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Type 1 autoimmune hepatitis (AIH-1) is an organ-specific autoimmune liver disease for which no tissue-specific autoantigen has yet been identified. We examined the reactivity by sensitive immunoblotting with enhanced chemiluminescence (IB-ECL) of 43 sera from patients with AIH-1 and 182 sera from patients with other diseases on hepatocyte plasma membrane derived from rat or human liver (RHPM, HHPM) and separated by aqueous two-phase partition. The sera studied were from patients with AIH-1, primary biliary cirrhosis, chronic viral hepatitis, and systemic lupus erythematosus (SLE); and from normal subjects. Specificity of reactivity by IB-ECL was sought: (i) by testing sera on human or rat liver membrane; (ii) by testing sera on liver or kidney membrane; (iii) by serial titration of reactive sera; and (iv) by testing reactive sera from AIH-1 before and after successful treatment with prednisolone. The results were that in AIH-1 there were multiple reactive components which were not species-specific, since they were detected with both RHPM and HHPM, but were mostly tissue-specific for liver. There was no significant correlation between antinuclear antibodies (ANA) titer and the frequencies of sera reactivities against RHPM. Most of these reactive components were demonstrable at a lesser frequency in other liver diseases and in SLE. There was a striking decrease in reactivity by IB-ECL of AIH-1 sera with liver membrane after clinical remission, further suggesting that differences between AIH-1 and other inflammatory liver diseases and SLE are predominantly quantitative rather than qualitative. However, our study did point to candidate liver membrane antigens with molecular sizes of 136, 116, 81, and 49 kDa, additional to components previously described by others. The molecular identification of these prominent reactants with AIH-1 sera could prove informative for ascertaining pathogenesis. [ABSTRACT FROM AUTHOR]

A 58-year-old Japanese man was admitted complaining of abdominal pain. An abdominal computed tomography examination demonstrated a tumor in the head of the pancreas and multiple calcifications. A laparotomy was performed and the tumor was removed by Whipple's operation. Histologically, the neoplasm that invaded the duodenal wall and the papilla of Vater was composed of nests of malignant squamous cells with intercellular bridges and showed the formation of keratinized pearls with a small area of concurrently neoplastic glandular and squamous elements. On the basis of these features, the diagnosis of adenosquamous carcinoma of the pancreas was made. The patient died 18 months after the operation. The neoplastic behavior of this rare primary pancreatic carcinoma is similar to that of duct cell carcinoma as well as pure squamous cell carcinoma of the pancreas. As the pancreas can be the target of metastases of squamous carcinomas from other organs it is wise to be aware of this rare entity. [ABSTRACT FROM AUTHOR]

In the integrated circuit manufacturing process, reverse osmosis (RO) membranes are widely used for wastewater reclamation. However, fouling by typical surfactants significantly reduces membrane efficiency and lifespan. This study investigates the fouling mechanisms of typical surfactants-cetyl trimethyl ammonium bromide (CTAB, cationic), sodium dodecyl sulfate (SDS, anionic), and polyoxyethylene octyl phenyl ether (TX, nonionic)-on RO membranes. Quartz crystal microbalance analysis results show that CTAB and TX exhibit significantly stronger adhesion to RO membranes than SDS. The order of adsorption mass on the membrane surface is CTAB > TX > SDS, with CTAB causing the most severe fouling. Molecular dynamics (MD) simulations indicate that unclustered CTAB molecules contribute to severe fouling by inserting into the membrane surface. As surfactant concentration increases, clustered CTAB is less likely to enter the membrane's surface layer. A comparison of oxidative technologies-continuous dual-wavelength ultraviolet (VUV/UV), intermittent VUV/UV, and intermittent VUV/UV with chlorine, ozone alone, chlorine alone, and ozone combined with chlorine (ozone/chlorine)- reveals that pre-treating surfactants with ozone/chlorine (simultaneous dosing at 10 mg/L each) before membrane filtration effectively controls fouling. After 30 min of treatment, 29 % of CTAB and 86 % of TX were degraded, respectively. Ozone/chlorine oxidation significantly alleviates membrane fouling, increasing the normalized steady-state permeate flux (J pss ) of CTAB and TX by 245 % and 151 %, respectively. The extended Derjaguin-Landau-Verwey-Overbeek theory calculations and MD simulations show that oxidation weakens the adhesion of CTAB and TX to RO membranes, reducing fouling. Ozone/chlorine treatment also effectively mitigates membrane fouling in actual wastewater from the electronics industry. Post-oxidation, the flux ratio (J/J 0 ) increased from 0.28 to 0.52, resulting in a 116.7 % improvement in the J pss . This study combines experimental data, theoretical calculations, and MD simulations, highlighting the significance of molecular clustering in surfactant-induced fouling before and after oxidation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Resistant bacteria have always been of research interest worldwide. In the urban water system, the increased disinfectant usage gives more chances for undesirable disinfection-resistant bacteria. As the strongest oxidative disinfectant in large-scale water treatment, ozone might select ozone-resistant bacteria (ORB), which, however, have rarely been reported and are inexplicit for their resistant mechanisms and physiological characteristics. In this study, six strains of ORB were screened from a water reclamation plant in Beijing. Three of them (O7, CR19, and O4) were more resistant to ozone than all previously reported ORB or even spores. The ozone consumption capacity of extracellular polymeric substances and cell walls was proved to be the main sources of bacterial ozone resistance, rather than intracellular antioxidant enzymes. The transcriptome results elucidated that strong ORB possessed a combined antioxidant mechanism consisting of the enhanced transcription of protein synthesis, protein export, and polysaccharide export genes ( LptF , LptB , NodJ , LivK , LviG , MetQ , MetN , and GltU ). This study confirmed the existence of ORB in urban water systems and brought doubts to the idea of a traditional control strategy against chlorine-resistant bacteria. A salient "trade-off" effect between the ozone resistance and propagation ability indicated the weakness and potential control approaches of ORB.

