Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups.

ABSTRACT: Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (White, 12% and Black, 25%). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (hazard ratio, 1.27; 95% confidence interval, 1.11-1.47; P < .001). This appeared to be driven by a marked difference in OS between White patients with and without DM but not in Black patients. In contrast, obesity was associated with better OS in Black patients but not in White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised nonobese diabetic (Rag1-/-/muscle creatinine kinase promoter expression of a human IGF1R [M] with a lysine [K] to arginine [R] point mutation) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with in controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phosphorylated S6 ribosomal protein (Ser235/236) levels, indicating greater activation of the mammalian target of rapamycin pathway. Our study is, to our knowledge, the first to evaluate racial differences in DM prevalence and survival in MM, as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients; and to improve survival in MM, DM management cannot be ignored.

Structure-Based Discovery of New Succinate Dehydrogenase Inhibitors via Scaffold Hopping Strategy.

Scaffold hopping strategy has become one of the most successful methods in the process of molecular design. Seeking to develop novel succinate dehydrogenase inhibitors (SDHIs), we employed a scaffold hopping strategy to design compounds featuring geminate dichloralkenes (gem-dichloralkenes) fragment. After stepwise modifications, a series of N-cyclopropyl-dichloralkenes-pyrazole-carboxamide derivatives was synthesized. Among them, compounds G28 (IC50 = 26.00 nM) and G40 (IC50 = 27.00 nM) were identified as the best inhibitory activity against porcine SDH, with IC50 values reaching the nanomolar range, outperforming the lead compound pydiflumetofen. Additionally, the greenhouse assay indicated that compounds G37 (EC90 = 0.031 mg/L) and G34 (EC90 = 1.67 mg/L) displayed extremely high activities against wheat powdery mildew (WPM) and cucumber powdery mildew (CPM), respectively. Computational results further revealed that the gem-dichloralkene fragment and fluorine substituted pyrazole form an extra hydrophobic interaction and dipolar-dipolar interaction with SDH. In summary, our study provides a novel gem-dichloralkene scaffold with outstanding fungicidal properties, obtained through scaffold hopping, that holds great potential for future research on PM control.

Range verification of a clinical proton beam in an abdominal phantom by co-registration of ionoacoustics and ultrasound.

Objective.The range uncertainty in proton radiotherapy is a limiting factor to achieve optimum dose conformity to the tumour volume. Ionoacoustics is a promising approach forin siturange verification, which would allow to reduce the size of the irradiated volume relative to the tumour volume. The energy deposition of a pulsed proton beam leads to an acoustic pressure wave (ionoacoustics), the detection of which allows conclusion about the distance between the Bragg peak and the acoustic detector. This information can be transferred into a co-registered ultrasound image, marking the Bragg peak position relative to the surrounding anatomy.Approach.A CIRS 3D abdominal phantom was irradiated with 126 MeV protons at a clinical proton therapy centre. Acoustic signals were recorded on the beam axis distal to the Bragg peak with a Cetacean C305X hydrophone. The ionoacoustic measurements were processed with a correlation filter using simulated filter templates. The hydrophone was rigidly attached to an ultrasound device (Interson GP-C01) recording ultrasound images of the irradiated region.Main results.The time of flight obtained from ionoacoustic measurements were transferred to an ultrasound image by means of an optoacoustic calibration measurement. The Bragg peak position was marked in the ultrasound image with a statistical uncertainty ofσ= 0.5 mm of 24 individual measurements depositing 1.2 Gy at the Bragg peak. The difference between the evaluated Bragg peak position and the one obtained from irradiation planning (1.0 mm) is smaller than the typical range uncertainty (≈4 mm) at the given penetration depth (10 cm).Significance.The measurements show that it is possible to determine the Bragg peak position of a clinical proton beam with submillimetre precision and transfer the information to an ultrasound image of the irradiated region. The dose required for this is smaller than that used for a typical irradiation fraction.

Proton beam range verification by means of ionoacoustic measurements at clinically relevant doses using a correlation-based evaluation.

