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Wang, Lin

Publications and source records attributed to Wang, Lin.

At least 37 records · Page 2

Non-small cell lung cancer cell–derived exosomal miR-17-5p promotes osteoclast differentiation by targeting PTEN

Highlights: • exosomes of SPC-A-1BM cell line prompt osteoclastogenesis. • miR-17-5p increased in exosomes of SPC-A-1BM cell line. • miR-17-5p prompt osteoclastogenesis. • miR-17-5p function through PTEN/PI3K/AKT pathway in osteoclastogenesis in NSCLC. Aberrant activity of bone resorbing osteoclasts plays a key role in the development of osteoporosis and cancer bone metastasis. The identification of novel and specific targets will be helpful for the development of new therapeutic strategies for bone metastasis in lung cancer. Herein, we examined microRNAs in tumor cell-derived exosomes to investigate the communication between the bone environment and tumor cells. TCGA database analysis showed that the level of miR-17-5p increased in non-small cell lung cancer tissues compared with non-tumor tissues. To investigate the function of exosomes in inducing osteoclastogenesis, osteoclast precursors were incubated with exosomes isolated from non-small cell lung cancer cell line, as well as receptor activator of NF-KB ligand and M-CSF to induce osteoclastogenesis. We found that exosomal miR-17-5p is upregulated in a non-small cell lung cancer cell line with bone metastasis compared with the original cell line. Overexpression of miR-17-5p enhanced the osteoclastogenesis of RAW264.7 cells. PTEN was identified as a direct target of miR-17-5p and showed negative effects on osteoclastogenesis. Importantly, treatment of LY294002 (an inhibitor of the PI3K/Akt pathway) attenuated miR-17-5p-mediated osteoclastogenesis effects. Taken together, our findings demonstrated that miR-17-5p promotes osteoclastogenesis through the PI3K/Akt pathway via targeting PTEN in lung cancer.

60 APPLIED LIFE SCIENCES↗

Metabolite discovery through global annotation of untargeted metabolomics data

Liquid chromatography–high-resolution mass spectrometry (LC-MS)-based metabolomics aims to identify and quantify all metabolites, but most LC-MS peaks remain unidentified. Here we present a global network optimization approach, NetID, to annotate untargeted LC-MS metabolomics data. The approach aims to generate, for all experimentally observed ion peaks, annotations that match the measured masses, retention times and (when available) tandem mass spectrometry fragmentation patterns. Peaks are connected based on mass differences reflecting adduction, fragmentation, isotopes, or feasible biochemical transformations. Global optimization generates a single network linking most observed ion peaks, enhances peak assignment accuracy, and produces chemically informative peak–peak relationships, including for peaks lacking tandem mass spectrometry spectra. Applying this approach to yeast and mouse data, we identified five previously unrecognized metabolites (thiamine derivatives and N-glucosyl-taurine). Isotope tracer studies indicate active flux through these metabolites. Furthermore, NetID applies existing metabolomic knowledge and global optimization to substantially improve annotation coverage and accuracy in untargeted metabolomics datasets, facilitating metabolite discovery.

59 BASIC BIOLOGICAL SCIENCES↗

In-situ anodic precipitation process for highly efficient separation of aluminum alloys

Electrorefining process has been widely used to separate and purify metals, but it is limited by deposition potential of the metal itself. Here we report in-situ anodic precipitation (IAP), a modified electrorefining process, to purify aluminium from contaminants that are more reactive. During IAP, the target metals that are more cathodic than aluminium are oxidized at the anode and forced to precipitate out in a low oxidation state. This strategy is fundamentally based on different solubilities of target metal chlorides in the NaAlCl4 molten salt rather than deposition potential of metals. The results suggest that IAP is able to efficiently and simply separate components of aluminum alloys with fast kinetics and high recovery yields, and it is also a valuable synthetic approach for metal chlorides in low oxidation states.

