Preparation of limonin monoclonal antibody and establishment of a sensitive icELISA for analyzing limonin in citrus and herbal samples.

Limonin is an intensely bitter and highly oxidized tetracyclic triterpenoid secondary metabolite, which is abundant in the Rutaceae and Meliaceae, especially in Citrus. In order to detect limonin content in complex substrates such as citrus and traditional Chinese medicine, monoclonal antibodies specifically recognizing limonin were prepared and an indirect competitive enzyme-linked immunosorbent assay (icELISA) was established. The median inhibition concentration (IC50) was 5.40 ng/mL and the linear range was 1.25-23.84 ng/mL. The average recoveries from citrus peel and pulp samples were 95.9%-118.8% and 77.5%-113.1%, respectively. Moreover, the contents of limonin in 6 citrus samples and 4 herbal samples were analyzed by icELISA and UPLC-MS, and the results of the two methods were consistent. This validation is sufficient to demonstrate that the developed immunoassay is applicable for the detection of limonin in citrus and herbal samples and has the advantage of high efficiency, sensitivity, and convenience.

Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine.

Selenium is an essential multifunctional trace element in diverse organisms. The only Se-glycosyltransferase identified that catalyzes the incorporation of selenium in selenoneine biosynthesis is SenB from Variovorax paradoxus. Although the biochemical function of SenB has been investigated, its substrate specificity, structure, and catalytic mechanism have not been elucidated. Here, we reveal that SenB exhibits sugar donor promiscuity and can utilize six UDP-sugars to generate selenosugars. We report crystal structures of SenB complexed with different UDP-sugars. The key elements N20/T23/E231 contribute to the sugar donor selectivity of SenB. A proposed catalytic mechanism is tested by structure-guided mutagenesis, revealing that SenB yields selenosugars by forming C-Se glycosidic bonds via spontaneous deprotonation and disrupting Se-P bonds by nucleophilic water attack, which is initiated by the critical residue K158. Furthermore, we functionally and structurally characterize two other Se-glycosyltransferases, CbSenB from Comamonadaceae bacterium and RsSenB from Ramlibacter sp., which also exhibit sugar donor promiscuity.

Bibliometric analysis of global literature productivity in systemic lupus erythematosus from 2013 to 2022.

BACKGROUND: Bibliometric analysis is a mature method for quantitative evaluation of academic productivity. In view of the rapid development of research in the field of systemic lupus erythematosus (SLE) in the past decade, we used bibliometric methods to comprehensively analyze the literature in the field of SLE from 2013 to 2022. METHODS: The relevant literature in the field of SLE from 2013 to 2022 was screened in the Web of Science Core Collection database. After obtaining and sorting out the data, CiteSpace and VOSviewer software were used to visualize the relevant data, and SPSS software was used for scientific statistics. RESULTS: A total of 18,450 publications were included in this study. The number of articles published over the past 10 years has generally shown an upward trend, while Altmetric attention scores have also shown a clear upward trend in general and in most countries. Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers. The USA, China, Japan, Italy, and the UK are the most productive countries, but China and Japan are significantly inferior to other countries in terms of research influence. Four of the top ten authors are at the center of the collaboration network. LUPUS is the most contributing journal. The theme of systemic lupus erythematosus research mainly focuses on the pathogenesis, treatment, and management of SLE, and the emerging trend is related research on machine learning and immune cells. CONCLUSION: This study shows the research status of SLE, clarifies the main contributors in this field, discusses and analyzes the research hotspots and trends in this field, and provides reference for further research in this field to promote the development of SLE research. Key Points • Through bibliometric analysis, Altmetric analysis, and visual analysis, we reveal the global productivity characteristics of SLE-related papers in the past 10 years. • The number of global SLE-related studies has shown a significant increase, indicating that SLE is still a hot topic and deserves further study. • Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers, and the attention of related literature among non-professional researchers is increasing. • The theme of SLE research mainly focuses on the pathogenesis, treatment, and management of SLE. The emerging trend is machine learning and immune cells, which may provide new strategies for the diagnosis and treatment of SLE in the future.

Effect of continuous instant pressure drop treatment on the rheological properties and volatile flavor compounds of whole highland barley flour.