Emerging electrochemical disinfection techniques provide a promising pathway to the biofouling control of reverse osmosis (RO) process. However, the comparative effectiveness and mechanism of it under flow-through conditions with low voltage remains unclear. This study investigated the effect of a flow-through electrode system (FES) with both direct current (DC) and alternating pulse current (AC) on RO biofouling control compared with chlorine disinfection. At the initial stage of biofouling development, the normalized flux of AC-FES (67% on Day 5) was saliently higher than the control group (56% on Day 5). Subsequently, the normalized fluxes of each group tended similarity in their differences until the 20th day. After mild chemical cleaning, the RO membrane in the AC-FES group reached the highest chemical cleaning efficiency of 58%, implying its foulant was more readily removable and the biofouling was more reversible. The biofouling layer in the DC-FES group was also found to be easily cleanable. Morphological analysis suggested that the thickness and compactness of the fouling layers were the major reasons for the fouling behavior difference. The abundance of 4 fouling-related abundant genera (>1%), which were Pseudomonas, Thiobacillus, Sphingopyxis, and Mycobacterium exhibited a salient correlation with the biofouling degree. The operating cost of FES was also lower than that of chlorine disinfection. In summary, AC-FES is a promising alternative to chlorine disinfection in RO biofouling control, as it caused less and easy-cleaning biofouling layer mainly due to two advantages: a) reducing the regrowth potential after disinfection of the bacteria, leading to alleviated initial fouling, (b) reshaping the microbial community to those with weaker biofilm formation capacity., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023. Published by Elsevier Ltd.)

With the increasingly serious shortage of water resources globally, it has been paid more attention on how to secure the biosafety of reclaimed water and other non-traditional water sources. However, the 3 most applied disinfection technics, which are chlorine, ultraviolet (UV), and ozone disinfection, all have their disadvantages of selecting undesired bacteria and low energy utilization efficiency. Electrode disinfection is a promising solution, but the current electrode disinfection process still needs to be optimized in terms of the use conditions of the configuration reactivation. In this paper, we built a flow electrode system (FES). To evaluate the disinfection techniques more precisely, we isolated ultraviolet-resistant bacteria (URB) bacteria from the water of the full-scale water plant and tested the disinfection performance of FES and UV. The inactivation rate, reactivation potential, and energy consumption were analyzed. FES could inactivate 99.99 % of the URB and cause irreversible damage to the residual bacteria. FES could make all bacteria strains apoptosis in the subsequent 24 h of storage after alternating pulse current (APC) treatment, 3 V, within 27.7 s. Besides, the energy consumption of FES is about 2 orders lower than that of UV disinfection under the same inactivation rate. In summary, APC-FES is an efficient and low-carbon alternative for future water disinfection, which could achieve the ideal disinfection effect of a high inactivation rate, no reactivation, and low energy consumption., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier B.V. All rights reserved.)

