Tibetan medicine Si-Wei-Qiang-Wei Powder ameliorates cholecystitis via inhibiting the production of pro-inflammatory cytokines and regulating the MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Wei-Qiang-Wei Powder (SWQ) is a formulated traditional Tibetan medicine preparation that has been used clinically to treat liver and gallbladder diseases for centuries. Previous work has confirmed its clinical effectiveness, however, the specific mechanism of SWQ is still unknown. AIM OF THE STUDY: This study aims to explore the anti-inflammatory effect of SWQ on cholecystitis and its possible mechanism. MATERIALS AND METHODS: The main chemical components of SWQ were analyzed by HPLC. The network pharmacology database was used to screen and construct the network of the main components and molecular targets of SWQ, and to predict the molecular pathways of its core targets. Cholecystitis guinea pig model and LPS stimulated cultured human gallbladder epithelial cells (HGBEC) were used, as in vivo and in vitro methods respectively, to study the anti-cholecystitis activity of SWQ. Specifically, gallbladder wall thickness, hematoxylin-eosin (H&E) staining, and liver function indexes were used to evaluate the anti-inflammatory activities of SWQ in cholecystitis; qRT-PCR and ELISA were used to detect the changes of the production of inflammatory cytokines; Western blot analysis was used to analyze the effects of SWQ on phosphorylation of P38, ERK1/2, JNK and AKT. RESULTS: SWQ decreased the indexes of ALT, AST, TBA, CHOL, DBIL in serum and TBIL, TC and Ca2+ in bile, and alleviated the wall thickness of gallbladder and hepatobiliary fibrosis in LCA-induced guinea pigs. In addition, SWQ attenuated the expression and production of TNF-α, IL-6, IL-1ß, COX-2 both in liver and gallbladder. Moreover, SWQ reversed the up-regulation of p-P38, p-ERK1/2, and p-JNK in animals with cholecystitis and LPS-induced HGBEC. Furthermore, mechanistic studies indicated that SWQ inhibited the activation of ERK1/2, thereby decreasing the expression of TNF-α, IL-6, IL-1ß and phosphorylation P38 and JNK. CONCLUSION: In summary, our research showed that SWQ relieves gallbladder inflammation by inhibiting the MAPK pathway.

Bibliometric Analysis of Research Trends on 3-Monochloropropane-1,2-Diol Esters in Foods.

3-Monochloropropane-1,2-diol esters (3-MCPDE) are common food contaminants mainly formed in the edible oil refining process. Due to their potential hazards, 3-MCPDE has become a widespread food safety concern. In this study, CiteSpace and VOSviewer were used to conduct a bibliometric analysis on the 3-MCPDE research papers collected in the Web of Science Core Collection from 1998 to 2022. The results showed that the number of research publications on 3-MCPDE has increased rapidly since 2010. Analysis of the hotspots in 3-MCPDE studies showed that more attention has been paid to the exposure assessment, formation mechanism, detection methods, mitigation methods and toxicity, and toxicology of 3-MCPDE. Finally, the future trends of research on 3-MCPDE were analyzed and proposed. The mitigation methods and toxicology studies of 3-MCPDE are still the research hotspots in the future. In addition, nutritional intervention for 3-MCPDE toxicity will be an emerging trend.

Antiasthmatic Compounds Targeting ß2-Adrenergic Receptor from Perilla frutescens Improved Lung Inflammation by Inhibiting the NF-κB Signaling Pathway.

