR (long terminal repeat) and satellite classes. Overall, facultative and constitutive heterochromatin show both similar and distinct multiscale alterations in the 3D map, chromatin accessibility, and gene expression leakage. This study provides an epigenomic map of heterochromatin reorganization during senescence.
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http://dx.doi.org/10.1101/gr.275235.121DOI Listing
June 2021

Exploration of a ternary deep eutectic solvent for the efficient extraction of plantamajoside, acteoside, quercetin and kaempferol from Plantago asiatica L.

Phytochem Anal 2021 Jun 16. Epub 2021 Jun 16.

College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330006, P.R. China.

Introduction: In the present study, ternary deep eutectic solvent-based ultrasound-assisted extraction was developed for the efficient extraction of plantamajoside, acteoside, quercetin and kaempferol from Plantago asiatica L.

Methodology: Six kinds of choline chloride-based ternary deep eutectic solvents (TDESs) were prepared as potential extraction solutions. In order to obtain optimal extraction efficiency, a series of extraction conditions were investigated by single-factor test and orthogonal test.

Results: The extraction efficiency of choline chloride/lactic acid/ethylene glycol (ChCl-LA-EG) was much higher than that of other TDESs. ChCl-LA-EG-11 synthesised with choline chloride, lactic acid and ethylene glycol (1:4:2) was considered to have a higher extraction efficiency. The optimal ultrasound-assisted extraction conditions were as follows: water content in ChCl-LA-EG-11, 50%; extraction temperature, 70°C; ratio of solid/liquid, 20 mg/mL; ultrasonic power, 60 W; extraction time, 35 min; pH of the solution, 8. Under the optimal extraction conditions, the extraction efficiencies of plantamajoside, acteoside, quercetin and kaempferol were 3.83 ± 0.41, 4.23 ± 0.45, 0.56 ± 0.15 and 0.19 ± 0.08 mg/g, respectively. The extraction efficiency of the total target components was 9.21 ± 0.63 mg/g, which was much higher than that of conventional solvents (water, methanol, ethanol, 50% methanol, 50% ethanol). The target components were isolated efficiently from the TDES solution by an AB-8 macroporous resin column with a recovery rate of 95.6%.

Conclusion: This study demonstrated that TDESs possessed excellent physical and chemical properties and had enormous potential for active component extraction of traditional Chinese medicinal materials.
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http://dx.doi.org/10.1002/pca.3071DOI Listing
June 2021

IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms.

J Immunother Cancer 2021 Jun;9(6)

Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France

Background: Pharmacological autophagy enhancement constitutes a preclinically validated strategy for preventing or treating most major age-associated diseases. Driven by this consideration, we performed a high-content/high-throughput screen on 65 000 distinct compounds on a robotized fluorescence microscopy platform to identify novel autophagy inducers.

Results: Here, we report the discovery of picropodophyllin (PPP) as a potent inducer of autophagic flux that acts on-target, as an inhibitor of the tyrosine kinase activity of the insulin-like growth factor-1 receptor (IGF1R). Thus, PPP lost its autophagy-stimulatory activity in cells engineered to lack IGF1R or to express a constitutively active AKT serine/threonine kinase 1 (AKT1) mutant. When administered to cancer-bearing mice, PPP improved the therapeutic efficacy of chemoimmunotherapy with a combination of immunogenic cytotoxicants and programmed cell death 1 (PDCD1, better known as PD-1) blockade. These PPP effects were lost when tumors were rendered PPP-insensitive or autophagy-incompetent. In combination with chemotherapy, PPP enhanced the infiltration of tumors by cytotoxic T lymphocytes, while reducing regulatory T cells. In human triple-negative breast cancer patients, the activating phosphorylation of IGF1R correlated with inhibited autophagy, an unfavorable local immune profile, and poor prognosis.

Conclusion: Altogether, these results suggest that IGF1R may constitute a novel and druggable therapeutic target for the treatment of cancer in conjunction with chemoimmunotherapies.
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http://dx.doi.org/10.1136/jitc-2021-002722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204183PMC
June 2021

Self-Constructed Multiple Plasmonic Hotspots on an Individual Fractal to Amplify Broadband Hot Electron Generation.

