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At least 37 records · Page 2Linked to original sources
PubMed2026

TNF-NF-κB signaling mediates immune-biomineralization crosstalk during shell repair under ocean acidification in Mytilus edulis.

Ocean acidification (OA) impairs biomineralization in bivalves, but its effects on immune-biomineralization crosstalk during shell repair remain unknown. Here, we exposed adult Mytilus edulis bearing standardized shell perforations to three pH levels (8.1, 7.9, and 7.7) for up to 40 days. OA slowed early repair and caused microstructural disorganization and an approximately 87% reduction of compressive strength at pH 7.7, yet the damaged area appeared largely closed by day 15, suggesting a decoupling between morphological closure and functional recovery. In addition, transcriptomic profiling of hemocytes and mantle tissue, based on an average of 6.5 Gb of clean reads per sample mapped to the M. edulis reference genome (NCBI Assembly GCF_000511035.1), revealed that these shell-level defects were accompanied by coordinated immune and metabolic reprogramming. Hemocytes, the primary immune effector cells of bivalves, exhibited pH- and time-dependent shifts with moderate acidification (pH 7.9) promoting inflammatory transcripts, whereas severe acidification (pH 7.7) suppressed these signals while upregulating stress-associated pathways; both treatments consistently downregulated lysosomal proteases and NF-κB negative regulators. The mantle, a primarily mineralizing organ, paradoxically upregulated immune-related genes while suppressing oxidative phosphorylation and extracellular matrix pathways. This tissue-level imbalance, with hemocytes recruited but functionally constrained and mantle metabolically suppressed yet immunologically activated, points to TNF-NF-κB pathway modulation as a key mediator of shell repair under acidification. Our findings demonstrate that visible shell closure masks underlying structural and mechanical failure, and that immune regulation, rather than simple suppression or activation, critically shapes the repair outcome. These results advocate for multifunctional indicators beyond closure area to assess shell integrity in acidified marine environments.

Animals↗
PubMed2026

Mitigating pH-induced instability in deruxtecan-based ADCs: an onboard-mixing icIEF approach for robust charge heterogeneity characterization.

Accurate charge variant analysis of antibody-drug conjugates (ADCs) is essential for understanding product heterogeneity and ensuring quality control. However, Deruxtecan (DXd)-based ADCs present a unique analytical challenge due to the intrinsic instability of the payload, where the lactone ring readily undergoes hydrolysis under alkaline conditions, resulting in time-dependent shifts in charge distribution during imaged capillary isoelectric focusing (icIEF). In this study, we describe the development of an onboard-mixing icIEF method designed to minimize pH-induced degradation during sample preparation. By separating ADC samples from carrier ampholytes (CAs) prior to injection and enabling real-time mixing within the instrument, this approach effectively suppresses premature lactone ring opening and stabilizes charge variant profiles. Comparative studies between conventional premixing and onboard-mixing approach demonstrated that the latter significantly enhances reproducibility, particularly for acidic variants that are highly sensitive to structural conversion. Comprehensive method validation confirmed excellent precision, linearity, and sensitivity, with consistent performance across run-to-run and intra-day analyses. The results underscore the importance of controlling microenvironmental pH exposure in the analysis of chemically instable ADCs. The proposed onboard-mixing strategy provides a robust and efficient solution for icIEF-based characterization, reducing analytical artifacts while simplifying method development. This approach is broadly applicable to ADCs and other biotherapeutics containing pH-sensitive functional groups.

Hydrogen-Ion Concentration↗
PubMed2026

Deciphering S-nitrosylation-regulated metabolic networks in postmortem beef based on label-free modificomics: Identification of ferroptosis as a novel quality-related pathway.

This study elucidated the molecular mechanisms of S-nitrosylation on postmortem beef metabolism and quality based on the label-free modificomics. Varying degrees of S-nitrosylation were exogenously induced in beef semimembranosus (SM) muscle. Results indicated that a high S-nitrosylation level significantly increased beef pH and Warner-Bratzler shear force (WBSF) while reducing centrifugal loss (P&#xa0;<&#xa0;0.05). A total of 828&#xa0;S-nitrosylated proteins and 1458 modification sites were identified, of which 114 sites on 81 proteins (DSNPs) exhibited differential modification abundance, representing an increase of 125% compared with previous proteomics studies. DSNPs were mainly involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, calcium signaling, cell structure, and ferroptosis. Notably, this study provides the first evidence in postmortem muscle that S-nitrosylation regulates key ferroptosis-related proteins, including ACSL, CP, and TF, offering new insights into the link between S-nitrosylation and the ferroptosis pathway in meat. Correlation analysis demonstrated that TF was significantly negatively correlated with pH and WBSF, but positively correlated with centrifugal loss (P&#xa0;<&#xa0;0.05). Collectively, protein S-nitrosylation critically modulates postmortem beef quality through the coordinated regulation of multiple metabolic processes. More importantly, the identification of ferroptosis as a S-nitrosylation-sensitive pathway provides a new perspective for regulating meat quality through protein post-translational modifications.

