[Determination of furosine in liquid milk by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Furosine is often used both domestically and internationally as an indicator of the degree of heating to evaluate milk quality. However, in actual detection, the complexity of the milk matrix may lead to the inaccurate quantification of furosine in liquid milk. Therefore, in this study, an efficient and accurate method based on high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was established to determine furosine in liquid milk. A 2.00 mL milk sample was hydrolyzed with 5 mL 12.00 mol/L hydrochloric acid solution and 1 mL water at 110 ℃ for 12 h. After hydrolysis, vortex-mixing and filtration were performed. The filtrate was diluted six times with 6.00 g/L ammonium acetate solution and then analyzed. Gradient elution was performed with 0.20% formic acid aqueous solution and acetonitrile solution as mobile phases, followed by chromatographic separation on an AQ-C18 column (150 mm×3.5 mm, 5 µm). The data were collected by Q-TOF/MS with an electrospray ionization source operated in positive-ion mode. The accuracy of the quantification of furosine in milk was assessed by investigating the effects of the hydrochloric acid concentration (0.30, 1.25, and 3.00 mol/L) in the furosine solution on the MS response. The results showed that high hydrochloric acid concentrations inhibited the response signals. A good linear relationship was obtained in the mass concentration range of 0.05-2.00 mg/L, with a correlation coefficient (r) of 0.994. The limit of detection of the method was 0.50 mg/100 g, which meets the requirements of actual sample detection. The average recoveries of furosine ranged from 79.9% to 119.7% at three spiked levels of 1.52, 3.03, and 15.17 mg/100 g, with relative standard deviations of 1.4%-2.6%. The method was applied to detect 303 samples from 101 batches of pasteurized milk sold in the market, and the contents of furosine in these samples ranged from 5.1 to 11.9 mg/100 g. The proposed method is characterized with high efficiency, recovery, sensitivity, and accuracy. Thus, it can be used for the determination of large quantities of samples and provides technical support for the continuous promotion of the high-quality development of the whole dairy industry chain.

Dosage optimization of tacrolimus based on the glucocorticoid dose and pharmacogenetics in adult patients with systemic lupus erythematosus.

BACKGROUND: The purpose of the study was to develop a genotype-incorporated population pharmacokinetic (PPK) model of tacrolimus (TAC) in adults with systemic lupus erythematosus (SLE) to investigate the factors influencing TAC pharmacokinetics and to develop an individualized dosing regimen based on the model. In addition, a non-genotype-incorporated model was also established to assess its predictive performance compared to the genotype-incorporated model. METHODS: A total of 365 trough concentrations from 133 adult SLE patients treated with TAC were collected to develop a genotype-incorporated PPK model and a non-genotype-incorporated PPK model of TAC using a nonlinear mixed-effects model (NONMEM). External validation of the two models was performed using data from an additional 29 patients. Goodness-of-fit diagnostic plots, bootstrap method, and normalized predictive distribution error test were used to validate the predictive performance and stability of the final models. The goodness-of-fit of the two final models was compared using the Akaike information criterion (AIC). The dosing regimen was optimized using Monte Carlo simulations based on the developed optimal model. RESULTS: The typical value of the apparent clearance (CL/F) of TAC estimated in the final genotype-incorporated model was 14.3 L h-1 with inter-individual variability of 27.6%. CYP3A5 polymorphism and coadministered medication were significant factors affecting TAC-CL/F. CYP3A5 rs776746 GG genotype carriers had only 77.3% of the TAC-CL/F of AA or AG genotype carriers. Omeprazole reduced TAC-CL/F by 3.7 L h-1 when combined with TAC, while TAC-CL/F increased nonlinearly as glucocorticoid dose increased. Similar findings were demonstrated in the non-genotype-incorporated PPK model. Comparing these two models, the genotype-incorporated PPK model was superior to the non-genotype-incorporated PPK model (AIC = 643.19 vs. 657.425). Monte Carlo simulation based on the genotype-incorporated PPK model indicated that CYP3A5 rs776746 AA or AG genotype carriers required a 1/2-1 fold higher dose of TAC than GG genotype carriers to achieve the target concentration. And as the daily dose of prednisone increases, the dose of TAC required to reach the target concentration increases appropriately. CONCLUSIONS: We developed the first pharmacogenetic-based PPK model of TAC in adult patients with SLE and proposed a dosing regimen based on glucocorticoid dose and CYP3A5 genotype according to the model, which could facilitate individualized dosing for TAC.