ACS Nano 2021 Jun 11;15(6):10553-10564. Epub 2021 Jun 11.

School of Materials Science and Engineering, Tianjin University, Tianjin 300350, P.R. China.

Plasmonic nanoparticles are ideal candidates for hot-electron-assisted applications, but their narrow resonance region and limited hotspot number hindered the energy utilization of broadband solar energy. Inspired by tree branches, we designed and chemically synthesized silver fractals, which enable self-constructed hotspots and multiple plasmonic resonances, extending the broadband generation of hot electrons for better matching with the solar radiation spectrum. We directly revealed the plasmonic origin, the spatial distribution, and the decay dynamics of hot electrons on the single-particle level by using simulation, dark-field spectroscopy, pump-probe measurements, and electron energy loss spectroscopy. Our results show that fractals with acute tips and narrow gaps can support broadband resonances (400-1100 nm) and a large number of randomly distributed hotspots, which can provide unpolarized enhanced near field and promote hot electron generation. As a proof-of-concept, hot-electron-triggered dimerization of -nitropthiophenol and hydrogen production are investigated under various irradiations, and the promoted hot electron generation on fractals was confirmed with significantly improved efficiency.
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http://dx.doi.org/10.1021/acsnano.1c03218DOI Listing
June 2021

Te-Pei Feng: a pioneer of neuromuscular physiology in China.

Protein Cell 2021 Jun 7. Epub 2021 Jun 7.

Social and Behavioral Sciences Faculty, Leiden University, 2333AC, Leiden, The Netherlands.

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http://dx.doi.org/10.1007/s13238-021-00850-xDOI Listing
June 2021

Interfacial Binding Energy between Calcium-Silicate-Hydrates and Epoxy Resin: A Molecular Dynamics Study.

Polymers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Guangdong Provincial Key Laboratory of Durability for Marine Civil Engineering, College of Civil and Transportation Engineering, Shenzhen University, Shenzhen 518060, China.

Microcapsules encapsulated within epoxy as a curing agent have been successfully applied in self-healing materials, in which the healing performance significantly depends on the binding behaviour of the epoxy curing agent with the cement matrix. In this paper, the binding energy was investigated by molecular dynamics simulation, which could overcome the shortcomings of traditional microscopic experimental methods. In addition to the construction of different molecular models of epoxy, curing agents, and dilutants, seven models were established to investigate the effects of chain length, curing agent, and epoxy resin chain direction on the interfacial binding energy. The results showed that an increase of chain length exhibited had limited effect on the binding energy, while the curing agent and the direction of the epoxy significantly affected the interfacial binding energy. Among different factors, the curing agent tetrethylenepentamine exhibited the highest value of interfacial binding energy by an increment of 31.03 kcal/mol, indicating a better binding ability of the microcapsule core and the cement matrix. This study provides a microscopic insight into the interface behaviour between the microcapsule core and the cement matrix.
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http://dx.doi.org/10.3390/polym13111683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196693PMC
May 2021

Bcl-xL mutant promotes cartilage differentiation of BMSCs by upregulating TGF-β/BMP expression levels.

Exp Ther Med 2021 Jul 9;22(1):736. Epub 2021 May 9.

Foot and Ankle Surgery, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.

Bcl-xL is a transmembrane molecule in the mitochondria, with apoptosis-related and pro-metabolic functions, that also plays a role in chondrogenesis and differentiation. A Bcl-xL mutant, in which the GRI sequence is replaced by ELN, has no anti-apoptotic effect, while other biological functions of this mutant remain unchanged. The present study investigated the impact of this Bcl-xL mutant on cartilage differentiation and the expression levels of TGF-β and bone morphogenetic protein (BMP). Human bone marrow mesenchymal stem cells (BMSCs) were transfected with Bcl-xL and Bcl-xL mutant (∆Bcl-xL) overexpression vectors. The cells were divided into four groups: Control (not subjected to any transfection), EV (empty pcDNA3.1-Bcl-xL vector), OV (Bcl-xL overexpression) and ∆OV (∆Bcl-xL overexpression). Saffron and toluidine blue staining was performed to observe cartilage tissue formation. Flow cytometry was conducted to measure BMSC apoptosis. The expression levels of TGF-β and BMP were evaluated using reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Compared with that in the control group, the expression levels of Bcl-xL in the OV group increased significantly (P<0.05). Western blotting and RT-qPCR results revealed that OV and ∆OV treatment increased the expression levels of TGF-β and BMP in transfected cells, compared to their expression in the control and EV groups (P<0.05). Saffron and toluidine blue staining results showed that cartilage formation was increased in the ∆OV and ∆OV + Bax-/Bak-groups to similar degrees. Cell apoptosis in the ∆OV group did not change compared with that in the control group. The Bcl-xL mutant promoted cartilage differentiation of BMSCs and upregulated TGF-β/BMP expression. This enhancement of chondrogenic differentiation was not related to the expression of Bax and Bak. Taken together, these findings provided for improved application of bone tissue engineering technology in the treatment of articular cartilage defects.
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http://dx.doi.org/10.3892/etm.2021.10168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138271PMC
July 2021

