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Biomedical subjects

Bing Liu

Publications and source records attributed to Bing Liu.

At least 19 recordsLinked to original sources

Phylogenomics and evolution of the Lauraceae based on targeted capture data.

The family Lauraceae, a hyper-diverse magnoliid family comprising approximately 63 genera and over 3,000 species, plays a key ecological role in tropical and subtropical forests. Yet deep relationships among its nine tribes remain unresolved, likely due to limited sampling and complex evolutionary processes such as incomplete lineage sorting (ILS) and gene flow. To address these challenges, we generated datasets of 255 single-copy nuclear genes and chloroplast genomes using a newly designed Lauraceae-specific probe set, achieving the most comprehensive genus-level sampling (84%) to date. Phylogenomic analyses reconstructed a robust nuclear tree, which resolved the Neocinnamomeae as sister to the Caryodaphnopsideae and revealed pronounced gene tree conflict and pervasive cytonuclear discordance. To investigate the evolutionary processes underlying these patterns, comprehensive analyses were conducted. The results indicate that conflicting nuclear gene trees reflect the combined effects of ILS, gene tree estimation error, and gene flow, with ILS dominating across the core Lauraceae, whereas cytonuclear discordance is primarily driven by extensive gene flow. Diversification analyses further indicate that episodes of rapid lineage accumulation coincide with major gene flow events, suggesting a potential role of gene flow in the diversification of Lauraceae. Overall, this study provides a robust nuclear phylogenomic framework for Lauraceae and demonstrates that gene flow had profound effects on its evolutionary history, shedding light on the contribution of gene flow to the diversification of hyper-diverse tropical plant lineages.

Cytonuclear discordance↗

Multi-omics uncovers the pleiotropic genetic mechanisms linking MASLD and cardiometabolic syndromes.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular-kidney-metabolic (CKM) syndrome are interrelated conditions with shared pathophysiological features; however, the genetic architecture underlying their relationship has not been fully elucidated. Deciphering this shared genetic basis holds promise for advancing mechanistic insights and therapeutic discovery. METHODS: We performed an integrated genome-wide cross-trait analysis using GWAS summary statistics for MASLD and 38 CKM traits. Our analysis estimated genetic correlations, inferred causal relationships, and identified pleiotropic variants. Candidate causal genes and druggable targets were subsequently prioritized through integrating multi-omics data. RESULTS: MASLD exhibited significant genetic correlations with 16 CKM traits, especially metabolic and cardiovascular conditions. Bidirectional causal relationships were observed between MASLD and T2D, adiposity, and lipid traits. We discovered 116 pleiotropic loci, including 65 shared causal variants such as rs429358 near APOE, which exerted influence across multiple traits. Gene-based analyses prioritized 152 unique candidate pleiotropic genes, enriched in lipid and cholesterol metabolism, and highly expressed in the liver, adipose, and immune-related cell types, such as macrophages and endothelial cells. Multi-omics integration validated 131 genes using eQTL and pQTL data from multiple tissues and cohorts. Notably, FTO and APOE emerged as central pleiotropic hubs, and druggability evaluation highlighted APOE, LPL, PPARG, and GPBAR1 as established therapeutic targets for metabolic diseases. CONCLUSION: This study provides a comprehensive map of the shared genetic architecture between MASLD and CKM syndrome, reveals novel causal genes and repurposable drug targets, and offers insights into precision medicine approaches for cardiometabolic and liver diseases.

Humans↗

An integrated multiscale air quality modelling framework for industrial park pollution: Linking local emissions to regional transport.

