Publications by authors named "Zhisong Wang"

56 Publications

Exploring polymerisation of methylglyoxal with NH or alanine to analyse the formation of typical polymers in melanoidins.

Food Chem 2022 Jun 11;394:133472. Epub 2022 Jun 11.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address:

To investigate the formation of typical melanoidin polymers, methylglyoxal (MGO) with NH or alanine (Ala) was used to form coloured compounds, with glyoxal or acetone used as controls. The products were characterised using chromatography, mass spectrometry, and spectroscopy. Spectroscopic results showed that the coloured compounds formed were similar to melanoidins in food. GC-MS results showed that the MGO-based reaction generated similar volatile compounds using the Maillard reaction. Mass spectrometry showed that the molecular weights of structural units in the polymers were mainly 162, 169, and 176 Da, and these could be reassembled using the basic units derived from MGO alone or in combination with nitrogen. Hence, polymers recombined using basic structural units should be considered while determining melanoidin biomarkers. The preparation of coloured compounds using MGO with NH can be used as a novel method to produce the control compounds for melanoidin after process optimization.
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http://dx.doi.org/10.1016/j.foodchem.2022.133472DOI Listing
June 2022

A high-fidelity light-powered nanomotor from a chemically fueled counterpart site-specific optomechanical fuel control.

Nanoscale 2022 Apr 14;14(15):5899-5914. Epub 2022 Apr 14.

Department of Physics, National University of Singapore, Singapore 117542.

Optically powered nanomotors are advantageous for clean nanotechnology over chemically fuelled nanomotors. The two motor types are further bounded by different physical principles. Despite the gap, we show here that an optically powered DNA bipedal nanomotor is readily created from a high-performing chemically fuelled counterpart by subjecting its fuel to cyclic site-specific optomechanical control - as if the fuel is optically recharged. Optimizing azobenzene-based control of the original nucleotide fuel selects a light-responsive fuel analog that replicates the different binding affinity of the fuel and reaction products. The resultant motor largely retains high-performing features of the original chemical motor, and achieves the highest directional fidelity among reported light-driven DNA nanomotors. This study thus demonstrates a novel strategy for transforming chemical nanomotors to optical ones for clean nanotechnology. The strategy is potentially applicable to many chemical nanomotors with oligomeric fuels like nucleotides, peptides and synthetic polymers, leading to a new class of light-powered nanomotors that are akin to chemical nanomotors and benefit from their generally high efficiency mechanistically. The motor from this study also provides a rare model system for studying the subtle boundary between chemical and optical nanomotors - a topic pertinent to chemomechanical and optomechanical energy conversion at the single-molecule level.
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http://dx.doi.org/10.1039/d1nr07964fDOI Listing
April 2022

Serum fibroblast growth factor 23 for early detection of acute kidney injury in critical illness.

Am J Transl Res 2021 15;13(11):12141-12151. Epub 2021 Nov 15.

Department of Urology, The 8th Medical Center of Chinese PLA General Hospital Beijing 100091, China.

Background: Serum fibroblast growth factor 23 (FGF23) is associated with acute kidney injury (AKI) and mortality in patients with critical illnesses. However, the accurate predictive performance of FGF23 on AKI remains inconclusive.

Methods: Meta-analysis was performed using data sources including PubMed, Web of Science, EMBASE, and Cochrane (until June 1, 2021). Cohort or observational studies including patients with AKI and serum FGF23 level as the index test were included. The primary outcome was the AKI detective accuracy. This study has been registered in PROSPERO (CRD42021249930).

Results: Eleven studies with 1946 patients in seven countries were included. Across all settings, the sensitivity and specificity for serum FGF23 levels to predict AKI were 82% (95% CI, 66-91%) and 77% (95% CI, 67-85%), respectively. The diagnostic odds ratio of FGF23 was 15.51 (95% CI, 4.89-49.19), with the pooled positive likelihood ratio of 3.62 (95% CI, 2.25-5.83) and a negative likelihood ratio of 0.23 (95% CI, 0.11-0.50). The area under the receiver operating characteristic curve to detect AKI was 0.86 (95% CI, 0.82-0.88). C-terminal FGF23 had a better performance than intact FGF23.

Conclusions: Plasma FGF23 is a valuable biomarker for incident AKI in critically ill patients. Comparisons of FGF23 with other biomarkers in AKI still need more studies to prove.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661170PMC
November 2021

Efficient mutagenesis targeting the gene in mice using a combination of Cas9 protein and dual gRNAs.

Am J Transl Res 2021 15;13(10):12094-12106. Epub 2021 Oct 15.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University Nanjing 210046, Jiangsu, China.

