239,139 results match your criteria spectrometry chemical

Fullerenol as a water-soluble MALDI-MS matrix for rapid analysis of small molecules and efficient quantification of saccharin sodium in foods.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jun 4;1178:122819. Epub 2021 Jun 4.

Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Key Laboratory of Green Chemical Media and Reactions of Ministry of Education, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, China. Electronic address:

Due to the strong background interferences in the low-mass region and poor reproducibility of conventional organic matrices, it is of great importance to develop a novel matrix for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to qualitatively and quantitatively analyze small molecules. In this work, water-soluble fullerenol C(OH) was selected as a MALDI matrix for the analysis of low-molecular-weight compounds in consideration of optical absorption property, water solubility and stability. Compared with the traditional matrices, fullerenol demonstrated lower background interference and stronger peak intensity. Read More

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Characterization of chemical constituents and metabolites in rat plasma after oral administration of San Miao Wan by ultra-high performance liquid chromatography tandem Q-Exactive Orbitrap mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 May 28;1178:122793. Epub 2021 May 28.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu Province, PR China; Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu Province, PR China. Electronic address:

San Miao Wan (SMW), composed of Phellodendri Chinensis Cortex, Atractylodis Lanceae Rhizoma and Achyranthis Bidentatae Radix, is widely used for the treatment of gout, hyperuricemia and other diseases. In the present study, an overall identification strategy based on ultra-high performance liquid chromatography tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method was established to characterize the multiple chemical constituents of SMW and its metabolites in rat plasma after oral administration of SMW. A total of 76 constituents including alkaloids, organic acids, lactones, terpenes, saponins, sterones and others types of components were identified in the extract of SMW. Read More

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Deeply Mining a Universe of Peptides Encoded by Long Noncoding RNAs.

Mol Cell Proteomics 2021 Jun 12:100109. Epub 2021 Jun 12.

Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Many small open reading frames (smORFs) embedded in lncRNA transcripts have been shown to encode biologically functional polypeptides (smORFs-encoded polypeptides, SEPs) in different organisms. Despite significant advances in genomics, bioinformatics and proteomics that largely enabled the discovery of novel SEPs, their identification across different biological samples is still hampered by their poor predictability, diminutive size and low relative abundance. Here, we take advantage of NONCODE, a repository containing the most complete collection and annotation of lncRNA transcripts from different species, to build a novel database that attempts to maximize a collection of SEPs from human and mouse lncRNA transcripts. Read More

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Trimethylacetic anhydride-based derivatization facilitates quantification of histone marks at the MS1 level.

Mol Cell Proteomics 2021 Jun 12:100114. Epub 2021 Jun 12.

Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic; Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. Electronic address:

Histone post-translational modifications (hPTMs) are epigenetic marks that strongly affect numerous processes, including cell cycling and protein interactions. They have been studied by both antibody- and mass spectrometry-based methods for years, but the analyses are still challenging, mainly due to the diversity of histones and their modifications arising from high contents of reactive amine groups in their amino acid sequences. Here, we introduce use of trimethylacetic anhydride (TMA) as a new reagent for efficient histone derivatization, which is a requirement for bottom-up proteomic hPTM analysis. Read More

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Dissecting the Flash Chemistry of Electrogenerated Reactive Intermediates by Microdroplet Fusion Mass Spectrometry.

Angew Chem Int Ed Engl 2021 Jun 15. Epub 2021 Jun 15.

Najing University, Chemistry, Xianlin Ave. 163, , 210023, Nanjing, CHINA.

A novel mass spectrometric method for probing the flash chemistry of electrogenerated reactive intermediates was developed based on rapid collision mixing of electrosprayed microdroplets by using a theta-glass capillary. The two individual microchannels of the theta-glass capillary are asymmetrically or symmetrically fabricated with a carbon bipolar electrode to produce intermediates in situ . Microdroplets containing the newly formed intermediates collide with those of the invoked reactants at sub-10 microsecond level, making it a powerful tool for exploring their ultrafast initial transformations. Read More

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Facile fabrication and characterization of kenaf core as natural biochar for the highly efficient removal of selected endocrine-disrupting compounds.

Environ Geochem Health 2021 Jun 15. Epub 2021 Jun 15.

Institute of Advanced Technology, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.

