-
The Journal of Neuroscience : the... Aug 2023Neurotransmission is shaped by extracellular pH. Alkalization enhances pH-sensitive transmitter release and receptor activation, whereas acidification inhibits these...
Neurotransmission is shaped by extracellular pH. Alkalization enhances pH-sensitive transmitter release and receptor activation, whereas acidification inhibits these processes and can activate acid-sensitive conductances in the synaptic cleft. Previous work has shown that the synaptic cleft can either acidify because of synaptic vesicular release and/or alkalize because of Ca extrusion by the plasma membrane ATPase (PMCA). The direction of change differs across synapse types. At the mammalian neuromuscular junction (NMJ), the direction and magnitude of pH transients in the synaptic cleft during transmission remain ambiguous. We set out to elucidate the extracellular pH transients that occur at this cholinergic synapse under near-physiological conditions and identify their sources. We monitored pH-dependent changes in the synaptic cleft of the mouse levator auris longus using viral expression of the pseudoratiometric probe pHusion-Ex in the muscle. Using mice from both sexes, a significant and prolonged alkalization occurred when stimulating the connected nerve for 5 s at 50 Hz, which was dependent on postsynaptic intracellular Ca release. Sustained stimulation for a longer duration (20 s at 50 Hz) caused additional prolonged net acidification at the cleft. To investigate the mechanism underlying cleft alkalization, we used muscle-expressed GCaMP3 to monitor the contribution of postsynaptic Ca Activity-induced liberation of intracellular Ca in muscle positively correlated with alkalization of the synaptic cleft, whereas inhibiting PMCA significantly decreased the extent of cleft alkalization. Thus, cholinergic synapses of the mouse NMJ typically alkalize because of cytosolic Ca liberated in muscle during activity, unless under highly strenuous conditions where acidification predominates. Changes in synaptic cleft pH alter neurotransmission, acting on receptors and channels on both sides of the synapse. Synaptic acidification has been associated with a myriad of diseases in the central and peripheral nervous system. Here, we report that in near-physiological recording conditions the cholinergic neuromuscular junction shows use-dependent bidirectional changes in synaptic cleft pH-immediate alkalinization and a long-lasting acidification under prolonged stimulation. These results provide further insight into physiologically relevant changes at cholinergic synapses that have not been defined previously. Understanding and identifying synaptic pH transients during and after neuronal activity provides insight into short-term synaptic plasticity synapses and may identify therapeutic targets for diseases.
Topics: Female; Male; Animals; Mice; Calcium; Synapses; Neuromuscular Junction; Synaptic Transmission; Cholinergic Agents; Mammals
PubMed: 37474311
DOI: 10.1523/JNEUROSCI.0815-23.2023 -
ACS Macro Letters Jan 2023Poly(xanthene)s (PXs) carrying trimethylammonium, methylpiperidinium, and quinuclidinium cations were synthesized and studied as a new class of anion exchange membranes...
Poly(xanthene)s (PXs) carrying trimethylammonium, methylpiperidinium, and quinuclidinium cations were synthesized and studied as a new class of anion exchange membranes (AEMs). The polymers were prepared in a superacid-mediated polyhydroxyalkylation involving 4,4'-biphenol and 1-bromo-3-(trifluoroacetylphenyl)-propane, followed by quaternization reactions with the corresponding amines. The architecture with a rigid PX backbone decorated with cations via flexible alkyl spacer chains resulted in AEMs with high ionic conductivity, thermal stability and alkali-resistance. For example, hydroxide conductivities up to 129 mS cm were reached at 80 °C, and all the AEMs showed excellent alkaline stability with less than 4% ionic loss after treatment in 2 M aq. NaOH at 90 °C during 720 h. Critically, the diaryl ether links of the PX backbone remained intact after the harsh alkaline treatment, as evidenced by both H NMR spectroscopy and thermogravimetry. Our combined findings suggest that PX AEMs are viable materials for application in alkaline fuel cells and electrolyzers.
Topics: Alkalies; Xanthenes; Membranes, Artificial; Cations
PubMed: 36538018
DOI: 10.1021/acsmacrolett.2c00672 -
International Journal of Molecular... May 2019Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent...
Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein-protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and GβL to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression.