Purpose: The Bragg peak located at the end of the ion beam range is one of the main advantages of ion beam therapy compared to X-Ray radiotherapy. However, verifying the exact position of the Bragg peak within the patient online is a major challenge. The goal of this work was to achieve submillimeter proton beam range verification for pulsed proton beams of an energy of up to 220 MeV using ionoacoustics for a clinically relevant dose deposition of typically 2 Gy per fraction by i) using optimal proton beam characteristics for ionoacoustic signal generation and ii) improved signal detection by correlating the signal with simulated filter templates. Methods: A water tank was irradiated with a preclinical 20 MeV proton beam using different pulse durations ranging from 50 ns up to 1 µs in order to maximise the signal-to-noise ratio (SNR) of ionoacoustic signals. The ionoacoustic signals were measured using a piezo-electric ultrasound transducer in the MHz frequency range. The signals were filtered using a cross correlation-based signal processing algorithm utilizing simulated templates, which enhances the SNR of the recorded signals. The range of the protons is evaluated by extracting the time of flight (ToF) of the ionoacoustic signals and compared to simulations from a Monte Carlo dose engine (FLUKA). Results: Optimised SNR of 28.0 ± 10.6 is obtained at a beam current of 4.5 µA and a pulse duration of 130 ns at a total peak dose deposition of 0.5 Gy. Evaluated ranges coincide with Monte Carlo simulations better than 0.1 mm at an absolute range of 4.21 mm. Higher beam energies require longer proton pulse durations for optimised signal generation. Using the correlation-based post-processing filter a SNR of 17.8 ± 5.5 is obtained for 220 MeV protons at a total peak dose deposition of 1.3 Gy. For this clinically relevant dose deposition and proton beam energy, submillimeter range verification was achieved at an absolute range of 303 mm in water. Conclusion: Optimal proton pulse durations ensure an ideal trade-off between maximising the ionoacoustic amplitude and minimising dose deposition. In combination with a correlation-based post-processing evaluation algorithm, a reasonable SNR can be achieved at low dose levels putting clinical applications for online proton or ion beam range verification into reach.

Discovery of N-Methoxy-(biphenyl-ethyl)-pyrazole-carboxamides as Novel Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase (SDH) inhibitor is one of the research hotspots for the development of fungicides. Herein, we describe the design and synthesis of N-methoxy-(biphenyl-ethyl)-pyrazole-carboxamide derivatives with enhanced fungicidal activity by employing fragment combination strategy. The SDH enzymatic activity was evaluated for 24 title compounds, and compound 7s was identified as the highest activity against porcine SDH with an IC50 value of 0.014 µM, 205-fold greater than that of fluxapyroxad. Furthermore, the greenhouse experiments showed that compound 7u exhibited potent fungicidal activity against wheat powdery mildew with an EC50 value of 0.633 mg/L, higher activity than fluxapyroxad and benzovindiflupyr. The computational results showed that the fluorine atom substituted on the pyrazole ring formed an extra dipolar-dipolar interaction with C_S42 and then increased the van der Waals interaction between the compound and SDH. The structural and mechanistic insights obtained from the present work will provide a valuable clue to developing novel SDH inhibitors.

A Probody T Cell-Engaging Bispecific Antibody Targeting EGFR and CD3 Inhibits Colon Cancer Growth with Limited Toxicity.

T cell-engaging bispecific antibodies (TCB) are highly potent therapeutics that can recruit and activate cytotoxic T cells to stimulate an antitumor immune response. However, the development of TCBs against solid tumors has been limited by significant on-target toxicity to normal tissues. Probody therapeutics have been developed as a novel class of recombinant, protease-activated antibody prodrugs that are "masked" to reduce antigen binding in healthy tissues but can become conditionally unmasked by proteases that are preferentially active in the tumor microenvironment (TME). Here, we describe the preclinical efficacy and safety of CI107, a Probody TCB targeting EGFR and CD3. In vitro, the protease-activated, unmasked CI107 effectively bound EGFR and CD3 expressed on the surface of cells and induced T-cell activation, cytokine release, and cytotoxicity toward tumor cells. In contrast, dually masked CI107 displayed a >500-fold reduction in antigen binding and >15,000-fold reduction in cytotoxic activity. In vivo, CI107 potently induced dose-dependent tumor regression of established colon cancer xenografts in mice engrafted with human peripheral blood mononuclear cells. Furthermore, the MTD of CI107 in cynomolgus monkeys was more than 60-fold higher than that of the unmasked TCB, and much lower levels of toxicity were observed in animals receiving CI107. Therefore, by localizing activity to the TME and thus limiting toxicity to normal tissues, this Probody TCB demonstrates the potential to expand clinical opportunities for TCBs as effective anticancer therapies for solid tumor indications. SIGNIFICANCE: A conditionally active EGFR-CD3 T cell-engaging Probody therapeutic expands the safety window of bispecific antibodies while maintaining efficacy in preclinical solid tumor settings.