Animals↗
PubMed2026

Acidic Stress Induces Proteomic Reprogramming and Virulence-Associated Adaptation in Paracoccidioides brasiliensis.

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis whose etiologic agents must adapt to acidic host niches such as phagolysosomes. Here, we used quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics to define the response of Paracoccidioides brasiliensis to acidic stress (pH 4.5) versus control pH (6.5) after 5 and 24 h. We identified and quantified 4374 proteins, including 327 and 722 differentially abundant proteins at 5 and 24 h, respectively, revealing time-dependent proteomic reprogramming. Enrichment analyses highlighted proteolysis, protein metabolism, organonitrogen metabolism, MAPK- and SNF1-like signaling, central carbon metabolism, tyrosine metabolism, and ergosterol biosynthesis as major acid-responsive processes. Complementary assays showed pH-dependent extracellular proteolytic activity, increased adhesion to A549 pulmonary epithelial cells, and dynamic ergosterol remodeling. The proteomic data further indicated increased abundance of moonlighting proteins linked to adhesion and metabolic enzymes associated with ATP generation and melanin precursor production. Together, these findings indicate that P. brasiliensis adapts to acidic environments through coordinated regulation of proteostasis, metabolism, signaling, host-cell interaction, and membrane homeostasis, supporting survival and virulence potential in acidic host microenvironments.

Paracoccidioides↗
PubMed1975

The effect of acid proteinase inhibitors on chicken pepsin.

1. The activity of chicken pepsin was partially inhibited by dimethyl-(2-hydroxy-5-nitrobenzyl)sulphonium bromide, but was unaffected by p-bromophenacyl bromide. 2. In the presence of Cu2+, diazoacetylnorleucine methyl ester completely inactivated chicken pepsin with the incorporation of 1 mol/mol. The mechanism of the reaction was similar to that with pig pepsin. 3. Chicken pepsin was completely inactivated by 2-diazo-4-bromoacetophenone in the presence of Cu2+. 4. Chicken pepsin was almost completely inactivated by 1,2-epoxy-3-(p-nitrophenoxy)propane at 25 degrees C, 3-4mol of inhibitor/mol being incorporated. The reaction at 10 degrees C was investigated briefly. 5. Calf chymosin was inactivated by 1,2-epoxy-3-(p-nitrophenoxy)propane at 10 degrees C, the incorporation of 1 mol/mol being required for complete inhibition. 6. The characteristics of the reactions of chicken pepsin with the above compounds were compared with those of other acid proteinases.

Acetophenones↗
PubMed2026

Impact of pH and Mycoplasma hominis endosymbiosis on Trichomonas vaginalis pathogenesis.

The parasite Trichomonas vaginalis colonizes the human vaginal tract and adheres to and lyses epithelial cells causing an inflammatory infection. The vaginal tract is typically acidic, ranging from pH 3.8 to 5.1; however, pathogenesis studies have previously been conducted on parasites grown at pH 5.9 to 6.2. Here we compared the adherence and cytotoxicity of T. vaginalis grown at pH 5.1 and pH 5.9, identifying changes in the surface proteome that contribute to increased pathogenesis of the parasite at pH 5.1. We show that growth of the parasite at pH 5.1 significantly enhances adherence to and lysis of host cells and that this is strongly amplified by the presence of a common bacterial endosymbiont, Mycoplasma hominis. Quantitative proteomics revealed the upregulation of putative surface proteins, three of which were found to be involved in increased parasite adherence and host cell killing. Mechanistic assays demonstrated that a Ricin B-like protein mediates parasite adherence dependent on host glycosaminoglycans via its carbohydrate-recognition domain, while an EF-hand-like protein is shown to promote Ca2+dependent adherence. Ricin B overexpression was found to reprogram host metabolism, activating ERK1/2 and HIF-1&#x3b1; and driving a Warburg-like glycolytic shift with greatly increased lactate release, which may create a nutrient-rich niche that supports parasite persistence and host cell cytotoxicity. These studies demonstrate a coordinated upregulation of multiple adhesins rather than a single factor at pH 5.1 in the presence of M. hominis and explore the mechanisms underlying the interaction of parasite surface proteins with the host cell.