Continuous instant pressure drop (CIPD) treatment effectively reduces microbial contamination in whole highland barley flour (WHBF). Base on it, this study further investigated its effects on flour properties (especially rheological properties) and volatile compounds (VOCs) profile of WHBF, and compared it with that of ultraviolet-C (UV-C), ozone and hot air (HA) treatments. The results showed that the damaged starch content (6.0%) of CIPD-treated WHBF was increased, leading to a rough surface and partial aggregation of starch particle, thereby increasing the particle size (18.06 µm of D10, 261.46 µm of D50 and 534.44 µm of D90). Besides, CIPD treatment exerted a positive influence on the structure and rheological properties of WHBF, including an elevation in pasting temperature and viscosity. Notably, CIPD-treated WHBF exhibited higher storage modulus and loss modulus compared to the other three groups of sterilization treatments, contributing to the formulation of a better-defined and stable gel strength (tan δ = 0.38). UV-C and ozone, as cold sterilization techniques, also induced alterations in specific characteristics of WHBF. UV-C treatment led to changes in WHBF's crystallinity, while ozone treatment caused modifications in the secondary protein structure of WHBF. A total of 68 VOCs were identified in raw WHBF (including 3 acids, 19 alcohols, 25 aldehydes, 1 alkene, 8 esters, 2 ethers, 3 furans, and 7 ketones). The maximum flavor-contributing VOC in CIPD-treated WHBF remained dimethyl sulfide monomer (cabbage aroma), consistent with the raw WHBF. Conversely, in HA-treated WHBF, the maximum flavor-contributing VOC shifted to 2-furanmethanethiol monomer (roasted coffee aroma), altering the initial flavor presentation. These findings will provide strong support for the application of CIPD technology in the powdery foods industry.

Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment.

Inflammatory Bowel Disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Though the pathogenesis of IBD remains unclear, diet is increasingly recognized as a pivotal factor influencing its onset and progression. Fatty acids, essential components of dietary lipids, play diverse roles in IBD, ranging from anti-inflammatory and immune-regulatory functions to gut-microbiota modulation and barrier maintenance. Short-chain fatty acids (SCFAs), products of indigestible dietary fiber fermentation by gut microbiota, have strong anti-inflammatory properties and are seen as key protective factors against IBD. Among long-chain fatty acids, saturated fatty acids, trans fatty acids, and ω-6 polyunsaturated fatty acids exhibit pro-inflammatory effects, while oleic acid and ω-3 polyunsaturated fatty acids display anti-inflammatory actions. Lipid mediators derived from polyunsaturated fatty acids serve as bioactive molecules, influencing immune cell functions and offering both pro-inflammatory and anti-inflammatory benefits. Recent research has also highlighted the potential of medium- and very long-chain fatty acids in modulating inflammation, mucosal barriers, and gut microbiota in IBD. Given these insights, dietary intervention and supplementation with short-chain fatty acids are emerging as potential therapeutic strategies for IBD. This review elucidates the impact of various fatty acids and lipid mediators on IBD and delves into potential therapeutic avenues stemming from these compounds.

Evidence summary on the non-pharmacological management of sleep disorders in shift workers.

PURPOSE: This study aimed to evaluate, and integrate the relevant evidence on the non-pharmacological management of sleep disorders in shift workers to provide a reference for improving sleep of shift workers. METHODS: According to the "6S" pyramid model of evidence, a comprehensive search was conducted in evidence-based databases, including BMJ-Best Practice, UpToDate, DynaMed, Cochrane Library, and Joanna Briggs Institute (JBI); clinical practice guideline websites, such as the Guidelines International Network; professional association websites, such as the World Sleep Society; and literature databases, including PubMed, Embase, CINAHL, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Biology Medicine disc (CBM) from inception to November 30, 2022. Two researchers independently evaluated the literature in accordance with the evaluation standards; conducted the extraction, classification, and synthesis of the evidence; and evaluated its grade and recommendation grade. RESULTS: A total of 18 studies were included, including 2 clinical decisions, 2 guidelines, 3 expert consensuses, and 11 systematic reviews. In total, 25 pieces of evidence were summarized from 6 aspects: sleep assessment, sleep scheduling, sleep hygiene, light therapy, workplace intervention, and other managements. CONCLUSION: This study summarized the best evidence for the non-pharmacological management of sleep disorders in shift workers. Shift workers should reasonably arrange their sleep time and develop good sleep hygiene. Additionally, work organizations should jointly promote sleep to improve the sleep conditions of shift workers and promote their physical and mental health.

Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: In the first interim analysis of the ORIENT-31 trial, compared with chemotherapy alone, sintilimab plus bevacizumab biosimilar IBI305 plus chemotherapy (pemetrexed and cisplatin) significantly improved progression-free survival in patients with EGFR-mutated non-squamous non-small-cell lung cancer (NSCLC) who progressed on EGFR tyrosine-kinase inhibitor treatment. However, the benefit of anti-PD-1 or PD-L1 antibody added to chemotherapy in this patient population remains unclear, with no prospective evidence from phase 3 trials globally. We report the results from the prespecified second interim analysis of progression-free survival between sintilimab plus chemotherapy and chemotherapy alone, the updated results of sintilimab plus IBI305 plus chemotherapy, and preliminary overall survival results. METHODS: This double-blind, randomised, placebo-controlled, phase 3 trial was done at 52 centres across China and included patients aged 18-75 years with locally advanced or metastatic (stage IIIB, IIIC, or IV according to the American Joint Committee on Cancer, eighth edition) EGFR-mutated non-squamous NSCLC, disease progression after EGFR tyrosine-kinase inhibitor treatment (according to the Response Evaluation Criteria in Solid Tumours version 1.1 [RECIST 1.1]), and at least one measurable lesion (according to RECIST 1.1). Patients were randomly assigned (1:1:1), using an interactive web response system, to receive sintilimab (200 mg) plus IBI305 (15 mg/kg) plus pemetrexed (500 mg/m2) and cisplatin (75 mg/m2), sintilimab plus chemotherapy, or chemotherapy alone on day 1 of each 3-week cycle for four cycles, followed by maintenance therapy of sintilimab, IBI305, and pemetrexed. All study drugs were administered intravenously. The primary endpoint was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee. Data cutoff was March 31, 2022, unless otherwise specified. The study is registered at ClinicalTrials.gov, NCT03802240 (ongoing). FINDINGS: Between July 11, 2019, and March 31, 2022, 1011 patients were screened and 476 were randomly assigned (158 to the sintilimab plus IBI305 plus chemotherapy group, 158 to the sintilimab plus chemotherapy group, and 160 to the chemotherapy alone group). The median follow-up duration for progression-free survival was 12·9 months (IQR 8·2-17·8) in the sintilimab plus IBI305 plus chemotherapy group, 15·1 months (8·0-19·5) in the sintilimab plus chemotherapy group, and 14·4 months (9·8-23·8) in the chemotherapy alone group. Sintilimab plus chemotherapy significantly improved progression-free survival compared with chemotherapy alone (median 5·5 months [95% CI 4·5-6·1] vs 4·3 months [4·1-5·3]; hazard ratio [HR] 0·72 [95% CI 0·55-0·94]; two-sided p=0·016). Significant progression-free survival benefit was sustained with sintilimab plus IBI305 plus chemotherapy compared with chemotherapy alone (median 7·2 months [95% CI 6·6-9·3]; HR: 0·51 [0·39-0·67]; two-sided p<0·0001). As of data cutoff (July 4, 2022), the median overall survival was 21·1 months (95% CI 17·5-23·9) for sintilimab plus IBI305 plus chemotherapy (HR 0·98 [0·72-1·34]) and 20·5 months (15·8-25·3) for sintilimab plus chemotherapy group (HR 0·97 [0·71-1·32]) versus 19·2 months (15·8-22·4) for chemotherapy alone; after adjusting for crossover, the HR for sintilimab plus IBI305 plus chemotherapy to chemotherapy alone ranged from 0·79 (0·57-1·09) to 0·84 (0·61-1·15) and the HR for sintilimab plus chemotherapy to chemotherapy alone ranged from 0·78 (0·57-1·08) to 0·84 (0·61-1·16). The safety results were