Asthma is a highly prevalent and heterogeneous chronic respiratory disease and is often treated with inhaled corticosteroids or in combination with a ß2-adrenergic receptor (ß2-AR) agonist. However, around 5% of asthma remains uncontrolled, and more effective antiasthmatic drugs with known mechanisms are in high demand. Herein, we immobilized ß2-AR on the polystyrene amino microsphere surface in a one-step fashion. The successful immobilization of ß2-AR was verified by scanning electron microscopy and chromatographic analysis. We screened rosmarinic acid (RA) as the bioactive compound targeting ß2-AR in Perilla frutescens (L.) Britton by mass spectroscopy. The binding constant between RA and ß2-AR was determined to be 2.95 × 104 M-1 by adsorption energy distribution and frontal analysis. The antiasthmatic effect and mechanism of RA were examined on a murine model of allergic asthma induced by ovalbumin (OVA) and aluminum hydroxide. The results showed that RA significantly reduced lung inflammatory cell numbers, the production of Th2 cytokines, and the secretion of total IgE, OVA-specific IgE, and eotaxin. The decreased inflammatory cell infiltration and mucus hypersecretion were associated with the inhibition of the NF-κB signaling pathway. Moreover, the mRNA expression levels of AMCase, CCL11, CCR3, Ym2, and E-selectin in the lung tissues were effectively reduced. It is the first time that RA was proven to target ß2-AR and be effective in counteracting allergic airway inflammation via the NF-κB signaling pathway. Therefore, the immobilized ß2-AR preserves the potential in screening antiasthmatic compounds from herbal medicine, and RA can be developed as an effective agent for the treatment of allergic asthma.

Structurally screening calixarenes as peptide transport activators.

Calixarenes are reportedly excellent activators that can remarkably improve the transport efficiencies of cell penetrating peptides. We employed eight calixarenes to systematically study the influence of structure on activation efficiency, which revealed that the scaffold, head group, and alkyl chain are all significant factors for activation efficiency by affecting affinities with the peptide and membrane.

New Internet-Based Warfarin Anticoagulation Management Approach After Mechanical Heart Valve Replacement: Prospective, Multicenter, Randomized Controlled Trial.

BACKGROUND: Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease; however, it subjects patient to lifelong warfarin therapy after MHVR with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown. OBJECTIVE: This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation. METHODS: This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, while bleeding, thrombosis, and other events were the secondary outcomes. RESULTS: A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the 2 groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs mean 0.46, SD 0.21; P<.001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs mean 0.42, SD 0.19; P<.001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events had a lower frequency in the internet-based group than in the conventional group (6.94% vs 12.74%; P=.01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P<.001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P=.01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P=.005). CONCLUSIONS: The internet-based warfarin management is superior to the conventional method, as it can reduce the anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016204; http://www.chictr.org.cn/showproj.aspx?proj=27518. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-032949.

EkFLS overexpression promotes flavonoid accumulation and abiotic stress tolerance in plant.

Flavonoids with great medicinal value play an important role in plant individual growth and stress resistance. Flavonol synthetase (FLS) is one of the key enzymes to synthesize flavonoids. However, the role of the FLS gene in flavonoid accumulation and tolerance to abiotic stresses, as well as its mechanism has not yet been investigated systematically in plants. The aim of this research is to evaluate the effect of FLS overexpression on the accumulation of active ingredients and stress resistance in Euphorbia kansui Liou. The results showed that when the EkFLS gene was overexpressed in Arabidopsis thaliana, the accumulation of flavonoids was improved. In addition, when the wild-type and EkFLS overexpressed Arabidopsis plants were treated with ABA and MeJA, compared with WT Arabidopsis, EkFLS overexpressed Arabidopsis promoted stomatal aperture to influence photosynthesis of the plants, which in turn can promote stress resistance. Meanwhile, under MeJA, NaCl, and PEG treatment, EkFLS overexpressed in Arabidopsis induced higher accumulation of flavonoids, which significantly enhanced peroxidase (POD) and superoxide dismutase (SOD) activities that can scavenge reactive oxygen species in cells to protect the plant. These results indicated that EkFLS overexpression is strongly correlated to the increase of flavonoid synthesis and therefore the tolerance to abiotic stresses in plants, providing a theoretical basis for further improving the quality of medicinal plants and their resistance to abiotic stresses simultaneously.

