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Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level. [ABSTRACT FROM AUTHOR]

Background: Chickpea is a key pulse crop grown in the spring in dryland regions. The cold resistance potential of chickpeas allows for the development of genotypes with varying sowing dates to take advantage of autumn and winter rainfall, particularly in dryland regions. In this study, we assessed grain yield, plant height, 100-seed weight, days to maturity, and days to flowering of 17 chickpea genotypes in five autumn-sown dryland regions from 2019 to 2021. Additionally, the response of selected chickpea genotypes to cold stress was examined at temperatures of -4 °C, 4 °C, and 22 °C by analyzing biochemical enzymes. Results: Mixed linear model of ANOVA revealed a significant genotype × environment interaction for all traits measured, indicating varying reactions of genotypes across test environments. This study reported low estimates of broad-sense heritability for days to flowering (0.34), days to maturity (0.13), and grain yield (0.08). Plant height and seed weight exhibited the highest heritability, with genotypic selection accuracies of 0.73 and 0.92, respectively. Moreover, partial least square regression highlighted the impactful role of rainfall during all months except of October, November, and February on grain yield and its interaction with environments in autumn-planted chickpeas. Among the genotypes studied, G9, G10, and G17 emerged as superior based on stability parameters and grain yield. In particular, genotype G9 stood out as a promising genotype for dryland regions, considering both MTSI and genotype by yield*trait aproaches. The cold assay indicated that − 4 °C is crucial for distinguishing between susceptible and resistant genotypes. The results showed the important role of the enzymes CAT and GPX in contributing to the cold tolerance of genotype G9 in autumn-sown chickpeas. Conclusions: Significant G×E for agro-morphological traits of chickpea shows prerequisite for multi-trial analysis. Chickpea's direct root system cause that monthly rainfall during plant establishment has no critical role in its yield interaction with dryland environment. Considering the importance of agro-morphological traits and their direct and indirect effects on grain yield, the utilization of multiple-trait stability approches is propose. Evaluation of chickpea germplasm reaction against cold stress is necessary for autumn-sowing. Finally, autumn sowing of genotype FLIP 10–128 C in dryland conditions can led to significant crop performance. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease characterized by the destruction of the small intrahepatic bile ducts, which can progress to liver cirrhosis. The gold standard in the treatment of PBC is ursodeoxycholic acid (UDCA), which is indicated in all patients with PBC because it improves not only biochemical parameters but also patients' survival. An important milestone in the identification of patients at risk is the assessment of biochemical response to UDCA. Patients who respond to treatment have a lower incidence of hepatic events and better prognosis than patients who do not. Several scoring systems can be used to assess the response and identify non-responders who will benefit from second-line treatment. Obeticholic acid (OCA) is currently the only approved second-line treatment for PBC, which is effective for non-responders to UDCA therapy or patients, who have not tolerated UDCA therapy. However, OCA is contraindicated in advanced liver cirrhosis and portal hypertension. Moreover, pruritus may be a limiting factor for the administration of OCA. Fibrates have shown promising data supporting their use in non-responders to UDCA because they improve the biochemical parameters and elastographic findings and have possible antipruritic effects. Therefore, the idea of a triple treatment seems interesting. Clinical research is focusing on several other groups of drugs: peroxisome proliferator-activated receptor (PPAR) δ- and α/δ agonists, non-steroidal farnesoid X receptor agonists, fibroblast growth factor 19 modulators, and inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4. [ABSTRACT FROM AUTHOR]

The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB‐FL) and without FL (non‐FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB‐FL patients as compared with non‐FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p =.04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p =.05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p =.89). However, at week 48, there were no statistically significant differences between CHB‐FL and non‐FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p =.67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p =.27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p =.58) with similar findings for week 96. BR rate was lower in CHB‐FL patients after 12 weeks of antiviral treatment. However, after a longer follow‐up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL. [ABSTRACT FROM AUTHOR]

Objective To investigate the value of baseline red cell distribution width (RDW) and alkaline phosphatase (ALP) level after ursodeoxycholic acid (UDCA) treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis (PBC) . Methods A retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology, The Third People’s Hospital of Jiangsu University, from January 2015 to July 2022, with data collected at baseline, after one month of treatment, and after one year of follow-up. Based on the Paris-I criteria, the patients were divided into good response group and poor response group, and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve (AUC) was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values, and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Results Compared with the good response group, the poor response group had significantly higher levels of total bilirubin, aspartate aminotransferase/alanine aminotransferase, ALP, RDW, and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment (Z=−4.792, −3.697, −2.399, −4.102, −3.220, and −4.236, all P<0.05) . Compared with the good response group, the poor response group had significantly lower levels of albumin, hemoglobin, lymphocytes, hematocrit, and body mass index at baseline (Z=−3.592, −3.603, −2.602, −3.829, −2.432, all P<0.05), as well as significantly lower levels of prealbumin, albumin/ globulin ratio, apolipoprotein A, and free triiodothyronine at baseline (t=4.530, 3.402, 3.485, and 3.639, all P<0.001) . Compared with the poor response group, the good response group had a significantly lower proportion of patients with liver cirrhosis, gallstones/cholecystitis, or anemia (χ² =20.815, 3.892, and 12.283, all P<0.05) . Baseline RDW (odds ratio ［OR］= 1.157, 95% confidence interval ［CI］：1.028—1.301, P=0.015) and ALP level after one month of treatment (OR=1.012, 95%CI： 1.005—1.020, P=0.002) were independent risk factors for response to UDCA, with an AUC of 0.713 and 0.720, respectively. The patients with baseline RDW≥upper limit of normal (ULN) and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate (42.6% vs 8.2%, χ² =20.813, P<0.001) . Conclusion Patients with baseline RDW≥ULN and ALP≥2.2× ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA. [ABSTRACT FROM AUTHOR]

Aims: Ursodeoxycholic acid is the first‐line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. Methods: This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. Results: Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). Conclusions: We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis. [ABSTRACT FROM AUTHOR]

Objective: To explore whether 68Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage. Methods: The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used. Results: Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12 months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68Ga-PSMA-11 PET/CT-derived parameters alone. Conclusions: Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients. [ABSTRACT FROM AUTHOR]

Temporally heterogeneous environments is hypothesized to correlate with greater plasticity of plants, which has rarely been supported by direct evidence. To address this issue, we subjected three species from different ranges of habitats to a first round of alternating full light and heavy shading (temporally heterogeneous light experience), constant moderate shading and full light conditions (temporally homogeneous light experiences, control) and a second round of light-gradient treatments. We measured plant performance in a series of morphological, biomass, physiological and biochemical traits at the end of each round. Compared to constant full light experience, temporally heterogeneous light conditions induced immediate active biochemical responses (in the first round) with improved late growth in biomass (during the second round); constant moderate shading experience increased photosynthetic physiological and biomass performances of plants in early response, and decreased their late growth in biomass. The karst endemic species of Kmeria septentrionalis showed greater improvement in late growth of biomass and lower decrease in biochemical performance, due to early heterogeneous experience, compared to the non-karst species of Lithocarpus glaber and the karst adaptable species of Celtis sinensis. Results suggested plants will prefer to produce morphological and physiological responses that are less reversible and more costly in the face of more reliable environmental cues at early stage in spite of decreased future growth potential, but to produce immediate biochemical responses for higher late growth potential when early environmental cues are less reliable, to avoid the loss of high costs and low profits. Typical karst species should be more able to benefit from early temporally heterogeneous experience, due to long-term adaptation to karst habitats of high environmental heterogeneity and low resource availability. [ABSTRACT FROM AUTHOR]

Salinization reduces soil health and quality, drastically limiting plants' growth and crop yield. This comprehensive research aimed to evaluate the impact of sodium chloride increment on growth factors, amount of oxidative stress biomarker (Malondialdehyde), osmotic response (evaluated by both proline and sugars contents), photosynthesis efficiency (expressed with chlorophyll fluorescence measurement) and activity of Malate dehydrogenases (MDHs) as a regulator under abiotic stress tolerantly in Aloe vera in Alzahra University, Tehran. Experiments were conducted in two studies at the following concentration of sodium chloride: 0 (control), 100, 200, and 300 (mM) NaCl for 30 days (short-term treatments) and: 0 (control), 54.7, 109.5, and 164.5 (mM) NaCl for 150 days (long-term treatments). Three replications in a completely randomized design were applied. The results showed that while the fresh weight of below ground biomass declined at higher salinity level (164.5 mM), no significant differences were reported in the short period of salt treatments. A considerable amount of free proline that was accumulated in both short (3.594 µg.g-1 dw) and long (2.20 µg.g-1 dw) term studies raised the role of proline in osmoregulation. Our results showed the decline of MDA amount (0.0003 mmol.g-1FW) in 54.7 NaCl (mM) may be due to less membrane damage in presence of moderate salinity, and indicated a variety of dependent differences in biochemical markers activity. [ABSTRACT FROM AUTHOR]

