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Association of Lung Quantitative CT Scan Textures With Systemic Inflammation and Mortality in COPD.

BACKGROUND: COPD is characterized by persistent inflammation that is responsible for remodeling the bronchovascular bundles (BVBs), which may lead to poor quality of life. Quantitative CT (QCT) scan textures of the lung can capture local disease patterns of inflammation and related respiratory morbidity. RESEARCH QUESTION: Are BVB textures, obtained from the adaptive multiple feature method, associated with systemic inflammation, morbidity, and mortality in COPD? STUDY DESIGN AND METHODS: We analyzed data from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS; n = 2,981) and the Genetic Epidemiology of COPD (COPDGene) study (n = 10,305). The predictors included 2 QCT scan biomarkers, the BVB and CT density gradient (CTDG) textures, age, sex, BMI, race, smoking status, pack-years of smoking, CT scan-detected emphysema, and square root of the wall area of a hypothetical airway with a 10-mm lumen perimeter (Pi10). Outcomes included plasma biomarker concentrations from Meso Scale Discovery proteomics assays and CBC counts, both as markers of inflammation, along with FEV1, FEV1 to FVC ratio, St. George's Respiratory Questionnaire score, 6-minute walk distance, and modified Medical Research Council dyspnea scale score. Associations of these QCT scan textures with FEV1 decline and all-cause mortality also were investigated. RESULTS: Increased BVB texture was associated significantly with elevated neutrophil and monocyte counts and the neutrophil to lymphocyte ratio, independent of clinical covariates, CT scan-detected emphysema, and Pi10. Elevated CTDG was associated with increased neutrophil count, NLR, and tumor necrosis factor &#x3b1;. Increased CTDG and BVB textures also were associated with a lower FEV1 and 6-minute walk distance. CTDG at baseline was also associated with decline in FEV1 at the 5-year follow-up in the COPDGene study. We observed a significant association of both BVB texture (SPIROMICS: hazard ratio [HR], 1.084 [95% CI, 1.035-1.135; P < .001]; COPDGene: HR, 1.106 [95% CI, 1.080-1.131; P < .001]) and CTDG texture (SPIROMICS: HR, 1.033 [95% CI, 1.003-1.064; P = .03]; COPDGene: HR, 1.079 [95% CI, 1.061-1.096; P < .001]) with all-cause mortality independent of CT scan-detected emphysema and Pi10. INTERPRETATION: QCT scan textures may provide imaging evidence of the spatial heterogeneity of lung inflammation and overall disease burden in COPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; Nos.: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene); URL: www. CLINICALTRIALS: gov.

Humans↗

Innate recognition of intracellular bacteria.

The molecular repertoire for innate recognition of bacterial pathogens has expanded rapidly in the past decade. These immunosensors include Toll-like receptors and the more recently defined NOD-like receptors (NLRs): NODs, NALPs, NAIP and IPAF. Toll-like receptors signal from the cell surface or endosome upon ligand binding, whereas NLRs are activated by characteristic bacterially derived molecules, such as peptidoglycan, RNA, toxins and flagellin, in the cytosol. Studies using animal and culture models of bacterial infection indicate a pro-inflammatory role for NLRs, mediated by signaling through nuclear transcription factor kappaB and activation of caspase-1 by the inflammasome. These data also support a synergistic role for extracellular and intracellular bacterial sensing in regulating inflammation. In humans, NLR mutations are often associated with autoinflammatory syndromes, suggesting a complex role for cytosolic surveillance in systemic innate immunity.

Animals↗

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 &#xd7; 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans↗

Spectrophotometric evaluation of stability constants of 1:1 weak complexes from continuous variation data.