We injected mouse zygotes with combinations of Cas9 protein, mRNA, and two gRNAs targeting a single exon of type I interferon receptor () to determine the gene targeting efficiencies. Cas9 protein produced on-target mutations more efficiently than mRNA when each was used with a single gRNA, regardless of which gRNA was used. When mRNA and Cas9 protein were co-injected, the on-target efficiency could reach 97.0% when both gRNAs were used, which was higher than when either gRNA was used alone (61.3% and 75.5%, respectively; P<0.05). Co-injection of Cas9 protein with both gRNAs produced the highest on-target mutation rate of any combination (100.0%). Most on-target mutations were deletions of 2 to 113 nucleotides, and there were few off-target mutations in mutant animals. The expression intensity of IFNAR1 was reduced in heterozygous mice (IF) and almost or completely absent in homozygous null mice compared with that in wild-type mice (IF and Western blot). When both gRNAs targeting were used simultaneously with two gRNAs targeting , the on-target editing efficiency on each gene was 96.8% and 85.5%, respectively. Co-injection of dual gRNAs and Cas9 protein is an efficient approach for knockout and multi-gene editing in mice and may be applied in other animal models and breeding livestock.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581890PMC
October 2021

Immune Modulating Antibody-Drug Conjugate (IM-ADC) for Cancer Immunotherapy.

J Med Chem 2021 11 3;64(21):15716-15726. Epub 2021 Nov 3.

School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.

Antibody-drug conjugate (ADC) and immune checkpoint blockade (ICB) offer promising approaches for cancer treatment. Here, we describe an ADC constructed by conjugating anti-PD-L1 THIOMAB with a bifunctional immunomodulator via a redox-cleavable linker. The resulting ADC not only triggers a potent antitumor immune response by blocking the PD-1/PD-L1 interaction and activating the Toll-like receptor 7/8 (TLR7/8) signaling pathway but also upregulates its targeted PD-L1 expression via epigenetic regulation and/or IFN-γ induction, thus conferring more sensitivity to the PD-1/PD-L1 blockade. We identify that ADC treatment could lead to more pronounced tumor suppression than the treatment of in combination with the anti-PD-L1 antibody. Accordingly, this study provides a novel ADC strategy to enhance the antitumor immune response to ICB therapy.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00961DOI Listing
November 2021

Single-molecule mechanical study of an autonomous artificial translational molecular motor beyond bridge-burning design.

Nanoscale 2021 Aug 27;13(31):13195-13207. Epub 2021 Jul 27.

Department of Physics, National University of Singapore, 117542 Singapore.

A key capability of molecular motors is sustainable force generation by a single motor copy. Direct force characterization at the single-motor level is still missing for artificial molecular motors, though long reported for their biological counterparts. Here we report single-molecule detection of sustained force-generating motility for an artificial track-walking molecular motor capable of autonomous chemically fueled operation. A single motor plus its track (both made of deoxyribonucleic acids or DNA) is assembled, operated and detected under magnetic tweezers by a method designed to overcome difficulty from the motor's soft double-stranded track. The motor shows self-directed walking by ∼16 nm steps up to a distance of 120 nm (covering the entire track), yielding a stall force of ∼2-3 pN. These results imply a reasonably efficient chemomechanical conversion of the motor compared to a high-efficiency biomotor. The stall force is near the level of translational biomotors powering human muscles and allows similar force-demanding applications by their artificial counterparts. This single-motor study reveals fast subsecond steps, suggesting big room for improvement in the speed of DNA motors in general. Besides, the established single-molecule method is applicable to force measurements of many other DNA motors with soft tracks.
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http://dx.doi.org/10.1039/d1nr02296bDOI Listing
August 2021

Site specificity of blastocyst hatching significantly influences pregnancy outcomes in mice.

FASEB J 2021 09;35(9):e21812

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.

Blastocysts hatch from the zona pellucida (ZP) to enable implantation into the uterine endometrial epithelium, but little is known regarding the effect of hatching sites on pregnancy outcomes. Murine hatching embryos were categorized into five groups based on initial trophectoderm projection (TEP)/ZP position corresponding to the inner cell mass center. In blastocysts (3.5 dpc) post-12 hours in vitro culture, TEP rates of A-site (44.4%) and B-site (38.6%) embryos were higher than those of C-site (12.5%) and D-site (3.1%) embryos, while the O-site (1.4%) was the lowest (P < .05). Post-ET A-site (55.6%) and B-site (65.6%) birth rates were higher than those of C-site embryos (21.3%) and controls (P < .05). Furthermore, live birth rate of B-site embryos remained higher than C-site embryos (68.8% vs 31.3%; P < .05) when both were transferred into the same recipients. Different TEP site blastocysts exhibited different implantation competences: the implantation rate of C-site embryos was lower than that of both A- and B-site groups (67.7% vs 84.3% and 83.2%, respectively; P < .05) at 2 days post-ET. C-site embryos also had a distinctly higher ratio of developmental defects (47.5%) than A- and B-site embryos (22.5% and 14.6%, respectively), with implantation failure mainly associated with poor birth rate, a finding corroborated by differential gene expression analysis such as LIF, LIFR, and S100a9. Surprisingly, acidified Tyrode's solution (AAH)-treated B-site blastocysts had a significantly increased birth rate (77.1%) than C-site (55.3%) and controls (43.4%). Site specificity and differential gene expression during embryo hatching can be applied in ART screening. More importantly, assisted hatching by AAH is effective and feasible for improving pregnancy and term development, particularly at the B-site, for humans and in animal husbandry.
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http://dx.doi.org/10.1096/fj.202100653RDOI Listing
September 2021

Development of a hydroxyl group-mediated biosynthetic schwertmannite as a persulfate activator for efficient degradation of RhB and Cr(VI) removal.