Topics: Alkalies; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line; Cell Proliferation; Curcumin; Glucose; Hep G2 Cells; Humans; Liver Neoplasms; Monocarboxylic Acid Transporters; Regulatory-Associated Protein of mTOR; Vacuolar Proton-Translocating ATPases
PubMed: 31091659
DOI: 10.3390/ijms20102375 -
Biosensors Mar 2022Alkali vapor cells are the core components of atomic sensing instruments such as atomic gyroscopes, atomic magnetometers, atomic clocks, etc. Emerging integrated atomic... (Review)
Review
Alkali vapor cells are the core components of atomic sensing instruments such as atomic gyroscopes, atomic magnetometers, atomic clocks, etc. Emerging integrated atomic sensing devices require high-performance miniaturized alkali vapor cells, especially micro-fabricated vapor cells. In this review, bonding methods for vapor cells of this kind are summarized in detail, including anodic bonding, sacrificial micro-channel bonding, and metal thermocompression bonding. Compared with traditional through-lighting schemes, researchers have developed novel methods for micro-fabricated vapor cells under both single- and double-beam schemes. In addition, emerging packaging methods for alkali metals in micro-fabricated vapor cells can be categorized as physical or chemical approaches. Physical methods include liquid transfer and wax pack filling. Chemical methods include the reaction of barium azide with rubidium chloride, ultraviolet light decomposition (of rubidium azide), and the high-temperature electrolysis of rubidium-rich glass. Finally, the application trend of micro-fabricated alkali vapor cells in the field of micro-scale gyroscopes, micro-scale atomic clocks, and especially micro-scale biomagnetometers is reviewed. Currently, the sensing industry has become a major driving force for the miniaturization of atomic sensing devices, and in the near future, the micro-fabricated alkali vapor cell technology of atomic sensing devices may experience extensive developments.
Topics: Alkalies; Electrodes; Gases; Metals
PubMed: 35323435
DOI: 10.3390/bios12030165 -
Kidney360 Apr 2022
Topics: Acidosis; Alkalies; Child; Humans; Renal Insufficiency, Chronic
PubMed: 35721614
DOI: 10.34067/KID.0000072022 -
Scientific Reports Apr 2018Concrete is a strong and fairly inexpensive building substance, but has several disadvantages like cracking that allows corrosion, thus reducing its lifespan. To...
Concrete is a strong and fairly inexpensive building substance, but has several disadvantages like cracking that allows corrosion, thus reducing its lifespan. To mitigate these complications, long-lasting microbial self-healing cement is an alternative that is eco-friendly and also actively repairs cracks. The present paper describes the detailed experimental investigation on compressive strength of cement mortars, mixed with six alkaliphilic bacteria, isolated from subsurface mica mines of high alkalinity. The experiments showed that the addition of alkaliphilic isolates at different cell concentrations (10 and 10 cells/ml) enhanced the compressive strength of cement mortar, because the rapid growth of bacteria at high alkalinity precipitates calcite crystals that lead to filling of pores and densifying the concrete mix. Thus, Bacillus subtilis (SVUNM4) showed the highest compressive strength (28.61%) of cement mortar at 10 cells/ml compared to those of other five alkaliphilic isolates (Brevibacillus sp., SVUNM15-22.1%; P. dendritiformis, SVUNM11-19.9%; B. methylotrophicus, SVUNM9-16%; B. licheniformis, SVUNM14-12.7% and S. maltophilia, SVUNM13-9.6%) and controlled cement mortar as well. This method resulted in the filling of cracks in concrete with calcite (CaCO), which was observed by scanning electron microscopy (SEM). Our results showed that the alkaliphilic bacterial isolates used in the study are effective in self-healing and repair of concrete cracks.
Topics: Alkalies; Bacillus; Bacillus subtilis; Brevibacillus; Calcium Carbonate; Compressive Strength; Construction Materials; Endospore-Forming Bacteria; Industrial Microbiology; Microscopy, Electron, Scanning; Paenibacillus; Stenotrophomonas
PubMed: 29691456
DOI: 10.1038/s41598-018-24730-3 -
American Journal of Physiology. Renal... Dec 2020Sodium bicarbonate (NaHCO) has been recognized as a possible therapy to target chronic kidney disease (CKD) progression. Several small clinical trials have demonstrated... (Review)
Review
Sodium bicarbonate (NaHCO) has been recognized as a possible therapy to target chronic kidney disease (CKD) progression. Several small clinical trials have demonstrated that supplementation with NaHCO or other alkalizing agents slows renal functional decline in patients with CKD. While the benefits of NaHCO treatment have been thought to result from restoring pH homeostasis, a number of studies have now indicated that NaHCO or other alkalis may provide benefit regardless of the presence of metabolic acidosis. These data have raised questions as to how NaHCO protects the kidneys. To date, the physiological mechanism(s) that mediates the reported protective effect of NaHCO in CKD remain unclear. In this review, we first examine the evidence from clinical trials in support of a beneficial effect of NaHCO and other alkali in slowing kidney disease progression and their relationship to acid-base status. Then, we discuss the physiological pathways that have been proposed to underlie these renoprotective effects and highlight strengths and weaknesses in the data supporting each pathway. Finally, we discuss how answering key questions regarding the physiological mechanism(s) mediating the beneficial actions of NaHCO therapy in CKD is likely to be important in the design of future clinical trials. We conclude that basic research in animal models is likely to be critical in identifying the physiological mechanisms underlying the benefits of NaHCO treatment in CKD. Gaining an understanding of these pathways may lead to the improved implementation of NaHCO as a therapy in CKD and perhaps other disease states.