A bilogarithmic hyperbolic cosine method for the spectrophotometric evaluation of stability constants of 1:1 weak complexes from continuous variation data has been devised and applied to literature data. A weighting scheme, however, is necessary in order to take into account the transformation for linearization. The method may be considered a useful alternative to methods in which one variable is involved on both sides of the basic equation (i.e. Heller and Schwarzenbach, Likussar and Adsul and Ramanathan). Classical least squares lead in those instances to biased and approximate stability constants and limiting absorbance values. The advantages of the proposed method are: the method gives a clear indication of the existence of only one complex in solution, it is flexible enough to allow for weighting of measurements and the computation procedure yield the best value of logbeta11 and its limit of error. The agreement between the values obtained by applying the weighted hyperbolic cosine method and the non-linear regression (NLR) method is good, being in both cases the mean quadratic error at a minimum.

Drug Stability↗

Stability of the ANAMMOX process in a gas-lift reactor and a SBR.

In the last years, the ANAerobic AMMonium OXidation (ANAMMOX) process has been put forward as a promising alternative to treat ammonium rich wastewaters. An ANAMMOX gas-lift reactor and a sequential batch reactor (SBR) were operated during around 200 days in this study, reaching nitrogen loading rates (NLRs) of 2.0 and 0.75 g l(-1) per day, respectively. The efficiency in the nitrite (limiting substrate) removal was 99%. The ammonium and nitrite influent concentrations were increased stepwise until biomass in the reactors started to float. These flotation events coincided with periods when the NLR exceeded the maximum specific ANAMMOX activity (MSAA) of the sludge. The MSAA, determined in batch experiments, was 0.9 and 0.44 g g(-1) per day for biomasses from the gas-lift reactor and the SBR, respectively. Flotation of the biomass occurred most likely due to a granule density decrease caused by dinitrogen gas accumulation inside the granules and an apparent breakage of the granules. Further research is needed to understand this phenomenon and to optimise the corresponding strategies to counteract the flotation.

Bacteria, Anaerobic↗

Effects of mechanical stress on Anammox granules in a sequencing batch reactor (SBR).

The effect of shear stress on Anammox process was studied in a sequencing batch reactor (SBR). The reactor was operated during 218 days under different stirring speeds (60-250 rpm) in order to expose the system to different shear conditions and to study the stability of the Anammox granules referred to their biological activity and size. The nitrogen loading rate (NLR) fed to the SBR was kept around 0.3g N(L day)(-1). The nitrite (limiting substrate) removal percentage was 98% during most of the operational period. The specific Anammox activity of the biomass was practically constant and around 0.4 g N(g VSSday)(-1) and the average feret diameter of the formed granules was 0.64 mm. Obtained results indicated that stirring speeds up to 180 rpm have no negative effect on the performance of the Anammox process, whereas Anammox activity decreased to 40% when a rotating speed of 250 rpm was tested and the average diameter decreased in 45%, the concentration of solids in the effluent increased to 0.2g TSSL(-1) and nitrite was accumulated in the reactor up to 60 mg NL(-1).

Anaerobiosis↗

Diagnostic analysis of experimental artefacts in DOSY NMR data by covariance matrix of the residuals.

Multivariate curve resolution (MCR) has been applied to separate pure spectra and pure decay profiles of DOSY NMR data. Given good initial guesses of the pure decay profiles, and combined with the nonlinear least square regression (NLR), MCR can result in good separation of the pure components. Nevertheless, due to the presence of artefacts in experimental data, validation of a MCR model is still necessary. In this paper, the covariance matrix of the residuals (CMR), obtained by postmultiplying the residual matrix with its transpose, is proposed to evaluate the quality of the results of an experimental data set. Plots of the rows of this matrix give a general impression of the covariance in the frequency domain of the residual matrix. Different patterns in the plot indicate possible causes of experimental imperfections. This new criterion can be used as diagnosis in order to improve experimental settings as well as suggest appropriate preprocessing of DOSY NMR data.

Journal Article↗

Naip5/Birc1e and susceptibility to Legionella pneumophila.

