Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel.

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation. Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel. Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine. Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

Cystine deprivation triggers CD36-mediated ferroptosis and dysfunction of tumor infiltrating CD8+ T cells.

Cancer cells develop multiple strategies to evade T cell-mediated killing. On one hand, cancer cells may preferentially rely on certain amino acids for rapid growth and metastasis. On the other hand, sufficient nutrient availability and uptake are necessary for mounting an effective T cell anti-tumor response in the tumor microenvironment (TME). Here we demonstrate that tumor cells outcompete T cells for cystine uptake due to high Slc7a11 expression. This competition induces T-cell exhaustion and ferroptosis, characterized by diminished memory formation and cytokine secretion, increased PD-1 and TIM-3 expression, as well as intracellular oxidative stress and lipid-peroxide accumulation. Importantly, either Slc7a11 deletion in tumor cells or intratumoral cystine supplementation improves T cell anti-tumor immunity. Mechanistically, cystine deprivation in T cells disrupts glutathione synthesis, but promotes CD36 mediated lipid uptake due to dysregulated cystine/glutamate exchange. Moreover, enforced expression of glutamate-cysteine ligase catalytic subunit (Gclc) promotes glutathione synthesis and prevents CD36 upregulation, thus boosting T cell anti-tumor immunity. Our findings reveal cystine as an intracellular metabolic checkpoint that orchestrates T-cell survival and differentiation, and highlight Gclc as a potential therapeutic target for enhancing T cell anti-tumor function.

The Neuroprotective Effects of Electroacupuncture on Parkinson's Disease and the Underlying Molecular Mechanisms.

Parkinson's disease (PD) is a chronic neurodegenerative disease whose main pathological features are the degeneration of dopamine neurons and deposition of α-synuclein in neurons. At present, the most important treatment strategy for PD is drugs, and one of the most used drugs is levodopa. However, this therapy shows many problems, such as tolerance and long-term effects, so other treatment strategies need to be explored. As a traditional Chinese medicine treatment method with effective and few side effects, electroacupuncture is considered a non-drug therapy. It serves as a novel, promising therapeutic approach for the treatment of PD. In this review, the application and the effects of electroacupuncture on PD have been described. Besides, the underlying molecular mechanisms of electroacupuncture on PD that contribute to protecting dopaminergic neurons and reducing α-synuclein levels have been illustrated, including ① anti-oxidant stress response, ② anti-neuroinflammatory response, ③ up-regulation of neurotrophic factors and reduction of nerve cell apoptosis, ④ down-regulation of endoplasmic reticulum stress and improvement of mitochondrial function, ⑤ improvement of the function of the ubiquitin-proteasome system, ⑥ anti-excitatory toxicity response, ⑦ activation of autophagy, and ⑧ modulation of gut microbiota. Achieving a better understanding of the neuroprotective effects of electroacupuncture on PD will provide a theoretical basis and facilitate the application of electroacupuncture on PD.

Effect of Different Phosphates on Pyrolysis Temperature-Dependent Carbon Sequestration and Phosphorus Release Performance in Biochar.

Carbon sequestration is the primary function of biochar. Hence, it is necessary to design biochar with high carbon (C) retention and low C loss. In this study, three P compounds, including KH2PO4, Ca(H2PO4)2, and NH4H2PO4, were premixed with corn stalk (1:4, w/w), aiming to produce biochars (CSB+K, CSB+Ca, and CSB+N) with high C sequestration and slow release of P at three temperatures (300, 500, and 700 °C). The addition of all P sources obviously increased C retention, with the order of NH4H2PO4 (65.6-83.5%) > Ca(H2PO4)2 (60.4-78.2%) > KH2PO4 (50.1-76.1%), compared with the pristine biochar (47.8-73.6%). The addition of Ca(H2PO4)2 and KH2PO4 led to an increase in aromaticity and graphitization, as evidenced by H/C, FTIR, Raman and XPS analysis, whereas an opposite result occurred on CSB+N. Furthermore, all three phosphates reduced C loss of biochars with H2O2 oxidation, and CSB+Ca showed the best effect. Ca(H2PO4)2 and KH2PO4 pretreated biochars had higher resistance to K2Cr2O7 oxidation and thermal treatment. In contrast, the C loss of NH4H2PO4-added biochar at 500 and 700 °C with K2Cr2O7 oxidation was increased by 54% and 36%, respectively. During the pyrolysis process, Ca(H2PO4)2 was transformed into insoluble Ca2P2O7, leading to the lowest P release rate of CSB+Ca. This study indicates that co-pyrolysis of corn stalk and Ca(H2PO4)2 is optimal for increasing C retention, enhancing C stability and improving slow-release performance of P regardless of pyrolysis temperature.

