Optimal optical Ferris wheel solitons in a nonlocal Rydberg medium.

We propose a scheme for the creation of stable optical Ferris wheel (OFW) solitons in a nonlocal Rydberg electromagnetically induced transparency (EIT) medium. Depending on a careful optimization of both the atomic density and the one-photon detuning, we obtain an appropriate nonlocal potential provided by the strong interatomic interaction in Rydberg states that can perfectly compensate for the diffraction of the probe OFW field. Numerical results show that the fidelity remains larger than 0.96, while the propagation distance has exceeded 160 diffraction lengths. Higher-order OFW solitons with arbitrary winding numbers are also discussed. Our study provides a straightforward route to generate spatial optical solitons in the nonlocal response region of cold Rydberg gases.

SAF-248, a novel PI3Kδ-selective inhibitor, potently suppresses the growth of diffuse large B-cell lymphoma.

PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use. In this study, we described a novel PI3Kδ inhibitor SAF-248, which exhibited high selectivity for PI3Kδ (IC50 = 30.6 nM) over other PI3K isoforms at both molecular and cellular levels, while sparing most of the other human protein kinases in the kinome profiling. SAF-248 exhibited superior antiproliferative activity against 27 human lymphoma and leukemia cell lines compared with the approved PI3Kδ inhibitor idelalisib. In particular, SAF-248 potently inhibited the proliferation of a panel of seven DLBCL cell lines (with GI50 values < 1 µM in 5 DLBCL cell lines). We demonstrated that SAF-248 concentration-dependently blocked PI3K signaling followed by inducing G1 phase arrest and apoptosis in DLBCL KARPAS-422, Pfeiffer and TMD8 cells. Its activity against the DLBCL cells was negatively correlated to the protein level of PI3Kα. Oral administration of SAF-248 dose-dependently inhibited the growth of xenografts derived from Pfeiffer and TMD8 cells. Activation of mTORC1, MYC and JAK/STAT signaling was observed upon prolonged treatment and co-targeting these pathways would potentiate the activity of SAF-248. Taken together, SAF-248 is a promising selective PI3Kδ inhibitor for the treatment of DLBCL and rational drug combination would further improve its efficacy.

SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.

The ROS1 fusion kinase is an attractive antitumor target. Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase. Novel ROS1is effective against mutations conferring secondary crizotinib resistance, especially G2032R, are urgently needed. In the present study, we evaluated the antitumor efficacy of SAF-189s, the new-generation ROS1/ALK inhibitor, against ROS1 fusion wild-type and crizotinib-resistant mutants. We showed that SAF-189s potently inhibited ROS1 kinase and its known acquired clinically resistant mutants, including the highly resistant G2032R mutant. SAF-189s displayed subnanomolar to nanomolar IC50 values against ROS1 wild-type and mutant kinase activity and a selectivity vs. other 288 protein kinases tested. SAF-189s blocked cellular ROS1 signaling, and in turn potently inhibited the cell proliferation in HCC78 cells and BaF3 cells expressing ROS1 fusion wild-type and resistance mutants. In nude mice bearing BaF3/CD74-ROS1 or BaF3/CD74-ROS1G2032R xenografts, oral administration of SAF-189s dose dependently suppressed the growth of both ROS1 wild-type- and G2032R mutant-driven tumors. In a patient-derived xenograft model of SDC4-ROS1 fusion NSCLC, oral administration of SAF-189s (20 mg/kg every day) induced tumor regression and exhibited notable prolonged and durable efficacy. In addition, SAF-189s was more potent than crizotinib and comparable to lorlatinib, the most advanced ROS1i known against the ROS1G2032R. Collectively, these results suggest the promising potential of SAF-189s for the treatment of patients with the ROS1 fusion G2032R mutation who relapse on crizotinib. It is now recruiting both crizotinib-relapsed and naive ROS1-positive NSCLC patients in a multicenter phase II trial (ClinicalTrials.gov Identifier: NCT04237805).

Robust Majorana edge modes with low frequency multiple time periodic driving.

Floquet Majorana edge modes capture the topological features of periodically driven p-wave superconductors. We present a Kitaev chain with multiple time periodic driving terms. Our results demonstrate how multiple driving will affect Floquet bands in frequency space, leading to more robust Floquet Majorana edge modes against driving frequency ω in comparison with the single driving scenario. Meanwhile, we have proposed how to predict Majorana edge modes via the Zak phase of Floquet bands. Besides, in contrast to the cases with single driving term, where the constant phase can be gauged out by properly choosing the initial time, we have shown the relative phase between multiple driving can not be gauged out and will play a dominant role in deciding topological phase transitions. For the sake of completeness, we also investigate the high frequency limit. Analytical results on effective Hamiltonian can be obtained via Magnus expansion and relative phase induced topological transitions can be shown explicitly.

Participatory Teaching Class for MBBS Students / 昆明医科大学学报

Objective To determine the effect of participatory teaching method in the Clinic teaching of internal medicine for MBBS students. Methods The 60 MBBS students were divided into group A and B, 30 students in each group. Participatory teaching was done in group A, and traditional teaching was carried out in group B,and the effects of the two types of teaching methods were compared. Results In the clinic teaching of internal medicine, the effects in improving students' clinical thinking and practical ability, creativeness, initiative and efficiency were better in the participatory teaching method than in traditional teaching method (P＜0.05) . Conclusion The effects of participatory teaching in the clinic teaching of internal medicine for MBBS students was better than the traditional teaching.

