Synthesis of difluoromethylated spiropyrazolones via [3 + 2] cycloaddition of difluoroacetohydrazonoyl bromides with alkylidene pyrazolones.

An effective [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with alkylidene pyrazolones was disclosed. This method provides an efficient approach for accessing a variety of highly functionalized fluoroalkyl spiropyrazolones in good yields. This protocol also features some advantages such as easily available and stable substrates, simple operation procedures, and atom and step economy. The formation of (cis)- and (trans)-products was discussed.

Visible-Light-Induced Four-Component Ritter-Type Reaction: Access to ß-Trifluoromethyl Imides.

A visible-light-induced four-component Ritter-type reaction was developed for the synthesis of ß-trifluoromethyl imides from CF3Br, alkenes, carboxylic acids, and nitriles. This protocol features mild reaction conditions, a broad substrate scope, and excellent functional group compatibility. Furthermore, this method has been proven to be suitable for the late-stage diversification of drug molecules. A mechanism involving a Ritter-type reaction and Mumm rearrangement was proposed on the basis of the control experiments.

Development of na HPLC-MS/MS method for the determination of ginsenosides Rg1 and Rb1 from 'Shenmai' Injection in beagle dogs after single and multiple doses and application in pharmacokinetics.

Shenmai Injection (SMI), which tonifies Qi and prevents exhaustion, nourishes Yin and generates body fluid, is usually used in the treatment of shock with deficiency of Qi and Yin, coronary artery disease, viral myocarditis, granulocytopenia and chronic pulmonary heart disease clinically. Ginsenosides Rg1 and Rb1 are the main active ingredients of SMI. In this study, high-performance liquid chromatography tandem mass spectrometry methods for quantification of Rb1 and Rg1 in beagle dogs were developed and validated according to international regulatory guidelines. The methods were applied to measure the pharmacokinetics parameters of the two ginsenoside after intravenous administration. The linear ranges of the analytes were 3.9-1,000 ng/ml for Rg1 and Rb1. After injection of single and multiple doses of SMI (1 ml/kg), the plasma concentration-time profiles of Rg1 and Rb1 met the characteristics of one-compartment and typical two-compartment intravenous injection.

Visible Light Promotes Cascade Trifluoromethylation/Cyclization, Leading to Trifluoromethylated Polycyclic Quinazolinones, Benzimidazoles and Indoles.

Efficient visible-light-induced radical cascade trifluoromethylation/cyclization of inactivated alkenes with CF3Br, which is a nonhygroscopic, noncorrosive, cheap and industrially abundant chemical, was developed in this work, producing trifluoromethyl polycyclic quinazolinones, benzimidazoles and indoles under mild reaction conditions. The method features wide functional group compatibility and a broad substrate scope, offering a facile strategy to pharmaceutically produce valuable CF3-containing polycyclic aza-heterocycles.

Case report: Right coronary artery rupture-A rare complication of cardiopulmonary resuscitation.

An 8-month-old female experienced a life-threatening right coronary artery rupture resulting from cardiopulmonary resuscitation (CPR) 1 week after corrective surgery for Tetralogy of Fallot (TOF). Emergency exploratory thoracotomy was performed due to uncorrectable hemorrhagic shock. During exploration, active bleeding was detected in the anterior branch of the right ventricular coronary artery. After the repair, the patient's condition improved. Coronary artery rupture is an extremely rare complication of CPR. Here, we present a case that provides new reflections and warnings to clinicians.

Super-resolution stimulated Raman scattering microscopy with the phase-shifted spatial frequency modulation.

We present a unique super-resolution stimulated Raman scattering (SRS) microscopy technique based on phase-shifted spatial frequency modulation (PSFM) under wide-field illumination, permitting super-resolution chemical imaging with single-pixel detection. Through projecting a series of the pump and Stokes laser patterns with varying spatial frequencies onto the sample and combining with the proposed π-phase shift, the higher spatial information can be rapidly retrieved by implementing the fast inverse Fourier-transform on the spatial frequency-encoded SRS data. We have derived the theory of the PSFM-SRS technique for super-resolution imaging. Our further modeling results confirm that PSFM-SRS microscopy provides a ∼2.2-fold improvement in spatial resolution but with a much-reduced laser excitation power density required as compared with conventional point-scan SRS microscopy, suggesting its potential for label-free super-resolution chemical imaging in cells and tissue.

