An integrated high-flux cold atomic beam source for strontium.

We present the design, construction, and characterization of an integrated cold atomic beam source for strontium (Sr), which is based on a compact Zeeman slower for slowing the thermal atomic beam and an atomic deflector for selecting the cold flux. By adopting arrays of permanent magnets to produce the magnetic fields of the slower and the deflector, we effectively reduce the system size and power compared to traditional systems with magnetic coils. After the slower cooling, one can employ additional transverse cooling in the radial direction and improve the atom collimation. The atomic deflectors employ two stages of two-dimensional magnetic-optical trapping (MOT) to deflect the cold flux, whose atomic speed is lower than 50 m/s, by 20° from the thermal atomic beam. We characterize the cold atomic beam flux of the source by measuring the loading rate of a three-dimensional MOT. The loading rates reach up to 109 atoms/s. The setup is compact, highly tunable, lightweight, and requires low electrical power, which addresses the challenge of reducing the complexity of building optical atomic clocks and quantum simulation devices based on Sr.

Contrasting effects of different light regimes on the photoreactivities of allochthonous and autochthonous chromophoric dissolved organic matter.

Chromophoric dissolved organic matter (CDOM) plays an important role in ultraviolet (UV) light absorption in the ocean. CDOM is known to originate from either an allochthonous or autochthonous source and has varying compositions and levels of reactivity; however, the effects of individual radiation treatments and the combined effects of UVA and UVB on allochthonous and autochthonous CDOM remain poorly understood. Thus, here, we measured changes in the common optical properties of CDOM collected from China's marginal seas and the Northwest Pacific, using full-spectrum, UVA (315-400 nm), and UVB (280-315 nm) irradiation to induce photodegradation over the same time period (60 h). Excitation-emission matrices (EEMs) combined with parallel factor analysis (PARAFAC) identified four components: marine humic-like C1, terrestrial humic-like C2, soil fulvic-like C3, and tryptophan-like C4. Although the behaviours of these components during full-spectrum irradiation exhibited similar decreasing tendencies, three components (C1, C3, and C4) underwent direct photodegradation under UVB exposure, whereas C2 was more susceptible to UVA degradation. The diverse photoreactivities of the source-dependent components to different light treatments led to differing photochemical behaviours of other optical indices [aCDOM(355), aCDOM(254), SR, HIX, and BIX]. The results indicate that irradiation preferentially reduced the high humification degree or humic substance content of allochthonous DOM, and promoted the transformation from the allochthonous humic DOM components to recently produced components. Although values for the samples from different sources overlapped frequently, principal component analysis (PCA) indicated that the overall optical signatures could be linked to the original CDOM source features. The degradation of CDOM humification, aromaticity, molecular weight, and autochthonous fractions under exposure can drive the CDOM biogeochemical cycle in marine environments. These findings can aid in a better understanding of the effects of different combinations of light treatments and CDOM characteristics on CDOM photochemical processes.

Discovery of 2H-chromone-4-one based sulfonamide derivatives as potent retinoic acid receptor-related orphan receptor γt inverse agonists.

Retinoic acid receptor related orphan receptor γt (RORγt), identified as the essential functional regulator of IL-17 producing Th17 cells, is an attractive drug target for treating autoimmune diseases. Starting from the reported GSK2981278 (Phase II), we structurally modified and synthesized a series of 2H-chromone-4-one based sulfonamide derivatives as novel RORγt inverse agonists, which significantly improved their human metabolic stabilities while maintaining a potent RORγt inverse agonist profile. Efforts in reducing the lipophilicity and improving the LLE values led to the discovery of c9, which demonstrated potent RORγt inverse agonistic activity and consistent metabolic stability. During in vivo studies, oral administration of compound c9 exhibited a robust and dose-dependent inhibition of IL-17A cytokine expression and significantly lessened the skin inflammatory symptoms in the mouse imiquimod-induced skin inflammation model. Docking analysis of the binding mode revealed that c9 can suitably occupy the active pocket, and the introduction of the morpholine pyridine group can interact with Leu396, His479, and Cys393. Thus, compound c9 was selected as a preclinical compound for treating Th17-driven autoimmune diseases.

Comparison of Clinical Efficacy and Safety of Metformin Sustained-Release Tablet (II) (Dulening) and Metformin Tablet (Glucophage) in Treatment of Type 2 Diabetes Mellitus.