Terpenoid Glucosides from Gentiana macrophylla That Attenuate TNF-α Induced Pulmonary Inflammation in A549 Cells.

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1ß and IL-8 and increase the expression of anti-inflammatory cytokine IL-10.

Autoimmune pancreatitis associated with inflammatory bowel diseases: A retrospectively bidirectional case-control study in China.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China. METHODS: A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types. RESULTS: The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008). CONCLUSIONS: Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.

Population pharmacokinetic analyses of tacrolimus in non-transplant patients: a systematic review.

BACKGROUND AND OBJECTIVES: Tacrolimus (TAC) has been increasingly used in patients with non-transplant settings. Because of its large between-subject variability, several population pharmacokinetic (PPK) studies have been performed to facilitate individualized therapy. This review summarized published PPK models of TAC in non-transplant patients, aiming to clarify factors affecting PKs of TAC and identify the knowledge gap that may require further research. METHODS: The PubMed, Embase databases, and Cochrane Library, as well as related references, were searched from the time of inception of the databases to February 2023, to identify TAC population pharmacokinetic studies modeled in non-transplant patients using a non-linear mixed-effects modeling approach. RESULTS: Sixteen studies, all from Asian countries (China and Korea), were included in this study. Of these studies, eleven and four were carried out in pediatric and adult patients, respectively. One-compartment models were the commonly used structural models for TAC. The apparent clearance (CL/F) of TAC ranged from 2.05 to 30.9 L·h-1 (median of 14.9 L·h-1). Coadministered medication, genetic factors, and weight were the most common covariates affecting TAC-CL/F, and variability in the apparent volume of distribution (V/F) was largely explained by weight. Coadministration with Wuzhi capsules reduced CL/F by about 19 to 43%. For patients with CYP3A5*1*1 and *1*3 genotypes, the CL/F was 39-149% higher CL/F than patients with CYP3A5*1*1. CONCLUSION: The optimal TAC dosage should be adjusted based on the patient's co-administration, body weight, and genetic information (especially CYP3A5 genotype). Further studies are needed to assess the generalizability of the published models to other ethnic groups. Moreover, external validation should be frequently performed to improve the clinical practicality of the models.

Diversity and community assembly mechanism of soil ectomycorrhizal fungi in urban parks of Baotou City, China.

Ectomycorrhizal (EM) fungi play an important role in forest ecosystems. However, little is known about the mechanisms driving diversity and community composition of soil EM fungi in urban forest parks which are intensively affected by anthropogenic activities. In this study, we investigated the EM fungal community using Illumina high-throughput sequencing with soil samples collected from three typical forest parks, including Olympic Park, Laodong Park, and Aerding Botanical Garden of Baotou City. The results showed that soil EM fungi richness index followed a pattern of Laodong Park (146.43±25.17) > Aerding Botanical Garden (102.71±15.31) > Olympic Park (68.86±6.83). Russula, Geopora, Inocybe, Tomentella, Hebeloma, Sebacina, Amanita, Rhizopogon, Amphinema, and Lactarius were the dominant genera in the three parks. EM fungal community composition was significantly different among the three parks. Results of linear discriminant analysis effect size (LEfSe) indicated that all parks had biomarker EM fungi that exhibiting significantly different abundance. The normalized stochasticity ratio (NST) and the inferring community assembly mechanisms by phylogenetic-bin-based null model analysis (iCAMP) showed that both stochastic and deterministic processes determined soil EM fungal communities in the three urban parks, with a dominant role of the stochastic process. Drift and dispersal limitation in the stochastic process and homogeneous selection in the deterministic process were the dominant ecological processes of soil EM fungal community assembly in the three urban parks.