36 MATERIALS SCIENCE↗

dGPredictor: Automated fragmentation method for metabolic reaction free energy prediction and de novo pathway design

Group contribution (GC) methods are conventionally used in thermodynamics analysis of metabolic pathways to estimate the standard Gibbs energy change ( Δ r G ′ o ) of enzymatic reactions from limited experimental measurements. However, these methods are limited by their dependence on manually curated groups and inability to capture stereochemical information, leading to low reaction coverage. Herein, we introduce an automated molecular fingerprint-based thermodynamic analysis tool called dGPredictor that enables the consideration of stereochemistry within metabolite structures and thus increases reaction coverage. dGPredictor has comparable prediction accuracy compared to existing GC methods and can capture Gibbs energy changes for isomerase and transferase reactions, which exhibit no overall group changes. We also demonstrate dGPredictor’s ability to predict the Gibbs energy change for novel reactions and seamless integration within de novo metabolic pathway design tools such as novoStoic for safeguarding against the inclusion of reaction steps with infeasible directionalities. To facilitate easy access to dGPredictor, we developed a graphical user interface to predict the standard Gibbs energy change for reactions at various pH and ionic strengths. The tool allows customized user input of known metabolites as KEGG IDs and novel metabolites as InChI strings ( https://github.com/maranasgroup/dGPredictor ).

59 BASIC BIOLOGICAL SCIENCES↗

Superconductivity and electron-phonon interaction in Sr x Bi 2 Se 3 under pressure

Pressure-induced superconductivity has been widely explored and observed in Bi 2 Se 3 -based topological materials to hunt for topological superconductors. Although their triggered superconductivity has a close connection to their pressure-induced structural phase transitions, the quest for the electron pairing mechanism of these superconducting semiconductors in both their initial rhombohedral and high-pressure phases remains unknown. In this work, we present a systematic study of the pressure effect on superconducting properties and lattice dynamics using a combination of electrical transport, Raman-scattering, and synchrotron x-ray diffraction measurements using diamond anvil cells. One key finding is our observation of a cooperative connection between the strength of the electron–phonon interaction (EPI) generated by optical branches and the pressure-tunable superconductivity in rhombohedral Sr x Bi 2 Se 3 crystal. The underlying suppression mechanism of the T c by pressure is ascribed to the weakening of the electrons' interaction with the optical phonon modes in the rhombohedral phase. In the intermediate monoclinic phase, the T c value underwent a sharp increase with carrier density accumulation accompanying the concurrent enhanced EPI. This is intuitively unusual since it is expected that the EPI shall be weakened by inducing more conducting carriers in a normal metal. In the tetragonal phase, the superconductivity is interpreted within BCS theory, since it is fully metallized and obeys the adiabatic Born–Oppenheimer approximation well. Our findings are important to fully understand unconventional superconductivity and the unusual pairing mechanism in the layered rhombohedral Bi 2 Se 3 -based superconductors.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

3D Bacterial flagella as both synthetic biotemplates and ultrathin spacers for enhanced inter-particle coupling and solar energy harvesting

Linear light-absorbing nanomaterials are ideal for film-based solar harvesting applications as they form porous structures that can maximize the absorption and minimize the reflection of the solar light. Conventional 1D nanochains of plasmonic nanoparticle assemblies can achieve significantly broadened optical absorption through surface plasmon coupling, but their optical bands are still not broad enough to absorb through the solar spectrum and thus are not efficient solar absorbers. Here we discovered first by simulation that 3D structured nanochains of plasmonic nanoparticles presented a remarkably increased optical broadening effect and much longer redshift of the optical peaks due to the enhanced inter-particle coupling effect. Then we fabricated 3D nanochains by assembling gold nanoparticles (AuNPs) around 14 nm ultrathin bionanofibers, the bacterial flagella. Additionally, the ultrathin biotemplates enabled the 3D arrangement of 50 nm AuNPs along the nanofiber with a very small inter-particle gap, allowing the strong coupling of surface plasmons in a 3D manner. Consistent with the theoretical prediction, the 3D nanochains, when assembled into films, could effectively convert nearly the full spectrum of solar energy into heat, which was further efficiently converted into electricity through a thermoelectric generation unit. Our work represents a nanobiomaterial approach to highly efficient solar thermal power generation.

36 MATERIALS SCIENCE↗

Quantification of Intrafraction and Interfraction Tumor Motion Amplitude and Prediction Error for Different Liver Tumor Trajectories in Cyberknife Synchrony Tracking

To research the fiducial-based, real-time tracking intrafraction (during the fraction [intra-]) and interfraction (between fractions [inter-]) tumor respiration amplitude, motion trajectory, and prediction error and quantify their relationships for different types of motion trajectories during Cyberknife-based stereotactic ablation radiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Controlled synthesis and ordered assembly of Co 3 O 4 nanowires using genetically engineered bacterial flagella as biotemplates (Final Technical Report)

The major goals of the project are to gain a fundamental understanding on the influence of the displayed peptides and other processing parameters on the flagella assembly and the resulting biomimetic control over the synthesis and assembly of Co 3 O 4 nanoparticles (NPs) and nanowires (NWs). To pursue these goals, we designed two specific aims: Aim 1: Understanding the self-assembly of genetically engineered flagella and its outcome for site-specific nucleation and growth of Co 3 O 4 NPs and NWs. Aim 2: Understanding controllable alignment of 1D Co 3 O 4 -flagella NWs into highly ordered 2D and 3D structures.