With the widespread use of chlorine disinfection, chlorine-resistant bacteria (CRB) in water treatment systems have gained public attention. Bacterial chlorine resistance has been found positively correlated with extracellular polymeric substance (EPS) secretion. In this study, we selected the most suitable CRB controlling method against eight bacterial strains with different chlorine resistance among chloramine, ozone, and ultraviolet (UV) disinfection, analyzed the resistance mechanisms, clarified the contribution of EPS to disinfection resistance, and explored the role of carbon source metabolism capacity. Among all the disinfectants, UV disinfection showed the highest disinfection capacity by achieving the highest average and median log inactivation rates for the tested strains. For Bacillus cereus CR19, the strain with the highest chlorine resistance, 40 mJ/cm 2 UV showed a 1.90 log inactivation, which was much higher than that of 2 mg-Cl 2 /L chlorine (0.67 log), 2 mg-Cl 2 /L chloramine (1.68 log), and 2 mg/L ozone (0.19 log). Meanwhile, the UV resistance of the bacteria did not correlate with EPS secretion. These characteristics render UV irradiation the best CRB controlling disinfection method. Chloramine was found to have a generally high inactivation efficiency for bacteria with high chlorine-resistance, but a low inactivation efficiency for low chlorine-resistant ones. Although EPS consumed up to 56.7% of chloramine which an intact bacterial cell consumed, EPS secretion could not explain chloramine resistance. Thus, chloramine is an acceptable CRB control method. Similar to chlorine, ozone generally selected high EPS-secreting bacteria, with EPS consuming up to 100% ozone. Therefore, ozone is not an appropriate method for controlling CRB with high EPS secretion. EPS played an important role in all types of disinfection resistance, and can be considered the main mechanism for bacterial chlorine and ozone disinfection resistance. However, as EPS was not the main resistance mechanism in UV and chloramine disinfection, CRB with high EPS secretion were inactivated more effectively. Furthermore, carbon source metabolism was found related to the multiple resistance of bacteria. Those with low carbon source metabolism capacity tended to have higher multiple resistance, especially to chlorine, ozone, and UV light. Distinctively, among the tested gram-negative bacteria, in contrast to other disinfectants, chloramine resistance was negatively correlated with EPS secretion and positively correlated with carbon source metabolism capacity, suggesting a special disinfection mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Membrane fouling is the Achilles' heel of the reverse osmosis (RO) system for high-quality reclaimed water production. Previous studies have found that after the significant selection effect of traditional disinfection, the remaining disinfection-residual bacteria (DRB) may possess more severe biofouling potentials. To provide more constructive advice for the prevention of biofouling, we compared the RO membrane fouling characteristics of DRB after using five commonly used disinfection methods (NaClO, NH 2 Cl, ClO 2 , UV, and O 3 ) and two novel disinfection methods (K 2 FeO 4 and the flow-through electrode system (FES)). Compared with the control group (undisinfected, 21.1 % flux drop), the UV-DRB biofilm aggravated biofouling of the RO membrane (23.4 % flux drop), while the FES, K 2 FeO 4 , and NH 2 Cl treatments showed less severe biofouling, with final flux drops of 6.9 %, 8.1 %, and 8.1 %, respectively. Adenosine triphosphate (ATP) was found to be a capable indicator for predicting the biofouling potential of DRB. Systematic analysis showed that the thickness and density of the DRB biofilms were most closely related to the different fouling degree of RO membranes. Moreover, the relative abundance of bacteria with higher extracellular polymeric substance (EPS) secretion levels, such as Pseudomonas and Sphingomonas, was found closely related with the biofouling degree of RO membranes., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ultrafiltration (UF) was often used as pretreatment in front of reverse osmosis (RO) unit because of its high rejection efficiency of microbes and particles. However, in some cases UF pretreatment might show adverse effects on the RO membrane flux. In this study, the effects of UF pretreatment on secondary effluent water quality and its RO membrane fouling characteristics were explored. There was almost no change of water quality after UF with different molecular weight cut-off (MWCO) membranes (100, 30 and 10 kDa), including total dissolved solid (TDS), alkalinity, conductivity, ion concentrations, etc., while pH increased a little and dissolved organic carbon (DOC) declined by about 1 mg/L. On the contrary, the RO membrane flux of UF permeates presented clear decline in comparison to the secondary effluent. The membrane fouling velocity and steady-state flux of secondary effluent was 0.052 and 0.656, while fouling velocity increased (0.077, 0.071, 0.067) and steady-state flux decreased significantly (0.397, 0.416, 0.448) after 100, 30, 10 kDa UF membrane pretreatment. Scanning electron microscope (SEM) images showed many crystals on the fouled membrane surfaces, which turned out to be CaCO 3 by Energy dispersive spectrometer (EDS) analysis and precipitation calculation. After the addition of UF retentates to UF permeates, scaling was prevented and crystals on the RO membrane almost disappeared, which implied the anti-scaling effect of the UF retentates with low concentration. According to anti-scaling performance experiments, the anti-scaling performance of 100 k, 30 k, 10 k retentates was 2.7%, 4.0% and 7.3%, respectively. Excitation emission matrix (EEM) and fourier transform infra-red (FTIR) results showed that these retentates retained by different MWCO membranes were similar and composed of protein-like substances and soluble microbial products. The effect of key minority components in RO system deserved further exploration., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Adsorption and coagulation were commonly used to alleviate reverse osmosis (RO) membrane fouling caused by dissolved organic matters (DOM), but the effects of changed composition and structure of DOM in dyeing wastewater after adsorption and coagulation on RO membrane fouling have seldom been studied. This study aimed at resolving the mechanism how the RO membrane fouling during dyeing wastewater treatment was alleviated by using adsorption and coagulation. The dyeing wastewater caused serious RO membrane fouling. Pretreatment with granular activated carbon (GAC), polyferric sulfate (PFS) and polyaluminum chloride (PACl) were conducted. It was shown that GAC could remove most of the DOM (95%) and preferred to adsorb protein, hydrophobic neutrals and fluorescent compounds. Both coagulants of PFS and PACl preferred to remove polysaccharides (the removal rate was 9-19% higher than that of DOM), high-MW compounds and these compounds with high fouling potential. Afterwards, the RO membrane fouling potential of the dyeing wastewater was tested. The GAC and PFS performed well to alleviate fouling. After GAC treatment, the decline rate of RO flux was similar to that of raw wastewater after 6-fold dilution. With pretreatment by PFS or PACl, the fouling potential of dyeing wastewater was much lower than that of raw wastewater after diluted to the same DOM content. Changes in polysaccharides content in the DOM had more effects on RO membrane fouling than that of proteins after these pretreatment. Although the DOM changed significantly after pretreatment, the fouling type was still intermediate blocking., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chlorine disinfection is often used as a pretreatment technology to control biofouling of reverse osmosis (RO) membranes. However, previous studies showed that biofouling of the RO system was aggravated after chlorine disinfection. Chlorine-resistant bacteria (CRB) were presumed to be closely related to the aggravation of fouling caused by chlorine disinfection. In order to analyze the membrane fouling mechanisms of CRB, 5 CRB strains were isolated from the surface of fouled RO membranes for wastewater reclamation, and 3 reference bacterial strains, Sphingopyxis soli BM1-1, Pseudomonas aeruginosa PAO1 and Escherichia coli CGMCC1.3373, were selected for comparative study. The chlorine resistance, membrane fouling potential, secretion and adhesion characteristics of these strains were evaluated. Among these isolated strains, 3 strains showed much higher chlorine resistance than PAO1 under the condition of 0.5, 2, 5 mg/L-Cl 2 , especially Bacillus CR19 and Bacillus CR2. Furthermore, a significant positive correlation was found between membrane fouling potential and chlorine resistance of all the strains in this study. The membrane fouling potential of the above 8 strains increased monotonically with the increase of chlorine resistance (under the condition of 0.5 mg/L-Cl 2 ). Serious fouling caused by extracellular substances was observed in biofouling layers of the strains with high chlorine resistance, which lead to more severe flux decline. Extracellular polymeric substances (EPS) amount per cell was found to be the main factor related to the chlorine resistance as well as the fouling potential. Computational fluid dynamics (CFD) simulation was used to demonstrate the filtration resistance induced by the secretion of EPS. However, CRB with higher EPS amount may not show higher membrane adhesion potential, and thus may not be the dominant strain on the RO membranes before chlorine disinfection. These CRB with high fouling potential but low membrane adhesion potential, such as Bacillus CR19 and Bacillus CR2, may become the dominant bacteria on the membrane surface after chlorine disinfection and thus aggravate membrane fouling significantly., (Copyright © 2021. Published by Elsevier Ltd.)