Gestational Diabetes, Subsequent Type 2 Diabetes, and Food Security Status: National Health and Nutrition Examination Survey, 2007-2018.

INTRODUCTION: Despite many studies linking various risk factors to the association between gestational diabetes and subsequent type 2 diabetes, little is known about how food insecurity affects their association. We aimed to assess how the association between gestational diabetes and subsequent type 2 diabetes varies by food security status among women in the US. METHODS: This study is a secondary data analysis of 9,505 US women aged 20 years or older who had at least 1 live birth; we used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2007 through 2018. The main outcome was a diagnosis of type 2 diabetes in the subsequent years after the first live birth. We used multivariable survey-weighted negative binomial regressions to examine whether the association between gestational diabetes and subsequent type 2 diabetes differed by food security status, with and without adjusting for health behavior factors. RESULTS: Gestational diabetes was significantly associated with subsequent type 2 diabetes (incidence rate ratio [IRR], 2.57; 95% CI, 2.45-2.69). The association between gestational diabetes and subsequent type 2 diabetes was significantly different by food security status (IRR, 2.34; 95% CI, 2.23-2.45 among food-secure women; IRR, 2.99; 95% CI, 2.70-3.28 among food-insecure women). CONCLUSION: The association between gestational diabetes and subsequent type 2 diabetes differs significantly by food security status. Public health and health care practitioners should consider food security status when designing and implementing diabetes prevention interventions for women with a history of gestational diabetes.

Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody-Drug Conjugate.

Probody therapeutics (Pb-Txs) are conditionally activated antibody-drug conjugates (ADCs) designed to remain inactive until proteolytically activated in the tumor microenvironment, enabling safer targeting of antigens expressed in both tumor and normal tissue. Previous attempts to target CD71, a highly expressed tumor antigen, have failed to establish an acceptable therapeutic window due to widespread normal tissue expression. This study evaluated whether a probody-drug conjugate targeting CD71 can demonstrate a favorable efficacy and tolerability profile in preclinical studies for the treatment of cancer. CX-2029, a Pb-Tx conjugated to maleimido-caproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E, was developed as a novel cancer therapeutic targeting CD71. Preclinical studies were performed to evaluate the efficacy and safety of this anti-CD71 PDC in patient-derived xenograft (PDX) mouse models and cynomolgus monkeys, respectively. CD71 expression was detected at high levels by IHC across a broad range of tumor and normal tissues. In vitro, the masked Pb-Tx form of the anti-CD71 PDC displayed a >50-fold reduced affinity for binding to CD71 on cells compared with protease-activated, unmasked anti-CD71 PDC. Potent in vivo tumor growth inhibition (stasis or regression) was observed in >80% of PDX models (28/34) at 3 or 6 mg/kg. Anti-CD71 PDC remained mostly masked (>80%) in circulation throughout dosing in cynomolgus monkeys at 2, 6, and 12 mg/kg and displayed a 10-fold improvement in tolerability compared with an anti-CD71 ADC, which was lethal. Preclinically, anti-CD71 PDC exhibits a highly efficacious and acceptable safety profile that demonstrates the utility of the Pb-Tx platform to target CD71, an otherwise undruggable target. These data support further clinical development of the anti-CD71 PDC CX-2029 as a novel cancer therapeutic.

Genetically encoded photo-switchable molecular sensors for optoacoustic and super-resolution imaging.

Reversibly photo-switchable proteins are essential for many super-resolution fluorescence microscopic and optoacoustic imaging methods. However, they have yet to be used as sensors that measure the distribution of specific analytes at the nanoscale or in the tissues of live animals. Here we constructed the prototype of a photo-switchable Ca2+ sensor based on GCaMP5G that can be switched with 405/488-nm light and describe its molecular mechanisms at the structural level, including the importance of the interaction of the core barrel structure of the fluorescent protein with the Ca2+ receptor moiety. We demonstrate super-resolution imaging of Ca2+ concentration in cultured cells and optoacoustic Ca2+ imaging in implanted tumor cells in mice under controlled Ca2+ conditions. Finally, we show the generalizability of the concept by constructing examples of photo-switching maltose and dopamine sensors based on periplasmatic binding protein and G-protein-coupled receptor-based sensors.