Evaluation of the effect of physical therapy on pain and dysfunction of knee osteoarthritis based on fNIRS: a randomized controlled trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disease that can cause joint pain and dysfunction, affecting the quality of life of patients. Nonsurgical treatment is the conventional treatment of KOA, among which physical therapy is widely used because of its simplicity, convenience and effectiveness. The functional biomarker will add to the clinical fidelity and diagnostic accuracy. Therefore, our study chose a more objective evaluation indicator, functional near-infrared spectroscopy (fNIRS), to identify between healthy people and KOA patients, and to detect the pain change before and after treatment of KOA patients. METHODS: The study will be conducted in the Rehabilitation Medical Center of West China Hospital of Sichuan University and divided into 2 stages. In the first stage, we will compare and determine the differences in baseline data between healthy volunteers and KOA patients. In the second stage, 72 KOA patients will be randomly divided into two groups: the drug therapy group (DT) and the combination therapy group (CT) for 10 treatments. Outcome measures will be measured at baseline and on the 5th and 10th days after the intervention, including the numerical rating scale (NRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain catastrophizing scale (PCS), the association of pain severity with task-state functional connectivity fNIRS and association of pain severity with task-activated fNIRS. DISCUSSION: By analyzing the fNIRS data of healthy volunteers and KOA patients, our study will be determined whether fNIRS can be used as a new indicator to reflect the severity of pain in KOA patients. Subsequently, the same fNIRS data for KOA patients before and after the intervention will be collected to provide an accurate evaluation criterion for the effect of physical therapy on KOA. TRIAL REGISTRATION: The study was registered on the Chinese Registry website (registered in ChiCTR.org with the identifiers ChiCTR2200064175 and 29/09/2022).

Effect of IoT-based power cycling and quadriceps training on pain and function in patients with knee osteoarthritis: A randomized controlled trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disease affecting the entire joint. Exercise therapy is the core treatment plan for non-surgical treatment of KOA, and tele-rehabilitation is also applied to KOA, but there is a lack of research on the comparison of pain and function recovery between different exercise methods combined Internet respectively. The study aims to compare the effects of power cycling and quadriceps training combined with online guidance separately on KOA mitigation of pain, recovery of function, quality of life, and adherence of participants in the community, compared to the control group. METHODS: This study is a single-blind, 12-week parallel randomized controlled trial. Seventy-two participants aged ≥ 50 years with KOA will be randomized into either the power cycling group, the quadriceps group or the control group. The intervention will be performed three times per week during 12 weeks. Outcome measures will be assessed at baseline, and at 4, 8, and 12 weeks after allocation. The primary outcome will be self-reported pain, assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes will include mitigation of knee pain, quality of life, improvement of functional physical performance, adherence of participants. DISCUSSION: By summarizing the study's strengths and limitations, this trial results may guide tele-rehabilitation of KOA in the community.Trial registration: The study was registered in the clinical trial registry ChiCTR2200059255, 27/04/2022.

Superior pancreatic lymphadenectomy with portal vein priority via posterior common hepatic artery approach in laparoscopic radical gastrectomy.

BACKGROUND: D2 lymph node dissection for advanced gastric cancer is advocated, and station 8p lymph node should be considered in selected patients, which is, however, technically difficult. AIM: To introduce a new and easy-to-perform procedure for dissection of the lymph nodes superior to the pancreas. METHODS: A series of patients who underwent laparoscopic gastrectomy for gastric cancer were retrospectively included with utilization of a new procedure for superior pancreatic lymphadenectomy (LND) with portal vein priority via the posterior common hepatic artery approach (SPLD-PPPH) based on a newly defined portal triangle. The surgical outcome of the patients, as well as the efficacy and safety of SPLD-PPPH are reported. RESULTS: A total of 51 patients were included with most of them being male (n = 34, 66.7%). According to the 8th edition of AJCC TNM staging, there were four (7.8%) patients in stage I, 13 (25.5%) in stage II, 33 (64.7%) in stage III and one (2.0%) in stage IV. The average duration for LND was about 1 h (67.7 ± 6.9 min). After surgery, four patients developed morbidities, but all were treated successfully with no perioperative mortality. Among the 51 patients included, the percentage of patients who had lymph node metastasis at station 8p was 9.8%. Of note, with a total of 14 lymph nodes harvested at station 8p, the incidence of nodal metastasis was 14.3%. CONCLUSION: About one in 10 patients with advanced gastric cancer had nodal metastasis at station 8p. The new approach of SPLD-PPPH is safe and effective for D2+ LND during laparoscopic radical gastrectomy.