generally consistent with those in the first interim analysis; in particular, treatment-related adverse events of grade 3 or worse occurred in 88 (56%) of 158 patients in the sintilimab plus IBI305 plus chemotherapy group, 64 (41%) of 156 patients in the sintilimab plus chemotherapy group, and 79 (49%) of 160 patients in the chemotherapy alone group. INTERPRETATION: This is the first prospective phase 3 trial to show the benefit of anti-PD-1 antibody plus chemotherapy in patients with EGFR-mutated NSCLC who progressed on treatment with tyrosine-kinase inhibitors. Compared with chemotherapy alone, sintilimab combined with pemetrexed and cisplatin showed significant and clinically meaningful improvement of progression-free survival with an optimal safety profile. Sintilimab plus IBI305 plus chemotherapy continued to show progression-free survival benefit compared with chemotherapy alone in this second interim analysis with an additional 8-month follow-up. FUNDING: National Natural Science Foundation of China, Shanghai Municipal Science & Technology Commission Research Project, and Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The antitumor effect of mycelia extract of the medicinal macrofungus Inonotus hispidus on HeLa cells via the mitochondrial-mediated pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Inonotus hispidus (I. hispidus), known as shaggy bracket, has been used extensively in China and some East Asian countries as a traditional medicinal macrofungus to treat difficult diseases, such as diabetes, gout, and arthritis. Modern pharmacological research has shown that I. hispidus has an important application value in antitumor treatment. However, the main anti-cervical cancer activity substances from its mycelia and its mechanisms are still not clear. AIMS OF THE STUDY: To enrich the germplasm resources of I. hispidus, to reveal the antitumor activity of the extract from the mycelium of I. hispidus against cervical cancer, and to preliminarily analyze its action mechanism. MATERIALS AND METHODS: The SH3 strain was isolated from wild fruiting bodies and identified by morphology and molecular biology. The antitumor active component from the mycelium of I. hispidus was isolated and identified with liquid chromatography-tandem mass spectrometry. The cell viability was assessed by MTT assay. The cell cycle distribution, apoptotic cell detection, and mitochondrial membrane potential were detected by flow cytometer. The expression of apoptosis-related proteins was assessed by Western blotting. The inhibition of tumor growth in vivo was assessed by a mouse xenograft model. RESULTS: The SH3 strain was isolated and identified as a new strain of I. hispidus. The antitumor active component containing cyclic peptides from the mycelium of I. hispidus (CCM) was isolated for the first time. In addition, we found that CCM had a strong inhibitory effect on HeLa proliferation in vitro and in vivo. Mechanically, the CCM blocked the cell cycle at the G0/G1 phase, decreased the mitochondrial membrane potential, and eventually promoted apoptosis of HeLa cells through the mitochondria-mediated pathway by upregulating the expression levels of Bax, cytochrome C, cleaved caspase-9, and cleaved caspase-3 and downregulating the expression level of Bcl-2. CONCLUSIONS: Our study not only enriches the strain resources of I. hispidus but also confirms that the mycelium of this strain has active components that can inhibit cervical cancer. This is highly significant for the development of active drugs and drug lead molecules for treating cervical cancer.