Objectives: This study investigated the clinical efficacy and safety of metformin hydrochloride sustained-release (SR) tablet (II) produced by Dulening and the original metformin hydrochloride tablet produced by Glucophage in the treatment of type 2 diabetes mellitus (T2DM). Methods: This randomized, open and parallel controlled clinical trial consecutively recruited a total of 886 patients with T2DM in 40 clinical centers between May 2016 and December 2018. These patients were randomly assigned to the Dulening group (n=446), in which patients were treated with Dulening metformin SR tablets, and the Glucophage group (n=440), in which patients were treated with Glucophage metformin tablets, for 16 weeks. The changes in the levels of glycated hemoglobin (HbAc1) and fasting blood glucose (FBG) as well as weight loss were compared between these two groups. Also, the overall incidence of adverse drug reactions (ADRs) and the incidence of ADR of the gastrointestinal system observed in patients of these two groups were also compared. Results: There were no significant differences in demographic and basal clinical characteristics between these two groups. The Dulening and Glucophage groups showed comparable levels of decrease in HbA1c levels, FBG and weight loss after 12-week treatment (all p>0.05). The Dulening group had a significantly lower overall incidence of ADRs as well as gastrointestinal ADR than the Glucophage group. Conclusions: Metformin SR tablets (II) and the original metformin tablets exhibit similar therapeutic efficacy in the treatment of T2DM, but metformin SR tablets (II) has the significantly lower incidence of ADRs than the original metformin tablets.

Comprehensive analysis of long non-coding RNA and mRNA expression profile in rectal cancer.

BACKGROUND: Rectal cancer (RC) is a malignant tumor that seriously threatens human health. Long non-coding RNAs (lncRNAs) play a vital role in tumor regulation. Nevertheless, their exact expression features and functions remain obscure, and therefore was the aim of the current study. METHODS: We utilized the Affymetrix human GeneChip to screen differentially expressed profiles of lncRNAs and mRNAs from the cancer tissues and matched paracancer tissues of 6 RC patients. Gene Ontology (GO) and pathway enrichment analyses identified crucial functions and pathways of the aberrantly expressed mRNAs. We used quantitative real-time polymerase chain reaction to verify the significant expression differences of 11 candidate lncRNAs between the cancer and paracancer tissues. LncRNA-mRNA coexpression networks were built by calculating the Pearson correlation value to identify significant correlation pairs. Online bioinformatics tools GEPIA2, ONCOMINE, and PROGgeneV2 were used to mine the expression and prognosis of three crucial mRNAs and six verified lncRNAs. Competing endogenous RNA networks were constructed by predicting microRNA response elements and calculating free energy. RESULTS: We found 1658 differentially expressed lncRNAs (778 up-regulated and 880 down-regulated) and 1783 aberrantly expressed mRNAs (909 up-regulated and 874 down-regulated). GO and pathway enrichment analyses revealed the vital functions of the differentially expressed mRNAs, including cell proliferation, cell migration, angiogenesis, and cellular response to zinc ion. The canonical signaling pathways mainly included the interleukin-17, cell cycle, Wnt, and mineral absorption signaling pathways. Six lncRNAs including AC017002.2 (P = 0.039), cancer susceptibility 19 (CASC19) (P = 0.021), LINC00152 (P = 0.013), NONHSAT058834 (P = 0.007), NONHSAT007692 (P = 0.045), and ENST00000415991.1 (P = 0.045) showed significant differences in expression levels between the cancer tissue and paracancer tissue groups. AC017002.2, NONHSAT058834, NONHSAT007692, and ENST00000415991.1 have not yet been reported in RC. The crucial mRNAs myelocytomatosis viral oncogene (MYC), transforming growth factor beta induced (TGFBI), and solute carrier family 7 member 5 (SLC7A5) were selected. AC017002.2 and LINC00152 were positively correlated with MYC, TGFBI, and cytochrome P450 family 2 sub-family B member 6 (All r > 0.900, P < 0.050). NONHSAT058834 was positively associated with MYC (r = 0.930, P < 0.001), and CASC19 was positively correlated with SLC7A5 (r = 0.922, P < 0.001). CONCLUSION: This study offers convincing evidence of differentially expressed lncRNAs and mRNAs as potential biomarkers in RC.