Genetic analysis in mice is a powerful approach for the identification of genes and proteins that have a key role at the interface of the host-pathogen interaction. The Lgn1 locus has been found to control the intracellular replication of Legionella pneumophila in murine macrophages. Using functional complementation in transgenic mice, the Naip5/Birc1e gene has been identified as responsible for the Lgn1 effect. The classification of Naip5/Birc1e as a member of the NLR protein family suggests that Naip5/Birc1e acts as an intracellular sensor of L. pneumophila. The nature of the signal transduced by Naip5/Birc1e in response to Legionella products is of great interest but is currently unknown. Here, several possible scenarios are presented.

Animals↗

Granulation in high-load denitrifying upflow sludge bed (USB) pulsed reactors.

In this work, the effect of the application of a pulse system to anoxic upflow sludge bed (USB) denitrifying reactors for enhancing sludge granulation was studied. In all, three 0.8 L reactors (two operated with flow pulsation, P1 with effluent recycling and P2 without recycling, and one without pulsation and effluent recycling, no pulsation (NP)) were fed with a mixture of NaNO3 and glucose and inoculated with methanogenic granular sludge. The organic loading rate (OLR) and the nitrogen loading rate (NLR) were progressively increased and, at the end of the experiment, extremely high values were obtained (67.5 kgCOD/m3d and 11.25 kgN-NO3-/m3 d). Ammonia and nitrite accumulation in reactor NP were important in the maturation stage, decreasing the denitrification efficiency to 90%, while in reactor P1 only low nitrite values were obtained in the last few days of the experiment. In reactor P2, nitrogen removal was 100% most of the time. Several operational problems (flotation and the subsequent wash out of biomass) appeared in the NP reactor when working at high denitrifying loading rates, while in reactors P1 and P2 there were no notable problems, mainly due to the good characteristics of the sludge developed and the efficient degasification produced by the pulsing flow. The sludge formed in the NP reactor presented a flocculent structure and a total disintegration of the initial methanogenic granules occurred, while a small-sized granular biomass with a high specific density was developed in the pulsed reactors due to the shear stress produced.

Ammonia↗

Recent gene duplication and structural remodeling drive rapid lineage-specific gene family evolution in plants.

Gene duplication promotes the generation of novel gene functions and trait diversity across species. Here, we present DupHIST, a computational pipeline that reconstructs the hierarchical timing of gene duplications by integrating maximum likelihood (ML)-based phylogeny with substitution-derived timing via statistical smoothing. Applied to over 4.5 million genes from 114 plant genomes, we successfully inferred duplication histories across nearly 130,000 orthogroups. This large-scale analysis showed that 53.0% of genes arose from recent, lineage-specific duplications, with high concentrations in particular multi-copy families. Among these, NLR, C48, and P450 families exemplified how recently duplicated genes undergo rapid stepwise structural remodeling. This process was primarily driven by small-scale mutations, including insertions, deletions, and frameshifts, that rapidly accumulated shortly after duplication. By resolving the precise duplication order, we reconstructed these architectural changes, thereby enabling both the inference of putative ancestral structures and the exploration of functional diversification arising from structural remodeling. Structure-based clustering further uncovered that recently duplicated, uncharacterized genes retain core domain structures resembling known functional proteins even across phylogenetically distant species lacking sequence homology. Our findings reveal that recent gene duplications and subsequent structural remodeling represent a widespread and lineage-specific force driving rapid diversification of gene families in plants.

Gene duplication history↗

Nitrification with high nitrite accumulation for the treatment of wastewater with high ammonia concentration.

