[Chlorogenic acid alleviates acute kidney injury in septic mice by inhibiting NLRP3 inflammasomes and the caspase-1 canonical pyroptosis pathway].

OBJECTIVE: To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid (CGA) treatment of acute kidney injury (AKI) in mice. METHOD: Twenty-four C57Bl/6J mice were randomized into sham-operated group, cecal ligation and puncture (CLP) group, CLP+dexamethasone group (CLP+DXM group), and CLP+CGA group (n=6) and subjected to either sham operation (laparotomy only) or CLP. After modeling the mice received intravenous infusion of 10 mg/kg normal saline (in sham and CLP groups), 1 µg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump. Eight hours after the infusion, renal morphology and histology, renal cell apoptosis, and the renal function parameters such as urea nitrogen (BUN), creatinine (Scr), and kidney injury molecule 1 (KIM-1) were compared among the 4 groups; the 7-day survival rates of the mice were recorded, and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected. RESULTS: CGA treatment significantly improved the 7-day survival rate, reduced renal pathologies of the septic mice (P < 0.05), and lowered the levels of BUN, Scr, KIM-1, NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway. CONCLUSION: CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

The integrated diagnostic suite of the C-2W experimental field-reversed configuration device and its applications.

In the current experimental device of TAE Technologies, C-2W (also called "Norman"), record breaking advanced beam-driven field-reversed configuration (FRC) plasmas are produced and sustained in steady state utilizing variable energy neutral beams (15-40 keV, total power up to 20 MW), advanced divertors, bias electrodes, and an active plasma control system. This fully operational experiment is coupled with a fully operational suite of advanced diagnostic systems. The suite consists of 60+ individual systems spanning 20 categories, including magnetic sensors, Thomson scattering, interferometry/polarimetry, spectroscopy, fast imaging, bolometry, reflectometry, charged and neutral particle analysis, fusion product detection, and electric probes. Recently, measurements of main ion temperatures via a diagnostic neutral beam, axial profiles of energy flux from an array of bolometers, and divertor and edge plasma parameters via an extensive set of electric probes, interferometers, and spectrometers have all been made available. All the diagnostics work together to provide a complete picture of the FRC, fast-ion inventory, and edge plasma details enabling tomographic reconstruction of plasma parameter profiles and real-time plasma control.

DT-13 inhibits breast cancer cell migration via non-muscle myosin II-A regulation in tumor microenvironment synchronized adaptations.

BACKGROUND: Tumor metastasis is a terrifying characteristic of cancer. Numerous studies have been conducted to overcome metastasis by targeting tumor microenvironment (TME). However, due to complexity of tumor microenvironment, it remained difficult for accurate targeting. Dwarf-lillytruf tuber monomer-13 (DT-13) possess good potential against TME. OBJECTIVE: As TME is supportive for tumor metastasis, alternatively it is a challenging for therapeutic intervention. In our present study, we explored molecular mechanism through which TME induced cell migration and how DT-13 interferes in this mechanism. METHODS: We used a novel model of co-culture system which is eventually developed in our lab. Tumor cells were co-cultured with hypoxia induced cancer-associated fibroblasts (CAF) or with chemically induced cancer-associated adipocytes (CAA). The effect of hypoxia in conditioned medium for CAF was assessed through expression of α-SMA and HIF by western blotting while oil red staining was done to assess the successful chemical induction for adipocytes (CAA), the effect of TME through conditioned medium on cell migration was analyzed by trans-well cell migration, and cell motility (wound healing) analyses. The expression changes in cellular proteins were assessed through western blotting and immunofluorescent studies. RESULTS AND CONCLUSION: Our results showed that tumor microenvironment has a direct role in promoting breast cancer cell migration by stromal cells; moreover, we found that DT-13 restricts this TME regulated cell migration via targeting stromal cells in vitro. Additionally we also found that DT-13 targets NMII-A for its effect on breast cancer cell migration for the regulation of stromal cells in TME.

Characterization and calibration of the Thomson scattering diagnostic suite for the C-2W field-reversed configuration experiment.

The new C-2W Thomson scattering (TS) diagnostic consists of two individual subsystems for monitoring electron temperature (Te) and density (ne): one system in the central region is currently operational, and the second system is being commissioned to monitor the open field line region. Validating the performance of the TS's custom designed system components and unique calibration of the detection system and diagnostic as a whole is crucial to obtaining high precision Te and ne profiles of C-2W's plasma. The major components include a diode-pumped Nd:YAG laser which produces 35 pulses at up to 20 kHz, uniquely designed collection lenses with a fast numerical aperture, and uniquely designed polychromators with filters sets to optimize a Te ranging from 10 eV to 2 keV. This paper describes the design principles and techniques used to characterize the main components of the TS diagnostic on C-2W, as well as the results of Rayleigh scattering calibrations performed for the whole system response.

Thomson scattering systems on C-2W field-reversed configuration plasma experiment.

