Ion Signal Research Articles

Enterobacter cloacae: a villain in CaOx stone disease?

To explore the roles microbiome of urinary tract played in calcium oxalate stones (CaOx) formation, we collected two sides’ pelvis urine of patients with unilateral CaOx stones to set self-control to diminish the influence of systemic factors. Patients with unilateral CaOx stones were recruited in our study according to strict criteria. 16S rRNA gene sequencing was applied to every pair of pelvis urine. Bacterial genome sequencing of Enterobacter cloacae was conducted and bioinformatic analysis was applied to explore the possible pathways of Enterobacter cloacae inducing CaOx stones formation. In vivo experiments were conducted to validate our claims. Von Kossa staining, TUNEL assay and Western Blot were applied to SD rats exploring the mechanism of stone formation. We found 26 significantly different bacteria between stone sides and non-stone sides’ pelvis urine, among which Enterobacter cloacae ranked the most different. Bacterial genome sequencing of Enterobacter cloacae revealed that its virulence factors included Flagellin, LPS and Fimbrial. GO and KEGG analysis revealed it probably induced CaOx stone formation via ion binging and signaling transduction pathways. The results of animal experiments indicated that Glyoxylic Acid could promote apoptosis and crystal depositions of kidney comparing with control group while pre-injected with Enterobacter cloacae could apparently compound the effects. While Western Blot demonstrated that Glyoxylic Acid or Enterobacter cloacae could increase the expression of IL-6, Mcp-1, BMP2 and OPN in rats’ kidney, Glyoxylic Acid and Enterobacter cloacae together could aggravate these increases. These findings indicated that Enterobacter cloacae might play important roles in CaOx stones formation. However, this study is just a preliminary exploration; further studies still need to be conducted.

Transcriptome profiling to elucidate mechanisms of the enhancement of the resistance to Botryosphaeria dothidea by nitric oxide in postharvest kiwifruit during storage

Nitric oxide (NO), as an important messenger in eukaryotes, is a novel chemical elicitor capable of inducing defense responses in fruit and vegetables. In this study, exogenous NO fumigation at a concentration of 15 μl L−1 remarkably alleviated the disease symptoms of postharvest kiwifruit inoculated with Botryosphaeria dothidea. The disease incidence in the NO-treated kiwifruit was approximately 30%, 20%, and 13% lower than the control fruit from 4 to 6 days post inoculation. At 7 days after inoculation, the lesion size of the NO-treated fruit was about 50% of that of the control fruit. Transcriptome analysis showed that 1275 genes (662 up-regulated and 613 down-regulated) were differentially expressed between NO-treated and control kiwifruit. Based on the functional information obtained, 46 of these genes are involved in pathogen-defense pathways. These key genes are associated with phenylalanine metabolism, mitogen-activated protein kinase signaling pathway, plant hormone signaling pathway, calcium ion signal decoding, and pathogenesis-related protein. Furthermore, the results of quantitative real-time polymerase chain reaction helped us to study the changes in the expression levels of candidate genes in different disease-resistant pathways. These results will help to understand the mechanisms of NO-induced pathogen resistance in postharvest kiwifruit.

Ionized Molecular Hydrogen Build-Up and Confinement Inside the Space Charge of a Continually Resupplied Electron Cloud

A cylindrically symmetric electromagnetic ion trap has been constructed that creates a potential well suitable for confining ions with the space charge of a continually resupplied electron cloud. The trap uses permanent magnets to form a linear array of magnetic field ring cusps in a cylindrical geometry and includes electrostatic plugging of the cusping magnetic fields. The ion source is electron bombardment ionization of a controlled leak of thermal molecular hydrogen directly inside the trap, and a potential well created by those selfsame electrons is the mechanism of ion confinement. The ion trap is unique in that the confinement volume has relatively minimal external static electric and magnetic field intrusion into the regions intended to confine ions and no overall axial magnetic field. Another standout feature is the inclusion of electrostatic elements in two locations inaccessible to electrons inside the trap that provide axial ion confinement in conjunction with electrons in the trap. Build-up of ions, and therefore confinement, was demonstrated via an ion signal that increased in intensity over a period of several dozen expected axial ion transit times while injecting electrons. A study has been conducted for a range of incident electron currents from the electron flood gun for several fixed partial pressures of molecular hydrogen and interpreted using a full particle-in-cell simulation of the trap. Data were acquired via a microchannel plate and phosphor screen assembly biased in a manner that could only be excited by positively charged particles exiting the trap. An order of magnitude estimate for mean lifetime is made using a combination of simulated charged particle population estimates and measured data.

