Extracellular Processes Research Articles

Boosting power output in microbial fuel cell with sulfur-doped MXene/polypyrrole hydrogel anode for enhanced extracellular electron transfer process

Boosting power output in microbial fuel cell with sulfur-doped MXene/polypyrrole hydrogel anode for enhanced extracellular electron transfer process

Protein disulfide isomerase A1 regulates fenestration dynamics in primary mouse liver sinusoidal endothelial cells (LSECs)

Protein disulfide isomerases (PDIs) are involved in many intracellular and extracellular processes, including cell adhesion and cytoskeletal reorganisation, but their contribution to the regulation of fenestrations in liver sinusoidal endothelial cells (LSECs) remains unknown. Given that fenestrations are supported on a cytoskeleton scaffold, this study aimed to investigate whether endothelial PDIs regulate fenestration dynamics in primary mouse LSECs.PDIA3 and PDIA1 were found to be the most abundant among PDI isoforms in LSECs. Taking advantage of atomic force microscopy, the effects of PDIA1 or PDIA3 inhibition on the fenestrations in LSECs were investigated using a classic PDIA1 inhibitor (bepristat) and novel aromatic N-sulfonamides of aziridine-2-carboxylic acid derivatives as PDIA1 (C-3389) or PDIA3 (C-3399) inhibitors. The effect of PDIA1 inhibition on liver perfusion was studied in vivo using dynamic contrast-enhanced magnetic resonance imaging. Additionally, PDIA1 inhibitors were examined in vitro in LSECs for effects on adhesion, cytoskeleton organisation, bioenergetics, and viability.Inhibition of PDIA1 with bepristat or C-3389 significantly reduced the number of fenestrations in LSECs, while inhibition of PDIA3 with C-3399 had no effect. Moreover, the blocking of free thiols by the cell-penetrating N-ethylmaleimide, but not by the non-cell-penetrating 4-chloromercuribenzenesulfonate, resulted in LSEC defenestration. Inhibition of PDIA1 did not affect LSEC adhesion, viability, and bioenergetics, nor did it induce a clear-cut rearrangement of the cytoskeleton. However, PDIA1-dependent defenestration was reversed by cytochalasin B, a known fenestration stimulator, pointing to the preserved ability of LSECs to form new pores. Importantly, systemic inhibition of PDIA1 in vivo affected intra-parenchymal uptake of contrast agent in mice consistent with LSEC defenestration.These results revealed the role of intracellular PDIA1 in the regulation of fenestration dynamics in LSECs, and in maintaining hepatic sinusoid homeostasis.

Hierarchical modulation of extracellular electron transfer processes in microbial fuel cell anodes for enhanced power output through improved Geobacter adhesion

Although microbial fuel cell (MFC) technology is nearing practical realization, the challenge of attaining higher power output continues to impede its widespread implementation. In this study, we successfully developed free-standing three-dimensional high-performance anode materials for MFCs using a straightforward "one-step" process based on garlic. The resulting anode not only promotes the accumulation of biomass and the enrichment of exoelectrogen Geobacter but also facilitates interfacial extracellular electron transfer. This led to rapid start-up within just three days, a robust power density of 12.37 W/m3, and an impressive 24.04 % coulombic efficiency in mixed-culture MFC reactors. Our investigation into the underlying mechanisms of exocellular electron transfer revealed improvements in both direct electron transfer and mediated electron transfer processes. Notably, the fabrication of carbonized garlic MFC anodes proves to be technically competitive and economically relevant. It not only paves the way for the development of high-performance MFCs but also provides valuable insights for the rational design of materials related to microbial electrochemical technologies.

