Loss-of-Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia.

BACKGROUND AND AIMS: Hypoxia is a common feature of the tumor microenvironment (TME), which promotes tumor progression, metastasis, and therapeutic drug resistance through a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclinical development of this approach is lacking in the study of HCC. APPROACH AND RESULTS: From a genome-wide CRISPR/CRISPR-associated 9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia. Knockdown of ALDOA in HCC cells leads to lactate depletion and consequently inhibits tumor growth. Supplementation with lactate partly rescues the inhibitory effects mediated by ALDOA knockdown. Upon hypoxia, ALDOA is induced by hypoxia-inducible factor-1α and fat mass and obesity-associated protein-mediated N6 -methyladenosine modification through transcriptional and posttranscriptional regulation, respectively. Analysis of The Cancer Genome Atlas shows that elevated levels of ALDOA are significantly correlated with poor prognosis of patients with HCC. In a screen of Food and Drug Administration-approved drugs based on structured hierarchical virtual platforms, we identified the sulfamonomethoxine derivative compound 5 (cpd-5) as a potential inhibitor to target ALDOA, evidenced by the antitumor activity of cpd-5 in preclinical patient-derived xenograft models of HCC. CONCLUSIONS: Our work identifies ALDOA as an essential driver for HCC cell growth under hypoxia, and we demonstrate that inhibition of ALDOA in the hypoxic TME is a promising therapeutic strategy for treating HCC.

Degradation of sulfamonomethoxine in solution using pulsed plasma discharge - identification of by-products and toxicity of treated solution to green algae.

This study investigated the degradation of sulfamonomethoxine (SMM) by pulsed plasma discharge. SMM was successfully degraded following the first-order kinetics model. The percentage removal of SMM was estimated by the total input energy of plasma discharge, which was dependent on the initial SMM concentration. In addition, three types of by-products were observed at an early reaction time, which were then degraded. In contrast, the ecotoxicity of the treated solution by plasma discharge was assessed by an acute toxicity test using the green alga Raphidocelis subcapitata. The plasma discharge in water generated hydrogen peroxide with a concentration higher than the EC50 for R. subcapitata. It is therefore necessary to remove H2O2 or prevent the generation of H2O2 for the degradation of antibiotics in solutions using plasma discharge.

Spatiotemporal distribution of chondroitin sulfate proteoglycans after optic nerve injury in rodents.

The accumulation of chondroitin sulfate proteoglycans (CSPGs) in the glial scar following acute damage to the central nervous system (CNS) limits the regeneration of injured axons. Given the rich diversity of CSPG core proteins and patterns of GAG sulfation, identifying the composition of these CSPGs is essential for understanding their roles in injury and repair. Differential expression of core proteins and sulfation patterns have been characterized in the brain and spinal cord of mice and rats, but a comprehensive study of these changes following optic nerve injury has not yet been performed. Here, we show that the composition of CSPGs in the optic nerve and retina following optic nerve crush (ONC) in mice and rats exhibits an increase in aggrecan, brevican, phosphacan, neurocan and versican, similar to changes following spinal cord injury. We also observe an increase in inhibitory 4-sulfated (4S) GAG chains, which suggests that the persistence of CSPGs in the glial scar opposes the growth of CNS axons, thereby contributing to the failure of regeneration and recovery of function.

Ionic liquid-modified magnetic polymeric microspheres as dispersive solid phase extraction adsorbent: a separation strategy applied to the screening of sulfamonomethoxine and sulfachloropyrazine from urine.