Artificial light has been used to control plant growth and secondary metabolite production. Artemisia annua L. plants were illuminated with three light-emitting diode (LED) spectra to investigate proteomic and biochemical responses. After 7 days, proteomic data revealed different protein numbers in leaves, stems, and roots under particular treatments. Results demonstrated increased accumulation of several proteins, including secondary metabolite-related proteins. The red light (R) (660 nm) highly induced terpenoid proteins. Similar biochemical profiles were observed in white light (W) (445, 544 nm) and blue light (B) (445 nm) conditions, while profiles from R treatment were different. Functional proteins of W and B treatments were involved in the MVA and MEP pathways and sesquiterpene biosynthesis. By contrast, unique proteins in R treatment were mainly expressed in sesquiterpene and tetraterpene biosynthesis. Specific relationships between biosynthetic proteins and sesquiterpenes were observed, suggesting the indispensable role of the light spectrum in regulating terpenoid biosynthesis. [ABSTRACT FROM AUTHOR]

Introduction: Targeted radionuclide therapy with [177Lu]Lu-prostate-specific membrane antigen (PSMA) has shown promising results for the treatment of castration-resistant prostate cancer (mCRPC). Nevertheless, a proportion of patients do not respond to this therapy. Here, we aimed to evaluate the prognostic significance of the pretreatment pathologic and laboratory factors for the prediction of biochemical response to the first cycle of [177Lu]Lu-PSMA therapy. Methods: In this retrospective study, mCRPC patients, referred for [177Lu]Lu-PSMA therapy, were included. We retrieved the data of patients, undergone [177Lu]Lu-PSMA, from March 2019 to March 2021. Multiple baseline pathologic and laboratory parameters were extracted and correlated with the response to the first cycle. The prostate-specific antigen (PSA) level was evaluated six weeks after [177Lu]Lu-PSMA therapy for the biochemical response. Results: Forty-three patients with a mean age of 69.8±10.2 were included. Bone and visceral metastases were present in 81.4% and 14.0% of the patients, respectively. Except for two, all patients had received hormone- and chemotherapy. The mean PSA level was 189.9±259.0 at baseline. Following one cycle of [177Lu]Lu-PSMA, "= 10% PSA response" and "= 50% PSA response" were seen in 81.4% and 44.2% of the patients, respectively. Patients with higher baseline PSA more frequently had = 10% PSA response (p= 0.004). Also, the reduction in the PSA level correlated with baseline PSA (p=0.013, r=0.375). Conclusion: [177Lu]Lu-PSMA therapy results in the biochemical response in a considerable number of patients after one cycle. In nearly half of patients, PSA declines more than 50%. Higher baseline PSA is correlated with the level of PSA response. [ABSTRACT FROM AUTHOR]

Starting life in space and implementing spaceflight missions requires raising of plants in special conditions, where various stresses, including microgravity, are applied to plant. The use of stimulants is known as a promising effective approach that enhances plant resistance encountered a variety of abiotic stresses. In this study, the impact of two stimulants, melatonin and chitosan, in reducing negative effects of clinorotation on Rocket (Eruca sativa L.) seedlings was investigated from a physiological and biochemical point of view. For this purpose, a completely randomized experiment was designed where the treatments included control (without stimulants and normal gravity), melatonin (100 μM), chitosan (230 M), microgravity, microgravity + melatonin, and microgravity + chitosan. The results disclosed that the microgravity significantly impaired the plant growth and morphology, while exogenous application of melatonin and chitosan improved the plant growth parameters under stress conditions. Under microgravity, there was a reduction of 46.15% in shoot length (4.9 mm) and 41.44% in root length (4.7 mm) compared with the control (9.1 mm; 8.03 mm), respectively. Clinorotation led to a marked increment in the enzymes activity, wherein the POD, SOD and CAT activities increased by 75.13%, 72.67%, and 53.42%, respectively, compared with the control seedlings. In addition, supply of these two stimulants strengthened the scavenging of radial oxygen species and helped the plant to tolerate stress conditions, by activated the enzymatic and non-enzymatic systems. These results can pave the road for more studies and broad application of biological stimuli to overcome the space harsh environmental conditions by plants. • Microgravity significantly impaired the plant growth and morphology of Rocket plant. • Melatonin and chitosan improved the plant growth parameters under stress conditions. • Clinorotation led to outstanding increment in POD, SOD and CAT enzymes activity. • activated the plant's immune response through increasing the production of antioxidants. [ABSTRACT FROM AUTHOR]

The assimilation of inorganic nutrients by phytoplankton strongly depends on environmental conditions such as the availability of nitrogen and temperature, especially warming. The acclimation or adaptation of different species to such changes remains poorly understood. Here, we used a multimethod approach to study the viability and physiological and biochemical responses of the marine diatom Chaetoceros pseudocurvisetus to different temperatures (15, 25, and 30 °C) and different N:P ratios. Nitrogen limitation had a greater effect than high temperature on cell growth and reproduction, leading to a marked elongation of setae, decreased phosphorus assimilation, increased lipid accumulation, and decreased protein synthesis. The elongation of setae observed under these conditions may serve to increase the surface area available for the uptake of inorganic and/or organic nitrogen. In contrast, high temperatures (30 °C) had a stronger effect than nitrogen deficiency on cell death, nitrogen assimilation, chlorophyll a accumulation, the cessation of setae formation, and cell lipid remodelling. Significant changes in thylakoid lipids were observed in cells maintained at 30 °C, with increased levels of digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol. These changes may be explained by the role of galactolipids in thylakoid membrane stabilization during heat stress. [ABSTRACT FROM AUTHOR]

Abstract Foliar application of sodium silicate (Si) was integrated to methyl jasmonate (MeJa) or salicylic acid (SA) sprays on the Pistachio trees in order to induce resistance to the common pistachio psylla, Agonoscena pistaciae. Pest population and leaf biochemical responses were evaluated. The highest population densities were recorded in control (14.65 ± 1.55 eggs/leaflet; 124.7 ± 8.17 nymphs/leaflet) while MeJa, SA, Si or MeJa + Si, and SA + Si harbored lower pests (2.80 ± 0.63 to 4.42 ± 1.22 eggs/leaflet; 1.82 ± 0.45 to 4.32 ± 1.0 nymphs/leaflet). Trees which received SA + Si and Si showed the lowest pest density. Leaf total phenolic content was decreased by 4-5% after spraying with SA and SA + Si. Leaf polyphenoloxidase activity was increased using MeJa, MeJa + Si, SA, SA + Si but not by single Si. Treatments did not change the phenylalanine amoniumlyase activity. Chlorophyll a was significantly higher in control, MeJa + Si, and SA but it was lower in Si treatments. These findings suggest that the integrated use of Si with each of the MeJa or SA can elicit the pistachio’s defense against this pest. [ABSTRACT FROM AUTHOR]

Background: To determine how much an augmented analysis approach could improve the efficiency of prostate-specific antigen (PSA) response analyses in clinical practice. PSA response rates are commonly used outcome measures in metastatic castration-resistant prostate cancer (mCRPC) trial reports. PSA response is evaluated by comparing continuous PSA data (e.g., change from baseline) to a threshold (e.g., 50% reduction). Consequently, information in the continuous data is discarded. Recent papers have proposed an augmented approach that retains the conventional response rate, but employs the continuous data to improve precision of estimation.Methods: A literature review identified published prostate cancer trials that included a waterfall plot of continuous PSA data. This continuous data was extracted to enable the conventional and augmented approaches to be compared.Results: Sixty-four articles, reporting results for 78 mCRPC treatment arms, were re-analysed. The median efficiency gain from using the augmented analysis, in terms of the implied increase to the sample size of the original study, was 103.2% (IQR [89.8,190.9%]).Conclusions: Augmented PSA response analysis requires no additional data to be collected and can be performed easily using available software. It improves precision of estimation to a degree that is equivalent to a substantial sample size increase. The implication of this work is that prostate cancer trials using PSA response as a primary endpoint could be delivered with fewer participants and, therefore, more rapidly with reduced cost. [ABSTRACT FROM AUTHOR]

Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant. In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n = 13), saroglitazar 2 mg (n = 14), or placebo (n = 10) daily for 16 weeks. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at Week 16. A significant reduction of mean ALP levels was observed at Week 16 relative to baseline in both the saroglitazar 4 mg (least-squares [LS] mean =-163.3 U/L, SE = 25.1, p <0.001) and 2 mg (LS mean =-155.8 U/L, SE = 24.4, p < 0.001) groups, compared with placebo (LS mean =-21.1 U/L, SE = 28.9). Treatment with saroglitazar resulted in a rapid reduction of ALP concentration at Week 4 that was sustained through the study duration. At least 1 treatment-emergent adverse event occurred in 11 (84.6%) patients in the saroglitazar 4 mg group, in 12 (85.7%) patients in the 2 mg group and in 8 (80%) patients in the placebo group. Study drug was discontinued in 4 patients (3 patients in the 4 mg group and 1 patient in the 2 mg group) due to aminotransferase increases that promptly returned to baseline values after drug discontinuation. Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are underway at a daily dose of 2 mg and 1 mg due to the higher incidence of elevated liver enzymes observed with the 4 mg dose. NCT03112681 Saroglitazar resulted in a rapid and sustained improvement in alkaline phosphatase levels in patients with primary biliary cholangitis. The mean percentage reductions in alkaline phosphatase levels were 49% and 51% in the saroglitazar 4 mg and 2 mg groups compared to 3% in the placebo group. [Display omitted] • Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). • A statistically significant reduction in ALP levels was observed at Week 16 in saroglitazar 4 mg and 2 mg groups compared to placebo. • The reduction in ALP levels corresponded to a mean % reduction of 49% and 51% in the saroglitazar 4 mg and 2 mg groups, respectively. [ABSTRACT FROM AUTHOR]

Spiny lobsters (Panulirus sp.) were valuable and one of the most popular Indonesian export commodities. Some approaches were made to increase the quantity and quality of cultivated spiny lobsters. Land-based mariculture with Recirculating Aquaculture System (RAS) was applied to increase lobster harvesting and optimize environmental quality by adjusting water alkalinity. This study aimed to determine the optimum level of alkalinity for spiny lobsters Panulirus homarus rearing in RAS. This study investigated the effects of applying four water alkalinity levels (Control, 125, 200, and 275 mg L-1 CaCO3) on the biochemical responses of P. homarus observed in the hemolymph in terms of Total Hemocyte Count (THC), glucose, total protein, calcium, and pH levels. Furthermore, we also studied the alkalinity effects on lobster production performance parameters in terms of body weight gain, body length, Survival Rate (SR), Specific Growth Rate (SGR), and Feed Conversion Ratio (FCR). Lobsters with an initial weight rate of 58.05±1.69 g and an initial total length rate of 115.33±1.52 mm were reared for 60 days in a recirculation system. Results of water quality parameters such as ammonia, nitrite, nitrate, dissolved oxygen, temperature, and salinity during the study were available for lobster rearing. Different alkalinity levels affected the biochemical responses and production performance of lobsters. The best alkalinity level to reared Panulirus sp. in the recirculation system during this study was 200 mg L-1 CaCO3 so that it could achieve the highest survival rate of 86.67% with SGR 0.60±0.01 % day-1. [ABSTRACT FROM AUTHOR]

Sepia pharaonis (cuttlefish) has a narrow salinity adaptation range, therefore, it is highly sensitive to changes in salinity. This limits breeding practices for Sepia pharaonis. The aim of this study was to explore effects of low salinity concentrations on gills of cuttlefish. Larvae were randomly categorized into two groups and acclimatized to 2 different salinity conditions (22 psu and 29 psu). Salinity was adjusted by diluting salinity water (29 psu) with fresh water then aeration was carried out overnight. Observation of gills under light and electron microscopy showed that cuttlefish survived up to 22 psu salinity levels. Further, light and transmission electron microscopic examination showed that gills exposed to low salinity stress (22 psu) showed significant pathological changes compared with the control group (29 psu). Biochemical and molecular analyses showed that Na+/K+‐ATPase, Ca2+/Mg2+‐ATPase, TIP4‐1 and Zfand4 were involved in regulation of osmotic pressure in S. pharaonis. [ABSTRACT FROM AUTHOR]

[Display omitted] • High concentrations of selenite caused a negative impact on P. tricornutum. • Fulvic acid alleviated the damage by selenite. • High quality of biofuel was retrieved under selenite and fulvic acid treatment. • Se removal and SeCys accumulation capabilities were assisted by fulvic acid. In this study, the biochemical response of Phaeodactylum tricornutum to varying concentrations of inorganic selenium (Se) was investigated. It was observed that, when combined with fulvic acid, P. tricornutum exhibited enhanced uptake and biotransformation of inorganic Se, as well as increased microalgal lipid biosynthesis. Notably, when subjected to moderate (5 and 10 mg/L) and high (20 and 40 mg/L) concentrations of selenite under fulvic acid treatment, there was a discernible redirection of carbon flux towards lipogenesis and protein biosynthesis from carbohydrates. In addition, the key parameters of microalgae-based biofuels aligned with the necessary criteria outlined in biofuel regulations. Furthermore, the Se removal capabilities of P. tricornutum , assisted by fulvic acid, were coupled with the accumulation of substantial amounts of organic Se, specifically SeCys. These findings present a viable and successful approach to establish a microalgae-based system for Se uptake and biotransformation. [ABSTRACT FROM AUTHOR]

The adaptability of cattle to thermal stress has been extensively studied however the exact dynamics of acclimatization is still less investigated. The present study was conducted to assess the acclimatization dynamics in crossbred cattle. In the present experiment non-pregnant dry crossbred cattle (n = 4) were exposed to 25°C and 40°C temperature with a relative humidity of 40–50% in a psychrometric chamber from 10:00 to 15:00 h/day for 21 days. The physiological parameters were recorded and blood samples were collected at 15:00 (after exposure) hours on day 1, 6, 11, 16 and 21. All the studied parameters except T3 altered significantly (P < 0.05) at 40°C temperature as compared to 25°C. At 40°C exposure a significant (P < 0.05) acclimatization response in respiratory rate was first observed on day 11. The dry matter intake increased significantly (P < 0.05) from day 6 onwards whereas water intake decreased at day 21 only. The LDH, AST, ALT activity, urea concentration and redox status did not reach to pre-stress levels even at day 21. Acclimatization in T4 and cortisol levels was observed on day 11 and 16, respectively. It can be concluded that in extreme heat stress conditions an acclimatization period of 6 to 21 days was required in crossbred cattle. [ABSTRACT FROM AUTHOR]

The biochemical biomarkers (Catalase (CAT), glutathione s-transferase (GST), cytochrome P4501A1 (CYP1A1450) activities and glutathione (GSH), malondialdehyde (MDA) levels) of D. polymorpha exposed to the basic blue 41 (BB41) solutions for 24 and 96 h before and after the Fenton process (FTP) were evaluated to investigate the efficiency of the FTP. The optimum conditions for the removal of BB41 were set using central composite design (CCD), which is a response surface methodology (RSM) module in the Design-Expert® software. The optimal conditions were found to be 27.87 min, 3.49 mg/L, and 0.04 for reaction time, initial BB41 concentration, and Fe2+/H2O2 molar ratio, respectively, resulting in maximum (99%) removal efficiency. After FTP, the MDA and GSH levels decreased significantly during the 24 and 96 h. CAT activities were increased after treatment. No statistically significant changes were observed in the CYP1A1 levels after FTP. GST activities decreased during 24 h but increased during 96 h after FTP. CYP1A1450, catalase, GST activities and MDA, GSH levels of D. polymorpha are useful biomarkers to evaluate the efficiency of FTP. This study suggests that BB41 dye must be further treated after the FTP to minimise the ecotoxicological risk. [ABSTRACT FROM AUTHOR]

Background: Mexico is considered the diversification center for chili species, but these crops are susceptible to infection by pathogens such as Colletotrichum spp., which causes anthracnose disease and postharvest decay in general. Studies have been carried out with isolated strains of Colletotrichum in Capsicum plants; however, under growing conditions, microorganisms generally interact with others, resulting in an increase or decrease of their ability to infect the roots of C. chinense seedlings and thus, cause disease. Results: Morphological changes were evident 24 h after inoculation (hai) with the microbial consortium, which consisted primarily of C. ignotum. High levels of diacylglycerol pyrophosphate (DGPP) and phosphatidic acid (PA) were found around 6 hai. These metabolic changes could be correlated with high transcription levels of diacylglycerol-kinase (CchDGK1 and CchDG31) at 3, 6 and 12 hai and also to pathogen gene markers, such as CchPR1 and CchPR5. Conclusions: Our data constitute the first evidence for the phospholipids signalling events, specifically DGPP and PA participation in the phospholipase C/DGK (PI-PLC/DGK) pathway, in the response of Capsicum to the consortium, offering new insights on chilis' defense responses to damping-off diseases. [ABSTRACT FROM AUTHOR]