The structural and functional properties of dietary fibre extracts obtained from highland barley bran through different steam explosion-assisted treatments.

The effects of steam explosion (SE)-assisted ultrasound (SEU), citric acid (SEC), sodium hydroxide (SEA), and cellulase (SEE) treatment on the properties of soluble dietary fibre (SDFP) extracted from highland barley bran were analysed. The results showed that SE pretreatment combined with other methods effectively improves the SDFP yield. The highest yield of SDF (20.01%) was obtained through SEA treatment. SEU-SDFP had a loose and porous structure, whereas the surface of SEC-SDFP and SEA-SDFP presented a complicated and dense texture. Although SE pretreatment reduced the thermal stability of SDFP, SEC and SEE treatment maintained its thermal stability. Furthermore, SEU-SDFP exhibited the highest water and oil holding capacities, and cholesterol and nitrite ion adsorption capacities. SEE-SDFP exhibited the best DPPH and ABTS radical scavenging abilities. In summary, four SE-assisted extraction methods had different advantages, and highland barley bran SDF can be considered as a potential functional additive in the food industry.

Compatibility between cold-natured medicine CP and hot-natured medicine AZ synergistically mitigates colitis mice through attenuating inflammation and restoring gut barrier.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a nonspecific intestinal inflammation with complex pathogenesis. Traditional Chinese Medicine (TCM) formula consists of several TCM herbs following the principle of herbal property and compatibility. Our previous studies found that Huanglian Ganjiang decoction (HGD) exhibited anti-colitis capacity and the compatibility between hot-natured medicine and cold-natured medicine was main compatibility. However, the association between compatibility mechanism of HGD and its anti-colitis effect has not been fully illustrated yet. AIM OF STUDY: Here, we would explore whether cold-natured medicine Coptis chinensis Franch. plus Phellodendron chinense C.K.Schneid. (CP) and hot-natured medicine Angelica sinensis (Oliv.) Diels plus Zingiber officinale Roscoe (AZ) in HGD respectively produce different impacts on UC, and exert synergistic effect on UC together. MATERIALS AND METHODS: UPLC/MS-MS was used to qualitatively analyze chemical profiles of CP, AZ and CPAZ extracts. CPAZ-UC target network was constructed using network pharmacology. Colitis mice was induced by 3% DSS for 7 days and treated with CP, AZ and CPAZ for another 7 days. The levels of multiple cytokines and proportions of innate and adaptive immune cells were determined to assess inflammatory profiles. The leakage of FITC-dextran, expressions of tight junction proteins were detected for evaluation of gut barrier function. RESULTS: CP, AZ and CPAZ could improve symptoms of colitis mice. CP showed superiority in reducing proportions of pro-inflammatory immune cells M1 cells, neutrophils, Th1 and Th17 cells, and levels of pro-inflammatory cytokines IFN-γ, IL-6, IL-10, TNF-α. In the contrast, AZ had advantage of elevating ratios of anti-inflammatory immune cells M2 and Treg cells as well as the production of anti-inflammatory cytokines IL-10 and TGF-ß. In addition, CP and AZ synergistically regulated M1/M2 macrophage polarization and the following IL-6, IL-10, TNF-α, IFN-γ production, thereby restoring intestinal mucosal barrier. CONCLUSION: Taken together, our study first demonstrated that cold-natured medicine CP and hot-natured medicine AZ took on different functions in treatment of colitis mice. Meanwhile, they exhibited synergistic effect on the alleviation of intestinal inflammation and reinforcement of gut barrier function and integrity.

Angelica oil restores the intestinal barrier function by suppressing S100A8/A9 signalling in mice with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) progression is driven by the activation of immune cells that release pro-inflammatory mediators to disrupt intestinal epithelial barrier integrity. This study aimed to investigate the potential protective effects of Angelica oil (AO) on the intestinal epithelial barrier in mice with UC and the underlying mechanisms. METHODS: Improvement of the disease state and protective effect of AO on the intestinal epithelial barrier were observed in mice with dextran sulphate sodium salt (DSS)-induced UC. Protein microarrays were used to screen AO-affected cytokine pools and their recruited immune cells for accumulation in the tissues. Furthermore, quantitative proteomics was applied to search for AO-acting molecules and to verify in vitro the functions of key molecules between inflammation and the intestinal mucosal barrier. RESULTS: AO significantly alleviated intestinal inflammation, reduced intestinal permeability, and retained barrier function in mice with UC. Furthermore, cytokines inhibited by AO mainly promoted monocyte and neutrophil activation or chemotaxis. Moreover, proteomic screening revealed that S100A8/A9 was a key molecule significantly regulated by AO, and its mediated TLR4/NF-κB pathway was also inhibited. Finally, we verified that AO inhibited the activation of the S100A8/A9/TLR4 signalling pathway and enhanced the expression of tight junctions (TJs) proteins using a cellular model of intestinal barrier damage induced by S100A8/A9 or macrophage-derived medium. And the enhancement of TJs in intestinal epithelial cells and the inhibition of inflammatory signalling by AO were significantly attenuated due to the application of S100A8/A9 monoclonal antibody. CONCLUSION: These results demonstrated that AO improves intestinal mucosal barrier damage in the inflammatory environment of mice with UC by inhibiting the expression of S100A8/A9 and the activation of its downstream TLR4/NF-κB signalling pathway.

An improved hybrid model on source-risk of polycyclic aromatic hydrocarbon in soils of the Yangtze River Delta urban agglomeration.