Ionic liquid-modified magnetic polymeric microspheres (ILMPM) were prepared based on Fe3O4 magnetic nanoparticles (MNPs) and ionic liquids (ILs) incorporated into a polymer. The composites were characterized using scanning electron microscopy, Fourier transform infrared analysis, thermogravimetric analysis, X-ray diffraction, and vibrating magnetometer, which indicated that ILMPM had a regularly spherical shape and strong magnetic property. The obtained ILMPM were successfully applied as a special adsorbent of magnetic dispersive solid phase extraction (MDSPE) for the rapid extraction and isolation of sulfamonomethoxine sodium and sulfachloropyrazine sodium in urine. The factors that affected extraction efficiency, such as adsorption conditions, desorption conditions, washing and elution solvents, and pH of the sample solution, were optimized. Under the optimum condition, good linearity in the range of 0.005-2.0 µg g(-1) (r ≥ 0.9996) was obtained for the two sulfonamides (SAs); the average recoveries at three spiked levels ranged from 86.9 to 102.1 %, with relative standard deviations of ≤4.3 %. The presented ILMPM-MDSPE method combined the advantages of ILs, MNPs, and MDSPE and therefore could be potentially applied for rapid screening of SAs in urine.

Pharmacokinetics of sulfamonomethoxine in tongue sole (Cynoglossus semilaevis) after intravenous and oral administration.

The pharmacokinetic profiles of sulfamonomethoxine (SMM) were investigated in flatfish tongue soles in the present study. After a single injection of SMM (40 mg/kg BW) to caudal vein of tongue sole at 20 °C, plasma drug concentration versus time data were best fitted to a three-compartment model, characterized with 0.2, 5.7, and 80.4 h for the half-life (t 1/2) of fast distribution, slow distribution, and elimination, respectively. The apparent volume of distribution was 0.1 L/kg, and the body clearance was 0.03 L/h/kg. After oral administration of SMM (200 mg/kg BW) to tongue soles at 20 °C, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t 1/2ka) and elimination (t 1/2ß ) were 1.7 and 95.7 h, respectively. The maximal absorption concentration (C max) was estimated as 58 mg/L at 2.5 h, and the mean systemic bioavailability (F) was 39.5 % in tongue soles after oral administration.

Unraveling how Fe-Mn modified biochar mitigates sulfamonomethoxine in soil water: The activated biodegradation and hydroxyl radicals formation.

This study indicated that the application of a novel Fe-Mn modified rice straw biochar (Fe/Mn-RS) as soil amendment facilitated the removal of sulfamonomethoxine (SMM) in soil water microcosms, primarily via activating degradation mechanism rather than adsorption. The similar enhancement on SMM removal did not occur using rice straw biochar (RS). Comparison of Fe/Mn-RS with RS showed that Fe/Mn-RS gains new physic-chemical properties such as abundant oxygenated C-centered persistent free radicals (PFRs). In the Fe/Mn-RS microcosms, the degradation contributed 79.5-83.8% of the total SMM removal, which was 1.28-1.70 times higher than that in the RS microcosms. Incubation experiments using sterilized and non-sterilized microcosms further revealed that Fe/Mn-RS triggered both the biodegradation and abiotic degradation of SMM. For abiotic degradation of SMM, the abundant •OH generation, induced by Fe/Mn-RS, was demonstrated to be the major contributor, according to EPR spectroscopy and free radical quenching experiments. Fenton-like bio-reaction occurred in this process where Fe (Ⅲ), Mn (Ⅲ) and Mn (Ⅳ) gained electrons, resulting in oxidative hydroxylation of SMM. This work provides new insights into the impacts of biochar on the fates of antibiotics in soil water and a potential solution for preventing antibiotic residues in agricultural soil becoming a non-point source pollutant.

Cooperation among nitrifying microorganisms promotes the irreversible biotransformation of sulfamonomethoxine.

Ammonia-oxidizing microorganisms, including AOA (ammonia-oxidizing archaea), AOB (ammonia-oxidizing bacteria), and Comammox (complete ammonia oxidization) Nitrospira, have been reported to possess the capability for the biotransformation of sulfonamide antibiotics. However, given that nitrifying microorganisms coexist and operate as communities in the nitrification process, it is surprising that there is a scarcity of studies investigating how their interactions would affect the biotransformation of sulfonamide antibiotics. This study aims to investigate the sulfamonomethoxine (SMM) removal efficiency and mechanisms among pure cultures of phylogenetically distinct nitrifiers and their combinations. Our findings revealed that AOA demonstrated the highest SMM removal efficiency and rate among the pure cultures, followed by Comammox Nitrospira, NOB, and AOB. However, the biotransformation of SMM by AOA N. gargensis is reversible, and the removal efficiency significantly decreased from 63.84 % at 167 h to 26.41 % at 807 h. On the contrary, the co-culture of AOA and NOB demonstrated enhanced and irreversible SMM removal efficiency compared to AOA alone. Furthermore, the presence of NOB altered the SMM biotransformation of AOA by metabolizing TP202 differently, possibly resulting from reduced nitrite accumulation. This study offers novel insights into the potential application of nitrifying communities for the removal of sulfonamide antibiotics (SAs) in engineered ecosystems.