The objective of this paper was to determine the best conditions for partial nitrification with nitrite accumulation of simulated industrial wastewater with high ammonia concentration, lowering the total oxygen needed in the nitrification step, which may mean great saving in aeration. Dissolved oxygen (DO) concentration and pH were selected as operational parameters to study the possibility of nitrite accumulation not affecting overall ammonia removal. A 2.5L activated sludge reactor was operated in nitrification mode, feeding a synthetic wastewater simulating an industrial wastewater with high ammonia concentration. During the start-up a pH of 7.85 and a DO of 5.5mg/L were used. The reactor was operated until stable operation was achieved at final nitrogen loading rate (NLR) of 3.3kgN- NH(4)(+)/m(3)d with an influent ammonia concentration of 610mg N-NH(4)(+)/L. The influence of pH was studied in continuous operation in the range of 6.15-9.05, changing the reactor pH in steps until ammonia accumulation (complete nitrification inhibition) took place. The influence of DO was studied in the same mode, changing the DO in steps from 5.5 to 0.5mg/L. The pH was not a useful operational parameter in order to accumulate nitrite, because in the range of pH 6.45-8.95 complete nitrification to nitrate occurs. At pH lower than 6.45 and higher than 8.95 complete inhibition of nitrification takes place. Setting DO concentration in the reactor at 0.7mg/L, it was possible to accumulate more than 65% of the loaded ammonia nitrogen as nitrite with a 98% ammonia conversion. Below 0.5mg/L of DO ammonia was accumulated and over a DO of 1.7mg/L complete nitrification to nitrate was achieved. In conclusion, it is possible under the conditions of this study, to treat high ammonia synthetic wastewater achieving an accumulation of at least 65% of the loaded nitrogen as nitrite, operating at a DO around 0.7mg/L. This represents a reduction close to 20% in the oxygen necessary, and therefore a considerable saving in aeration.

Ammonia↗

Susceptibility to morphine place conditioning: relationship with stress-induced locomotion and novelty-seeking behavior in juvenile and adult rats.

Previous studies demonstrated that the rewarding effect of psychostimulants, such as amphetamine and cocaine, can be predicted by locomotor activity toward novelty in a free-choice situation but not motor response developed in inescapable environment. However, whether this relationship also exists with narcotic morphine remains unclear. In the present study, the relationship between morphine place conditioning and open field as well as novelty-seeking behavior was examined in both juvenile and adult rats. By using arena open field and the same arena containing novel object, we investigated the initial open-field activity and novelty-seeking behavior after familiarization process, respectively, in juvenile and adult rats. Subsequently, the relationship between morphine (2 mg/kg) place conditioning and the above two behaviors was examined. Our results demonstrated that morphine place conditioning effect was readily acquired in both groups. The magnitude of this effect positively correlated with novelty-seeking intensity but not with open-field activity. This is the case whether juvenile or adult group was examined separately or across ages. However, only rats with high response to novelty (NHR) from their respective group expressed significant duration increase in drug-paired compartment. Rats with low response to novelty (NLR) showed no sign of this effect after the same drug training, suggesting slow acquisition of this effect in NLRs. These results also indicated that novelty-seeking actions and the rewarding effect of morphine possessed a common pathway and that neural and hormonal substrates activated in a mild stress environment like in the open field may not be critically involved in this process. The ontogenetic specificity and nonspecificity between different-aged rats as with the above relationship were discussed in this paper.

Age Factors↗

Binding of sodium salicylate by beta-cyclodextrin or 2,6-di-O-methyl-beta-cyclodextrin in aqueous solution.

Speed of sound and conductivity experiments have been done at 298.15 K to study the encapsulation process of sodium salicylate (NaSA) by beta-cyclodextrin (beta-CD) and 2,6-di-O-methyl-beta-cyclodextrin (DIMEB) in aqueous solutions. Since the concentration of the salicyclic form (HSA), coming from the hydrolysis of SA-, is negligible at biological pH, the binding process studied in this work is that of the SA- species. The stoichiometries of the complexes DIMEB: SA- and beta-CD:SA- have been found to be 1:1, as usually determined for most CD:drug complexes. Their association constants and their ionic molar conductivities at infinite dilution have been obtained by fitting the experimental conductivity data with a nonlinear regression method (NLR). For that purpose, a model based on that of Gelb and co-workers has been used. From the values of K beta-CD:SA- = (105 +/- 15)M-1 and KDIMEB:SA- = (140 +/- 20)M-1 obtained, the bioavailability of the salicylate drug in the complexed form has been discussed.