Abstract 5156: Is the formation of Stroma AReactive Invasion Front Areas in colorectal cancer driven by characteristic extracellular matrix reorganization processes based on the plasmin/plasminogen system

Abstract Background: As patient stratification still needs to be refined in colorectal cancer (CRC), we established SARIFA (Stroma AReactive Invasion Front Areas) as a novel H&E-based prognostic biomarker that is defined by a direct tumor-adipocyte interaction with a lack of desmoplastic reaction. Even though we could prove the high prognostic relevance of SARIFA now in multiple cohorts in gastric, colorectal, and pancreatic cancer, as well as could link an upregulation of lipid metabolism and immune alterations to this specific aggressive tumor biology, it remains an open question how SARIFAs are formed mechanistically. Materials/Methods: Based on the results of our recently established SARIFA-scores in the TCGA-CRC (TCGA-COAD & TCGA-READ cohorts; SARIFA-positive n=69, SARIFA-negative n=138) and the corresponding differential gene expression analysis, which are part of a previous study, protein levels (in ng/mL) measured by commercially available uPA and PAI1 enzyme-linked immunosorbent assays (ELISAs) were compared between SARIFA-positive and SARIFA-negative CRC patients (SARIFA-positive n=35, SARIFA-negative n=62). Additionally, immunohistochemistry for FABP4 as a key player in lipid metabolism was performed. Moreover, spatial transcriptomics (digital spatial profiling, DSP) was performed with tumor and stroma section segmentation on a subset of cases. Results: In TCGA-CRC, SERPINE1 (PAI1), as well as PLAU (uPA), are both significantly upregulated on mRNA level (LFC: 1.14 and 0.74, respectively; both adjusted p-values ≤0.001). Logically, SERPINE1 and PLAU are highly expressed in mesenchymal CMS4 CRCs, which overlap with SARIFA-positivity. This is reflected by an upregulation of matrix metalloproteinases in predicted functional protein networks (STRING analysis). In our local cohort, we could now validate this upregulation of uPA in SARIFA-positive CRCs on protein level (p=0.0027). For PAI1, a trend towards higher protein levels in SARIFA-positive CRCs could be observed (p=0.209). Moreover, SARIFA-positive CRCs show a higher number of tumor buds (p=0.013) as well as increased FABP4 expression at the invasion front (p<0.001) in our local cohort. In DSP analysis, the stroma fraction of SARIFA-positive CRCs showed significant changes compared to SARIFA-negative cases. Conclusion: Our current data shows that the formation of SARIFAs and the consecutive direct tumor-adipocyte interaction with a tumor-promoting increase in lipid metabolism may rely on alterations in the plasmin/plasminogen system, which could be a novel potential drug target in the aggressive subset of SARIFA-positive CRCs. Citation Format: Bianca Grosser, Nic G. Reitsam, Florian Sommer, Jochen Hardt, Bruno Märkl. Is the formation of Stroma AReactive Invasion Front Areas in colorectal cancer driven by characteristic extracellular matrix reorganization processes based on the plasmin/plasminogen system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5156.

An integrated constructed wetland-Microbial fuel cell system with sewage sludge-biochar to enhance treatment and energy recovery efficiencies

Constructed wetlands and microbial fuel cells (CW-MFCs) are a promising green and sustainable wastewater treatment technology. However, the power production performance of CW-MFCs has long been limited by low-performance cathodes. In this study, we designed two CW-MFC systems using cheap and readily available sewage sludge biochar (SSB) as the substrate for the experimental units. The integration of SSB significantly facilitated the removal of chemical oxygen demand, ammonium nitrogen, total nitrogen, and total phosphorus. Moreover, SSB enhanced the electrochemical performance of the air cathode, resulting in higher power density (44.64 mW/m2) and lower internal resistance (900.00 Ω) compared to gravel-integrated CW-MFC (0.88 mW/m2, 2057.14 Ω). In addition, a typical electroactive bacterium---Geobacter was enriched in the SSB-integrated CW-MFC system. The iron oxides and graphic nitrogen of the SSB favor the growth of Geobacter, and the redox-active groups on the surface of SSB accelerate the extracellular electron transfer process, contributing to the enhancement of treatment performance. Meanwhile, the metal and nitrogen doping improves the oxygen reduction reaction activity and conductivity of SSB, enhancing the cathode area of CW-MFC and improving the energy recovery. Overall, these results demonstrated that SSB-integrated CW-MFC can be a competitive technology for effective wastewater treatment and energy recovery.

Retraction for Yadav et al., "The bidirectional extracellular electron transfer process aids iron cycling by Geoalkalibacter halelectricus in a highly saline-alkaline condition".