Effects of sulfamonomethoxine and trimethoprim co-exposures at different environmentally relevant concentrations on microalgal growth and nutrient assimilation.

In aquaculture around the world, sulfamonomethoxine (SMM), a long-acting antibiotic that harms microalgae, is widely employed in combination with trimethoprim (TMP), a synergist. However, their combined toxicity to microalgae under long-term exposures at environmentally relevant concentrations remains poorly understood. Therefore, we studied the effects of SMM single-exposures and co-exposures (SMM:TMP=5:1) at concentrations of 5 µg/L and 500 µg/L on Chlorella pyrenoidosa within one aquacultural drainage cycle (15 days). Photosynthetic activity and N assimilating enzyme activities were employed to evaluate microalgal nutrient assimilation. Oxidative stress and flow cytometry analysis for microalgal proliferation and death jointly revealed mechanisms of inhibition and subsequent self-adaptation. Results showed that exposures at 5 µg/L significantly inhibited microalgal nutrient assimilation and induced oxidative stress on day 7, with a recovery to levels comparable to the control by day 15. This self-adaptation and over 95 % removal of antibiotics jointly contributed to promoting microalgal growth and proliferation while reducing membrane-damaged cells. Under 500 µg/L SMM single-exposure, microalgae self-adapted to interferences on nutrient assimilation, maintaining unaffected growth and proliferation. However, over 60 % of SMM remained, leading to sustained oxidative stress and apoptosis. Remarkably, under 500 µg/L SMM-TMP co-exposure, the synergistic toxicity of SMM and TMP significantly impaired microalgal nutrient assimilation, reducing the degradation efficiency of SMM to about 20 %. Consequently, microalgal growth and proliferation were markedly inhibited, with rates of 9.15 % and 17.7 %, respectively, and a 1.36-fold increase in the proportion of cells with damaged membranes was observed. Sustained and severe oxidative stress was identified as the primary cause of these adverse effects. These findings shed light on the potential impacts of antibiotic mixtures at environmental concentrations on microalgae, facilitating responsible evaluation of the ecological risks of antibiotics in aquaculture ponds.

Oral pharmacokinetics of sulfadiazine and sulfamonomethoxine in female Holstein milking cows.

The efficacy of orally administered drugs in cattle is thought to be slow because of the anatomical and physiological features of their forestomach. Thus, parenteral routes are mainly preferred to administer drugs. However, the effect of some drugs with unique physicochemical properties was promptly obtained even after oral administration in clinically ill cattle. Therefore, the present study aimed to investigate pharmacokinetically the usefulness of the oral route in cattle by comparing the oral pharmacokinetic properties of two sulfonamides with different physicochemical properties. Sulfadiazine (SDZ) and sulfamonomethoxine (SMM) were administered by intravenous and oral route to four female Holstein cows with a 4-weeks washout period. Blood samples were collected over time, and SDZ and SMM concentrations in plasma were analyzed by HPLC. Data obtained from the same animal after intravenous and oral administration were simultaneously analyzed with the one compartment model, and kinetic parameters were calculated. The Tmax (mean ± SD) of SMM (2.75 ± 0.96 hr) was significantly achieved earlier than that of SDZ (5.00 ± 1.15 hr). Further, the mean absorption time of SMM (5.24 ± 0.69 hr) was significantly shorter than that of SDZ (5.92 ± 1.11 hr). Also, the half-life of absorption of SMM (3.91 ± 0.51 hr) was significantly shorter than that of SDZ (4.51 ± 0.82 hr). These data suggest that the absorption rates of highly unionized drugs (such as SMM) from the forestomach of cattle may be markedly higher than less unionized ones (such as SDZ).

