[Contamination Characteristics and Ecological Risk of Antibiotics in Contaminated Sites of Typical Pharmaceutical Factories in China].

To understand the contamination characteristics and ecological risk of antibiotics in contaminated fields of pharmaceutical plants， samples of the surface soil， soil column， wastewater treatment process water， ground water， and residue dregs were collected from two typical antibiotic pharmaceutical plants in South and North China. A total of 87 commonly used antibiotics were quantified using ultrasound extraction-solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry. The results showed that a total of 31 antibiotics of five classes were detected in all types of samples， and the maximum concentrations at each sampling point in the surface soil， soil column， residue dregs， wastewater treatment process water， and groundwater were 420 ng·g-1， 595 ng·g-1， 139 ng·g-1， 1 151 ng·L-1， and 6.65 ng·L-1， respectively. Most of the antibiotics were found in the surface soil， showing a decreasing trend with the depth of the soil column. The ecological risk assessment indicated that sulfamethazine， sulfaquinoxaline， tetracycline， chlorotetracycline， and D-sorbitol were at higher risk. Improving the efficiency of antibiotic removal from pharmaceutical wastewater and preventing production shop leaks are effective measures of controlling antibiotic contamination into and around fields in pharmaceutical plants.

Brain Structural Connectivity Guided Vision Transformers for Identification of Functional Connectivity Characteristics in Preterm Neonates.

Preterm birth is the leading cause of death in children under five years old, and is associated with a wide sequence of complications in both short and long term. In view of rapid neurodevelopment during the neonatal period, preterm neonates may exhibit considerable functional alterations compared to term ones. However, the identified functional alterations in previous studies merely achieve moderate classification performance, while more accurate functional characteristics with satisfying discrimination ability for better diagnosis and therapeutic treatment is underexplored. To address this problem, we propose a novel brain structural connectivity (SC) guided Vision Transformer (SCG-ViT) to identify functional connectivity (FC) differences among three neonatal groups: preterm, preterm with early postnatal experience, and term. Particularly, inspired by the neuroscience-derived information, a novel patch token of SC/FC matrix is defined, and the SC matrix is then adopted as an effective mask into the ViT model to screen out input FC patch embeddings with weaker SC, and to focus on stronger ones for better classification and identification of FC differences among the three groups. The experimental results on multi-modal MRI data of 437 neonatal brains from publicly released Developing Human Connectome Project (dHCP) demonstrate that SCG-ViT achieves superior classification ability compared to baseline models, and successfully identifies holistically different FC patterns among the three groups. Moreover, these different FCs are significantly correlated with the differential gene expressions of the three groups. In summary, SCG-ViT provides a powerfully brain-guided pipeline of adopting large-scale and data-intensive deep learning models for medical imaging-based diagnosis.

Effects of herbivorous fish on shallow lake ecosystems increase at moderate nutrient conditions.

Submerged macrophytes are vital in shallow lakes, as they provide critical ecosystem functions and services and can stabilize the clear-water conditions by various mechanisms. Nutrient enrichment reduces the resilience of macrophyte dominance in shallow lakes, thereby making them susceptible to shifts towards phytoplankton dominance following perturbations. Here, we conducted a mesocosm experiment to examine the individual and combined effects of nutrient enrichment and the addition of grass carp (Ctenopharyngodon idella) on the abundance of submerged macrophytes, epiphyton, and phytoplankton. We hypothesized that moderate nutrient enrichment facilitates macrophyte abundance, but also phytoplankton abundance after macrophyte removal by herbivorous fish. Our data showed that herbivory by grass carp could trigger a shift from macrophytes to algal dominance in mesocosms with moderate nutrient concentrations, but not in those with low nutrient concentrations. Moderate nutrient enrichment alone promoted submerged macrophyte growth, whereas the introduction of grass carp induced a collapse of submerged macrophytes regardless of nutrient conditions. Moreover, the introduction of grass carp showed more negative effects on light conditions of the water column in mesocosms with moderate nutrient concentrations compared to those with low nutrient concentrations. A recovery of submerged macrophytes might thus be limited by low light availability in lakes with moderate nutrient conditions suffering grass carp perturbation. Our results suggest that submerged macrophyte-dominated shallow lakes with moderate nutrient conditions are vulnerable to perturbation by herbivorous fish such as grass carp. In turn, managing the abundance of herbivores in these lakes can support the dominance of macrophytes and associated clear water conditions.

