Self-powered, light-controlled, bioresorbable platforms for programmed drug delivery.

Degradable polymer matrices and porous scaffolds provide powerful mechanisms for passive, sustained release of drugs relevant to the treatment of a broad range of diseases and conditions. Growing interest is in active control of pharmacokinetics tailored to the needs of the patient via programmable engineering platforms that include power sources, delivery mechanisms, communication hardware, and associated electronics, most typically in forms that require surgical extraction after a period of use. Here we report a light-controlled, self-powered technology that bypasses key disadvantages of these systems, in an overall design that is bioresorbable. Programmability relies on the use of an external light source to illuminate an implanted, wavelength-sensitive phototransistor to trigger a short circuit in an electrochemical cell structure that includes a metal gate valve as its anode. Consequent electrochemical corrosion eliminates the gate, thereby opening an underlying reservoir to release a dose of drugs by passive diffusion into surrounding tissue. A wavelength-division multiplexing strategy allows release to be programmed from any one or any arbitrary combination of a collection of reservoirs built into an integrated device. Studies of various bioresorbable electrode materials define the key considerations and guide optimized choices in designs. In vivo demonstrations of programmed release of lidocaine adjacent the sciatic nerves in rat models illustrate the functionality in the context of pain management, an essential aspect of patient care that could benefit from the results presented here.

Development towards high-resolution kHz-speed rotation-free volumetric imaging.

X-ray multi-projection imaging (XMPI) has the potential to provide rotation-free 3D movies of optically opaque samples. The absence of rotation enables superior imaging speed and preserves fragile sample dynamics by avoiding the centrifugal forces introduced by conventional rotary tomography. Here, we present our XMPI observations at the ID19 beamline (ESRF, France) of 3D dynamics in melted aluminum with 1000 frames per second and 8 µm resolution per projection using the full dynamical range of our detectors. Since XMPI is a method under development, we also provide different tests for the instrumentation of up to 3000 frames per second. As the high-brilliance of 4th generation light-sources becomes more available, XMPI is a promising technique for current and future X-ray imaging instruments.

Co-encapsulation of curcumin and anthocyanins in bovine serum album-fucoidan nanocomplex with a two-step pH-driven method.

BACKGROUND: Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide-protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)-fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. RESULTS: Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ⁓ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA-FUC nanocomplex was pH-dependent by showing the maximum CUR emission wavelength shifting from 546 nm (CUR-loaded BSA-FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA-FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. CONCLUSION: In summary, the BSA-FUC nanocomposites produced by a two-step pH-driven method could be used for the co-delivery of hydrophilic and hydrophobic nutraceuticals. © 2023 Society of Chemical Industry.

Wireless-Channel Key Distribution Based on Laser Synchronization.

We propose and experimentally demonstrate a wireless-channel key distribution scheme based on laser synchronization induced by a common wireless random signal. Two semiconductor lasers are synchronized under injection of the drive signal after electrical-optical conversion and emit irregular outputs that are used to generate shared keys. Our proof-of-concept experiment using a complex drive signal achieved a secure key generation rate of up to 150 Mbit/s with a bit error rate below 3.8 × 10-3. Numerical simulation results show that the proposed scheme has the potential to achieve a distribution distance of several hundred meters. It is believed that common-signal-induced laser synchronization paves the way for high-speed wireless physical-layer key distribution.

Interfullerene Electronic Interactions and Excited-State Dynamics in Fullerene Dumbbell Conjugates.

Several dumbbell conjugates featuring M3N@Ih-C80 (M = Sc, Y) and C60 were prepared to systematically investigate interfullerene electronic interactions and excited state dynamics. From electrochemical investigations, we concluded that the redox potentials of our M3N@Ih-C80 (M = Sc, Y) dumbbells depend largely on the interfullerene electronic interactions. Assisted by DFT calculation, the unique role of metal atoms was highlighted. Most importantly, ultrafast spectroscopy experiments revealed symmetry-breaking charge separation in Sc3N@C80-dumbbell to yield an unprecedented (Sc3N@C80)•+-(Sc3N@C80)•- charge separated state. This is, to the best of our knowledge, the first time that symmetry-breaking charge separation following photoexcitation is corroborated in a fullerene system. As such, our work shed light on the significance of interfullerene electronic interactions and their uniqueness for modulating excited state properties.

Online dynamic flat-field correction for MHz microscopy data at European XFEL.