Trichomonas vaginalis↗
PubMed1975

Separation of (3') deoxynucleotides with cation exchange columns.

A procedure is described for a one-step separation of synthetic (3') deoxynucleotides purchased commercially or those purified and isolated from the enzymatic digests of DNA. The method is simple. A 50 ml buret was used for column which was filled with the resin slurry and packed at water aspirator pressure. The compounds were eluted from the column at atmospheric pressure under gravity flow using a fraction collector and read on a Beckman DU spectrophotometer. Recoveries were in excess of 90% and no accessory devices were required. The use of a volatile buffer, e.g. ammonium formate facilitated the recovery of the purified material by allowing the evaporation of the medium in which the sample was eluted.

Cation Exchange Resins↗
PubMed1976

Physical and chemical changes of ACD-preserved blood: a comparison of blood in glass bottles and plastic bags.

ACD blood was preserved in glass bottles with or without aeration and in plastic bags in air or nitrogen gas at 4.5 degrees C. The blood was examined for physical and chemical changes of erythrocyte membrane resistance, hemoglobin in the plasma, the viscosity of the blood, pH of plasma, and ATP and 2,3-DPG content of erythrocytes. The blood preserved in plastic bags showed less changes than blood in glass bottles. The presence of air or nitrogen gas in blood seems to increase the pH perhaps by elimination of carbon dioxide (CO2) which in turn causes the different rates of glycolysis in the erythrocytes.

Adenosine Triphosphate↗
PubMed1976

Surface balance study of the interaction between microorganisms and lipid monolayer at the air/water interface.

Using the surface balance technique, we have compared the interaction between Acholeplasma laidlawii and some marine bacteria towards different types of monolayered lipid films. Cells from A. laidlawii and Serratia marinorubra penetrate the film, whereas cells from Psuedomonas fluorescens form a layer underneath the film. The forces that bind microorganisms to the air/water interface are not strong enough to scatter a condensed monolayer but increase the strength of loosely packed monolayers.

Acholeplasma laidlawii↗
PubMed1975

Sarcotubular anomalous rectification of frog sartorius muscle.

The membrane site responsible for anomalous rectification was determined in frog sartorius muscle fibers. The total current-voltage relation of glycerol-treated fibers which represents mainly the properties of the sarcolemma was linear for membrane potentials between about -90 and -50 mV. Thus moderate depolarization-induced anomalous rectification in intact fibers represents a property of the sarcotubular system. The absence of slow hyperpolarization in glycerol-treated fibers was caused by the abolition of early conductance increase, and the sarcotubular system is responsible for the inward rectifier. Picrotoxin selectively inhibited both moderate depolarization-induced anomalous rectification and hyperpolarization-induced early conductance increase. This suggests that the same component in the sarcotubular system is responsible for these conductance changes. The inhibition with picrotoxin of moderate depolarization-induced anomalous rectification suggests the possibility that it is caused by an electrogenic effect rather than a decrease in K conductance. A sarcolemmal hyperpolarization-activated slow conductance increase was revealed.

Animals↗
PubMed1975

Properties of sarcolemmal delayed rectification in glycerol-treated fibers of frog sartorius muscle.

Total current-voltage relations were analyzed on nine glycerol-treated surface fibers of frog sartorius muscles in tetrodotoxin-containing isotonic normal Ringer solution. The results indicate that delayed rectification occurs in the sarcolemma on large depolarization and that delayed rectification is only partially inactivated during 1 sec of depolarization and not converted into anomalous rectification. The time to peak, the time course of inactivation and the potassium activation potential determined in glycerol-treated fibers were comparable to those analyzed previously in intact fibers. The value of the conductance increase during delayed rectification in glycerol-treated fibers appeared to be smaller than that in intact fibers.

Animals↗
PubMed1975

Sarcolemmal slow conductance increase of frog sartorius fibers during hyperpolarization.