Disruption of the autism-related gene Pak1 causes stereocilia disorganization, hair cell loss, and deafness in mice.

J Genet Genomics 2021 Apr 24. Epub 2021 Apr 24.

State Key Laboratory of Bioelectronics, School of Life Sciences and Technology, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, Jiangsu 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226019, China; Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing 100864, China; Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing 100069, China. Electronic address:

Several clinical studies have reported that hearing loss is correlated with autism in children. However, little is known about the underlying mechanism between hearing loss and autism. p21-activated kinases (PAKs) are a family of serine/threonine kinases that can be activated by multiple signaling molecules, particularly the Rho family of small GTPases. Previous studies have shown that Pak1 mutations are associated with autism. In the present study, we take advantage of Pak1 knockout (Pak1) mice to investigate the role of PAK1 in hearing function. We find that PAK1 is highly expressed in the postnatal mouse cochlea and that PAK1 deficiency leads to hair cell (HC) apoptosis and severe hearing loss. Further investigation indicates that PAK1 deficiency downregulates the phosphorylation of cofilin and ezrin-radixin-moesin and the expression of βII-spectrin, which further decreases the HC synapse density in the basal turn of cochlea and disorganized the HC stereocilia in all three turns of cochlea in Pak1 mice. Overall, our work demonstrates that the autism-related gene Pak1 plays a crucial role in hearing function. As the first candidate gene linking autism and hearing loss, Pak1 may serve as a potential target for the clinical diagnosis of autism-related hearing loss.
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http://dx.doi.org/10.1016/j.jgg.2021.03.010DOI Listing
April 2021

N-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation.

Cancer Cell 2021 Jul 27;39(7):958-972.e8. Epub 2021 May 27.

Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

N-Methyladenosine (mA) on mRNAs mediates different biological processes and its dysregulation contributes to tumorigenesis. How mA dictates its diverse molecular and cellular effects in leukemias remains unknown. We found that YTHDC1 is the essential mA reader in myeloid leukemia from a genome-wide CRISPR screen and that mA is required for YTHDC1 to undergo liquid-liquid phase separation and form nuclear YTHDC1-mA condensates (nYACs). The number of nYACs increases in acute myeloid leukemia (AML) cells compared with normal hematopoietic stem and progenitor cells. AML cells require the nYACs to maintain cell survival and the undifferentiated state that is critical for leukemia maintenance. Furthermore, nYACs enable YTHDC1 to protect mA-mRNAs from the PAXT complex and exosome-associated RNA degradation. Collectively, mA is required for the formation of a nuclear body mediated by phase separation that maintains mRNA stability and control cancer cell survival and differentiation.
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http://dx.doi.org/10.1016/j.ccell.2021.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282764PMC
July 2021

Reinforcement Learning Assisted Oxygen Therapy for COVID-19 Patients Under Intensive Care.

ArXiv 2021 May 19. Epub 2021 May 19.