This study aimed to assess the effect of cadmium (Cd2+) concentrations on biovolume, pigments, malondialdehyde (MDA), hydrogen peroxide, proline, total phenolic compounds, total protein, and total carbohydrate contents of Cladophora glomerata. Cultivations of the alga (8.0 ± 0.1 g as fresh weight) were exposed to 7.5, 15, 30, and 60 mg/L of Cd2+ ions in 500 mL flasks containing 400 mL of the medium on a shaker at 120 rpm for 7 days. Results of Fourier transform infrared analyses indicated that the amide, anionic, and amino groups had significant rolesin the binding of Cd2+ on C. glomerata. The detrimental effects of the Cd2+ dose not only observed the morphology of the algal cell but also changed the biochemical compounds of C. glomerata. Growth gradually decreased when the alga was exposed to Cd2+ at 15 and 60 mg/L in comparison with the control. High Cd2+ ions concentrations decreased in chlorophyll-a (from 14.27 mg/g in control to 9.97 mg/g at 60 mg/L Cd) and protein content (from 43.60 mg/g in control to 21.66 mg/g at 60 mg/L Cd) in the treated cells compared to the control group, whereas they increased stress molecules (e.g., MDA and proline) as biomarkers in the response mechanisms of algae to Cd2+ exposure. Results indicated that this alga had wide tolerance to high cadmium concentrations, and the stress compounds in the alga with exposure of Cd2+ seemed to be parameters as a biomarker for metal-induced oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Primary biliary cholangitis (PBC) is often overlapping with other autoimmune conditions, including systemic lupus erythematosus (SLE). Since the concomitant PBC and SLE are rare, the impacts of SLE on the response and prognosis in ursodeoxycholic acid (UDCA)–treated patients with PBC remain unclear. Methods: A PBC database of 769 patients at West China hospital was used to identify 26 patients with concomitant PBC and SLE. The clinical and biochemical characteristics of these patients were collected and analyzed. Propensity score matching was used to compensate for the differences in age, total bilirubin, and alkaline phosphatase. The biochemical responses and prognoses were compared between the patients with and without concomitant SLE. Results: The female-to-male ratio was 25:1 in the PBC patients with concomitant SLE. Compared with the group with PBC alone, the median hemoglobin and albumin values in the PBC-SLE group at the time of diagnosis of PBC were lower (both P < 0.05). After treatment, the group with PBC alone showed lower alanine aminotransferase and glutamyltransferase values and aspartate aminotransferase/platelet ratio indices at the final visit (all P < 0.05). The Kaplan-Meier estimate showed that the adverse event–free survival did not differ between the patients with and without concomitant SLE (P = 0.564). Conclusion: The results of this retrospective, single-center study suggested that the concomitant SLE status might have a negative impact on the biochemical responses to the treatment, while the effect of concomitant SLE on PBC progression remains to be further defined. Key Points • The prevalence of SLE in the PBC population being in a large PBC cohort was as low as 3.4%. • Compared with PBC-SLE group, the group with PBC alone showed lower alanine aminotransferase and glutamyltransferase values and aspartate aminotransferase/platelet ratio indices at the final visit, indicating that the concomitant SLE may have a negative impact on the biochemical responses to the treatment of PBC. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the effect of copper (as CuSO4, 5H2O) supply (0, 25 and 50 μM) on performance of cilantro (Coriandrum sativum L.) plants grown under hydroponic conditions. All applied Cu concentrations drastically reduced the biomass production, length of the shoots and the roots and disturbed the ions (Cu, Ca, Fe, Zn and Mg) homeostasis. Either Cu-starvation (0 μM) or Cu-toxicity (25 and 50 μM) significantly reduced the net photosynthetic rate, stomatal conductance and transpiration rate resulting in reduced water use efficiency. Under Cu-toxicity, the variations in gas exchange parameters were associated with a remarkable decline in the photosynthetic pigments including Chlorophyll a, Chlorophyllb, Chlorophyll (a + b) and carotenoids. Additionally, an enhanced lipid peroxidation (evaluated as Malondialdehyde (MDA) contents) with a concomitant increase in proline, total soluble sugars and melanoidins contents were observed under these conditions. The increased MDA levels resulted in decrease in total lipid content and alteration of the fatty acid profiles in both shoots and roots with a general tendency toward the accumulation of saturated fatty acids that mirrors a decline in the desaturases activity. Although the increased activity of enzymatic antioxidants including catalase (CAT), gaiacol peroxidase (GPX) and ascorbate peroxidase (APX), the oxidative-induced injuries caused by 25 and 50 μM Cu were found to be irreversible and the optimal growth parameters were not achieved. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis(PBC) is an immune-mediated chronic and progressive intrahepatic cholestasis disease. Treatment with ursodeoxycholic acid(UDCA) can significantly improve the prognosis of patients with PBC, but some patients still have poor response to UDCA, which is the main risk factor for disease progression. Several evaluation models and scoring systems based on biochemical response have been applied to screen out patients with poor response in clinical practice. Integrated traditional Chinese and Western medicine therapy for PBC has certain advantages in improving the symptoms, liver biochemistry, fibrosis indices, and biochemical response rate of PBC patients and thus holds promise for clinical application; however, further improvement is needed for experimental design and efficacy evaluation. [ABSTRACT FROM AUTHOR]

In recent years, lutetium-177 (177Lu)-labeled prostate-specific membrane antigen (PSMA)-617 has become a promising new therapeutic agent in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we report on an early experience of177Lu-PSMA therapy with an evaluation of its efficacy and safety in mCRPC patients. Twenty-one mCRPC patients with a mean age of 70.3 ± 9.6 (54–88)-year-old were treated with one to four therapy cycles (median two cycles) and administered activity of 3.7–29.6 GBq (mean of 15.4 GBq). A prostate-specific antigen (PSA) decline ≥ 50% was considered to be a biochemical response (BCR). To evaluate the clinical response, the Eastern Cooperative Oncology Group (ECOG) status was used. Within 2 weeks before and 1 and 2 months after each therapy cycle, hematology, renal function, liver status, alkaline phosphatase, and PSA were checked. The Common Terminology Criteria for Adverse Events was used for grading adverse events induced by177Lu-PSMA. Furthermore, overall survival (OS) was calculated and analyzed. During the treatment, a BCR was seen in 62% of patients; 19% of patients showed progression and 19% of patients showed stable disease. ECOG status was improved after treatment, and OS was 62.7 weeks. After the treatment, two patients showed Grade II toxicity of white blood cells, Grade I thrombocytopenia was observed in two patients, one patient showed Grade II toxicity in serum creatinine and transient Grade I toxicity in creatinine was seen in two patients. In total, our initial experience demonstrates that177Lu-PSMA therapy has the potential to positively affect the development and maturation of radioligand practices in selected mCRPC patients, even in resource limited, developing country environments. However, some challenges, such as practitioner training, poor initial acceptance by colleagues and financial concerns, particularly in developing nations, still exist. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of acute exposure (96 h) to Cd in gills, digestive gland and muscle of the Tehuelche scallop Aequipecten tehuelchus from San José gulf in Patagonia, Argentina. Scallops were exposed to Cd concentrations of 0, 25, 50, 100, 150, 204, 275, 371, and 500 μg/L, and mortality rates were recorded after 96 h of exposure. Surviving organisms were analyzed for the biochemical response through reactive oxygen and nitrogen species (RONS), activities of catalase (CAT) and glutathione-S-transferase (GST), metallothioneins (MT), lipid peroxidation (LPO) and liposoluble antioxidants α-tocopherol (α-T) and β-carotene (β-C). The mean lethal concentration (LC 50) was 155.8 μg Cd/L, a lower value than other scallops' species, showing that A. tehuelchus has a particular sensitivity to Cd. In the three tissues, at all exposure concentrations, there was no significant response in RONS levels, GST activity or LPO. Nevertheless, CAT activity and α-T levels decreased in the gills but increased in the digestive gland, with no significant response in the muscle. Two-way ANOVA revealed a significant interaction between Cd concentration and tissue on MT, which increased significantly in gills, decreased in digestive gland with 100 compared to 50 μg Cd/L; whereas in muscle a significant increase was observed with 25 μg Cd/L compared to control. The results show a significant effect of Cd in scallop's gills on CAT activity and α-T levels, highlighting this tissue as the primary target against relevant concentrations of metal in seawater. The effect on digestive gland and muscle was minimal. The overall results suggest that Cd toxicity is tissue-specific. This study will help reduce the existence knowledge gap regarding potential impacts of acute exposure to Cd in a bivalve species with high ecological and commercial importance, as well as identifying the most responsive biomarkers associated with Cd stress for monitoring assessment. [Display omitted] • Tehuelche scallop is more sensitive to Cd than other species (LC50: 155.8 μg Cd/L). • CAT and α-T decrease in gills, increase in digestive gland, no response in muscle. • MT significantly rises in gills. • No Cd effect on RONS, GST, or LPO in any tissue. • Gill is the most affected tissue, digestive gland and muscle show no clear response. [ABSTRACT FROM AUTHOR]