Long-term survival in patients with PMP: a single-institutional retrospective study from China.

BACKGROUND: As the standard treatment for pseudomyxoma peritonei (PMP), cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) can significantly prolong the survival of PMP patients, and some patients can even achieve long-term survival (LTS) or clinical cure. The purpose of this study was to analyze the clinicopathological and treatment features of PMP patients with LTS and to explore the survival benefit factors of PMP patients. METHODS: The clinicopathological and prognostic data of PMP patients who received CRS + HIPEC at our center from December 2004 to May 2023 were retrospectively analyzed. PMP patients were divided into LTS group (≥ 10 years) and short-term survival (STS) group (< 5 years) according to the length of natural history. Univariate and multivariate analyses were performed to explore the beneficial factors of PMP patients with LTS. RESULTS: A total of 609 patients with PMP received CRS + HIPEC treatment at our center. Two-hundred one patients with PMP were included in the study after screening, including 39 patients (19.4%) in the LTS group and 162 patients (80.6%) in the STS group. In STS group and LTS group, median overall survival based on natural history was 29.2 (2.4-59.9) vs. 138.9 (120.3-416.7) months. Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: gender, chemotherapy history, previous surgical score, Karnofsky Performance Status score, pathological diagnosis, lymphatic metastasis, peritoneal cancer index, and completeness of cytoreduction (CC). Multivariate analysis identified only two factors independently associated with LTS of PMP patients: CC and pathological diagnosis. CONCLUSION: Complete CRS and pathological features are two key factors affecting LTS in PMP patients.

Spectral CT - a new supplementary method for preoperative assessment of pathological grades of esophageal squamous cell carcinoma.

BACKGROUND: Spectral CT imaging parameters have been reported to be useful in the differentiation of pathological grades in different malignancies. This study aims to investigate the value of spectral CT in the quantitative assessment of esophageal squamous cell carcinoma (ESCC) with different degrees of differentiation. METHODS: There were 191 patients with proven ESCC who underwent enhanced spectral CT from June 2018 to March 2020 retrospectively enrolled. These patients were divided into three groups based on pathological results: well differentiated ESCC, moderately differentiated ESCC, and poorly differentiated ESCC. Virtual monoenergetic 40 keV-equivalent image (VMI40keV), iodine concentration (IC), water concentration (WC), effective atomic number (Eff-Z), and the slope of the spectral curve(λHU) of the arterial phase (AP) and venous phase (VP) were measured or calculated. The quantitative parameters of the three groups were compared by using one-way ANOVA and pairwise comparisons were performed with LSD. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of these parameters in poorly differentiated groups and non-poorly differentiated groups. RESULTS: There were significant differences in VMI40keV, IC, Eff-Z, and λHU in AP and VP among the three groups (all p < 0.05) except for WC (p > 0.05). The VMI40keV, IC, Eff-Z, and λHU in the poorly differentiated group were significantly higher than those in the other groups both in AP and VP (all p < 0.05). In the ROC analysis, IC performed the best in the identification of the poorly differentiated group and non-poorly differentiated group in VP (AUC = 0.729, Sensitivity = 0.829, and Specificity = 0.569 under the threshold of 21.08 mg/ml). CONCLUSIONS: Quantitative parameters of spectral CT could offer supplemental information for the preoperative differential diagnosis of ESCC with different degrees of differentiation.