Coordination between multiple bacterial communities using potassium ion signaling

In Bacillus subtilis biofilms, potassium ion signaling allows for long-distance communication and coordination between cells in mature colonies to regulate nutrient consumption. This intra-colony communication improves the robustness of a biofilm by increasing nutrient availability for cells in the interior. Less is known about electrochemical communication between multiple independent biofilms, where it has been observed that a state of nutrient starvation can be sensed by neighboring colonies.

Understanding the loss of CXCR4-mediated signalling in the presence of oxysterols

CXCR4 is the G-Protein Coupled Receptor (GPCR) which mediates signalling for cell migration. The only known ligand is CXCL12 or SDF-1, which initiates the signalling process. It is well-known that cholesterol plays a significant role in modulating GPCR signalling across the membrane. Further, studies have shown that reduced cholesterol concentration leads to a decreased level of calcium ion signalling. Nevertheless, it is unknown how the presence of oxysterols affects the signalling process of a GPCR.

Integrated lipidomics and network pharmacology analysis of the protective effects and mechanism of Yuanzhi San on rats with cognitive impairment

Cognitive impairment (CI) can seriously affect people's mental and physical health. Yuanzhi San (YZS) is a classic prescription for treating CI, but the mechanisms need further exploration. The aim of this study is to explore the effect of YZS on promoting the learning and memory ability of CI rats induced by d-galactose combined with aluminum chloride. Behavioral experiments had been used to comprehensively evaluate the established CI model. Brain histological morphology and the expressions of calcium ion signaling pathway related factors in serum were used to evaluate the effect of YZS against CI. Lipids in rat serum were analyzed by ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS) and chemical pattern recognition methods. Network pharmacology was used to find potential chemical compounds, targets, and related signaling pathways against CI with treatment of YZS. The integrated lipidomics and network pharmacology analysis were conducted by Cytoscape software. The results showed that YZS could alleviate neurodegenerative impairment. It was verified that model rats had longer latency time, shorter exploration paths, lower new objects recognition indexes, and shorter exercise time and distances compared with the normal rats in behavioral experiments, indicating that the model rats were successfully established. Rats of YZS 6.67 had significant differences in retention time (p < 0.05), number of entrances (p < 0.01), new object recognition indexes (p < 0.05, p < 0.01), exercise time (p < 0.05), and content of Ca [2]+, CAM, APP, CREB (p < 0.01), CAMK2 (p < 0.05). Rats of YZS 6.67 had five cell layers in hippocampus histological morphology. Behavioral experiments results showed that YZS had an active effect on CI rats. From lipidomics analysis, 129 lipids were screened out by conditions of VIP > 1 and p < 0.05, and 17 lipid markers were identified from the databases, which were divided mainly into five types. Pathway analysis indicated that linoleic acid, α-linolenic acid, arachidonic acid, and glycerophospholipid metabolisms were potential target pathways closely involved in the mechanism YZS’s effects against CI. Network pharmacology focused on 84 chemical compounds, 130 intersection targets, and 10 hub genes of YZS’s effects against CI. Six hub genes and four lipid compounds had intrinsic contact with arachidonic acid metabolism, glycerophospholipid metabolism and linoleate metabolism. The study revealed that YZS could improve animal cognitive behaviors, the expression of factors associated with memory in serum and the histological morphology of hippocampus. Four lipid compounds, three metabolic pathways, and six hub genes of YZS could effectively modulated CI. These results collectively suggest that the main mechanism of YZS in improving CI involves lipid metabolism, which affects biological processes and targets of action in the body.