The Value of Using sPESI Score Combined with hs-TnT in the Evaluation of Short-term Prognosis in Hemodynamically Stable Pulmonary Embolism / 昆明医科大学学报

Objective To explore the value of using sPESI score and hs-TnT in the evaluation of short-term prognosis in hemodynamically stable pulmonary embolism. Methods We collected 99 patients with hemodynamically stable PE from our department. According to the sPESI score and hs-TnT, patients were divided into high risk group (sPESI score≥1) and low risk group (sPESI score=0), positive group (hs-TnT≥0.014 ng/mL) and negative group (hs-TnT＜0.014 ng/mL) . Then all patients were treated and followed up for 30 days. The sensitivity, specificity, positive predictive value and negative predictive value of adverse events of prognosis were calculated, and ROC curve was drawn to analyze the values in different grouping methods for the prognostic evaluation.Results Thirteen adverse events occurred in all patients. The single test showed that sensitivity, specificity, positive predictive value, and negative predictive value of hs-TnT for predicting adverse events were respectively 84.6%,55.2%,22%,and 96%. When sPESI was used alone, sensitivity, specificity, positive predictive value and negative predictive value were 92.3%, 48.8%, 21.1% , and 97.7% . Results of combined testing showed 100% sensitivity, 29% specificity, 17.6% positive predictive value, and 100% negative predictive value. The ROC curve area of the sPESI, hs-TnT, sPESI and hs-TnT are 0.832 (95% CI, 0.705-0.958), 0.825 (95%CI, 0.694-0.957),0.872 (95%CI, 0.773-0.971) . Conclusions PESI and hs-TnT have clinical value in evaluating the short-term prognosis of hemodynamically stable pulmonary embolism. sPESI combined with hs-TnT has higher significance, especially in patients with low-risk PE.

Effects of interleukin 27 and its receptor on TGFβinduced murine pulmonary fibroblast proliferation and transformation / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of interleukin-27 (IL-27) and its receptor (WSX-1) on the proliferation, transformation and collagen synthesis of the mouse lung fibroblasts.</p><p><b>METHODS</b>Cultured mouse lung fibroblasts were treated with TGF-β1, recombinant murine IL-27, a IL-27 receptor (IL-27R) overexpression vector IL-27R/pCDNA3.1, IL-27 and IL-27R, or all the 3 combined. MTT assay was used to assess the proliferation of the cells, and RT-PCR and Western blotting were employed to examine the mRNA and protein expressions of a-smooth muscle actin (α-SMA) and types I and III collagen; immunofluorescence assay was used to test the expression and location of α-SMA.</p><p><b>RESULTS</b>TGF-β1 promoted the cell proliferation and obviously enhanced α-SMA expression and types I and III collagen synthesis in the fibroblasts. Both IL-27 and IL-27R significantly inhibited the proliferation of the pulmonary fibroblasts and obviously decreased their α-SMA expression and types I and III collagen synthesis, but when combined,they produced no obvious inhibitory effect on TGF-1-induced proliferation and transformation of pulmonary fibroblasts.</p><p><b>CONCLUSION</b>Both IL-27 and IL-27R alone can suppress the proliferation, transformation, and collagen synthesis of mouse pulmonary fibroblasts, but their combined treatment produces no such inhibitory effect because of the neutralization of exogenous IL-27 by IL-27R to result in the failure of activating the cell signaling pathways.</p>

tert-Butyl 6-amino-5-cyano-2-(2-meth-oxy-eth-yl)nicotinate.

The title compound, C(14)H(19)N(3)O(3), was synthesized by the reaction of 3-meth-oxy-propionitrile, tert-butyl bromo-acetate and eth-oxy-methyl-enemalononitrile. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into chains propagating along the b axis.

Therapeutic effect of intravenous bone marrow-derived mesenchymal stem cell transplantation on early-stage LPS-induced acute lung injury in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of intravenous bone marrow-derived mesenchymal stem cell (MSC) transplantation for early intervention of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.</p><p><b>METHODS</b>Thirty-six mice were randomized into control group, PBS-treated ALI group, and MSC-treated ALI group. In the latter two groups, mouse models of ALI were established by intranasal instillation of LPS, and 1 h later, the 4th passage of MSCs isolated from the bone marrow of mice or PBS were administered via the tail vein. The histological findings, lung wet/dry (W/D) weight ratio, neutrophil count and protein and cytokine contents in the bronchoalveolar lavage fluid (BALF), and myeloperoxidase (MPO) level in the lung tissue were analyzed at 24 h after MSC administration. Engraftment of MSCs in the recipient lung was determined by fluorescent PKH26 staining and flow cytometry.</p><p><b>RESULTS</b>Compared with the control group, PBS-treated ALI group showed significantly higher protein levels, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and neutrophil count in the BALF and MPO content in the lung tissue, with also severe damage of lung histology. MSCs administration significantly reduced the lung W/D weight ratio, the levels of protein, TNF-α, IL-6 and neutrophil count in the BALF and MPO content in the lung tissue, and obviously lessened the lung injury 24 h after the transplantation. MSC administration also significantly increased the level of IL-10 in the BALF.</p><p><b>CONCLUSION</b>Intravenous MSC transplantation can effectively improve the lung histology, attenuate the inflammatory response, reduce pulmonary edema in the early stage of LPS-induced ALI in mice, and such effects are independent of MSC engraftment in the lungs.</p>