A self-immolative near-infrared fluorescent probe for identification of cancer cells and facilitating its apoptosis.

Hydrogen sulfide (H2S) plays a significant role in the onset and progression of cancer. It has led to increased interest in its potential as a diagnostic tool owing to its overexpression in cancer. However, research into the anti-cancer activity of H2S, particularly its ability to promote apoptosis, is hindered by the lack of effective detection tools. To gain a comprehensive understanding of the targeted efficacy of H2S in promoting cancer cell apoptosis, we designed and synthesized a self-immolative near-infrared fluorescent diagnostic probe, named YH-NO2. The activation of this self-immolative reaction is dependent on the presence of nitroreductase (NTR) overexpressed in tumor cells. The design of YH-NO2 involves releasing fluorophores through the activated self-immolative reaction for detection, while simultaneously releasing H2S-loaded self-immolative spacers to promote cancer cell apoptosis. Consequently, YH-NO2 achieves a seamless integration of recognizing and promoting cancer cell apoptosis through its self-immolative structure. This dual function allows YH-NO2 to recognize NTR activity in cells under varying hypoxia levels and differentiate between normal cells and cancer cells using imaging technology. Notably, YH-NO2 exhibits remarkable stability in cellular environments, providing controlled and selective H2S release, thereby targeting the elimination of cancer cells through the promotion of apoptosis. Furthermore, in vivo experiments have demonstrated that YH-NO2 can accurately identify tumor tissue and effectively reduce its size by utilizing its apoptosis-promoting properties. These findings not only provide further evidence for the anti-cancer activity of H2S but also offer valuable tools for understanding the complex relationship between H2S and cancer.

Background-penalty-free waveguide enhancement of CARS signal in air-filled anti-resonance hollow-core fiber.

We study coherent anti-Stokes Raman spectroscopy in air-filled anti-resonance hollow-core photonic crystal fiber, otherwise known as "revolver" fiber. We compare the vibrational coherent anti-Stokes Raman signal of N2, at ∼2331 cm-1, generated in ambient air (no fiber present), with the one generated in a 2.96 cm of a revolver fiber. We show a ∼170 times enhancement for the signal produced in the fiber, due to an increased interaction path. Remarkably, the N2 signal obtained in the revolver fiber shows near-zero non-resonant background, due to near-zero overlap between the laser field and the fiber cladding. Through our study, we find that the revolver fiber properties make it an ideal candidate for the coherent Raman spectroscopy signal enhancement.

Fabrication of a smart drug delivery system based on hollow Ag2S@mSiO2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy.

A novel near-infrared (NIR) light-triggered smart nanoplatform has been developed for cancer targeting and imaging-guided combined photothermal-chemo treatment. Notably, Ag2S has a dual function of photothermal therapy and fluorescence imaging, which greatly simplifies the structure of the system. It can emit fluorescence at 820 nm under an excitation wavelength of 560 nm. The phase-change molecule of 1-tetradecanol (TD) is introduced as a temperature-sensitive gatekeeper to provide the nanocarrier with controlled release capability of doxorubicin (DOX). The nanocarrier (HAg2S@mSiO2-TD/DOX) shows a high drug loading capacity of 26.3% and exhibits an apparent NIR-responsive DOX release property. Under NIR irradiation, the photothermal effect of HAg2S nanocores facilitated the release of DOX through the melting of TD. The cytotoxicity test shows that the nanocarriers have good biocompatibility. As the same time, the synergistic combination leads to a better cancer inhibition effect than individual therapy alone in vitro. Cell uptake tests indicate that the carriers have excellent fluorescence imaging ability and high cellular uptake for HepG2 cells. This work provides a new strategy for the fabrication of smart nanocarriers with simple structures for fluorescence-mediated combination cancer therapy. Fabrication of a smart drug delivery system based on hollow Ag2S@mSiO2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy.

Neutron Total Scattering Investigation of the Dissolution Mechanism of Trehalose in Alkali/Urea Aqueous Solution.