Foliar fungal blast and bacterial leaf blight have significant impacts on rice production, and their management through host resistance and agrochemicals has proven inadequate. To achieve their sustainable management, innovative approaches like leveraging the foliar microbiome, which collaborates with plants and competes against pathogens, are essential. In our study, we isolated three Pantoea strains (P. agglomerans Os-Ep-PPA-1b, P. vagans Os-Ep-PPA-3b, and P. deleyi Os-Ep-VPA-9a) from the rice phylloplane. These isolates exhibited antimicrobial action through their metabolome and volatilome, while also promoting rice growth. Our analysis, using Gas Chromatography-Mass Spectrometry (GC-MS), revealed the presence of various antimicrobial compounds such as esters and fatty acids produced by these Pantoea isolates. Inoculating rice seedlings with P. agglomerans and P. vagans led to increased root and shoot growth. Additionally, bacterized seedlings displayed enhanced immunocompetence, as evidenced by upregulated expressions of defense genes (OsEDS1, OsFLS2, OsPDF2.2, OsACO4, OsICS OsPR1a, OsNPR1.3, OsPAD4, OsCERK1.1), along with heightened activities of defense enzymes like Polyphenol Oxidase and Peroxidase. These plants also exhibited elevated levels of total phenols. In field trials, the Pantoea isolates contributed to improved plant growth, exemplified by increased flag-leaf length, panicle number, and grains per panicle, while simultaneously reducing the incidence of chaffy grains. Hypersensitivity assays performed on a model plant, tobacco, confirmed the non-pathogenic nature of these Pantoea isolates. In summary, our study underscores the potential of Pantoea bacteria in combatting rice foliar diseases. Coupled with their remarkable growth-promoting and biostimulant capabilities, these findings position Pantoea as promising agents for enhancing rice cultivation. Graphical Abstract of Rice Foliar-Adapted Pantoea Species: Promising Microbial Biostimulants Enhancing Rice Resilience Against Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae ; three rice phylloplane Pantoea strains: P. agglomerans, P. vagans, and P. deleyi enhanced plant growth and conferred immunocompetence against blast and bacterial blight disease in rice. [Display omitted] • Rice phyllosphere adapted Pantoea agglomerans, P. vagans, and P. deleyi , suppressed rice foliar blast and bacterial blight. • Foliar bacterization significantly elevated the expression of defense genes in rice showcasing heightened immunocompetence. • Bacterization induced defense-associated enzymes, namely Polyphenol Oxidase, Peroxidase, and total phenols, in rice seedlings. • Foliar spray of Pantoea enhanced flag-leaf length, panicles, and grains per panicle, concurrently reducing the chaffy grains. • Hypersensitivity on tobacco, and sorbitol utilization assays confirmed the non-pathogenic nature of Pantoea isolates. [ABSTRACT FROM AUTHOR]

Soil habitat quality is thought to influence metal toxicity via changes in speciation and thereby toxicokinetics. Here, we assessed the toxicokinetic and toxicodynamic effects of habitat quality on mite, Oppia nitens when exposed to zinc (Zn) contaminated soils. Forty-seven soils were ranked into three habitat qualities; high, medium, and low based on biological reproduction of Folsomia candida, Enchytraeus crypticus , and Elymus lanceolatus. From the 47 soils, eighteen soils (comprising of six soils from each habitat quality) were randomly selected and dosed with field relevant concentrations of Zn. Mite survival and reproduction were assessed after 28 days. Total Zn, bioaccessible Zn, Zn bioavailability, Zn body burden, lactate dehydrogenase activity (LDH) and glucose-6-phosphate dehydrogenase (G6PDH) activities of the mites were determined. Zinc toxicity and potency were much less in the high compared to low quality soils and the mites in the high habitat quality soils tolerated higher zinc body burdens (2040 ± 130 μg/g b.w) than the lower habitat quality (1180 ± 310 μg/g b.w). Lower LDH activity (20 ± 2 μU mg−1) in the high quality soils compared to lower quality soils (50 ± 8 μU mg−1) suggested that there was less stress in the high habitat quality mites. Despite changes in speciation across habitat qualities, bioavailability of zinc was similar (∼20%) irrespective of habitat quality. Our results suggest that the influence of soil properties on survival is modulated by toxicodynamics rather than toxicokinetics. Restoring habitat quality may be more important for soil invertebrate protection than metal concentration at contaminated sites. • Habitat quality influenced Zn toxicity to mites through toxicodynamics rather than toxicokinetics. • Potency and toxicity of Zn to mites were lower in high habitat quality soils than low habitat quality soils. • Regardless of Zn speciation differences, Zn bioavailability was similar in all habitat qualities. • Mites in higher habitat quality soils were less stressed than mites in the lower habitat quality soils. [ABSTRACT FROM AUTHOR]

Objective: To assess the proportion of PBC patients with a biochemical response to ursodeoxycholic acid (UDCA) in a population-based cohort and the association of biochemical response with outcomes. Methods: All patients diagnosed with PBC in Iceland from 1991–2015 were identified. Patients taking UDCA for an adequate period of time were analyzed for treatment response according to the Barcelona, Paris I, Paris II and Toronto criteria and outcomes. Results: Overall 182 females and 40 males were diagnosed with PBC and 135 patients were treated with UDCA. Overall 99 (73%) patients had adequate data on UDCA treatment and results of liver tests to assess biochemical response according to the Barcelona criteria, 95 (70%) according to the Toronto criterion and 85 (63%) according to the Paris I and II criteria. In all 74% (n = 63), 67% (n = 64), 54% (n = 53) and 46% (n = 39) responded to treatment according to the Paris I, Toronto, Barcelona and Paris II criteria. Among nonresponders according to the Paris I, Toronto, Paris II and Barcelona criteria, 50%, 39%, 33% and 30% developed cirrhosis versus 10%, 6%, 5% and 11% of responders, HR 5.36 (p =.002), 6.61 (p =.002), 10.94 (p =.003) and 2.21(p =.11), respectively. Age-adjusted mortality was significantly lower among responders according to the Paris I and Paris II criteria, HR 0.33 (p =.02) and 0.31 (p =.02), respectively. Conclusion: Development of cirrhosis and higher mortality was significantly associated with a lack of biochemical response to UDCA. Frequent development of cirrhosis and increased mortality in nonresponders underlines the need for a more effective therapy than UDCA for this sizeable subgroup of patients. [ABSTRACT FROM AUTHOR]