Biotransformation of sulfamonomethoxine in a granular sludge system: Pathways and mechanisms.

The biotransformation of sulfamonomethoxine (SMM) was studied in an aerobic granular sludge (AGS) system to understand the role of sorption by microbial cells and extracellular polymeric substances (EPS) and the role of functional microbe/enzyme biodegradation. Biodegradation played a more important role than adsorption, while microbial cells covered with tightly bound EPS (TB-EPS) showed higher adsorption capacity than microbial cells themselves or microbial cells covered with both loosely bound EPS (LB-EPS) and TB-EPS. The binding tests between EPS and SMM and the spectroscopic analyses (3D-EEM, UV-Vis, and FTIR) were performed to obtain more information about the adsorption process. The data showed that SMM could interact with EPS by combining with aromatic protein compounds, fulvic acid-like substances, protein amide II, and nucleic acids. Batch tests with various substances showed that SMM removal rates were in an order of NH2OH (60.43 ± 2.21 µg/g SS) > NH4Cl (52.96 ± 0.30 µg/g SS) > NaNO3 (31.88 ± 1.20 µg/g SS) > NaNO2 (21.80 ± 0.42 µg/g SS). Hydroxylamine and hydroxylamine oxidoreductase (HAO) favored SMM biotransformation and the hydroxylamine-mediated biotransformation of SMM was more effective than others. In addition, both ammonia monooxygenase (AMO) and CYP450 were able to co-metabolize SMM. Analysis of UPLC-QTOF-MS indicated the biotransformation mechanisms, revealing that acetylation of arylamine, glucuronidation of sulfonamide, deamination, SO2 extrusion, and δ cleavage were the five major transformation pathways. The detection of TP202 in the hydroxylamine-fed Group C indicated a new biotransformation pathway through HAO. This study contributes to a better understanding of the biotransformation of SMM.

Spatiotemporal distribution of veterinary and human drugs and its predictability in Japanese catchments.

Little is known about the predictability of mass flows of veterinary drugs in Asian catchments, where effluent from livestock farms is a major source. We therefore conducted this study to understand the applicability and limitations of a population-based emission model, which assumed usage of veterinary and human drugs to be evenly distributed over the national livestock or human population throughout the year, and sources to be effluent discharges at livestock farms, households, and sewage treatment plants in Japanese catchments. We monitored five veterinary drugs (lincomycin, sulfamonomethoxine, tiamulin, tylosin, and tilmicosin), two human and livestock drugs (sulfamethoxazole and trimethoprim), two human drugs (carbamazepine and clarithromycin), and a metabolite (sulfapyridine) of a human drug once a month over 2 years in eight Japanese rivers which have active livestock farming in their catchments. Mass flows of carbamazepine and sulfapyridine were stable, while those of veterinary drugs fluctuated widely, especially sulfamonomethoxine and tilmicosin, whose 25 %-100 % ranges averaged 1.5 and 1.2 log units, respectively, attributable mainly to their usage patterns. The model accurately predicted mean mass flows of carbamazepine in the rivers with errors of <±0.3 log unit. Although it slightly to moderately overestimated those of the other four human-related compounds, the incorporation of an empirical correction factor, determined to minimize mean absolute error (MAE) among the rivers, substantially lowered their MAEs to <0.23 log units. However, the MAEs of the five veterinary drugs were as high as 0.42 (sulfamonomethoxine) to 0.60 (tiamulin) log units even with the coefficient, likely due mainly to the spatial distribution of their usage per capita. So as not to overlook spatiotemporal elevation of risks of veterinary drugs, a stochastic method should be applied in their management. This is the first study to assess the use of spatiotemporal homogeneity in usage per capita of veterinary drugs in Asian catchments.

Detection of fluoroquinolone and sulfonamide residues in poultry eggs in Kunming city, southwest China.