The atomic picture of cellulose dissolution in alkali/urea aqueous solution is still not clear. To reveal it, we use trehalose as the model molecule and total scattering as the main tool. Three kinds of alkali solution, i.e., LiOH, NaOH and KOH are compared. The most probable all-atom structures of the solution are thus obtained. The hydration shell of trehalose has a layered structure. The smaller alkali ions can penetrate into the glucose rings around oxygen atoms to form the first hydration layer. The larger urea molecules interact with hydroxide groups to form complexations. Then, the electronegative complexation can form the second hydration layer around alkali ions via electrostatic interaction. Therefore, the solubility of alkali aqueous solution for cellulose decreases with the alkali cation radius, i.e., LiOH > NaOH > KOH. Our findings are helpful for designing better green solvents for cellulose.

Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution.

Tip-enhanced Raman scattering (TERS) is a promising optical and analytical technique for chemical imaging and sensing at single molecule resolution. In particular, TERS signals generated by a gap-mode configuration where a silver tip is coupled with a gold substrate can resolve a single-stranded DNA (ssDNA) molecule with a spatial resolution below 1 nm. To demonstrate the proof of subnanometer resolution, we show direct nucleic acid sequencing using TERS of a phage ssDNA (M13mp18). M13mp18 provides a known sequence and, through our deposition strategy, can be stretched (uncoiled) and attached to the substrate by its phosphate groups, while exposing its nucleobases to the tip. After deposition, we scan the silver tip along the ssDNA and collect TERS signals with a step of 0.5 nm, comparable to the bond length between two adjacent DNA bases. By demonstrating the real-time profiling of a ssDNA configuration and furthermore, with unique TERS signals of monomeric units of other biopolymers, we anticipate that this technique can be extended to the high-resolution imaging of various nanostructures as well as the direct sequencing of other important biopolymers including RNA, polysaccharides, and polypeptides.

The multi-slit very small angle neutron scattering instrument at the China Spallation Neutron Source.

A multi-slit very small angle neutron scattering (MS-VSANS) instrument has been finally accepted at the China Spallation Neutron Source (CSNS). It is the first spallation neutron source based VSANS instrument. MS-VSANS has a good signal-to-noise ratio and can cover a wide scattering vector magnitude range from 0.00028 to 1.4 Å-1. In its primary flight path, a combined curved multichannel beam bender and sections of rotary exchange drums are installed to minimize the background downstream of the instrument. An exchangeable multi-slit beam focusing system is integrated into the primary flight path, enabling access to a minimum scattering vector magnitude of 0.00028 Å-1. MS-VSANS has three modes, namely conventional SANS, polarizing SANS and VSANS modes. In the SANS mode, three motorized high-efficiency 3He tube detectors inside the detector tank cover scattering angles from 0.12 to 35° simultaneously. In the polarizing SANS mode, a double-V cavity provides highly polarized neutrons and a high-efficiency 3He polarization analyser allows full polarization analysis. In the VSANS mode, an innovative high-resolution gas electron multiplier detector covers scattering angles from 0.016 to 0.447°. The absolute scattering intensities of a selection of standard samples are obtained using the direct-beam technique; the effectiveness of this method is verified by testing the standard samples and comparing the results with those from a benchmark instrument. The MS-VSANS instrument is designed to be flexible and versatile and all the design goals have been achieved.

Optical multiband polarimetric modulation sensing for gender and species identification of flying native solitary pollinators.

Native pollinators are crucial to local ecosystems but are under threat with the introduction of managed pollinators, e.g., honeybees (Apis mellifera). We explored the feasibility of employing the entomological lidar technique in native pollinator abundance studies. This study included individuals of both genders of three common solitary bee species, Osmia californica, Osmia lignaria, and Osmia ribifloris, native to North America. Properties including optical cross-section, degree of linear polarization, and wingbeat power spectra at all three wavelengths have been extracted from the insect signals collected by a compact stand-off sensing system. These properties are then used in the classification analysis. For species with temporal and spatial overlapping, the highest accuracies of our method exceed 96% (O. ribifloris & O. lignaria) and 93% (O. lignaria & O. californica). The benefit of employing the seasonal activity and foraging preference information in enhancing identification accuracy has been emphasized.