Background & Aims: As surrogate markers for autoimmune hepatitis (AIH), serum alanine aminotransferase (ALT) and immunoglobulin G (IgG) are convenient to measure under immunosuppression. However, the long‐term prognosis of patients who achieve complete biochemical remission (CBR) in comparison with patients who achieve only biochemical remission (BR) is uncertain. Methods: A total of 291 patients (89.7% female) diagnosed with AIH were retrospectively reviewed. CBR was defined as normal ALT and IgG levels with immunosuppression, while BR was defined as normal ALT levels. CBR was further divided into early CBR (<1year) and late CBR (≥1year) by the timing of remission. Liver‐related adverse outcomes including liver‐related death, liver transplantation and hepatocellular carcinoma were evaluated. Results: With immunosuppressive treatment, 222 (76.3%) patients achieved CBR (early CBR: 168 and late CBR: 54). BR was achieved in 55 (18.9%) patients and 14 (4.8%) patients remained non‐remission. With a median follow‐up duration of 6.6 years, the risk of liver‐related mortality was the lowest in patients with CBR, followed by patients with late CBR, BR and non‐response. The cumulative risk of liver‐related adverse outcomes was the highest in patients with non‐response (8.51/100 person‐years [PYs]), followed by BR (1.95/100 PYs), late CBR (1.89/100 PYs) and early CBR (0.75/100 PYs). By multivariable analysis, age, cirrhosis and treatment responses were independently associated with liver‐related adverse outcomes. Conclusions: Patients with CBR within 1 year after treatment initiation had the lowest risk of liver‐related adverse outcomes. Patients with late CBR and those with only BR had a comparable risk of long‐term outcomes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Two strains of non-acidophilic microalgae (NAM) were acclimated to pH 3.0. • Flow cytometry analysis indicated their ability to withstand acidic pH. • Both the acclimated strains yielded good amounts of biomass and neutral lipids. • FTIR analysis confirmed accumulation of more triacylglycerols in NAM strains. • First report on biodiesel production in good amounts by NAM strains at pH 3.0. Abstract The overwhelming response towards algal biodiesel production has been well-recognized recently as a sustainable alternative to conventional fuels. Most microalgae cannot grow well at acidic pH. The present study, therefore, investigated whether non-acidophilic microalgae Desmodesmus sp. MAS1 and Heterochlorella sp. MAS3 can be acclimated to extreme-acidic pH for sustainable production of biomass and biodiesel. Growth analysis indicated that both the microalgal strains possessed a passive uptake of CO 2 at pH 3.0 with biomass production of 0.25 g dry wt. L−1 in Desmodemus sp. and 0.45 g dry wt. L−1 in Heterochlorella sp.. Flow-cytometry analysis for reactive oxygen species, membrane permeability and neutral-lipids revealed the capabilities of both strains to adapt to the stress imposed by acidic pH. Lipid production was doubled in both the strains when grown at pH 3.0. In-situ transesterification of biomass resulted in 13–15% FAME yield in the selected microalgae, indicating their great potential in biofuel production. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Terpene-based acyl-thiourea derivatives were synthetized and exhibit fungicide activity. • Myrtenyl-based acyl-thiourea showed better antifungal activity against T. cucumeris. • Physicochemical properties related to antifungal activity were assessed. • Electronic and steric effects and energy differences markedly affected activity. Abstract The development of efficient terpenoid fungicides and exploration of its action mechanism is of great significance for the prevention and control of agricultural diseases. To confirm our previous findings on naturally occurring antifungal products with ecofriendly features, 40 terpene-based acyl-thiourea derivatives were synthesized and structurally characterized by 1H NMR, ESI-MS, elemental analysis and IR spectroscopy. Their inhibitory activities against several fungi, including Botrytis cinerea , Sclerotinia sclerotiorum and Thanatephorus cucumeris , were assessed by the growth rate method and the in vivo antifungal effects of these compounds against Thanatephorus cucumeris were performed evaluated using detached leaves. The majority of these compounds showed moderate to marked antifungal activities. Of all compounds, myrtenyl-based acylthiourea (8i) displayed more pronounced antifungal activity against Thanatephorus cucumeris (EC 50 = 0.412 mg/L) compared with carbendazim (EC 50 = 0.436 mg/L). In vivo antifungal of compound 8i efficiency against Thanatephorus cucumeris was also excellent. Treatment with 8i of Thanatephorus cucumeris resulted in significantly influenced morphology, markedly increased cell membrane permeability, and reduced ATP amounts and ATPase activity in comparison with untreated controls. A total of four descriptors linking structures and antifungal activities against Thanatephorus cucumeris were determined, including q S max , HOMO - LUMO , log MS and q N max , and employed to build a quantitative structure-activity relationship (QSAR) model (R 2 = 0.9673). Preliminary structure-activity relationship (SAR) and QSAR assessments revealed that electronic and steric effects as well as energy differences of various molecules markedly affected antifungal effects. These findings provide novel insights into the modes of action of terpene-based acyl-thiourea derivatives, which could constitute potential substitutes for current fungicides or leads for novel antifungal agent development. [ABSTRACT FROM AUTHOR]

Non-invasive predictors for the development of cirrhosis-related conditions are needed for patients with primary biliary cholangitis (PBC). We investigated the association between cytokeratin-18 fragments (M30 and M65) and liver histology, treatment response and the development of cirrhosis-related conditions in patients with PBC. We retrospectively reviewed the clinical data of 111 individuals with biopsy-proven PBC. Serum M30 and M65 levels were measured using stored sera. M30 were significantly decreased after treatment, but there was no significant change in the M65 levels. M65 was significantly higher in non-responders according to the Paris-I and Paris-II definitions. In the multivariate analysis, high levels of M65 were significantly associated with advanced Scheuer stage (odds ratio 5.86; 95% confidence interval 0.55-22.2; P = 0.009) and with the development of cirrhosis-related conditions (hazard ratio 3.94; 95% confidence interval: 1.06-14.5, P = 0.039). Among PBC patients without cirrhosis, those with high serum M65 levels at baseline were at higher risk of developing cirrhosis-related conditions (log-rank test; P = 0.001). High levels of serum M65 may be a non-invasive and early predictor of the development of cirrhosis-related conditions in PBC patients. Our findings may help initiate therapies earlier for those at risk for cirrhosis. [ABSTRACT FROM AUTHOR]

Insect damage leads to changes in biochemical profile of plants. Response of three Brassica juncea-fruticulosa introgression lines (already reported resistant to Lipaphis erysimi) in terms of changes in biochemical constituents after aphid infestation was studied along with B. fruticulosa (resistant parent), B. juncea var. PBR −210 (susceptible parent) and B. rapa ecotype brown sarson BSH-1 (susceptible check). These six genotypes were grown under aphid infested and uninfested conditions and were sampled at peak aphid infestation to analyze the biochemical changes caused by aphid feeding from top 10 cm central twig of plant. A significant reduction in glucosinolates content in aphid infested plants of three introgression lines (I8, I79 and I82) was observed while opposite was observed in B. fruticulosa, PBR-210 and BSH-1. Exactly opposite trend was observed for total phenols where aphid infestation resulted in significant increase in phenols content in the three introgression lines while a decrease was observed in B. fruticulosa, PBR-210 and BSH-1. A general trend of decline in flavonols, total sugars and free amino acids content was observed after aphid infestation in all the genotypes. Glucosinolates and total phenols served as biochemical bases of resistance in the three introgression lines since there was downregulation of glucosinolates and upregulation of total phenols as against opposite trend observed in BSH-1 and PBR-210. [ABSTRACT FROM AUTHOR]

In the current study, baseline sensitivity of Valsa mali to propamidine was determined using 80 strains collected from apple orchards in Shaanxi Province, China. The median effective concentration (EC 50 ) values for propamidine inhibiting mycelial growth ranged from 0.086 to 0.852 μg/mL, with a mean of 0.405 ± 0.137 μg/mL. After treated with propamidine, mycelia were contorted with an increased number of branches, loss of fruiting body production, and decreased cell membrane permeability. Moreover, the enzyme activities of the complexes I, II, IV and ATPase in the mitochondrial respiratory chain were increased significantly, while the enzyme activities of complexes III decreased. Importantly, both on detached leaves and branches of apple trees, propamidine applied at 100 μg/mL exhibited over 75% protective and curative efficacies, which were even better than the efficacies obtained by carbendazim at the same concentration. These results indicated that propamidine could be used as an alternative compound in controlling Valsa canker and mitochondrial respiratory chains might be correlated with the action mode of propamidine. This study encourages further investigation for the action mechanism of propamidine against plant pathogens and the information could be valuable for synthesis of new antifungal drugs with novel modes of action. [ABSTRACT FROM AUTHOR]