In our paper, we reported the bidirectional extracellular electron transfer capability of Geoalkalibacter halelectricus based on biochemical (i.e., with insoluble Fe-oxide and Fe(0)) and bioelectrochemical (i.e., with electrodes) experimental approaches. We noticed some issues and limitations of the methods and techniques that were used to analyze Fe species, particularly the reduced Fe ions in insoluble and precipitated Fe(II) minerals that led to incorrect interpretation of the results, specifically the reduction of Fe(III) to Fe(0) in this study. We were made aware of thermodynamic constraints that would make the biological reduction of Fe(III) to Fe(0) implausible. Hence, the conclusion about microbial Fe(III)-oxide reduction to Fe(0) is invalid. We also noticed errors in estimating the protein-based iron reduction/oxidation rates and faradic efficiencies, besides the limitations of the methods used for Fe analysis. For these reasons, we retract this article and sincerely apologize for the inconvenience it may have caused to the readers.

Microbial corrosion of CoCrMnNi high entropy alloy by Pseudomonas aeruginosa through electron transfer between Mn and microbe

The microbiologically influenced corrosion of CoCrMnNi high entropy alloy induced by P. aeruginosa was investigated in this work. The results of electrochemical tests, time-of-flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy showed that the thickness of passive film was significantly decreased in the presence of P. aeruginosa and the corrosion of HEA was accelerated. When the organic nutrients were deficient, the extracellular electron transfer process was promoted and the corrosion resistance of the HEA was further decreased according to the results of potentiodynamic polarization and Mott-Schottky. The effect of nutrients deficiency on MIC acceleration was more prominent after the degradation of the passive film. Mn metal in the HEA substrate preferentially participated in the bacterial metabolism as an alternative energy source due to the high activity.

Effects of Ghrelin on Plasminogen Activator Activity in Human Umbilical Vein Endothelial Cells

Ghrelin and its growth hormone secretagogue receptor (GHSR) have been found in the placenta, both in endothelial and trophoblast cells. Ghrelin has been shown to decrease blood pressure in several systems and improve endothelial function by stimulating VEGF production. Because locally increased Ghrelin was detected in the preeclamptic fetoplacental unit, we hypothesized its involvement in the fibrinolysis and vascular tone typically observed in preeclamptic patients. This study aimed to evaluate the synthesis of plasminogen activators (PAs), PA inhibitor-1 (PAI-1), and urokinase-type PA (uPA) receptor (uPAR) in human umbilical vein endothelial cells (HUVECs) since the components of the PA/plasmin system are vital players in the extracellular matrix remodeling process necessary for angiogenesis. HUVECs were treated for 24 h with increasing concentrations of Ghrelin (10−11–10−7 M) or IL-1β (0.1 ng/mL). PAs, PAI-1, and uPAR mRNAs were determined by real-time PCR and PA activity was determined by casein underlay. We demonstrated an increase in uPA, tissue-type PA (tPA), and uPAR mRNA; a reduction in PAI-1 mRNA in HUVECs treated with Ghrelin; and an increase in total uPA activity. In conclusion, our results suggest a potential compensatory physiological mechanism for Ghrelin in response to the maternal endothelial dysfunction observed in the preeclamptic fetoplacental unit.

Unique corrosion reinforcement mechanism of pipeline oil sludge with sulfate-reducing bacteria on X60 steel and the targeted long-term inhibition of dazomet delivery

The mutual promotion behavior of pipeline oil sludge and wild SRB on pipeline steel corrosion was investigated. The resistance probe technique was used for long-term monitoring of MIC underneath SRB oil sludge. Corrosion of pipeline steel under oil sludge was the result of multifactorial coupling. SRB biofilm enhanced the conductivity of the oil sludge that serves as an electron transfer "bridge" between the SRB and carbon steel, accelerating the extracellular electron transfer process of MIC, and hence the dissolution of the carbon steel. Delivery of dazomet (DMTT) was a long-term strategy for mitigating pipeline corrosion under SRB oil sludge.