J Hazard Mater 2021 10 26;419:126496. Epub 2021 Jun 26.

School of Minerals Processing and Bioengineering, Key Laboratory of Biohydrometallurgy of Ministry of Education, Central South University, Changsha 410083, China. Electronic address:

Recently, sulfate radical-based advanced oxidation processes (SR-AOPs) have shown broad potential for restoring the water environment. However, the application of SR-AOPs to simultaneously remove organic pollutants and Cr(VI) has rarely been reported. Herein, we developed a modified schwertmannite (Sch-PVA) synthesized via the mediation of Acidithiobacillus ferrooxidans in the introduction of polyvinyl alcohol (PVA). This modification significantly changed the morphology and structure of the schwertmannite (Sch). The specific surface area and the density of functional sites also increased. Sch-PVA significantly increased the persulfate (PDS) activation efficiency. Even in 100 mg L rhodamine B (RhB) conditions, 96.3% of RhB was eliminated by 0.5 g LSch-PVA and 6 mM PDS in 120 min. Moreover, excellent performance was exhibited over a wide pH range. The dissolution of the passivation layer facilitated the exposure of new adsorption and reduction sites, thereby enhancing the simultaneous removal of RhB and Cr(VI). Quenching experiments and electron spin resonance (ESR) measurements verified that sulfate and hydroxyl radicals were generated. The hydroxyl groups on the Sch-PVA surface played a key role in the bonding with and the activation of PDS. In conclusion, Sch-PVA provides new insights into the catalyst application for simultaneous removal of organic pollutants and Cr(VI).
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http://dx.doi.org/10.1016/j.jhazmat.2021.126496DOI Listing
October 2021

Chromosome-level genome assembly of Scapharca kagoshimensis reveals the expanded molecular basis of heme biosynthesis in ark shells.

Mol Ecol Resour 2022 Jan 13;22(1):295-306. Epub 2021 Jul 13.

Liaoning Ocean and Fisheries Science Research Institute and Dalian Key Laboratory of Genetic Resources for Marine Shellfish, Dalian, China.

Ark shells are commercially important clam species that inhabit in muddy sediments of shallow coasts in East Asia. For a long time, the lack of genome resources has hindered scientific research of ark shells. Here, we report a high-quality chromosome-level genome assembly of Scapharca kagoshimensis, with an aim to unravel the molecular basis of heme biosynthesis, and develop genomic resources for genetic breeding and population genetics in ark shells. Nineteen scaffolds corresponding to 19 chromosomes were constructed from 938 contigs (contig N50 = 2.01 Mb) to produce a final high-quality assembly with a total length of 1.11 Gb and scaffold N50 around 60.64 Mb. The genome assembly represents 93.4% completeness via matching 303 eukaryota core conserved genes. A total of 24,908 protein-coding genes were predicted and 24,551 genes (98.56%) of which were functionally annotated. The enrichment analyses suggested that genes in heme biosynthesis pathways were expanded and positive selection of the haemoglobin genes was also found in the genome of S. kagoshimensis, which gives important insights into the molecular mechanisms and evolution of the heme biosynthesis in mollusca. The valuable genome assembly of S. kagoshimensis would provide a solid foundation for investigating the molecular mechanisms that underlie the diverse biological functions and evolutionary adaptations of S. kagoshimensis.
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http://dx.doi.org/10.1111/1755-0998.13460DOI Listing
January 2022

Structure-Based Design of Highly Potent Toll-like Receptor 7/8 Dual Agonists for Cancer Immunotherapy.

J Med Chem 2021 06 28;64(11):7507-7532. Epub 2021 May 28.

School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Advanced Innovation Center for Human Brain Protection, Tsinghua University, Beijing 100084, China.

Activation of the toll-like receptors 7 and 8 has emerged as a promising strategy for cancer immunotherapy. Herein, we report the design and synthesis of a series of pyrido[3,2-]pyrimidine-based toll-like receptor 7/8 dual agonists that exhibited potent and near-equivalent agonistic activities toward TLR7 and TLR8. In vitro, compounds and significantly induced the secretion of IFN-α, IFN-γ, TNF-α, IL-1β, IL-12p40, and IP-10 in human peripheral blood mononuclear cell assays. In vivo, compounds , , and significantly suppressed tumor growth in CT26 tumor-bearing mice by remodeling the tumor microenvironment. Additionally, compounds , , and markedly improved the antitumor activity of PD-1/PD-L1 blockade. In particular, compound combined with the anti-PD-L1 antibody led to complete tumor regression. These results demonstrated that TLR7/8 agonists (, , and ) held great potential as single agents or in combination with PD-1/PD-L1 blockade for cancer immunotherapy.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00179DOI Listing
June 2021

Formation mechanisms and characterisation of the typical polymers in melanoidins from vinegar, coffee and model experiments.