TAE Technologies' newly constructed C-2W experiment aims to improve the ion and electron temperatures in a sustained field-reversed configuration plasma. A suite of Thomson scattering systems has been designed and constructed for electron temperature and density profile measurements. The systems are designed for electron densities of 1 × 1012 cm-3 to 2 × 1014 cm-3 and temperature ranges from 10 eV to 2 keV. The central system will provide profile measurements of Te and ne at 16 radial locations from r = -9 cm to r = 64 cm with a temporal resolution of 20 kHz for 4 pulses or 1 kHz for 30 pulses. The jet system will provide profile measurements of Te and ne at 5 radial locations in the open field region from r = -5 cm to r = 15 cm with a temporal resolution of 100 Hz. The central system and its components have been characterized, calibrated, installed, and commissioned. A maximum-likelihood algorithm has been applied for data processing and analysis.

[Comparisons of prevalence and clinical and environmental characteristics between Tibetan and Han Women with polycystic ovarian syndrome in Tibetan Plateau].

Objective: By the preliminary comparison study on the constituent ratio and clinical characteristics of polycystic ovary syndrome (PCOS) in Tibetan and Han women in Tibetan Plateau, we aimed to find the relevance of its pathogenic factors, and to guide the treatment of PCOS in the plateau region and improve the prognosis. Methods: The general situation and clinical data of 165 patients who were diagnosed with PCOS from December 1, 2015 to November 30, 2016 in the Department of Obstetrics and Gynecology of the People's Hospital of Tibet Autonomous Region were analyzed retrospectively. The prevalence of PCOS among Tibetan and Han women in Tibetan Plateau were compared. Results: (1) A total of 1 520 patients were treated in the Tibet Autonomous Region People's Hospital gynecological endocrinology clinics in one year (Tibetan 865 cases, Han 617 cases, other ethnic groups 38 cases), of which patients with PCOS accounted for 10.9% (165/1520). (2) The incidence of Tibetan PCOS patients with oligomenorrhea, infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI≥24), and waist circumference >80 cm were 21.2% (35/165), 20.6% (34/165), 16.4% (27/165), 28.5% (47/165), 17% (28/165), 38.2% (63/165), 23.6% (39/165), and 36.4% (60/165), respectively. The incidence of Han PCOS patients with oligomenorrhea, infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI≥24), and waist circumference >80 cm were 7.9% (13/165), 10.3% (17/165), 9.1% (15/165), 15.2% (25/165), 9.7% (16/165), 14.5% (24/165), 10.9% (18/165) and 19.4% (32/165), respectively. The proportion of high testosterone in Tibetan PCOS patients was higher than that in Han PCOS patients with statistically significant. (3) The chief complaint of Tibetan PCOS patients were oligomenorrhea and infertility, and the chief complaint of Han PCOS patients were infertility and amenorrhea. (4) The constituent ratio of outpatient clinics in Nyingchi who were with PCOS at an average elevation of about 3 000 meters in the Tibetan Plateau was 7.9% (13/165), and the average constituent ratio in Lhasa, Xigatse and Nagqu over 3 500 meters above sea level was 35.8% (59/165), 16.9% (28/165) and 15.8% (26/165), respectively. Conclusion: The prevalence of PCOS in Tibetan areas is slightly higher than that in the international community. The clinical manifestations of Tibetan patients with PCOS are significantly different from those of Han patients with PCOS. The higher the altitude, the higher the incidence of PCOS.

The upgrade of the Thomson scattering system for measurement on the C-2/C-2U devices.

The C-2/C-2U Thomson scattering system has been substantially upgraded during the latter phase of C-2/C-2U program. A Rayleigh channel has been added to each of the three polychromators of the C-2/C-2U Thomson scattering system. Onsite spectral calibration has been applied to avoid the issue of different channel responses at different spots on the photomultiplier tube surface. With the added Rayleigh channel, the absolute intensity response of the system is calibrated with Rayleigh scattering in argon gas from 0.1 to 4 Torr, where the Rayleigh scattering signal is comparable to the Thomson scattering signal at electron densities from 1 × 1013 to 4 × 1014 cm-3. A new signal processing algorithm, using a maximum likelihood method and including detailed analysis of different noise contributions within the system, has been developed to obtain electron temperature and density profiles. The system setup, spectral and intensity calibration procedure and its outcome, data analysis, and the results of electron temperature/density profile measurements will be presented.

Genetic characterization of Toxoplasma gondii from domestic animals in central China.