Patients with severe Coronavirus disease 19 (COVID-19) typically require supplemental oxygen as an essential treatment. We developed a machine learning algorithm, based on a deep Reinforcement Learning (RL), for continuous management of oxygen flow rate for critical ill patients under intensive care, which can identify the optimal personalized oxygen flow rate with strong potentials to reduce mortality rate relative to the current clinical practice. Basically, we modeled the oxygen flow trajectory of COVID-19 patients and their health outcomes as a Markov decision process. Based on individual patient characteristics and health status, a reinforcement learning based oxygen control policy is learned and real-time recommends the oxygen flow rate to reduce the mortality rate. We assessed the performance of proposed methods through cross validation by using a retrospective cohort of 1,372 critically ill patients with COVID-19 from New York University Langone Health ambulatory care with electronic health records from April 2020 to January 2021. The mean mortality rate under the RL algorithm is lower than standard of care by 2.57% (95% CI: 2.08- 3.06) reduction (P<0.001) from 7.94% under the standard of care to 5.37 % under our algorithm and the averaged recommended oxygen flow rate is 1.28 L/min (95% CI: 1.14-1.42) lower than the rate actually delivered to patients. Thus, the RL algorithm could potentially lead to better intensive care treatment that can reduce mortality rate, while saving the oxygen scarce resources. It can reduce the oxygen shortage issue and improve public health during the COVID-19 pandemic.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142656PMC
May 2021

Tolerogenic dendritic cells suppress titanium particle-induced inflammation.

Exp Ther Med 2021 Jul 3;22(1):712. Epub 2021 May 3.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Aseptic loosening is a major complication of prosthetic joint surgery. The leading cause of arthroplasty failure is particulate wear debris such as titanium particles. Dendritic cells (DCs) are one type of immune cells that play an important role in the initiation and progression of inflammatory processes. DCs can develop into tolerogenic DCs (tolDCs), which present an alternative therapeutic strategy for inflammatory disorders. Previously, antigen-specific tolDCs were generated, which showed a promising effect in treating inflammatory arthritis and immune thrombocytopenia. The present study reports that tolDCs effectively inhibited titanium particle-induced inflammation in an air-pouch mouse model by decreasing pro-inflammatory cytokines. In addition, a mechanistic study demonstrated that tolDCs significantly protected against titanium particle-induced inflammatory processes by releasing anti-inflammatory cytokines, such as interleukin-10. Collectively, these findings not only demonstrate that tolDCs play an important role in inhibiting titanium particle-induced inflammation but also provide a potential alternative for the prevention or treatment of titanium particle-induced inflammation.
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http://dx.doi.org/10.3892/etm.2021.10144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120651PMC
July 2021

Identification and coregulation pattern analysis of long noncoding RNAs following subacute spinal cord injury.

J Orthop Res 2021 May 15. Epub 2021 May 15.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Long noncoding RNAs (lncRNAs) have been demonstrated to play critical regulatory roles in posttranscriptional and transcriptional regulation in eukaryotic cells. However, the characteristics of many lncRNAs, particularly their expression patterns in the lesion epicenter of spinal tissues following subacute spinal cord injury (SCI), remain unclear. In this study, we determined the expression profiles of lncRNAs in the lesion epicenter of spinal tissues after traumatic SCI and predicted latent regulatory networks. Standard Allen's drop surgery was conducted on mice, and hematoxylin and eosin staining was used to observe the damaged area. High-throughput sequencing was performed to identify the differential expression profiles of lncRNAs. Quantitative real-time polymerase chain reaction was conducted to evaluate the quality of the sequencing results. Bioinformatics analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, coexpression analysis, and protein-protein interaction analysis, were performed. Targeted binding of lncRNA-miRNA-mRNA was predicted by TargetScan and miRanda. A total of 230 differentially expressed lncRNAs were identified and preliminarily verified, and some potential regulatory networks were constructed. These findings improve our understanding of the mechanisms underlying subacute SCI; differentially expressed lncRNAs are closely involved in pathophysiological processes by regulating multiple pathways. Further studies are essential for revealing the exact mechanism underlying competing endogenous RNA pathways in vivo and in vitro.
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http://dx.doi.org/10.1002/jor.25101DOI Listing
May 2021

Estimated assessment of dietary exposure to artificial sweeteners from processed food in Nanjing, China.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2021 Jul 14;38(7):1105-1117. Epub 2021 May 14.

Department of Nutrition and Food Hygiene, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, Jiangsu, China.