Fouling of RO membranes has long been a complex but inevitable problem in wastewater reclamation. In this study, a modified intermediate blocking model with two parameters was applied to describe the flux change of RO membranes treating various water samples, including municipal secondary effluent, treated industrial wastewater, surface water, and groundwater. The model was validated by 55 sets of data reported by 13 articles, and the results were promising, with 90% of the determination coefficient (R 2 ) exceeding 0.90. Relatively large flux and high operational pressure were found likely to aggravate membrane fouling. Treated industrial wastewater had the highest fouling potential (fouling constant k: 0.061-2.433) compared to municipal wastewater secondary effluent, surface water, and groundwater, even with similar dissolved organic carbon concentration. With industrial wastewater excluded, water samples exhibited lower fouling potential than organic matter solutions, with the majority (25%∼75%) of k distributing in 0.03-0.12, much lower compared to the major k range of the latter (0.05-0.28). This suggested a deviation in fouling behaviors between model organic matters and real water samples. Xanthan gum and guar gum were proposed to be model polysaccharides based on their model parameters, which were relatively close to real water samples., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Membrane fouling is a prominent problem that hinders the stable and efficient operation of the reverse osmosis (RO) system for wastewater reclamation. Previous studies showed that chlorine disinfection, which was commonly used in industrial RO systems as pretreatment, could lead to significant change in microbial community structure and resulted in serious biofouling. In order to prevent biofouling during wastewater reclamation, the effect of ultraviolet (UV) disinfection on RO membrane fouling was investigated and the mechanism was also revealed in this study. With the disinfection pretreatment by UV of 20, 40 and 80 mJ/cm 2 , the bacteria in the feed water were inactivated significantly with a log reduction of 1.11, 2.55 and 3.61-log, respectively. However, RO membrane fouling aggravated with higher UV dosage. Especially, in the group with the UV dosage of 80 mJ/cm 2 , the normalized RO membrane flux decreased by 15% compared with the control group after 19-day operation. The morphology of the fouled RO membranes indicated serious biofouling in all groups. The analysis on the microbial amount of the foulants showed that the heterotrophic plate counts (HPC) and ATP content on the fouled RO membranes with and without UV disinfection were at the same level. However, the total organic carbon content of the foulants with the UV dosage of 40 and 80 mJ/cm 2 was significantly higher than the control group, with higher content of proteins and polysaccharides as indicated by EEM and FTIR spectrum. Microbial community structure analysis showed that some typical UV-resistant bacteria were selected and remained on the RO membrane after disinfection with high UV dosage, including. These residual bacteria after disinfection with high UV dosage showed higher extracellular polymeric substances (EPS) secretion compared with those without UV disinfection, and thus aggravated RO membrane fouling. Thicker EPS could decrease the transmission of UV rays, and thus bacteria with higher EPS secretion might be selected after UV disinfection., Competing Interests: Declaration of Competing Interest There is no financial and personal relationship with other people or organizations that could inappropriately influence the current work., (Copyright © 2021. Published by Elsevier Ltd.)

