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Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS-CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific neutralizing capability of these plasmas was assessed with SARS-CoV-2 spike pseudotyped virus. ADCC activity was assessed with a calcein release assay. SARS-CoV-2 specific IgG antibodies were detected in all COVID-19 subjects studied. All but three COVID-19 subjects contained nAb at high potency (>80% neutralization). Plasma from 19/20 of COVID-19 subjects also demonstrated strong ADCC activity against SARS-CoV-2 spike glycoprotein, including two individuals without nAb against SARS-CoV-2. Both neutralizing and non-neutralizing COVID-19 plasmas can mediate ADCC. Our findings argue that evaluation of potential vaccines against SARS-CoV-2 should include investigation of the magnitude and durability of ADCC, in addition to nAb.

Background: As an anti-inflammatory and antioxidant, sodium pyruvate significantly reduces inflammatory cytokines and oxygen radicals such as interleukin (IL) IL-6, IL-8, Monocyte Chemoattractant Protein-1, and hydrogen peroxide. Thus, sodium pyruvate holds promise as a treatment for many respiratory diseases, including allergic rhinitis (AR). Novel treatments for AR are needed as current medications, including steroids, often fail to treat severe symptoms. Methods: The data from five human clinical studies were analyzed to determine the effect of 20 mM sodium pyruvate nasal spray (N115) in patients with AR. Nasal inflammation scores were compared to a placebo control or a no-treatment baseline control. Three studies were open-labeled and two were appropriately blinded to both patients and clinicians using computer randomization of subjects. Results: The intranasal administration of sodium pyruvate significantly improved nasal inflammation scores in all five clinical trials of patients with AR (p < 0.0001 in all trials). Conclusions: These results give credence to the overall ability of sodium pyruvate, administered by nasal spray, to treat inflammation of the nasal airways.

Nitrogen removal by microorganisms has attracted increasing attention in wastewater treatment. In the present study, a heterotrophic nitrification bacterium was isolated from tannery wastewater and identified as Klebsiella sp. TN-10 based on phenotypic and phylogenetic characteristics. The optimal conditions for cell growth and nitrogen removal were investigated, and the results showed that the greatest ammonium removal rate and maximum biomass were achieved by using sodium pyruvate (7 g/L) as carbon source, C/N 12, pH 7, and temperature 30 °C. Under optimal conditions, the removal rate of ammonia nitrogen reached 96%. Besides, the growth characteristic and the ability of utilizing nitrate and nitrite were investigated. The results demonstrated that strain TN-10 exhibited excellent characteristics to remove both nitrate and nitrite, with the removal rate of 95.44% and 99.87%, respectively. In addition, the nitrite reductase (NiR) and nitrate reductase (NR) involved in denitrification were both active, with the activities of 0.0815 and 0.0283 U/mg proteins, respectively. Furthermore, the aggregation ability, auto-aggregation kinetics, and the relationship between zeta potentials and flocculating efficiency were determined. These results indicated that the strain Klebsiella sp. TN-10, with efficient heterotrophic nitrification-aerobic denitrification ability, has potential application in wastewater treatment.

Atmospheric secondary aerosols are often internally mixed with organic and inorganic components, particularly dicarboxylic acids, ammonium, sulfate, nitrate, and chloride. These complex compositions enable aqueous reaction between organic and inorganic species, significantly complicating aerosol phase behavior during aging and making phase predictions challenging. We investigated carboxylate–ammonium salt mixtures using attenuated total reflection Fourier-transformed infrared spectroscopy (ATR-FTIR). The mono-, di-, and tricarboxylates included sodium pyruvate (SP), sodium tartrate (ST), and sodium citrate (SC), while the ammonium salts included NH4NO3, NH4Cl, and (NH4)2SO4. Our results demonstrated that aqueous replacement reactions between carboxylates and ammonium salts were promoted by the formation and depletion of NH3 as relative humidity (RH) changed. For SP/ammonium aerosols, NaNO3 and Na2SO4 crystallized from 35.7 % to 12.7 % and from 65.7 % to 60.1 % RH, respectively, which is lower than the values for pure inorganics (62.5 ± 9 %–32 % RH for NaNO3 and 82 ± 7 %–68 ± 5 % RH for Na2SO4). Upon hydration, the crystalline Na2SO4 and NaNO3 deliquesced at 88.8 %–95.2 % and 76.5 ± 2 %–81.9 %, which is higher than the values of pure Na2SO4 (74 ± 4 %–98 % RH) and NaNO3 (65 %–77.1 ± 3 % RH). In contrast, reaction between ST or SC and (NH4)2SO4 was incomplete due to the gel structure at low RH. Unexpectedly, aqueous Na2SO4 crystallized upon humidification in ST/(NH4)2SO4 particles at 43.6 % RH and then deliquesced with increasing RH. This is attributed to increased ion mobility in viscous particles, leading to nucleation and growth of Na2SO4 crystals. Our findings highlight the intricate interplay between chemical components within organic/inorganic aerosol and the impact of replacement reactions on aerosol aging, phase state, and subsequently atmospheric processes.