59 BASIC BIOLOGICAL SCIENCES↗

A Genome-Scale Metabolic Model of Anabaena 33047 to Guide Genetic Modifications to Overproduce Nylon Monomers

Nitrogen fixing-cyanobacteria can significantly improve the economic feasibility of cyanobacterial production processes by eliminating the requirement for reduced nitrogen. Anabaena sp. ATCC 33047 is a marine, heterocyst forming, nitrogen fixing cyanobacteria with a very short doubling time of 3.8 h. We developed a comprehensive genome-scale metabolic (GSM) model, iAnC892, for this organism using annotations and content obtained from multiple databases. iAnC892 describes both the vegetative and heterocyst cell types found in the filaments of Anabaena sp. ATCC 33047. iAnC892 includes 953 unique reactions and accounts for the annotation of 892 genes. Comparison of iAnC892 reaction content with the GSM of Anabaena sp. PCC 7120 revealed that there are 109 reactions including uptake hydrogenase, pyruvate decarboxylase, and pyruvate-formate lyase unique to iAnC892. iAnC892 enabled the analysis of energy production pathways in the heterocyst by allowing the cell specific deactivation of light dependent electron transport chain and glucose-6-phosphate metabolizing pathways. The analysis revealed the importance of light dependent electron transport in generating ATP and NADPH at the required ratio for optimal N2 fixation. When used alongside the strain design algorithm, OptForce, iAnC892 recapitulated several of the experimentally successful genetic intervention strategies that over produced valerolactam and caprolactam precursors.

59 BASIC BIOLOGICAL SCIENCES↗

The stability of subducted glaucophane with the Earth’s secular cooling

The blueschist to eclogite transition is one of the major geochemical–metamorphic processes typifying the subduction zone, which releases fluids triggering earthquakes and arc volcanism. Although glaucophane is an index hydrous mineral for the blueschist facies, its stability at mantle depths in diverse subduction regimes of contemporary and early Earth has not been experimentally determined. Here, we show that the maximum depth of glaucophane stability increases with decreasing thermal gradients of the subduction system. Along cold subduction geotherm, glaucophane remains stable down ca. 240 km depth, whereas it dehydrates and breaks down at as shallow as ca. 40 km depth under warm subduction geotherm or the Proterozoic tectonic setting. Our results imply that secular cooling of the Earth has extended the stability of glaucophane and consequently enabled the transportation of water into deeper interior of the Earth, suppressing arc magmatism, volcanism, and seismic activities along subduction zones.

58 GEOSCIENCES↗

Green synthesis of sulfur‐doped g‐C 3 N 4 nanosheets for enhanced removal of oxytetracycline under visible‐light irradiation and reduction of its N ‐nitrosodimethylamine formation potential

Abstract BACKGROUND In this study, sulfur‐doped g‐C 3 N 4 (SCN) nanosheets were synthesized using thiourea as a precursor, and then used to catalyze the degradation of oxytetracycline (OTC) under visible‐light irradiation. OTC was chosen as target contaminant because of it being an important precursor of N ‐nitrosodimethylamine (NDMA). RESULTS The removal of OTC was influenced by its initial concentration, initial pH, SCN dosage and water matrices. OTC (≤10 mg L −1 ) was almost completely removed in 40 min under the conditions of an initial pH of 7.0 and a SCN dose of 1.0 g L −1 , and its degradation was well described by the pseudo‐first‐order kinetics model. Water matrices would also influence the degradation of OTC in the system. Electron paramagnetic resonance analysis and trapping experiments confirmed that the function of the radicals for OTC removal followed the order of • O 2 − > • OH > h + . Eight transformation products were determined during the degradation of OTC, it being removed through four pathways: methyl oxidization, demethylation, decarbonylation and secondary alcohol oxidation. SCN was stable in the system, as the removal efficiency of OTC was not significantly reduced even after three recycles. In addition, 55.5% of NDMA formation potential of OTC was reduced after SCN catalytic oxidation. CONCLUSIONS The results imply that the visible‐light‐driven SCN catalytic oxidation is an effective technology not only for the removal of OTC but also for the reduction of NDMA formation potential. © 2021 Society of Chemical Industry