This study aims to formulate and fabricate the optimum condition of modified kenaf core (MKC) for the removal of targeted endocrine-disrupting compounds in a batch adsorption system. Kenaf core was chemically modified using phosphoric acid as an activating agent, which involved the pyrolysis step. Results indicated a significant difference (p < 0. Read More

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Cheetah-MS: a web server to model protein complexes using tandem cross-linking mass spectrometry data.

Bioinformatics 2021 Jun 15. Epub 2021 Jun 15.

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Sweden.

Summary: Protein-protein interactions (PPI) are central in many biological processes but difficult to characterize, especially in complex, unfractionated samples. Chemical cross-linking combined with mass spectrometry (MS) and computational modeling is gaining recognition as a viable tool in protein interaction studies. Here, we introduce Cheetah-MS, a web server for predicting the PPIs in a complex mixture of samples. Read More

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Plasma-based ambient mass spectrometry: Recent progress and applications.

Mass Spectrom Rev 2021 Jun 15. Epub 2021 Jun 15.

College of Life Sciences, Sichuan University, Chengdu, China.

Ambient mass spectrometry (AMS) has grown as a group of advanced analytical techniques that allow for the direct sampling and ionization of the analytes in different statuses from their native environment without or with minimum sample pretreatments. As a significant category of AMS, plasma-based AMS has gained a lot of attention due to its features that allow rapid, real-time, high-throughput, in vivo, and in situ analysis in various fields, including bioanalysis, pharmaceuticals, forensics, food safety, and mass spectrometry imaging. Tens of new methods have been developed since the introduction of the first plasma-based AMS technique direct analysis in real-time. Read More

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Development of a miniature time-of-flight mass spectrometer coupled with an improved substrate-enhanced laser-induced acoustic desorption source (SE-LIAD/TOF-MS).

Analyst 2021 Jun 15. Epub 2021 Jun 15.

State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

A novel, compact and sensitive SE-LIAD/TOF-MS has been described. It facilitates fast sample preparation, and a full mass spectrum is acquired efficiently and sensitively. More importantly, it features the detection of non-acidic and non-basic or non-polar species, which is not suitable for determination by ESI and MALDI techniques. Read More

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Synthesis of L-[5-11C]Leucine and L-alfa-[5-11C]Methylleucine via Pd0-mediated 11C-Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging.

ChemMedChem 2021 Jun 14. Epub 2021 Jun 14.

RIKEN Kobe Institute, Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, 650-0047, Kobe, JAPAN.

The efficient synthesis of L-[5-11C]leucine and L-alfa-[5-11C]methylleucine has been investigated using a continuous two-step sequence of rapid reactions consisting of Pd0-mediated 11C-methylation and microfluidic hydrogenation. The synthesis of L-[5-11C]leucine and L-alfa-[5-11C]methylleucine was accomplished within 40 min with a decay-corrected radiochemical yield of 15-38% based on [11C]CH3I, radiochemical purity of 95-99%, and chemical purity of 95-99%. The Pd impurities in the injectable solution measured using inductively coupled plasma mass spectrometry met the international criteria for human use. Read More

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Production, purification, and characterization of Streptomyces sp. strain MPPS2 extracellular pyomelanin pigment.

Sinan Bayram

Arch Microbiol 2021 Jun 14. Epub 2021 Jun 14.

Department of Medical Services and Techniques, Vocational School of Health Services, Bayburt University, 69000, Bayburt, Turkey.

Melanins are natural pigments widely distributed in nature from bacteria to humans. These complex, negatively charged, amorphous, high molecular mass natural biopolymers have many different bioactive properties such as antimicrobial, antiviral, antioxidant, liver protective effects, etc. In this study, some chemical and physical properties of the purified extracellular pyomelanin pigment were investigated via XRD (X-ray diffraction), FT-IR (Fourier transform infrared), and H NMR (Nuclear magnetic resonance). Read More

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Metabolomic profiling of single enlarged lysosomes.

Nat Methods 2021 Jun 14. Epub 2021 Jun 14.

Institute on Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.

Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. Read More

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The assessment of effectiveness of SEM- EDX and ICP-MS methods in the process of determining the mineralogical and geochemical composition of particulate matter deposited on spider webs.

Chemosphere 2021 Sep 31;278:130454. Epub 2021 Mar 31.

Faculty of Earth Science and Environmental Management, University of Wrocław, Cybulskiego 32, 50-205, Wrocław, Poland; Department of Environmental Protection, Wroclaw University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland. Electronic address:

Air pollution can be monitored using many different methods. In this paper, we aimed to test and validate two analytical techniques based on complex mineralogical and geochemical analyses with the use of spider webs as a passive sampler. The samples of spider webs were collected in 2018 in polluted areas in the vicinity of the copper smelter Głogów (Poland). Read More

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September 2021

Chemical tagging for sensitive determination of uridine modifications in RNA.