Photoinduced Trifluoromethylation with CF3Br as a Trifluoromethyl Source: Synthesis of α-CF3-Substituted Ketones.

An efficient and novel photoinduced trifluoromethylation employing CF3Br as a trifluoromethyl source is described. With commercially accessible fac-Ir(III)(ppy)3 as the catalyst, radical trifluoromethylation between O-silyl enol ether and CF3Br occurs successfully. This method provides various α-CF3-substituted ketones with a broad substrate scope in good yields under mild reaction conditions.

Synthesis of 3-Trifluoromethyl-1,2,4-triazolines and 1,2,4-Triazoles via Tandem Addition/Cyclization of Trifluoromethyl N-Acylhydrazones with Cyanamide.

A tandem addition/cyclization reaction between trifluoromethyl N-acylhydrazones and cyanamide is described, which provides a novel and efficient process for the synthesis of polysubstituted 3-trifluoromethyl-1,2,4-triazolines and their derivatives. The method has the advantages of mild reaction conditions, a broad substrate scope, good product yields, and atom economy.

Channeled imaging spectropolarimeter reconstruction by neural networks.

Snapshot channeled imaging spectropolarimetry (SCISP), which can achieve spectral and polarization imaging without scanning (a single exposure), is a promising optical technique. As Fourier transform is used to reconstruct information, SCISP has its inherent limitations such as channel crosstalk, resolution and accuracy drop, the complex phase calibration, et al. To overcome these drawbacks, a nonlinear technique based on neural networks (NNs) is introduced to replace the role of Fourier reconstruction. Herein, abundant spectral and polarization datasets were built through specially designed generators. The established NNs can effectively learn the forward conversion procedure through minimizing a loss function, subsequently enabling a stable output containing spectral, polarization, and spatial information. The utility and reliability of the proposed technique is confirmed by experiments, which are proved to maintain high spectral and polarization accuracy.

Ray tracing method for removing sidelobe laser interference in AOTF-based hyperspectral imaging.

The sidelobe phenomenon of acousto-optic tunable filter (AOTF)-based hyperspectral imaging is the result of the phase mismatching condition, which will reduce the quality of hyperspectral imaging data. This phenomenon can be observed in two specified scenes, namely, high brightness panchromatic target imaging and high brightness monochromatic target imaging. In this paper, the acousto-optic interaction in these two scenes is discussed using the phase matching condition. As a follow-up work of the previous related research, this paper studies laser interference in AOTF imaging, which is a typical example of the second case. A method to remove laser sidelobes in AOTF-based hyperspectral imaging is proposed, which combines a series of procedures including laser point extraction, reverse imaging before AOTF, ray tracing in AOTF, forward imaging process after AOTF, and laser elimination. Experimental results have verified the effectiveness of the proposed method.

Snapshot spectral polarimetric light field imaging using a single detector.

In this Letter, we investigate a snapshot spectral-polarimetric-volumetric imaging (SSPVI) system using a single detector. Through compressed acquisition and reconstruction, SSPVI can achieve spectral imaging (x,y,λ), polarization imaging (x,y,ψ,χ), and light field imaging (x,y,θ,φ) simultaneously. The newly discovered performance is showcased by attaining the spectral-polarimetric-volumetric video and different laboratory accuracy experiments. These never-seen-before capacities of the camera open new prospects for many applications, such as biological analysis, object recognition, and remote sensing.

Plenoptic Face Presentation Attack Detection.

The vulnerability of current face recognition systems to presentation attacks significantly limits their application in biometrics. Herein, we present a passive presentation attack detection method based on a complete plenoptic imaging system which can derive the complete plenoptic function of light rays using a single detector. Moreover, we constructed a multi-dimensional face database with 50 subjects and seven different types of presentation attacks. We experimentally demonstrated that our approach outperforms the state-of-the-art methods on all types of presentation attacks.

