Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family

The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC50 of 0.75μM against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition

The symmetric representation of the rigid body equations and their discretization

This paper analyses continuous and discrete versions of the generalized rigid body equations and the role of these equations in numerical analysis, optimal control and integrable Hamiltonian systems. In particular, we present a symmetric representation of the rigid body equations on the Cartesian product SO(n)×SO(n) and study its associated symplectic structure. We describe the relationship of these ideas with the Moser-Veselov theory of discrete integrable systems and with the theory of variational symplectic integrators. Preliminary work on the ideas discussed in this paper may be found in Bloch et al (Bloch A M, Crouch P, Marsden J E and Ratiu T S 1998 Proc. IEEE Conf. on Decision and Control 37 2249-54).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49076/2/no2416.pd

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

The Influence of Phthalocyanine Aggregation in Complexes with CdSe/ZnS Quantum Dots on the Photophysical Properties of the Complexes

The formation of nonluminescent aggregates of aluminium sulfonated phthalocyanine in complexes with CdSe/ZnS quantum dots causes a decrease of the intracomplex energy transfer efficiency with increasing phthalocyanine concentration. This was confirmed by steady-state absorption and photoluminescent spectroscopy. A corresponding physical model was developed that describes well the experimental data. The results can be used at designing of QD/molecule systems with the desired spatial arrangement for photodynamic therapy

Reversible Photoluminescence Quenchin of CdSe/ZnS Quantum Dots Embedded in Porous Glass by Ammonia Vapor

The photoluminescence response of semiconductor CdSe/ZnS quantum dots embedded in a borosilicate porous glass matrix to exposure to ammonia vapor is investigated. Formation of surface complexes on the quantum dots results in quenching of the photoluminescence and a shortening of the luminescence decay time. The process is reversible, desorption of ammonia molecules from the quantum dot surface causes the photoluminescence to recover. The sensitivity of the quantum dot luminescence intensity and decay time to the interaction time and the reversibility of the photoluminescence changes makes the CdSe/ZnS quantum dot in porous glass system a candidate for use as an optical sensor of ammonia. Keywords: Quantum dots, ammonia, porous glass, photoluminescenc

Low-Temperature In-Induced Holes Formation in Native-SiOx/Si(111) Substrates for Self-Catalyzed MBE Growth of GaAs Nanowires

The reduction of substrate temperature is important in view of the integration of III–V materials with a Si platform. Here, we show the way to significantly decrease substrate temperature by introducing a procedure to create nanoscale holes in the native-SiOx layer on Si(111) substrate via In-induced drilling. Using the fabricated template, we successfully grew self-catalyzed GaAs nanowires by molecular-beam epitaxy. Energy-dispersive X-ray analysis reveals no indium atoms inside the nanowires. This unambiguously manifests that the procedure proposed can be used for the growth of ultra-pure GaAs nanowires