SYSTEMS BIOLOGY OF HUMAN AGING - NETWORK MODEL 2023

Abstract This network is presented to aid in conceptualizing the many processes of aging, the causal chains of events, the interactions among them, feedback, and vicious cycles. It suggests promising intervention points for therapy development. The signs of human senescence are hypothesized to result from several primary causes. This network includes both intracellular and extracellular processes, ranging from molecular to whole-body. Lifestyle, environment, and proposed interventions are highlighted. Important pathways include: Nuclear mutations, transposon insertions, telomere shortening, chromosome breaks, chromatin alterations, epigenetic DNA adducts. Extracellular protein damage results in stiffness, weakness, inflammation. Altered niches for cells cause transdifferentiation, arrested cell division, cell death, cancer, stem cell depletion, tissue wasting, neurodegeneration, organ malfunction. Stiffer blood vessels promote stroke, heart disease. Lysosomes accumulate reactive, crosslinked Lipofuscin, which impairs autophagic turnover of macromolecules and organelles. Lipofuscin leaking into cytosol triggers apoptosis. Mitochondrial DNA Mutates; Lamin-A progerin, accumulates in nuclear scaffold, impairing mitosis and telomere maintenance. Nuclear Envelope Pore Proteins become oxidized, allowing inappropriate traffic of other proteins into and out of nucleus. Oxidized Aggregates in cytoplasm crosslink, resist turnover, inhibit proteasome activity, increase redox poise, and physically interfere with intracellular transport in axons. Proteasomes inhibited, reduce turnover of damaged molecules and expired molecular signals. Increased Redox Poise alters signaling and enzyme activities, and erodes telomeres. Inflammatory Cascades, promoted by damaged molecules and sick cells, further damage tissues. Neuroendocrine and immune systems degrade. Misfolded Proteins accumulate in Endoplasmic Reticulum. This diagram is maintained on the Web as a reference for researchers and students. www.LegendaryPharma.com/chartbg.html

Loss of the centrosomal protein ALMS1 alters lipid metabolism and the regulation of extracellular matrix-related processes

BackgroundAlström syndrome (ALMS) is a rare autosomal recessive disease that is associated with mutations in ALMS1 gene. The main clinical manifestations of ALMS are retinal dystrophy, obesity, type 2 diabetes mellitus, dilated cardiomyopathy and multi-organ fibrosis, characteristic in kidneys and liver. Depletion of the protein encoded by ALMS1 has been associated with the alteration of different processes regulated via the primary cilium, such as the NOTCH or TGF-β signalling pathways. However, the cellular impact of these deregulated pathways in the absence of ALMS1 remains unknown.MethodsIn this study, we integrated RNA-seq and proteomic analysis to determine the gene expression profile of hTERT-BJ-5ta ALMS1 knockout fibroblasts after TGF-β stimulation. In addition, we studied alterations in cross-signalling between the TGF-β pathway and the AKT pathway in this cell line.ResultsWe found that ALMS1 depletion affects the TGF-β pathway and its cross-signalling with other pathways such as PI3K/AKT, EGFR1 or p53. In addition, alterations associated with ALMS1 depletion clustered around the processes of extracellular matrix regulation and lipid metabolism in both the transcriptome and proteome. By studying the enriched pathways of common genes differentially expressed in the transcriptome and proteome, collagen fibril organisation, β-oxidation of fatty acids and eicosanoid metabolism emerged as key processes altered by the absence of ALMS1. Finally, an overactivation of the AKT pathway was determined in the absence of ALMS1 that could be explained by a decrease in PTEN gene expression.ConclusionALMS1 deficiency disrupts cross-signalling between the TGF-β pathway and other dependent pathways in hTERT-BJ-5ta cells. Furthermore, altered cross-signalling impacts the regulation of extracellular matrix-related processes and fatty acid metabolism, and leads to over-activation of the AKT pathway.

Mass spectrometry imaging of natural carbonyl products directly from agar-based microbial interactions using 4-APEBA derivatization.