Vanadium is a hazardous, pro-oxidant element that contributes to environmental pollution and has been reported as a risk factor for human health through occupational or environmental exposure. Pyruvate, on the other hand, is a natural alpha-keto acid with exceptional antioxidant and cytoprotective properties. Therefore, the aim of this study was to evaluate the mitigating effect of exogenous pyruvate against vanadium-induced toxicity in cultured Chinese hamster ovary (CHO)-K1 cells. To this end, CHO-K1 cells were exposed to 100 μM vanadyl sulfate (VOSO 4 ) for 24 h in the presence of 4.5 and 8 mM sodium pyruvate. Cell proliferation and morphological changes, cellular ATP levels, antioxidant stress (GSH) levels and apoptosis markers (caspase 3, 9, annexin V binding) were assessed to investigate the effect of sodium pyruvate on VOSO 4 -induced damage in CHO-K1 cells. The results showed that VOSO 4 induced morphological changes, inhibited cell proliferation, decreased cellular ATP and reduced glutathione levels. Co-treatment of VOSO 4 -intoxicated CHO-K1 cells with sodium pyruvate significantly reduced these cytotoxic effects. Analysis of apoptosis and necrosis showed that VOSO 4 slightly induced apoptosis and necrosis, and exogenous pyruvate inhibited the cytotoxicity of the tested vanadium dose in CHO-K1 cells, mainly by reducing the necrosis effect. The cytoprotective effect of exogenous pyruvate was also confirmed in normal mouse fibroblast (NIH/3T3) cells demonstrating that the protective properties of pyruvate are not cell specific.

Porphyromonas gingivalis ( P. gingivalis ) is a gram-negative, black-pigmented, anaerobic pathogen known for its biofilm formation and its central role in periodontal disease. More recently, P. gingivalis has been implicated in various systemic conditions, including atherosclerosis, Alzheimer’s disease, and certain types of cancer, such as pancreatic and oral cancer. This bacterium employs several mechanisms to evade environmental stress, thereby contributing to its pathogenicity. The viable but non-culturable (VBNC) state is characterized by bacteria that remain viable but have reduced metabolic activity and are unable to form colonies on conventional culture media. To induce the VBNC state in P. gingivalis , we subjected the bacterium to oxidative stress using H 2 O 2 and subsequently resuscitated it from this state with sodium pyruvate. We utilized viability staining, confocal microscopy, and flow cytometry (FC) to count live and dead bacteria, confirming the presence of significant numbers of viable P. gingivalis cells both before and after stress induction. Despite being viable, the stressed P. gingivalis failed to form colonies on blood agar plates after seven days of incubation, indicating it had entered the VBNC state. We were then able to resuscitate the VBNC P. gingivalis by adding sodium pyruvate, and the growth of the resuscitated bacteria on plates was comparable to that of control P. gingivalis . Investigation into the invasiveness of P. gingivalis in the VBNC state was conducted using human coronary artery endothelial cells (HCAECs). P. gingivalis in the VBNC state demonstrated the ability to invade and based on live/dead staining, showed that a substantial proportion of the VBNC P. gingivalis remained viable within the host cells for extended periods. In this study, we explore the VBNC survival strategy previously described in many aerobic bacteria but not previously reported in anaerobes such as P. gingivalis . The objectives of this study are to verify the VBNC state in P. gingivalis, determine whether this state can be reversed and assess the extent to which it impacts the ability of P. gingivalis to invade host cells. Understanding the VBNC and resuscitation states will be instrumental in guiding the development of more effective therapies for periodontitis and other diseases associated with P. gingivalis infection.