The source, exposure and risks of polycyclic aromatic hydrocarbons (PAHs) in soil environments are of great importance to evaluate soil quality. However, understanding the risks of specific sources of PAHs in soils remains poorly understood. In this study, we determined the source, exposure and risks of PAHs in the Yangtze River Delta urban agglomeration. The source analysis receptor model combined with land use types significantly increased the identification of pollution sources and improved the prediction accuracy of PAH concentrations. There is a strong correlation between the measured and predicted values of high ring PAH. The correlations of BbF, InP and Pyr are 0.947, 0.896 and 0.906 respectively, which is significantly higher than the unmodified model. By combining the ecological risk assessment and health risk assessment models of PAHs, we established an improved mixed source-risk model. The PAHs in urban soils had the highest ecological risk and health risk, with risk probabilities of 56.3 % and 28.2 %, respectively. The average contamination severity index values of PAHs caused by oil combustion sources, coal combustion sources, coking furnace sources, and fuel (biomass, petroleum, and diesel) combustion sources were 0.13, 0.10, 0.16 and 0.17, respectively. The average noncarcinogenic risks of PAHs from oil combustion sources, coal combustion sources, coking furnace sources and biomass, petroleum volatilization and diesel combustion sources to children were 0.12, 0.11, 0.08 and 0.13, respectively. Approximately half of the PAH pollution risk in forestland and grassland soil were associated with the combustion of petroleum fossil fuels. This study quantitatively analyzed the contribution of different PAHs pollution sources in different land types of soils, further calculated the risks of each pollution source to the ecological environment and human health, and proposed corresponding treatment measures, which provided scientific and systematic methods and technologies for soil pollution management in other regions of the world.

[Phytoestrogen-like effect of Siwu Decoction and molecular mechanism: based on network pharmacology and in vivo experiment].

This study explored the phytoestrogen-like effect of Siwu Decoction(SWD) and the estrogen receptor(ER)-mediated molecular mechanism based on network pharmacology and in vivo experiment. The active components and targets of SWD were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and related targets of "estrogen" from GeneCards and Online Mendelian Inheritance in Man(OMIM). Cytoscape and STRING were employed to construct the protein-protein interaction(PPI) network and "chemical component-target-disease" network and core targets were identified, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets by R software. For the in vivo experiment, the 22-day-old SD female rats were treated(ig) with SWD for 4 days. Via hematoxylin-eosin(HE) staining, the morphological changes of rat uterus were observed. Reverse transcriptase-polymerase chain reaction(RT-PCR) was performed to detect mRNA expression of ER subtypes, estrogen-related targets, and the main regulatory factors in the estrogen signaling pathway. The results indicated 74 targets of SWD exerted phytoestrogen-like effect. KEGG pathway enrichment result suggested that estrogen signaling pathway was closely related to the phytoestrogen-like effect of SWD. Rats in SWD group demonstrated significantly thickened endometrium and significantly decreased expression of ERα, ERß, and G protein-coupled estrogen receptor(GPER) mRNA in ovarian tissue. In addition, significant lowering of ERα and ERß mRNA expression and significant rise of GPER mRNA expression in uterine tissue were observed in the SWD group. The expression of mitogen-activated protein kinase(MAPK) p38, MEK1/2 and extracellular signal-regulated kinase(ERK)1/2 mRNA was significantly low while that of epidermal growth factor receptor(EGFR) mRNA was significantly high in both ovarian and uterine tissues of SWD group compared with those in the control group. In conclusion, the phytoestrogen-like effect of SWD is closely related to the estrogen signaling pathway. The result lays a basis for revealing molecular mechanism of SWD in the treatment of gynecological diseases.

Kill two birds with one stone: Ceramisite production using organic contaminated soil.

Disposal of organic-contaminated soil through ceramsite production can not only generate ceramsite with acceptable properties but also completely remediate the organic-contaminated soil owing to high treatment temperature. However, the removal mechanism of organic pollutants and the gas-solid phase distribution of the pollutants remain unclear. In this study, coking contaminated soils with high concentrations of polycyclic aromatic hydrocarbons (PAHs) and petroleum hydrocarbon (PHC) were used to prepare ceramsite at 1160 °C. The quality of ceramsite met the required product standard when the disposal ratio of contaminated soil was up to 60%. The concentration of PAHs and PHC in the soil was 57.7 mg kg-1 and 255 mg kg-1. After the experiment, almost no PAHs and PHC were found in the ceramsite. High-ring PAHs were dominant in the flue gas when using model soil spiked with PAHs. Computed tomography scanning indicated that cracks developed in the ceramsite when the temperature was higher than 200 °C. High-temperature in-situ thermal analysis showed that when the temperature was increased to 400 °C, the pollutant from the interior of ceramsite would flow into the flue gas with the released volatile matter. Thermal desorption and degradation of PAHs were the main mechanisms of pollutant removal.

Enhanced Nutrient Removal in A2N Effluent by Reclaimed Biochar Adsorption.

