Fruquintinib-induced renal-limited thrombotic microangiopathy: a case report.

BACKGROUND: Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature. CASE PRESENTATION: In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy. CONCLUSION: This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.

Occurrence, distribution and potential environmental risks of pollutants in aquaculture ponds during pond cleaning in Taihu Lake Basin, China.

During the process of cleaning aquaculture ponds, the drainage contributes significantly to antibiotic pollution in the surrounding water environment. Therefore, we conducted a study on the distribution of 26 antibiotics in 57 ponds within the Taihu Lake basin. The results revealed that the detection frequency of antibiotics ranged from 1.75 % to 80.7 %, with the overall detection concentrations ranging from 3.27 to 708.72 ng/L. Among them, the detection rate of 8 antibiotics exceeded 50 %. Regarding the spatial distribution, the concentration of antibiotics was relatively high in aquaculture ponds located in the Changzhou area, with the highest concentration reaching 708.72 ng/L. This observation is likely due to the large size and intensive breeding practices in Changzhou. Fish ponds exhibited a significantly higher total antibiotic concentration of 3.27 to 445.57 ng/L compared to crab ponds (13.01 to 206.30 ng/L) and shrimp ponds (23.17 to 107.40 ng/L). Quinolones and sulfonamides were the predominant antibiotic classes found in fish ponds, accounting for 51.49 % of the total antibiotic concentration. Notably, sulfamethoxazole (SMX) and enrofloxacin (ENR) exhibited the highest antibiotic concentrations. Risk assessments demonstrated that SMX, ENR, and ofloxacin (OFX) contributed significantly to ecological risks. Furthermore, the study found that the tertiary constructed wetland treatment process achieved a remarkable removal rate of 92.44 % for antibiotics in aquaculture wastewater, while other treatment processes displayed limited effectiveness in removing antibiotics. This study addresses the knowledge gap concerning antibiotic pollution during the cleaning process of aquaculture ponds within the Taihu Lake basin.

Identification of Adulteration of Flaxseed Oil From QINGHAI Area Using GC-MS Profiling of Phytosterol Composition and Chemometrics.

Flaxseed oil is an important source of vegetable oil with a polyunsaturated fatty acid. It is significant to establish a method to quickly identify adulterated flaxseed oil. In the present study, the qualitative and quantitative analysis of phytosterol of flaxseed oil from different varieties and different production areas in the Qinghai area was first performed by gas chromatography-mass spectrometry (GC-MS) and the phytosterol standard profile of flaxseed oil was established. Then, a combination of similarity evaluation and cluster analysis was used to distinguish pure flaxseed oil from flaxseed oil adulterated with concentrations of 10-50% rapeseed oil, peanut oil, sunflower oil, and sesame oil, and discriminant analysis was used to identify the types of adulterated flaxseed oil. The results showed that similarity evaluation combined with cluster analysis can distinguish pure and adulterated flaxseed oil when the concentration of the adulterant was greater than 10%. Discriminant analysis models accurately identified the types of adulterating oil in flaxseed oil when the concentration of rapeseed, peanut, or sunflower oil was greater than 20%, and that of sesame oil was greater than 30%. This study shows that the determination of the phytosterol composition and chemometrics is a valuable tool to evaluate the purity of flaxseed oil.

Unraveling the evolution of dissolved organic matter in full-scale A/A/O wastewater treatment process using size exclusion chromatography with PARAFAC and nonnegative matrix factorization analysis.

Changes in spectral features and molecular weight (MW) of dissolved organic matter (DOM) along the A/A/O processes in eight full-scale wastewater treatment plants (WWTPs) were characterized using size exclusion chromatography with a diode array detector, a fluorescence detector and an organic carbon detector in tandem (SEC-DAD-FLD-OCD) as well as bulk water quality parameters. The parallel factor (PARAFAC) and the nonnegative matrix factorization (NMF) analyses have been effectively applied to the postprocessing of SEC-FLD fingerprints and SEC-OCD chromatograms, respectively. Individual SEC-FLD-PARAFAC or SEC-OCD-NMF components may span a broad range of MW, indicating that these SEC fractions within the same component were cognate and varied coherently across the dataset samples. The SEC-FLD-PARAFAC modeling and SEC-OCD-NMF analysis have clearly and concisely presented that the dramatic decreases of dissolved organic carbon, UV absorbance at 254 nm and protein-like fluorescence at Ex280/Em350 nm in the anaerobic process were primarily associated with the degradation of the large MW proteinaceous and polysaccharide-like biopolymers. It has also revealed that fluorescence of humic acid-like fractions increased significantly during the anaerobic process, but fluorescence of fulvic acid-like and humic substances' building blocks decreased slightly. Laboratory experiments further confirmed the presence of the humification process in anaerobic processes, and the formation of humic acid-like fluorophores may be associated with carbohydrate metabolism. The combination of SEC-FLD-PARAFAC and SEC-OCD-NMF helped to establish the links between changes in bulk water quality parameters and the evolution of SEC MW fractions, which provides a more in-depth insight into wastewater DOM treatability and enables the optimization of wastewater treatment processes.

