The role of the cytochrome P450 superfamily in the skin.

In mammals, the skin acts as a barrier to prevent harmful environmental stimuli from entering the circulation. CYP450s are involved in drug biotransformation, exogenous and endogenous substrate metabolism, and maintaining the normal physiological function of the skin, as well as facilitating homeostasis of the internal environment. The expression pattern of CYP450s in the skin is tissue-specific and thus differs from the liver and other organs. The development of skin topical medications, and knowledge of the toxicity and side effects of these medications require a detailed understanding of the expression and function of skin-specific CYP450s. Thus, we summarized the expression of CYP450s in the skin, their function in endogenous metabolic physiology, aberrant CYP450 expression in skin diseases and the influence of environmental variables and medications. This information will serve as a crucial foundation for future studies on the skin, as well as for the design and development of new drugs for skin diseases including topical medications.

A 3D Hierarchical Host with Gradient-Distributed Dielectric Properties toward Dendrite-free Lithium Metal Anode.

The conventional conductive three-dimensional (3D) host fails to effectively stabilize lithium metal anodes (LMAs) due to the internal incongruity arising from nonuniform lithium-ion gradient and uniform electric fields. This results in undesirable Li "top-growth" behavior and dendritic Li growth, significantly impeding the practical application of LMAs. Herein, we construct a 3D hierarchical host with gradient-distributed dielectric properties (GDD-CH) that effectively regulate Li-ion diffusion and deposition behavior. It comprises a 3D carbon fiber host modified by layer-by-layer bottom-up attenuating Sb particles, which could promote Li-ion homogeneously distribution and reduce ion concentration gradient via unique gradient dielectric polarization. Sb transforms into superionic conductive Li3Sb alloy during cycling, facilitating Li-ion dredging and pumps towards the bottom, dominating a bottom-up deposition regime confirmed by COMSOL Multiphysics simulations and physicochemical characterizations. Consequently, a stable cycling performance of symmetrical cells over 2000 h under a high current density of 10 mA cm-2 is achieved. The GDD-CH-based lithium metal battery shows remarkable cycling stability and ultra-high energy density of 378 Wh kg-1 with a low N/P ratio (1.51). This strategy of dielectric gradient design broadens the perspective for regulating the Li deposition mechanism and paves the way for developing high-energy-density lithium metal anodes with long durability.

[Patent application of intelligent quality control technology in traditional Chinese medicine production process: a review].

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.

[Dissolution test and evaluation of Guizhi Fuling Capsules].

Because of the complex components, simple content determination can hardly reflect the overall quality of Guizhi Fuling Capsules. Therefore, it is necessary to carry out a multi-component dissolution test. The variability of quality among different batches of products from different manufacturers is a common problem of Chinese medicine solid preparations. To comprehensively control the quality of Guizhi Fuling Capsules, we studied the dissolution behaviors of 7 index components in the capsules under different conditions, and investigated the consistency of dissolution behaviors among different batches of products from the same manufacturer. The basket method of general rule 0931 in Chinese Pharmacopoeia was adopted, and the rotating speeds were set at 50, 75, and 100 r·min~(-1), respectively. The hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.0), pure water, and phosphate buffer solution(pH 6.8) were used as the dissolution media. Automatic sampling was carried out at the time points of 5, 10, 20, 30, 45, and 60 min, respectively. The cumulative dissolution of 7 index components was measured through ultra-performance liquid chromatography(UPLC). The difference factor f_1 and similarity factor f_2 were calculated to comprehensively evaluate the similarity of the dissolution curves among 8 batches of Guizhi Fuling Capsules, and a variety of dissolution and release equations were fitted. The results showed that multiple components had faster dissolution rates at higher rotating speed and in hydrochloric acid medium. The 8 batches of Guizhi Fuling capsules showed the average f_1 value lower than 15 and the average f_2 value higher than 50, which indicated that different batches of products had similar dissolution behaviors. Most components had synchronous dissolution behaviors and similar release cha-racteristics. This study provides a reference for the quality consistency evaluation among batches, processing optimization, and dosage form improvement of Guizhi Fuling Capsules.

[Effects and evaluation of different processing and drying methods on components in Paeoniae Radix Alba].