Capturing the spatiotemporal distribution of pollutants in industrial parks remains challenging for regional air quality models because of their coarse resolution (3 km), resulting in uncertainties in local emission quantification. To address this, we developed the Integrated Multiscale Air Quality Modelling System for Industry (IAQMS-Industry), coupling the regional Nested Air Quality Prediction Modelling System (NAQPMS) with a city-scale chemical transport model. This framework integrates point-source locations and Gaussian plume dispersion to simulate particulate matter with a diameter smaller than 2.5 micrometres (PM2.5) at 100 m resolution. Applied to the Beijing Yi Zhuang and Tangshan industrial parks and evaluated against observations. The coupled model achieved a normalized mean bias (NMB) ranging from 3.1 % to 6.2 %, improving upon NAQPMS (-16.9 % to -7.7 %). Spatial analysis revealed that coarse regional grids underestimated the PM2.5​ concentrations at industrial sites by smoothing gradients, whereas IAQMS-Industry successfully resolved spatial patterns. Industrial point emissions accounted for 22.9 %-26.4 % of PM2.5 in the coupled model, which was significantly greater than the regional model estimates of 1.6 %-13.7 %. These findings indicate that regional models overestimate pollutant dispersion processes in industrial parks while underestimating local industrial impacts. By explicitly resolving point-source dynamics and linking them to regional transport, IAQMS-Industry provides a robust tool for designing targeted emission controls in industrial cities and balancing local air quality improvements with minimized regional pollution outflow. This study underscores the necessity of multiscale modelling for accurate source apportionment and informed environmental governance in industrial zones.

Air Pollution↗

Electrochemical grafting of an aryl fluorosulfonimide electrolyte onto glassy carbon.

Robust bonded layers of an aromatic fluorosulfonimide electrolyte were created on glassy carbon disk and plate electrodes by electroreduction of a new fluorosulfonimide aryl diazonium zwitterion. Formation of the bonded layer was confirmed by XPS of the modified surfaces and also by the effect of the bound layer on reduction/oxidation of redox-active probe molecules. Surface coverage in the monolayer range was achieved. Counterions for as-formed layers were initially tetra-alkylammonium ions from the coating electrolyte but could subsequently be exchanged for other cations by exposure to salt solutions. The bonded layers are very stable with respect to treatment with solvents (water and/or acetonitrile), dry heat (120 degrees C), and hot acid (triflic acid, 80 degrees C, neat and containing 50 wt % water); however, they are unstable with respect to electro-oxidative scanning in aqueous electrolyte solutions.

Journal Article↗

Obligate multivalent recognition of cell surface tomoregulin following selection from a multivalent phage antibody library.

A therapeutic antibody candidate (AT-19) isolated using multivalent phage display binds native tomoregulin (TR) as a mul-timer not as a monomer. This report raises the importance of screening and selecting phage antibodies on native antigen and reemphasizes the possibility that potentially valuable antibodies are discarded when a monomeric phage display system is used for screening. A detailed live cell panning selection and screening method to isolate multivalently active antibodies is described. AT-19 is a fully human antibody recognizing the cell surface protein TR, a proposed prostate cancer target for therapeutic antibody internalization. AT-19 was isolated from a multivalent single-chain variable fragment (scFv) antibody library rescued with hyperphage. The required multivalency for isolation of AT-19 is supported by fluorescence activated cell sorting data demonstrating binding of the multivalent AT-19 phage particles at high phage concentrations and failure of monovalent particles to bind. Pure monomeric scFv AT-19 does not bind native receptor on cells, whereas dimeric scFv or immunoglobulin G binds with nanomolar affinity. The isolation of AT-19 antibody with obligate bivalent binding activity to native TR is attributed to the use of a multivalent display of scFv on phage and the method for selecting and screening by alternate use of 2 recombinant cell lines.

Animals↗

Impact of EGFR point mutations on the sensitivity to gefitinib: insights from comparative structural analyses and molecular dynamics simulations.

Emergence of resistant mutations in drug targets represents a serious problem in the targeted chemotherapy. One challenging issue is to understand the atomic-detailed effect of the mutation on the target. Another intriguing issue is how to predict specific mutations that would show up in the clinical setting, leading to drug resistance. By computational approaches, we have investigated structural, dynamics and energetic effects of a series of EGFR mutations identified from the lung cancer patients. We demonstrated mutation L858R caused gefitinib move closer to the hinge region, whereas T790M caused the ligand escape from the binding pocket. In particular, the T790M decreased the size of the hydrophobic slot formed by L718 and G796. This suggests that, to be effective against the T790M mutant, the inhibitors should avoid interactions with the hydrophobic slot. Mutations T790M, L858R, and their combinations are found to cause different conformational redistribution and to perturb the electrostatic potential at the ATP-binding pocket. Normal mode analysis revealed the mutations resulted in changes in the correlated movements in the protein. In an attempt to develop a computational descriptor for predicting the functional effect of EGFR mutations, we have developed a Plarm algorithm, and the Plarm score was found to be an excellent predictor of the functional impact of six clinical relevant mutations in EGFR tyrosine kinase domains, including T790M, L858R, G719C, L861Q, T790M + L858R double mutant, and delL747-P753insS. The Plarm algorithm could be readily extended to investigate other drug targets.