Topics: Acid-Base Equilibrium; Acidosis; Alkalies; Glomerular Filtration Rate; Humans; Hydrogen-Ion Concentration; Kidney; Renal Insufficiency, Chronic; Sodium Bicarbonate; Treatment Outcome
PubMed: 33166183
DOI: 10.1152/ajprenal.00343.2020 -
BMC Plant Biology Nov 2022Soil salinization and alkalization are widespread environmental problems that limit grapevine (Vitis vinifera L.) growth and yield. However, little is known about the...
BACKGROUND
Soil salinization and alkalization are widespread environmental problems that limit grapevine (Vitis vinifera L.) growth and yield. However, little is known about the response of grapevine to alkali stress. This study investigated the differences in physiological characteristics, chloroplast structure, transcriptome, and metabolome in grapevine plants under salt stress and alkali stress.
RESULTS
We found that grapevine plants under salt stress and alkali stress showed leaf chlorosis, a decline in photosynthetic capacity, a decrease in chlorophyll content and Rubisco activity, an imbalance of Na and K, and damaged chloroplast ultrastructure. Fv/Fm decreased under salt stress and alkali stress. NPQ increased under salt stress whereas decreased under alkali stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed the differentially expressed genes (DEGs) induced by salt stress and alkali stress were involved in different biological processes and have varied molecular functions. The expression of stress genes involved in the ABA and MAPK signaling pathways was markedly altered by salt stress and alkali stress. The genes encoding ion transporter (AKT1, HKT1, NHX1, NHX2, TPC1A, TPC1B) were up-regulated under salt stress and alkali stress. Down-regulation in the expression of numerous genes in the 'Porphyrin and chlorophyll metabolism', 'Photosynthesis-antenna proteins', and 'Photosynthesis' pathways were observed under alkali stress. Many genes in the 'Carbon fixation in photosynthetic organisms' pathway in salt stress and alkali stress were down-regulated. Metabolome showed that 431 and 378 differentially accumulated metabolites (DAMs) were identified in salt stress and alkali stress, respectively. L-Glutamic acid and 5-Aminolevulinate involved in chlorophyll synthesis decreased under salt stress and alkali stress. The abundance of 19 DAMs under salt stress related to photosynthesis decreased. The abundance of 16 organic acids in salt stress and 22 in alkali stress increased respectively.
CONCLUSIONS
Our findings suggested that alkali stress had more adverse effects on grapevine leaves, chloroplast structure, ion balance, and photosynthesis than salt stress. Transcriptional and metabolic profiling showed that there were significant differences in the effects of salt stress and alkali stress on the expression of key genes and the abundance of pivotal metabolites in grapevine plants.
Topics: Vitis; Gene Expression Regulation, Plant; Alkalies; Plant Proteins; Gene Expression Profiling; Salt Stress; Transcriptome; Chlorophyll
PubMed: 36376811
DOI: 10.1186/s12870-022-03907-z -
PloS One 2023The pacific white shrimp (Litopenaeus vannamei) is now a more common aquaculture species in saline-alkali waters, while alkalinity stress is considered to be one of the...