The high pulse intensity and repetition rate of the European X-ray Free-Electron Laser (EuXFEL) provide superior temporal resolution compared with other X-ray sources. In combination with MHz X-ray microscopy techniques, it offers a unique opportunity to achieve superior contrast and spatial resolution in applications demanding high temporal resolution. In both live visualization and offline data analysis for microscopy experiments, baseline normalization is essential for further processing steps such as phase retrieval and modal decomposition. In addition, access to normalized projections during data acquisition can play an important role in decision-making and improve the quality of the data. However, the stochastic nature of X-ray free-electron laser sources hinders the use of standard flat-field normalization methods during MHz X-ray microscopy experiments. Here, an online (i.e. near real-time) dynamic flat-field correction method based on principal component analysis of dynamically evolving flat-field images is presented. The method is used for the normalization of individual X-ray projections and has been implemented as a near real-time analysis tool at the Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) instrument of EuXFEL.

Chaos synchronization of VCSELs with common injection of polarization-random light.

We propose and numerically demonstrate chaos synchronization of two vertical-cavity surface-emitting lasers (VCSELs) induced by common injection of constant-amplitude random-polarization light for physical key distribution. Results show that synchronization is sensitive to polarization rotation of injection light, and synchronization coefficients larger than 0.9 can be achieved as the rotation-degree mismatch is smaller than ±10°. Therefore, polarization rotation degree can serve as a hardware key parameter. Furthermore, each laser's output has no correlation to the constant amplitude of the injected light. Their components with identical polarization state, e.g. x or y polarization of VCSEL, also have low correlation coefficient smaller than 0.2. It is therefore believed that this synchronization scheme can provide a security-enhanced method of physical key distribution.

Security optimization of synchronization in DFB lasers under constant-amplitude random-phase drive light by reducing drive-response correlation.

Common-signal-induced laser synchronization promoted a promising paradigm of high-speed physical key distribution. Constant-amplitude and random-phase (CARP) light was proposed as the common drive signal to enhance security by reducing the correlation between the drive and the laser response in intensity. However, the correlation in light phase is not examined. Here, we numerically reveal that the correlation coefficient of the CARP light phase and the response laser intensity (denoted as CCR-φD) can reach a value close to 0.6. Effects of parameters including optical frequency detuning, and modulation depth and noise bandwidth and transparency carrier density for CARP light generation are investigated in detail. By optimizing the optical frequency, modulation depth, and noise bandwidth, respectively, CCR-φD can be reduced to 0.32, 0.18, and 0.10. In the meantime, CCR-φD can be further reduced through secondary optimizing of parameters. CCR-φD can be further reduced by increasing transparent carrier density provided response laser synchronization is achieved. This work gives a new insight about the laser synchronization induced by common CARP light, and also contributes a suggestion of security improvement for physical key distribution based on laser synchronization.

Physical-layer key distribution based on commonly-driven laser synchronization with random modulation of drive light.

We propose and experimentally demonstrate a physical-layer key distribution scheme using commonly-driven laser synchronization with random modulation of drive light. Two parameter-matched semiconductor lasers injected by a common complex drive light are used as entropy sources for legitimate users. Legitimate users generate their own random signal by randomly time-division multiplexing of two random sequences with a certain duration according to individual control codes, and then independently modulate the drive light. Laser synchronization is achieved during time slots when the modulation sequences of two users are identical, and thus provide highly correlated randomness for extracting random numbers as shared keys. Experimental results show that the random modulation of the drive light reduces the correlation between the drive light and laser outputs. In addition, laser synchronization is sensitive to the modulation delay and then the latter can be used as an additional hardware parameter. These mean that security is enhanced. In addition, the proposed method has a short laser synchronization recovery time of lower than 1.1 ns, meaning a high rate of key distribution. The upper limit of final key rate of 2.55 Gb/s with a criterion of bit error rate of 1.68 × 10-3 is achieved in experiments. Our results provide a promising candidate for protecting the security of optical fiber communication.

Effect of gastrodin against cognitive impairment and neurodegeneration in APP/PS1 mice via regulating gut microbiota-gut-brain axis.

Gastrodin (Gas) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of Gas against cognitive impairment via regulating gut microbiota. APPswe/PSEN1dE9 transgenic (APP/PS1) mice were treated intragastrically with Gas for 4 weeks, and then cognitive deficits, deposits of amyloid-ß (Aß) and phosphorylation of tau were analyzed. The expression levels of insulin-like growth factor-1 (IGF-1) pathway-related proteins, such as cAMP response element-binding protein (CREB), were detected. Meanwhile, gut microbiota composition was evaluated. Our results showed that Gas treatment significantly improved cognitive deficits and Aß deposition in APP/PS1 mice. Moreover, Gas treatment increased the level of Bcl-2 and decreased level of Bax and ultimately inhibited neuronal apoptosis. Gas treatment markedly increased the expression levels of IGF-1 and CREB in APP/PS1 mice. Moreover, Gas treatment improved abnormal composition and structure of gut microbiota in APP/PS1 mice. These findings revealed that Gas actively participated in regulating the IGF-1 pathway to inhibit neuronal apoptosis via the gut-brain axis and that it can be considered a new therapeutic strategy against Alzheimer's disease.