Nonalcoholic Fatty Liver Disease as an Emerging Risk Factor and Potential Intervention Target for Atherosclerotic Cardiovascular Diseases.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is an underappreciated independent risk factor for atherosclerotic cardiovascular diseases (ASCVDs). In recent years, the risk of ASCVD has increased along with the prevalence of NAFLD. ASCVD events are highly prevalent and are the main contributor to death in patients with NAFLD. The association between NAFLD and ASCVD has been validated in numerous observational, cohort, and genetic studies. Most of these studies agree that NAFLD significantly increases the risk of developing atherosclerosis and ASCVD. In addition, the underlying proatherosclerotic mechanisms of NAFLD have been gradually revealed; both disorders share several common pathophysiologic mechanisms including insulin resistance, whereas systemic inflammation and dyslipidemia driven by NAFLD directly promote atherosclerosis. Recently, NAFLD, as an emerging risk enhancer for ASCVD, has attracted attention as a potential treatment target for ASCVD. This brief review aims to illustrate the potential mechanistic insights, present recent clinically relevant investigations, and further explore the emerging therapies such as novel antidiabetic and lipid-lowering agents that could improve NAFLD and reduce ASCVD risk.

Changes of dissolved organic matter fractions and formation of oxidation byproducts during electrochemical treatment of landfill leachates: Development of spectroscopic indicators for process optimization.

Electrochemical oxidation (EO) is an attractive option for treatment of dissolved organic matter (DOM) in landfill leachate but concerns remain over the energy efficiency and formation of oxidation byproducts ClO3- and ClO4-. In this study, EO treatment of landfill leachates was carried out using representative active and nonactive anode materials, cell configurations and current densities. Size exclusion chromatograms coupled with 2D synchronous and asynchronous correlation analysis showed that the sensitivity of DOM fractions to EO degradation was dependent on the anode material. The nonactive boron-doped diamond (BDD) anode demonstrated the best performance for DOM oxidation. The humic acid-like fraction (HA, 2.5-20 kDa) predominated the visible absorbance of landfill leachates at λ ≥400 nm, and it generally had the highest reaction rates except the occurrence of the pH-induced denaturation and precipitation of the proteinaceous biopolymer fraction (BP, >20 kDa). During the EO treatment of landfill leachate with BDD anode, the UV absorbance spectra of landfill leachates at wavelengths <400 nm were affected by the formation of free chlorine. Instead, the decrease of Abs420 was found to be a good indicator of the shift of the oxidation from predominantly HA fraction to the proteinaceous BP fraction. The behavior of the Abs420 parameter was also indicative of the transition from the energy-efficient oxidation of DOM to the dominance of side reactions of chlorine evolution and the subsequent formation of ClO3- and ClO4-. These findings suggest that the EO treatment of landfill leachate can be optimized by adjusting the current density with feedback signals from the online monitoring of Abs420, to achieve a trade-off between degradation of DOM and control of ClO3- and ClO4-.

Release and removal of algal organic matter during prechlorination and coagulation treatment of cyanobacteria-laden water: Are we on track?

A better understanding of the physicochemical properties and fate of algae-derived organic matter (AOM) in water treatments significantly benefits the control of algae-derived disinfection byprodcuts and process parameter optimization. In this study, we conducted a comprehensive investigation of the release and treatability of dissolved organic matter during prechlorination and postcoagulation treatments of cyanobacteria-laden source water via size-exclusion chromatography-tandem diode array detector, fluorescence detector and organic carbon detector. The results revealed that the allochthonous humic substances could protect algal cell membrane from damage during prechlorination at a low level of chlorine dose. Due to the release and oxidation of biopterins during prechlorination of M. aeruginosa cells, the variation of the humic-like fluorescence can be used to indicate the chlorine dose for a sufficient membrane damage of algae cells. The prechlorination of M. aeruginosa cells induced minimal release of large MW biopolymer fractions but much more release of low MW fractions E1 and E2 (i.e., unknown carbonaceous substances and fluorescent nitrogenous biopterins). The physically extracted AOM contained a large proportion of biopolymers and could not well represent those released during prechlorination treatment. During coagulation, the negative effect of humic substances on the coagulant demand to achieve algae removal was more remarkable than AOM released by prechlorination. The high-MW biopolymers and humic substances can be removed over 50% by coagulation. Among the low-MW carbonaceous fractions, E1 released by prechlorination can also be effectively removed via coagulation while fractions C, D (possibly oligopeptides or secondary aromatic metabolites & low MW acids) and nitrogenous biopterins were recalcitrant to coagulation. This study highlights the differences of AOM properties between physical extraction and prechlorination and provides a basis for drinking water treatment plants to give more attention to the recalcitrant low MW fractions in coagulation when treating algae-laden source water.

Developing a restricted chlorine-dosing strategy for UV/chlorine and post-chlorination under different pH and UV irradiation wavelength conditions.

