Facile synthesis of ultrabright luminogens with specific lipid droplets targeting feature for in vivo two-photon fluorescence retina imaging

The application of fluorescent probes for in vivo retinal imaging is of great importance, which could provide direct and crucial imaging evidence for a better understanding of common eye diseases. Herein, a group of bright organic luminogens with typical electron-donating (D) and electron-accepting (A) structures (abbreviated as LDs-BDM, LDs-BTM, and LDs-BHM) was synthesized through a simple single-step reaction. They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70% (e.g., 83.7% for LDs-BTM). Their light-emission properties could be tuned by the modulation of π-conjugation effect with methoxy groups at different substituent positions. Their resulting fluorescent nanoparticles (NPs) were demonstrated as specific lipid droplets (LDs) targeting probes with high brightness, good biocompatibility, and satisfactory photostability. LDs-BTM NPs with a large two-photon absorption cross section (σ₂ = 249 GM) were further utilized as ultrabright two-photon fluorescence (2PF) nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration (0.5 µmol/L). Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated. This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique. These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.     

Black phosphorus nanosheets-based tumor microenvironment responsive multifunctional nanosystem for highly efficient photo-/sono-synergistic therapy of non-Hodgkin lymphoma

Finding improved therapeutic protocols against non-Hodgkin's lymphoma (NHL) remains an unmet clinical demand. Phototherapy is a promising alternative treatment for traditional clinical therapeutic methods, but the limited tissue penetration blocks the therapeutics. Inspired by the excellent physical and chemical properties of black phosphorus nanosheets (BPNSs), a fluorescence and thermal imaging guided photo-/sono-synergistic treatment platform BPNSs@PEG-SS-IR780/RGD is developed. This ingenious multifunctional theranostic platform not only exhibits outstanding photothermal conversion efficiency and highly efficient reactive oxygen species generation, but also has good biocompatibility, tumor-targeting and tumor microenvironment responsiveness. In addition, BPNSs@PEG-SS-IR780/RGD could actively target the tumor sites and generate excellent photothermal, photodynamic and sonodynamic therapeutic efficacy. Both in vitro and in vivo experiments indicate that BPNSs@PEG-SS-IR780/RGD can be a promising nanomaterial for NHL imaging and therapy. Taken together, this study not only expands the application field of black phosphorus materials, but also provides a possibility to design a new generation of NHL treatment regimens with clinical application potential.     

Bandgap-Engineered Germanene Nanosheets as an Efficient Photodynamic Agent for Cancer Therapy

Two-dimensional (2D) monoelemental materials (Xenes) show considerable potential in bioapplications owing to their unique 2D physicochemical features and the favored biosafety resulting from their monoelemental composition. However, the narrow band gaps of Xenes prevent their broad applications in biosensors, bioimaging and phototherapeutics. In this study, it is demonstrated that 2D germanene terminated with −H via surface chemical engineering, shows a much broadened direct band gap of 1.65 eV, which enables the material to be used as a novel inorganic photosensitizer for the photodynamic therapy of singlet oxygen. Through theoretical analysis and in vitro studies, H-germanene nanosheets demonstrate a substantially enlarged band gap and favorable biodegradability, demonstrating a substantial cancer treatment capacity. This study demonstrates the feasibility of constructing novel therapeutic photodynamic agents by surface covalent engineering for catalytic tumor therapy.     

Cottoquinazolines E and F from Neosartorya fischeri NRRL 181

Two new norfumiquinazolines, cottoquinazolines E and F ( 1 and 2 , resp.), together with pyripyropene A ( 3 ), were isolated from the fungus Neosartorya fischeri NRRL 181. The structures of the new isolates were established by spectroscopic methods, including UV, IR, HR‐ESI‐MS, and extensive 1D‐ and 2D‐NMR techniques. To the best of our knowledge, this is the first report on norfumiquinazolines and pyripyropenes produced by the genus Neosartorya.     

Local dynamics and viscoelastic properties of cell biological systems

How the cytoskeleton, a heterogeneous network of dynamic filamentous proteins, provides the cell with structural support is not well understood. Particle-tracking methods, which probe local mechanical properties, are well suited to test existing hypotheses derived from in vitro models of reconstituted cytoskeleton networks. This paper reviews recent applications of single- and multiple-particle tracking microrheology, with an emphasis on the semiflexible polymer F-actin and the flexible polymer keratin, two ubiquitous proteins of the cytoskeleton. Extensive knowledge of the properties of these polymers allows a rigorous comparison between theory and experiments to a level rarely matched by synthetic polymers.     

MR virtual endoscopy of the pancreaticobiliary tract

Purpose: To evaluate the feasibility of surface-rendered magnetic resonance virtual endoscopy (MRVE) of magnetic resonance cholangiopancreatography (MRCP) data sets. We retrospectively reviewed MR cholangiopancreatography data sets of 120 patients with biliary stone (n = 40), inflammatory ampullary stenosis (n = 12), pancreatic tumor (n = 8), cholangiocarcinoma (n = 7), stenosis of surgical bilio-enteric anastomosis (n = 4), extrinsic localized common bile duct stenosis (n = 2), ampullary carcinoma (n = 2), pancreatic duct stone (n = 1), tumor of the gallbladder (n = 1), and normal pancreaticobiliary tree (n = 43). MRVE views were generated with Navigator software. Segmentation of the acquired data sets was performed with a thresholding technique. Navigation sequences were simulated through the entire biliary tract. MRVE was obtained in 27 (63%) of the 43 normal patients. Endoscopic views were generated in all 77 patients with partial or complete obstruction of the pancreaticobiliary tree. Among these, three groups of patterns were identified: 36 (47%) endoluminal masses (polyp-like masses), 17 (22%) luminal stenoses, 24 (31%) luminal occlusion. In 29 cases, hole artifacts through the internal wall were observed and interpreted as mistakes of segmentation. MRVE proved to show the internal anatomy of the biliary tract and endoluminal changes due to pathological condition. Further investigations are needed to test the usefulness and the potentialities of this technique.     

Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library

Staphylococcus aureus is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-N-acetylehyl-l-alanine and d-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by S. aureus. Because S. aureus is resistant to most existing antibiotics, it is necessary to develop new inhibitors. In this study, Schrodinger 11.5 Prime homology modeling was selected to prepare the protein model of MurD enzyme, and its structure was optimized. We used a virtual screening program and similarity screening to screen 47163 compounds from three marine natural product libraries to explore new inhibitors of S. aureus. ADME provides analysis of the physicochemical properties of the best performing compounds during the screening process. To determine the stability of the docking effect, a 100 ns molecular dynamics was performed to verify how tightly the compound was bound to the protein. By docking analysis and molecular dynamics analysis, both 46604 and 46608 have strong interaction with the docking pocket, have good pharmacological properties, and maintain stable conformation with the target protein, so they have a chance to become drugs for S. aureus. Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for S. aureus.     

The nature of the anchimeric assistance by the acetoxy group in solvolysis of (Me3Si)2C(SiMe2)OCOMe) (SiMe2Cl)

Solvolysis of (Me₃Si)₂C(SiMe₂OCOMe)(SiMe₂Cl) in 3/2 v/v MeOH/dioxane at 35°C is ca. 11–14 times as fast as that of (Me₃Si)₂C(SiMe₂OMe)(SiMe₂Cl), which suggests that the anchimeric assistance by the acetoxy group is provided through the carbonyl oxygen.     

兼具抗癌和药物递送作用的硒掺杂羟基磷灰石微球

利用碳酸钙作为处理模板,通过共沉淀联合水热法,制备了硒元素掺杂羟基磷灰石微球(HASe),期望硒掺杂能提高HA对溶菌酶的加载,并增强HASe微球的杀菌活性。所合成的HASe微球经SEM、TEM、DLS、XRD、FTIR和TGA测试对其理化性能进行了表征。并且利用姜黄素作为模式药物,评估了它们的药物加载及控释效能。结果发现,所合成的HASe产物为直径约1.0μm的球体,球壁粘附有许多羟基磷灰石纳米棒(长约150 nm﹑宽约20 nm)。该HASe微球对姜黄素具有高的药物加载和缓慢稳定的控释效应。其药物加载量为(88.72±0.01)mg·g~(-1),在0~159 h内仅有不到1.5 mg的姜黄素被释放,且无爆释现象。此外,还通过血液分析和细胞实验评估了HASe微球的毒性行为。与无硒HA微球相比,HASe微球的血液毒性低,对细胞损伤少,然而对骨肉瘤细胞生长却具有强的抑制作用。     

Determination of Cd,Hg, Pb and Se in sediments slurries by isotopic dilution calibration ICP-MS after chemical vapor generation using an on-line system or retention in an electrothermal vaporizer treated with iridium

A method for the determination of Cd, Hg, Pb and Se in sediments reference materials by slurry sampling chemical vapor generation (CVG) using isotopic dilution (ID) calibration and detection by inductively coupled plasma mass spectrometry (ICP-MS) is proposed. Two different systems were used for the investigation: an on-line flow injection system (FI-CVG-ICP-MS) and an off-line system with in situ trapping electrothermal vaporization (CVG-ETV-ICP-MS). About 100 mg of the reference material, ground to a particle size ≤50 μm, was mixed with acid solutions (aqua regia, HF and HCl) in an ultrasonic bath. The enriched isotopes ¹¹¹Cd, ¹⁹⁸Hg, ²⁰⁶Pb and ⁷⁷Se were then added to the slurry in an adequate amount in order to produce an altered isotopic ratio close to 1. For the on-line system, a standing time for the slurry of 12 h before measurement was required, while for the batch system, no standing time is needed to obtain accurate results. The conditions for the formation of the analyte vapor were optimized for the evaluated systems. The following altered isotope ratios were measured: ¹¹¹Cd/¹¹⁴Cd, ¹⁹⁸Hg/¹⁹⁹Hg, ²⁰⁶Pb/²⁰⁸Pb e ⁷⁷Se/⁸²Se. The obtained detection limits in the on-line system, in μg g⁻¹, were: Cd: 0.15; Hg: 0.09; Pb: 6.0 and Se: 0.03. Similar detection limits were obtained with the system that uses the ETV: 0.21 for Hg, 6.0 for Pb and 0.06 μg g⁻¹ for Se. No signal for Cd was obtained in this system. One estuarine, two marine and two river certified sediments were analyzed to check the accuracy. The obtained values by both systems were generally in agreement with the certified concentrations, according to the t-test for a confidence level of 95%, demonstrating that isotope equilibration was attained in the slurries submitted to a chemical vapor generation procedure and detection by ICP-MS. The relative standard deviations were lower than 10%, adequate for slurry analysis. The almost quantitative analytes extractions to the aqueous phase of the slurry must favor equilibration of the added enriched isotope with the isotope in the sample, allowing the use of isotopic dilution calibration for slurry analysis.