The present study evaluates different processing and drying methods and investigates their effects on the chemical components in Paeoniae Radix Alba via content determination. The fresh medicinal materials of Paeoniae Radix Alba collected from Bozhou of Anhui province were processed(boiled and peeled) and dried(hot air-dried, infrared-dried, and microwave-dried) at different temperatures(40, 50, 60 and 70 ℃), and the 11 components(monoterpene glycosides, polyphenols, tannin, and benzoic acid) in Paeoniae Radix Alba were determined by ultra-performance liquid chromatography coupled to triple quadrupole with electrospray tandem mass spectrometry(UPLC-TQ-MS). Then the compounds in processed and dried samples were analyzed by partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA), and the contribution rates of differential components were evaluated by variable important in projection(VIP). The results indicated that the samples obtained by different processing and drying methods could be distinguished. Albiflorin, gallic acid, 1,2,3,4,6-pentakis-O-galloyl-ß-D-glucose, and benzoic acid were the common differential components in boiled Paeoniae Radix Alba. Benzoic acid was the common differential component in peeled Paeoniae Radix Alba. Gallic acid was the common differential component in Paeoniae Radix Alba dried by different methods. The samples could not be distinguished after drying at different temperatures due to the lack of common differential components. This study is expected to provide a reference for the selection of processing and drying methods and the optimization of processing parameters.

Uptake and Translocation of Perfluorooctanoic Acid (PFOA) and Perfluorooctanesulfonic Acid (PFOS) by Wetland Plants: Tissue- and Cell-Level Distribution Visualization with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) and Transmission Electron Microscopy Equipped with Energy-Dispersive Spectroscopy (TEM-EDS).

Perfluoroalkyl substances (PFASs) are persistent chemicals in the environment. So far, little is known about their uptake potential in wetland plants. Here, we investigated the uptake and translocation of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in eight common wetland plants, namely, Canna indica (Ci), Thalia dealbata (Td), Cyperus alternifolius (Ca), Phragmites australis (Pa), Arundo donax (Ad), Pontederia cordata (Pc), Cyperus papyrus (Cp), and Alisma orientale (Ao) by hydroponic experiments and visualized their tissue- and cell-level distribution with desorption electrospray ionization mass spectrometry (DESI-MS) and transmission electron microscopy equipped with energy-dispersive spectroscopy (TEM-EDS). The results showed that the PFASs accumulated in plants accounted for 1.67-16.7% of the total mass spiked into the hydroponic systems, and PFOS accumulated largely in roots (48.8-95.8%), while PFOA was stored mostly in the aboveground part (29.3-77.4%). DESI-MS and TEM-EDS analysis showed that PFASs in Ci, Td, Pa, and Ca were transported from the hydroponic solution to the root cortex via both apoplastic (e.g., across cell walls and/or intercellular spaces) and symplastic routes (e.g., across plasma membranes or via plasmodesmata) and further to the vascular bundle via symplastic route in Td and Pa and via both routes in Ci and Ca. These two chemicals were transported from roots to stems mainly through the cortex in Td and through both the cortex and vascular bundles in Ci and Ca.

WSN-Assisted UAV Trajectory Adjustment for Pesticide Drift Control.

Unmanned Aerial Vehicles (UAVs) have been widely applied for pesticide spraying as they have high efficiency and operational flexibility. However, the pesticide droplet drift caused by wind may decrease the pesticide spraying efficiency and pollute the environment. A precision spraying system based on an airborne meteorological monitoring platform on manned agricultural aircrafts is not adaptable for. So far, there is no better solution for controlling droplet drift outside the target area caused by wind, especially by wind gusts. In this regard, a UAV trajectory adjustment system based on Wireless Sensor Network (WSN) for pesticide drift control was proposed in this research. By collecting data from ground WSN, the UAV utilizes the wind speed and wind direction as inputs to autonomously adjust its trajectory for keeping droplet deposition in the target spraying area. Two optimized algorithms, namely deep reinforcement learning and particle swarm optimization, were applied to generate the newly modified flight route. At the same time, a simplified pesticide droplet drift model that includes wind speed and wind direction as parameters was developed and adopted to simulate and compute the drift distance of pesticide droplets. Moreover, an LSTM-based wind speed prediction model and a RNN-based wind direction prediction model were established, so as to address the problem of missing the latest wind data caused by communication latency or a lack of connection with the ground nodes. Finally, experiments were carried out to test the communication latency between UAV and ground WSN, and to evaluate the proposed scheme with embedded Raspberry Pi boards in UAV for feasibility verification. Results show that the WSN-assisted UAV trajectory adjustment system is capable of providing a better performance of on-target droplet deposition for real time pesticide spraying with UAV.

[A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province].

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (rs=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (rs=0.196, P<0.01). CONCLUSIONS: Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.

[Comparative study on differences of Paeonia lactiflora from different habitats based on fingerprint and chemometrics].