Increasing concern has been focused on the potential risks associated with the trophic transfer to aquatic organisms of ambient contaminants in the presence of titanium dioxide nanoparticles (nano-TiO 2 ). This study investigated the influence of nano-TiO 2 on the trophic transfer of arsenic ( As ) from the microalgae Nannochloropsis maritima to the brine shrimp Artemia salina nauplii. We found that nano-TiO 2 could significantly facilitate As sorption on N. maritima within an exposure period of 24 h, and this sorption subsequently led to higher As trophic transfer from the algae to A. salina according to trophic transfer factors (TTF As +nano-TiO2  > TTF As ). However, after 48 h of depuration, the retention of As in A. salina fed As- nano-TiO 2 -contaminated algae was even lower than that in A. salina fed As -contaminated algae at the same exposure concentrations. This result indicates that the increased food chain transfer of As in the presence of nano-TiO 2 can be explained by adsorption of As onto nano-TiO 2 in contaminated food (algae), but the bioavailability of As in A. salina is reduced after the introduction of nanoparticles. Although the stress enzyme activities of superoxide dismutase (SOD) and acetylcholinesterase (AChE) in A. salina at a lower As concentration treatment in the presence of nano-TiO 2 were not significantly changed, they increased with higher exposure concentrations of As with or without nano-TiO 2 . Our study highlighted the complex role of nanomaterials in the transfer of ambient contaminants via trophic chains and the potential of nano-TiO 2 to reduce the bioavailability of As via trophic transfer to saltwater zooplankton. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the study was to investigate the effect of a flavonoid‐rich fresh fruit juice on cardiovascular, oxidative stress, and biochemical parameters during the yo‐yo intermittent recovery test (YYIRT). Twenty‐two healthy males subjects participated in this study divided into two groups: An experimental group (EG: n = 11) who consumed the antioxidant supplement and a control group (CG: n = 11). All participants performed two test sessions at 07:00 hr before and after 2 weeks of supplementation with Opuntia ficus‐indica juice. Blood samples were taken before (P1) and immediately (P2) after the YYIRT. Our results showed that following the 2,2‐diphenyl‐1‐ picrylhydrazyl (DPPH●) test, the Opuntia ficus‐indica juice has an antioxidant capacity for capturing free radicals (p < .05) and reducing oxidative stress related to exercise. Concerning biochemical and cardiovascular parameters, our results showed a significant increase on total cholesterol (TC) (p < .01), triglycerides (TG) (p < .05), high‐density lipoprotein (HDL) (p < .01), low‐density lipoprotein (LDL) (p < .01), creatine kinase (CK) (p < .01), lactate deshydrogenase (LDH) (p < .01), glucose (GLC) (p < .01), systolic (SBP), and diastolic blood pressure (DBP) (p < .01) immediately after exercise. However, TC (p < .05), TG (p < .05) and LDL (p < .05), the maximal heart rate (HRmax), the CK (p < .05), and LDH (p < .01) as well as the malondialdehyde (MDA) (p < .01) demonstrated a significant decrease after supplementation of Opuntia ficus‐indica juice before and immediately after YYIRT. However, no significant effect on HDL (p > .05), GLC (p > .05) levels nor the SBP and DBP (p > .05) was observed after supplementation with Opuntia ficus‐indica juice. The supplementation leads to an improvement on YYIRT performance (The total distance covered during the YYIRT, VO2max, VMA) and the rating of perceived exertion (RPE). Opuntia ficus‐indica juice has a potent antioxidant activity that reduces total and LDL‐cholesterol with only a moderate lowering of HDL‐cholesterol and oxidative stress. Moreover, supplementation decreases muscle damage caused by the endurance exercise. [ABSTRACT FROM AUTHOR]

Propamidine is an aromatic diamidine compound. In the current study, baseline sensitivity of Sclerotinia sclerotiorum to propamidine was determined using 78 strains collected from the oilseed rape fields without a previous history of propamidine usage. The median effective concentration (EC 50 ) values for propamidine inhibiting mycelial growth ranged from 0.406 to 3.647 μg/mL, with a mean of 1.616 ± 0.217 μg/mL. There was no correlation between sensitivity to propamidine and sensitivity to dimethachlon or carbendazim. After treated with propamidine, mycelia were thinner with irregular distortion and more branches; cell wall became thicker with uneven distribution of cytoplasm than untreated control. In addition, sclerotia production, cell membrane permeability and oxalic acid content significantly decreased. On detached oilseed rape leaves, propamidine exhibited better control efficacy than carbendazim at the same concentration whether the leaves were inoculated with carbendazim-sensitive or resistant strains. All the results showed that propamidine exhibited strong antifungal activity and potential application in controlling S . sclerotiorum . Importantly, these data will provide more information on understanding the mode of action of propamidine against S . sclerotiorum and should be valuable for development of new antifungal drugs. [ABSTRACT FROM AUTHOR]

Phytophthora blight of pepper caused by Phytophthora capsici Leonian is a destructive disease throughout the world. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to the benzoic acid chemical class. In this study, the sensitivity and biochemical response of P. capsici to cuminic acid was determined. The mean EC50 (50% effective concentration) values for cuminic acid in inhibiting mycelial growth and zoospore germination of the 54 studied P. capsici isolates were 14.54 ± 5.23 μg/mL and 6.97 ± 2.82 μg/mL, respectively. After treatment with cuminic acid, mycelial morphology, sporangium formation and mycelial respiration were significantly influenced; cell membrane permeability and DNA content increased markedly, but pyruvic acid content, adenosine triphosphate (ATP) content, and ATPase activity decreased compared with the untreated control. In pot experiments, cuminic acid exhibited both protective and curative activity. Importantly, POD and PAL activity of the pepper leaves increased after being treated with cuminic acid. These indicated that cuminic acid not only showed antifungal activity, but also could improve the defense capacity of the plants. All the results suggested that cuminic acid exhibits the potential to be developed as a new phytochemical fungicide, and this information increases our understanding of the mechanism of action of cuminic acid against Phytophthora capsici. [ABSTRACT FROM AUTHOR]

Background A complete biochemical response (BR) immediately after surgery could be considered an indicator of optimal cancer control after radical prostatectomy (RP). Objective To evaluate the prognostic value of early postoperative prostate-specific antigen (PSA) levels after RP in patients with lymph node invasion (LNI). Design, setting, and participants The study included 319 prostate cancer patients with LNI who were treated with RP and extended pelvic lymph node dissection (ePLND) at a single institution between 1998 and 2013. All men had complete clinical, pathologic, and follow-up data, including PSA value at 6 wk after surgery. Patients were divided into two groups according to PSA value at 6 wk after surgery: complete BR (PSA <0.1 ng/ml) and PSA persistence (PSA ≥0.1 ng/ml). Outcome measurements and statistical analysis Kaplan-Meier analyses were used to assess 8-yr clinical recurrence (CR) and cancer-specific mortality (CSM) rates according to PSA persistence after RP. Multivariable Cox regression analysis was used to test the association between PSA persistence and CR. Covariates consisted of pathologic Gleason score (≤7 vs ≥8), number of positive nodes, surgical margins status (negative vs positive), and adjuvant therapies (none vs androgen deprivation therapy (ADT) vs adjuvant radiotherapy plus ADT). When we performed multivariable analyses assessing the association between PSA persistence and CSM pathologic Gleason score represented the only covariate due to the low number of events ( n = 13). Results and limitations Overall, 83 patients (26%) had PSA persistence. Men with PSA persistence had higher 8-yr CR and CSM rates than those with complete BR (69% vs 12% and 16% vs 4.2%, respectively; all p ≤ 0.002). This was confirmed in multivariable analyses, where PSA persistence at 6 wk after surgery was an independent predictor of both CR (hazard ratio [HR]: 8.3; 95% confidence interval [CI], 4.73–14.7; p ≤ 0.001) and CSM (HR: 2.16; 95% CI, 1.63–2.86; p ≤ 0.001). Pathologic stage lower than pT3a, biopsy and pathologic Gleason score ≥8, positive surgical margins, and three or more positive lymph nodes were significantly associated with PSA persistence (all p ≤ 0.04). Our study is limited by its retrospective design. Conclusions Early BR can be achieved in approximately 75% of men with LNI submitted to RP and ePLND. PSA assessment early after surgery has an important prognostic role in the prediction of CR and CSM in node-positive patients. A risk stratification of these patients based on PSA persistence could guide physicians to properly select patients who may benefit the most from timely multimodal treatments. Patient summary The risk of clinical recurrence and cancer-specific mortality is heterogeneous in patients with prostate cancer with lymph node invasion. Node-positive patients with complete biochemical response early after surgery share more favorable oncologic outcomes than those with PSA persistence. These results are important to plan the optimal postoperative patient management. [ABSTRACT FROM AUTHOR]

Background: Acute cardiac response to right ventricular pacing is unknown. We aimed to assess the acute haemodynamic, biochemical and hormonal response to asynchronous right ventricular pacing and investigate whether there is a difference between an apical and outflow tract site.Methods: In 21 patients with normal cardiac function, haemodynamics, brain natriuretic peptide and high sensitive troponin T were measured in response to 10minutes of pacing at each site in a randomised crossover fashion and compared.Results: Pacing both sites there were significant increases in pulmonary capillary wedge pressures (p<0.001) and QRS width (p< 0.01). In comparison to baseline, apical pacing demonstrated significant (p<0.05) increases in arterial peptide and troponin levels and venous peptide levels. Outflow tract pacing compared to baseline demonstrated significant (p<0.05) increases in arterial peptide and venous, arterial and coronary sinus troponin. There were no significant differences in responses between sites.Conclusion: Asynchronous right ventricular pacing demonstrated significant increases in filling pressures, cardiac hormonal and biochemical response above baseline with very short durations of pacing (10minutes). There was no difference in response between sites. These findings imply that even very short periods of right ventricular based pacing are potentially deleterious. [ABSTRACT FROM AUTHOR]