Ion mobility spectrometry of &lt;i&gt;N&lt;/i&gt;-methylimidazole and possibilities of its determination

Objectives. To determine the ion mobility of N-methylimidazole, establish the structure of ions corresponding to characteristic signals, and determine the detection limit of N-methylimidazole on the ion-drift detector Kerber.Methods. Ion mobility spectrometry was used to study the ionization processes. The enthalpies of the reactions of monomer and dimer ions were calculated in the ORCA 4.1.1 software by the B3LYP density functional method with a set of basic functions 6-31G (d, p).Results. The drift time and ion mobility values of N-methylimidazole were determined. A method for mathematical processing of spectra and a program for its implementation was developed. The changing peculiarities of the ion mobility spectrum during measurement at a given time were studied. According to the interpretation of the spectrum signals, the structure of the generated ions was proposed, and the enthalpies of ion formation were determined.Conclusions. The characteristic signal of the N-methylimidazole ion protonated at the nitrogen atom of the pyridine type was revealed. It was found that two signals in the ion mobility spectra of N-methylimidazole correspond to the presence of the monomer and dimer ions. The detection limit of N-methylimidazole on the ion-drift detector Kerber was determined, amounting to 3 pg.

Differential target multiplexed spinal cord stimulation programming modulates proteins involved in ion regulation in an animal model of neuropathic pain.

The effect of spinal cord stimulation (SCS) using differential target multiplexed programming (DTMP) on proteins involved in the regulation of ion transport in spinal cord (SC) tissue of an animal model of neuropathic pain was evaluated in comparison to low rate (LR) SCS. Rats subjected to the spared nerve injury model (SNI) and implanted with a SCS lead were assigned to DTMP or LR and stimulated for 48 h. A No-SCS group received no stimulation, and a Sham group received no SNI or stimulation. Proteins in the dorsal ipsilateral quadrant of the stimulated SC were identified and quantified using mass spectrometry. Proteins significantly modulated by DTMP or LR relative to No-SCS were identified. Bioinformatic tools were used to identify proteins related to ion transport regulation. DTMP modulated a larger number of proteins than LR. More than 40 proteins significantly involved in the regulation of chloride (Cl−), potassium (K+), sodium (Na+), or calcium (Ca2+) ions were identified. SNI affected proteins that promote the increase of intracellular Ca2+, Na+, and K+ and decrease of intracellular Cl−. DTMP modulated proteins involved in glial response to neural injury that affect Ca2+ signaling. DTMP decreased levels of proteins related to Ca2+ transport that may result in the reduction of intracellular Ca2+. Presynaptic proteins involved in GABA vesicle formation and release were upregulated by DTMP. DTMP also upregulated postsynaptic proteins involved with elevated intracellular Cl−, while modulating proteins, expressed by astrocytes, that regulate postsynaptic Cl− inhibition. DTMP downregulated K+ regulatory proteins affected by SNI that affect neuronal depolarization, and upregulated proteins that are associated with a decrease of intracellular neuronal K+ and astrocyte uptake of extracellular K+. DTMP treatment modulated the expression of proteins with the potential to facilitate a reversal of dysregulation of ion transport and signaling associated with a model of neuropathic pain.

Suppressing Effect of Na+/Ca2+ Exchanger (NCX) Inhibitors on the Growth of Melanoma Cells.

The role of calcium ion (Ca2+) signaling in tumorigenicity has received increasing attention in melanoma research. Previous Ca2+ signaling studies focused on Ca2+ entry routes, but rarely explored the role of Ca2+ extrusion. Functioning of the Na+/Ca2+ exchanger (NCX) on the plasma membrane is the major way of Ca2+ extrusion, but very few associations between NCX and melanoma have been reported. Here, we explored whether pharmacological modulation of the NCX could suppress melanoma and promise new therapeutic strategies. Methods included cell viability assay, Ca2+ imaging, immunoblotting, and cell death analysis. The NCX inhibitors SN-6 and YM-244769 were used to selectively block reverse operation of the NCX. Bepridil, KB-R7943, and CB-DMB blocked either reverse or forward NCX operation. We found that blocking the reverse NCX with SN-6 or YM-244769 (5–100 μM) did not affect melanoma cells or increase cytosolic Ca2+. Bepridil, KB-R7943, and CB-DMB all significantly suppressed melanoma cells with IC50 values of 3–20 μM. Bepridil and KB-R7943 elevated intracellular Ca2+ level of melanoma. Bepridil-induced melanoma cell death came from cell cycle arrest and enhanced apoptosis, which were all attenuated by the Ca2+ chelator BAPTA-AM. As compared with melanoma, normal melanocytes had lower NCX1 expression and were less sensitive to the cytotoxicity of bepridil. In conclusion, blockade of the forward but not the reverse NCX leads to Ca2+-related cell death in melanoma and the NCX is a potential drug target for cancer therapy.