Chlorine-resistant bacteria (CRB) are commonly defined as bacteria with high resistance to chlorine disinfection or bacteria which can survive or even regrow in the residual chlorine. Chlorine disinfection cannot completely control the risks of CRB, such as risks of pathogenicity, antibiotic resistance and microbial growth. Currently, researchers pay more attention to CRB with pathogenicity or antibiotic resistance. The microbial growth risks of non-pathogenic CRB in water treatment and reclamation systems have been neglected to some extent. In this review, these three kinds of risks are all analyzed, and the last one is also highlighted. In order to study CRB, various methods are used to evaluate chlorine resistance. This review summarizes the evaluating methods for chlorine resistance reported in the literatures, and collects the important information about the typical isolated CRB strains including their genera, sources and levels of chlorine resistance. To our knowledge, few review papers have provided such systematic information about CRB. Among 44 typical CRB strains from 17 genera isolated by researchers, Mycobacterium, Bacillus, Legionella, Pseudomonas and Sphingomonas were the five genera with the highest frequency of occurrence in literatures. They are all pathogenic or opportunistic pathogenic bacteria. In addition, although there are many studies on CRB, information about chlorine resistance level is still limited to specie level or strain level. The difference in chlorine resistance level among different bacterial genera is less well understood. An inconvenient truth is that there is still no widely-accepted method to evaluate chlorine resistance and to identify CRB. Due to the lack of a unified method, it is difficult to compare the results about chlorine resistance level of bacterial strains in different literatures. A recommended evaluating method using logarithmic removal rate as an index and E. coli as a reference strain is proposed in this review based on the summary of the current evaluating methods. This method can provide common range of chlorine resistance of each genus and it is conducive to analyzing the distribution and abundance of CRB in the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