Construction of Double-Shelled Hollow Ag2S@Polydopamine Nanocomposites for Fluorescence-Guided, Dual Stimuli-Responsive Drug Delivery and Photothermal Therapy.

The design and preparation of multifunctional drug carriers for combined photothermal-chemotherapy of cancer have attracted extensive attention over the past few decades. However, the development of simple-structured stimuli-responsive theranostic agents as both photothermal agents and chemotherapeutic agents remains a big challenge. Herein, a novel double-shelled nanocarrier composed of hollow Ag2S (HAg2S) nanospheres and a mesoporous polydopamine (MPDA) exterior shell was fabricated through a facile process. Notably, HAg2S possesses both fluorescence and photothermal properties. MPDA acts as a drug carrier and photothermal agent. Meanwhile, the cavity structure between HAg2S and MPDA provides more space for drug loading. The nanocarrier presents a high drug loading rate of 23.4%. It exhibits an apparent pH-responsive DOX release property due to the acidic sensitivity of PDA. In addition, the release of DOX is promoted under NIR irradiation, which is attributed to the heating action generated by the photothermal effect of HAg2S and MPDA. The cytotoxicity test shows that the nanocarriers possess good biocompatibility. Compared with single photothermal therapy or chemotherapy, the combined treatment represents a synergistic effect with higher therapeutic efficacy. In addition, the nanocarriers exhibit excellent fluorescence imaging capability and can target HepG2 cells. These simple-structured smart nanocarriers have a great potential for fluorescence-mediated combination cancer therapy.

Structure and dynamics of supercooled water in the hydration layer of poly(ethylene glycol).

The statics and dynamics of supercooled water in the hydration layer of poly(ethylene glycol) (PEG) were studied by a combination of quasi-elastic neutron scattering (QENS) and molecular dynamics (MD) simulations. Two samples, that is, hydrogenated PEG/deuterated water (h-PEG/D2O) and fully deuterated PEG/hydrogenated water (d-PEG/H2O) with the same molar ratio of ethylene glycol (EG) monomer to water, 1:1, are compared. The QENS data of h-PEG/D2O show the dynamics of PEG, and that of d-PEG/H2O reveals the motion of water. The temperature-dependent elastic scattering intensity of both samples has shown transitions at supercooled temperature, and these transition temperatures depend on the energy resolution of the instruments. Therefore, neither one is a phase transition, but undergoes dynamic process. The dynamic of water can be described as an Arrhenius to super-Arrhenius transition, and it reveals the hydrogen bonding network relaxation of hydration water around PEG at supercooled temperature. Since the PEG-water hydrogen bond structural relaxation time from MD is in good agreement with the average relaxation time from QENS (d-PEG/H2O), MD may further reveal the atomic pictures of the supercooled hydration water. It shows that hydration water molecules form a series of pools around the hydrophilic oxygen atom of PEG. At supercooled temperature, they have a more bond ordered structure than bulk water, proceed a trapping sites diffusion on the PEG surface, and facilitate the structural relaxation of PEG backbone.

The Relationship between Free Volume and Cooperative Rearrangement: From the Temperature-Dependent Neutron Total Scattering Experiment of Polystyrene.

Although many theories have been proposed to describe the nature of glass formation, its microscopic picture is still missing. Here, by a combination of neutron scattering and molecular dynamics simulation, we present the temperature-dependent atomic structure variation of polystyrene at the glass formation, free volume and cooperative rearrangement. When it is close to glass formation, the polymer is confined in tubes, whose diameter is the main chain-main chain distance, in a "static cage" from its neighbors. This definition can not only account for the kinetic pathway dependence of Williams-Landel-Ferry (WLF) free volume, but also be testified in a set of six polymers. However, the free volume which allows a monomer to move cannot be found in any frame of its real-space image. Monomers, thus, have to move cooperatively to be out of the cage. During glass formation, dynamic heterogeneity develops, and string-like cooperative rearrangement region (CRR) grows over a long range of time and length scales. All of these CRRs tend to walk through loose "static cages". Our observation unifies the concepts of free volume and cooperative rearrangement. The former is a statistical average leading to a polydisperse "static cage" formation; while a loose "static cage" provides the way that CRRs move.