Background:Systemic sclerosis (SSc), an autoimmune disease with features including fibroblast transition and over-synthesis of extracellular matrix, yet has limited treatment options. Recent studies demonstrate that aberrant fibroblast activation is, at least in part, a consequence of mitochondrial dysfunction and associated metabolic reshaping. Sodium pyruvate, widely used as a nutritional supplement, is the stable form of pyruvate acid which acts as a central hub in several key metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle and fatty acid metabolism.Objectives:In the current study, we tested the hypothesis that pyruvate supplementation may improve mitochondrial fitness to ameliorate the metabolic alterations in SSc, and that metabolic rebalancing may exert an anti-fibrotic therapeutic effect in a preclinical model of SSc.Methods:The effect of sodium pyruvate on metabolism, mitochondrial fitness, collagen production and fibroblast-to-myofibroblast transition was evaluated in cultured human dermal fibroblasts derived from SSc patients and healthy donors, in mice with bleomycin-induced experimental skin fibrosis and in precision-cut human skin slices. Outcomes included metabolic flux assays, real-time PCR, IF and IHC staining, cellomics, histomorphometry, hyodroxyproline assays, RNA-seq analysis and data mining of published SSc skin transcriptomic data.Results:Several key regulatory components of pyruvate metabolism such as MPC1, PC and PDK2 were observed to be dysregulated in the skin of SSc patients compared to matched healthy donors in the PRESS cohort. Treatment of SSc fibroblasts with sodium pyruvate improved oxidative phosphorylation (OXPHOS) and mitochondrial potential. Notably, this metabolic correction upon pyruvate supplementation were associated with decreased expression of fibrosis-related genes, including COL1A1 and ACTA2, and decreased synthesis of extracellular matrix. In mice with bleomycin-induced dermal fibrosis, pyruvate supplementation demonstrated pronounced antifibrotic effects at well-tolerated doses, with reduced dermal thickening, hydroxyproline content and myofibroblast numbers. Of note, pyruvate treatment also reduced the upregulation of profibrotic genes, including COL1A1 and ACTA2, in response to TGFbeta in precision-cut slices of healthy human skin. Most notably, RNA sequencing of pyruvate-treated precision cut SSc patient skin sections demonstrated a partial reversal of the SSc-specific gene signature by pyruvate treatment.Conclusion:Sodium pyruvate ameliorates the metabolic alterations and improves mitochondrial fitness to inhibit fibroblast-to-myofibroblast transition and collagen in human dermal fibroblasts, in experimental mouse models of fibrosis and directly in human skin. Our study provides evidence that metabolically targeted therapy offer potential for antifibrotic therapies in SSc.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Xiang Zhou: None declared, Thuong Trinh-Minh: None declared, Cuong Tran-Manh: None declared, Andrea-Hermina Györfi is paid as a speaker by Boehringer Ingelheim and Abbvie, Alexandru-Emil Matei: None declared, Honglin Zhu: None declared, Xuezhi Hong: None declared, Tim Filla: None declared, Jiucun Wang: None declared, Jörg Distler JHWD is stock owner of 4D Science and Scientific Lead of FibroCure., JHWD has consultancy relationships with AbbVie, Active Biotech, Anamar, ARXX, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, Genentech, GSK, Inventiva, Janssen, Novartis, Pfizer, Roche and UCB., JHWD has received research funding from AbbVie, Anamar, Argenx, ARXX, BMS, Bayer Pharma, Boehringer Ingelheim, Cantargia, Celgene, CSL Behring, ExoTherapeutics, Galapagos, GSK, Inventiva, Kiniksa, Lassen, Novartis, Sanofi-Aventis, RedX, UCB.

