Syntheses of 1beta-methylcarbapenems bearing 5-methyl-4-hydroxypyrrolidinone

A new series of 1beta-methylcarbapenems 1a-d bearing 5-methyl-4-mercaptopyrrolidinone rings has been prepared and evaluated for in vitro antibacterial activity and pharmacokinetic parameters. Most compounds showed excellent antibacterial activity and high stability to dehydropeptidase-1. We have synthesized optically active 5-methyl-4-hydroxypyrrolidinones from enantiomerically pure aziridine esters.     

New synthesis of 3′-deoxypurine nucleosides using samarium(III) iodide complex

Regio- and stereoselective iodinative cleavage of 2′,3′-anhydropurine nucleosides was achieved with samarium diiodide and ethyl bromoacetate to produce the corresponding 3′-iodopurine nucleosides, which were then converted to 3′-deoxypurine nucleosides including the natural product cordycepin.     

Lithium isotope separation by chemical exchange with polymer-bound azacrown compounds

The chromatographic separation of lithium isotopes was investigated by chemical exchange with the recently synthesized polymer-bound dibenzo pyridino diamide azacrown (DBPDA) and reduced dibenzo pyridino diamide azacrown (RDBPDA). Column chromatography was employed for the determination of the effect of solvents and ligand conformation on the separation coefficients. The maximum separation coefficients, , for the DBPDA and RDBPDA at 20.0±0.02°C with acetonitrile as eluent, were found to be 0.034±0.002 and 0.035±0.002, respectively. The isotope separation coefficient and adsorption capability of the lithium ion on the DBPDA and RDBPDA were only slightly dependent on ligand structure, but strongly dependent on the solvent. DBPDA and RDBPDA appeared to have almost the same value for the isotope separation coefficient of lithium.     

Force acting on a dielectric particle in a concentration gradient by ionic concentration polarization under an externally applied DC electric field

There is a concentration-polarization (CP) force acting on a particle submerged in an electrolyte solution with a concentration (conductivity) gradient under an externally applied DC electric field. This force originates from the two mechanisms: (i) gradient of electrohydrodynamic pressure around the particle developed by the Coulombic force acting on induced free charges by the concentration polarization, and (ii) dielectric force due to nonuniform electric field induced by the conductivity gradient. A perturbation analysis is performed for the electric field, the concentration field, and the hydrodynamic field, under the assumptions of creeping flow and small concentration gradient. The leading order component of this force acting on a dielectric spherical particle is obtained by integrating the Maxwell and the hydrodynamic stress tensors. The analytical results are validated by comparing the surface pressure and the skin friction to those of a numerical analysis. The CP force is proportional to square of the applied electric field, effective for electrically neutral particles, and always directs towards the region of higher ionic concentration. The magnitude of the CP force is compared to that of the electrophoretic and the conventional dielectrophoretic forces.     

catena‐Poly[[copper(II)‐μ‐2‐[bis­(2‐pyridylmeth­yl)amino]butyrato‐κ4N,N′,N′′,O:κO′] perchlorate]

The copper(II) ion in the syn–anti carboxyl­ate‐bridged one‐dimensional zigzag chain title complex, {[Cu(C₁₆H₁₈N₃O₂)]ClO₄}_n, exhibits a distorted trigonal–bipyramidal environment. Two N atoms and one carboxyl­ate O atom of the ligand form the basal plane, while the axial positions are filled by an N atom of the ligand and one O atom belonging to the carboxyl­ate group of an adjacent mol­ecule. The crystal packing is enhanced by C—H⋯O(perchlorate) hydrogen bonds.     

Xanthine Sensors Based on Anodic and Cathodic Detection of Enzymatically Generated Hydrogen Peroxide

A xanthine biosensor was fabricated by the covalent immobilization of xanthine oxidase (XO) onto a functionalized conducting polymer (Poly‐5, 2′: 5′, 2″‐terthiophine‐3‐carboxylic acid), poly‐TTCA through the formation of amide bond between carboxylic acid groups of poly‐TTCA and amine groups of enzyme. The immobilization of XO onto the conducting polymer (XO/poly‐TTCA) was characterized using cyclic voltammetry, quartz crystal microbalance (QCM), and X‐ray photoelectron spectroscopy (XPS) techniques. The direct electron transfer of the immobilized XO at poly‐TTCA was found to be quasireversible and the electron transfer rate constant was determined to be 0.73 s^?1. The biosensor efficiently detected xanthine through oxidation at +0.35 V and reduction at ?0.25 V (versus Ag/AgCl) of enzymatically generated hydrogen peroxide. Various experimental parameters, such as pH, temperature, and applied potential were optimized. The linear dynamic ranges of anodic and cathodic detections of xanthine were between 5.0×10^?6?1.0×10^?4 M and 5.0×10^?7 to 1.0×10^?4 M, respectively. The detection limits were determined to be of 1.0×10^?6 M and 9.0×10^?8 M with anodic and cathodic processes, respectively. The applicability of the biosensor was tested by detecting xanthine in blood serum and urine real samples.     