During the operation of the RO system, it's significant to predict the flux change over time. Previous research conducted detailed exploration on the dynamics of RO membrane fouling, and provided a solid database for modelling. In this study, a modified intermediate blocking model with two parameters was proposed to describe the flux change of RO membranes under a huge variety of conditions. Raw data reported by over 20 research groups from 11 different countries was used to validate the feasibility of this model. It proved applicable to describe the flux change of RO membranes fouled by pure organic matter or mixture and tertiary treated wastewater. In order to reveal the relationship between model parameters and foulant concentrations, RO membrane fouling behaviors of typical foulants (sodium alginate (SA), bovine serum albumin (BSA) and mixture) were further investigated. We found that the change of model parameters with SA concentrations was in accordance with Langmuir adsorption isotherm model. Therefore, the model parameters could be calculated by SA concentrations under certain optional conditions, and then the flux change could be predicted by this model. In this way, a novel time-course model was established, which could predict the flux change of RO membranes over time only with SA concentrations. Besides, the synergic effect between SA and BSA on RO membrane fouling was directly quantified., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A process of denitrification filter (DNF) coupled with ultrafiltration (UF) and ozonation (DNF-UF-O 3 ) has been widely applied to advanced nitrogen removal for wastewater reclamation. Despite of the effective removal of nitrogen by DNF, the influence of DNF stage on the operation of UF was still unclear. In this study, a laboratory filtration system was used to investigate the membrane fouling potential of DNF effluent and the fouling control of ozonation. The membrane fouling potential was proved to be increased significantly after DNF stage and alleviated with ozonation treatment. With the help of UV-vis, fluorescence spectroscopy, scanning electron microscopy (SEM) and molecular weight (MW) analysis, the change of DOM component characteristics was proved to be in accordance with the change of fouling potential. The water samples were further fractionated into six hydrophobic/hydrophilic acidic/basic/neutral fractions, among which hydrophobic acids (HOA) and hydrophobic neutrals (HON) dominated the membrane fouling potential of DNF effluent. Detailed study of each fraction revealed that higher MW components in HOA and HON played a crucial role in the fouling of UF membrane. The dominant component of membrane fouling could be degraded and removed by ozonation, and therefore significant fouling alleviation was achieved. These results indicated that in the process of wastewater reclamation, besides conventional water quality indexes, more detailed water features should also be taken into consideration to optimize the whole process. Moreover, the control effects by ozonation could be monitored simply according to the change of specific UV absorbance (SUVA) and fluorescence intensity as surrogates in engineering applications. According to these results, a modified DNF-O 3 -UF process with O 3 dosage of 3 mg/L was proposed simply by reversing the sequence of UF and O 3 with no more infrastructure. This modified DNF-O 3 -UF process was expected to enlarge the produce capacity of reclaimed water with much lower electricity costs and chemical consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Membrane fouling is an inevitable disadvantage of the reverse osmosis (RO) process for wastewater reclamation. In order to clarify the development process of membrane fouling, all the fouled membranes along a feed channel of a two-stage industrial-scale RO system for wastewater reclamation (six elements in each stage) were autopsied and analyzed. The water flux and salt rejection efficiency of the fouled membranes at the head and tail were the lowest among 12 elements, thereby indicating more severe fouling on these membranes. In this RO system, most of the organic compounds deposited on the head elements of each stage were mainly composed of proteins, polysaccharides, and fulvic acid. The ATP concentrations of the foulants on the first and twelfth elements were much higher than those of the other elements, suggesting severe biofouling. Although microbes can cause organic fouling owing to extracellular polymeric substances production, no clear correlation was found between organic fouling and biofouling in this study. For example, the ATP concentrations on the second element and seventh element were similar (1.16 ng/cm 2 and 1.26 ng/cm 2 , respectively), thereby suggesting a similar extent of biofouling, but organic fouling of the second element was relatively slight (DOC: 24.8 mg/m 2 ) compared with that of the seventh element (DOC: 46.2 mg/m 2 ). The seventh element (ATP: 1.26 ng/cm 2 ) was more severely biofouled than the eighth element (ATP: 0.15 ng/cm 2 ), but they suffered from the same level of organic fouling (DOC: 46.2 mg/m 2 and 47.1 mg/m 2 , respectively). Approximately 70% of metallic elements, predominantly Fe, were deposited on the first element. Although the concentration of Fe in the feed water was much lower than those of Ca and Mg, the concentration of Fe on the first three elements was significantly higher than that of any other element, suggesting that Fe was more easily deposited on the RO membranes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In reverse osmosis (RO) system for wastewater reclamation, biofouling is an inevitable issue. Chlorine disinfection is commonly used in pretreatment to control biofouling. Some chlorine-resistant bacteria could survive after chlorine disinfection and the microbial community structure in feed water changes significantly, thus leading to the change of biofouling potential. In this study, the effect of chlorine disinfection on the biofouling of RO membrane was investigated using a laboratory cross-flow RO system. Chlorine disinfection inactivated most bacteria in feed water. However, during the operation of RO system, with the increase of chlorine dosage the flux decline became more severe after a period of operation. The final normalized flux after 21 days was 0.27, 0.26, 0.20, and 0.21 with 0, 1, 5, and 15 mg-Cl 2 /L chlorine as pretreatment, respectively. After the operation, the numbers of active bacteria in the foulants on the fouled membrane were on the same level regardless of the chlorine dosage, whereas the thickness of the foulants increased with the chlorine dosage significantly. Additionally, the higher total organic carbon concentration indicated more extracellular polymeric substances (EPS) in foulants. Microbial community structure analysis showed that the abundance and the species number of chlorine-resistant bacteria increased significantly with the chlorine dosage. Typical chlorine-resistant bacteria, including Methylobacterium, Pseudomonas, Sphingomonas, and Acinetobacter, were identified as significantly distinctive genera in the foulants after the pretreatment by 15 mg-Cl 2 /L chlorine. Compared with the bacteria without chlorine disinfection, these remaining bacteria produced more EPS with higher molecular weight, which could be the major contribution to more severe RO membrane fouling after chlorine disinfection., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Biofouling represents the "Achilles' heel" for reverse osmosis (RO) processes due to the growth of bacteria and their production of extracellular polymeric substances (EPSs). Although the microbial community structure on the RO membrane has been analysed previously, the bacterial species with a high potential of causing RO membrane fouling have not yet been identified clearly. The key components in EPSs causing RO membrane fouling have not been revealed either. In this study, seven different bacterial species were isolated from fouled RO membranes, and their EPSs were analysed in terms of the content of polysaccharides and proteins, fluorescence characteristics and molecular weight (MW) distributions. The membrane fouling potentials of these bacterial species and EPSs were evaluated based on normalized flux decline. Generally, under the same growth conditions, bacterial species with higher EPS concentrations, rather than higher cell numbers, resulted in more severe flux decline. The flux decline showed an apparent positive correlation with the EPS concentration, indicating that the concentration of EPS rather than the bacterial number mainly contributed to biofouling. Furthermore, it was found that the MW distribution was the key factor affecting the RO membrane fouling potential of EPSs from different bacterial species. With the increase in the percentage of the high-MW fraction (>10 kDa) in the EPSs from 12.6% to 74.4%, the normalized flux decline increased from 0.4 to 0.59. The components in EPSs with a MW over 10 kDa were also separated by the ultrafiltration membrane and were proven to have a higher membrane fouling potential., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This study analyzed the mutation of 21-hydroxylase deficiency (21-OHD) in 36 unrelated Japanese patients with congenital adrenal hyperplasia (CAH)., Methods: All the exons of the functional CYP21 gene (CYP21A2) were analyzed by polymerase chain reaction (PCR) and PCR direct sequencing., Results: Apparent gene deletions and conversions were present in 23.6% of the 72 CAH alleles, in which the most frequent mutation was the IVS2-13 A/C>G (27.8%), followed by I172N (26.3%), consistent with the frequencies reported for other countries. Previously described mutations were not present in three unrelated cases. Sequence analysis of the complete functional CYP21A2 gene revealed three, not yet described mutations that represent a common pseudogene sequence. These three putative novel mutations are located in exon 1 (M1I), in exon 5 (1210-1211insT), and in exon 3 (R124H)., Conclusions: In this study, we have identified three putative novel mutations. It remains to be determined whether these three mutations are responsible for the significant number of as yet uncharacterized CAH patients in Japan., (Copyright 2004 S. Karger AG, Basel)

Background and Aims: Primary biliary cirrhosis (PBC) is a cholestatic autoimmune liver disease characterized by antimitochondrial autoantibodies (AMA) in serum, for which the reactants are E2 subunits of the three 2-oxoacid dehydrogenase (2-OAD) enzymes, particularly pyruvate dehydrogenase complex (PDC-E2). Some 70% of patients with PBC have a coexisting autoimmune disease including Sjögren's syndrome. We aimed to ascertain the frequency and isotype of AMA in saliva in PBC., Methods: Serum and saliva from 12 patients with PBC were tested for AMA by immunoblotting on bovine heart mitochondria, and by an automated microassay based on inhibition of the enzymatic activity of PDC., Results: Autoantibodies of the immunoglobulin (Ig)G, IgM, and IgA immunoglobulin isotypes against the E2 subunits of 2-OAD enzymes were demonstrable in PBC in serum (12 of 12 cases) and saliva (nine of 12 cases). Salivary autoantibodies, like serum autoantibodies, were predominantly reactive with PDC and of the IgG isotype. Results for serum and saliva corresponded closely with regard to reactivity with individual enzymes of the 2-OAD enzyme family, and to the autoantibody isotype that was predominantly expressed, and also in the capacity to inhibit the enzymatic activity of PDC., Conclusions: The presence of AMA in saliva to 2-OAD enzymes indicates that salivary glands could participate in the pathogenetic process of PBC. The detection of salivary AMA by a semi-automated enzyme inhibition assay offers possibilities for rapid population screening for detection of preclinical PBC among at-risk individuals, middle-aged to older women.