Chem Sci 2020 Jan 8;11(7):1878-1891. Epub 2020 Jan 8.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University Wuhan 430072 P.R. China +86-27-68755595 +86-27-68755595.

The discovery of dynamic and reversible modifications in messenger RNA (mRNA) is opening new directions in RNA modification-mediated regulation of biological processes. Methylation is the most prevalent modification occurring in mRNA and the methyl group is mainly decorated in the adenine, cytosine, and guanine base or in the 2'-hydroxyl group of ribose. However, methylation of the uracil base (5-methyluridine, mU) has not been discovered in mRNA of eukaryotes. Read More

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January 2020

Towards theoretical spectroscopy with error bars: systematic quantification of the structural sensitivity of calculated spectra.

Chem Sci 2019 Dec 27;11(7):1862-1877. Epub 2019 Dec 27.

Technische Universität Braunschweig, Institute of Physical and Theoretical Chemistry Gaußstraße 17 38106 Braunschweig Germany

Molecular spectra calculated with quantum-chemical methods are subject to a number of uncertainties (, errors introduced by the computational methodology) that hamper the direct comparison of experiment and computation. Judging these uncertainties is crucial for drawing reliable conclusions from the interplay of experimental and theoretical spectroscopy, but largely relies on subjective judgment. Here, we explore the application of methods from uncertainty quantification to theoretical spectroscopy, with the ultimate goal of providing systematic error bars for calculated spectra. Read More

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December 2019

Screening of chemicals migrating from plastic food contact materials for oven and microwave applications by liquid and gas chromatography - Orbitrap mass spectrometry.

J Chromatogr A 2021 May 19;1651:462261. Epub 2021 May 19.

USDA Food Safety and Inspection Service, 2150 Centre Avenue, Fort Collins, CO, 80526, USA.

Contamination of food with chemicals migrating from food contact materials (FCMs) is an important area of food safety. This study was aimed to investigate migration of chemicals from plastic FCMs used for microwave and conventional oven heating. Migration tests were conducted for samples of microwave trays, microwave oven bags, and oven bags. Read More

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A Deep Dive into the Complex Chemical Mixture and Toxicity of Tire Wear Particle Leachate in Fathead Minnow.

Environ Toxicol Chem 2021 Jun 14. Epub 2021 Jun 14.

University of Toronto, Department of Ecology and Evolutionary Biology, Toronto, ON, Canada.

The ecological impact of tire wear particles in aquatic ecosystems is a growing environmental concern. In this study, we combined toxicity testing, using fathead minnow (Pimephales promelas) embryos, with non-target high-resolution liquid chromatography Orbitrap mass spectrometry to characterize the toxicity and chemical mixture of organic chemicals associated with tire particle (TP) leachates. We assessed: (a) exposure to TP leachates after leaching for 1-, 3- and 10-days, and (b) the effect of the presence and absence of small tire particulates in the leachates. Read More

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Gas Chromatography-Mass Spectrometry Paired with Total Vaporization Solid-Phase Microextraction as a Forensic Tool.

J Vis Exp 2021 May 25(171). Epub 2021 May 25.

Department of Chemistry & Chemical Biology, Indiana University - Purdue University Indianapolis; Forensic & Investigative Sciences Program, Indiana University - Purdue University Indianapolis;

Gas Chromatography - Mass Spectrometry (GC-MS) is a frequently used technique for the analysis of numerous analytes of forensic interest, including controlled substances, ignitable liquids, and explosives. GC-MS can be coupled with Solid-Phase Microextraction (SPME), in which a fiber with a sorptive coating is placed into the headspace above a sample or immersed in a liquid sample. Analytes are sorbed onto the fiber which is then placed inside the heated GC inlet for desorption. Read More

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and blood compatibility of concentrated polymer brushes.

J Mater Chem B 2021 Jun 14. Epub 2021 Jun 14.

Soft Materials Chemistry, Institute for Materials Chemistry and Engineering, Kyushu University, Build. CE41, 744 Motooka Nishi-ku, Fukuoka 819-0395, Japan and Former Frontier Center for Organic Materials, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan.