Food Chem 2021 Sep 3;355:129444. Epub 2021 Mar 3.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China. Electronic address:

Melanoidins, are of increasing interest for their potential biological activities. However, little knowledge is available on their structure. In the present study, vinegar, coffee and model melanoidins were degraded by NaBH, and the resultant reaction products were characterised by chromatography, mass spectrometry and spectrometry methods to elucidate the mechanism of formation of melanoidin skeleton molecules. The study identified a typical polymer with a molecular weight (MW) interval of 74 Da, which was polymerised by aldol condensation and reduced by NaBH, followed by intermolecular dehydration. MW of the theoretically derived typical polymers matched the detected polymers, validating the speculated pathway involved in the formation of melanoidins skeleton molecules. The study also revealed that melanoidins from different sources contain polymers with the same MW and different binding preferences, contributing to the heterogeneity of melanoidins. Overall, these findings indicated that the identified polymers could be used as potential candidate biomarkers for melanoidins.
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http://dx.doi.org/10.1016/j.foodchem.2021.129444DOI Listing
September 2021

Thermodynamic marking of FF ATP synthase.

Biochim Biophys Acta Bioenerg 2021 04 14;1862(4):148369. Epub 2021 Jan 14.

Department of Physics and NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117542, Singapore.

FF ATP synthase is a ~100% efficient molecular machine for energy conversion in biology, and holds great lessons for man-made energy technology and nanotechnology. In light of formidable biocomplexity of the FF machinery, its modeling from pure physical principles remains difficult and rare. Here we construct a thermodynamic model of FF from experimentally accessible quantities plus a single entropy production that generally has vanishingly small values (<1k). Based on the physical inputs, this model captures FF performance observed over an exhaustively wide range of proton-motive force and nucleotide concentrations. The model predicts a distinct 1/8kT slope for ATP synthesis rate versus proton-motive force, which is verified by experimental data and represents a profound thermodynamic marking of this amazingly efficient machine operating near a universal limit of the 2nd law of thermodynamics. The model further predicts two symmetries of heat productions, which are testable by available experimental techniques and offer quantitative constraints on FF's possible mechanisms behind its ~100% efficiency.
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http://dx.doi.org/10.1016/j.bbabio.2021.148369DOI Listing
April 2021

Transient reaction process and mechanism of cornstarch/air and CH/cornstarch/air in a closed container: Quantitative research based on experiments and simulations.

J Hazard Mater 2021 May 5;409:124475. Epub 2020 Nov 5.

China Academy of Launch Vehicle Technology, Beijing 100076, China.

Both dust/air explosion and flammable gas/dust/air explosion are common forms of energy release. Experiments and simulation models with a multi-step chemical reaction mechanism were used to study the intensity parameters and mechanism of the CH/air explosion, cornstarch/air explosion and CH/cornstarch/air explosion in a closed container. Results showed that the peak overpressure, maximum flame temperature, and average flame propagation speed of the stoichiometric CH/air explosion reach 0.84 MPa, 2614 K and 3.5 m/s, respectively. The optimal concentration of cornstarch explosion is 750 g/m, and its peak overpressure, maximum flame temperature and average flame propagation speed are 0.76 MPa, 2098 K and 1.77 m/s, respectively. For a three-components system, adding methane can significantly increase the explosive intensity and combustion performance of cornstarch. The explosive intensity parameters (peak overpressure, maximum flame temperature, average flame propagation speed) of a certain concentration of cornstarch first increase and then decrease with the increase of methane concentration. The maximum explosion intensity parameters of a three-components system with a certain concentration of lean-methane/air are higher than that of single-phase, but always lower than that of the stoichiometric methane/air. Moreover, the mutual coordination of dust and combustible gas in energy release and the mutual competition mechanism in oxygen consumption are described.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124475DOI Listing
May 2021

Correlation of neutrophil-to-lymphocyte ratio with the prognosis of non-ST-segment elevation in patients with acute coronary syndrome undergoing selective percutaneous coronary intervention.

J Int Med Res 2020 Oct;48(10):300060520959510

Department of Cardiology, Changshu Hospital affiliated to Soochow University, Changshu No. 1 People's Hospital, Changshu, Jiangsu Province, China.

Objective: We aimed to explore the relationship between neutrophil-to-lymphocyte ratio (NLR) at three timepoints and prognosis of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing elective percutaneous coronary intervention (PCI) within 1 year of PCI.

Methods: This retrospective study enrolled 231 patients with NSTE-ACS who received PCI and were followed for 1 year after PCI. The study population was divided into major adverse cardiovascular and cerebrovascular events (MACE) and non-MACE groups.

Results: In total, 214 patients completed the 1-year follow-up; 32 patients (15.0%) had MACE and 182 (85.0%) had no MACE. The MACE and non-MACE groups differed significantly in age, preoperative neutrophil count, preoperative and postoperative NLR, proportion of three-vessel lesion disease, preoperative lymphocyte count, postoperative lymphocyte count within 24 hours, postoperative lymphocyte count over 24 hours, and left ventricular ejection fraction (LVEF). Multivariate logistic regression analysis showed that preoperative NLR, postoperative NLR within 24 hours, age, and LVEF values were independent risk factors for MACE in patients with NSTE-ACS after elective PCI.

Conclusion: Compared with preoperative NLR, postoperative NLR (within 24 hours) may have a stronger ability to predict the occurrence of MACE in NSTE-ACS patients within 1 year after elective PCI.
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http://dx.doi.org/10.1177/0300060520959510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570302PMC
October 2020

Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade.

Sci Transl Med 2020 09;12(560)

School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Beijing Advanced Innovation Center for Human Brain Protection, Tsinghua University, Beijing 100084, China.

Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules that increased KDM5A abundance, we identified one (D18) that increased the efficacy of various ICB agents in three murine cancer models when used as a combination therapy. D18 potentiated ICB efficacy through two orthogonal mechanisms: (i) increasing KDM5A abundance, which suppressed expression of the gene (encoding phosphatase and tensin homolog) and increased programmed cell death ligand 1 abundance through a pathway involving PI3K-AKT-S6K1, and (ii) activating Toll-like receptors 7 and 8 (TLR7/8) signaling pathways. Combination treatment increased T cell activation and expansion, CD103 tumor-infiltrating dendritic cells, and tumor-associated M1 macrophages, ultimately enhancing the overall recruitment of activated CD8 T cells to tumors. In patients with melanoma, a high gene signature correlated with expression and could potentially serve as a marker of response to anti-PD-1 immunotherapy. Furthermore, our results indicated that bifunctional agents that enhance both KDM5A and TLR activity warrant investigation as combination therapies with ICB agents.
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http://dx.doi.org/10.1126/scitranslmed.aax2282DOI Listing
September 2020

Magnesium is a critical element for competent development of bovine embryos.

Theriogenology 2019 Dec 13;140:109-116. Epub 2019 Aug 13.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, PR China; Renova Life, Inc., College Park, MD, 20742, USA. Electronic address:

The study was designed to determine the impact of magnesium (Mg) on bovine embryo development. We found that two commercially available sources of bovine serum albumin (BSA) and fetal bovine serum (FBS) contained different amounts of Mg residue: 4 ppm in ICPbio BSA, 114 ppm in Sigma BSA, and 44 ppm in FBS. When CR1 was used as basal medium, PVA and ICPbio BSA produced the lowest blastocyst yield (2.2-2.3%), whereas Sigma BSA increased blastocyst yield to 18.9% (P < 0.05). Supplementation of 1.4 mM MgCl into the medium increased the blastocyst rate in the ICPbio BSA group (29.4%) but not in the PVA group (5.4%; P < 0.05) to a level comparable to that of the FBS group (33.7%; P > 0.05). We next found that increasing concentrations of MgCl in the culture medium (ICPbio BSA) elevated blastocyst rate from 2.6% (0 mM), 38.4% (0.35 mM) to 50.2% (1.4 mM; P < 0.05), further maintained at 44.9% (2.1 mM) and 43.4% (2.8 mM) (P > 0.05). However, blastocyst rate was reduced to 31.4% (4.2 mM) and 29.4% (5.6 mM) when MgCl supplement was increased (P < 0.05). Comparable blastocyst development was achieved in both ICPbio BSA (30.0-33.1%) and Sigma BSA (37.4-38.7%) groups when 1.4 mM Mg was supplemented regardless of its source (MgCl vs. MgSO; P > 0.05). In embryo transfer experiments, higher rates of pregnancy (54.3 vs. 41.5%) and calving (44.3 vs. 32.5%) were achieved in the CR1-Mg-supplemented BSA group compared with the FBS group with co-culture, respectively (P < 0.05). These results demonstrate that Mg is a key ion that promotes competent blastocyst and term development. Therefore, a simple and efficient defined medium (CR1-Mg-BSA) can successfully replace complex serum and somatic cell co-culture.
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http://dx.doi.org/10.1016/j.theriogenology.2019.08.015DOI Listing
December 2019

Polymer-Based Accurate Positioning: An Exact Worm-like-Chain Study.

ACS Omega 2018 Oct 29;3(10):14318-14326. Epub 2018 Oct 29.

Department of Physics, National University of Singapore, 117542, Singapore.

Precise positioning of molecular objects from one location to another is important for nanomanipulation and is also involved in molecular motors. Here, we study single-polymer-based positioning on the basis of the exact solution to the realistic three-dimensional worm-like-chain (WLC) model. The results suggest the possibility of a surprisingly accurate flyfishing-like positioning in which tilting one end of a flexible short polymer enables positioning of the other diffusing end to a distant location within an error of ∼1 nm. This offers a new mechanism for designing molecular positioning devices. The flyfishing effect (and reverse process) likely plays a role in biological molecular motors and may be used to improve speed of artificial counterparts. To facilitate these applications, a new force-extension formula is obtained from the exact WLC solution. This formula has an improved accuracy over the widely used Marko-Siggia formula for stretched polymers and is valid for compressed polymers too. The new formula is useful in analysis of single-molecule stretching experiments and in estimating intramolecular forces of molecular motors, especially those involving both stretched and compressed polymer components.
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http://dx.doi.org/10.1021/acsomega.8b01448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644801PMC
October 2018

Track-walking molecular motors: a new generation beyond bridge-burning designs.

Nanoscale 2019 May;11(19):9240-9263

Department of Physics, National University of Singapore, Singapore 117542, Singapore.