Correction to: The 3'UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1.

After publication of this article [1], it came to our attention that there was an error in Fig. 4b and 4c. In Fig.4b, the migration images of vector groups were incorrect based on this error, the authors re-constructed the migration experiments of Fig. 4b, and the consistent results were obtained. In Fig. 4c, the tube formation image of the Z2P-UTR-siRNA&Z1-UTR group (MCF-7) of Fig. 7d was accidentally misused in control group (MCF-7) and vector group (MCF-7) of Fig. 4c. The corrected Fig. 4 is provided below. This error did not impact the conclusions of the article. The authors apologize for this error.

Recent Progress in Time-Resolved Biosensing and Bioimaging Based on Lanthanide-Doped Nanoparticles.

Luminescent nanomaterials have attracted great attention in luminescence-based bioanalysis due to their abundant optical and tunable surface physicochemical properties. However, luminescent nanomaterials often suffer from serious autofluorescence and light scattering interference when applied to complex biological samples. Time-resolved luminescence methodology can efficiently eliminate autofluorescence and light scattering interference by collecting the luminescence signal of a long-lived probe after the background signals decays completely. Lanthanides have a unique [Xe]4fN electronic configuration and ladder-like energy states, which endow lanthanide-doped nanoparticles with many desirable optical properties, such as long luminescence lifetimes, large Stokes/anti-Stokes shifts, and sharp emission bands. Due to their long luminescence lifetimes, lanthanide-doped nanoparticles are widely used for high-sensitive biosensing and high-contrast bioimaging via time-resolved luminescence methodology. In this review, recent progress in the development of lanthanide-doped nanoparticles and their application in time-resolved biosensing and bioimaging are summarized. At the end of this review, the current challenges and perspectives of lanthanide-doped nanoparticles for time-resolved bioapplications are discussed.

Solution-Processable Two-Dimensional In2 Se3 Nanosheets as Efficient Photothermal Agents for Elimination of Bacteria.

Two-dimensional (2D) nanoflakes represent an appealing class of materials for optoelectronics applications due to their unique layered structures and excellent electronic properties. However, the lack of easy-to-manipulate and effective methods for large-scale production of these 2D materials limits their potential for applications. Also, few efforts have been made to explore their applications in biological fields. This work reports the preparation of large quantities of 2D In2 Se3 nanosheets through a solvent exfoliation technique. Transmission electron microscopy and atomic force microscopy results show that the In2 Se3 nanosheets are obtained with lateral sizes of tens of nanometers to hundreds of nanometers and thickness of 2-17 layers. Raman features coupled with the X-ray diffractometry results unequivocally confirm the as-prepared In2 Se3 nanosheets to be α phase. Moreover, these α-In2 Se3 nanosheets exhibit an excellent near-infrared (NIR) photothermal performance under an 808 nm laser irradiation. NIR photo-excitation of the α-In2 Se3 nanosheets in the presence of bacteria leads to a significant antibacterial effect, suggesting that these nanosheets have great potential to be photothermal antibacterial agents. Our work on α-In2 Se3 nanosheets presents an available method for exfoliating 2D layered materials, and highlights the potential application in chemical and biological fields of α-In2 Se3 nanosheets.

Redefining Molecular Amphipathicity in Reversing the "Coffee-Ring Effect": Implications for Single Base Mutation Detection.

The "coffee ring effect" is a natural phenomenon wherein sessile drops leave ring-shaped structures on the solid surfaces upon drying. It drives a nonuniform deposition of suspended compounds on the substrates, which adversely affects many processes, including surface-assisted biosensing and molecular self-assembly. In this study, we describe how the coffee ring effect can be eliminated by controlling the amphipathicity of the suspended compounds, for example, DNA modified with hydrophobic dye. Specifically, nuclease digestion of the hydrophilic DNA end converts the dye-labeled molecule into an amphipathic molecule (one with comparably weighted hydrophobic and hydrophilic ends) and reverses the coffee ring effect and results in a uniform disk-shaped feature deposition of the dye. The amphipathic product decreases the surface tension of the sessile drops and induces the Marangoni flow, which drives the uniform distribution of the amphipathic dye-labeled product in the drops. As a proof of concept, this strategy was used in a novel enzymatic amplification method for biosensing to eliminate the coffee ring effect on a nitrocellulose membrane and increase assay reliability and sensitivity. Importantly, the reported strategy for eliminating the coffee ring effect can be extended to other sessile drop systems for potentially improving assay reliability and sensitivity.