Establishment of a Bayesian network model to predict the survival of malignant peritoneal mesothelioma patients after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

OBJECTIVES: To establish a Bayesian network (BN) model to predict the survival of patients with malignant peritoneal mesothelioma (MPM) treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The clinicopathological data of 154 MPM patients treated with CRS + HIPEC at our hospital from April 2015 to November 2022 were retrospectively analyzed. They were randomly divided into two groups in a 7:3 ratio. Survival analysis was conducted on the training set and a BN model was established. The accuracy of the model was validated using a confusion matrix of the testing set. The receiver operating characteristic (ROC) curve and area under the curve were used to evaluate the overall performance of the BN model. RESULTS: Survival analysis of 107 patients (69.5%) in the training set found ten factors affecting patient prognosis: age, Karnofsky performance score, surgical history, ascites volume, peritoneal cancer index, organ resections, red blood cell transfusion, pathological types, lymphatic metastasis, and Ki-67 index (all p < 0.05). The BN model was successfully established after the above factors were included, and the BN model structure was adjusted according to previous research and clinical experience. The results of confusion matrix obtained by internal validation of 47 cases in the testing set showed that the accuracy of BN model was 72.7%, and the area under ROC was 0.74. CONCLUSIONS: The BN model was established successfully with good overall performance and can be used as a clinical decision reference.

Biomass valorization toward sustainable asphalt pavements: Progress and prospects.

To cope with the global climate crisis and assist in achieving the carbon neutrality, the use of biomass materials to fully or partially replace petroleum-based products and unrenewable resources is expected to become a widespread solution. Based on the analysis of the existing literature, this paper firstly classified biomass materials with potential application prospects in pavement engineering according to their application and summarized their respective preparation methods and characteristics. The pavement performance of asphalt mixtures with biomass materials was analyzed and summarized, and the economic and environmental benefits of bio-asphalt binder were evaluated. The analysis shows that pavement biomass materials with potential for practical application can be divided into three categories: bio-oil, bio-fiber, and bio-filler. Adding bio-oil to modify or extend the virgin asphalt binder can mostly improve the low temperature performance of asphalt binder. Adding styrene-butadienestyrene (SBS) or other preferable bio-components for composite modification will have a further improved effect. Most of the asphalt mixtures prepared by using bio-oil modified asphalt binders have improved the low temperature crack resistance and fatigue resistance of asphalt mixtures, but the high temperature stability and moisture resistance may decrease. As a rejuvenator, most bio-oils can restore the high and low temperature performance of aged asphalt and recycled asphalt mixture, and improve fatigue resistance. Adding bio-fiber could significantly improve the high temperature stability, low temperature crack resistance and moisture resistance of asphalt mixtures. Biochar as a bio-filler can slow down the asphalt aging process and some other bio-fillers can improve the high temperature stability and fatigue resistance of asphalt binders. Through calculation, it is found that the cost performance of bio-asphalt has the ability to surpass conventional asphalt and has economic benefits. The use of biomass materials for pavements not only reduces pollutants, but also reduces the dependence on petroleum-based products. It has significant environmental benefits and development potential.

Multifunctional nano-system for multi-mode targeted imaging and enhanced photothermal therapy of metastatic prostate cancer.

Prostate cancer (PCa) routinely employs magnetic resonance (MR) imaging, while metastatic PCa needs more complicated detection methods for precise localization. The inconvenience of using different methods to detect PCa and its metastases in patients and the limitations of single-mode imaging have brought great challenges to clinicians. Meanwhile, clinical treatments for metastatic PCa are still limited. Herein, we report a targeted theranostic platform of Au/Mn nanodots-luteinising hormone releasing hormone (AMNDs-LHRH) nano-system for multi-mode imaging guided photothermal therapy of PCa. The nano-system not only can simultaneously target Gonadotropin-Releasing Hormone Receptor (GnRH-R) positive PCa and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence (FL) visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. Meanwhile, the AMNDs-LHRH with promising targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic PCa. The AMNDs-LHRH nano-system guarantees the diagnostic accuracy and enhanced therapeutic effect, which provides a promising platform for clinical diagnosis and treatment of metastatic PCa. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of prostate cancer and its metastases is challenging. A targeted theranostic platform of AMNDs-LHRH nano-system for multi-mode imaging (FL/CT/MR) guided photothermal therapy of metastatic prostate cancer has been reported. The nano-system not only can simultaneously target prostate cancer and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. The nano-system with great targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic prostate cancer. Overall, the AMNDs-LHRH nano-system integrates tumor targeting, multi-mode imaging and enhanced therapeutic effect, which can provide an effective strategy for the clinical diagnosis and treatment of metastatic PCa.