Nanometerization of thiamethoxam by a cationic star polymer nanocarrier efficiently enhances the contact and plant-uptake dependent stomach toxicity against green peach aphids.

BACKGROUND: The utilization efficiency of conventional insecticides is comparatively low in agricultural production, which leads to their excessive application and environmental pollution. Insecticide nanometerization by polymers and polymeric materials has advantages, particularly increased utilization efficiency and reduced insecticide application. RESULTS: To increase the utilization efficiency of insecticides, a star polycation (SPc) was selected as a drug carrier that could be complexed with thiamethoxam through electrostatic interaction. Formation of the complex decreased the particle size of thiamethoxam from 575.77 to 116.16 nm in aqueous solution. Plant uptake of SPc-delivered thiamethoxam was increased 1.69-1.84 times compared with thiamethoxam alone. Nano-sized thiamethoxam/SPc complexes showed enhanced contact and stomach toxicity against green peach aphids. CONCLUSION: SPc is a promising insecticide adjuvant for insecticide nanometerization, and is beneficial in improving insecticidal activity and decreasing the application amounts and application rates of conventional insecticides. © 2020 Society of Chemical Industry.

Raman Characterization of Fungal DHN and DOPA Melanin Biosynthesis Pathways.

Fungal melanins represent a resource for important breakthroughs in industry and medicine, but the characterization of their composition, synthesis, and structure is not well understood. Raman spectroscopy is a powerful tool for the elucidation of molecular composition and structure. In this work, we characterize the Raman spectra of wild-type Aspergillus fumigatus and Cryptococcus neoformans and their melanin biosynthetic mutants and provide a rough "map" of the DHN (A. fumigatus) and DOPA (C. neoformans) melanin biosynthetic pathways. We compare this map to the Raman spectral data of Aspergillus nidulans wild-type and melanin biosynthetic mutants obtained from a previous study. We find that the fully polymerized A. nidulans melanin cannot be classified according to the DOPA pathway; nor can it be solely classified according to the DHN pathway, consistent with mutational analysis and chemical inhibition studies. Our approach points the way forward for an increased understanding of, and methodology for, investigating fungal melanins.

Neutron total scattering investigation on the dissolution mechanism of trehalose in NaOH/urea aqueous solution.

Trehalose is chosen as a model molecule to investigate the dissolution mechanism of cellulose in NaOH/urea aqueous solution. The combination of neutron total scattering and empirical potential structure refinement yields the most probable all-atom positions in the complex fluid and reveals the cooperative dynamic effects of NaOH, urea, and water molecules in the dissolution process. NaOH directly interacts with glucose rings by breaking the inter- and intra-molecular hydrogen bonding. Na+, thus, accumulates around electronegative oxygen atoms in the hydration shell of trehalose. Its local concentration is thereby 2-9 times higher than that in the bulk fluid. Urea molecules are too large to interpenetrate into trehalose and too complex to form hydrogen bonds with trehalose. They can only participate in the formation of the hydration shell around trehalose via Na+ bridging. As the main component in the complex fluid, water molecules have a disturbed tetrahedral structure in the presence of NaOH and urea. The structure of the mixed solvent does not change when it is cooled to -12 °C. This indicates that the dissolution may be a dynamic process, i.e., a competition between hydration shell formation and inter-molecule hydrogen bonding determines its dissolution. We, therefore, predict that alkali with smaller ions, such as LiOH, has better solubility for cellulose.

Identification of toxic mold species through Raman spectroscopy of fungal conidia.