Aliphatic carboxylic acids, aldehydes, and ketones play diverse roles in microbial adaptation to their microenvironment, from excretion as toxins to adaptive metabolites for membrane fluidity. However, the spatial distribution of these molecules throughout biofilms and how microbes in these environments exchange these molecules remain elusive for many of these bioactive species due to inefficient molecular imaging strategies. Herein, we apply on-tissue chemical derivatization (OTCD) using 4-(2-((4-bromophenethyl)dimethylammonio)ethoxy)benzenaminium dibromide (4-APEBA) on a co-culture of a soil bacterium (Bacillus subtilis NCIB 3610) and fungus (Fusarium sp. DS 682) grown on agar as our model system. Using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), we spatially resolved more than 300 different metabolites containing carbonyl groups within this model system. Various spatial patterns are observable in these species, which indicate possible extracellular or intercellular processes of the metabolites and their up- or downregulation during microbial interaction. The unique chemistry of our approach allowed us to bring additional confidence in accurate carbonyl identification, especially when multiple isomeric candidates were possible, and this provided the ability to generate hypotheses about the potential role of some aliphatic carbonyls in this B. subtilis/Fusarium sp. interaction. The results shown here demonstrate the utility of 4-ABEBA-based OTCD MALDI-MSI in probing interkingdom interactions directly from microbial co-cultures, and these methods will enable future microbial interaction studies with expanded metabolic coverage.IMPORTANCEThe metabolic profiles within microbial biofilms and interkingdom interactions are extremely complex and serve a variety of functions, which include promoting colonization, growth, and survival within competitive and symbiotic environments. However, measuring and differentiating many of these molecules, especially in an in situ fashion, remains a significant analytical challenge. We demonstrate a chemical derivatization strategy that enabled highly sensitive, multiplexed mass spectrometry imaging of over 300 metabolites from a model microbial co-culture. Notably, this approach afforded us to visualize over two dozen classes of ketone-, aldehyde-, and carboxyl-containing molecules, which were previously undetectable from colonies grown on agar. We also demonstrate that this chemical derivatization strategy can enable the discrimination of isobaric and isomeric metabolites without the need for orthogonal separation (e.g., online chromatography or ion mobility). We anticipate that this approach will further enhance our knowledge of metabolic regulation within microbiomes and microbial systems used in bioengineering applications.

Real-Time Spatiotemporal Measurement of Extracellular Signaling Molecules Using an Aptamer Switch-Conjugated Hydrogel Matrix.

Cells rely on secreted signaling molecules to coordinate essential biological functions including development, metabolism, and immunity. Unfortunately, such signaling processes remain difficult to measure with sufficient chemical specificity and temporal resolution. To address this need, an aptamer-conjugated hydrogel matrix that enables continuous fluorescent measurement of specific secreted analytes - in two dimensions, in real-time is developed. As a proof of concept, real-time imaging of inter-cellular cyclic adenosine 3',5'-monophosphate (cAMP) signals in Dictyostelium discoideum amoeba cells is performed. A set of aptamer switches that generate a rapid and reversible change in fluorescence in response to cAMP signals is engineered. By combining multiple switches with different dynamic ranges, measure cAMP concentrations spanning three orders of magnitude in a single experiment can be measured. These sensors are embedded within a biocompatible hydrogel on which cells are cultured and their cAMP secretions can be imaged using fluorescent microscopy. Using this aptamer-hydrogel material system, the first direct measurements of oscillatory cAMP signaling that correlate closely with previous indirect measurements are achieved. Using different aptamer switches, this approach can be generalized for measuring other secreted molecules to directly visualize diverse extracellular signaling processes and the biological effects that they trigger in recipient cells.

A cluster of blood-based protein biomarkers associated with decreased cerebral blood flow relates to future cardiovascular events in patients with cardiovascular disease

Abstract Introduction Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes. Methods In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, CBF was measured with MRI in normal-appearing grey matter with pseudo-continuous arterial spin labeling. We assessed the relation between 92 plasma proteins from the Olink® cardiovascular III panel and CBF using cluster-based analyses and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up. Results Thirteen proteins were associated with CBF (ρSpearman range: -0.10 to -0.19, pFDR-corrected <0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected <0.05) and was associated with cardiovascular risk (p <0.001) and cardiovascular events (OR 2.05, p <0.01). Conclusions We identified a cluster of plasma biomarkers related to CBF, which is related to future cardiovascular events in patients with CVD. The cluster primarily reflected extracellular matrix organization processes, which represent potential targets to preserve CBF in patients with CVD.