Dou, Yicheng↗

HPRT promotes proliferation and metastasis in head and neck squamous cell carcinoma through direct interaction with STAT3

Highlights: • The higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. • Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers. • HPRT directly interacted with STAT3. • Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect against HNSCC xenografts. Increasing effort has been put into finding novel molecular pathways to improve the efficiency of EGFR inhibitors against head and neck squamous cell cancer (HNSCC). In this study, we performed data mining and bioinformatically analysed RNA-Seq data downloaded from TCGA and confirmed that higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. Then, we conducted in vitro and in vivo loss- and gain-of-function experiments to demonstrate the role of HPRT in HNSCC cell lines. Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers via direct interaction with STAT3. Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect of EGFR inhibitors against HNSCC xenografts. In conclusion, HPRT is a binding partner of STAT3 that promotes EMT and proliferation. Our findings support HPRT as a promising prognostic indicator and potential therapeutic target for HNSCC.

60 APPLIED LIFE SCIENCES↗

Probing the Electronic Band Gap of Solid Hydrogen by Inelastic X-Ray Scattering up to 90 GPa

Metallization of hydrogen as a key problem in modern physics is the pressure-induced evolution of the hydrogen electronic band from a wide-gap insulator to a closed gap metal. However, due to its remarkably high energy, the electronic band gap of insulating hydrogen has never before been directly observed under pressure. Using high-brilliance, high-energy synchrotron radiation, we developed an inelastic x-ray probe to yield the hydrogen electronic band information in situ under high pressures in a diamond-anvil cell. Here, the dynamic structure factor of hydrogen was measured over a large energy range of 45 eV. The electronic band gap was found to decrease linearly from 10.9 to 6.57 eV, with an 8.6 times densification (ρ/ρ 0 ~ 8.6 ) from zero pressure up to 90 GPa.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Investigation on nanoscale material removal process of BK7 and fused silica glass during chemical‐mechanical polishing

Abstract Understanding the nanoscale material removal process in chemical mechanical polishing (CMP) is of fundamental importance for the operation and further development of CMP. In this study, the nanoscale material removal processes of both fused silica glass and BK7 glass were investigated based on single‐pad‐asperity polishing experiments. The results indicate that the material removal characteristics are highly dependent on the composition and structure of glass materials. In the mechanically induced chemical bonding removal mode, only atoms locate near the outermost several layers can participate in the formation and breakage of interfacial bridge bonds. Moreover, the force on the abrasive particle must exceed a threshold value to induce significant removal of Si atoms from the glass substrate, because as the breakage of Si glass –O backbonds does not occur in low‐stress conditions. We reveal for the first time that the chemical and mechanical properties of the topmost layer, which is recognized as densification, hydrated, or redeposition layer, have not been significantly affected by the mechanical action of the abrasive particles when polishing in this kind of material removal mode. The results are expected to provide a deeper insight into the nanoscale material removal mechanism during glass CMP.

Wang, Lin↗

Building kinetic models for metabolic engineering

Kinetic formalisms of metabolism link metabolic fluxes to enzyme levels, metabolite concentrations and their allosteric regulatory interactions. Though they require the identification of physiologically relevant values for numerous parameters, kinetic formalisms uniquely establish a mechanistic link across heterogeneous omics datasets and provide an overarching vantage point to effectively inform metabolic engineering strategies. Advances in computational power, gene annotation coverage, and formalism standardization have led to significant progress over the past few years. However, careful interpretation of model predictions, limited metabolic flux datasets, and assessment of parameter sensitivity remain as challenges. In this study we highlight fundamental considerations which influence model quality and prediction, advances in methodologies, and success stories of deploying kinetic models to guide metabolic engineering.

59 BASIC BIOLOGICAL SCIENCES↗

Recent advances in constraint and machine learning-based metabolic modeling by leveraging stoichiometric balances, thermodynamic feasibility and kinetic law formalisms

Understanding the governing principles behind organisms’ metabolism and growth underpins their effective deployment as bioproduction chassis. A central objective of metabolic modeling is predicting how metabolism and growth are affected by both external environmental factors and internal genotypic perturbations. The fundamental concepts of reaction stoichiometry, thermodynamics, and mass action kinetics have emerged as the foundational principles of many modeling frameworks designed to describe how and why organisms allocate resources towards both growth and bioproduction. Furthermore, this review focuses on the latest algorithmic advancements that have integrated these foundational principles into increasingly sophisticated quantitative frameworks.

59 BASIC BIOLOGICAL SCIENCES↗