Influence of anthropogenic nitrogen inputs and legacy nitrogen change on riverine nitrogen export in areas with high agricultural activity.

Increased riverine nitrogen (N) concentrations due to human activities is one of the leading causes of water quality decline, worldwide. Therefore, quantitative information about the N exported from watershed to the river (TN exports) is essential for defining N pollution control practices. This paper evaluated the changes in net anthropogenic N inputs (NANI) and the N stored in land ecosystems (legacy N) in the Jianghan Plain (JHP) from 1990 to 2019 and their impacts on TN exports. Moreover, an empirical model was developed to estimate TN exports, trace its source, and predict its future variations in 2020-2035 under different scenarios. According to the results, NANI exhibited a rise-decrease-rise-decrease M-shaped trend, with N fertilizer application being the dominant driver for NANI change. In terms of the NANI components, non-point-source was the primary N input form (96%). Noteworthy is that the correlation between NANI and TN exports became weaker over time, and large differences in changing trends were observed after 2014. A likely cause for this abnormal trend was that the accumulation of N surplus in soil led to N saturation in agricultural areas. Legacy N was also an important source of TN exports. However, the contribution of legacy N has rarely been considered when defining N pollution control strategies. An empirical model, incorporating legacy N, agricultural irrigation water use, and cropland area ratio, was developed. Based on this model, legacy N contributed a large proportion (15-31%). Furthermore, the results of future predictions indicated that legacy N had a larger impact on future TN exports changes compared to other factors, and increased irrigation water would increase rather than decrease TN exports. Therefore, an integrated N management strategy considering the impact of NANI, legacy N, and irrigation water use is crucial to control N pollution in areas with intensive agriculture.

Vacuum-assisted thermal bonding of ß-cyclodextrin and its derivatives as chiral stationary phases for high-performance liquid chromatography.

In this work, the vacuum-assisted thermal bonding method was proposed for the covalent coupling of ß-cyclodextrin (ß-CD) (CD-CSP), hexamethylene diisocyanate cross-linked ß-CD (HDI-CSP) and 3, 5-dimethylphenyl isocyanate modified ß-CD (DMPI-CSP) onto the isocyanate silane modified silica gel. Under vacuum conditions, the side reaction due to the water residue from the organic solvent, air, reaction vessels and silica gel could be avoided, and the optimal temperature and time of vacuum-assisted thermal bonding method were determined as 160°C and 3 h. These three CSPs were characterized by FT-IR, TGA, elemental analysis and the nitrogen adsorption-desorption isotherms. The surface coverage of CD-CSP and HDI-CSP on silica gel was determined as ∼0.2 µmol m-2, respectively. The chromatographic performances of these three CSPs were systematically evaluated by separating 7 flavanones, 9 triazoles and 6 chiral alcohols enantiomers under the reversed-phase condition. It was found that the chiral resolution ability of CD-CSP, HDI-CSP and DMPI-CSP was complementary to each other. Among them, CD-CSP could separate all 7 flavanones enantiomers with the resolution of 1.09-2.48. HDI-CSP had a good separation performance for triazoles enantiomers with one chiral center. DMPI-CSP showed excellent separation performance for chiral alcohol enantiomers, among which the resolution of trans-1, 3-diphenyl-2-propen-1-ol reached 12.01. Generally, the vacuum-assisted thermal bonding had been demonstrated as a direct and efficient method for the preparation of chiral stationary phases of ß-CD and its derivatives.