Determination of 22 alternative plasticizers in wrap film by solid phase extraction and ultra-high performance supercritical fluid chromatography-tandem mass spectrometry.

A rapid, accurate and novel analytical method based on ultra-high performance supercritical fluid chromatography-tandem mass spectrometry for determination of 22 alternative plasticizers in wrap film was developed. Instrumental analysis and sample preparation procedures were systematically optimized. The targets were separated on Torus 1-AA column (100 mm × 3 mm, 1.7 µm). Mobile phase A was supercritical carbon dioxide, and mobile phase B was ethanol/methanol (7:3, v/v) containing 0.1% formic acid and 0.5 mM ammonium acetate. Gradient elution was performed. The analytes were extracted by 10 mL n-hexane/dichloromethane (1:1, v/v), and further purified on silica solid phase extraction cartridges. The analytes were quantified by ultra-high performance supercritical fluid chromatography-tandem mass spectrometry with electrospray ionization source, and detection was performed on multiple reaction monitoring mode. Two commercially available isotopically-labelled internal standards were used for quantification calibration, and analytes were divided into two groups according to the more appropriate internal standards (chemistry similarity, closeness of retention time). Method validation was performed in terms of recovery, repeatability, linearity, sensitivity and matrix effect. Linearity was assessed using matrix-matched standard calibration. Satisfactory linearity (r2 ≥ 0.995), intra-day precision (RSDs ≤ 9.6%), inter-day precision (RSDs ≤ 10.9%), recovery (75.6-124.5%) as well as good selectivity was observed. The limits of detection were 0.04-10 µg/kg, while the limits of quantification were 1.0-50 µg/kg. Most targets did not show significant matrix effect. Validation results verified that the proposed method was efficient, rapid and sensitive. Eventually it was successfully applied to food wrap film analysis, and results indicated that DEHA, ATBC, DBA and TnBP were the most frequently detected plasticizers in wrap film samples,which was worthy of attention.

Anti-oxidant, anti-inflammatory and anti-fibrosis effects of ganoderic acid A on carbon tetrachloride induced nephrotoxicity by regulating the Trx/TrxR and JAK/ROCK pathway.

Ganoderic acid A (GAA), one of the major triterpenoid components extracted from Ganoderma mushroom has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of GAA on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. The male mice were treated with 25 and 50 mg/mg GAA after stimulated with CCl4. Our results showed that GAA improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. GAA ameliorated CCl4-induced indices of inflammation. GAA suppressed oxidative stress by regulating the glutathione antioxidant system and the thioredoxin antioxidant system. GAA increased the activations of thioredoxin reductase (TrxR), Trx, GSH, SOD, GPx. Furthermore, GAA supplementation inhibited the JAK and STAT3 pathway. GAA inhibited the activations of RhoA, ROCK, NF-κB, TGF-ß and Smad3. Thus, this study demonstrated that GAA possesses immune-protective properties through regulating the Trx/TrxR, JAK2/STAT3 and RhoA/ROCK pathways.

Nephroprotective effect of gastrodin against lead-induced oxidative stress and inflammation in mice by the GSH, Trx, Nrf2 antioxidant system, and the HMGB1 pathway.