Antibiotic residues contained in poultry eggs pose threat to human health. However, the classes and concentrations of antibiotics in poultry egg in southwestern China is unknown due to insufficient monitoring and research. A total of 513 egg samples were collected from supermarkets and farm markets in Kunming city in 2020 and the levels of 7 antibiotics were analyzed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. The linear correlation coefficients were above 0.990 for all antibiotics tested. The limits of detection and limits of quantification in poultry eggs were 0.002 to 0.010 µg/g and 0.007 to 0.033 µg/g, respectively. The average recoveries of the 7 analytes from poultry egg samples were 80.00 to 128.01%, with relative standard deviations of less than 13.97%. A total of 93 (18.13%) samples tested positive for antibiotics, with the highest concentration being 2.48 µg/g. The concentration range of ofloxacin, danofloxacin, difloxacin, sulfadimethoxine, sulfamonomethoxine, sulfamethoxypyridazine, and sulfamethoxazole in poultry eggs was 0.01 to 0.37 µg/g, 0.06 to 0.48 µg/g, 0.05 to 0.29 µg/g, 0.03 to 0.16 µg/g, 0.06 to 1.00 µg/g, 0.05 to 0.37, and 0.07 to 2.48 µg/g, respectively. Sulfamonomethoxine was detected from hen eggs with the highest concentration level at 1.00 µg/g. Sulfamethoxazole was detected with the highest concentration level from both duck and quail eggs, at 1.87 and 2.48 µg/g, respectively. The antibiotic with the highest residue level in pheasant eggs was danofloxacin, which was 0.37 µg/g. Sulfamethoxypyridazine was identified in 30 samples with the highest positive rate of 5.85%, sulfadimethoxine was identified in 3 samples with the lowest positive rate of 0.58%. We observed that 7 targeted antibiotic residues in quail eggs and 3 targeted antibiotic residues in pheasant eggs. We also found that there were antibiotic residues in free-range hen eggs and the concentration was not low. The antibiotic with the highest residue level in free-range eggs was sulfamonomethoxine, which was 1.00 µg/g. These findings suggest that continual antibiotic residue monitoring of poultry eggs is essential in China.

Removal of antibiotics from milk via ozonation in a vortex reactor.

Antibiotics (ABX) residues occur frequently in milk, causing considerable wastage of medicated milk and serious economic losses, and making the issue a burden for the dairy industry. Improper disposal of medicated milk harms dairy production, animal welfare, and the environment. This work studies the use of ozonation in a vortex reactor for removing ceftiofur hydrochloride (CEF), sulfamonomethoxine sodium (SMM), marbofloxacin (MAR) and oxytetracycline (OTC) from milk. In terms of residual concentration, O3 efficiency and the degradation kinetics of the various O3-involving processes in the vortex reactor, ABX removal via ozonation is better using stronger vortexing, which induces hydrodynamic cavitation. CEF undergoes the fastest degradation, followed by SMM, MAR, and OTC. High ABX hydrophobicity favors ABX degradation via ozonation, O3/H2O2, and O3/Na2S2O8. ABX oxidation by •OH at the O3 gas-bubble/milk interface is the principle degradation pathway, except for MAR. ABX degradation follows pseudo-first-order kinetics and is affected by initial ABX concentration, O3 concentration/flow rate, reaction temperature, and milk components to varying degrees. Under optimal ozonation conditions, ABX residues meet the maximum limits as set by the European Commission and no antimicrobial activity was observed. The decontaminated milk was therefore suggested to be reused as calf food, animal feed, organic fertilizer, etc.

Expression and the role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma.