Effect of the Laser Pulse Width in MALDI-2: A Comparative Study of Picosecond versus Nanosecond Wide Pulses for Laser Postionization.

MALDI-2 is a recently introduced technique for postionization (PI) in matrix-assisted laser desorption/ionization (MALDI). It is based on an initial photoionization of neutrally desorbed matrix molecules and subsequent charge-transfer reactions in a fine vacuum or atmospheric pressure ion source. MALDI-2 significantly increases the ion yields for numerous classes of analytes, including lipids, glycans, and a range of pharmaceuticals. To obtain insights into the ionization mechanisms underlying the primary step of PI in MALDI-2, we here conducted a set of experiments with two lasers at 266 nm wavelength and pulse durations of 28 ps and 6 ns, respectively, on a modified orthogonal-extracting time-of-flight mass spectrometer (QTOF, Synapt). 2,5-Dihydroxybenzoic acid (DHB) and 2,5-dihydroxyacetophenone (DHAP) were investigated as MALDI matrices in the positive-ion mode with standardized lipid samples. Analyte- and matrix-derived ion signals were recorded as a function of PI laser pulse energies. The ion signal intensity displays a quadratic dependency on PI-laser pulse energy for low to moderate intensities of up to ∼107 W/cm2. This behavior suggests the involvement of resonance enhanced two-photon ionization (REMPI) of neutral matrix molecules in the ionization pathways. Comparing nanosecond and picosecond pulses at the same PI laser pulse energy, higher photon density produced by the shorter pulses generally produced sizably higher ion signal intensities, also corroborating an involvement of REMPI-like processes. Based on a theoretical description of the MALDI-2 process derived from prevalent REMPI theory, comparative measurements allow us to determine the lifetime of the excited states of the employed matrices. Resulting values for both matrices are in good agreement with the literature and corroborate the REMPI-based approach.

Solvent-Mediated Proton-Transfer Catalysis of the Gas-Phase Isomerization of Ciprofloxacin Protomers.

Understanding how neutral molecules become protonated during positive-ion electrospray ionization (ESI) mass spectrometry is critically important to ensure analytes can be efficiently ionized, detected, and unambiguously identified. The ESI solvent is one of several parameters that can alter the dominant site of protonation in polyfunctional molecules and thus, in turn, can significantly change the collision-induced dissociation (CID) mass spectra relied upon for compound identification. Ciprofloxacin─a common fluoroquinolone antibiotic─is one such example whereby positive-ion ESI can result in gas-phase [M + H]+ ions protonated at either the keto-oxygen or the piperazine-nitrogen. Here, we demonstrate that these protonation isomers (or protomers) of ciprofloxacin can be resolved by differential ion mobility spectrometry and give rise to distinctive CID mass spectra following both charge-directed and charge-remote mechanisms. Interaction of mobility-selected protomers with methanol vapor (added via the throttle gas supply) was found to irreversibly convert the piperazine N-protomer to the keto-O-protomer. This methanol-mediated proton-transport catalysis is driven by the overall exothermicity of the reaction, which is computed to favor the O-protomer by 93 kJ mol-1 (in the gas phase). Conversely, gas phase interactions of mobility-selected ions with acetonitrile vapor selectively depletes the N-protomer ion signal as formation of stable [M + H + CH3CN]+ cluster ions skews the apparent protomer population ratio, as the O-protomer is unaffected. These findings provide a mechanistic basis for tuning protomer populations to ensure faithful characterization of multifunctional molecules by tandem mass spectrometry.