Simultaneous Visualization and Quantitation of Multiple Steroid Hormones Based on Signal-Amplified Biosensing with Duplex Molecular Recognition.

The simultaneous quantitation of multiple steroid hormones in real time is of great importance in medical diagnosis. In this study, a portable hormone biosensor based on duplex molecular recognition coupled with a signal-amplified substrate was successfully developed for the simultaneous visualization and quantitation of multiple steroid hormones. Aptamer-functionalized upconversion nanoparticles (UCNPs) with different emission peaks are immobilized on the photonic crystal (PC) substrate as the nanoprobes, leading to the specific and simultaneous assay of multiple steroid hormones. Coupled with the luminescence-enhanced effect of the PC substrate, nanomolar quantification limits of multiple hormones are achieved. This well-designed biosensor is also promising in the quantification of multiple hormones in serum samples. The amplified luminescence signals can be visualized with the naked eye and captured by an unmodified phone camera. This hormone quantitation biosensor exhibits the advantages of multi-detection, visualization, high sensitivity, and selectivity for potential applications in clinical disease diagnosis.

Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection.

The gastric bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans and plays a critical role in the development of gastritis, peptic ulceration and gastric adenocarcinoma. Consequently, the eradication of H. pylori might contribute to the prevention of H. pylori-associated gastric diseases. In this study, a multi-epitope vaccine CTB-UE (CUE) was displayed on the surface of non-genetically modified Lactococcus lactis particles (GEM) to enhance immunogenicity. This particulate vaccine CUE-GEM induced serum and mucosal specific antibody responses against native H. pylori urease and provided potent protection to eliminate H. pylori colonization and relieve gastritis in an H. pylori-infected BALB/c mouse model. The immuno-protective mechanisms are highly associated with CD4(+) Th cell-mediated and humoral immunity, especially local immunity. There might be two main aspects of this association. One aspect is related to the suppression of urease activity by promotion of the production of specific mucosal neutralizing antibody. The other aspect is correlated with alleviating gastritis by regulating the gastric pro-inflammatory cytokine profile, especially IFN-γ and IL-17. These results demonstrated that conjugating antigen vaccines with GEM particles could lead to promising oral therapeutic vaccine formulations against H. pylori infection.

A novel chimeric flagellum fused with the multi-epitope vaccine CTB-UE prevents Helicobacter pylori-induced gastric cancer in a BALB/c mouse model.

Helicobacter pylori (H. pylori) infection causes peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. The eradication of H. pylori might be an effective means of preventing gastric cancer. A dual-antigen epitope and dual-adjuvant vaccine called CTB-UE-CF (CCF) was constructed by combining a multi-epitope vaccine CTB-UE with a novel chimeric flagellum (CF) to simultaneously activate Toll-like receptor (TLR) 5-agonist activity and preserve the immunogenicity of H. pylori flagellum FlaA. The evaluation of efficacy to reduce H. pylori colonization was performed using BALB/c mice by oral immunization with a triple dose of this vaccine strain. Two weeks after the last immunization, mice were sacrificed to determine specific antibody levels and proinflammatory cytokine production. To determine the presence of H. pylori, we detected the number of H. pylori by real-time quantitative PCR (qPCR) and measured the urease activity in the gastric tissue. The results showed that the immunogenicity and mucosal immune responses of CCF performed significantly better than those of CTB-UE. This dual-antigen epitope and dual-adjuvant system might greatly contribute to the development of a safe and efficient therapeutic vaccine for humans against H. pylori infection.