Autoantibodies to mitochondria (AMA, anti-M2) are a serologic hallmark of primary biliary cirrhosis (PBC). These react with three structurally and functionally related multienzymic complexes, the 2-oxoacid dehydrogenase complexes, but chiefly with the E2 subunit of pyruvate dehydrogenase complex (PDC-E2). Their very dose (95%) and specific association with PBC underpins the autoimmune concept of pathogenesis of that disease, notwithstanding several non-congruent features. Detailed studies, including structural analysis of epitopes, do not disclose how these autoantibodies originate. Their ubiquity in PBC has overshadowed the existence of a second set of relatively PBC-specific autoantibodies to nuclear antigens for which reactants have been cloned and characterized. These include centromeric proteins; proteins of the nuclear pore complex; nuclear dot proteins, which include Sp-100 and the promyelocytic leukemia antigen; and a recently identified autoantigen, SOX13. Certain of these reactants are DNA-binding proteins with transcriptional regulatory activity. Thus serum from individuals with the same clinical syndrome can have autoimmune reactivity to disparate mitochondrial and nuclear constituents in different cellular compartments. Antibody probing of phage displayed random peptide libraries, together with epitope scanning using overlapping sequential octameric peptides from the PDC-E2 sequence, showed that the discontinuous motifs MH, FV(E) and SYP contributed to a predicted conformational antibody epitope in the inner lipoyl domain of PDC-E2.

Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia and some may produce insulin-like growth factor II (IGF-II). To our knowledge, IGF-II-producing pancreatic tumors associated with hypoglycemia have not been reported previously. We describe what we believe to be the first case of "big" IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented with a history of recurrent hypoglycemia. Abdominal computed tomography scan and magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the tail of the pancreas and two low-density areas in the liver. Low serum glucose was associated with low insulin levels and high levels of hormones (i.e., glucagon and IGF-II) that are functionally opposite to insulin. Although serum IGF-II level was within the normal range, most IGF-II was of the high molecular weight form, as determined by Western immunoblot analysis. Based on these findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic tumor was made. Surgery was not possible because of the patient's poor general condition. The patient ultimately died as a result of malignant cachexia. At autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a histopathologic diagnosis of acinar cell carcinoma was made. Immunohistologically, the tumor cells contained IGF-II in an irregular staining pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor producing "big" IGF-II.

A rare case of malignant lymphoma of the stomach after treatment for hepatocellular carcinoma (HCC) is reported. A 72-year old man presented with a large mass on the right hypochondrium, which was diagnosed as HCC associated with chronic hepatitis C with cirrhosis. The inoperable tumor was treated conservatively with cisplatin, etoposide, carboplatin, and Lipiodol infused into the hepatic artery, together with transcatheter arterial embolization. The patient presented 38 months later with features suggestive of gastric ulceration. Endoscopy and histological examination of biopsy material confirmed the presence of malignant lymphoma of the stomach. He ultimately died as a result of hepatic failure. The clinical presentation suggests that gastric lymphoma was possibly related to the lymphotropic effect of hepatitis C virus (HCV) and exacerbated by intraarterial injection of the cytotoxic drugs.

To explore the relationship between mutant p53 and Pgp expression, we have examined the levels of both proteins in human colorectal adenocarcinomas. Serial frozen sections of 40 surgical samples were stained with an anti-Pgp (MRK16) and two different anti-p53 protein antibodies (Abs), PAb421 and PAb1801. Nineteen (47.5%) of 40 samples examined were positive for Pgp, and 18 (45%) of 40 were positive for p53. The samples that stained positively with PAb421 also stained positively with PAb1801. Pgp expression was detected in 13 (76.5%) of 17 samples that were positive for p53 using PAb421 and in 15 (83.3%) of 18 samples that were positive for p53 using PAb1801. Thus, we found that p53 and Pgp were co-expressed in a significant number of samples (P < 0.002). There was no relationship between Pgp or p53 protein accumulation and histologic grade or stage. The present results demonstrate that Pgp expression is closely associated with p53 protein accumulation in human colorectal cancers. These data provide evidence to support the idea that mutant p53 activates the MDR1 gene in vivo.