A rapid and label-free platform for virus capture and identification from clinical samples.

Emerging and reemerging viruses are responsible for a number of recent epidemic outbreaks. A crucial step in predicting and controlling outbreaks is the timely and accurate characterization of emerging virus strains. We present a portable microfluidic platform containing carbon nanotube arrays with differential filtration porosity for the rapid enrichment and optical identification of viruses. Different emerging strains (or unknown viruses) can be enriched and identified in real time through a multivirus capture component in conjunction with surface-enhanced Raman spectroscopy. More importantly, after viral capture and detection on a chip, viruses remain viable and get purified in a microdevice that permits subsequent in-depth characterizations by various conventional methods. We validated this platform using different subtypes of avian influenza A viruses and human samples with respiratory infections. This technology successfully enriched rhinovirus, influenza virus, and parainfluenza viruses, and maintained the stoichiometric viral proportions when the samples contained more than one type of virus, thus emulating coinfection. Viral capture and detection took only a few minutes with a 70-fold enrichment enhancement; detection could be achieved with as little as 102 EID50/mL (50% egg infective dose per microliter), with a virus specificity of 90%. After enrichment using the device, we demonstrated by sequencing that the abundance of viral-specific reads significantly increased from 4.1 to 31.8% for parainfluenza and from 0.08 to 0.44% for influenza virus. This enrichment method coupled to Raman virus identification constitutes an innovative system that could be used to quickly track and monitor viral outbreaks in real time.

Programmable Complex Shape Changing of Polysiloxane Main-Chain Liquid Crystalline Elastomers.

Liquid crystal elastomers (LCEs) are shape-morphing materials whose large and reversible shape transformations are caused by the coupling between the mobile anisotropic properties of liquid crystal (LC) units and the rubber elastic of polymer networks. Their shape-changing behaviors under certain stimuli are largely directed by the LC orientation; therefore, various strategies have been developed to spatially modulate the LC alignments. However, most of these methods are limited as they require complex fabrication technologies or have intrinsic limitations in applicability. To address this issue, programmable complex shape changes in some LCE types, such as polysiloxane side-chain LCEs, thiol-acrylate main-chain LCEs, etc., were achieved by using a mechanical alignment programming process coupled with two-step crosslinking. Here, we report a polysiloxane main-chain LCE with programmable 2- and 3D shape-changing abilities that were created by mechanically programming the polydomain LCE with two crosslinking steps. The resulting LCEs exhibited a reversible thermal-induced shape transformation between the initial and programmed shapes due to the two-way memory between the first and second network structures. Our findings expand on the applications of LCE materials in actuators, soft robotics, and smart structures where arbitrary and easily programmed shape morphing is needed.

Regioisomeric Benzidine-Fullerenes: Tuning of the Diverse Hole-Distribution to Influence Charge Separation Patterns.

Understanding the influence of molecular structure on charge distribution and charge separation (CS) provides essential guidance for optoelectronic materials design. Here we propose a regioisomeric strategy to tune the diverse hole-distribution, and probe the influence on CS patterns. Para-, meta- and ortho-substituted benzidine-fullerene, named 1 p, 1 m and 1 o are designed. Following CS, hole-delocalization occurs in 1 p, while hole-localization exists in 1 m and 1 o. The rates of charge separation (4.02×1011  s-1 ) and recombination (9.8×109  s-1 ) of 1 p is about 20 and 12 times faster than 1 m and 1 o, indicating that para-determined delocalization promotes ultrafast CS, while meta- and ortho-generated localization contributes to long-lived CS states. Computational analysis further implies that localization results from the destruction of electronic conjugation for 1 m, and limitation of conformational relaxation for 1 o. Given that the universality and simplicity of regional isomerism, this work opens up new thoughts for molecular design with tunable charge separation patterns.

Exogenously applied spermidine alleviates hypoxia stress in Phyllostachys praecox seedlings via changes in endogenous hormones and gene expression.