Track-walking molecular motors are the core bottom-up mechanism for nanometre-resolved translational movements - a fundamental technological capability at the root of numerous applications ranging from nanoscale assembly lines and chemical synthesis to molecular robots and shape-changing materials. Over the last 10 years, artificial molecular walkers (or nanowalkers) have evolved from the 1st generation of bridge-burning designs to the 2nd generation capable of truly sustainable movements. Invention of non-bridge-burning nanowalkers was slow at first, but has picked up speed since 2012, and is now close to breaking major barriers for wide-spread development. Here we review the 2nd generation of artificial nanowalkers, which are mostly made of DNA molecules and draw energy from light illumination or from chemical fuels for entirely autonomous operation. They are typically symmetric dimeric motors walking on entirely periodic tracks, yet the motors possess an inherent direction for large-scale amplification of the action of many motor copies. These translational motors encompass the function of rotational molecular motors on circular or linear tracks, and may involve molecular shuttles as 'engine' motifs. Some rules of thumb are provided to help readers design similar motors from DNA or other molecular building blocks. Opportunities and challenges for future development are discussed, especially in the areas of molecular robotics and active materials based on the advanced motors.
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http://dx.doi.org/10.1039/c9nr00033jDOI Listing
May 2019

Genetic diversities and phylogenetic analyses of three Chinese main ethnic groups in southwest China: A Y-Chromosomal STR study.

Sci Rep 2018 10 18;8(1):15339. Epub 2018 Oct 18.

School of Public Health, Zunyi Medical University, Zunyi, Guizhou, China.

Short tandem repeats (STRs) located on the Y chromosome with the properties of male-specific inheritance and haploidy are widely used in forensics to analyze paternal genealogies and match male trace donors to evidence. Besides, Y-chromosomal haplotypes play an important role in providing breathtaking insights into population genetic history. However, the genetic diversity and forensic characteristics of Y-STRs in Guizhou main ethnic groups (Hans, Miaos and Bouyeis) remain uncharacterized. Here, we obtained Y-chromosomal 23-marker haplotypes in three Guizhou populations and submitted the first batch of Y-STR haplotype data to the YHRD. The HD in the aforementioned three populations are 0.99990, 0.99983, and 0.99979, respectively, and DC values are 0.9902, 0.9908, and 0.97959, respectively. Subsequently, genetic differentiation between our newly studied populations and reference groups along ethnic/administrative divisions, as well as national/continental boundaries were investigated via AMOVA, MDS, and phylogenetic relationship reconstruction. Significant genetic differentiations from our subjects and other groups are identified in ethnically, linguistically and geographically diverse populations, including most prominently Tibetans and Uyghurs among 30 mainland Chinese populations, Taiwanese groups and others among 58 Asian populations, as well as African groups and others among 89 worldwide populations. Qiannan Bouyei has a close genetic relationship with Guangxi Zhuang, and Zunyi Han and Qiandongnan Miao have close genetic affinity with Hunan Han and Guizhou Shui, respectively. Collectively, this new-generation Y-STR amplification system can be used as a supplementary tool in forensic identification and male parentage testing and even pedigree search.
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http://dx.doi.org/10.1038/s41598-018-33751-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193932PMC
October 2018

How Well Can DNA Rupture DNA? Shearing and Unzipping Forces inside DNA Nanostructures.

ACS Omega 2018 Jan 10;3(1):292-301. Epub 2018 Jan 10.

Department of Physics, National University of Singapore, 2 Science Drive 3, 117542 Singapore.

A purely DNA nanomachine must support internal stresses across short DNA segments with finite rigidity, producing effects that can be qualitatively very different from experimental observations of isolated DNA in fixed-force ensembles. In this article, computational simulations are used to study how well the rigidity of a driving DNA duplex can rupture a double-stranded DNA target into single-stranded segments and how well this stress can discriminate between unzipping or shearing geometries. This discrimination is found to be maximized at an optimal length but deteriorates as the driving duplex is either lengthened or shortened. This differs markedly from a fixed-force ensemble and has implications for the design parameters and limitations of dynamic DNA nanomachines.
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http://dx.doi.org/10.1021/acsomega.7b01692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044922PMC
January 2018

Mechanical transduction via a single soft polymer.

Phys Rev E 2018 Apr;97(4-1):042504

NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119076.

Molecular machines from biology and nanotechnology often depend on soft structures to perform mechanical functions, but the underlying mechanisms and advantages or disadvantages over rigid structures are not fully understood. We report here a rigorous study of mechanical transduction along a single soft polymer based on exact solutions to the realistic three-dimensional wormlike-chain model and augmented with analytical relations derived from simpler polymer models. The results reveal surprisingly that a soft polymer with vanishingly small persistence length below a single chemical bond still transduces biased displacement and mechanical work up to practically significant amounts. This "soft" approach possesses unique advantages over the conventional wisdom of rigidity-based transduction, and potentially leads to a unified mechanism for effective allosterylike transduction and relay of mechanical actions, information, control, and molecules from one position to another in molecular devices and motors. This study also identifies an entropy limit unique to the soft transduction, and thereby suggests a possibility of detecting higher efficiency for kinesin motor and mutants in future experiments.
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http://dx.doi.org/10.1103/PhysRevE.97.042504DOI Listing
April 2018

Translation-rotation-translation interconversions.

Authors:
Zhisong Wang

Nat Nanotechnol 2018 06;13(6):439-440

Department of Physics, National University of Singapore, Singapore, Singapore.

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http://dx.doi.org/10.1038/s41565-018-0140-0DOI Listing
June 2018

Generic maps of optimality reveal two chemomechanical coupling regimes for motor proteins: from F-ATPase and kinesin to myosin and cytoplasmic dynein.