Gastrodin (GAS), the main phenolic glycoside derivative from Gastrodiaelata Blume, has several bio-activities. However, the molecular mechanisms of these protective actions currently remain unclear. This study aimed to investigate the mechanisms of GAS on lead (Pb)-induced oxidative stress and inflammation in the kidneys and primary kidney mesangial cells. Results indicated that GAS improved Pb-induced renal dysfunction and morphological changes in mice. GAS ameliorated Pb-induced inflammation in kidneys by reducing the TNF-α and IL-6 levels. GAS inhibited Pb-induced oxidative stress by regulating the glutathione, thioredoxin (Trx), and Nrf2 antioxidant systems. Furthermore, GAS supplementation increased the activation of SOD, GPx, HO-1, and NQO1 in the kidneys. GAS decreased the expression levels of HMGB1, TLR4, RAGE, MyD88, and NF-κB. These results were further confirmed in primary kidney mesangial cells. Collectively, this study demonstrated that GAS alleviated Pb-induced kidney oxidative stress and inflammation by regulating the antioxidant systems and the Nrf2 signaling pathway. Highlights Gastrodin ameliorated Pb-induced kidney injury in mice.Gastrodin inhibited oxidative stress and inflammation in kidneys.Gastrodin activated the GSH, Trx and Nrf2 antioxidant system in kidneys.Gastrodin inhibited the activities of HMGB1. RAGE, TLR4, and MyD88.

Bixin attenuates carbon tetrachloride induced oxidative stress, inflammation and fibrosis in kidney by regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-ß1/Smad3 pathway.

Bixin, an natural carotenoid extracted from the seeds of the Bixa orellana has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of Bixin on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. Our results showed that Bixin improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. Bixin ameliorated CCl4-induced inflammation in kidneys by reducing the levels of TNF-α and IL-1ß. Bixin suppressed oxidative stress by decreasing the MDA level and increasing the activation of SOD, CAT and GPx. Furthermore, Bixin increased the levels of PPAR-γ, NQO1, HO-1 and the nuclear translocation of Nrf2 in the kidneys of mice. Bixin supplementation inhibited the activation of TLR4, MyD88, NF-κB, TGF-ß and Smad3. Thus, this study demonstrated that Bixin possesses anti-oxidant, anti-inflammatory and anti-fibrosis properties through regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-ß1/Smad3 pathways.

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway.

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aß). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/ß-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK/Nrf2/HMGB1 pathway.

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibits potential renoprotective properties. Here, we examined the protective effects of GAS on carbon tetrachloride (CCl4)-induced kidney inflammation and fibrosis in mice, and explored its underlying mechanisms. Our research findings revealed that GAS improved CCl4-induced renal damage in mice. GAS inhibited kidney fibrosis and the deposition of collagen and α-smooth muscle actin (α-SMA). GAS suppressed CCl4-induced inflammation in kidney tissue, as indicated by the decreased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The renoprotective effects of GAS were associated with inhibiting oxidative stress by regulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling and increasing adenosine 5'-monophosphate activated protein kinase (AMPK) activation. Furthermore, GAS supplementation inactivated the receptor for advanced glycation end products (RAGE) and the high-mobility group box-1 (HMGB1) pathway. GAS inhibited the activation of Toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB) and transforming growth factor (TGF)-ß. Collectively, this study clarified that GAS attenuates CCl4-induced kidney inflammation and fibrosis via the AMPK/Nrf2/HMGB1 pathway.

Magnetooptical Properties of Chiral [Co2Ln] Clusters.

Two pairs of enantiomeric 3d-4f metal clusters, [Co2Ln[(R)/(S)-L]4]·Cl5·(H2O)2·CH3OH·CH3CH2OH [Co2Ln; Ln = Gd (1S and 1R), Dy (2S and 2R)], were synthesized by the reaction of chiral Schiff-base ligand (R)/(S)-3-[(2-hydroxybenzylidene) amino]propane-1,2-diol [(R)/(S)-HL] with CoCl2·6H2O and LnCl3·6H2O. The circular dichroism spectra of (S)/(R)-Co2Ln display a mirror-symmetry effect with seven peaks at 210-800 nm, which can be ascribed to π-π* transitions, exciton coupling, charge-transfer transitions between ligands and Co3+, and characteristic d-d transitions of Co3+ ions. Interestingly, the chiral Co2Ln metal clusters display strong magnetic circular dichroism signals at room temperature. This work suggests that the chiromagnetic metal cluster is expected to show a strong magnetooptical response.