Bifunctional flexible fabrics with excellent Joule heating and electromagnetic interference shielding performance based on copper sulfide/glass fiber composites.

Flexible and wearable electronic technology is in great demand with the rise of smart electronic systems. Among these, multifunctional systems with high performance at low cost have attracted extensive attention of scholars from the practical application perspective. However, the fabrication of devices with multifunctionality without sacrificing their connatural flexibility advantages remains a huge challenge. In this study, a CuS-modified glass fiber first acts as a bifunctional wearable electronic device for superior thermal management and electromagnetic interference (EMI) shielding. Specifically, the inherent glass fiber was initially modified with a silane coupling agent for the amino group (-NH2) functionalization followed by further CuS deposition via a facile electroless plating technology. Interestingly, due to the strong interaction between CuS and the glass fiber through the coordinate -NH2 and Cu2+, the prepared copper sulfide/glass fibers (CuS/GFs) not only keep the inherent flexibility and lightness of the fiber substrate, but also have excellent electrothermal conversion performance accompanied by a wide temperature range (38 °C-209 °C), low working voltage (0.3 V-1.5 V), and rapid response time (reaching 209 °C within 10 s at 1.5 V). Moreover, the prepared CuS/GF textile also exhibits interesting electromagnetic interference shielding efficiency (EMI SE) of 61 dB as well as a high specific shielding effectiveness up to 6130.65 dB cm2 g-1 with a CuS mass loading of 9.95 mg cm-2. These features confirm the potential of CuS/GFs as a flexible, wearable, and efficient electrical heater and EMI shielding material for the new type of intelligent electronic devices.

Noninvasive visualization of electrical conductivity in tissues at the micrometer scale.

Despite its importance in regulating cellular or tissue function, electrical conductivity can only be visualized in tissue indirectly as voltage potentials using fluorescent techniques, or directly with radio waves. These either requires invasive procedures like genetic modification or suffers from limited resolution. Here, we introduce radio-frequency thermoacoustic mesoscopy (RThAM) for the noninvasive imaging of conductivity by exploiting the direct absorption of near-field ultrashort radio-frequency pulses to stimulate the emission of broadband ultrasound waves. Detection of ultrasound rather than radio waves enables micrometer-scale resolutions, over several millimeters of tissue depth. We confirm an imaging resolution of <30 µm in phantoms and demonstrate microscopic imaging of conductivity correlating to physical structures in 1- and 512-cell zebrafish embryos, as well as larvae. These results support RThAM as a promising method for high-resolution, label-free assessment of conductivity in tissues.

Croconaine-based nanoparticles enable efficient optoacoustic imaging of murine brain tumors.

Contrast enhancement in optoacoustic (photoacoustic) imaging can be achieved with agents that exhibit high absorption cross-sections, high photostability, low quantum yield, low toxicity, and preferential bio-distribution and clearance profiles. Based on advantageous photophysical properties of croconaine dyes, we explored croconaine-based nanoparticles (CR780RGD-NPs) as highly efficient contrast agents for targeted optoacoustic imaging of challenging preclinical tumor targets. Initial characterization of the CR780 dye was followed by modifications using polyethylene glycol and the cancer-targeting c(RGDyC) peptide, resulting in self-assembled ultrasmall particles with long circulation time and active tumor targeting. Preferential bio-distribution was demonstrated in orthotopic mouse brain tumor models by multispectral optoacoustic tomography (MSOT) imaging and histological analysis. Our findings showcase particle accumulation in brain tumors with sustainable strong optoacoustic signals and minimal toxic side effects. This work points to CR780RGD-NPs as a promising optoacoustic contrast agent for potential use in the diagnosis and image-guided resection of brain tumors.

Comparison of Gut Microbiota Between Infants with Atopic Dermatitis and Healthy Controls in Guangzhou, China.