[Systematic review and Meta-analysis of efficacy and safety of Tangmaikang Granules in treatment of diabetic peripheral neuropathy].

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.

Development of a polyurethane-coated thin film solid phase microextraction device for multi-residue monitoring of pesticides in fruit and tea beverages.

A novel solid-phase microextraction device coated with an efficient and cheap thin film of polyurethane was developed for trace determination of 13 widely used pesticides in fruit and tea beverages. A round-shaped polyurethane film covering the bottom of a glass vial was fabricated as the sorbent to exhibit a superior capacity for preconcentrating target compounds and reducing matrix interferences. After optimization of the key parameters including the film type, extraction time, solution pH, ionic strength, desorption solvent, and conditions, this device allowed an efficient adsorption-desorption cycle for the pesticides accomplished in one vial. Coupled with gas chromatography-electron capture detection, the polyurethane-coated thin film microextraction method was successfully established and applied for the analysis of real fruit and tea drinks, showing low limits of detection (0.001-0.015 µg/L), wide linear ranges (1.0-500.0 µg/L, r2  > 0.9931), good relative recoveries (77.2%-106.3%) and negligible matrix effects (86.1%-107.5%) for the target pesticides. The proposed approach revealed strong potential of extending its application by flexibly modifying the type or size of the coating film. This study provides insights into the enrichment of contaminants from complex samples using inexpensive and reusable microextraction devices that can limit the environmental and health impact of the sample preparation protocol.

Selenium-Enriched Soybean Peptides as Novel Organic Selenium Compound Supplements: Inhibition of Occupational Air Pollution Exposure-Induced Apoptosis in Lung Epithelial Cells.

The occupational groups exposed to air pollutants, particularly PM2.5, are closely linked to the initiation and advancement of respiratory disorders. The aim of this study is to investigate the potential protective properties of selenium-enriched soybean peptides (Se-SPeps), a novel Se supplement, in mitigating apoptosis triggered by PM2.5 in A549 lung epithelial cells. The results indicate a concentration-dependent reduction in the viability of A549 cells caused by PM2.5, while Se-SPeps at concentrations of 62.5-500 µg/mL showed no significant effect. Additionally, the Se-SPeps reduced the production of ROS, proinflammatory cytokines, and apoptosis in response to PM2.5 exposure. The Se-SPeps suppressed the PM2.5-induced upregulation of Bax/Bcl-2 and caspase-3, while also restoring reductions in p-Akt in A549 cells. The antiapoptotic effects of Se-SPeps have been found to be more effective compared to SPeps, SeMet, and Na2SeO3 when evaluated at an equivalent protein or Se concentration. Our study results furnish evidence that supports the role of Se-SPeps in reducing the harmful effects of PM2.5, particularly in relation to its effect on apoptosis, oxidative stress, and inflammation.

Uncovering the pharmacological mechanisms of Zizhu ointment against diabetic ulcer by integrating network analysis and experimental evaluation in vivo and in vitro.