Target Identification of Active Constituents of Shen Qi Wan to Treat Kidney Yang Deficiency Using Computational Target Fishing and Network Pharmacology.

Background: Kidney yang deficiency syndrome (KYDS) is one of the most common syndromes treated with traditional Chinese medicine (TCM) among elderly patients. Shen Qi Wan (SQW) has been effectively used in treating various diseases associated with KYDS for hundreds of years. However, due to the complex composition of SQW, the mechanism of action remains unknown. Purpose: To identify the mechanism of the SQW in the treatment of KYDS and determine the molecular targets of SQW. Methods: The potential targets of active ingredients in SQW were predicted using PharmMapper. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the Molecule Annotation System (MAS3.0). The protein-protein interaction (PPI) network of these potential targets and "components-targets-pathways" interaction networks were constructed using Cytoscape. We also established a KYDS rat model induced by adenine to investigate the therapeutic effects of SQW. Body weight, rectal temperature, holding power, water intake, urinary output, blood urea nitrogen (BUN), serum creatinine (Scr), adrenocorticotrophic hormone (ACTH), cortisol (CORT), urine total protein (U-TP), and 17-hydroxy-corticosteroid (17-OHCS) were measured. Additionally, the mRNA expression levels of candidates were detected by qPCR. Results: KYDS-caused changes in body weight, rectal temperature, holding power, water intake, urinary output, BUN, Scr, ACTH, CORT, U-TP, and 17-OHCS were corrected to the baseline values after SQW treatment. We selected the top 10 targets of each component and obtained 79 potential targets, which were mainly enriched in the proteolysis, protein binding, transferase activity, T cell receptor signaling pathway, and focal adhesion. SRC, MAPK14, HRAS, HSP90AA1, F2, LCK, CDK2, and MMP9 were identified as targets of SQW in the treatment of KYDS. The administration of SQW significantly suppressed the expression of SRC, HSP90AA1, LCK, and CDK2 and markedly increased the expression of MAPK14, MMP9, and F2. However, HRAS levels remained unchanged. Conclusion: These findings demonstrated that SQW corrected hypothalamic-pituitary-target gland axis disorder in rats caused by KYDS. SRC, MAPK14, HRAS, HSP90AA1, F2, LCK, CDK2, and MMP9 were determined to the therapeutic target for the further investigation of SQW to ameliorate KYDS.

A review of pretreatment and analytical methods of biogenic amines in food and biological samples since 2010.

Biogenic amines (BAs), mainly produced by amino acid decarboxylation, are widespread in foods and human organisms. Appropriate intake of BAs is beneficial to the human body, while excessive consumption may cause discomfort. Meanwhile, BAs are a kind of chemical marker for evaluating meat freshness. For these reasons, simple, rapid and efficient methods have been developed for the determination of BAs in food and biological products. This review introduces the provenance, classification and physiological activity of eight essential BAs and summarizes the dominant pretreatment and analysis methods since 2010. Pretreatment technologies mainly include the "dilute and shoot" method, ultrasonic assisted extraction, solid-phase extraction, matrix solid-phase dispersion, dispersive liquid-liquid microextraction, etc. Determination methods include liquid chromatography coupled to ultraviolet or fluorescence detectors, liquid chromatography tandem mass spectrometry, capillary electrophoresis, biosensors and so on.

High-Nuclearity Chiral 3 d-4 f Heterometallic Clusters Ln6Cu24 and Ln6Cu12.