Anti-Inflammatory Agents, Non-Steroidal↗

RNA expression from a site-specific non-LTR retrotransposon microinjected into Xenopus oocytes.

Tx1L is a site-specific non-LTR retrotransposon (NLR) that has been identified in the genome of Xenopus laevis. Using microinjection into Xenopus oocytes, several aspects of RNA expression by these elements were investigated. With constructs carrying various parts of the element we saw no evidence of promoter activity, unlike what has been shown for several other elements of this class. Tx1L transcription was induced by linking a whole element to a promoter that is active in oocytes. Among the RNAs produced, about half had 3' ends located near the end of the element, suggesting that instruction for 3' end formation are encoded in the element or its target. Deletion of the 3' UTR of Tx1L and of surrounding target sequences indicated that these regions are not required for termination or processing of the RNA. PolyA or very A-rich sequences were added at these 3' ends, despite the absence of canonical polyA addition signals. A significant proportion of non-A residues was found in the 3' untemplated tails, and this is reminiscent of non-templated insertions often found at the 3' junction of new genomic copies of some NLRs.

3' Untranslated Regions↗

Inflammatory caspases and inflammasomes: master switches of inflammation.

Fifteen years have passed since the cloning and characterization of the interleukin-1beta-converting enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11 and caspase -12. Efforts to elucidate the molecular mechanisms involved in the activation of these proteases have uncovered an important role for the NLR family members, NALPs, NAIP and IPAF. These proteins promote the assembly of multiprotein complexes termed inflammasomes, which are required for activation of inflammatory caspases. This article will review some evolutionary aspects, biochemical evidences and genetic studies, underlining the role of inflammasomes and inflammatory caspases in innate immunity against pathogens, autoinflammatory syndromes and in the biology of reproduction.

Adaptor Proteins, Signal Transducing↗

The CATERPILLER protein monarch-1 is an antagonist of toll-like receptor-, tumor necrosis factor alpha-, and Mycobacterium tuberculosis-induced pro-inflammatory signals.

The CATERPILLER (CLR, also NOD and NLR) proteins share structural similarities with the nucleotide binding domain (NBD)-leucine-rich repeat (LRR) superfamily of plant disease-resistance (R) proteins and are emerging as important immune regulators in animals. CLR proteins contain NBD-LRR motifs and are linked to a limited number of distinct N-terminal domains including transactivation, CARD (caspase activation and recruitment), and pyrin domains (PyD). The CLR gene, Monarch-1/Pypaf7, is expressed by resting primary myeloid/monocytic cells, and its expression in these cells is reduced by Toll-like receptor (TLR) agonists tumor necrosis factor (TNF) alpha and Mycobacterium tuberculosis. Monarch-1 reduces NFkappaB activation by TLR-signaling molecules MyD88, IRAK-1 (type I interleukin-1 receptor-associated protein kinase), and TRAF6 (TNF receptor (TNFR)-associated factor) as well as TNFR signaling molecules TRAF2 and RIP1 but not the downstream NFkappaB subunit p65. This indicates that Monarch-1 is a negative regulator of both TLR and TNFR pathways. Reducing Monarch-1 expression with small interference RNA in myeloid/monocytic cells caused a dramatic increase in NFkappaB activation and cytokine expression in response to TLR2/TLR4 agonists, TNFalpha, or M. tuberculosis infection, suggesting that Monarch-1 is a negative regulator of inflammation. Because Monarch-1 is the first CLR protein that interferes with both TLR2 and TLR4 activation, the mechanism of this interference is significant. We find that Monarch-1 associates with IRAK-1 but not MyD88, resulting in the blockage of IRAK-1 hyperphosphorylation. Mutants containing the NBD-LRR or PyD-NBD also blocked IRAK-1 activation. This is the first example of a CLR protein that antagonizes inflammatory responses initiated by TLR agonists via interference with IRAK-1 activation.