We use a 785 nm shifted excitation Raman difference (SERDS) technique to measure the Raman spectra of the conidia of 10 mold species of especial toxicological, medical, and industrial importance, including Stachybotrys chartarum, Penicillium chrysogenum, Aspergillus fumigatus, Aspergillus flavus, Aspergillus oryzae, Aspergillus niger, and others. We find that both the pure Raman and fluorescence signals support the hypothesis that for an excitation wavelength of 785 nm the Raman signal originates from the melanin pigments bound within the cell wall of the conidium. In addition, the major features of the pure Raman spectra group into profiles that we hypothesize may be due to differences in the complex melanin biosynthesis pathways. We then combine the Raman spectral data with neural network models to predict species classification with an accuracy above 99%. Finally, the Raman spectral data of all species investigated is made freely available for download and use.

Molecular origin of the Raman signal from Aspergillus nidulans conidia and observation of fluorescence vibrational structure at room temperature.

Successful approaches to identification and/or biological characterization of fungal specimens through Raman spectroscopy may require the determination of the molecular origin of the Raman response as well as its separation from the background fluorescence. The presence of fluorescence can interfere with Raman detection and is virtually impossible to avoid. Fluorescence leads to a multiplicity of problems: one is noise, while another is "fake" spectral structure that can easily be confused for spontaneous Raman peaks. One solution for these problems is Shifted Excitation Raman Difference Spectroscopy (SERDS), in which a tunable light source generates two spectra with different excitation frequencies in order to eliminate fluorescence from the measured signal. We combine a SERDS technique with genetic breeding of mutant populations and demonstrate that the Raman signal from Aspergillus nidulans conidia originates in pigment molecules within the cell wall. In addition, we observe unambiguous vibrational fine-structure in the fluorescence response at room temperature. We hypothesize that the vibrational fine-structure in the fluorescence results from the formation of flexible, long-lived molecular cages in the bio-polymer matrix of the cell wall that partially shield target molecules from the immediate environment and also constrain their degrees of freedom.

Enhancing sensitivity of lateral flow assay with application to SARS-CoV-2.

Lateral flow assay (LFA) has long been used as a biomarker detection technique. It has advantages such as low cost, rapid readout, portability, and ease of use. However, its qualitative readout process and lack of sensitivity are limiting factors. We report a photon-counting approach to accurately quantify LFAs while enhancing sensitivity. In particular, we demonstrate that the density of SARS-CoV-2 antibodies can be quantified and measured with an enhanced sensitivity using this simple laser optical analysis.

CARS spectroscopy of Aspergillus nidulans spores.

Coherent Anti-Stokes Raman Spectroscopy (CARS) is performed on single spores (conidia) of the fungus Aspergillus nidulans in order to establish a baseline measurement for fungal spores. Chemical maps of single spores are generated and spectral differentiation between the cell wall and the cytoplasm is achieved. Principal Component Analysis of the measured spectra is then completed as a means to quantify spore heterogeneity. Applications range from the quick and accurate diagnosis of public health concerns to real-time agricultural and environmental sensing of fungal symbionts and pathogens.

Quantum plasmonic control of trions in a picocavity with monolayer WS2.

Monitoring and controlling the neutral and charged excitons (trions) in two-dimensional (2D) materials are essential for the development of high-performance devices. However, nanoscale control is challenging because of diffraction-limited spatial resolution of conventional far-field techniques. Here, we extend the classical tip-enhanced photoluminescence based on tip-substrate nanocavity to quantum regime and demonstrate controlled nano-optical imaging, namely, tip-enhanced quantum plasmonics. In addition to improving the spatial resolution, we use the scanning probe to control the optoelectronic response of monolayer WS2 by varying the neutral/charged exciton ratio via charge tunneling in Au-Ag picocavity. We observe trion "hot spots" generated by varying the picometer-scale probe-sample distance and show the effects of weak and strong coupling, which depend on the spatial location. Our experimental results are in agreement with simulations and open an unprecedented view of a new range of quantum plasmonic phenomena with 2D materials that will help to design new quantum optoelectronic devices.