The objective of this study was to measure the concentrations of three intensity sweeteners (Acesulfame-K, cyclamate and saccharin) in different categories of food available on the Nanjing market, and to investigate whether the Nanjing general population was at risk for exceeding the ADI of sweeteners. A set of 1885 foods was collected and analysed using the National Food Safety Standard procedure in order to establish the concentration levels of the sweeteners. Dietary exposure was estimated using probabilistic modelling software and compared directly with each sweetener's ADI. Consumption data from the China National Nutrition and Health Survey (conducted in 2010-2013) and the actual concentrations of sweeteners in the collected food products were used to perform the intake assessment. The results indicated that Acesulfame-K and cyclamate were commonly used in processed food, and processed nuts, preserved fruit, beverages, and bakery products are the main sources of sweeteners in Nanjing. The estimated exposure of sweeteners in Nanjing was well below the ADIs, as relative intakes at the 95th percentile were 29.7% for saccharin, 79.8% for cyclamate, and 35.9% for Acesulfame-K of the respective ADIs. It was concluded that adults were not at risk of exceeding ADIs for these sweeteners, but the intake of cyclamate at the higher percentiles by children may approach or slightly exceed ADI values.
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http://dx.doi.org/10.1080/19440049.2021.1905883DOI Listing
July 2021

Decoding brain encoded by genome.

Yi Chuan 2021 May;43(5):393-396

The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China.

Human brain is the most complicated living organ in nature. How the human genome encodes the structure and function of brain is a fundamental question to understand the essence of mind. Currently, it is still an unsolved scientific problem requiring the further breakthrough of comprehensive technologies. Here, we summarize the recent advances in brain development/function OMICS studies, and discuss the huge challenges and prospects in understanding how brain is encoded by genome.
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http://dx.doi.org/10.16288/j.yczz.21-019DOI Listing
May 2021

PD-1 blockade combined with IL-33 enhances the antitumor immune response in a type-1 lymphocyte-mediated manner.

Cancer Treat Res Commun 2021 Apr 23;28:100379. Epub 2021 Apr 23.

Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou 215006, China; Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address:

PD-1 immune checkpoint blockade and cytokine IL-33 have shown significant therapeutic effects in tumor immunotherapy. These therapies promote CD8 T cell activation, proliferation, and effector functions. However, there were few research about the combined therapy efficacy. In this study, we established B16-empty vector and B16-IL33 melanoma mouse models and treated with PD-1 monoclonal antibody. We reported that PD-1 blockade combined with cytokine IL-33 further inhibited tumor progression and prolonged the survival of tumor-bearing mice. Mechanistically, the combination therapy was found to further facilitate CD4 and CD8 T lymphocytes accumulation, and enhance the antitumor effects of CD4or CD8tumor-infiltrating lymphocytes by promoting type-1 immune response within the tumor microenvironment using flow cytometry and quantitative real time polymerase chain reaction. Thus, PD-1 blockade combined with IL-33 has application potential in tumor immunotherapy. Further, this study provides a new promising strategy and theoretical basis for tumor combination immunotherapy.
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http://dx.doi.org/10.1016/j.ctarc.2021.100379DOI Listing
April 2021

Mechanistic Insight into the Peptide Binding Modes to Two MazF Toxins.

Toxins (Basel) 2021 04 28;13(5). Epub 2021 Apr 28.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou 510006, China.

Tuberculosis (TB) is a contagious disease caused by (). It is regarded as a major health threat all over the world, mainly because of its high mortality and drug-resistant nature. Toxin-antitoxin (TA) systems are modules ubiquitously found in prokaryotic organisms, and the well-studied MazEF systems (MazE means "what is it?" in Hebrew) are implicated in the formation of "persister cells" in the pathogen. Here, we report cocrystal structures of MazF-mt1 and -mt9, two important MazF members responsible for specific mRNA and tRNA cleavages, respectively, in complexes with truncated forms of their cognate antitoxin peptides. These peptides bind to the toxins with comparable affinities to their full-length antitoxins, which would reduce the RNA-cleavage capacities of the toxins in vitro. After structural analysis of the binding modes, we systemically tested the influence of the substitutions of individual residues in the truncated MazE-mt9 peptide on its affinity. This study provides structural insight into the binding modes and the inhibition mechanisms between the MazE/F-mt TA pairs. More importantly, it contributes to the future design of peptide-based antimicrobial agents against TB and potentially relieves the drug-resistance problems by targeting novel proteins.
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http://dx.doi.org/10.3390/toxins13050319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145246PMC
April 2021

Asprosin-neutralizing antibodies as a treatment for metabolic syndrome.