This study aims to compare the differences of Paeonia lactiflora from different habitats by establishing fingerprint. The fingerprint of P. lactiflora was established by UPLC. The samples collected from Sichuan,Hebei,Henan,Shanxi and Anhui were analyzed. The common peaks were identified by UPLC-Q-TOF/MS. The relative peak area of the common peaks was analyzed through similarity evaluation system( 2012 edition) for chromatographic fingerprint of traditional Chinese medicine developed by the National Pharmacopoeia Commission. Twelve common peaks were obtained and ten components were identified by reference substance and literature comparison. The similarity of each sample to the reference fingerprint is greater than 0. 900. However,all samples were clearly divided into 5 groups according to habitats after PLS-DA analysis. The peaks 2,6( ethyl gallate),10( galloypaeoniflorin) and 12( benzoyl paeoniflorin) were found to be the main difference components between the samples from five different habitats through the VIP value map. The study found that the variety of ingredients in the different areas are basically similar. But there are some differences in the content of the four components. The results of this study can provide reference at choosing and utilizing P. lactiflora from different places comprehensively.

Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. METHODS: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. RESULTS: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. CONCLUSIONS: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

[HTRF-based high-throughput PGE2 release prohibition model and application in discovering traditional Chinese medicine active ingredients].

Prostaglandin (PG) E2 is an active substance in pathological and physiological mechanisms, such as inflammation and pain. The in vitro high-throughput assay for screening the inhibitors of reducing PEG2 production is a useful method for finding out antiphlogistic and analgesic candidates. The assay was based on LPS-induced PGE2 production model using a homogeneous time-resolved fluorescence(HTRF) PGE2 testing kit combined with liquid handling automation and detection instruments. The critical steps, including the cell density optimization and IC50 values determination of a positive compound, were taken to verify the stability and sensibility of the assay. Low intra-plate, inter-plate and day-to-day variability were observed in this 384-well, high-throughput format assay. Totally 5 121 samples were selected from the company's traditional Chinese medicine(TCM) material base library and used to screen PGE2 inhibitors. In this model, the cell plating density was 2 000 cells for each well; the average IC50 value for positive compounds was (7.3±0.1) µmol; the Z' factor for test plates was more than 0.5 and averaged at 0.7. Among the 5 121 samples, 228 components exhibited a PGE2 production prohibition rate of more than 50%, and 23 components exhibited more than 80%. This model reached the expected standards in data stability and accuracy, indicating the reliability and authenticity of the screening results. The automated screening system was introduced to make the model fast and efficient, with a average daily screening amount exceeding 14 000 data points and provide a new model for discovering new anti-inflammatory and analgesic drug and quickly screening effective constituents of TCM in the early stage.

Indoxyl sulfate, not P-cresyl sulfate, is associated with advanced glycation end products in patients on long-term hemodialysis.

BACKGROUND/AIMS: Advanced glycation end products (AGEs) are pro-inflammatory and pro-oxidative compounds that play a critical role in endothelial dysfunction and atherosclerosis. Protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), inhibit endothelial function. We explored the association of IS and PCS with AGEs in a hemodialysis (HD) cohort. METHODS: This study was a cross-sectional study that recruited 129 stable patients on maintenance HD in a single medical center from July 1 to July 15, 2011. Serum levels of total and free IS, PCS and AGEs were measured concurrently. General laboratory results and patient background were also investigated. RESULTS: Serum levels of AGEs were associated with total IS (r = 2.7, p < 0.01) but not total PCS (r = 0.01, NS), free IS (r = 0.11, NS) or free PCS (r = 0.04, NS) using Pearson's analysis. Multiple linear regression analysis showed that total IS was significantly related to AGEs (ß = 0.296, p < 0.01), free IS (ß = 0.502, p < 0.01) and creatinine (ß = 0.294, p < 0.01). Serum AGEs levels were also independently correlated with diabetes status (ß = 0.250, p = 0.01) and total IS (ß = 0.341, p < 0.01) concentrations after adjusting for other confounding variables. Moreover, patients with diabetes had higher serum AGEs levels than patients without diabetes (p < 0.01). CONCLUSIONS: These findings suggest that serum levels of total IS were associated with AGEs levels, which may participate in the process of atherosclerosis.

[Main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule].

Guizhi Fuling capsule is a traditional Chinese medicine composed of five kinds of medicinal plants, Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen, and Paeoniae Radix Alba. Pharmacology studies have shown that Guizhi Fuling capsule has many activities: anti-inflammatory, analgesic, anti-tumor, regulating smooth muscle, endocrine regulation and enhancing immunity. It achieved obvious effects in the treatment of uterine fibroids, pelvic inflammatory disease, dysmenorrheal, endometriosis, ovarian cysts, breast hyperplasia and other gynecological diseases. This paper reviewed the main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule in recent years.

