Multifunctional Photonic Janus Particles.

Photonic Janus particles with a sphere fused to a cone are created from the phase separation of dendronized brush block copolymers (den-BBCP) and poly(4-vinylpyridine)-r-polystyrene (P4VP-r-PS) during the solvent evaporation of oil-in-water emulsions. Rapid self-assembly of den-BBCP generates well-ordered lamellar structures stacking along the long axis of the particles, producing structural colors that are dependent on the incident light angle. The colors are tunable over the visible spectrum by varying the molecular weight of den-BBCP. The P4VP-r-PS phase can undergo further surface modifications to produce multifunctional photonic Janus particles. Specifically, real-time magnetic control of the reflected color is achieved by coating the P4VP-r-PS phase with citric acid-capped Fe3O4 nanoparticles. Charged biomolecules (i.e., antibodies) are electrostatically immobilized to the Fe3O4 coating for potential applications in biosensing. As a demonstration, a new photonic sensor for the foodborne pathogen Salmonella is developed with antibody-modified photonic Janus particles, where the angle-dependent structural color plays a key role in the sensing mechanism.

Generation of fully human anti-GPC3 antibodies with high-affinity recognition of GPC3 positive tumors.

The acceleration of therapeutic antibody development has been motivated by the benefit to and their demand for human health. In particular, humanized transgenic antibody discovery platforms, combined with immunization, hybridoma fusion and/or single cell DNA sequencing are the most reliable and rapid methods for mining the human monoclonal antibodies. Human GPC3 protein is an oncofetal antigen, and it is highly expressed in most hepatocellular carcinomas and some types of squamous cell carcinomas. Currently, no fully human anti-GPC3 therapeutic antibodies have been reported and evaluated in extensive tumor tissues. Here, we utilized a new humanized transgenic mouse antibody discovery platform (CAMouse) that contains large V(D)J -regions and human gamma-constant regions of human immunoglobulin in authentic configurations to generate fully human anti-GPC3 antibodies. Our experiments resulted in four anti-GPC3 antibodies with high-specific binding and cytotoxicity to GPC3 positive cancer cells, and the antibody affinities are in the nanomolar range. Immunohistochemistry analysis demonstrated that these antibodies can recognize GPC3 protein on many types of solid tumors. In summary, the human anti-human GPC3 monoclonal antibodies described here are leading candidates for further preclinical studies of cancer therapy, further, the CAMouse platform is a robust tool for human therapeutic antibody discovery.

Switchable Full-Color Reflective Photonic Ellipsoidal Particles.

Full-color reflective photonic ellipsoidal polymer particles, capable of a dynamic color change, are created from dendronized brush block copolymers (den-BBCPs) self-assembled by solvent-evaporation from an emulsion. Surfactants composed of dendritic monomer units allow for the precise modulation of the interfacial properties of den-BBCP particles to transition in shape from spheres to striped ellipsoids. Strong steric repulsions between wedge-type monomers promote rapid self-assembly of polymers into large domains (i.e., 153 nm ≤ D ≤ 298 nm). Of note, highly ordered axially stacked lamellae (i.e., number of layers >100) within an ellipsoid give rise to a near-perfect photonic multilayer. The reflecting color is readily tunable across the entire visible spectrum by alteration of the molecular weight from 477 to 1144 kDa. Finally, the photonic ellipsoids are functionalized with magnetic nanoparticles organized into bands on the particle surface to produce real-time on/off coloration by magnetic field-assisted activation. In total, the reported photonic ellipsoidal particles represent a new class of switchable photonic materials.

Square Grid Metal-Chloranilate Networks as Robust Host Systems for Guest Sorption.

Reaction of the chloranilate dianion with Y(NO3 )3 in the presence of Et4 N+ in the appropriate proportions results in the formation of (Et4 N)[Y(can)2 ], which consists of anionic square-grid coordination polymer sheets with interleaved layers of counter-cations. These counter-cations, which serve as squat pillars between [Y(can)2 ] sheets, lead to alignment of the square grid sheets and the subsequent generation of square channels running perpendicular to the sheets. The crystals are found to be porous and retain crystallinity following cycles of adsorption and desorption. This compound exhibits a high affinity for volatile guest molecules, which could be identified within the framework by crystallographic methods. In situ neutron powder diffraction indicates a size-shape complementarity leading to a strong interaction between host and guest for CO2 and CH4 . Single-crystal X-ray diffraction experiments indicate significant interactions between the host framework and discrete I2 or Br2 molecules. A series of isostructural compounds (cat)[MIII (X-an)2 ] with M=Sc, Gd, Tb, Dy, Ho, Er, Yb, Lu, Bi or In, cat=Et4 N, Me4 N and X-an=chloranilate, bromanilate or cyanochloranilate bridging ligands have been generated. The magnetic properties of representative examples (Et4 N)[Gd(can)2 ] and (Et4 N)[Dy(can)2 ] are reported with normal DC susceptibility but unusual AC susceptibility data noted for (Et4 N)[Gd(can)2 ].