Sulfation represents an essential modification for various molecules and regulates many biological processes. The sulfation of glycans requires a specific transporter for 3'-phosphoadenosine 5'-phosphosulfate (PAPS) on the Golgi apparatus. This study investigated the expression of PAPS transporter genes in colorectal carcinomas and the significance of Golgi-specific sulfation in the proliferation of colorectal carcinoma cells. The relative amount of PAPST1 transcripts was found to be higher than those of PAPST2 in colorectal cancerous tissues. Immunohistochemically, the enhanced expression of PAPST1 was observed in fibroblasts in the vicinity of invasive cancer cells, whereas the expression of PAPST2 was decreased in the epithelial cells. RNA interference of either of the two PAPS transporter genes reduced the extent of sulfation of cellular proteins and cellular proliferation of DLD-1 human colorectal carcinoma cells. Silencing the PAPS transporter genes reduced fibroblast growth factor signaling in DLD-1 cells. These findings indicate that PAPS transporters play a role in the proliferation of colorectal carcinoma cells themselves and take part in a desmoplastic reaction to support cancer growth by controlling their sulfation status.

Age-related differences in human skin proteoglycans.

Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human skin.

Photocatalytic degradation of sulfamonomethoxine by mesoporous phosphorus-doped titania under simulated solar light irradiation.

Photocatalytic degradation of sulfamonomethoxine (SMM) by mesoporous phosphorus-doped TiO2 (P-TiO2) was studied under simulated solar light irradiation. The morphological structure and chemical composition of P-TiO2 were analyzed by XRD, SEM, HRTEM, BET, XPS and FTIR. Using the central composite design (CCD) of response surface methodology (RSM), the degradation of SMM was investigated with a range of antibiotic concentrations (4-8 mg L-1), catalyst dosages (400-900 mg L-1), P doping amounts (5-15 wt %) and irradiation time (90-150 min). The Ti-O-P bond formed during the calcination of TiO2, thereby generating plate-like P-TiO2, where P was uniformly distributed. Phosphorus doping can stabilize anatase TiO2, which has a larger specific surface area and a lower average particle and pore size than bare TiO2. The result obtained from the RSM model showed a significant correlation between the predicted values and the experimental results of SMM degradation (P < 0.05). Under the optimal experimental conditions (antibiotic concentration = 6 mg/L, catalyst dosage = 800 mg/L, P doping = 5 wt% and irradiation time = 90 min), the degradation rate of SMM was 99.51%, and the TOC was 50%. Toxicity showed a considerable reduction towards Vibrio-qinghaiensis sp.-Q67 after SMM photocatalytic degradation. Through free radical capture experiments, LC-MS detection and DFT calculations, the possible photocatalytic degradation mechanism of SMM using P-TiO2 as the catalyst was revealed.

Multi-spectroscopic and molecular docking studies of human serum albumin interactions with sulfametoxydiazine and sulfamonomethoxine.

Sulfonamides are a kind of antibiotics which have been widely used as feed additives for livestock and poultry. However, sulfa drugs have raised worldwide concerns because of their adverse impact on human health. In this study, two sulfonamides, sulfametoxydiazine (SMD) and sulfamonomethoxine (SMM), were selected to explore the binding modes with human serum albumin (HSA). The spectroscopic approaches revealed that SMD or SMM could spontaneously enter into the binding site I of HSA through hydrogen bond interactions and van der Waals forces, and that SMD exhibited much stronger binding affinity toward HSA than SMM at different temperatures (p < 0.01, n = 3). The binding constants for SMD-HSA and SMM-HSA were determined to be (8.297 ± 0.010) × 104 L·mol-1 and (1.178 ± 0.008) × 104 L·mol-1 at 298 K, respectively. The interaction of SMD or SMM to HSA induced microenvironmental and conformational changes in HSA, where SMD had a greater effect on the α-helix content of HSA. Results from molecular docking implied that the amino acid residues of HSA, such as Arg222, Ala291 and Leu238, played key roles in the sulfonamide-HSA binding process. Meanwhile, hydrogen bonds might be a key factor contributing to the binding affinity of sulfa drugs and HSA. Additionally, the combined use of SMD and SMM led to an obvious variation in Ka values of binary systems (p < 0.01, n = 3). These findings might be helpful to understand the biological effects of sulfonamides in humans.

Transformation kinetics and pathways of sulfamonomethoxine by UV/H2O2 in swine wastewater.