Diabetic ulcer (DU) has been recognized as one of the most prevalent and serious complications of diabetes. However, the clinical efficacy of standard treatments for DU remains poor. Traditional Chinese medicine (TCM) shows a positive therapeutic effect on DU. Specifically, Zizhu ointment (ZZO) has been widely used to treat DU in long-term clinical practice, but the exact mechanism by which it promotes DU wound healing remains unknown. In this study, network analysis and high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) were conducted to identify the active compounds of ZZO. We detected isovalerylshikonin (ISO), mandenol, daidzein, kaempferol, and formononetin in both network analysis and UPLC-HRMS. Moreover, ZZO could ameliorate DU by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and inflammation signaling pathways, according to the results of KEGG analysis. We established a DU mouse model with a high-fat diet and streptozotocin injection in vivo to evaluate the network analysis result. The experimental results showed that ZZO could inhibit inflammation, remodel fibrous tissue, and promote angiogenesis in the DU area, facilitating wound healing in DU mice. Moreover, the PI3K/AKT signaling pathway was indeed activated by ZZO treatment, promoting macrophage M2 polarization. In addition, we used molecular docking technology to evaluate the binding sites between ZZO and the PI3K/AKT pathway. The results showed that ISO has a good binding interaction with AKT. Moreover, ISO promoted M2 polarization in macrophages in a dose-dependent manner in vitro. Our study found that ZZO could promote DU wound healing by inhibiting inflammation, which was achieved by macrophage M2 polarization through activating the PI3K/AKT pathway. Further studies have demonstrated that ISO plays major role in the above process. These findings provide a theoretical basis for further preclinical evaluation and lay a foundation for nano-gel compound treatment with ZZO.

Molecular dynamics simulation on water/oil interface with model asphaltene subjected to electric field.

HYPOTHESIS: The droplet-medium interfaces of petroleum emulsions are often stabilized by the indigenous surface-active compounds (e.g., asphaltenes), causing undesired issues. While demulsification by electric field is a promising technique, fundamental study on the droplet-medium interface influenced by electric field is limited. Molecular dynamics (MD) simulations are expected to provide microscopic insights into the nano-scaled water/oil interface. METHODS: MD simulations are conducted to study the adsorption of model asphaltene molecules (represented by N-(1-hexylheptyl)-N'-(5-carboxylicpentyl) perylene-3,4,9,10-tetracarboxylic bisimide (C5Pe)) on a water-toluene interface under various strengths of electric field. The adsorption amount and structural feature of C5Pe molecules at water-toluene interface are investigated, and the effects of electric field and salt are discussed. FINDINGS: C5Pe molecules tend to adsorb on the water-oil interface. As the electric field strength increases, the adsorption amount first slightly increases (or remains constant) and then decreases. The electric field disrupts the compact π-π stacking between C5Pe molecules and increases their mobility, causing a dispersed distribution of the molecules with a wide range of orientations relative to the interface. Within the studied range, the addition of salt ions appears to stabilize the interface at high electric field. These results provide useful insights into the mechanism and feasibility of demulsification under electric field.

Dynamic characteristics of net anthropogenic phosphorus input and legacy phosphorus reserves under high human activity - A case study in the Jianghan Plain.

The increase of phosphorus (P) input related to human activities is one of the main reasons for eutrophication. Notably, in areas with high population densities and intensive agricultural activities, eutrophication has occurred frequently in the Jianghan Plain, so quantitative evaluation of anthropogenic P input is of great significance for the formulation of P pollution control measures. This study estimated net anthropogenic P input (NAPI), riverine total P exports (TP exports), and the pool of P stored in the terrestrial system (legacy P reserves) at the county scale from 1990 to 2019 in the Jianghan Plain. The results showed that NAPI increased from 2645 kg·km-2·yr-1 in 1991 to 5812 kg·km-2·yr-1 in 2014, and then decreased to 4509 kg·km-2·yr-1 in 2019. Non-point sources were the main form of NAPI, of which 75-96% came from agricultural systems. Meanwhile, P fertilizer input was the largest source of NAPI. It is worth noting that the contribution of seed P input in some counties, such as Jiangling County, is relatively high, even exceeding that of net food/feed P input. The P fertilizer application and livestock density were the main drivers for NAPI change. Only 3% of NAPI was exported into rivers, so a large amount of legacy P accumulated in the terrestrial system. An empirical model incorporating NAPI components, cultivated land area ratio, and annual precipitation was established. Based on this model, the average contribution of annual NAPI and the sum of legacy P and natural background sources to TP exports were calculated to be 71% and 29%, respectively. So it is necessary to control P pollution by improving fertilizer use efficiency and enhancing manure management. The results provide a scientific basis for targeted solutions to the sources of P nutrient and its control measures in the middle reach of the Yangtze River.