Bromine adatom promoted C-H bond activation in terminal alkynes at room temperature on Ag(111).

The activation of C-H bonds in terminal alkynyl groups at room temperature was achieved in the reaction of 2,5-diethynyl-1,4-bis(4-bromophenylethynyl)benzene on Ag(111). Scanning tunneling microscopy studies showed the formation of organometallic species, whose stabilization was confirmed by density functional theory calculations, at room temperature as the product of C-H bond activation. The partial conversion of organometallic structures into covalent products of the homocoupling between the terminal alkynes was achieved by further annealing the sample at 420 K. Detached Br adatoms were suggested to play a key role in promoting the C-H bond activation. This proposal was supported by the theoretical study based on a simplified model of the system, showing the weakening of the C-H bond in the alkynyl group by an approaching Br atom. The results provide a new strategy for on-surface C-H bond activation under mild conditions, which register great potential applications in on-surface synthesis and bottom-up preparation of functional nanomaterials.

Highly Contorted Rigid Nitrogen-Rich Nanographene with Four Heptagons.

Nucleophilic substitution of 9,10-dichlorooctafluoroanthracene with 3,4-diethylpyrrole and subsequent Scholl reaction give the annularly fused decapyrrollyl anthracene. Single crystal X-ray analysis revealed a highly contorted geometry induced by a combination of adjacent heptagons, forming a unique 7-7-6-7-7 topology. The end-to-end twist angle along the acene moiety is 90°. Cyclic voltammetry studies reveal 6-electron oxidation waves. Density functional theory calculations provided further insights into the aromaticity and electronic properties of this highly twisted, nitrogen-rich nanographene. The structural rigidity and high racemization energy barrier have been studied theoretically and experimentally by VT-NMR.

A novel technology for rapid identification of hemp fibers by terahertz spectroscopy.

A novel method for the rapid identification of hemp fibers is proposed in this paper, utilizing terahertz time-domain spectroscopy (THz-TDS) combined with the LargeVis (LV) dimensionality reduction technique. This approach takes advantage of the strengths of THz-TDS while enhancing classification accuracy through LV. To verify the efficacy of this method, terahertz absorption spectral data from three types of hemp fibers were processed. The THz absorption spectra were initially preprocessed using Hanning filtering. Following this, the filtered data underwent dimensionality reduction through three distinct methods: linear Principal Component Analysis (PCA), nonlinear t-Distributed Stochastic Neighbor Embedding (t-SNE), and the LV method. This sequence of steps resulted in a two-dimensional feature data matrix derived from the THz source spectral data. The resultant feature data matrices were then input into both K-Nearest Neighbors (KNN) and Decision Tree (DT) classifiers for analysis. The classification accuracies of six models were evaluated, revealing that the LV-KNN model achieved a 86.67% accuracy rate for the three hemp fiber types. Impressively, the LV-DT model achieved a perfect 100.00% accuracy rate for the same fibers. The LV-DT model, when integrated with THz spectroscopy technology, offers a quick and precise method for identifying various types of hemp fibers. This development introduces an innovative optical measurement scheme for the characterization of textile materials.

Study on the Influence Mechanism and Space Distribution Characteristics of Rail Transit Station Area Accessibility Based on MGWR.

The accessibility of rail transit station areas is an important factor affecting the efficiency of rail transit. Taking the Beijing rail transit station area as our research object, this paper took a 15 min walking distance as the index of station area accessibility, and investigated the status quo and influencing factors of the unbalanced distribution of rail transit station area accessibility in Beijing. In this paper, the data of Beijing rail transit stations were obtained from the Amap open platform, and the accessibility of the station area was calculated using the path planning service provided by the Amap API. The Getis-Ord Gi* method was used to analyze the overall distribution characteristics of the accessibility of the Beijing rail transit station area, then the high accessibility area and the low accessibility area were determined. To explore the factors influencing domain accessibility, multi-source data were obtained, a total of 11 indicators were constructed, and the random forest model was used to identify feature importance. Using the eight selected influencing factors, the OLS regression model, GWR model, and MGWR model were used to study the spatial heterogeneity of influencing factors. By comparison, it was concluded that the MGWR model can not only effectively analyze the spatial heterogeneity of rail transit station accessibility, which can automatically mediate the bandwidth of different influencing factors, and then reflect the spatial changes of the influencing factors of rail transit station accessibility more truly. The results show that (1) the accessibility of the Beijing rail transit station area shows obvious spatial agglomeration characteristics in space. The accessibility of the station area in the fourth ring is higher than that outside of the fourth ring road, and the accessibility near the south and north fifth ring road is higher than that of the east fifth ring road and the west fifth ring road. (2) The basic influencing factors of rail transit station accessibility include road density and functional mixing degree.