End-labeled free-solution electrophoresis of DNA

DNA is a free-draining polymer. This subtle but "unfortunate" property of highly charged polyelectrolytes makes it impossible to separate nucleic acids by free-flow electrophoresis. This is why one must typically use a sieving matrix, such as a gel or an entangled polymer solution, in order to obtain some electrophoretic size separation. An alternative approach consists of breaking the charge to friction balance of free-draining DNA molecules. This can be achieved by labeling the DNA with a large, uncharged molecule (essentially a hydrodynamic parachute, which we also call a drag-tag) prior to electrophoresis; the resulting methodology is called end-labeled free-solution electrophoresis (ELFSE). In this article, we review the development of ELFSE over the last decade. In particular, we examine the theoretical concepts used to predict the ultimate performance of ELFSE for single-stranded (ssDNA) sequencing, the experimental results showing that ELFSE can indeed overcome the free-draining issue raised above, and the technological advances that are needed to speed the development of competitive ELFSE-based sequencing and separation technologies. Finally, we also review the reverse process, called free-solution conjugate electrophoresis (FSCE), wherein uncharged polymers of different sizes can be analyzed using a short DNA molecule as an electrophoretic engine.     

Synthesis of nanosized TiO2/SiO2 particles using microwave processes and their photocatalytic activity on the decomposition of orange II

The nanosized titania and TiO₂/SiO₂ particles were prepared by the microwave-hydrothermal method. The effect of physical properties TTIP/TEOS ratio and calcination temperature has been investigated. The major phase of the pure TiO₂ particle is of the anatase structure, and a rutile peak was observed above 800°C. In TiO₂/SiO₂ particles, however, no significant rutile phase was observed, although the calcination temperature was 900°C. No peaks for the silica crystal phase were observed at either silica/titania ratio. The crystallite size of TiO₂/SiO₂ particles decreases as compared to pure TiO₂ at high calcination temperatures. The TiO₂/SiO₂ particles show higher activity on the photocatalytic decomposition of orange II as compared to pure TiO₂ particles.     

Pt‐Nanoparticle Incorporated Carbon Paste Electrode for the Determination of Cu(II) Ion by Anodic Stripping Voltammetry

Pt‐nanoparticles were synthesized and introduced into a carbon paste electrode (CPE), and the resulting modified electrode was applied to the anodic stripping voltammetry of copper(II) ions. The synthesized Pt‐nanoparticles were characterized by cyclic voltammetry, scanning electron microscopy and X‐ray photoelectron spectroscopy techniques to confirm the purity and the size of the prepared Pt‐nanoparticles (ca. 20 nm). This incorporated material seems to act as catalysts with preconcentration sites for copper(II) species that enhances the sensitivity of Cu(II) ions to Cu(I) species at a deposition potential of ?0.6 V in an aqueous solution. The experimental conditions, such as, the electrode composition, pH of the solution, pre‐concentration time, were optimized for the determination of Cu(II) ion using as‐prepared electrode. The sensitivity changes on the different binder materials and the presence of surfactants in the test solution. The interference effect of the coexisted metals were also investigated. In the presence of surfactants, especially TritonX‐100, the Cu(II) detection limit was lowered to 3.9×10^?9 M. However, the Pt‐nanoparticle modified CPE begins to degrade when the period of deposition exceeds to 10 min. Linear response for copper(II) was found in the concentration range between 3.9×10^?8 M and 1.6×10^?6 M, with an estimated detection limit of 1.6×10^?8 M (1.0 ppb) and relative standard deviation was 4.2% (n=5).     

Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced cancers. However, the tumor microenvironment (TME) functions as a formidable barrier that severely impairs the efficacy of ICIs. While the crosstalk between tumor vessels and immune cells determines the nature of anti-tumor immunity, it is skewed toward a destructive cycle in growing tumors. First, the disorganized tumor vessels hinder CD8⁺ T cell trafficking into the TME, disable effector functions, and even kill T cells. Moreover, VEGF, the key driver of angiogenesis, interferes with the maturation of dendritic cells, thereby suppressing T cell priming, and VEGF also induces TOX-mediated exhaustion of CD8⁺ T cells. Meanwhile, a variety of innate and adaptive immune cells contribute to the malformation of tumor vessels. Protumoral M2-like macrophages as well as T_H2 and Treg cells secrete pro-angiogenic factors that accelerate uncontrolled angiogenesis and promote vascular immaturity. While CD8⁺ T and CD4⁺ T_H1 cells suppress angiogenesis and induce vascular maturation by secreting IFN-γ, they are unable to infiltrate the TME due to malformed tumor vessels. These findings led to preclinical studies that demonstrated that simultaneous targeting of tumor vessels and immunity is a viable strategy to normalize aberrant vascular-immune crosstalk and potentiate cancer immunotherapy. Furthermore, this combination strategy has been evidently demonstrated through recent pivotal clinical trials, granted approval from FDA, and is now being used in patients with kidney, liver, lung, or uterine cancer. Overall, combining anti-angiogenic therapy and ICI is a valid therapeutic strategy that can enhance cancer immunity and will further expand the landscape of cancer treatment.Subject terms: Cancer immunotherapy, Cancer microenvironment, Tumour angiogenesis, Tumour immunology, Targeted therapies