Encapsulation of Curcumin in a Ternary Nanocomplex Prepared with Carboxymethyl Short Linear Glucan-Sodium-Caseinate-Pectin Via Electrostatic Interactions.

This work chemically modified short linear glucan (SLG) by introducing a surface carboxymethyl group to obtain carboxymethylated SLG (CMSLG), then prepared CMSLG-based ternary nanocomplex particles based on electrostatic interactions with sodium-caseinate (NaCas) and pectin. These nanocomplex particles are homogeneous, generally exhibiting sizes of <200 nm with spherical shape and negative surface charge. In addition, the results showed the increase in both the mass ratio of CMSLG and NaCas and the synthesis temperature can improve the colloidal stability of nanocomplex particles when they are exposed to simulated gastrointestinal fluids containing digestive enzymes. Moreover, nanocomplex particles have an exceptional capability to encapsulate curcumin, and this encapsulation efficiency increased as the mass ratios of CMSLG and NaCas were increased. The study also investigated the antioxidant activity and in vitro release properties of curcumin encapsulated by nanocomplex particles and found that CMSLG/NaCas/pectin had improved higher ABTS radical scavenging capacity and allowed for the controlled, sustained release of curcumin in simulated gastrointestinal fluid within 6 hours. Thus, this study provides new insights into the design of a CMSLG-based ternary nanocomplex and its use as a potential oral delivery system for lipophilic bioactive compounds. PRACTICAL APPLICATION: Curcumin, as a sort of natural polyphenolic compound, has many physiologic functions such as anti-oxidation, anticancer, and prevention of Alzheimer's disease. However, the application of the curcumin has been limited by its poor water solubility and unstable physicochemical property. To solve this problem, the nanotechnology has been used to prepare the nano-delivery carriers for curcumin. This work prepared a ternary nanoparticle based on the carboxymethyl short linear glucan, sodium-caseinate, and pectin. The ternary nanoparticle can achieve a higher encapsulation efficiency for curcumin. In addition, the ternary nanoparticle can enhance the ABTS radical scavenging capacity and provided control and sustained release of curcumin in the simulated gastrointestinal fluid.

Biological composition analysis of a natural medicine, Faeces Vespertilionis, with complex sources using DNA metabarcoding.

Faeces Vespertilionis is a commonly used fecal traditional Chinese medicine. Traditionally, it is identified relying only on morphological characters. This poses a serious challenge to the composition analysis accuracy of this complex biological mixture. Thus, for quality control purposes, an accurate and effective method should be provided for taxonomic identification of Faeces Vespertilionis. In this study, 26 samples of Faeces Vespertilionis from ten provinces in China were tested using DNA metabarcoding. Seven operational taxonomic units (OTUs) were detected as belonging to bats. Among them, Hipposideros armiger (Hodgson, 1835) and Rhinolophus ferrumequinum (Schober and Grimmberger, 1997) were the main host sources of Faeces Vespertilionis samples, with average relative abundances of 59.3% and 24.1%, respectively. Biodiversity analysis showed that Diptera and Lepidoptera were the most frequently consumed insects. At the species level, 19 taxa were clearly identified. Overall, our study used DNA metabarcoding to analyze the biological composition of Faeces Vespertilionis, which provides a new idea for the quality control of this special traditional Chinese medicine.

One-step synthesis of garlic peel derived biochar by concentrated sulfuric acid: Enhanced adsorption capacities for Enrofloxacin and interfacial interaction mechanisms.