Adenosine Triphosphate↗

Protective effect of aspirin against dexamethasone-induced cataract in cultured rat lens.

PURPOSE: To investigate the effect of aspirin on dexamethasone-induced cataract formation in cultured rat lenses. METHODS: One hundred and forty-eight lenses were divided into 3 groups and cultured in vitro: control (DMEM), cataract (DMEM + 10 microM dexamethasone), aspirin (DMEM + 10 muM dexamethasone + 2 mM aspirin). Following incubation, the transparency of the lenses was evaluated daily using a dissecting microscope. Twelve lenses from each group were homogenized and the activities of enzymes (catalase, superoxide dismutase and lactate dehydrogenase) from supernatants were measured after 1, 3, 5 and 7 days of incubation, respectively. The ultrastructure of lenses from the control and cataract groups was observed on the completion of 7-day incubation. RESULTS: Opacity was induced by dexamethasone in the nuclear region of the rat lenses. Lenses in the control group exhibited mist-like opacity and lenses in the cataract group showed dense nuclear opacity, whereas lenses in the aspirin-treated group only had a visible demarcation between nuclear and cortical regions at day 7. The activities of catalase, superoxide dismutase and lactate dehydrogenase in the cataract group decreased in a time-dependent manner. There was no significant loss of enzyme activities in either the control or the aspirin group throughout the incubation period. An orderly arrangement of fiber cells was noted, and the cell membrane, cell junction and organelles were normal in the control group. However, in the cataract group the arrangement of fiber cells was untidy and the lenses contained abnormal-appearing cells. The group exhibited swollen mitochondria, a large number of vacuoles and expanded extracellular lacunae. CONCLUSIONS: Dexamethasone induces nuclear cataract in the organ-cultured rat lens by chemically modifying proteins, including enzymes. The enzymes, including those that normally eliminate radial oxygen species, could be especially vulnerable. Aspirin significantly inhibits dexamethasone-induced cataract formation by inhibiting inactivation of those enzymes.

Animals↗

Exploring candidate genes for human brain diseases from a brain-specific gene network.

It is believed that large numbers of genes are involved in common human brain diseases. Here, we propose a novel computational strategy for simultaneously identifying multiple candidate genes for genetic human brain diseases from a brain-specific gene network-level perspective. By integrating diverse genomic and proteomic datasets based on Bayesian statistical model, we built a large-scale human brain-specific gene network. Based on this network and minor prior knowledge of a specific brain disease, we can effectively identify multiple candidate genes for this disease. When four known Alzheimer's disease genes were used as the prior knowledge, among the top 46 high-scoring genes that we have found, 37 were previously reported to be associated with Alzheimer's disease. And the higher score a gene has, the more likely this gene is a disease-related one. The results suggest that the proposed method is effective, convenient, and applicable in the future genetic studies.

Alzheimer Disease↗

Incorporation of a new type of transition metal complex into the thioarsenate anion: syntheses, structures, and properties of two novel compounds [Mn3(2,2'-bipy)3(AsVS4)2]n.nH2O and Mn2(2,2'-bipy)As2IIIS5.

The incorporation of [Mn(2,2'-bipy)2]2+ with thioarsenate resulted in the formation of two novel compounds, [Mn3(2,2'-bipy)3(As(V)S4)2]n.nH2O (1) and Mn2(2,2'-bipy)As2(III)S5 (2), in which the main-group chalcogenide framework is incorporated with a [tm(2,2'-bipy)m]n+ complex. Meanwhile, the tetrathioarsenate(V) anion acts as a new mu3-1kappaS:1,2kappaS':2,3kappaS":3kappaS'" ligand in 1, in which all four S atoms of the [As(V)S4]3- anion are coordinating to metal. As a result, the two compounds exhibit semiconducting properties (Eg = 2.18 eV (1) and 1.83 eV (2)) and strong blue photoluminescence, with the emission maximum occurring at about 440 nm. Magnetic measurements show that both compounds have AF ordered states with Néel temperatures of 19 and 24 K for 1 and 2, respectively.