Effect of standardized fluid management on cardiac function after CRS + HIPEC in patients with PMP: a single-center case-control study.

OBJECTIVE: To investigate the effects of standardized fluid management (SFM) on cardiac function in patients with pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: Patients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. The patients were divided into control and study groups according to whether SFM was applied after CRS + HIPEC. We compared the preoperative and postoperative cardiac and renal function parameters, daily fluid volume three days after CRS, and cardiovascular-related adverse events. Univariate and multivariate analyses were performed to identify the indicators affecting clinical prognosis. RESULT: Among the 104 patients, 42 (40.4%) were in the control group and 62 (59.6%) in the study group. There were no statistically significant differences between the two groups in the main clinicopathological characteristics, preoperative cardiac and renal function parameters, and CRS + HIPEC-related indicators. The incidences of cardiac troponin I (CTNI) > upper limit of normal (ULN), >2 × ULN, >3 × ULN, serum creatinine > ULN, and blood urea nitrogen > ULN were higher in the control group than in the study group (p < 0.05). The median daily fluid volume of the control group was higher than that of the study group 3 days after CRS (p < 0.05). Postoperative CTNI > 2 × ULN was an independent risk factor for serious circulatory adverse events. Survival analysis revealed pathological grading, completeness of cytoreduction score, and postoperative CTNI > ULN as independent prognostic factors. CONCLUSIONS: SFM after CRS + HIPEC in patients with PMP may reduce cardiovascular adverse events risk and improve clinical outcomes.

Near-infrared AIE-active phosphorescent iridium(III) complex for mitochondria-targeted photodynamic therapy.

Mitochondria-targeted photodynamic therapy (PDT) has recently been recognized as a promising strategy for effective cancer treatment. In this work, a mitochondria-targeted near-infrared (NIR) aggregation-induced emission (AIE)-active phosphorescent Ir(III) complex (Ir1) is reported with highly favourable mitochondria-targeted bioimaging and cancer PDT properties. Complex Ir1 has strong absorption in the visible light region (∼500 nm) and can effectively produce singlet oxygen (1O2) under green light (525 nm) irradiation. It preferentially accumulates in the mitochondria of human breast cancer MDA-MB-231 cells as revealed by colocalization analysis. Complex Ir1 displays high phototoxicity toward human breast cancer MDA-MB-231 cells and mouse breast cancer 4T1 cells. Complex Ir1 induces reactive oxygen species (ROS) production, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in MDA-MB-231 cells upon photoirradiation, leading to apoptotic cell death. The favorable PDT performance of Ir1in vivo has been further demonstrated in tumour-bearing mice. Together, the results suggest that Ir1 is a promising photosensitizer for mitochondria-targeted imaging and cancer phototherapy.

Intelligent analysis of carbendazim in agricultural products based on a ZSHPC/MWCNT/SPE portable nanosensor combined with machine learning methods.

A nano-ZnS-decorated hierarchically porous carbon (ZSHPC) was mixed with MWCNTs to obtain ZSHPC/MWCNT nanocomposites. Then, ZSHPC/MWCNTs were used to modify a screen-printed electrode, and a portable electrochemical detection system combined with machine learning methods was used to investigate carbendazim (CBZ) residues in rice and tea. The electrochemical performance of the constructed electrode showed that the electrode had good electrocatalytic ability, large effective surface area, strong stability and anti-interference ability. Support Vector Machine (SVM), Least Square Support Vector Machine (LS-SVM) and Back Propagation-Artificial Neural Network (BP-ANN) were used to establish the prediction model for CBZ residues in rice and tea, and the traditional linear regression was developed. The investigated results showed that the LS-SVM model had the best prediction performance and the lowest prediction error compared with the traditional linear regression, BP-ANN and SVM models. The R2, RMSE, and MAE for the training set samples were 0.9969, 0.3605 and 0.2968, respectively. The R2, RMSE, MAE and RPD for the prediction set samples were 0.9924, 0.6190, 0.5360 and 10.3097, respectively. The average recovery range of CBZ in tea and rice was 98.77-109.32% and that of RSD was 0.47-2.58%, indicating that the rapid analysis of CBZ pesticide residues in agricultural products based on a portable electrochemical detection system combined with machine learning was feasible.

