[M8L4]8+-Type Squares Self-Assembled by Dipalladium Corners and Bridging Aromatic Dipyrazole Ligands for Iodine Capture.

Square-like metallamacrocyclic palladium(II) complexes [M8L4]8+ (1-7) were synthesized by reacting aromatic dipyrazole ligands (H2L1-H2L3 with pyromellitic arylimide-, 1,4,5,8-naphthalenetetracarboxylic arylimide-, and anthracene-based aromatic groups, respectively) with dipalladium corners ([(bpy)2Pd2(NO3)2](NO3)2, [(dmbpy)2Pd2(NO3)2](NO3)2, or [(phen)2Pd2(NO3)2](NO3)2, where bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine, and phen = 1,10-phenanthroline) in aqueous solutions via metal-directed self-assembly. Metallamacrocycles 1-7 were fully characterized by 1H and 13C nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry, and the square structure of 7·8NO3- was further confirmed via single crystal X-ray diffraction. These square-like metallamacrocycles exhibit effective performance for iodine adsorption.

A Sample and Sensitive HPLC-MS/MS Method for Simultaneous Determination of Ziyuglycoside I and Its Metabolite Ziyuglycoside II in Rat Pharmacokinetics.

Ziyuglycoside I (ZGS1) is a promising drug candidate for the treatment of leucopenia. Currently, information on ZGS1 and its in vivo metabolite ziyuglycoside II (ZGS2) is limited. The objective of this study was to investigate the pharmacokinetics, tissue distribution, and excretion of ziyuglycoside I (ZGS1) and its metabolite ziyuglycoside II (ZGS2) in rats. In our study, a simple and sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was established for simultaneous determination of ZGS1 and its metabolite for Sprague-Dawley rat pharmacokinetics studies. The method was validated following internationally-approved guidelines. The results presented in this study indicated that subcutaneous administration of ZGS1 prolonged its extension time and increased the area under the curve (AUC0-t) of ZGS2 during 0 to t minutes. In summary, in this study, the pharmacokinetic characteristics of ZGS1 and its metabolite ZGS2 were defined and its tissue distribution, and excretion in rats were described. Our finding may be beneficial for leucopenia drug that focus on ZGS1.

[Genetic Recombiniation and Protein Expression Detection of Listeria-based tuberculosis Vaccine Candidates.]

OBJECTIVES: Genetic construction of tuberculosis vaccine candidates based on Listeria(L.) monocytogenes,L.ivanovii,and evaluation their protein expression,in order to provide a novel method for research on tuberculosis controlling. METHODS: Two kinds of gene cassettes carrying tuberculosis antigen encoding gene Rv3875 or Rv0129c were inserted into targeting vector harboring L.monocytogenes,L.ivanovii homologous sequences via genetic connection methods and plasmid transformation technology in vitro.Targeting plasmids were electroporated into L.monocytogenes,L.ivanovii,and the recombinant strains were experienced serial passage at 42 °C and 30 °C.Subsequently,the tuberculosis antigen gene cassettes in targeting plasmids were integrated into L.monocytogenes and L.ivanovii attenuated strain (knocking out of virulence gene actA and plcB) and L.ivanovii wild type strain by homologous recombination and gene targeting technology.The recombinant strains were screened by blue-white spot and antibiotic resistance test;the intracellular and extracellular proteins of the recombinant strains were tested by Western blot. RESULTS: Five recombination strains carried antigen gene cassette were constructed,and the recombinant genome were confirmed by PCR and sequencing.No erythromycin resistance gene was found in 5 strains,which was coincident to expection.Recombination strains Li-Rv0129c,Li-ΔactAplcB-Rv0129c and Li-ΔactAplcB-Rv3875 expressed Mycobacterium tuberculosis antigenic protein,Ag85C or ESAT-6,as expected.But L.monocytogenes strains did not express proper antigenic protein. CONCLUSIONS: Three novel L.ivanovii-based tuberculosis vaccine candicates,carrying Mycobacterium tuberculosis Rv0129c antigen gene cassette (coding for Ag85C) or Rv3875 gene cassette (coding for ESAT-6),and expressing relevant antigenic proteins have been successfully selected.

MAGE-A3 regulates tumor stemness in gastric cancer through the PI3K/AKT pathway.

Gastric cancer remains a malignant disease of the digestive tract with high mortality and morbidity worldwide. However, due to its complex pathological mechanisms and lack of effective clinical therapies, the survival rate of patients after receiving treatment is not satisfactory. A increasing number of studies have focused on cancer stem cells and their regulatory properties. In this study, we first constructed a co-expression network based on the WGCNA algorithm to identify modules with different degrees of association with tumor stemness indices. After selecting the most positively correlated modules of the stemness index, we performed a consensus clustering analysis on gastric cancer samples and constructed the co-expression network again. We then selected the modules of interest and applied univariate COX regression analysis to the genes in this module for preliminary screening. The results of the screening were then used in LASSO regression analysis to construct a risk prognostic model and subsequently a sixteen-gene model was obtained. Finally, after verifying the accuracy of the module and screening for risk genes, we identified MAGE-A3 as the final study subject. We then performed in vivo and in vitro experiments to verify its effect on tumor stemness and tumour proliferation. Our data supports that MAGE-A3 is a tumor stemness regulator and a potent prognostic biomarker which can help the prediction and treatment of gastric cancer patients.

miR-497-5p-RSPO2 axis inhibits cell growth and metastasis in glioblastoma.