UV/chlorine and chlorination processes have drawn great interests of water treatment utilities for oxidation and disinfection purposes. This work proposed a restricted chlorine-dosing strategy for UV/chlorine and post-chlorination under different pH and UV irradiation conditions by comprehensively assessing the oxidation of natural organic matter (NOM), formation of 9 haloacetic acids (HAA9) and bromate, and alteration of toxicity. During UV/chlorine with restricted chlorine doses, the oxidation of NOM chromophores (i.e., ΔUVA254) showed an apparent dependence on cumulative exposures of free available chlorine (CTFAC); Meanwhile, HAA9 formation was determined by CTFAC values and could be linearly correlated with ΔUVA254 irrespective of pH and UV irradiation wavelength. Irradiated by 254 nm LP-Hg lamp, the faster chlorine photolysis produced relatively higher steady-state concentrations of Cl• and HO• species but resulted in lower CTFAC. Reducing CTFAC values by operation parameters (pH, UV wavelength and irradiation fluence) could mitigate HAA9 formation during UV/chlorine at a specific chlorine dose. Additionally, high bromide concentration and acidic pH promoted more bromo-HAAs formation, and the presence of NOM significantly suppressed bromate formation. Analogous to ozonation, the UV/chlorine pre-oxidation could reduce the HAA9 formation potentials during post-chlorination at mildly alkaline pH. The photobacterium bioassay further demonstrated that although the UV/chlorine treatment might have increased the acute toxicity, the post-chlorination treatment could polish the acute toxicity to the level of chlorination alone. These results suggest that with the restricted chlorine-dosing strategy, the trade-off between oxidation/disinfection efficiency and DBPs formation can be controlled by monitoring CTFAC and ΔUVA254 values during UV/chlorine treatment.

Characterizing property and treatability of dissolved effluent organic matter using size exclusion chromatography with an array of absorbance, fluorescence, organic nitrogen and organic carbon detectors.

In this study, size exclusion chromatography with an array of absorbance, fluorescence, organic nitrogen and organic carbon detectors was used for characterizing property and treatability of effluent organic matter (EfOM) from 12 wastewater treatment plants. According to their apparent molecular weight (AMW), EfOM fractions were assigned to biopolymers (>20 kDa), humic substances that comprise sub-fractions of humic-like acids (HA-I & HA-II, 2.3-7.0 kDa) and fulvic-like acids (FA, 1.5-2.3 kDa), building blocks (0.55-1.5 kDa) and low molecular weight neutral substances (<550 Da). The fractions of biopolymers and low molecular weight neutral substances didn't show humic-like fluorescence, while the fractions of HA-II, FA and building blocks usually had signatures of both humic-like and protein-like fluorescence. Humic substances generally contributed the largest proportion of dissolved organic carbon and nitrogen (DOC & DON) in effluents. Coagulation removed EfOM fractions following the order of biopolymers > HA subfraction > FA subfraction > building blocks, while little removal of protein-like fluorescence in HA-II and FA subfractions was detected. Anion exchange treatment could effectively reduce DOC and DON concentrations; the sequence of the treatment efficiency was humic substances > biopolymers > building blocks. Increasing O3 doses caused DOC and DON of EfOM to be gradually transformed from large AMW fractions into small AMW fractions, while chromophores and fluorophores in HA subfractions were relatively more refractory than those in the other fractions. Size exclusion chromatography with multiple detectors are suggested to be an informative technique for estimating treatability of EfOM by advanced wastewater treatment processes.

Cloning identification and functional analysis of human IL-17A promoter.

OBJECTIVE: To conduct the cloning identification and characterization of the sequence of human IL-17A promoter so as to analyze the regulatory mechanism of the gene expression of IL-17. METHODS: First of all, the potential promoter region of IL-17A was found by means of the bioinformatics methods. Then, it was cloned into the reporter vector with PCR technique. Finally, the activity of the test promoter was determined by dual luciferase reporter system. RESULTS: Two transcriptional start points of the upper region, 600 bp and 1000 bp, of IL-17A were obtained by PCR clone and proved to have certain activities by dual luciferase reporter system. Also, they could be activated by IL-17A activator STAT3, which could start the expression of the reported gene. CONCLUSIONS: Clone established the regulatory region of human IL-17A promoter, which provided bases to the subsequent function research.

NLRP3 Activation Was Regulated by DNA Methylation Modification during Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (Mtb) infection activates the NLRP3 inflammasome in macrophages and dendritic cells. Much attention has been paid to the mechanisms for regulation of NLRP3 against Mtb. However, whether epigenetic mechanisms participated in NLRP3 activation is still little known. Here we showed that NLRP3 activation was regulated by DNA methylation modification. Mtb infection promoted NLRP3 activation and inflammatory cytokines expression. NLRP3 promoter was cloned and subsequently identified by Dual-Luciferase Reporter System. The results showed that NLRP3 promoter activity was decreased after methylation by DNA methylase Sss I in vitro. Meanwhile, DNA methyltransferases inhibitor DAC could upregulate the expression of NLRP3. Furthermore, promoter region of NLRP3 gene was demethylated after Mtb H37Rv strain infection. These data revealed that DNA methylation was involved in NLRP3 inflammasome activation during Mtb infection and provided a new insight into the relationship between host and pathogens.