PURPOSE: Evidence on the role of the gut microbiota in atopic dermatitis is inconsistent as human intestinal microbiota is influenced by geography. This cross-sectional study therefore aimed to compare differences in the gut microbiota of infants with atopic dermatitis and healthy infants in Guangzhou, China, by analyzing their stool. PATIENTS AND METHODS: The composition of the intestinal microbiota was analyzed from the stool samples of 20 infants with atopic dermatitis (AD group) and 25 healthy infants (non-AD group) (1-6 months old), using full-length 16S rRNA gene sequencing. The Wilcoxon test was used to analyze the relative abundance of bacteria by phylum, family, genus, and species between groups; microbial community richness and diversity were compared between the two groups. RESULTS: There were no significant differences in the microbial community richness and diversity between the two groups. At the phylum level, 11 bacterial phyla were found; most sequences belonged to one of the three dominant bacterial phyla - Firmicutes, Proteobacteria, and Bacteroidetes. The top 10 microbes at the phylum, family, and genus levels showed no significant changes in their composition within the gut microbiota between the AD and non-AD groups. A decrease in the ratio of the Streptococcus genus was found in atopic dermatitis group when compared with healthy controls (p=0.048). CONCLUSION: A decrease in the abundance of Streptococcus was found in children with AD. The role of Streptococcus in the development of AD needs to be confirmed in a large cohort study.

Hydrogen Evolution and Oxygen Reduction Reactions in Acidic Media Catalyzed by Pd4 S Decorated N/S Doped Carbon Derived from Pd Coordination Polymer.

The template-free synthesis and the characterization of an active electrocatalyst are performed for both the hydrogen evolution and oxygen reduction reactions in acidic media. In this work, the unique chelation mode of benzene-1,4-dithiocarboxamide (BDCA) is first used to synthesize a novel palladium-BDCA coordination polymer (PdBDCA) as a precursor of palladium sulfide nanoparticles-decorated nitrogen and sulfur doped carbon (Pd4 S-SNC). The newly synthesized PdBDCA and Pd4 S-SNC nanoparticles are characterized using chemical, electrochemical, and surface analysis methods. Notably, the nanoparticles obtained at 700 °C exhibit the remarkable catalytic property for the hydrogen evolution reaction in 0.5 m H2 SO4 , showing the overpotential of 32 mV (vs reversible hydrogen electrode (RHE)) and Tafel slope of 52 mV dec-1 , which are comparable to that of Pt/C. The catalyst also shows a high oxygen reduction activity, offering the half-wave and onset potentials of 0.92 and 0.77 V (vs RHE) in 0.5 m H2 SO4 , with improved methanol tolerance and long-term stability compared with Pt/C. The present study gives a way for the design of excellent electrocatalyst for the energy conversion devices in the corrosive acidic environment.

Sequence characteristics and phylogenetic analysis of H9N2 subtype avian influenza A viruses detected from poultry and the environment in China, 2018.

H9N2 subtype avian influenza A virus (AIV) is a causative agent that poses serious threats to both the poultry industry and global public health. In this study, we performed active surveillance to identify H9N2 AIVs from poultry (chicken, duck, and goose) and the environment of different regions in China, and we phylogenetically characterized the sequences. AIV subtype-specific reverse transcription polymerase chain reaction (RT-PCR) showed that 5.43% (83/1529) samples were AIV positive, and 87.02% (67/77) of which were H9N2 AIVs. Phylogenetic analysis revealed that all H9N2 field viruses belonged to the Y280-like lineage, exhibiting 93.9-100% and 94.6-100% of homology in the hemagglutinin (HA) gene and 94.4-100% and 96.3-100% in the neuraminidase (NA) gene, at the nucleotide (nt) and amino acid (aa) levels, respectively. All field viruses shared relatively lower identities with vaccine strains, ranging from 89.4% to 97.7%. The aa sequence at the cleavage site (aa 333-340) in HA of all the isolated H9N2 AIVs was PSRSSRG/L, which is a characteristic of low pathogenic avian influenza virus (LPAIV). Notably, all the H9N2 field viruses harbored eight glycosylation sites, whereas a glycosylation site 218 NRT was missing and a new site 313 NCS was inserted. All field viruses had NGLMR as their receptor binding sites (RBS) at aa position 224-229, showing high conservation with many recently-isolated H9N2 strains. All H9N2 field isolates at position 226 had the aa Leucine (L), indicating their ability to bind to sialic acid (SA) α, a 2-6 receptor of mammals that poses the potential risk of transmission to humans. Our results suggest that H9N2 AIVs circulating in poultry populations that have genetic variation and the potential of infecting mammalian species are of great significance when monitoring H9N2 AIVs in China.

Challenging a Preconception: Optoacoustic Spectrum Differs from the Optical Absorption Spectrum of Proteins and Dyes for Molecular Imaging.