Journal Article↗

Purification and characterization of two types of chitosanase from a Microbacterium sp.

Two extracellular chitosanases (ChiX and ChiN) were extracted from Microbacterium sp. OU01 with Mr values of 81 kDa (ChiX) and 30 kDa (ChiN). ChiN was optimally active at pH 6.2 and 50 degrees C and ChiX at pH 6.6 and 60 degrees C (assayed over 15 min). Both the activities increased with the degree of deacetylation (DDA) of chitosan. ChiN hydrolyzed oligomers of glucosamine (GlcN) larger than chitopentaose, and chitosan with 62-100% DDA; but ChiX acted on chitosan and released GlcN. Hydrolysis of chitosan with 99% DDA by ChiN released chitobiose, chitotriose and chitotetraose as the major products.

Actinomycetales↗

A possible hypoxia-induced endothelial proliferation in the pathogenesis of epithelioid hemangioma.

Epithelioid hemangioma is an uncommon benign vascular lesion with distinct clinicopathological characteristics. Histologically, this entity mainly composed of well-formed but often immature vessels lined by epithelioid endothelial cells with prominent chronic inflammatory component. There is considerable controversy whether epithelioid hemangioma is a reactive lesion or a true neoplasm. We postulated that the local hypoxia may play a role in the pathogenesis of this vascular tumor. This local hypoxic condition may caused by many incidences such as congenital vascular malformation or trauma. The hypoxia will lead to the proliferation of endothelial cells and the formation of this vascular tumor, which may lead by putative stimulators VEGF and HIF-1. Hypoxia may also promote endothelial cell proliferation through the renin-angiotensin-aldosterone system. Additionally, the inflammatory cells including eosinophils and mast cells may contribute to the endothelial cell proliferation in EH. Further study investigating the associated factors of hypoxia may lead to new, potentially important insights into epithelioid hemangioma, and might also contribute to novel strategies for the management of this entity.

Arteriovenous Malformations↗

Three-dimensional finite element analysis of weakened roots restored with different cements in combination with titanium alloy posts.

BACKGROUND: It is very difficult and relatively unpredictable to preserve and restore severely weakened pulpless roots. To provide much needed benefit basis for clinical practice, this study was carried out to analyze the stress distribution in weakened roots restored with different cements in combination with titanium alloy posts. Finite element analysis (FEA) was employed in the study. METHODS: A pseudo three-dimensional model of a maxillary central incisor with flared root canal, theoretically restored with titanium alloy posts in combination with different cements, was established. The analysis was performed by use of ANSYS software. The tooth was assumed to be isotropic, homogenous and elastic. A load of 100 N at an angle of 45 degrees to the longitudinal axis was applied at the palatal surface of the crown. The distributions of stresses in weakened roots filled with cements of different elastic modulus were analyzed by the three-dimensional FEA model. RESULTS: Several stress trends were observed when the stress cloud atlas obtained in the study was analyzed. With the increase of the elastic modulus of cements from 1.8 GPa to 22.4 GPa, the stress values in dentin decreased from 39.58 MPa to 31.43 MPa and from 24.51 MPa to 20.76 MPa (respectively, for maximum principle stress values and Von Mises stress values). When Panavia F and zinc phosphate cement were used, the stress peak values in dentin were very small with no significant difference observed, and the Von Mises stress values were 20.87 MPa and 20.76 MPa respectively. On the other hand, maximum principle stress value and Von Mises stress value in cement layer increased with the increase of the elastic modulus of cements. CONCLUSIONS: The result of this study demonstrated that elastic modulus was indeed one of the important parameters to evaluate property of the cements. Our three-dimensional FEA model study also found that the cement with elastic modulus similar to that of dentin could reinforce weakened root and reduce the stress in dentin. Thus, it may be a better choice for the restoration of weakened roots in clinical practice.