Toxoplasma gondii is an obligate intracellular parasite that has a remarkable ability to infect almost all warm-blooded animals, including humans. This study was aimed to determine the genetic characteristics of T. gondii isolates from domestic animals in Henan Province, central China. A total of 363 DNA samples, including 208 from hilar lymph nodes of pigs, 36 from blood samples of cats, 12 from tissues of aborted bovine fetuses and 107 from blood samples of dams with history of abortion in Henan Province, were examined for the presence of T. gondii by nested PCR based on B1 gene. The positive DNA samples were further genotyped by PCR-RFLP at 11 markers, including SAG1, (3'+ 5') SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico. DNA samples from 9 pigs, 5 cats, and 4 dairy cows were T. gondii B1 gene positive. Nine samples were successfully genotyped at all genetic loci, of which 5 samples from pigs, and 2 from cats were identified as ToxoDB genotype #9, and 2 samples from cows belonged to ToxoDB genotype #225. To our knowledge, the present study is the second report of genetic typing of T. gondii isolates from cattle in China, and the first report of T. gondii ToxoDB#225 from cattle.

Genetic characterization of Toxoplasma gondii from domestic animals in central China

Toxoplasma gondii is an obligate intracellular parasite that has a remarkable ability to infect almost all warm-blooded animals, including humans. This study was aimed to determine the genetic characteristics of T. gondii isolates from domestic animals in Henan Province, central China. A total of 363 DNA samples, including 208 from hilar lymph nodes of pigs, 36 from blood samples of cats, 12 from tissues of aborted bovine fetuses and 107 from blood samples of dams with history of abortion in Henan Province, were examined for the presence of T. gondii by nested PCR based on B1 gene. The positive DNA samples were further genotyped by PCR-RFLP at 11 markers, including SAG1, (3’+ 5’) SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico. DNA samples from 9 pigs, 5 cats, and 4 dairy cows were T. gondii B1 gene positive. Nine samples were successfully genotyped at all genetic loci, of which 5 samples from pigs, and 2 from cats were identified as ToxoDB genotype #9, and 2 samples from cows belonged to ToxoDB genotype #225. To our knowledge, the present study is the second report of genetic typing of T. gondii isolates from cattle in China, and the first report of T. gondii ToxoDB#225 from cattle.

Simultaneous HPLC determination of four active compounds in fengshiding capsules, a chinese medicine.

A high performance liquid chromatography method was established for simultaneously determining four bioactive components, salicin, liquiritin, paeonolum, and imperatorin in Fengshiding capsule, a widely used traditional Chinese medicine for treating rheumatic disease. The chromatographic separation was performed on a Shimadzu Shim-pack Stable Bond C18 column using gradient elution with methanol and water. The analytical method was validated through precision, repeatability and stability, and the relative standard deviation values were less than 3%, respectively. The recoveries of the four investigated compounds ranged from 95.80 to 101.21% with relative standard deviation values less than 3.2%. Then this proposed method was successfully applied to determine six batches of Fengshiding commercial products of capsule dosage form from two pharmaceutical factories. This study might provide a basis for quality control for this traditional Chinese medicine preparation.

Alteration of vascular reactivity in heart failure: role of phosphodiesterases 3 and 4.

BACKGROUND AND PURPOSE: This study examined the role of the main vascular cAMP-hydrolysing phosphodiesterases (cAMP-PDE) in the regulation of basal vascular tone and relaxation of rat aorta mediated by ß-adrenoceptors, following heart failure (HF). EXPERIMENTAL APPROACH: Twenty-two weeks after proximal aortic stenosis, to induce HF, or SHAM surgery in rats, we evaluated the expression, activity and function of cAMP-PDE in the descending thoracic aorta. KEY RESULTS: HF rat aortas exhibited signs of endothelial dysfunction, with alterations of the NO pathway, and alteration of PDE3 and PDE4 subtype expression, without changing total aortic cAMP-hydrolytic activity and PDE1, PDE3 and PDE4 activities. Vascular reactivity experiments using PDE inhibitors showed that PDE3 and PDE4 controlled the level of PGF2α -stimulated contraction in SHAM aorta. PDE3 function was partially inhibited by endothelial NO, whereas PDE4 function required a functional endothelium and was under the negative control of PDE3. In HF, PDE3 function was preserved, but its regulation by endothelial NO was altered. PDE4 function was abolished and restored by PDE3 inhibition. In PGF2α -precontracted arteries, ß-adrenoceptor stimulation-induced relaxation in SHAM aorta, which was abolished in the absence of functional endothelium, as well as in HF aortas, but restored after PDE3 inhibition in all unresponsive arteries. CONCLUSIONS AND IMPLICATIONS: Our study underlines the key role of the endothelium in controlling the contribution of smooth muscle PDE to contractile function. In HF, endothelial dysfunction had a major effect on PDE3 function and PDE3 inhibition restored a functional relaxation to ß-adrenoceptor stimulation.

Experimental demonstration of improved neoclassical transport with quasihelical symmetry.

Differences in the electron particle and thermal transport are reported between plasmas produced in a quasihelically symmetric (QHS) magnetic field and a configuration with the symmetry broken. The thermal diffusivity is reduced in the QHS configuration, resulting in higher electron temperatures than in the nonsymmetric configuration for a fixed power input. The density profile in QHS plasmas is centrally peaked, and in the nonsymmetric configuration the core density profile is hollow. The hollow profile is due to neoclassical thermodiffusion, which is reduced in the QHS configuration.