Authors:
Zhisong Wang

Integr Biol (Camb) 2018 01;10(1):34-47

Department of Physics, National University of Singapore, Singapore 117542, Singapore.

Many motor proteins achieve high efficiency for chemomechanical conversion, and single-molecule force-resisting experiments are a major tool to detect the chemomechanical coupling of efficient motors. Here, we introduce several quantitative relations that involve only parameters extracted from force-resisting experiments and offer new benchmarks beyond mere efficiency to judge the chemomechanical optimality or deficit of evolutionary remote motors on the same footing. The relations are verified by the experimental data from F-ATPase, kinesin-1, myosin V and cytoplasmic dynein, which are representative members of four motor protein families. A double-fitting procedure yields the chemomechanical parameters that can be cross-checked for consistency. Using the extracted parameters, two generic maps of chemomechanical optimality are constructed on which motors across families can be quantitatively compared. The maps reveal two chemomechanical coupling regimes, one conducive to high efficiency and high directionality, and the other advantageous to force generation. Surprisingly, an F rotor and a kinesin-1 walker belong to the first regime despite their obvious evolutionary gap, while myosin V and cytoplasmic dynein follow the second regime. This analysis also predicts the symmetries of directional biases and heat productions for the motors, which impose constraints on their chemomechanical coupling and are open to future experimental tests. The verified relations, six in total, present a unified fitting framework to analyze force-resisting experiments. The generic maps of optimality, to which many more motors can be added in future, provide a rigorous method for a systematic cross-family comparison of motors to expose their evolutionary connections and mechanistic similarities.
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http://dx.doi.org/10.1039/c7ib00142hDOI Listing
January 2018

Biomimetic Autonomous Enzymatic Nanowalker of High Fuel Efficiency.

ACS Nano 2016 06 17;10(6):5882-90. Epub 2016 Jun 17.

Department of Physics and ‡NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore , Singapore 117542.

Replicating efficient chemical energy utilization of biological nanomotors is one ultimate goal of nanotechnology and energy technology. Here, we report a rationally designed autonomous bipedal nanowalker made of DNA that achieves a fuel efficiency of less than two fuel molecules decomposed per productive forward step, hence breaking a general threshold for chemically powered machines invented to date. As a genuine enzymatic nanomotor without changing itself nor the track, the walker demonstrates a sustained motion on an extended double-stranded track at a speed comparable to previous burn-bridge motors. Like its biological counterparts, this artificial nanowalker realizes multiple chemomechanical gatings, especially a bias-generating product control unique to chemically powered nanomotors. This study yields rich insights into how pure physical effects facilitate harvest of chemical energy at the single-molecule level and provides a rarely available motor system for future development toward replicating the efficient, repeatable, automatic, and mechanistically sophisticated transportation seen in biomotor-based intracellular transport but beyond the capacity of the current burn-bridge motors.
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http://dx.doi.org/10.1021/acsnano.6b01035DOI Listing
June 2016

From bistate molecular switches to self-directed track-walking nanomotors.

ACS Nano 2014 Oct 2;8(10):10293-304. Epub 2014 Oct 2.

Department of Physics, ‡NUS Graduate School for Integrative Sciences and Engineering, §Center for Computational Science and Engineering, National University of Singapore , Singapore 117542.

Track-walking nanomotors and larger systems integrating these motors are important for wide real-world applications of nanotechnology. However, inventing these nanomotors remains difficult, a sharp contrast to the widespread success of simpler switch-like nanodevices, even though the latter already encompasses basic elements of the former such as engine-like bistate contraction/extension or leg-like controllable binding. This conspicuous gap reflects an impeding bottleneck for the nanomotor development, namely, lack of a modularized construction by which spatially and functionally separable "engines" and "legs" are flexibly assembled into a self-directed motor. Indeed, all track-walking nanomotors reported to date combine the engine and leg functions in the same molecular part, which largely underpins the device-motor gap. Here we propose a general design principle allowing the modularized nanomotor construction from disentangled engine-like and leg-like motifs, and provide an experimental proof of concept by implementing a bipedal DNA nanomotor up to a best working regime of this versatile design principle. The motor uses a light-powered contraction-extension switch to drive a coordinated hand-over-hand directional walking on a DNA track. Systematic fluorescence experiments confirm the motor's directional motion and suggest that the motor possesses two directional biases, one for rear leg dissociation and one for forward leg binding. This study opens a viable route to develop track-walking nanomotors from numerous molecular switches and binding motifs available from nanodevice research and biology.
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http://dx.doi.org/10.1021/nn5034983DOI Listing
October 2014

Asymmetric information hiding and noise-free recovery based on rotating analyzer ellipsometry and quick-response code.