Low serum calcium and phosphorus and their clinical performance in detecting COVID-19 patients.

BACKGROUND: This study aimed to evaluate the clinical performance of low serum calcium and phosphorus in discriminative diagnosis of the severity of patients with coronavirus disease 2019 (COVID-19). We conducted a single-center hospital-based study and consecutively recruited 122 suspected and 104 confirmed patients with COVID-19 during January 24 to April 25, 2020. Clinical risk factors of COVID-19 were identified. The discriminative power of low calcium and phosphorus regarding the disease severity was evaluated. Low calcium and low phosphorus are more prevalent in severe or critical COVID-19 patients than moderate COVID-19 patients (odds ratio [OR], 15.07; 95% confidence interval [CI], 1.59-143.18 for calcium; OR, 6.90; 95% CI, 2.43-19.64 for phosphorus). The specificity in detecting the severe or critical patients among COVID-19 patients reached 98.5% (95% CI, 92.0%-99.7%) and 84.8% (95% CI, 74.3%-91.6%) by low calcium and low phosphorus, respectively, albeit with suboptimal sensitivity. Calcium and phosphorus combined with lymphocyte count could obtain the best discriminative performance for the severe COVID-19 patients (area under the curve [AUC] = 0.80), and combined with oxygenation index was promising (AUC = 0.71). Similar discriminative performances of low calcium and low phosphorus were found between suspected and confirmed COVID-19 patient. Low calcium and low phosphorus could indicate the severity of COVID-19 patients, and may be utilized as promising clinical biomarkers for discriminative diagnosis.

Metal-organic frameworks based fluorescent sensor array for discrimination of flavonoids.

Metal-organic frameworks (MOFs) are hotly investigated as a novel kind of fluorescent sensing materials in recent years. However, the application of MOF sensing to drug analysis is still very difficult yet, because the structural similarity among drug homolog-ues exceeds the discrimination ability of MOFs. Array sensing technique, which relies on the combined responses of a group of sensing materials, is a viable way to solve this problem. In this work, we chose five luminescent MOFs with different fluorophores to construct a fluorescent sensor array for the analysis of flavonoids. With the response pattern of these MOFs and the statistical methods of linear discriminant analysis and hierarchical cluster analysis, nine flavonoids with similar structures were correctly discriminated. By the combination with UV spectrum, our method could even realize the qualification and quantification of the flavonoid samples with unknown concentrations. This work is the first time of using MOFs to successfully distinguish multiple drug homolog-ues.

Rivaroxaban, Aspirin, or Both to Prevent Early Coronary Bypass Graft Occlusion: The COMPASS-CABG Study.

BACKGROUND: Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. OBJECTIVES: This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. METHODS: The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. RESULTS: The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. CONCLUSIONS: The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424).

Evaluating the effects of metal oxide nanoparticles (TiO2, Al2O3, SiO2 and CeO2) on anammox process: Performance, microflora and sludge properties.

The increasing use of engineered metal oxide nanoparticles (MONPs) in consumer products raises great concerns about their environmental impacts, but their potential impacts on anaerobic ammonium oxidation (anammox) process in wastewater treatment remain unclear. In this study, the presence of MONPs (1, 50, 200 mg L-1) exhibited no visible effects on the nitrogen removal performance of anammox reactors, but high levels (200 mg L-1) of SiO2NPs, Al2O3NPs and CeO2NPs had a distinct effect on shaping the anammox community. Long-term exposure of MONPs caused different responses in the relative abundance of Ca. Kuenenia, the level of functional gene HzsA and the activities of three key enzymes involved in anammox metabolism, but no significant inhibition effects on specific anammox activity were detected. Overall, the effects of MONPs on anammox community structure and sludge properties depended on their types and levels and followed the order SiO2 > CeO2 > Al2O3 > TiO2.