Elife 2021 Apr 27;10. Epub 2021 Apr 27.

Harrington Discovery Institute, University Hospitals, Cleveland, United States.

Background: Recently, we discovered a new glucogenic and centrally acting orexigenic hormone - asprosin. Asprosin is elevated in metabolic syndrome (MS) patients, and its genetic loss results in reduced appetite, leanness, and blood glucose burden, leading to protection from MS.

Methods: We generated three independent monoclonal antibodies (mAbs) that recognize unique asprosin epitopes and investigated their preclinical efficacy and tolerability in the treatment of MS.

Results: Anti-asprosin mAbs from three distinct species lowered appetite and body weight, and reduced blood glucose in a dose-dependent and epitope-agnostic fashion in three independent MS mouse models, with an IC50 of ~1.5 mg/kg. The mAbs displayed a half-life of over 3days in vivo, with equilibrium dissociation-constants in picomolar to low nanomolar range.

Conclusions: We demonstrate that anti-asprosin mAbs are dual-effect pharmacologic therapy that targets two key pillars of MS - over-nutrition and hyperglycemia. This evidence paves the way for further development towards an investigational new drug application and subsequent human trials for treatment of MS, a defining physical ailment of our time.

Funding: DK118290 and DK125403 (R01; National Institute of Diabetes and Digestive and Kidney Diseases), DK102529 (K08; National Institute of Diabetes and Digestive and Kidney Diseases), Caroline Wiess Law Scholarship (Baylor College of Medicine, Harrington Investigatorship Harrington Discovery Institute at University Hospitals, Cleveland); Chao Physician Scientist Award (Baylor College of Medicine); RP150551 and RP190561 (Cancer Prevention and Research Institute of Texas [CPRIT]).
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http://dx.doi.org/10.7554/eLife.63784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102062PMC
April 2021

OsMORF9 is necessary for chloroplast development and seedling survival in rice.

Plant Sci 2021 Jun 7;307:110907. Epub 2021 Apr 7.

State Key Lab of Rice Biology, China National Rice Research Institute, Hangzhou, 310006, China. Electronic address:

Chloroplasts are closely associated with the growth and development of higher plants. Accumulating evidence has revealed that the multiple organellar RNA editing factors (MORF) family of proteins influences plastidic and mitochondrial development through post-transcriptional regulation. However, the role of MORFs in regulating the development of chloroplasts in rice is still unclear. The OsMORF9 gene belongs to a small family of 7 genes in rice and is highly expressed in young leaves. We used the CRISPR/Cas9 system to mutate OsMORF9. The resulting knockout lines osmorf9-1 and osmorf9-2 exhibited an albino seedling lethal phenotype. Besides, the expression of many plastid-encoded genes involved in photosynthesis, the biogenesis of plastidic ribosomes and the editing and splicing of specific plastidic RNA molecules were severely affected in these two OsMORF9 mutants. Furthermore, yeast two-hybrid analysis revealed that OsMORF9 could interact with OsSLA4 and DUA1 which are members of the pentatricopeptide repeat (PPR) family of proteins. Analysis of subcellular localization of OsMORF9 also suggested that it might function in chloroplasts. The findings from the present study demonstrated the critical role of OsMORF9 in the biogenesis of chloroplast ribosomes, chloroplast development and seedling survival. This therefore provides new insights on the function of MORF proteins in rice.
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http://dx.doi.org/10.1016/j.plantsci.2021.110907DOI Listing
June 2021

[Clinical application of self-made minimally invasive hood-assisted transforaminal lumbar interbody fusion via modified bilateral Wiltse approach in the treatment of lumbar degenerative diseases].

Zhongguo Gu Shang 2021 Apr;34(4):297-303

Hubei 672 Integrated Chinese and Western Medicine Orthopaedics Hospital, Wuhan 430000, Hubei, China.