[Changes in the structure and function of soil prokaryotic communities in subalpine Picea asperata plantations]. / äºšé«˜å±±ç²—æžäº‘æ‰äººå·¥æž—åœŸå£¤åŽŸæ ¸å¾®ç”Ÿç‰©ç¾¤è½ç»“æž„ä¸ŽåŠŸèƒ½å˜åŒ–.

The structural and functional characteristics of soil prokaryotic community are important for maintaining ecosystem functions. In this study, we examined the diversity and compositions, the key drivers, as well as functional characteristics of prokaryotic communities in the rhizosphere and non-rhizosphere soils of Picea asperata with different stand ages using high-throughput sequencing technique and bioinformatics methods. The results showed that ß-diversity of soil prokaryotic communities in both rhizosphere and non-rhizosphere showed significant differences among different stand ages, but no significant difference between rhizosphere and non-rhizosphere in the same stand age. In terms of community composition at the phylum level, the relative abundances of Proteobacteria and Rokubacteria showed an increasing trend with the increases of stand age, while the relative abundance of Actinobacteria showed a decreasing trend, but no significant difference was observed between 75 year-old planted forests (PF75) and natural forests (NF). The relative abundances of Firmicutes and Thaumarchaeota in the soil of the 25 year-old planted forests (PF25) were significantly higher than in other planted forests and NF. At the genus level, the relative abundances of RB41, Terrimonas and Acidibacter showed an increasing trend with the increases of stand age, and RB41 and Terrimonas in rhizosphere soil of PF75 were significantly higher than those in NF. Soil properties and vegetation characteristics jointly influenced the structure of soil prokaryotic communities, with herb layer coverage, soil pH, total phosphorus, and total nitrogen as major drivers. The functional characteristics of soil prokaryotic communities were significantly different among different stand ages. The relative abundances of functions involved in carbon and nitrogen cycle, e.g., cellulolysis and nitrification, decreased with the increases of stand age, whereas that of sulfate respiration involved in the sulfur cycle increased. We proposed that the structure and functional characteristics of soil prokaryotic communities could serve as important indicators of the development stages of P. asperata forests. In the later stages of plantation forest development, soil nutrient availability could be improved by mediating phosphorus-dissolving and nitrogen-enhancing microorganisms to maintain the stability of the plantation ecosystem.

A reliable method of high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry for determining selenoamino acids in selenoproteins from Lactococcus lactis.

A reliable method for simultaneous determination of four organic selenium species by HPLC-ICP-MS was developed and implemented in determining organic selenoamino acids (Se-AAs) in selenoproteins from Lactococcus lactis (L. lactis) NZ9000. The method consisted of liberating Se-AAs from selenoproteins using ultrasound-assisted protease hydrolysis, and quantitatively detecting Se-AA speciations by HPLC-ICP-MS. After optimizations of proteolysis conditions, chromatographic conditions and determination conditions, the established method could efficiently separate the four Se-AAs, including SeCys, SeCys2, SeMeCys and SeMet within 10 min. It presented high sensitivity with the limits of detection and quantitation in the range of 0.197∼0.240 µg∙L-1 and 0.788∼0.960 µg∙L-1, respectively, good repeatability with a relative standard deviation (RSD) of less than 5%, and good recovery in the desired floating range of 90%∼105%, verifying the good accuracy. The method successfully detected four selenium species in the purified glutathione peroxidase (LlGPx) overexpressed in L. lactis NZ9000, SeCys (0.9716∼1.6784 µg∙g-1), SeCys2 (1.0695∼1.2124 µg∙g-1), SeMeCys (0.7288∼0.7984 µg∙g-1) and SeMet (1.0058∼1.9571 µg∙g-1), accounting for up to 80.14% of total selenium. There was no difference of order of magnitude in the four Se-AAs, indirectly indicating the random incorporation of selenium into selenoprotein LlGPx in L. lactis NZ9000. This work throws new light on the identification and biosynthesis of organic selenium species in selenoproteins and selenium-riched organisms like L. lactis.