Spatial-temporal variation, ecological risk, and source identification of nutrients and heavy metals in sediments in the peri-urban riverine system.

A great deal of attention has been directed to the toxicity, enrichment, and accumulation of urban river sediment pollution. To understand the spatial-temporal variation, ecological risk and source of nutrients, and heavy metals in sediments from the Weihe River, the concentrations of total nitrogen (TN), total phosphorus (TP), organic matter (OM), and 10 heavy metals (Cd, Sb, As, Co, Cu, Pb, Ni, Cr, Zn, and Mn) in sediments at 14 sampling sites along the river were investigated. The results showed that nutrients and heavy metals had an interannual decreasing trend, and that the high-value regions were concentrated in urban locations within the study area. Ecological risk assessment results showed that TN was between the security level (no toxic effect) and the lowest level (tolerable for organisms), TP was at the lowest level, and OM was within the security level, all mainly from external sources. The geoaccumulation index (Igeo) and enrichment factor (EF) of 10 heavy metals were all within the unpolluted level, while the pollution load index (PLI) of 12 sampling sites had reached the moderate pollution level. The results of Pearson correlation, principal component analysis, and cluster analysis showed that heavy metals originated mainly from industrial and domestic sources, geochemical environments, and agricultural activities, indicating that heavy metals in the Weihe River sediments were influenced significantly by anthropogenic activities. The results are expected to provide a scientific basis for the development and utilization of the Weihe River water resources.

Janus Emulsion Biosensors for Anti-SARS-CoV-2 Spike Antibody.

The spread of the COVID-19 pandemic around the world has revealed that it is urgently important to develop rapid and inexpensive assays for antibodies in general and anti-SARS-CoV-2 IgG antibody (anti-SARS-CoV-2 spike glycoprotein S1 antibody) in particular. Herein we report a method to detect the anti-SARS-CoV-2 spike antibody level by using Janus emulsions or Janus particles as biosensors. Janus emulsions are composed of two immiscible hydrocarbon and fluorocarbon oils. The hydrocarbon/water interfaces are functionalized with a secondary antibody of IgG protein and SARS-CoV-2 spike receptor binding domain (RBD), to produce two different Janus emulsions. Mixtures of these Janus droplets enable the detection of the anti-SARS-CoV-2 spike IgG antibody in an agglutination assay caused by the antibody's binding to both the secondary antibody of IgG antibody and SARS-CoV-2 spike protein RBD. Both qualitative optical images and quantitative fluorescence spectra are able to detect the level of anti-SARS-CoV-2 spike antibody at concentrations as low as 0.2 µg/mL in 2 h. The detection results of clinical human serum samples using this agglutination assay confirm that this method is applicable to clinical samples with good sensitivity and specificity. The reported method is generalizable and can be used to detect other analytes by attaching different biomolecular recognition elements to the surface of the Janus droplets.

Trace Hydrogen Sulfide Sensing Inspired by Polyoxometalate-Mediated Aerobic Oxidation.

A high-performance chemiresistive gas sensor is described for the detection of hydrogen sulfide (H2S), an acutely toxic and corrosive gas. The chemiresistor operates at room temperature with low power requirements potentially suitable for wearable sensors or for rapid in-field detection of H2S in settings such as pipelines and wastewater treatment plants. Specifically, we report chemiresistors based on single-walled carbon nanotubes (SWCNTs) containing highly oxidizing platinum-polyoxometalate (Pt-POM) selectors. We show that by tuning the vanadium content and thereby the oxidation reactivity of the constituent POMs, an efficient chemiresistive sensor is obtained that is proposed to operate by modulating CNT doping during aerobic H2S oxidation. The sensor shows exceptional sensitivity to trace H2S in air with a ppb-level detection limit, multimonth stability under ambient conditions, and high selectivity for H2S over a wide range of interferants, including thiols, thioethers, and thiophene. Finally, we demonstrate that the robust sensing material can be used to fabricate flexible devices by covalently immobilizing the SWCNT-P4VP network onto a polyimide substrate, further extending the potentially broad utility of the chemiresistors. The strategy presented herein highlights the applicability of concepts in molecular aerobic oxidation catalysis to the development of low-cost analyte detection technologies.

Detection of sivelestat and its metabolite in small volumes of plasma from Chinese ALI/ARDS patients with SIRS via high-throughput UPLC-MS/MS: A pharmacokinetic study.