The excessive nitrogen and phosphorus discharged into the water environment will cause water eutrophication and thus disrupt the water ecosystem and even exert biological toxicities. In this study, the absorption removal of nitrogen and phosphorus from the anaerobic tank in an anaerobic−anoxic/nitrifying system using four different kinds of biowaste-reclaimed biochars were investigated and compared. The effects of temperature and pH on nutrient adsorption removal were further investigated. The four kinds of biochar were successfully prepared and well characterized using a scanning electron microscope, fourier transform infrared spectroscopy, X-ray diffraction and Brunner−Emmet−Teller methods. Generally, there was no significant change in chemical oxygen demand (COD) and NH4+-N removal efficiencies when treated by the different biochars, while the activated sludge biochar (ASB) displayed the highest total phosphorus (TP) removal efficiency. The initial TP concentrations (<40 mg/L) displayed no remarkable effects on the TP adsorption removal, while the increase of temperature generally enhanced TP and NH4+-N adsorptions on the ASB. Besides, the increase of pH significantly promoted NH4+-N removal but depressed TP removal. Moreover, the adsorption process of TP by the ASB complies with the secondary kinetic model, suggesting the chemical precipitation and physical electrostatic interaction mechanisms of TP adsorption removal. However, the adsorption of NH4+-N conformed to the inner-particle diffusion model, indicating that the NH4+-N adsorption was mainly involved with pore diffusions in the particles.

Capsaicin ameliorates intermittent high glucose-mediated endothelial senescence via the TRPV1/SIRT1 pathway.

BACKGROUND: Patients with diabetes have accelerated vascular aging when compared with healthy individuals. Hyperglycemia, especially intermittent high glucose (IHG), is the main cause of vascular endothelial senescence. Capsaicin, a major component of chili pepper is thought to contribute to cardiovascular protection by spicy food. OBJECTIVE: To investigate the pathway related with the effects of capsaicin on endothelial cell senescence induced by IHG. METHODS: HUVECs were exposed to IHG (5 mM or 33 mM glucose, alternating every 12 hours for 3 days) and treated with capsaicin at 0.3, 1 and 3 µM. To determine endothelial cell senescence, we examined the senescence-related ß-galactosidase staining, cell cycle arrest, cell viability, as well as production of reactive oxygen species (ROS). To evaluate the involvement of TRPV1/[Ca2+]i/CaMKII/AMPK/SIRT1 pathway in anti- senescence effects of capsaicin, HUVECs were treated with CAPZ (a TRPV1 antagonist), BAPTA-AM (an intracellular calcium chelator), KN62 (a CaMKII antagonist), compound C (an AMPK inhibitor), or EX527 (a SIRT1 inhibitor). To knockdown TRPV1, HUVECs were transfected with shRNA lentivirus targeting TRPV1. The levels of SIRT1, p21, TRPV1, AMPK and phospho-AMPK were evaluated by western blotting. RESULTS: IHG suppressed the levels of SIRT1 and enhanced endothelial senescence. Capsaicin upregulated SIRT1 expression and downregulated the senescence marker, p21, thereby protecting endothelial cells from IHG-induced senescence as indicated by relieved G0/G1 phase arrest, improved cell viabilities, and reduced counts of senescent cells and ROS production. Pre-treatment with CAPZ, BAPTA-AM, KN62 or compound C abrogated the anti-senescence effects of capsaicin. Capsaicin restored AMPK phosphorylation and IHG-inhibited TRPV1 expression. Moreover, TRPV1 silencing suppressed SIRT1 expression and abolished the anti-senescence effects of capsaicin. CONCLUSION: Capsaicin elevates SIRT1 levels through TRPV1/[Ca2+]i/CaMKII/AMPK pathway and suppresses IHG-mediated endothelial cell senescence. This study provides initial evidence that capsaicin is a potential candidate for the prevention of vascular aging in diabetes.

All-Trans Retinoic Acid Prevents the Progression of Gastric Precancerous Lesions by Regulating Disordered Retinoic Acid Metabolism.

