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Background and Aims: Current treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier., Methods: Five hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion., Results: A new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC., Conclusions: Xi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches., (© 2022. The Author(s).)

As filter-feeders, bivalves naturally come into direct contact with microcystins (MCs) in eutrophic water bodies suffering from cyanobacteria blooms. To date, however, no studies have quantified the dynamics of microcystin accumulation and depuration in the edible freshwater bivalve Corbicula fluminea when exposed to dense bloom concentrations of Microcystis aeruginosa, while considering dynamic changes of biochemical indexes and feeding structure. In the present study, the bioaccumulation and detoxification of microcystin-LR (MC-LR) in C. fluminea were investigated. Our results showed that C. fluminea would graze equally efficiently on green algae and M. aeruginosa, irrespective of whether the M. aeruginosa strains were toxic or non-toxic. MCs could be accumulated and depurated by C. fluminea efficiently. In addition, linear and exposure time-dependent MC-LR accumulation patterns were observed in C. fluminea. Activities of biotransformation (glutathione S-transferase, GST) and antioxidant enzymes (superoxide dismutase, SOD, and catalase, CAT) and malondialdehyde (MDA) contents in various tissues of treated clams were stimulated by MCs in a tissue-specific manner. Our findings indicated that C. fluminea hepatopancreas was the primary target organ for MC-LR detoxification processes, as evidenced by a significant increase in GST activity. Besides, gills and mantle were more sensitive than the other tissues to oxidative stress in the initial microcystin exposure period with a significant increase in SOD activity. The scanning electron microscopy (SEM) observations revealed that the lateral cilia in the gill aperture were well developed during the MCs exposure period, which could perform the filter-feeding function instead of the damaged frontal cilium. This study provides insight into the possible tolerance of C. fluminea exposed to dense bloom concentrations of M. aeruginosa., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Understanding the response of medicinal plants to elevated CO 2 concentrations is crucial to evaluate the climate change impacts on medicinal plant's productivity together with the accumulation of biochemical constituents counting nutrients wealth. The present study investigated the effect of elevated CO 2 concentrations (ambient-~400±4, 600±12, and 800±16 μmol CO 2 mol -1 ) on the biochemical constituents (viz. chlorophyll, carotenoids, ascorbic acid, protein, total sugars, and carbon partitioning) and accumulation of mineral nutrients (viz. potassium, phosphorus, and magnesium) in different plant parts (viz. leaf, stem, and root) of Asparagus racemosus Willd., an endangered medicinal plant species. The results confirmed that the elevated CO 2 concentration significantly (p ≤ 0.05) enhanced the leaves biochemical constituents, viz. chlorophyll, protein, total sugars, and carbon content while conversely diminishes the ascorbic acid content in leaf. The accumulation of nutrients especially potassium and magnesium were significantly (p ≤ 0.05) improved while it is reverse in case of phosphorus under the elevated CO 2 concentration. Moreover, elevated CO 2 notably altered protein, sugars, carbon, and nutrients partitioning in leaf, stem, and root tissues. This study will be helpful in anticipating the effect of rising atmospheric CO 2 concentration on medicinal and threatened plants and require further intensive studies to comprehend the effects of elevated CO 2 concentration., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed., Methods: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment., Results: Kaplan-Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293-12.054, p = 0.016 and HR 6.040, 95% CI 1.969-18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231-88.936, p = 0.032 and HR 10.824, 95% CI 1.252-93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008-1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919-0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098-12.128, p = 0.035) at the time of diagnosis., Conclusions: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients.

This study focused on the study of earthworm survival, growth, reproduction, enzyme activities, and protein contents to evaluate and predict the effects of different soil pH levels and determine the optimal risk assessment indicators for the effects. Survival rate, growth rate, and cocoon number as well as four enzyme (glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)) activities and two proteins (total protein (TP) and metallothionein (MT)) contents in earthworms were determined to characterize the responses of earthworm activity to five soil pH levels. These biological datasets (survival, growth, and reproduction) were compared with biochemical indexes (GSH-PX, SOD, POD, CAT, TP, and MT), mainly using biphasic dose-response models. The results indicated that the soil pH value had significant inhibitory effects on the survival, growth, and reproduction of earthworms beginning with 3.0, 4.0, and 5.2, respectively. The dose-response models (J-shaped and inverted U-shaped curves) statistics indicated that the critical values (EC ZEP ) of the GSH-PX, SOD, POD, CAT, TP, and MT inhibited by soil acid stress were 3.46, 3.76, 3.35, 3.54, 3.50, and 3.96 (average 3.60), respectively. In the present study, the fitting curve analysis showed that the responses of the CAT activities and TP and MT contents in earthworm in response to soil pH have the behavior of hormesis.

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.