In this study, we developed a sensitive and efficient analytical approach combining a 96-well plate-based protein precipitation strategy with ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-MS/MS) in order to assess the pharmacokinetic (PK) properties of sivelestat and its metabolite XW-IMP-A in samples of plasma from ALI/ARDS patients with SIRS. The samples were separated via gradient elution with a C18 column (Phenomenex Kinetex, C18, 2.6 µm, 100 Å, 50 × 2.1 mm) using 0.1 % formic acid aqueous solution (A) and acetonitrile-methanol (1:1, V:V) (B) as a mobile phase at a 0.6 mL/min flow rate. UPLC-MS/MS spectra were generated in positive ion mode, and multiple reaction monitoring (MRM) was used to detect the following transitions: m/z 435.1 → 360.0 for sivelestat, m/z 469.0 → 394.0 for sivelestat-IS, m/z 351.0 → 276.0 for XW-IMP-A, and m/z 384.9 → 310.0 for XW-IMP-A-IS. This assay was run for 2.5 min in total, and achieved lowest limit of quantitation values of 2.0 ng/mL and 0.5 ng/mL for sivelestat and XW-IMP-A, respectively, while remaining highly linear from 2-500 ng/mL for sivelestat (r2 ≥ 0.9900) and from 0.5-125 ng/mL for XW-IMP-A (r2 ≥ 0.9900). These validated data were consistent with US Food and Drug Administration (FDA) and European Medicines Agency (EMA) acceptance criteria. In addition, this method was successfully applied to the steady-state PK evaluation of ALI/ARDS patients with SIRS.

A polycyclic aromatic hydrocarbon diradical with pH-responsive magnetic properties.

By integrating azulene with a quinoid moiety, a novel non-alternant polycyclic aromatic hydrocarbon molecule BCHF1 exhibiting manifold zwitterionic, quinoidal and diradical behaviors is designed and synthesized. Its zwitterionic feature is evidenced by the changes shown by the 1H-NMR and absorption spectra when the molecule undergoes reversible protonation and deprotonation reactions at varied pH. The diradical facet, manifesting a small singlet-triplet energy gap (ΔE S-T), is characterized with a paramagnetic resonance signal detected by the EPR spectroscopy at room temperature. As the diradical properties are not observed in the protonated form, BCHF1+H+ , a pH-controlled reversible magnetic switching behavior is illustrated by monitoring the on and off cycles of EPR signals upon successively adding bases and acids to a solution or exposing a thin film of BCHF1+H+ to base vapor followed by acid vapor.

A novel targeted GPC3/CD3 bispecific antibody for the treatment hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer but has shown limited success to date in the treatment of advanced stage. Recruitment of T cells for cancer treatment is a rapidly growing strategy in immunotherapy such as chimeric antigen receptor T cells and bispecific antibodies. However, unwanted aggregations, structural instability or short serum half-life are major challenges of bispecific antibodies. Here, we developed a new format of T cell-redirecting antibody that is bispecific for membrane proteoglycans GPC3 of HCC and the T-cell-specific antigen CD3, which demonstrated to be favorable stability and productivity. Cross-linking of T cells with GPC3 positive tumor cells by the anti-GPC3/CD3 bispecific antibody-mediated potent GPC3-dependent and concentration-dependent cytotoxicity in vitro. Administration of the bispecific antibody with different concentrations in murine xenograft models of human HCC significantly inhibited tumor growth. In addition, no effects on tumor growth were observed in the absence of human effector cells or the bispecific antibody. Taken together, the anti-GPC3/CD3 bispecific antibody might be a potential therapeutic treatment for HCC.

[Application of magnetic particle antibody immunoassay in detection of anti-Schistosoma japonicum egg antibody].

OBJECTIVE: To establish a magnetic particle antibody immunoassay (MPAIA) for the detection of specific antibody in sera of schistosomiasis patients. METHODS: Fluorescein isothiocyanate (FITC) was used to label Schistosoma japonicum soluble egg antigen (Sj-SEA). Anti-human IgG coated with alkaline phosphatase (ALP) as enzyme-labeled second antibody, and magnetic beads were coupled with sheep anti-FITC antibody as solid phase. Phenolphthale in monophosphate was used as substrate to set up MPAIA for the detection. Serum samples from cases with schistosomiasis or other helminth infections were tested. RESULTS: The positive rate of MPAIA was 96.7% (116/120) with the sera of S. japonicum-infected cases. No cross reaction was observed with sera of trichinellosis, paragonimiasis or cysticercosis cases. The positive titer with reference sample was 1: 1,600. The precision was lower than 10%. The MPAIA tips can be stored at 4 degrees C for 12 months. CONCLUSION: MPAIA shows a high sensitivity, proper specificity and long-term validity for schistosomiasis detection.