Molecular cloning and characterisation of scavenger receptor class B in pearl oyster Pinctada fuctada martensii

Background: Molluscs can accumulate carotenoids in their body tissues by predominantly feeding on aquatic plant sources. Carotenoid transport and absorption are determined by the regulation of various proteins such as Scavenger receptor class B(SR-BI). We report the identification and characterisation of pearl oyster Pinctada fuctada martensii SR-BI (PmSR-BI). The correlation between total carotenoid content (TCC) and gene expression was also estimated. Results: The full-length cDNA of PmSR-BI was 1828 bp, including an open-reading frame encoding of 1518 bp with a pI value of 5.83. PmSR-BI protein contains a hydrophobic CD36 domain and four centrally clustered cysteine residues for the arrangement of disulphide bridges. The deduced amino acid sequence had an identity of 30% to 60% with the SR-B of other organisms. Reverse transcription polymerase chain reaction analysis showed that mRNA transcripts were expressed in multiple tissues of adult pearl oyster. A higher expression of PmSR-BI gene was observed in the hepatopancreas than in the adductor muscle, gill and mantle. The TCC and gene expression of PmSR-BI were significantly correlated (P b 0.05), with a correlation coefficient of 0.978. Conclusions: The results suggested that PmSR-BI is involved in the absorption of carotenoids in the pearl oyster P. fuctada martensii.

Computational prediction of candidate miRNAs and their potential functions in biomineralization in pearl oyster Pinctada martensii.

MicroRNAs (miRNAs) are a class of non-coding RNA molecules with presumed post-transcriptional regulatory activity in various biological processes, such as development and biomineralization. Pinctada martensii is one of the main species cultured for marine pearl production in China and Japan. In our previous research, 258 pm-miRNAs had been identified by solexa deep sequencing in P. martensii, while it is far from the number of miRNAs found in other species. In this study, based on the transcriptome database of pearl sac, we identified 30 candidate pm-miRNAs by computational prediction. Among the obtained 30 pm-miRNAs, 13 pm-miRNAs were generated from the complementary strand of protein-coding mRNAs, and 17 pm-miRNAs could not be annotated using blastx and tblastn analysis. Notably, 10 of the 30 pm-miRNAs, such as pm-miR-1b, pm-miR-205b and pm-miR-375b, were homologous with the reported pm-miRNAs, respectively. To validate the existence of the identified pm-miRNAs, eight randomly selected pm-miRNAs were tested by stem loop quantitative RT-PCR analyses using 5.8S as the internal reference gene. Target prediction between the obtained pm-miRNAs and biomineralization-related genes by microTar, miRanda and RNA22 indicated pm-miR-2386 and pm-miR-13b may be the key factors in the regulation network by regulating the formation of organic matrix or the differentiation of mineralogenic cell during shell formation. Thus, this study enriched miRNA databases of pearl oyster and provided a new way to understand biomineralization.

Start-up of granule-based denitrifying reactors with multiple magnesium supplementation strategies.

In the present work, the effect of Mg(2+) supplementation on the start-up of a denitrification process and the granulation of denitrifying sludge was investigated in three upflow anaerobic sludge blanket (UASB) reactors. The reactors R1 and R2 were continuously and intermittently, respectively, supplied with 50 mg L(-1) Mg(2+), whereas R0 was used as the control. The nitrogen loading rate (NLR) and organic loading rate (OLR) gradually increased, and extremely high values were obtained (36.0 kgN m(-3) d(-1) and 216.0 kgCOD m(-3) d(-1), respectively). Granulation occurred in R1 first, but the reactor capacities were comparable. Suffering from starvation, the R0-R2 performances were comparable. At the end of the experiment, the average diameter of the granules in R0, R1, and R2 were 1.67, 1.72 and 1.68 mm, respectively, and the settling velocities of the granules in R1 and R2 were 1.14-fold the speed of R0. The specific denitrifying activity (SDA) of the sludge from the reactors supplied with Mg(2+) was greater than the reactor without Mg(2+). Intermittent Mg(2+) supplementation was identified as the best choice to be utilized to cultivate denitrifying granules, which was consistent with kinetic analysis.