Objective: To explore the advantages of self made minimally invasive hook assisted transforaminal lumbar interbody fusion (TLIF) via modified bilateral Wiltse approach in the treatment of lumbar degenerative diseases.

Methods: The clinical data of 140 patients underwent lumbar spine fusion surgery from October 2016 to October 2017 were retrospectively analyzed. Among them, 72 cases were treated by self-made minimally invasive hook-assisted TLIF via modified bilateral Wiltse approach (group A), there were 37 males and 35 females, aged (48±16) years old;68 cases were treated by TLIF via traditional posterior median approach (group B ), there were 38 males and 30 females, aged (45±15) years old. The surgical incision size, operation time, intraoperative blood loss volume, postoperative drainage volume, postoperative wound healing, and intervertebral fusion rate at the final follow-up were recorded between two groups. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to assess the clinical efficacy.

Results: All the patients were followed up for 3 to 13 (8±5) months. The wound in group A healed well after operation, and 1 case in group B occurred wound necrosis after operation, and healed after debridement and suture. There were no significant differences in operation time and postoperative fusion rate between two surgical methods (>0.05). Group A had obvious advantages in surgical incision size, intraoperative blood loss volume and postoperative drainage volume (<0.05), and the postoperative VAS score of low back pain and ODI were better than group B (<0.05).

Conclusion: The self made minimally invasive hook assistedTLIF via modified bilateral Wiltse approach has the characteristics of minimally invasive, less intraoperative blood loss, less postoperative drainage, fewer complications, and more stable fusion in the treatment of lumbar degenerative desease.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.04.002DOI Listing
April 2021

Predictive Factors for In-Hospital Preoperative Rupture in Hyperacute Type A Aortic Dissection.

Heart Surg Forum 2021 04 23;24(2):E379-E386. Epub 2021 Apr 23.

Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing China.

Objective: This study aims to figure out risk factors of in-hospital preoperative rupture of hyperacute type A aortic dissection (haTAAD) patients and build a prediction and risk stratification model.

Methods: From January 2011 to December 2019, 830 patients diagnosed as haTAAD from Nanjing Drum Tower Hospital were enrolled. Among them, 799 patients received prompt surgery and 31 suffered aortic rupture before operation. The association between in-hospital preoperative rupture and perioperative parameters were examined. Best subset selection was used for feature selection and ROC curve was used to identify the model.

Results: Age, winter season, back pain, preoperative hypotension, albumin and globulin ratio, high serum phosphorus level are risk factors for in-hospital preoperative rupture of haTAAD. On the basis of six variables with AUC 0.828, a nomogram was established. According to the robustness test, actual in-hospital preoperative ruptures were fitted well.

Conclusions: The in-hospital rupture prediction model was developed using logistic regression analysis. High serum phosphorus level is one of the strongest predictors. This nomogram may be useful when evaluating the risk of aortic dissection in-hospital rupture in future trials.
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http://dx.doi.org/10.1532/hsf.3765DOI Listing
April 2021

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19.

J Antimicrob Chemother 2021 06;76(7):1874-1885

Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, RJ, Brazil.

Background: Current approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity.

Methods: SARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19.

Results: Daclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 μM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans.

Conclusions: Daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy.
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http://dx.doi.org/10.1093/jac/dkab072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083231PMC
June 2021

Surface plasmon mediates the visible light-responsive lithium-oxygen battery with Au nanoparticles on defective carbon nitride.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Renewable Energy Conversion and Storage Center, College of Chemistry, Nankai University, Tianjin 300071, China.

Aprotic lithium-oxygen (Li-O) batteries have gained extensive interest in the past decade, but are plagued by slow reaction kinetics and induced large-voltage hysteresis. Herein, we use a plasmonic heterojunction of Au nanoparticle (NP)-decorated CN with nitrogen vacancies (Au/N-CN) as a bifunctional catalyst to promote oxygen cathode reactions of the visible light-responsive Li-O battery. The nitrogen vacancies on N-CN can adsorb and activate O molecules, which are subsequently converted to LiO as the discharge product by photogenerated hot electrons from plasmonic Au NPs. While charging, the holes on Au NPs drive the reverse decomposition of LiO with a reduced applied voltage. The discharge voltage of the Li-O battery with Au/N-CN is significantly raised to 3.16 V under illumination, exceeding its equilibrium voltage, and the decreased charge voltage of 3.26 V has good rate capability and cycle stability. This is ascribed to the plasmonic hot electrons on Au NPs pumped from the conduction bands of N-CN and the prolonged carrier life span of Au/N-CN This work highlights the vital role of plasmonic enhancement and sheds light on the design of semiconductors for visible light-mediated Li-O batteries and beyond.
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http://dx.doi.org/10.1073/pnas.2024619118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092409PMC
April 2021