Adaptor Proteins, Signal Transducing↗

Diagnostic and prognostic value of fibroblast growth factor 23 in acute kidney injury: systematic review and meta-analysis.

Background: Acute kidney injury (AKI) is associated with high mortality and adverse outcomes. Fibroblast growth factor 23 (FGF23) has emerged as a potential biomarker for AKI; however, its diagnostic and prognostic utility remains inconsistent.Methods: We conducted a systematic review and meta-analysis of studies evaluating circulating intact FGF23 (iFGF23) or C-terminal FGF23 (cFGF23) (PROSPERO: CRD42022302659). PubMed, EMBASE, CNKI, and Wanfang databases were searched through June 9, 2026. QUADAS-2 was used for quality assessment. A random-effects bivariate model pooled sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (SROC AUC).Results: Twenty-three studies were included: 17 diagnostic, 6 prognostic (one addressing both). For AKI diagnosis, the pooled sensitivity was 0.79 (95% CI 0.73-0.86), specificity 0.82 (95% CI 0.75-0.89), PLR 4.40 (95% CI 2.59-6.21), NLR 0.25 (95% CI 0.16-0.34), DOR 17.49 (95% CI 8.67-35.16), and SROC AUC 0.87 (95% CI 0.81-0.92). Substantial heterogeneity was observed (I2 = 67%), with iFGF23 demonstrating higher accuracy than cFGF23 (AUC 0.91 vs 0.81). For AKI mortality, pooled sensitivity was 0.77 (95% CI 0.69-0.84), specificity 0.76 (95% CI 0.70-0.82), DOR 10.89 (95% CI 6.86-17.30), and SROC AUC 0.77 (95% CI 0.70-0.83). Significant heterogeneity was noted (I2 = 86.2% for sensitivity, 80.4% for specificity). No significant publication bias was detected.Conclusions: Circulating FGF23 exhibits moderate-to-high diagnostic and moderate prognostic performance in AKI, though interpretation is limited by substantial heterogeneity. It may serve as a complementary biomarker for risk stratification, pending further validation with standardized protocols.

Humans↗

Improving the biological nitrogen removal process in pharmaceutical wastewater treatment plants: a case study.

The Biological Nitrogen Removal (BNR) process of some pharmaceutical wastewater treatment plants has important operational problems. This study shows that, in order to solve these problems, the design of industrial BNR processes should start by analysing three key parameters: the characteristics of the wastewater load, the determination of the maximum TKN removal rate and the detection of toxic or inhibitory compounds in the wastewater. A case study of this analysis in pharmaceutical wastewater is presented here. In this case, the conventional TKN analytical method does not make an accurate characterisation of the wastewater load because it measures a concentration of 100 mg TKN l(-1) whereas the real concentration, determined with a modified TKN analytical method, is 150-500 mg TKN l(-1). Also, the TKN removal of the treatment system is insufficient in some periods because it falls below legal requirements. This problem might be a consequence of the wrong characterisation of wastewater during the design process. The maximum TKN removal at 27 degrees C (24 mg N g VSS(-1) d(-1) or 197 mg N l(-1) d(-1)) was evaluated in a pilot-scale plant. This value is six times greater than the average NLR applied in the full-scale plant. Finally, some of the components of the wastewater, such as p-phenylenediamine, might have inhibitory or toxic effects on the biological process. P-phenylenediamine causes a large decrease in the nitrification rate. This effect was determined by respirometry. This methodology shows that the effect is mainly inhibitory with a contact time of 30 min and if the contact time is longer, 14 hours, a toxic effect is observed.

Bioreactors↗