Critical period plasticity at adult-born neuron synapses is widely believed to contribute to the learning and memory functions of the hippocampus. Experience regulates circuit integration and for a transient interval, until cells are ~6 weeks old, new neurons display enhanced long-term potentiation (LTP) at afferent and efferent synapses. Since neurogenesis declines substantially with age, this raises questions about the extent of lasting plasticity offered by adult-born neurons. Notably, however, the hippocampus receives sensory information from two major cortical pathways. Broadly speaking, the medial entorhinal cortex conveys spatial information to the hippocampus via the medial perforant path (MPP), and the lateral entorhinal cortex, via the lateral perforant path (LPP), codes for the cues and items that make experiences unique. While enhanced critical period plasticity at MPP synapses is relatively well characterized, no studies have examined long-term plasticity at LPP synapses onto adult-born neurons, even though the lateral entorhinal cortex is uniquely vulnerable to aging and Alzheimer’s pathology. We therefore investigated LTP at LPP inputs both within (4–6 weeks) and beyond (8 + weeks) the traditional critical period. At immature stages, adult-born neurons did not undergo significant LTP at LPP synapses, and often displayed long-term depression after theta burst stimulation. However, over the course of 3–4 months, adult-born neurons displayed increasingly greater amounts of LTP. Analyses of short-term plasticity point towards a presynaptic mechanism, where transmitter release probability declines as cells mature, providing a greater dynamic range for strengthening synapses. Collectively, our findings identify a novel form of new neuron plasticity that develops over an extended interval, and may therefore be relevant for maintaining cognitive function in aging.

Endogenous phytohormones play a vital role in the growth and secondary metabolism performance of microalgae and their secretion is significantly affected by external environmental conditions. In this study, the combined influences of three carbon sources (glucose, sodium pyruvate, and sodium acetate) and three pH levels (6, 8 and 10) on growth, astaxanthin accumulation, and contents of four endogenous phytohormones (indole-3-acetic acid, IAA; zeatin riboside, ZR; gibberellic acid 3, GA3; abscisic acid, ABA) of Haematococcus pluvialis were investigated. The results showed that carbon source and pH level had significant isolated and interactive effects on growth, astaxanthin accumulation, and endogenous phytohormone secretion. The cell density, specific growth rate and cell dry weight reached the highest levels in the glucose treatment at pH 8. The maximum astaxanthin concentration and productivity occurred in the glucose treatment with pH 10. The contents of IAA, ZR and GA3 significantly increased at the green stage (vegetative cell stage), indicating their potential involvement in cell proliferation. ABA contents, in contrast, significantly increased at the red stage (red cyst cell stage), probably contributing to astaxanthin accumulation. This experiment provided valuable insights for optimizing the mixotrophic cultivation conditions of H. pluvialis and successfully developing biological regulators.

Adipose tissue mobilization increases circulating fatty acid (FA) concentrations, leads to increased hepatic FA uptake, and influences hepatic metabolism. Our objective was to trace carbon flux through metabolic pathways in primary bovine neonatal hepatocytes challenged with FA, and to examine the effect of FA challenge on oxidative stress. Primary bovine neonatal hepatocytes were isolated from 4 Holstein bull calves and maintained for 24 h before treatment with either 0 or 1 mM FA cocktail. After 21 h, either [1- 14 C]C16:0 or [2- 14 C]sodium pyruvate was added to measure complete and incomplete oxidation and cellular glycogen. Cellular and media triglyceride (TG), and glucose and ß-hydroxybutyrate (BHB) export were quantified, as well as reactive oxygen species and cellular glutathione (GSH/GSSH). Fatty acid treatment increased cellular, but not media TG, and although complete oxidation of [1- 14 C]C16:0 was not affected by FA, BHB export was increased. Reactive oxygen species were increased with FA treatment and GSSH was marginally increased such that the ratio of GSH:GSSG was marginally decreased. Glucose export increased, and cellular glycogen marginally increased with FA treatment while [2- 14 C]sodium pyruvate oxidation was decreased. These data suggest that FA treatment shifts cellular energy metabolism in a substrate-specific manner, spares pyruvate carbon from oxidation, and stimulates glucose synthesis.