Populational genomic insights of Paraclostridium bifermentans as an emerging human pathogen.

Paraclostridium bifermentans (P.b) is an emerging human pathogen that is phylogenomically close to Paeniclostridium sordellii (P.s), while their populational genomic features and virulence capacity remain understudied. Here, we performed comparative genomic analyses of P.b and compared their pan-genomic features and virulence coding profiles to those of P.s. Our results revealed that P.b has a more plastic pangenome, a larger genome size, and a higher GC content than P.s. Interestingly, the P.b and P.s share similar core-genomic functions, but P.b encodes more functions in nutrient metabolism and energy conversion and fewer functions in host defense in their accessory-genomes. The P.b may initiate extracellular infection processes similar to those of P.s and Clostridium perfringens by encoding three toxin homologs (i.e., microbial collagenase, thiol-activated cytolysin, phospholipase C, which are involved in extracellular matrices degradation and membrane damaging) in their core-genomes. However, P.b is less toxic than the P.s by encoding fewer secretion toxins in the core-genome and fewer lethal toxins in the accessory-genome. Notably, P.b carries more toxins genes in their accessory-genomes, particularly those of plasmid origin. Moreover, three within-species and highly conserved plasmid groups, encoding virulence, gene acquisition, and adaptation, were carried by 25-33% of P.b strains and clustered by isolation source rather than geography. This study characterized the pan-genomic virulence features of P.b for the first time, and revealed that P. bifermentans is an emerging pathogen that can threaten human health in many aspects, emphasizing the importance of phenotypic and genomic characterizations of in situ clinical isolates.

Toward a modeling, optimization, and predictive control framework for fed-batch metabolic cybergenetics.

Biotechnology offers many opportunities for the sustainable manufacturing of valuable products. The toolbox to optimize bioprocesses includes extracellular process elements such as the bioreactor design and mode of operation, medium formulation, culture conditions, feeding rates, and so on. However, these elements are frequently insufficient for achieving optimal process performance or precise product composition. One can use metabolic and genetic engineering methods for optimization at the intracellular level. Nevertheless, those are often of static nature, failing when applied to dynamic processes or if disturbances occur. Furthermore, many bioprocesses are optimized empirically and implemented with little-to-no feedback control to counteract disturbances. The concept of cybergenetics has opened new possibilities to optimize bioprocesses by enabling online modulation of the gene expression of metabolism-relevant proteins via external inputs (e.g., light intensity in optogenetics). Here, we fuse cybergenetics with model-based optimization and predictive control for optimizing dynamic bioprocesses. To do so, we propose to use dynamic constraint-based models that integrate the dynamics of metabolic reactions, resource allocation, and inducible gene expression. We formulate a model-based optimal control problem to find the optimal process inputs. Furthermore, we propose using model predictive control to address uncertainties via online feedback. We focus on fed-batch processes, where the substrate feeding rate is an additional optimization variable. As a simulation example, we show the optogenetic control of the ATPase enzyme complex for dynamic modulation of enforced ATP wasting to adjust product yield and productivity.

Quinone-mediated extracellular electron transfer processes in ex situ biomethanation reactors

Redox mediators are used in a wide diversity of systems including biological ones. We investigated the effect of adding an artificial quinone (2,7-AQDS) as external redox molecule to an anaerobic digester system dominated by hydrogenotrophic methanogens. When oxidized AQDS was present, the methanogens diverted electrons from H2 to reduce AQDS instead of CO2. The AQDS reduction process was accompanied by a temporary CH4 inhibition, which was re-established several days after the full reduction of AQDS to AH2QDS. The presence of AQDS furthermore resulted in a community shift from Methanobacterium as the dominant methanogen to a more diverse community of methanogens. Protein expression profiles showed a shift in cofactor preference of the adapted community, as a potential response mechanism to AQDS inhibition. AH2QDS was only used as electron donor to a limited extent. Stable isotope incorporation experiments here indicated that the acetogen Acetoanaerobium used AH2QDS to reduce CO2 into acetate.