The pacific white shrimp (Litopenaeus vannamei) is now a more common aquaculture species in saline-alkali waters, while alkalinity stress is considered to be one of the stressors for shrimp. Thus, an understanding of the molecular response to alkalinity stress is critical for advancing the sustainability of culture in pacific white shrimp. In this study, we aimed to explore the response mechanism to acute high-alkaline stress by RNA-seq at low-alkaline (50 mg/L) and high-alkaline (350 mg/L). We identified 215 differentially expressed mRNAs (DEGs) and 35 differentially expressed miRNAs (DEMs), of which 180 DEGs and 28 DEMs were up-regulated, 35 DEGs and 7 DEMs were down-regulated, respectively. The DEGs were enriched in several pathways, including carbohydrate digestion and absorption, pancreatic secretion, starch and sucrose metabolism, antigen processing and presentation and glutathione metabolism. The DEMs involved in lysosome and ion transport related pathways were significantly up-regulated. We also achieved 42 DEGs, which were targeted by DEMs. miRNA-mRNA regulatory network was constructed by integrated analysis of miRNA-mRNA data. We detected several genes and miRNAs which were identified as candidate regulators of alkalinity stress, and expression patterns of key genes related to alkalinity stress in pacific white shrimp. Among these genes, the expression levels of most key genes enriched in ion regulation, digestion and immunity were increased, and the expression levels of genes enriched in metabolism were down-regulated. This research indicated that the homeostatic regulation and digestion changed significantly under acute alkaline stress, and the variations from metabolic and immunity can cope with the osmotic shock of alkalinity stress in pacific white shrimp. This study provides key clues for exploring the molecular mechanism of pacific white shrimp under acute alkalinity stress, and also gives scientific basis for the optimisation of saline-alkaline aquaculture technology.
Topics: Animals; Penaeidae; Alkalies; Antigen Presentation; RNA, Messenger; MicroRNAs
PubMed: 37590243
DOI: 10.1371/journal.pone.0290157 -
Stem Cell Research & Therapy Feb 2024Corneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing...
BACKGROUND
Corneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing outcomes. Previous studies have found that chitosan-based in situ hydrogel loaded with limbal epithelium stem cells (LESCs) has a certain reparative effect on corneal alkali burns. However, the inconsistent pore sizes of the carriers and low cell loading rates have resulted in suboptimal repair outcomes. In this study, 4D bioprinting technology was used to prepare a chitosan-based thermosensitive gel carrier (4D-CTH) with uniform pore size and adjustable shape to improve the transfer capacity of LESCs.
METHODS
Prepare solutions of chitosan acetate, carboxymethyl chitosan, and β-glycerophosphate sodium at specific concentrations, and mix them in certain proportions to create a pore-size uniform scaffold using 4D bioprinting technology. Extract and culture rat LESCs (rLESCs) in vitro, perform immunofluorescence experiments to observe the positivity rate of deltaNp63 cells for cell identification. Conduct a series of experiments to validate the cell compatibility of 4D-CTH, including CCK-8 assay to assess cell toxicity, scratch assay to evaluate the effect of 4D-CTH on rLESCs migration, and Calcein-AM/PI cell staining experiment to examine the impact of 4D-CTH on rLESCs proliferation and morphology. Establish a severe alkali burn model in rat corneas, transplant rLESCs onto the injured cornea using 4D-CTH, periodically observe corneal opacity and neovascularization using a slit lamp, and evaluate epithelial healing by fluorescein sodium staining. Assess the therapeutic effect 4D-CTH-loaded rLESCs on corneal alkali burn through histological evaluation of corneal tissue paraffin sections stained with hematoxylin and eosin, as well as immunofluorescence staining of frozen sections.
RESULTS
Using the 4D-CTH, rLESCs were transferred to the alkali burn wounds of rats. Compared with the traditional treatment group (chitosan in situ hydrogel encapsulating rLESCs), the 4D-CTH-rLESC group had significantly higher repair efficiency of corneal injury, such as lower corneal opacity score (1.2 ± 0.4472 vs 0.4 ± 0.5477, p < 0.05) and neovascularization score (5.5 ± 1.118 vs 2.6 ± 0.9618, p < 0.01), and significantly higher corneal epithelial wound healing rate (72.09 ± 3.568% vs 86.60 ± 5.004%, p < 0.01).
CONCLUSION
In summary, the corneas of the 4D-CTH-rLESC treatment group were similar to the normal corneas and had a complete corneal structure. These findings suggested that LESCs encapsulated by 4D-CTH significantly accelerated corneal wound healing after alkali burn and can be considered as a rapid and effective method for treating epithelial defects.
Topics: Rats; Animals; Burns, Chemical; Chitosan; Alkalies; Wound Healing; Cornea; Corneal Injuries; Corneal Opacity; Stem Cells; Hydrogels
PubMed: 38355568
DOI: 10.1186/s13287-024-03653-z