The Amyloid Aggregation Accelerator Diacetyl Prevents Cognitive Decline in Alzheimer's Mouse Models.

Chem Res Toxicol 2021 May 15;34(5):1355-1366. Epub 2021 Apr 15.

Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.

Diacetyl (DA), a food flavorant, is linked with occupational lung disease. Our experiments described the formation of a covalent adduct by DA with Arg of the Aβ peptide, which resulted in only a transient increase in neurotoxicity in SH-SY5Y cells. However, implications of these effects on Alzheimer's disease (AD) pathogenesis and the underlying mechanisms remain poorly understood. In the APP/PS1 transgenic AD mouse model, DA treatment did not exacerbate learning and memory deficits in the Morris water maze test. Moreover, DA increased the Aβ plaque burden and decreased neuronal inflammation in the transgenic AD mice. Additionally, cognitive impairment induced by intracerebroventricular Aβ was restored by the DA treatment, as assessed by the T-maze test. A corresponding mitigation of neuronal inflammation was also observed in the hippocampus of these nontransgenic mice due to the acceleration of Aβ aggregation by DA into nontoxic plaques. The data from SDS-PAGE, dot-blot, and TEM experiments corroborated the acceleration of the Aβ aggregation observed in AD animal models and characterized the DA-induced formation of Aβ fibrils. Such Aβ-DA fibrils were unstable in the presence of detergent and amenable to detection by the thioflavin T reagent, thus underscoring the distinct assembly of these fibrils compared to that of the fibrils of the native Aβ. Taken together, the results of this study present for the first time the implications of the DA-induced acceleration of Aβ and may provide a strategy for the rational design of Aβ aggregation accelerators as AD therapeutics that promote oligomer-free Aβ fibril formation.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00089DOI Listing
May 2021

Prompt surgery is effective for acute type A aortic dissection with cerebral ischemia.

J Thorac Dis 2021 Mar;13(3):1403-1412

Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

Background: Acute type A aortic dissection (aTAAD) with preoperative cerebral ischemia (CI) is common and lethal, but the timing and treatment method remain uncertain. We retrospectively reviewed our aTAAD patients with CI and analyzed the outcomes and related risk factors.

Methods: From January 2011 to December 2019, 1,173 patients diagnosed with aTAAD from Nanjing Drum Tower Hospital were enrolled. Among them, 131 patients had CI preoperatively (CI group), and 1,042 patients were in the non-CI group. One hundred eight in the CI group and 984 in the non-CI group received central repair surgery. Fifteen patients had postoperative cerebral complications (CC) and 93 had non-CCs. ROC curves were used to identify the safe duration of preoperative CI.

Results: The CI group was older (56.3 . 53.2 years, P=0.013) and had lower rates of pain, chest pain and back pain (77.9% . 94.4%, 75.4% . 87.5% and 30.8% . 42.3%, respectively) than the non-CI group. The CI group had a higher rate of preoperative hypotension and tamponade (13.7% . 6.0%, 26.9% . 10.4%, respectively; P=0.000). More patients in the CI group did not receive central repair surgery, and the CI had higher mortality (28.2% . 15.9%). CI without central repair surgery was a strong risk factor for mortality. CI patients with CC after central repair had a higher mortality, and preoperative coma was the strongest risk factor for postoperative CC.A duration between CI symptoms and central repair surgery of less than 12.75 hours is recommended.

Conclusions: Prompt surgery is effective for aTAAD with CI, and preoperative coma and a safe duration longer than 12.75 hours would predict worse outcomes.
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http://dx.doi.org/10.21037/jtd-20-2349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024860PMC
March 2021