Concentrated polymer brushes (CPBs) and semi-dilute polymer brushes (SDPBs) of poly(2-hydroxyethyl methacrylate), poly(2-hydroxyethyl acrylate), poly[poly(ethylene glycol)methyl ether methacrylate] (PPEGMA) and poly(2-methoxyetyl acrylate) were prepared on silica particles and silicon wafers by surface-initiated atom transfer radical polymerization (SI-ATRP). In order to evaluate in vitro blood compatibility, plasma protein adsorption on the brushes was quantified with a BCA protein assay, and the adsorbed proteins on the brushes were identified using high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). All four CPBs displayed much less protein adsorption than their corresponding SDPBs. Read More

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Qualitative and quantitative determination of trace aldehydes and ketones in food preservative propionic acid for quality improvement.

Anal Methods 2021 Jun 14. Epub 2021 Jun 14.

College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China.

Aiming at the difficulty in qualitative and quantitative analysis of trace compositions in food preservative propionic acid, the trace compositions and the key components influencing the total aldehyde content in propionic acid were analyzed by gas chromatography-mass spectrometry (GC-MS), high performance liquid chromatography (HPLC) and gas chromatography (GC) in this paper. The results show that the food preservative propionic acid contains 18 trace compositions. The main compositions affecting the total aldehyde content in propionic acid are acetaldehyde, propionaldehyde, 1-cyclopropyl-1-propanone and 2-methyl-2-pentenal, which account for ∼90% of the total aldehyde content in propionic acid. Read More

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Thermal Decomposition of Cocaine and Methamphetamine Investigated by Infrared Spectroscopy and Quantum Chemical Simulations.

ACS Omega 2021 Jun 26;6(22):14447-14457. Epub 2021 May 26.

J. Heyrovský Institute of Physical Chemistry, Czech Academy of Sciences, Dolejškova 3, 18223 Prague 8, Czech Republic.

Examination of thermal decomposition of street samples of cocaine and methamphetamine shows that typical products detected in previous studies are accompanied by a wide palette of simple volatile compounds easily detectable by spectral techniques. These molecules increase smoke toxicity and their spectral detection can be potentially used for identification of drug samples by well-controlled laboratory thermolysis in temperature progression. In our study, street samples of cocaine and methamphetamine have been thermolyzed under vacuum over the temperature range of 350-650 °C. Read More

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Combination of UPLC-Q-TOF/MS and Network Pharmacology to Reveal the Mechanism of Qizhen Decoction in the Treatment of Colon Cancer.

ACS Omega 2021 Jun 26;6(22):14341-14360. Epub 2021 May 26.

College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Traditional Chinese medicine (TCM) has been utilized for the treatment of colon cancer. Qizhen decoction (QZD), a potential compound prescription of TCM, possesses multiple biological activities. It has been proven clinically effective in the treatment of colon cancer. Read More

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Sensitive Quantification of Nicotine in Bronchoalveolar Lavage Fluid by Acetone Precipitation Combined With Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry.

ACS Omega 2021 Jun 25;6(22):13962-13969. Epub 2021 May 25.

Tobacco and Volatiles Branch, Division of Laboratory Sciences, National Center for Environmental Health, U.S. Centers for Disease Control and Prevention (CDC), 4770 Buford Highway, Mail Stop S103-3, Atlanta, Georgia 30341, United States.

The United States experienced an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in August 2019. Patient diagnosis and treatment sometimes involved bronchoscopy and collection of the bronchoalveolar lavage (BAL) fluid. Although this matrix has been useful for understanding some chemical exposures in the lungs, no methods existed for measuring the nicotine content. Read More

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Identification of Two Novel Compound Heterozygous Mutations Underlying Wolcott-Rallison Syndrome in a Chinese Family.

Front Pediatr 2021 26;9:679646. Epub 2021 May 26.

Institutes of Biomedical Sciences, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.

Wolcott-Rallison syndrome is a rare autosomal recessive inheritance disorder caused by the defectiveness of eukaryotic translation initiation factor 2 alpha kinase 3 (), which encodes the PKR-like endoplasmic reticulum kinase (PERK). Defect in results in a permanent diabetes in early infancy or newborn period, a tendency to develop skeletal fractures and other associated disorders such as severe liver and renal dysfunction, and central hypothyroidism. Two patients with Wolcott-Rallison syndrome-like manifestations in a Chinese family and family members were genetically analyzed to identify if any variations that occurred in , which may cause Wolcott-Rallison syndrome. Read More

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Metallodrugs are unique: opportunities and challenges of discovery and development.