Retinoic acid (RA) is the most biologically active metabolite of vitamin A and is important for stomach physiological function. However, little is known about the metabolic status of RA in human gastric lesions. From 2015 to 2018, 1,392 local residents in Lujiang County were recruited into a cross-sectional survey program, which included a questionnaire interview and blood collection. We detected the mRNA and protein expression of RA metabolism-relevant factors in gastric tissues from 68 local patients with gastric lesions. The effects of all-trans retinoic acid (ATRA) supplementation were investigated in a gastric precancerous lesions (GPLs) rat model. In the cross-sectional survey, no significant differences in the level of RA precursor (P > 0.05) between the H. pylori seronegative and seropositive residents were observed. However, the mRNA and protein expression of RA synthesizing enzymes (RDH10 and ALDH1A1) were significantly decreased and catabolic enzyme (CYP26B1) was significantly increased in the patients (P < 0.05). Consistently, in the GPL rat model, we observed a similar disorder; however, ATRA supplementation significantly not only corrected the disorder by increasing Rdh10, Aldh1a1 and decreasing Cyp26b1, but also reduced claudin-18 (P < 0.05). Our study suggested that RA metabolism is disrupted in individuals with gastric lesions, while ATRA supplementation can prevent GPL from progressing to gastric cancer.

Clinical guidelines for microwave ablation of spinal metastases.

Spinal metastases are the most common source of morbidity in patients with cancer. Recently, microwave ablation has produced satisfactory results in the management of spinal metastases. However, there is still controversy in terms of clinical treatment, such as indication, power, time, and temperature. To standardize the application of microwave ablation technology and reduce the risk of surgical-related complications in spinal metastases, in this report, we aimed to summarize the current evidence and clinical experience of microwave ablation and developed a clinical guideline, initiated by the Musculoskeletal Tumor Group of the Committee for Minimally Invasive Therapy in Oncology of the Chinese Anti-Cancer Association. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used in to rate the quality of evidence and the strength of recommendations, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist was strictly followed to report the guideline. Finally, 15 evidence-based recommendations were formulated based on the 15 most concerned clinical questions among orthopedic surgeons, oncologists, and interventional radiologists in China. This guideline aims to promote the science-based normalization of microwave ablation for the treatment of spinal metastases.

Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.

Cardiac voltage-gated ion channels (VGICs) play critical roles in mediating cardiac electrophysiological signals, such as action potentials, to maintain normal heart excitability and contraction. Inherited or acquired alterations in the structure, expression, or function of VGICs, as well as VGIC-related side effects of pharmaceutical drug delivery can result in abnormal cellular electrophysiological processes that induce life-threatening cardiac arrhythmias or even sudden cardiac death. Hence, to reduce possible heart-related risks, VGICs must be acknowledged as important targets in drug discovery and safety studies related to cardiac disease. In this review, we first summarize the development and application of electrophysiological techniques that are employed in cardiac VGIC studies alone or in combination with other techniques such as cryoelectron microscopy, optical imaging and optogenetics. Subsequently, we describe the characteristics, structure, mechanisms, and functions of various well-studied VGICs in ventricular myocytes and analyze their roles in and contributions to both physiological cardiac excitability and inherited cardiac diseases. Finally, we address the implications of the structure and function of ventricular VGICs for drug safety evaluation. In summary, multidisciplinary studies on VGICs help researchers discover potential targets of VGICs and novel VGICs in heart, enrich their knowledge of the properties and functions, determine the operation mechanisms of pathological VGICs, and introduce groundbreaking trends in drug therapy strategies, and drug safety evaluation.

Agarose oligosaccharide- silver nanoparticle- antimicrobial peptide- composite for wound dressing.

Marine polysaccharides or oligosaccharides have potential to promote wound healing due to their biocompatibility and physicochemical properties. However, microbial infection delays wound healing process, and novel antimicrobial wound dressings are urgently needed. Here, agarose oligosaccharides (AGO) obtained from marine red algae were used as a reducing and stabilizer for green synthesis of silver nanoparticles (AgNPs), and further successfully connected with odorranain A (OA), one of antimicrobial peptides (AMPs), to obtain a novel composite nanomaterial (AGO-AgNPs-OA). Transmission electron microscopy (TEM) and Malvern particle size analyzer showed that AGO-AgNPs-OA was spherical or elliptic with average size of about 100 nm. Circular dichroism (CD) spectroscopy showed that AGO-AgNPs stabilized the α-helical structure of OA. AGO-AgNPs-OA showed stronger anti-bacterial activities than AGO-AgNPs, and had good biocompatibility and significant promoting effect on wound healing. Our data suggest that AMPs conjugated marine oligosaccharides and AgNPs may be effective and safe antibacterial materials for wound therapy.