Numerous studies have found a relationship between cancer formation and aberrant microRNA expression, however the biological significance of miR-497-5p in glioblastoma (GBM) is still unknown. Compared to normal brain glial cells, miR-497-5p expression in GBM tissues was substantially lower in our study. The microRNA miR-497-5p targets R-spondin 2 (RSPO2) only when it is present. RSPO2 silencing has the same effect on GBM cells as miR-497-5p silencing, as demonstrated before. Additional mechanistic investigations have shown that miR-497-5p suppresses the Wnt/ß-catenin signaling pathway by targeting RSPO2 to reduce cell proliferation, migration, and invasion. A negative correlation was discovered between MiR-497-5p and RSPO2 in 37 of the GBM tumors studied. MiR-497-5p-RSPO2 axis controls Wnt/ß-catenin signaling and plays a function in GBM carcinogenesis, suggesting that it may be a therapeutic target to reduce GBM growth, as shown by our research findings.

Simultaneous Determination of Three Coumarins in Rat Plasma by HPLC-MS/MS for Pharmacokinetic Studies Following Oral Administration of Chimonanthi Radix Extract.

Chimonanthi Radix (CR) is widely used in the treatment of influenza in China. Extensive studies revealed that the major bioactive constituents of CR were coumarins. However, pharmacokinetic study of coumarins in CR has not been fully studied. The purpose of this study was to establish a convenient and effective high-performance liquid chromatography-tandem mass spectrometry method that was used to simultaneously determine scopoletin, scopolin and isofraxidin in rat plasma after oral administration of CR extract using xanthotoxin as the internal standard. The chromatographic separation was carried out on a COSMOCORE C18 column (100 × 2 mm, 2.6 µm), using gradient elution with the mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). Three coumarins and IS were quantified by positive ion electrospray ionization in multiple reaction monitoring mode. The method was fully validated in terms of specificity, accuracy, precision (intra- and inter-day), matrix effect, recovery as well as the stability of the analytes under various conditions. The results could provide further research foundation for anti-influenza mechanism of three coumarins in CR.

Calcium-Polystyrene Sulfonate Decreases Inter-Dialytic Hyperkalemia in Patients Undergoing Maintenance Hemodialysis: A Prospective, Randomized, Crossover Study.

Hyperkalemia is a life-threatening emergency in maintenance hemodialysis (MHD) patients. This clinical trial investigated the efficacy and safety of calcium-polystyrene sulfonate (Ca-PS) in MHD patients with interdialytic hyperkalemia. A total of 58 hemodialysis patients with hyperkalemia (≥5.5 mol/L) were selected and administered either a 3-week Ca-PS (3 × 5 g/day) or a blank control following the model of a prospective, randomized, crossover clinical trial with a 1-week washout period. All patients were followed up for another 3 weeks for safety evaluations. The primary outcome was the magnitude of the change in serum potassium levels. The secondary outcomes were electrocardiography (ECG) changes and treatment safety (volume overload, electrolyte imbalance). Compared with the control group, Ca-PS treatment significantly reduced serum potassium levels (P <0.01). More patients in the Ca-PS group had lower serum potassium levels than the safety level of <5.5 mmol/L (32% for control vs. 61% for Ca-PS, P <0.01). Peaked T-wave occurred less frequently in patients in the Ca-PS group (13.8% for Ca-PS vs. 31.03% for control, P <0.01). In addition, Ca-PS reduced serum phosphorus levels with no effects on serum levels of calcium and sodium, fluid volume, blood pressure, or interdialytic weight gain. Ca-PS treatment decreases serum levels of potassium and phosphorus in MHD patients with interdialytic hyperkalemia. Ca-PS does not induce volume overload or disrupt electrolyte balance.

An acute gastroenteritis outbreak caused by GII.P16-GII.2 norovirus associated with airborne transmission via the air conditioning unit in a kindergarten in Lianyungang, China.

Noroviruses are a common cause of acute gastroenteritis outbreaks in institutions including schools and kindergartens around the world. An outbreak caused by GII.P16-GII.2 norovirus in a kindergarten in Lianyungang, Jiangsu Province, China is reported here. An epidemiological investigation was conducted, and pathogen detection was performed. The descriptive analysis indicated that this outbreak in middle class 1 had a point source. Twenty cases of acute gastroenteritis occurred in this class within a period of 8.5h; the attack rate was 52.6% (20/38). Airborne transmission via the air conditioning unit in a confined restroom could have played a critical role in this outbreak. Sequence analysis of GII-positive samples confirmed that the norovirus GII.P16-GII.2 variant was the etiological agent of this outbreak.