The properties of the hyperpolarization-activated sarcolemmal slow conductance increase in frog sartorius muscle fibers have been investigated using ethylenediaminetetraacetic acid disodium salt (EDTA) and propionate Ringer solution. More than 1 sec was required for maximum activation of the sarcolemmal slwo conductance increase. It is suggested that, although the sarcolemmal slow conductance increase was affected by deterioration, the conductance increase is not a direct product of deterioration but it represents a property of the sarcolemma which is encountered in physiological range. The sarcolemmal conductance increase was rather insensitive to the change in pH of Ringer solution. It is inferred that the absence of bellying in newly penetrated intact fibers at neutral and alkaline pHs is caused mainly by the shunting effect of large parallel conductance. Apparent augmentation with EDTA of the sarcolemmal conductance increase infers that Ca ions affect the conductance increase. The conductance increase occurred also in the EDTA-containing Cl-deficient solution. The sarcolemmal slow conductance increase has been compared with the change in Cl conductance reported by Hutter and Warner, and Warner.

Animals↗
PubMed1975

Semen cahracteristics before and after ligation of the left internal spermatic veins in men with varicocele.

The semen from 20 men with varicocele was studied before and after surgical correction of the varicocele. The effect on sperm quality was only marginal and could not explain the fairly high conception rate (20%) after operation. The recommendation that varicocele in men with long-term infertility should be eliminated by ligation of the internal spermatic veins is still justified despite the absence of positive effects on sperm quality.

Acid Phosphatase↗
PubMed2026

A Novel Moisturizer Formulated With Micronized Centella asiatica and Mandelic Acid Improves Mature, Crepey Skin.

BACKGROUND: Dermatoporosis is a condition of fragile, aging skin that manifests as altered pH, wrinkles, laxity, easy bruising, and hyperpigmentation. This study evaluated efficacy, safety, and subject perception after the use of a novel cream, GC (Galderma Laboratories, LP, Fort Worth, TX), on subjects with mature, aging skin. METHODS: A 12-week multicenter, randomized, blinded, in-use study enrolled female and male subjects aged 40 to 60 years of all races, ethnicities, and Fitzpatrick skin types. Subjects were required to have a history of fragile skin and dry, crepey skin on the knees and thighs. GC cream was applied to knee and upper thigh skin twice daily. Assessments included clinical grading, digital photography, bioinstrumentation (skin texture, pH, and heatmap hydration), standard safety assessments, and satisfaction. RESULTS: Use of GC cream for 12 weeks resulted in significant improvements in skin crepiness, photodamage, and firmness, as well as decreased skin pH and early improvements in skin roughness and smoothness from baseline. Corneometer heatmapping documented improved skin hydration over baseline. No adverse events were reported; the GC cream was well tolerated, and subjects reported high satisfaction. CONCLUSION: Twice-daily application of the novel GC skin cream significantly improved the overall skin quality of mature, aging skin, including crepiness, photodamage, firmness, texture, pH, and hydration. GC cream was well tolerated with high subject satisfaction. These data are intended to help guide healthcare providers and patients in choosing an effective moisturizer that was specifically designed for patients with fragile, mature skin.

Humans↗
PubMed1977

Response of type B and E Botulinum toxins to purified sulfhydryl-dependent protease produced by Clostridium botulinum type F.

A sulfhydryl-dependent protease (SHP) was purified from a culture of Clostridium botulinum type F. The enzyme can activate type E progenitor toxin completely but type B progenitor toxin only partially. This may suggest that SHP by itself could completely activate the toxin of proteolytic C. botulinum types A and F in culture. The toxicity of type E progenitor toxin potentiated by the treatment with SHP persisted, whereas that of derivative toxin decreased rapidly by further incubation with SHP. This may indicate that only the progenitor toxin, the complex of the toxic and nontoxic components, activated by SHP withstands the subsequent exposure to the enzyme in cultures of proteolytic C. botulinum.

Amidohydrolases↗
PubMed1976

[Effect of pH on properties of the cholinoreceptive membrane of snail neurons].

The influence of pH on acetylcholine (ACh)-induced responses in completely isolated neurons of Lymnaea stagnalis was studied under voltage clapm conditions. The pH drop lead to a decrease in sensitivity of cholinoreceptive membrane; at pH 5.8-6.0 ACh-responses were eliminated completely. When raising the external pH (up to 10.6) there were no changes in the ACh effect. A group responsible for sensitivity changes of the cholinoreceptive membrane appears to have pK about 6.7. It is shown that the pH drop does not influence the ionic channel functional groups. The results can be explained in the assumption that some functionally important groups in the cholinoreceptor active site are protonated at low pH.

Acetylcholine↗