Chem Sci 2020 Nov 12;11(48):12888-12917. Epub 2020 Nov 12.

Department of Chemistry, University of Warwick Gibbet Hill Road Coventry CV4 7AL UK

Metals play vital roles in nutrients and medicines and provide chemical functionalities that are not accessible to purely organic compounds. At least 10 metals are essential for human life and about 46 other non-essential metals (including radionuclides) are also used in drug therapies and diagnostic agents. These include platinum drugs (in 50% of cancer chemotherapies), lithium (bipolar disorders), silver (antimicrobials), and bismuth (broad-spectrum antibiotics). Read More

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November 2020

Elusive structural changes of New Delhi metallo-β-lactamase revealed by ultraviolet photodissociation mass spectrometry.

Chem Sci 2020 Aug 11;11(33):8999-9010. Epub 2020 Aug 11.

Department of Chemistry, University of Texas at Austin Austin TX 78712 USA

We use mass spectrometry (MS), under denaturing and non-denaturing solution conditions, along with ultraviolet photodissociation (UVPD) to characterize structural variations in New Delhi metallo-β-lactamase (NDM) upon perturbation by ligands or mutation. Mapping changes in the abundances and distributions of fragment ions enables sensitive detection of structural alterations throughout the protein. Binding of three covalent inhibitors was characterized: a pentafluorphenyl ester, an -aryloxycarbonyl hydroxamate, and ebselen. Read More

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Interrogating surface intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates.

Chem Sci 2020 Jul 7;11(30):7871-7883. Epub 2020 Jul 7.

Max Planck Institute for Medical Research, Department of Chemical Biology Jahnstr. 29 69120 Heidelberg Germany.

Employing self-labelling protein tags for the attachment of fluorescent dyes has become a routine and powerful technique in optical microscopy to visualize and track fused proteins. However, membrane permeability of the dyes and the associated background signals can interfere with the analysis of extracellular labelling sites. Here we describe a novel approach to improve extracellular labelling by functionalizing the SNAP-tag substrate benzyl guanine ("BG") with a charged sulfonate ("SBG"). Read More

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Introducing charge tag click reaction in living cells for single cell mass spectrometry.

Chem Sci 2020 Jun 23;11(28):7308-7312. Epub 2020 Jun 23.

Hefei National Laboratory for Physical Sciences at the Microscale, School of Chemistry and Materials Science, University of Science and Technology of China Hefei Anhui 230026 P. R. China

For single living cell mass spectrometry measurement, sensitivity is of great significance due to the extremely complicated chemical components of the cytoplasm. Higher sensitivity is always highly desired, especially for chemicals with low concentrations or poor mass spectrometry responses. Here, a quaternary ammonium salt group-based charge tag was designed to enhance the analytical performance for cysteine within single cells using induced nanoelectrospray mass spectrometry. Read More

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Protease-responsive mass barcoded nanotranslators for simultaneously quantifying the intracellular activity of cascaded caspases in apoptosis pathways.

Chem Sci 2020 May 4;11(20):5280-5288. Epub 2020 May 4.

State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210023 P. R. China

Quantitatively delineating the activation network of multiple proteases that participate in cellular processes is highly essential for understanding the physiological and pathological states of cells. In this study, protease-responsive mass barcoded nanotranslators (PRMNTs) were engineered for revealing the activity of cascaded caspases in apoptosis in a multiplex and quantitative manner. In the PRMNTs, a series of mass tag-decorated gold nanoparticles (AuNPs) were tethered onto magnetic FeO nanospheres a linker containing the substrate peptide of the target protease to form a "one-to-many" core-satellite structure. Read More

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Chemical Composition and Antimicrobial Activity of Two Sri Lankan Lichens, , and against Methicillin-Sensitive and Methicillin-Resistant .

Evid Based Complement Alternat Med 2021 1;2021:9985325. Epub 2021 Jun 1.

Instrument Center, Faculty of Applied Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.

Introduction: Medicinal utility of lichens is ascribed to the presence of various secondary metabolites of low molecular weight and they have been used in traditional medicine including Ayurveda in the treatment of wounds and skin disorders. Despite the urgent need to effectively address the antibiotic resistance worldwide, the discovery of new antibacterial drugs has declined in the recent past. This emphasizes the increasing importance of investigating and developing new classes of antibiotics that can withstand antibiotic resistance. Read More

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