Sorafenib-Loaded Copper Peroxide Nanoparticles with Redox Balance Disrupting Capacity for Enhanced Chemodynamic Therapy against Tumor Cells.

Chemodynamic therapy (CDT) is a promising hydroxyl radical (•OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of •OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved •OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.

Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus.

OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Self-triggered fluorescent metal-organic framework mimic enzyme for competitive immunoassay of hypoglycemic drug in functional tea.

Colorimetric or fluorescent biosensors based on mimic enzymes have come into the spotlight in virtue of their visual detection. In traditional visual sensors, fluorescent-changing or color-changing substances should be introduced for the catalytic reaction with mimic enzymes. Herein, a mimic enzyme (Au@Fe-MIL-88B) with self-triggered fluorescent property was prepared. By incorporating Au nanoparticles (Au NPs) in Fe-MIL-88B, a higher peroxidase activity of Au@Fe-MIL-88B was monitored due to the synergistic effect between Au NPs and Fe-MIL-88B. Besides, Au NPs can change the valence of Fe ion in metal organic framework (MOF), thus lower background fluorescence was discovered, but the addition of H2O2 can trigger the self-fluorescence of Au@Fe-MIL-88B. By using Au@Fe-MIL-88B as a label to anchor secondary antibody, a competitive immunosensor based on fluorescence and photoelectrochemistry was constructed for the immunoassay of rosiglitazone (RSG), a kind of hypoglycemic drug. Finally, a portable instrument was homemade for the on-site and convenient detection of RSG in functional tea. This self-triggered fluorescent MOF may provide a possible route to design biosensors for the detection of hazardous materials.

Location Analysis of Volatile Oil in Angelicae Sinensis Radix by Frozen Section and Fluorescence Imaging / 中国实验方剂学杂志

ObjectiveTo establish a simple， fast and accurate method for locating the volatile oil in Angelicae Sinensis Radix based on frozen section and fluorescence imaging technology， and to reveal the distribution and accumulation of volatile oil in the roots of this herbal medicine. MethodAngelicae Sinensis Radix was used as the research material， the best frozen section conditions for the research material were established by comparing the effects of different cryoprotectants on the quality of frozen sections of Angelicae Sinensis Radix. The suitability of Sudan Ⅲ chemical staining and fluorescence localization for positioning the volatile oil were compared according to the loss of volatile oil and the complexity of operation process. ResultA new method for evaluating the quality of frozen sections of Angelicae Sinensis Radix was established. According to the evaluation equation， it was found that the highest score was obtained when the head， body and tail positions of Angelicae Sinensis Radix were treated with 20% glycerol， 15% glycerol and 20% sucrose， respectively. There was yellowish-brown oily substance in the oil chambers of phelloderm and secondary phloem， and oil canal of the secondary xylem of Angelicae Sinensis Radix， which could be stained orange red or orange yellow by Sudan Ⅲ， and there was green spontaneous fluorescence in the same part under the fluorescence microscope. ConclusionThe relatively complete section of Angelicae Sinensis Radix can be obtained after being treated with cryoprotectant. The volatile oil exists in the oil chambers of phelloderm and secondary phloem， and oil canal of the secondary xylem of Angelicae Sinensis Radix. This study can provide reference for observation of the accumulation sites of volatile oil in other plants.

Flavonoids from Hypericum patulum enhance glucose consumption and attenuate lipid accumulation in HepG2 cells.

Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound-healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin-resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)-treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n-dotriacontanol (1), shikimic acid (2), 1-O-caffeoylquinic acid methyl ester (3), 5-O-caffeoylquinic acid methyl ester (4), 5-O-coumaroylquinic acid methyl ester (5), 5-O-caffeoylquinic acid butyl ester (6), quercetin-3-O-α-L-rhamnoside (7), quercetin (8), quercetin-3-O-(4×´-methoxy)-α-L-rahmnopyranosyl (9), hyperoside (10), and rutin (11). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin-resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 µM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 µM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA-treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. PRACTICAL APPLICATIONS: Hypericum patulum is a well-known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin-resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA-treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1, 2, 3, 5, 6, 9, 10, and 11 were isolated from the plant for the first time. Quercetin-3-O-(4"-methoxy)-α-L-rahmnopyranosyl (9) and hyperoside (10) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum.

Pharmacokinetics and Tissue Distribution of Combined Triptolide and Paeoniflorin Regimen for Percutaneous Administration in Rats Assessed by Liquid Chromatography-Tandem Mass Spectrometry.

Triptolide (TP) has shown potential in rheumatoid arthritis (RA) treatment, but the narrow therapeutic window limits its clinical application. In clinical practice, the compatibility of Tripterygium wilfordii and Paeonia lactiflora is often used to attenuate the toxicity of TP, but its compatibility mechanism has not been fully elucidated. The aim of this study was to investigate the pharmacokinetics and tissue distribution of a combined regimen of TP and paeoniflorin (PF) after transdermal administration in male and female Sprague Dawley (SD) rats via a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The results showed that after percutaneous administration of TP and PF, there was no significant difference in AUC (0-t) (area under the curve) of TP, the peak concentration decreased by 58.17%, and the peak time was delayed. The AUC (0-t) of PF increased significantly (P < 0.01), the peak-reaching concentration and AUC (0-∞) increased, and the half-life and average retention time were shortened, indicating that TP absorption in rats may be delayed. After percutaneous administration of TP and PF, the content of TP in the heart, liver, spleen, lungs, and kidneys of male rats significantly decreased at 2 h (P < 0.05) and the drug concentration in the liver tissues significantly decreased at 2 h, 4 h, and 8 h (P < 0.05). The TP content in the spleen of female rats significantly decreased at 2 h and 4 h (P < 0.05) and also decreased in other tissues, but not significantly. After percutaneous administration of TP and PF, the PF content in the heart, liver, spleen, lungs, and kidneys of male and female rats had no significant difference. However, after percutaneous administration of TP and PF, the TP concentration in the skin increased, suggesting that the amount of TP retained in the skin increased, thereby reducing its content in blood and tissues, producing a reduction in toxicity effect.

APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia.

The E4 allele of the apolipoprotein E gene (APOE) has been established as a genetic risk factor for many diseases including cardiovascular diseases and Alzheimer's disease (AD), yet its mechanism of action remains poorly understood. APOE is a lipid transport protein, and the dysregulation of lipids has recently emerged as a key feature of several neurodegenerative diseases including AD. However, it is unclear how APOE4 perturbs the intracellular lipid state. Here, we report that APOE4, but not APOE3, disrupted the cellular lipidomes of human induced pluripotent stem cell (iPSC)-derived astrocytes generated from fibroblasts of APOE4 or APOE3 carriers, and of yeast expressing human APOE isoforms. We combined lipidomics and unbiased genome-wide screens in yeast with functional and genetic characterization to demonstrate that human APOE4 induced altered lipid homeostasis. These changes resulted in increased unsaturation of fatty acids and accumulation of intracellular lipid droplets both in yeast and in APOE4-expressing human iPSC-derived astrocytes. We then identified genetic and chemical modulators of this lipid disruption. We showed that supplementation of the culture medium with choline (a soluble phospholipid precursor) restored the cellular lipidome to its basal state in APOE4-expressing human iPSC-derived astrocytes and in yeast expressing human APOE4 Our study illuminates key molecular disruptions in lipid metabolism that may contribute to the disease risk linked to the APOE4 genotype. Our study suggests that manipulating lipid metabolism could be a therapeutic approach to help alleviate the consequences of carrying the APOE4 allele.