Optoacoustic (photoacoustic) imaging has seen marked advances in detection and data analysis, but there is less progress in understanding the photophysics of common optoacoustic contrast agents. This gap blocks the development of novel agents and the accurate analysis and interpretation of multispectral optoacoustic images. To close it, we developed a multimodal laser spectrometer (MLS) to enable the simultaneous measurement of optoacoustic, absorbance, and fluorescence spectra. Herein, we employ MLS to analyze contrast agents (methylene blue, rhodamine 800, Alexa Fluor 750, IRDye 800CW, and indocyanine green) and proteins (sfGFP, mCherry, mKate, HcRed, iRFP720, and smURFP). We found that the optical absorption spectrum does not correlate with the optoacoustic spectrum for the majority of the analytes. We determined that for dyes, the transition underlying an aggregation state has more optoacoustic signal generation efficiency than the monomer transition. For proteins we found a favored optoacoustic relaxation that stems from the neutral or zwitterionic chromophores and unreported photoswitching behavior of tdTomato and HcRed. We then crystalized HcRed in its photoswitch optoacoustic state, confirming structurally the change in isomerization with respect to HcReds' fluorescence state. Finally, on the example of the widely used label tdTomato and the dye indocyanine green, we show the importance of correct photophysical (e.g., spectral and kinetic) information as a prerequisite for spectral-unmixing for in vivo imaging.

Multiplexed whole-animal imaging with reversibly switchable optoacoustic proteins.

We introduce two photochromic proteins for cell-specific in vivo optoacoustic (OA) imaging with signal unmixing in the temporal domain. We show highly sensitive, multiplexed visualization of T lymphocytes, bacteria, and tumors in the mouse body and brain. We developed machine learning-based software for commercial imaging systems for temporal unmixed OA imaging, enabling its routine use in life sciences.

Structure-Based Mutagenesis of Phycobiliprotein smURFP for Optoacoustic Imaging.

Photo- or optoacoustics (OA) imaging is increasingly being used as a non-invasive imaging method that can simultaneously reveal structure and function in deep tissue. However, the most frequent transgenic OA labels are current fluorescent proteins that are not optimized for OA imaging. Thus, they lack OA signal strength, and their absorption maxima are positioned at short wavelengths, thus giving small penetration depths and strong background signals. Here, we apply insights from our recent determination of the structure of the fluorescent phycobiliprotein smURFP to mutate a range of residues to promote the nonradiative decay pathway that generates the OA signal. We identified hydrophobic and aromatic substitutions within the chromophore-binding pocket that substantially increase the intensity of the OA signal and red-shift the absorption. Our results demonstrate the feasibility of structure-based mutagenesis to repurpose fluorescent probes for OA imaging, and they may provide structure-function insights for de novo engineering of transgenic OA probes.

Blood vessel imaging using radiofrequency-induced second harmonic acoustic response.

We introduce a contrast mechanism for visualizing blood vessels based on radiofrequency-induced second harmonic acoustic (RISHA) signals sensing blood conductivity. We develop a novel imaging system using commonly available inexpensive components, and demonstrate in vivo RISHA visualization of blood vessels based on low-power quasi-continuous radiofrequency excitation of tissue at frequencies of a few MHz. We show how the novel approach also implicitly enables radiofrequency-induced passive ultrasound imaging and can be readily applied to non-invasive imaging of blood vessels ex vivo and in vivo. We discuss the implications of non-invasive conductivity measurements in the context of biomedical applications.

Electrolytic conductivity-related radiofrequency heating of aqueous suspensions of nanoparticles for biomedicine.

The development of suitable contrast agents can significantly enhance the efficiency of modern imaging and treatment techniques, such as thermoacoustic (TA) tomography and radio-frequency (RF) hyperthermia of cancer. Here, we examine the heating of aqueous suspensions of silicon (Si) and gold (Au) nanoparticles (NPs) under RF irradiation in the MHz frequency range. The heating rate of aqueous suspensions of Si NPs exhibited non-monotonic dependency on the electrical conductivity of the suspension. The experimental results were explained by the mathematical model considering oscillating solvated ions as the main source of Joule heating. These ions could be the product of the dissolution of Si NPs or organic coating of Au NPs. Thus, the ions governed the conductivity of the suspensions, which in turn governs both the heating rate and the near-field RF TA response. The model predicted the contrast in different tissues taking into account both Joule heating and dielectric losses.