Pathogenetic Mechanisms of the Relationship Between Osteoarthritis and Intestinal Dysbiosis

The potential association between dysbiosis of the gut microbiota and osteoarthritis is confirming by a growing number of studies. Given the social significance, the high prevalence of osteoarthritis, and evidences that quantitative and qualitative modification of the gut microbiota affects its progression, it seems important to clarify the underlying mechanisms of this association. Osteoarthritis is a multifactorial joint disease, which is based primarily on the progressive degeneration of articular cartilage. Impaired metabolic activity of chondrocytes, consisting in an imbalance in the extracellular matrix synthesis and degradation processes, causes the persistent release of molecular patterns associated with damage. This leads to the activation of a wide range of innate immune cells receptors and is the basis for the development of an inflammatory reaction in the joint. The involvement of macrophages in the synovial membrane and their activation leads to the production of pro-inflammatory cytokines, leading to the development of chronic low-grade inflammation in the joint, supporting the synthesis of catabolic enzymes by chondrocytes and escalating the cartilage degeneration. Microbial dysbiosis, defined as an adverse modification in the diversity, structure, or metabolic activity of the gut microbiota, is a hidden risk factor, accompanied by metabolic endotoxemia and, consequently, by increased production of pro-inflammatory cytokines, that support the systematic low-grade inflammation and pathophysiological mechanisms of osteoarthritis. It has been shown that dysbiosis of the gut microbiota intestinal takes part in the formation of other osteoarthritis risk factors for, for example, obesity and metabolic disorders. The identification of important interrelated pathophysiological mechanisms of these pathologies will contribute to the development of new pathogenetic treatment methods with their subsequent active introduction into clinical practice.

The competitive advantage of Microcystis aeruginosa over Scenedesmus obliquus weakened by exposure to polylactic acid microplastics

Aquatic ecosystems are heavily affected by microplastics (MPs), and its impacts on aquatic life have received extensive attention. However, it is still unclear how biodegradable MPs influence the growth and competition of phytoplankton. In this study, the response of growth dynamics, alternation in algal cell morphology and toxin-producing capability, and changes in the extracellular process of Microcystis aeruginosa (M. aeruginosa) and Scenedesmus obliquus (S. obliquus) were systematically studied in monoculture and co-culture conditions with and without the presence of polylactic acid MPs (PLA-MPs). The results indicated that although the loss of cell integrity was observed, PLA-MPs addition (50 mg/L) caused a 1.40- and 1.36-fold increase in cell densities of M. aeruginosa and S. obliquus in monoculture systems, respectively. This suggests the PLA-MPs more favored the growth of M. aeruginosa. This effect was manifested in co-culture conditions, because the degradation of PLA-MPs provided additional inorganic carbon in the experimental systems and benefited the growth of both M. aeruginosa and S. obliquus. Meanwhile, the synthesis of microcystins from the toxic M. aeruginosa was substantially reduced upon PLA-MPs exposure, which reduced the competitive advantage of M. aeruginosa over S. obliquus. Thus; the cell density of M. aeruginosa and S. obliquus showed 1.15- and 1.88-folds increasing compared to that without PLA-MPs addition. This interaction between PLA-MPs and algae weakened the competitive advantage of M. aeruginosa over S. obliquus, but their competitive outcomes remained unchanged. The results provided new insights into understanding the potential ecological risks of biodegradable plastics in aquatic ecosystems.

Progress in constructing functional coacervate systems using microfluidics

AbstractCoacervates formed by liquid‐liquid phase separation play significant roles in a variety of intracellular and extracellular biological processes. Recently, substantial efforts have been invested in creating protocells using coacervates. Microfluidic technology has rapidly gained prominence in this area due to its capability to construct monodisperse and stable coacervate droplets. This review highlights recent advancements in utilizing microfluidic devices to construct coacervate‐core‐vesicle (COV) systems. These COV systems can be employed to realize the sequestration and release of biomolecules as well as to control enzymatic reactions within the coacervate systems in a spatiotemporal manner. Lastly, we delve into the current challenges and opportunities related to the development of functional coacervate systems based on microfluidic technology.