Adult↗

Functional expression of transient receptor potential vanilloid 4 in the mouse cochlea.

Transient receptor potential vanilloid 4, the Ca2+-permeable cation channel has been proposed as an osmosensitive and a mechanosensitive channel. We investigated functional expression of transient receptor potential vanilloid 4 in inner hair cells, outer hair cells, and spiral ganglion neurons of the mouse cochlea. Transient receptor potential vanilloid 4 mRNA and protein were expressed in inner hair cells, outer hair cells, and spiral ganglion neurons on the basis of the findings of reverse transcriptase-polymerase chain reaction, single-cell reverse transcriptase-polymerase chain reaction, and immunohistochemistry, whereas they were negative in transient receptor potential vanilloid 4-/- mice cochleae. Hypotonic stimulation and 4-alpha-phorbol 12,13-didecanoate, a transient receptor potential vanilloid 4 synthetic activator, increased the intracellular Ca2+ concentrations in wild-type outer hair cells, whereas in transient receptor potential vanilloid 4-/- mice, outer hair cells failed to exhibit a Ca2+ response to both stimulations. In conclusion, transient receptor potential vanilloid 4 may function as an osmosensory and a mechanosensory receptor in the cochlea.

Animals↗

Nucleoplasmin facilitates reprogramming and in vivo development of bovine nuclear transfer embryos.

Successful cloning by somatic cell nuclear transfer (NT) involves an oocyte-driven transition in gene expression from an inherited somatic pattern, to an embryonic form, during early development. This reprogramming of gene expression is thought to require the remodeling of somatic chromatin and as such, faulty and/or incomplete chromatin remodeling may contribute to the aberrant gene expression and abnormal development observed in NT embryos. We used a novel approach to supplement the oocyte with chromatin remodeling factors and determined the impact of these molecules on gene expression and development of bovine NT embryos. Nucleoplasmin (NPL) or polyglutamic acid (PGA) was injected into bovine oocytes at different concentrations, either before (pre-NT) or after (post-NT) NT. Pre-implantation embryos were then transferred to bovine recipients to assess in vivo development. Microinjection of remodeling factors resulted in apparent differences in the rate of blastocyst development and in pregnancy initiation rates in both NPL- and PGA-injected embryos, and these differences were dependent on factor concentration and/or the time of injection. Post-NT NPL-injected embryos that produced the highest rate of pregnancy also demonstrated differentially expressed genes relative to pre-NT NPL embryos and control NT embryos, both of which had lower pregnancy rates. Over 200 genes were upregulated following post-NT NPL injection. Several of these genes were previously shown to be downregulated in NT embryos when compared to bovine IVF embryos. These data suggest that addition of chromatin remodeling factors to the oocyte may improve development of NT embryos by facilitating reprogramming of the somatic nucleus.

Animals↗

Ginsenoside R(e) increases fertile and asthenozoospermic infertile human sperm motility by induction of nitric oxide synthase.

We investigated the effects of Ginsenoside R(e) on human sperm motility in fertile and asthenozoospermic infertile individuals in vitro and the mechanism by which the Ginsenosides play their roles. The semen samples were obtained from 10 fertile volunteers and 10 asthenozoospermic infertile patients. Spermatozoa were separated by Percoll and incubated with 0, 1, 10 or 100 microM of Ginsenoside R(e). Total sperm motility and progressive motility were measured by computer-aided sperm analyzer (CASA). Nitric oxide synthase (NOS) activity was determined by the 3H-arginine to 3H-citrulline conversion assay, and the NOS protein was examined by the Western blot analysis. The production of sperm nitric oxide (NO) was detected using the Griess reaction. The results showed that Ginsenoside R(e) significantly enhanced both fertile and infertile sperm motility, NOS activity and NO production in a concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside R(e). And pretreatment with a NOS inhibitor N(omega)-Nitro-L-arginine methyl ester (L-NAME, 100 microM) or a NO scavenger N-Acetyl-L-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside R(e). Data suggested that Ginsenoside R(e) is beneficial to sperm motility, and that induction of NOS to increase NO production may be involved in this benefit.

Acetylcysteine↗