New SIMS method to characterize hydrogen in polysilicon films

A new analysis protocol for profiling the hydrogen (H) concentration depth distributions in polysilicon (poly-Si) thin films on Si oxide was developed by using secondary ion mass spectrometry (SIMS). Traditional SIMS determination of H concentrations in poly-Si films is to monitor and collect the atomic H−, but this analysis method presents some challenges for providing stable and repeatable H depth profiles, especially, for shallow profiling in thinner poly-Si films on thicker Si oxide films. In this paper, we present a thorough study of the SIMS characterization of H levels in poly-Si thin films on Si oxide. We describe an approach for the use of cluster SiH− instead of atomic H− to determine the H concentrations. The utilization of the SiH− cluster ion minimizes both H adsorption effects on the film surface regions and sample surface charging effects arising from the Si oxide layer underneath, thus enhancing the secondary ion signal stability in poly-Si films, as discussed with secondary ion energy distribution on the samples. This method differs from the conventional SIMS analysis of H in thin films and significantly improves the data quality and accuracy. Fourier transform infrared spectroscopy analysis was used to study the Si–H chemical bonding information for investigating the nature of the SIMS collected SiH− cluster ions. Both the H implant sample with no significant Si–H bonding and the poly-Si samples with high levels of H and the weak Si–H bonding exhibited strong SiH− secondary cluster ion intensities in our studies. This indicates the cluster ion signals arise from either the combination of Si and H ions through the physics formation process or weak chemically bonded Si and H.

Visualization of a curated Oryza sativa L. CDPKs Protein-Protein Interaction Network (CDPK-OsPPIN).

Calcium-Dependent Protein Kinases (CDPKs) translate calcium ion (Ca2+) signals into direct phosphorylation of proteins involved in stress response and plant growth. To get a clear picture of CDPKs functions, we must identify and explore the CDPKs targets and their respective roles in plant physiology. Here, we present a manually curated Oryza sativa L. CDPK Protein-Protein Interaction Network (CDPK-OsPPIN). The CDPK-OsPPIN provides an interactive graphical tool to assist hypothesis generation by researchers investigating CDPK roles and functional diversity.

Recent advances in structural studies of 14-3-3 protein complexes.

Being phosphopeptide-binding hubs, 14-3-3 proteins coordinate multiple cellular processes in eukaryotes, including the regulation of apoptosis, cell cycle, ion channels trafficking, transcription, signal transduction, and hormone biosynthesis. Forming constitutive α-helical dimers, 14-3-3 proteins predominantly recognize specifically phosphorylated Ser/Thr sites within their partners; this generally stabilizes phosphotarget conformation and affects its activity, intracellular distribution, dephosphorylation, degradation and interactions with other proteins. Not surprisingly, 14-3-3 complexes are involved in the development of a range of diseases and are considered promising drug targets. The wide interactome of 14-3-3 proteins encompasses hundreds of different phosphoproteins, for many of which the interaction is well-documented in vitro and in vivo but lack the structural data that would help better understand underlying regulatory mechanisms and develop new drugs. Despite obtaining structural information on 14-3-3 complexes is still lagging behind the research of 14-3-3 interactions on a proteome-wide scale, recent works provided some advances, including methodological improvements and accumulation of new interesting structural data, that are discussed in this review.

Research on Gas Type Discrimination and Emission Regulation of Fully Premixed Condensing Gas Boiler Based on Flame Ion Signal

Research on Gas Type Discrimination and Emission Regulation of Fully Premixed Condensing Gas Boiler Based on Flame Ion Signal

Products of Prolonged Autoxidation of Simple Dihydric Phenols in the Presence of Copper(II) Ions – An Electron Spin Resonance Study

Electron spin resonance (ESR) spectroscopy was used for characterizing the products obtained by prolonged autoxidation of simple dihydric phenols (hydroquinone, catechol, and 4-methylcatechol) in the presence of copper(II) ions. Room temperature ESR spectra revealed that both paramagnetic copper(II) ions and organic radicals are present in obtained autoxidation products similarly to the humic acid complexed copper(II) ions. The ratio of organic radical signal intensity to the copper(II) ion signal intensity suggests that the smallest amount of copper(II) ions is incorporated in the hydroquinone autoxidation product while the highest amount of copper(II) ions is incorporated in the autoxidation product of catechol. Satisfactory computer simulations of experimental ESR spectra were obtained by considering only one type of copper(II) ion binding site for hydroquinone autoxidation product and two distinct types of copper(II) ion binding sites for catechol and 4-methylcatechol autoxidation products. Parameters obtained by the computer simulation of ESR spectra indicated prevalent ionic bonding of copper(II) ions in polymeric matrices with tetrahedral distortion at copper(II) ion binding sites and negligible exchange interactions between them. Products obtained by the hydroquinone and catechol autoxidation have more similar characteristics in comparison to the product obtained by the 4-methylcatechol autoxidation where more expressed ionic bonding of copper(II) ions, and smaller tetrahedral distortion are present. Due to the dipolar interactions of oxygen-centered organic radicals in autoxidation products with paramagnetic copper(II) ions, their ESR linewidths are larger and g-values smaller in comparison to the values found in humic acids from various soil types.