[Study on anti-inflammation and immunoloregulation effect of Guizhi Fuling capsule ingredients using high content screening].

The present study sought to investigate the anti-inflammation and immunoloregulation effect of 17 Guizhi Fuling capsule ingredients. The anti-inflammatory ingredients on LPS-induced RAW264. 7 cell injury were assessed with ELISA and immunofluorescence. The release of IL-1ß, TNF-α, PGE2 were detected with ELISA and the expression of COX-2 was detected with immunofluorescence. The effects of them on promoting splenic lymphocyte proliferation were assessed with MTT and Hoechst 33342 staining method. The results showed that 15 ingredients had obviously anti-inflammatory activity on LPS- induced injury and play the immunoloregulation roles. This study suggested that the 15 ingredients may be the active ingredients on pelvic infection.

[Monitor on influence of quality standard improvement upon Guizhi Fuling capsules efficacy].

In 2012, the preparation process and quality standard for Guizhi Fuling capsule were improved. To compare the effects and differences of capsules before (2011) and after(2012-2014) the improvement, evaluation models for intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma were applied in rats. Models were induced by oxytocin, liqiud bacteria mixture and estrogen loading, respectively. The capsules (12 batchs/year, 48 bathcs in all), sampled randomly in 2011-2014, the effects were assessed using the three models. In anti-dysmenorrhea models, remarked reduction of writhing frequency, ET-1 and PGF2α content in uterus could be detected, as well as extension of writhing latency. In pelvic inflammation rats, depression of TNF-α and raise of IL-2 were induced by earh batch of capsules. In hysteromyoma model, uterine weight and smooth muscle proliferation, including E2 and P level in plasma, were lowered obviously by all batchs of capsules. Secondly, Guizhi Fuling capsules produced in 2012-2014 revealed better effectiveness than the ones manufactured in 2011. Moreover, pharmacodynamics indexes of the samples made in 2011 differed significantly between groups, which could not be observed in the ones ot 2012-2014. After tne preparation process and quality standard improvement, the effectiveness and homogeneity of Guizhi Fuling capsules were enhanced.

[Study of effective components and molecular mechanism for Guizhi Fuling formula treatment of dysmenorrhea, pelvic inflammatory disease and uterine fibroids].

In this study, the active components and potential molecular .mechanism of Guizhi Fuling formula in treatment on dysmenorrhea, pelvic inflammation, and hysteromyoma were investigated using network pharmacological methods. Sterols and pentacyclic triterpenes, with high moleculal network degree, revealed promising effects on anti-inflammatory, analgesic, anti-tumor, and immune-regulation, according to D-T network analysis. On the other hand, the targets with high degree were involved in inflammatory, coagulation, angiopoiesis, smooth muscle contraction, and cell reproduction, which showed the novel function in anti-dysmenorrhea, pelvic inflammation, and hysteromyoma. Furthermore, the formula was indicated to play a key role in smooth muscle proliferation, inhibition of new vessels, circulation improvement, reduction of hormone secretion, alleviation of smooth muscle, block of arachidonic acid metabolism, and inflammation in uterus. Thus, the main mechanism of Guizhi Fuling formula was summarized. In conclusion, Guizhi Fuling formula was proven to alleviated dysmenorrhea, pelvic inflammation, and hysteromyoma by acting on multiple targets through several bioactive compounds, regulating 21 biological pathways.

Application of environmental DNA metabarcoding to identify fish community characteristics in subtropical river systems.

Fish are vital in river ecosystems; however, traditional investigations of fish usually cause ecological damage. Extracting DNA from aquatic environments and identifying DNA sequences offer an alternative, noninvasive approach for detecting fish species. In this study, the effects of environmental DNA (eDNA), coupled with PCR and next-generation sequencing, and electrofishing for identifying fish community composition and diversity were compared. In three subtropical rivers of southern China, fish specimens and eDNA in water were collected along the longitudinal (upstream-downstream) gradient of the rivers. Both fish population parameters, including species abundance and biomass, and eDNA OTU richness grouped 38 sampling sites into eight spatial zones with significant differences in local fish community composition. Compared with order-/family-level grouping, genus-/species-level grouping could more accurately reveal the differences between upstream zones I-III, midstream zones IV-V, and downstream zones VI-VIII. From the headwaters to the estuary, two environmental gradients significantly influenced the longitudinal distribution of the fish species, including the first gradient composed of habitat and physical water parameters and the second gradient composed of chemical water parameters. The high regression coefficient of alpha diversity between eDNA and electrofishing methods as well as the accurate identification of dominant, alien, and biomarker species in each spatial zone indicated that eDNA could characterize fish community attributes at a level similar to that of traditional approaches. Overall, our results demonstrated that eDNA metabarcoding can be used as an effective tool for revealing fish composition and diversity, which is important for using the eDNA technique in aquatic field monitoring.