Management of focal atrial tachycardias originating from the atrial appendage with the combination of radiofrequency catheter ablation and minimally invasive atrial appendectomy.

BACKGROUND: Focal atrial tachycardias (ATs) originating from the left and the right atrial appendage (AA) were the most difficult to eliminate. OBJECTIVE: To evaluate the safety and long-term efficacy of minimally invasive surgical atrial appendectomy in combination with radiofrequency catheter ablation (RFCA) in the management of focal atrial appendage tachycardias (AATs). METHODS: We included 42 consecutive patients with 42 AATs confirmed by activation mapping and contrast venography. Thirty of them were successfully managed with RFCA (RFCA-successful group), while the remaining 12 (28.6%) finally resorted to video-assisted thoracoscopic atrial appendectomy owing to RFCA failure (resort-to-surgery group). We searched for predictors of RFCA failure, and the need for surgery by using a binomial logistic regression model. RESULTS: In the RFCA-successful group, 6 (20.0%) patients experienced recurrence and re-do ablation and 11 (36.7%) AATs originated from distal AAs. In the resort-to-surgery group, the tachycardias involved exclusively distal AAs and required more RFCA attempts compared with those of the RFCA-successful group (1.58 ± 0.51 vs 1.20 ± 0.41; P = .0165). During atrial appendectomy, incessant ATs were terminated immediately after resection of the AA at the base. Long-term success was achieved in all 42 patients with a follow-up of 29.1 ± 17.5 months. No complications occurred. Fourteen patients with tachycardia-induced cardiomyopathy recovered fully. We identified origin at distal AATs and longer time to tachycardia termination by ablation as predictors of RFCA failure and the need for surgical intervention. CONCLUSION: ATs originating from the distal portion of AA were more refractory to RFCA. The combination of catheter ablation and video-assisted thoracoscopic atrial appendectomy was an effective strategy to manage AATs.

Subthalamic deep brain stimulation for Parkinson's disease: correlation between locations of oscillatory activity and optimal site of stimulation.

Subthalamic nucleus deep brain stimulation (STN DBS) is an effective surgical treatment for Parkinson's disease (PD). Recent studies demonstrated that pathological oscillations are seen largely within the dorsolateral portion of the STN, which is the same location that predicts optimal therapeutic benefit with DBS; however, the precise nature of the relationship between these two phenomena remains unclear. The purpose of this study was to explore localization of oscillatory activity in relation to the optimal contacts of DBS which results in the best motor improvement. We studied 23 PD patients who underwent electrode implantation into the STN for motor symptoms. Microelectrode recordings were taken from the STN during surgery and neuronal activity was analyzed offline. Spectral characteristics were calculated. Clinical outcomes were evaluated pre- and post-STN DBS implantation using the Unified Parkinson's Disease Rating Scale (UPDRS III). The position of optimal electrode contacts was assessed by postoperative magnetic resonance imaging (MRI) and was compared to the location of oscillatory activity within the STN as well as its dorsal margin (where STN neuronal activity was first detected). Of the total 188 neurons obtained, 51 (27.1%) neurons showed significant oscillatory activity. Of those, 47 (92.2%) were localized in the dorsal portion of the STN. Furthermore, there was no significant difference between the averaged coordinates of the position of 40 optimal contacts and the coordinates of the dorsal margin of the STN. The data indicate that the positions of the best contacts correlate with the locations of the oscillatory neurons supporting the prediction that stimulation of the dorsolateral oscillatory region leads to an effective clinical outcome for STN DBS surgery.

Two new compounds from Ixeris sonchifolia.

Two new compounds, named as sonchifolactone E (1) and sonchifolinin B (2), have been isolated from the whole plant of Ixeris sonchifolia, along with one known compound, sonchifolatone A (3). Their structures and stereochemistry were determined by spectroscopic methods.