In this study, crucian carp (Carassius auratus) was exposed to the increasing concentrations of municipal sewage treatment plant effluent (MSTPE) for 15 days, and the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and acetylcholinesterase (AChE), together with the contents of malondialdehyde (MDA) and glutathione (GSH) in the liver of C. auratus were investigated. Moreover, the integrated biomarker response (IBR) approach was applied to assess the adverse effects of MSTPE in freshwater. The aim of the study was to provide an effective biological indicator for evaluating the toxicity effects and ecological risks of MSTPE in the freshwater environment quantitatively. Results showed that MSTPE could cause oxidative damage to the liver of C. auratus, which reflected through the increasing MDA content over the exposure period. MSTPE also led to the biochemical responses of antioxidant defense in C. auratus liver, such as the enhancement of SOD, CAT, and GPx activities, as well as the inhibition of AChE activity and GSH content. It was found that MDA, SOD, GPx, and GSH could be used as the biomarkers for reflecting the adverse effects of MSTPE in the receiving freshwater on the 12th day of exposure. A significant increase of IBR values was observed as the increasing concentration of MSTPE, and the IBR values presented a significant positive correlation (r = 0.891, P < 0.05) with the increasing concentrations of MSTPE, indicating that IBR approach is a promising tool for assessing the toxicity effects of MSTPE in environmental freshwater.

In order to evaluate the potential ecological risk and the toxic effect of landfill leachate (LL), Phanerochaete chrysosporium was exposed to LL and their biochemical response was observed by using antioxidant parameters. Phanerochaete chrysosporium, ME 446, was kept at 4 °C after being sub-cultured at 28 °C on Sabouraud Dextrose Agar (SDA). Superoxide dismutase (SOD), catalase (CAT) activities, and malaondialdehyde (MDA) and glutathione (GSH) levels of P. chrysosporium exposed to different dilution rates of leachate (1/10 and 1/20) for 24 and 96 h were analyzed by using the ELISA method. The physiochemical parameters such as pH, conductivity, total dissolved solids (TDS), dissolved oxygen (DO), chemical oxygen demand (COD) of leachate, and reference water were analyzed by using the YSI Professional Plus handheld multiparameter meter. In this study, SOD activities were decreased in the application groups compared with the Control Group at the 24th and 96th hours. CAT activities and GSH levels increased in the application groups compared with the Control Group at the 24th hour but decreased at the 96th hours. MDA levels increased in all of the application groups when compared with the Control Group for both 24 and 96 h. Different concentration of LL induces oxidative stress in P. chrysosporium, increased CAT activity and MDA levels, and decreased SOD activity and GSH levels.

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.

Agricultural utilization of sewage sludge (SS) and fly ash (FA) has become both, a common practice and an alternative disposal method for these wastes all around the world. The present study was conducted to assess the effect and viability of co-application of SS and FA (SLASH) in four mixing ratios denoted as A [4 (SS): 1(FA)], B [4 (SS): 2 (FA)], C [4 (SS): 3 (FA)] and D [4 (SS): 4(FA)] at three application rates viz. 20, 40 and 60% (w/w) with agricultural soil on biochemical, physiological and growth response of Palak (Beta vulgaris L. var. Allgreen H-1), a commonly used green leafy vegetable. SLASH amendment modified the physico-chemical properties of soil and increased the concentration of heavy metals (Cd, Cr, Cu, Fe, Ni, Pb, Zn) in soil and plant parts however, within the Indian permissible limit except for Cr, Cd and Zn in shoot. Experimental results revealed decrease in morphological and growth parameters such as root and shoot length, leaf area, root, shoot biomass etc. Lipid peroxidation, ascorbic acid, proline and protein content increased however, total chlorophyll and carotenoid content decreased indicating towards heavy metal stress induced biochemical and physiological response in Palak plants. Significant increase in yield was seen in some of the treatments viz. three mixing ratios B, C and D, with maximum increment shown by mixture D at 20 and 40% amendment rate. The results of this study suggest that though SLASH amendment for growing Palak improved the physico-chemical properties of soil amended and also the yield of the plants in some treatments, it may not be a good option due to risk of contamination of heavy metals such as Cr, Cd and Zn showing higher accumulation.

The individual and combined biochemical responses of erythromycin and ketoconazole have been examined in an organism representative of the aquatic environment, crucian carp (Carassius auratus). The possible interactions between erythromycin and ketoconazole were investigated on the bioaccumulation and the expression of biotransformation enzymes 7-ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST), and an antioxidant defense enzyme superoxide dismutase (SOD) in fish tissues. After 14 days of combined exposure (erythromycin + ketoconazole), the addition of ketoconazole at nominal concentrations of 0.2, 2, and 20 μg/L significantly increased the accumulation of erythromycin in fish bile; however, elevated erythromycin accumulation levels were not observed in the other test tissues. The inductions of EROD and SOD activity to erythromycin were inhibited by the combined exposure of ketoconazole in most cases; however, the GST activity returned to normal with exposure time and concentration of combined administration. From the tested pharmaceutical mixtures, it indicated that certain specific combinations may pose some perturbations in biochemical responses in fish and also provide a better understanding of the effects of toxic mixtures.