Based on the anion template and chiral ligand inducting role, two series of high-nuclearity 3 d-4 f heterometallic clusters with formulas [NO3@Ln6Cu24(µ3-OH)30(µ2-OH)3(OAc)6( R/ S-L)12(H2O)24](NO3)14· x(H2O) (Ln = Dy, x = 30 for 1a( R-L) and 1b( S-L); Ln = Tb, x = 40 for 2a( R-L) and 2b( S-L)) and (Et3NH)4[Ln6Cu12(µ3-OH)14(µ2-Cl)6Cl12( R/ S-L)12]Cl2· x(H2O) (Ln = Dy, x = 28 for 3a( R-L) and 3b( S-L); Ln = Tb, x = 33 for 4a ( R-L) and 4b( S-L); HL = ( R/ S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), have been synthesized and characterized. Structural analysis reveals that the metal skeleton of compounds 1 and 2 display a Ln6Cu12 octahedral inner core encapsulated by six outer Cu2 units. In the Ln6Cu12 octahedron, 6 Ln3+ ions located at the six vertices and 12 inner Cu2+ ions located at the 12 edges of octahedron, and one NO3- locates in the center of the octahedron. The metal core of compounds 3 and 4 can be viewed as a Ln6 octahedron encapsulated by six Cu2 units. It is interesting that the different inorganic anions involved in the reaction result in the difference in the structures of 1 to 2 and 3 to 4. Circular dichroism spectra of 1-4 display obvious mirror symmetry effect at 600-800 nm of d-d transition of Cu2+, suggesting that the chirality transferred from chiral R- and S-ligand to Cu2+ ions in this system. Notably, the CD peak at the Cu2+ d-d transition position of Ln6Cu12 cluster is obviously blue-shifted compared with that of Ln6Cu24 due to the different coordinated environments of Cu2+. Magnetic studies indicate that 1a and 2a show weak ferromagnetic interactions, while 3a and 4a display antiferromagnetic interactions.

Intracerebroventricular injection of Aß1-42 combined with two-vessel occlusion accelerate Alzheimer's disease development in rats.

Numerous experimental studies and clinical observations suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD). Two-vessel occlusion caused cerebral ischemia model is often used in the study of vascular dementia (VaD). But how cerebral ischemia works on AD rat model which induced by intracerebroventricular injection of Aß1-42 remains unclear. In the following study, we investigated the characteristics of rat model caused by intracerebroventricular injection of Aß1-42 or two-vessel occlusion (2-VO) only and by both of the two operations. The animal cognitive functions were accessed by the Morris water maze. Regional cerebral blood flow was detected by Laser Doppler Blood Flowmeter. HE&Nissl staining, Congo red staining and immunohistochemistry were used to observe the status of neuronal loss, Aß deposition and the phosphorylated tau expression in hippocampus, respectively. We also measured the contents of AchE and ChAT in serum and hippocampus by Enzyme Linked Immunosorbent Assay. The MWM results showed that rats of Aß1-42+2-VO group had a disorder in cognitive functions, at an early stage of one week after modeling, comparing with rats of sham group. The regional cerebral blood flow (rCBF) was significantly reduced in Aß1-42+2-VO and 2-VO group one week after modeling, and still maintained low perfusion levels four weeks after modeling. HE and Nissl staining showed that Aß1-42+2-VO rats' hippocampal CA1 neurons were in disorder, degeneration and necrosis, severe neuronal loss from the first week to the fourth week, while this phenomenon only appeared in the fourth week after modeling in rats of Aß1-42 group and 2-VO group. Congo red staining showed that Aß1-42 + 2-VO group rats' hippocampus CA1 had amyloid deposits from the first week to the fourth week, Aß1-42 group were not find amyloid deposition significantly until four weeks after modeling, however, 2-VO group had no significant amyloid deposition all the time. Notably, IHC showed that, two weeks after modeling, the p-tau positive total area and integrated optical density of hippocampal CA1 region were significantly increased in Aß1-42 + 2-VO group rats, while 2-VO group and Aß1-42 group rats had no significantly changes all the time. We also found that the content of AchE was increased both in serum and hippocampus of Aß1-42 + 2-VO group rats, and ChAT was decreased. However, there was no significantly change in cortex of content of AchE: acetylcholinesterase (AchE) and choline acetylase (ChAT) all three groups. Together, our study suggest that intracerebroventricular injection of Aß1-42 combined with two-vessel occlusion may accelerate Alzheimer's disease development in rats. Also, this may serve as a less-time consuming new model to study the Alzheimer's disease and especially AD accompanied by cerebral ischemia.