Preoperative assessment of complicated appendicitis through stress reaction and clinical manifestations.

This study assessed the severity of the disease through the preoperative clinical manifestations and inflammatory reaction indicators of acute appendicitis, and established a score table to predict complicated appendicitis (CA).The clinical data of 238 patients with acute appendicitis in our hospital were retrospectively analyzed, which included 18 patients with acute simple appendicitis (7.6%), 170 patients with acute purulent appendicitis (72.0%), and 48 patients with acute gangrene and perforation (20.3%). The clinical manifestations and inflammatory reaction indicators were analyzed by univariate logistic regression. Multivariate logistic regression analysis was performed to screen out the independent risk factors of CA. The ß coefficients of independent risk factors entering the multivariate model were assigned by rounding, and the total score was the sum of values of all factors. Finally, verification and analysis were performed for the predictive model, and the operating characteristic curve (ROC) curve was drawn. Then, the area under the curve (AUC) was compared with the THRIVE scale, and the Hosmer-Lemeshow method was used to evaluate whether the model fitted well.The multivariate logistic regression analysis of independent risk factors was performed, and the values were rounded to the variable assignment based on the ß coefficient values. The plotted ROC and AUC was calculated as 0.857 (P < .001). Using the Hosmer-Lemeshow method, the X-value was 12.430, suggesting that the prediction model fitted well.The scoring system can quickly determine whether this is a CA, allowing for an earlier and correct diagnosis and treatment. Furthermore, the scoring system was convenient, economical, and affordable. Moreover, it is easy to popularized and promote.

Glucagon-like peptide-1 receptor regulates endoplasmic reticulum stress-induced apoptosis and the associated inflammatory response in chondrocytes and the progression of osteoarthritis in rat.

Treatments for osteoarthritis (OA) are designed to restore chondrocyte function and inhibit cell apoptosis. Previous studies have shown that activation of the glucagon-like peptide-1 receptor (GLP-1R) leads to anti-inflammatory and anti-apoptotic effects. However, the role of GLP-1R in the pathological process of OA is unclear. In present work, we aimed to demonstrate the potential effect of GLP-1R on chondrocytes and elucidate its underlying mechanisms. We found that activation of GLP-1R with liraglutide could protect chondrocytes against endoplasmic reticulum stress and apoptosis induced by interleukin (IL)-1ß or triglycerides (TGs). These effects were partially attenuated by GLP-1R small interfering RNA treatment. Moreover, inhibiting PI3K/Akt signaling abolished the protective effects of GLP-1R by increase the apoptosis activity and ER stress. Activating GLP-1R suppressed the nuclear factor kappa-B pathway, decreased the release of inflammatory mediators (IL-6, tumor necrosis factor α), and reduced matrix catabolism in TG-treated chondrocytes; these effects were abolished by GLP-1R knockdown. In the end, liraglutide attenuated rat cartilage degeneration in an OA model of knee joints in vivo. Our results indicate that GLP-1R is a therapeutic target for the treatment of OA, and that liraglutide could be a therapeutic candidate for this clinical application.

[Spatial variations of heavy metals in precipitation at Mount Taishan region].

Zn, Al, Mn, Fe, Pb, Cu, Ni, Cr, As, Cd in rain samples collected from two sites at Mount Taishan region were determined by ICP-MS, to evaluate the spatial variation characteristics of heavy metals in precipitation. Individual rain events were sampled for one whole year from Jan. to Dec. 2006. High concentrations of heavy metals were found at both sites, indicating serious heavy metal pollution. Zn was the most abundant element, accounting for 54% - 57% of the total metals concentrations. Its volume-weighted mean concentrations of precipitation at Mt-top and Mt-foot sites were 92.94 microg/L and 70.41 microg/L respectively. The following elements were Fe, Al and Mn and their concentrations were much higher than toxic heavy metals (As, Cd and Cd) except Pb (8.04 microg/L and 7.79 microg/L at two sites respectively). Comparison results between two sites suggested that heavy metal characteristics of precipitation at two sites were different, due to the influences of different ambient air conditions. Correlation analysis between two sites showed that Al, Mn, Fe, As, Cd, Pb influenced by air mass origin greatly, while Ni, Cu, Zn affected by other different factors.