This study put forward a one-step carbonization method by concentrated sulfuric acid to prepare garlic peel derived biochar, and the synthetic conditions were optimized by L16(45) orthogonal experiments. Notably, in order to study the differences between the proposed synthetic method and the conventional pyrolysis method, the concentrated sulfuric acid carbonized garlic peels biochar (CSGPB) was compared with pyrolysis derived garlic peel biochar (HTGPB) in characterization and adsorption capacities for Enrofloxacin (ENR). Results showed that CSGPB exhibited more graphite-like structures with more active functional groups on the surface, and the equilibrium adsorption capacity of CSGPB (142.3 mg g-1) was 13.7 times of HTGPB (10.4 mg g-1) under identical conditions. Moreover, the adsorption behaviors including adsorption kinetics, isotherms and thermodynamics of CSGPB for ENR were fully investigated and discussed. Based on the above experiments, density functional theory (DFT) simulations were performed to reveal the interfacial interaction and adsorption mechanism. Results showed π-π interaction between quinolone moieties of ENR and graphite-like structures in CSGPB might be the dominant mechanism. As for the functional groups, the adsorption energies were -40.46, -15.21 and -5.96 kJ mol-1 for -SO3H, -OH and -COOH, respectively, which indicated -SO3H was the most active functional groups on the surface of CSGPB. This study provided a new sustainable perspective for the design of efficient biochars, and explored the interfacial interaction mechanism of antibiotics removal on biochars.

Grape Seed Proanthocyanidin Ameliorates FB1-Induced Meiotic Defects in Porcine Oocytes.

Fumonisin B1 (FB1), as the most prevalent and toxic fumonisin, poses a health threat to humans and animals. The cytotoxicity of FB1 is closely related to oxidative stress and apoptosis. The purpose of this study is to explore whether Grape seed proanthocyanidin (GSP), a natural antioxidant, could alleviate the meiotic maturation defects of oocytes caused by FB1 exposure. Porcine cumulus oocyte complexes (COCs) were treated with 30 µM FB1 alone or cotreated with 100, 200 and 300 µM GSP during in vitro maturation for 44 h. The results show that 200 µM GSP cotreatment observably ameliorated the toxic effects of FB1 exposure, showing to be promoting first polar body extrusion and improving the subsequent cleavage rate and blastocyst development rate. Moreover, 200 µM GSP cotreatment restored cell cycle progression, reduced the proportion of aberrant spindles, improved actin distribution and protected mitochondrial function in FB1-exposed oocytes. Furthermore, reactive oxygen species (ROS) generation was significantly decreased and the mRNA levels of CAT, SOD2 and GSH-PX were obviously increased in the 200 µM GSP cotreatment group. Notably, the incidence of early apoptosis and autophagy level were also significantly decreased after GSP cotreatment and the mRNA expression levels of BAX, CASPASE3, LC3 and ATG5 were markedly decreased, whereas BCL2 and mTOR were observably increased in the oocytes after GSP cotreatment. Together, these results indicate that GSP could exert significant preventive effects on FB1-induced oocyte defects by ameliorating oxidative stress through repairing mitochondrial dysfunction.

Immunomodulatory effects of selenium-enriched peptides from soybean in cyclophosphamide-induced immunosuppressed mice.

In this study, selenium-enriched soybean peptides (<3 kDa, named Se-SPep) was isolated and purified from the selenium-enriched soybean protein (Se-SPro) hydrolysate by ultrafiltration. The in-vivo immunomodulatory effects of Se-SPep were investigated in cyclophosphamide-induced immunosuppressed mice. Se-SPep treatment could alleviate the atrophy of immune organs and weight loss observed in immunosuppressive mice. Besides, Se-SPep administration could dramatically improve total protein, albumin, white blood cell, immunoglobulin (Ig) M, IgG, and IgA levels in blood. Moreover, Se-SPep strongly stimulated interleukin-2 (IL-2), interferon-gamma (IFN-γ), nitric oxide (NO), and cyclic guanosine monophosphate productions by up-regulating mRNA expressions of IL-2, IFN-γ, and inducible NO synthase in spleen tissue. Furthermore, Se-SPep exhibits more effective immunomodulatory activity compared to Se-SPro and SPep. In conclusion, Se-SPep could effectively enhance the immune capacity of immunosuppressive mice. These findings confirm Se-SPep is an effective immunomodulator with potential application in functional foods or dietary supplements.