High content drug screening of primary cardiomyocytes based on microfluidics and real-time ultra-large-scale high-resolution imaging.

High content screening (HCS) plays an important role in biological applications and drug development. Existing techniques fail to simultaneously meet multiple needs of throughput, efficiency in sample and chemical consumption, and real-time imaging of a large view at high resolution. Leveraging advances in microfluidics and imaging technology, we setup a new paradigm of large-scale, high-content drug screening solutions for rapid biological processes, like cardiotoxicity. The designed microfluidic chips enable 10 types of drugs each with 5 concentrations to be assayed simultaneously. The imaging system has 30 Hz video rate for a centimeter filed-of-view at 0.8 μm resolution. Using the HCS system, we assayed 12 small molecules through their effects on the Ca2+ ion signal of cardiomyocytes. Experimental results demonstrated the unparalleled capability of the system in revealing the spatiotemporal patterns of Ca2+ imaging of cardiomyocytes, and validated the cardiotoxicity of certain molecules. We envision that this new HCS paradigm and cutting-edge platform offer the most advanced alternative to well-plate based methods.

Phosphopeptide Enrichment Techniques: A Pivotal Step for Phosphoproteomic Studies.

Many pathological conditions are caused by dysregulation of cell signaling, which can generate a cascade of abnormal responses and completely change the functions of a cell or tissue. A large portion of the regulation of these signals is via protein phosphorylation, in which cell responses can be activated or inhibited. Proteins that are both downstream and upstream of a phosphorylated protein can be modified, altering metabolism and other biological processes. Recently, the number of phosphoproteomic studies based on mass spectrometry has increased, constantly aiming to obtain a higher coverage of proteins and increase the number and location of their phospho-sites, as well as better understand their respective phosphorylation states. In this way, it is possible to better understand biological processes as a whole and their roles in cellular dysfunctions and diseases. To study changes at the phosphoproteome level, the stochiometric imbalance between the non-phosphorylated and phosphorylated peptides must be overcome, since higher quantities and comparatively better ionization of non-phosphorylated peptides can suppress the ion signals of the phosphorylated peptides. It is for this reason that phosphophopeptides are rarely found in samples that did not pass through a phospho-enrichment step, highlighting the importance of performing enrichment steps in phosphoproteomic studies. The numbers of identified phosphopeptides and phosphorylation sites are extremely important to the quality of a phosphoproteomic analysis; therefore, the efficiency of the enrichment process is critical. Here, phospho-enrichment techniques are presented to offer insight into the applicability of these methods to different experiment types and consequently support the growth of phosphoproteomic studies overall.

Wavelength dependent photoionisation of ethanol clusters: generation of hydrogen like C5+ ions at terawatt laser intensity.

Photoionisation of ethanol clusters has been investigated at different laser wavelengths over the intensity range of ∼1012-1013 W cm-2. Under 266 nm ionisation, singly charged fragments and protonated cluster ions (up to (C2H5OH)9H+) were observed in the mass spectrum. Moreover, small ion signals corresponding to doubly charged carbon ions (C2+) were also observed. At longer laser wavelengths (i.e. 355, 532 and 1064 nm), the charge states of multiply charged ions of C and O were found to increase systematically and the maximum observed charge states were C5+ and O6+ at 1064 nm. Generation of C5+ ions (IE: 392 eV) is noteworthy as it requires removal of a core shell electron from a carbon atom. A comprehensive study has been carried out to appreciate the ionisation mechanism of such higher charge state formation in an ethanol cluster at terawatt laser intensity. A laser power dependency study suggests the role of multiphoton ionsation in creating initial charge centres within the cluster. Subsequently the ionised electrons produced upon multiphoton ionisation gain energy from the laser field and cause further ionisation via electron impact ionisation. Energisation of electrons and generation of multiply charged atomic ions were found to depend on the stability of clusters in the laser field which in turn is related to intermolecular interactions of ethanol clusters. Moreover, anionic fragment ions were observed in the ionisation of ethanol clusters at ∼1012 W cm-2 which also influences the ionisation dynamics of the cluster.

Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate (Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.