The apparent coexistence of primary biliary cirrhosis (PBC) and autoimmune hepatitis in the same patient raises unresolved problems for nosology and therapy. These are exemplified by a 45-year-old Japanese woman with overlapping clinical, serological and histological features of autoimmune cholangitis and autoimmune hepatitis. The classical serological test for PBC, antimitochondrial antibody (AMA) by immunofluorescence, was atypical. By immunoblotting there was reactivity with one of the enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) family, now recognized as autoantigens responsible for AMA reactivity. Also there was reactivity by immunofluorescence for antinuclear antibodies (ANA), one showing the typical speckled pattern of anti-Sp-100 and the other the peripheral pattern of antinuclear membrane antibody, both with titres > 10(6). There was also a positive result to the lupus erythematosus (LE) cell test. Treatment with ursodeoxycholic acid was beneficial. Thus while the clinical presentation suggested the overlapping syndrome of autoimmune hepatitis and PBC, PBC eventually proved to be the likely diagnosis. We suggest that apparent cases of overlapping PBC-autoimmune cholangitis-hepatitis syndromes, after detailed testing, will mostly align with PBC.

Multidrug resistance-associated protein (MRP) is a 190 kD transmembrane protein and a potentially important drug-transporter protein in human cancers. While the MRP gene is expressed in normal cells and tissues, the expression in solid tumors is not sufficiently determined. MRP and mdr1 mRNA expressions were examined in normal lung parenchyma and in tumor tissues from six small cell lung cancer (SCLC) patients who had received preoperative chemotherapy and eleven nonsmall cell lung cancer (NSCLC) patients. The reverse transcriptase polymerase chain reaction was used. Normal lung tissues and all SCLCs expressed abundant levels of MRP mRNA, while the NSCLCs expressed a wide range of levels from low to high. Most tumor tissues coexpressed both MRP and mdr1, but the levels of mdrl expression was low except in two SCLCs and one NSCLC. MRP is more likely than mdr1 to be one of the clinical multidrug resistance mechanisms found in lung cancer.

Background: Irinotecan--or CPT-11; 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptotheci n--is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is severe diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Cisplatin (CDDP; cis-diamminedichloroplatinum) and CPT-11 exhibit synergistic antitumor activity and have been used in combination-chemotherapy regimens. Single-agent chemotherapy with conventional doses of CDDP does not cause clinically relevant diarrhea., Purpose: To elucidate the mechanisms of induction of diarrhea by high-dose CPT-11 and to compare them with those of diarrhea induced by high-dose CDDP, we used histopathologic and immunohistochemical methods to examine the intestines of mice treated with either CPT-11, CDDP, or saline (control)., Methods: Male ICR mice were administered intraperitoneally either 100 mg/kg CPT-11 daily for 4 days, 10 mg/kg CDDP daily for 3 days, or phosphate-buffered saline (control) daily for 4 days (10 mice per group). Preliminary experiments indicated that diarrhea was induced in mice approximately 6 days after administration of CPT-11 or CDDP; therefore, in the experiments described, animals were killed 6 days after the first dose. Serial paraffin-embedded sections of the intestine were stained with hematoxylin-eosin, Grimelius (to identify endocrine cells), or high-iron diamine-alcian blue (stains sialomucin blue and sulfomucin brown-black). Immunohistochemical analyses were performed with the use of anti-proliferating cell nuclear antigen (anti-PCNA; to assay proliferation), anti-Le(y) (BM-1; indirect measure of apoptosis), and anti-synaptophysin antibodies (to identify the enteric nervous system and enterochromaffin cells). A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) method was used to detect DNA fragmentation in situ (i.e., apoptosis). The concentrations of two intestinally active secretogogues, plasma serotonin and vasoactive intestinal polypeptide, were also measured., Results: The levels of plasma intestinal hormones were similar in control, CPT-11, and CDDP groups. No active necrotic changes were observed in the intestines of CPT-11- and CDDP-treated mice, even though marked thinning of the intestinal walls was observed in both cases. The intestines of CPT-11-treated mice, but not those of control or CDDP-treated mice, were characterized by epithelial vacuolation of the ileum (associated with increased apoptosis as measured by BM-1 and TUNEL) and goblet-cell hyperplasia with excessive amount of sulfomucin in the cecum (suggesting induction of differentiation). By contrast, CDDP treatment of mice reduced the number of villi in the jejunum and destroyed crypt cells containing large Paneth (secretory) granules in the ileum., Conclusions: CPT-11 may produce characteristic mucosal changes in the intestine by inducing apoptosis and cell differentiation. The observed changes are likely to cause malabsorption of water and electrolytes and hypersecretion of mucin. These structural and functional effects are probably the main causes of CPT-11-induced diarrhea. CDDP appears to cause diarrhea in mice by causing diffuse mucosal damage in the intestines.

An antibody to the ret proto-oncogene product (RET) was raised and applied to formalin-fixed, paraffin-embedded neuroblastic tumors (NBTs) to investigate its usefulness in diagnosis and evaluation of cell differentiation. In normal neural crest-derived tissues, most ganglion cells were moderately stained while large ganglion cells were weakly stained. In NBTs, the intensity of the staining in moderately differentiated neuroblasts and small ganglion cells was more prominent than in undifferentiated neuroblasts, while the cytoplasm of large ganglionic cells was weakly stained as in normal ganglion cells. The RET immunoreactivity was compared with that of nine neural and neuroendocrine markers. The results revealed a parallelism with the protein gene product 9.5 (PGP9.5), neuron specific enolase (NSE) and NF-150 kD (NF = M). These findings indicated that the RET immunoreactivity was correlated with ganglionic differentiation and maturation. Thus, RET was considered to be a new marker that would be implemented in diagnosis and estimation of neuronal differentiation of NBTs.