Sulfamonomethoxine (SMM), as one of the most predominant antibiotics in animal wastewater, is pending for effective control to minimize its environmental risks. Transformation kinetics and pathways of SMM by UV/H2O2 in swine wastewater were systematically investigated in this study. Direct UV photolysis (as a dominant role) and ∙OH oxidation contributed to SMM degradation in UV/H2O2 system. The less effective reaction rate of SMM in real wastewater than synthetic wastewater (0.1-0.17 vs. ∼0.2-1.5 min-1, despite higher H2O2 dosage and extended reaction time) resulted mainly from the abundant presence of conventional contaminants (indicated by COD, a notable competitor of SMM) in real wastewater. SMM degradation benefited from higher H2O2 dosage and neutral and weak alkaline conditions. However, the effect of initial SMM concentration on SMM degradation in synthetic and real wastewater showed opposite trends, owning to the different probability of SMM molecules to interact with UV and H2O2 in different matrices. Carbonate had an inhibitory effect on SMM degradation by scavenging ∙OH and pH-variation induced effect, while nitrate promoted SMM degradation by generating more ∙OH. The removal efficiency of SMM in real wastewater reached 91% under the reaction conditions of H2O2 of 10 mM, reaction time of 60 min, and pH 6.7-6.9. SMM degradation pathway was proposed as hydroxylation of benzene and pyrimidine rings, and secondary amine, and the subsequent cleavage of S-N bond.

The effect of sulfamonomethoxine treatment on the gut microbiota of Nile tilapia (Oreochromis niloticus).

To investigate the possible effects of sulfamonomethoxine (SMM) on Nile tilapia (Oreochromis niloticus), we quantitatively evaluated the microbial shifts in the intestines of Nile tilapia in response to different doses of SMM (200 and 300 mg/kg) using 16S rRNA gene sequencing. At the phylum level, the control group (0 mg kg-1  SMM) was dominated by Actinobacteria, Proteobacteria, and Firmicutes. In the treatment groups, Firmicutes, Proteobacteria, and Chloroflexi were the dominant phyla. Cluster analysis indicated that the two groups treated with SMM clustered together. Similarly, the bacterial families that dominated the control group differed from those dominating the treatment groups. The changes in intestinal microbial composition over time were similar between the two SMM treatment groups. In both groups, the abundances of some families, including the Bacillaceae, Streptococcaceae, and Pseudomonadaceae, increased first and then decreased. Overall, the addition of SMM to the feed changed the structure of the intestinal microbiota in Nile tilapia. This study improves our understanding of the impact of SMM on the intestinal microenvironment of Nile tilapia. Our results provide guidelines for the feasibility of SMM use in aquaculture production.

Eco-toxic effects of sulfadiazine sodium, sulfamonomethoxine sodium and enrofloxacin on wheat, Chinese cabbage and tomato.

Investigation of the toxic effects of three veterinary drugs [sulfadiazine sodium (SDS), sulfamonomethoxine sodium (SMMS), and enrofloxacin (EFLX)] on seed germination, root elongation and shoot elongation of wheat (Triticum aestivum L.), Chinese cabbage (Brassica campestris L.) and tomato (Cyphomandra betacea) was carried out. Significant linear relationships between the root and shoot elongation and the concentration of veterinary drugs addition were observed. The effects of the three veterinary drugs on seed germination of wheat, Chinese cabbages and tomato were not significant (P > 0.05), but on shoot and root elongation they were markedly significant (P < 0.05). The inhibitory rates of veterinary drugs on root and shoot elongation of crops were significantly stronger than that on seed germination. Based on IC(50) (drugs concentration when 50% plants show inhibition) of root elongation, wheat was the most sensitive plant to the toxicity of SDS with a IC(50) value as high as 28.1 mg/kg; Chinese cabbage was the most sensitive plant to the toxicity of SMMS with a IC(50) value as high as 27.1 mg/kg; tomato was the most sensitive plant to the toxicity of EFLX with a IC(50) value as high as 125.7 mg/kg. The toxic effects of sulfadiazine sodium and sulfamonometh-oxine sodium on the three crops were much higher than that of enrofloxacin.