This study presents a comparative account of biochemical responses evoked by a high-zinc-accumulating (HZnG) and a low-zinc-accumulating (LZnG) genotype of chickpea ( Cicer arietinum L.) under conditions of zinc deficiency (0 mg ZnSO kg soil) and on exogenous zinc supply (2.5, 5, and 10 mg ZnSO kg soil), at different growth stages (pre-flowering, flowering, and post-flowering) of the crop. Both the genotypes exhibited significant variation in contents of chlorophyll, protein, nitrate, and leghemoglobin, and in the activity of enzymes (nitrate reductase, superoxide dismutase, and carbonic anhydrase), under zinc-limiting condition. The HZnG maintained a significantly higher level of biochemical parameters at deficient zinc levels, while LZnG was more affected by Zn deficiency (with reduced biochemical attributes), compared to HZnG. However, application of soil zinc alleviated the Zn-induced disturbance and improved the biochemical parameters in both genotypes. The differential biochemical response of plants to Zn deficiency indicated existence of genotypic variation in efficient utilization of the available Zn. The HZnG was more effective in overcoming Zn deficiency than the LZnG. This study suggests that metal-dependent biochemical parameters can be used as reliable indices for selection of genotypes with a better Zn utilization capacity, i.e., the Zn-efficient genotypes. [ABSTRACT FROM AUTHOR]

The use of biomarkers to evaluate the biological effects of pollutants in marine organisms represents a recent tool in biomontoring programs. The cyclopoida copepod Apocyclops borneoensis was exposed to different Ni treatments [0 (control), 10, 100, 1000 μg l-1Ni] for 1, 2, 4, 7, 14 days. At each exposure time, acetylchlinesterase (AChE), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione (GSH) were analyzed. Additionally, lipid peroxidation (LPO) level was measured after a 14-day exposure. The results show that Ni treatment significantly stimulated copepod's antioxidants SOD, GST and GSH at environmentally relevant concentrations after a certain exposure time. On the other hand, the exposure time significantly affected SOD and GSH. In contrast, Ni exposure significantly decreased LPO level, implying that the factor involved in LPO might not significantly depend on the operations and functions in the antioxidant defense system. In addition, Ni might also be a neurotoxic agent to copepods via changing AChE activity. [ABSTRACT FROM AUTHOR]

Abstract: Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that mainly targets the cholangiocytes of the interlobular bile ducts in the liver. It is a rare disease with prevalence of less than one in 2000. Its prevalence in developing countries is increasing presumably because of growth in recognition and knowledge of the disease. PBC is thought to result from a combination of multiple genetic factors and superimposed environmental triggers. The contribution of the genetic predisposition is evidenced by familial clustering. Several risk factors, including exposure to infectious agents and chemical xenobiotics, have been suggested. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The prognosis of PBC has improved because of early diagnosis and use of ursodeoxycholic acid, the only established medical treatment for this disorder. When administered at adequate doses of 13-15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. However, some patients do not respond adequately to ursodeoxycholic acid and might need alternative therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective: Anticarcinogenic activity of ribavirin combination therapy for hepatitis C virus (HCV)-related compensated cirrhosis is still unclear. Methods: In study 1, in 157 consecutive patients with HCV-related compensated cirrhosis, treatment efficacy with interferon plus ribavirin therapy was evaluated for 48 weeks of HCV genotype 1b (HCV-1b) or 24 weeks of HCV-2a/2b. In study 2, in 185 consecutive patients with HCV-related compensated cirrhosis, who showed no sustained virological response following the first course of interferon monotherapy, hepatocarcinogenesis rates were evaluated according to the additional treatment, and they were classified into three groups: no treatment, interferon monotherapy, and ribavirin combination therapy. Results: In study 1, in HCV-1b, rates of sustained virological response and sustained biochemical response were 21 and 56%, respectively. In HCV-2a/2b, rates of sustained virological response and sustained biochemical response were 70 and 78%, respectively. In HCV-1b, sustained biochemical response rates were significantly higher than those of sustained virological response. In study 2, the hepatocarcinogenesis rates in ribavirin combination therapy were significantly lower than those in interferon monotherapy and no treatment, respectively. Conclusion: Ribavirin combination therapy for HCV-related compensated cirrhosis reduces the risk of hepatocarcinogenesis in comparison with interferon monotherapy, and higher rates of sustained biochemical response might be associated with lower hepatocarcinogenesis rates. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background & Aims: The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC) correlates with the long-term prognosis and thus could allow the identification of the patients needing new therapeutic approaches. Due to variation in both endpoints and studied populations, there is still no full agreement on the definition of the biochemical response. The aim of our study was to determine, in a population of patients with only early-stage disease, the best biochemical criteria of response to UDCA allowing to predict the absence of poor outcome, as defined by liver-related death, liver transplantation, complications of cirrhosis, or histological evidence of cirrhosis development. Methods: The efficiency of several combinations of serum bilirubin, alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcome was assessed after 1year of UDCA in 165 patients with early-stage PBC followed up for an average 7years. The Barcelona, Paris, Rotterdam, and Toronto criteria were also assessed. Results: The most accurate discrimination of the patients according to the multiple endpoints was given by the following criteria: ALP and AST⩽1.5× upper limit of normal, with a normal bilirubin level. Responders and non-responders were equally distributed, while all adverse events were observed in non-responders (p <0.001). These criteria remained valid when early PBC was defined by both normal bilirubin and albumin concentrations at baseline. Conclusions: This study defines the best efficient biochemical response to UDCA that identifies patients with early PBC at very low risk of long-term development of liver failure or cirrhosis. [ABSTRACT FROM AUTHOR]

Abstract: Lead (Pb) pollution poses great threats to human health and can trigger serious environmental consequences. Athyrium wardii (Hook.), a new plant with the potential for phytostabilization of Pb, was identified in a field survey of plant species in a lead–zinc mine tailing located in Sichuan Province, China. The growth, Pb concentration and some physiological and biochemical characteristics of mining ecotypes (ME) and non-mining ecotypes (NME) were analyzed by pot experiment employing different concentrations of Pb(NO3)2 in tested soil during four weeks period. The results showed that the A. wardii has a higher tolerance to excessive levels of Pb soil contamination. The concentrations of Pb in the shoots and roots of the ME were 3.5 and 3.0 times higher, respectively, than those of the NME when plants were supplied with Pb at 800mgPbkg−1. A. wardii of ME showed higher bio-activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) and lower concentrations of malondialdehyde (MDA) and membrane permeability under higher Pb levels, while the opposite tendency was observed in NME. These findings demonstrated that the mining ecotype of A. wardii has the potential for phytostabilization of Pb contaminated soils. [Copyright &y& Elsevier]

Truusalu K, Kullisaar T, Hütt P, Mahlapuu R, Aunapuu M, Arend A, Zilmer M, Mikelsaar R-H, Mikelsaar M. Immunological, antioxidative, and morphological response in combined treatment of ofloxacin and Lactobacillus fermentum ME-3 probiotic in Salmonella Typhimurium murine model. APMIS 2010; 118: 867-72. We aimed to elucidate the immunological (cytokines), biochemical (antioxidative), and patho-morphological responses in the gut and liver evoked by the addition of Lactobacillus fermentum ME-3 to ofloxacin (OFX) treatment in an experimental infection model of Salmonella enterica serovar Typhimurium. After challenge with S. Typhimurium and treatment according to different schemes, either with OFX and/or addition of L. fermentum ME-3, the mice were killed. Blood, liver, spleen, and small intestine samples were plated to detect S. Typhimurium and lactobacilli. Histological slides were prepared from the liver and ileum. The cytokines (IL-10, IFN-γ, and TNF-α), the glutathione peroxidase and reductase, the glutathione ratio, and the lipid peroxides (LPO) in mucosa of the small intestine and liver were estimated. The addition of L. fermentum ME-3 to OFX increased the eradication of S. Typhimurium from tested sites because of antagonistic and antioxidative properties, reduced the presence of typhoid nodules in the liver, and decreased the values of LPO. The immunological response included the reduction of pro-inflammatory cytokines interferon-γ and tumour necrosis factor-α and the increase in anti-inflammatory cytokine interleukin-10 in the livers of mice without typhoid nodules. [ABSTRACT FROM AUTHOR]