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

Combination of polyurethane and polymethyl methacrylate thin films as a microextraction sorbent for rapid adsorption and sensitive determination of neonicotinoid insecticides in fruit juice and tea by ultra high performance liquid chromatography with tandem mass spectrometry.

An economical and effective thin film microextraction (TFME) for simultaneous analysis of ten neonicotinoid insecticides and metabolites in fruit juice and tea, was developed based on the combination of polyurethane (PU) and polymethyl methacrylate (PMMA) films as the sorbent followed by ultra high performance liquid chromatography with tandem mass spectrometry. The PU/PMMA composite was evidenced to possess rapid adsorption and strong accumulation towards neonicotinoids compared with the films used alone. A series of parameters were optimized, and the agitation mode, film size, ionic strength, desorption solvent and sample pH were found to dominate the microextraction process rather than the extraction temperature, agitation time and sample volume. The thin films are cost effective and efficient for single use analysis, but still can be reused at least 8 times with no significant loss in performance. The ten neonicotinoids were measured with good recoveries (81.1-107.9%), high enrichment factors (up to 135), low limits of detection (0.001-0.1 µg L-1), and wide linearity range (1-500 µg L-1, r2>0.9981) in fruit juice (apple, lemon, and pomegranate) and tea (green tea and black tea) samples. The proposed method was successfully applied to commercial fruit and tea drinks, and no samples were tested positive on target neonicotinoids. The PU/PMMA based TFME has shown great potential as an alternative to exhaustive extraction techniques for routine screening of trace neonicotinoids in fruit juice and tea by simplifying the analytical procedure, shortening the operation time, and lowering the material expense.

Xueshuantong Injection in Treating Deep Venous Thrombosis: A Systematic Review and Trial Sequential Analysis.

AIMS: In recent years, the incidence of deep venous thrombosis (DVT) presents an increasing trend year by year. The current evidence regarding the efficacy and safety of Xueshuantong injection for DVT is controversial. This systematic review (SR) aimed to assess the efficacy and safety of Xueshuantong injection in the treatment of DVT systematically and provide an evidence-based reference for clinical treatment. METHODS: Nine electronic databases were used to identify the literature consisting of randomized controlled trials (RCTs) with a date of search of 1 November 2020. Clinical effective rate and incidence rate of adverse events were investigated as primary outcomes. Patency rate of femoral vein, patency rate of popliteal vein, patency rate of posterior tibial vein, circumference difference, activated partial thromboplastin time (APTT), and D-dimer (D-D) were investigated as secondary outcomes. Revman 5.4.1 was used to analyze the results. Analysis of the power of evidence was performed with Trial Sequential Analysis (TSA). RESULTS: A total of 12 articles including 1018 patients were included. The results of the meta-analysis showed that the clinical effective rate in the experimental group was higher than that in the control group, the incidence rate of adverse events in the experimental group was higher than that in the control group; after the operation, the patency rate of femoral vein, patency rate of popliteal vein, patency rate of posterior tibial vein, circumference difference, APTT, and D-D in the experimental group were significantly improved compared with those in the control group, and the difference between the groups was statistically significant. TSA suggested that the meta-analysis concerning the clinical effectiveness of Xueshuantong injection in the treatment of DVT was of adequate power to reach firm conclusions. CONCLUSION: Based on the current analysis, Xueshuantong injection as an add-on treatment provided better treatment effect for DVT with adequate power but this benefit should be considered with caution because of the small number of studies included in the meta-analysis and the high or unclear risk of bias of the included trials, suggesting that further studies are needed.