J Opt Soc Am A Opt Image Sci Vis 2014 Aug;31(8):1895-903

We report an asymmetric optical information hiding method based on a rotating analyzer ellipsometry technique. This asymmetric hiding architecture not only avoids the interception of keys during transmission or distribution but also makes the cyphertext more inconspicuous for attackers. A new kind of one-way optical trapdoor function is constructed based on the fact that the state of polarization (SOP) of elliptical polarized light cannot be recovered with only the knowledge of intensity captured after passing through a linear polarizer. Meanwhile, the SOP of a polarization ellipse could be calculated by rotating the polarizer to record two scenes of intensity after it. Introduction of a quick response code as a container leads to noise-free recovery for original information and enhances practicality of the proposed cryptosystem with versatile key sensitivity and fault tolerance capability. Numerical simulation results that support theoretical analysis are presented. Analysis on the relationship between hiding effect or quality of decryption and parameters of the algorithm also is provided.
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http://dx.doi.org/10.1364/JOSAA.31.001895DOI Listing
August 2014

Optical asymmetric cryptography based on elliptical polarized light linear truncation and a numerical reconstruction technique.

Appl Opt 2014 Jun;53(18):3920-8

We demonstrate a novel optical asymmetric cryptosystem based on the principle of elliptical polarized light linear truncation and a numerical reconstruction technique. The device of an array of linear polarizers is introduced to achieve linear truncation on the spatially resolved elliptical polarization distribution during image encryption. This encoding process can be characterized as confusion-based optical cryptography that involves no Fourier lens and diffusion operation. Based on the Jones matrix formalism, the intensity transmittance for this truncation is deduced to perform elliptical polarized light reconstruction based on two intensity measurements. Use of a quick response code makes the proposed cryptosystem practical, with versatile key sensitivity and fault tolerance. Both simulation and preliminary experimental results that support theoretical analysis are presented. An analysis of the resistance of the proposed method on a known public key attack is also provided.
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http://dx.doi.org/10.1364/AO.53.003920DOI Listing
June 2014

A bioinspired design principle for DNA nanomotors: mechanics-mediated symmetry breaking and experimental demonstration.

Methods 2014 May 3;67(2):227-33. Epub 2014 Mar 3.

Department of Physics, National University of Singapore, Singapore 117542, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117542, Singapore. Electronic address:

DNA nanotechnology is a powerful tool to fabricate nanoscale motors, but the DNA nanomotors to date are largely limited to the simplistic burn-the-bridge design principle that prevents re-use of a fabricated motor-track system and is unseen in biological nanomotors. Here we propose and experimentally demonstrate a scheme to implement a conceptually new design principle by which a symmetric bipedal nanomotor autonomously gains a direction not by damaging the traversed track but by fine-tuning the motor's size.
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http://dx.doi.org/10.1016/j.ymeth.2014.02.029DOI Listing
May 2014

Autonomous synergic control of nanomotors.

ACS Nano 2014 Feb 16;8(2):1792-803. Epub 2014 Jan 16.

Department of Physics, ‡NUS Graduate School for Integrative Sciences and Engineering, and §Center for Computational Science and Engineering, National University of Singapore , Singapore 117542.

Control is a hallmark of machines; effective control over a nanoscale system is necessary to turn it into a nanomachine. Nanomotors from biology often integrate a ratchet-like passive control and a power-stroke-like active control, and this synergic active-plus-passive control is critical to efficient utilization of energy. It remains a challenge to integrate the two differing types of control in rationally designed nanomotor systems. Recently a light-powered track-walking DNA nanomotor was developed from a bioinspired design principle that has the potential to integrate both controls. However, it is difficult to separate experimental signals for either control due to a tight coupling of both controls. Here we present a systematic study of the motor and new derivatives using different fluorescence labeling schemes and light operations. The experimental data suggest that the motor achieves the two controls autonomously through a mechanics-mediated symmetry breaking. This study presents an experimental validation for the bioinspired design principle of mechanical breaking of symmetry for synergic ratchet-plus-power stroke control. Augmented by mechanical and kinetic modeling, this experimental study provides mechanistic insights that may help advance molecular control in future nanotechnological systems.
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http://dx.doi.org/10.1021/nn406187uDOI Listing
February 2014

Role of directional fidelity in multiple aspects of extreme performance of the F(1)-ATPase motor.

Phys Rev E Stat Nonlin Soft Matter Phys 2013 Aug 8;88(2):022703. Epub 2013 Aug 8.

Department of Physics, National University of Singapore, Singapore 117542 and Center for Computational Science and Engineering, National University of Singapore, Singapore 117542.

Quantitative understanding of the best possible performance of nanomotors allowed by physical laws pertains to the study of nanomotors from biology as well as nanotechnology. The biological nanomotor F(1) ATPase is the best available model system as it is the only nanomotor known for extreme energy conversion near the limit of energy conservation. Using a unified theoretical framework centered on a concept called directional fidelity, we analyze recent experiments in which the F(1) motor's performance was measured for controlled chemical potentials and expose from the experiments quantitative evidence for the motor's multiple extreme performances in directional fidelity, speed, and catalytic capability close to physical limits. Specifically, the motor nearly exhausts the available energy from the fuel to retain the highest possible directional fidelity for an arbitrary load, encompassing the motor's extreme energy conversion and beyond. The theory-experiment comparison implies a tight chemomechanical coupling up to stalemate as futile steps occur, but unlikely involve fuel consumption. The F(1)-motor data also help clarify the relation between directional fidelity and experimentally measured stepping ratio.
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http://dx.doi.org/10.1103/PhysRevE.88.022703DOI Listing
August 2013
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