Occurrence, distribution, and risk assessment of antibiotics in a typical aquaculture area around the Dongzhai Harbor mangrove forest on Hainan Island.

The trees of the Dongzhai Harbor mangrove forest suffer from antibiotic contamination from surrounding aquaculture areas. Despite this being one of the largest mangrove forests in China, few studies have focused on the antibiotic pollution status in these aquaculture areas. In the present study, the occurrence, distribution, and risk assessment of 37 antibiotics in surface water and sediment samples from aquaculture areas around Dongzhai Harbor mangrove forests were analyzed. The concentration of total antibiotics (∑antibiotics) ranged from 78.4 ng/L to 225.6 ng/L in surface water (except S14-A2) and from 19.5 ng/g dry weight (dw) to 229 ng/g dw in sediment. In the sediment, the concentrations of ∑antibiotics were relatively low (19.5-52.3 ng/g dw) at 75 % of the sampling sites, while they were high (95.7-229.0 ng/g dw) at a few sampling sites (S13-A1, S13D, S8D). The correlation analysis results showed that the Kd values of the 9 antibiotics were significantly positively correlated with molecular weight (MW), Kow, and LogKow. Risk assessment revealed that sulfamethoxazole (SMX) in surface water and SMX, enoxacin (ENX), ciprofloxacin (CFX), enrofloxacin (EFX), ofloxacin (OFX), and norfloxacin (NFX) in sediment had medium/high risk quotients (RQs) at 62.5 % and 25-100 %, respectively, of the sampling sites. The antibiotic mixture in surface water (0.06-3.36) and sediment (0.43-309) posed a high risk at 37.5 % and 66.7 %, respectively, of the sampling sites. SMX was selected as an indicator of antibiotic pollution in surface water to assist regulatory authorities in monitoring and managing antibiotic pollution in the aquaculture zone of Dongzhai Harbor. Overall, the results of the present study provide a comprehensive and detailed analysis of the characteristics of antibiotics in the aquaculture environment around the Dongzhai Harbor mangrove system and provide a theoretical basis for the source control of antibiotics in mangrove systems.

Isolation, characterization, and molecular modeling of a rheumatoid factor from a Hepatitis C virus infected patient with Sjögren's syndrome.

We have previously isolated several IgG rheumatoid factors (RFs) from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren's syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6 × 10⁻8 M. This effect resulted from longer complementarity-determining region (CDR) combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren's syndrome and may play an important role in the pathogenesis of this autoimmune disease.

Circ_0001666 upregulation promotes intestinal epithelial cell fibrosis in pediatric Crohn's disease via the SRSF1/BMP7 axis.

The epithelial-mesenchymal transition (EMT) is closely associated with Crohn's disease (CD) related intestinal fibrosis, a condition whose prevalence is increasing annually among children. Recently, the CD marker gene microarray screening revealed an upregulation of circ_0001666 in the colon tissues of CD patients, but its underlying mechanisms remain unclear. In this study, we explored the molecular mechanism of circ_0001666 in regulating EMT-mediated fibrosis in CD in vitro. The levels of circ_0001666 and EMT-associated proteins were assessed in CD clinical samples, and a CD cell model was established using TGF-ß1 to induce human intestinal epithelial cells (HIECs). Additionally, the expression levels of genes and proteins related to EMT and fibrosis were analyzed by quantitative real-time PCR and western blot, cell migration, and invasion were assessed via wound healing assay and transwell, respectively, and RNA pull-down and RNA immunoprecipitation assays were performed to verify the relationship between SRSF1 and BMP7 or circ_0001666. Circ_0001666 was overexpressed in the intestinal mucosal tissues of CD patients and was positively correlated with EMT. Silencing circ_0001666 inhibited the migration, invasion, EMT, and fibrosis of HIECs induced by TGF-ß1. Mechanistically, circ_0001666 regulated BMP7 expression by interacting with SRSF1. Furthermore, the effects of inhibiting circ_0001666 on HIECs could be partially reversed by overexpressing SRSF1 or silencing BMP7. Collectively, circ_0001666 regulates TGF-ß1-induced HIEC migration, invasion, EMT, and fibrosis. Circ_0001666 also promoted EMT-mediated fibrosis by interacting with SRSF1 to accelerate BMP7 mRNA decay. These findings provide new insights into the pathogenesis of CD and suggest that circ_0001666 might be a potential therapeutic target for CD.