BACKGROUND: Hypoxia stress is thought to be one of the major abiotic stresses that inhibits the growth and development of higher plants. Phyllostachys pracecox is sensitive to oxygen and suffers soil hypoxia during cultivation; however, the corresponding solutions to mitigate this stress are still limited in practice. In this study, Spermidine (Spd) was tested for regulating the growth of P. praecox seedlings under the hypoxia stress with flooding. RESULTS: A batch experiment was carried out in seedlings treated with 1 mM and 2 mM Spd under flooding for eight days. Application of 1 mM and 2 mM Spd could alleviate plant growth inhibition and reduce oxidative damage from hypoxia stress. Exogenous Spd significantly (P < 0.05) increased proline, soluble protein content, catalase (CAT), superoxide dismutase (SOD), and S-adenosylmethionine decarboxylase (SAMDC) activity, enhanced abscisic acid (ABA) and indole-3-acetic acid (IAA) content, and reduced ethylene emission, hydrogen peroxide (H2O2), superoxide radical (O2·-) production rate, ACC oxidase (ACO) and ACC synthase (ACS) to protect membranes from lipid peroxidation under flooding. Moreover, exogenous Spd up-regulated the expression of auxin-related genes auxin responsive factor1 (ARF1), auxin1 protein (AUX1), auxin2 protein (AUX2), auxin3 protein (AUX3) and auxin4 protein (AUX4), and down-regulated the expression of ethylene-related ACO and ACS genes during flooding. CONCLUSION: The results indicated that exogenous Spd altered hormone concentrations and the expression of hormone-related genes, thereby protecting the bamboo growth under flooding. Our data suggest that Spd can be used to reduce hypoxia-induced cell damage and improve the adaptability of P. praecox to flooding stress.

Dose-efficient multimodal microscopy of human tissue at a hard X-ray nanoprobe beamline.

X-ray fluorescence microscopy performed at nanofocusing synchrotron beamlines produces quantitative elemental distribution maps at unprecedented resolution (down to a few tens of nanometres), at the expense of relatively long measuring times and high absorbed doses. In this work, a method was implemented in which fast low-dose in-line holography was used to produce quantitative electron density maps at the mesoscale prior to nanoscale X-ray fluorescence acquisition. These maps ensure more efficient fluorescence scans and the reduction of the total absorbed dose, often relevant for radiation-sensitive (e.g. biological) samples. This multimodal microscopy approach was demonstrated on human sural nerve tissue. The two imaging modes provide complementary information at a comparable resolution, ultimately limited by the focal spot size. The experimental setup presented allows the user to swap between them in a flexible and reproducible fashion, as well as to easily adapt the scanning parameters during an experiment to fine-tune resolution and field of view.

X-ray in-line holography and holotomography at the NanoMAX beamline.

Coherent X-ray imaging techniques, such as in-line holography, exploit the high brilliance provided by diffraction-limited storage rings to perform imaging sensitive to the electron density through contrast due to the phase shift, rather than conventional attenuation contrast. Thus, coherent X-ray imaging techniques enable high-sensitivity and low-dose imaging, especially for low-atomic-number (Z) chemical elements and materials with similar attenuation contrast. Here, the first implementation of in-line holography at the NanoMAX beamline is presented, which benefits from the exceptional focusing capabilities and the high brilliance provided by MAX IV, the first operational diffraction-limited storage ring up to approximately 300 eV. It is demonstrated that in-line holography at NanoMAX can provide 2D diffraction-limited images, where the achievable resolution is only limited by the 70 nm focal spot at 13 keV X-ray energy. Also, the 3D capabilities of this instrument are demonstrated by performing holotomography on a chalk sample at a mesoscale resolution of around 155 nm. It is foreseen that in-line holography will broaden the spectra of capabilities of MAX IV by providing fast 2D and 3D electron density images from mesoscale down to nanoscale resolution.

Shot-to-shot flat-field correction at X-ray free-electron lasers.

X-ray free-electron lasers (XFELs) provide high-brilliance pulses, which offer unique opportunities for coherent X-ray imaging techniques, such as in-line holography. One of the fundamental steps to process in-line holographic data is flat-field correction, which mitigates imaging artifacts and, in turn, enables phase reconstructions. However, conventional flat-field correction approaches cannot correct single XFEL pulses due to the stochastic nature of the self-amplified spontaneous emission (SASE), the mechanism responsible for the high brilliance of XFELs. Here, we demonstrate on simulated and megahertz imaging data, measured at the European XFEL, the possibility of overcoming such a limitation by using two different methods based on principal component analysis and deep learning. These methods retrieve flat-field corrected images from individual frames by separating the sample and flat-field signal contributions; thus, enabling advanced phase-retrieval reconstructions. We anticipate that the proposed methods can be implemented in a real-time processing pipeline, which will enable online data analysis and phase reconstructions of coherent full-field imaging techniques such as in-line holography at XFELs.

Microbiota-derived metabolite Indoles induced aryl hydrocarbon receptor activation and inhibited neuroinflammation in APP/PS1 mice.

Gut microbiota alterations might affect the development of Alzheimer's disease (AD) through microbiota-derived metabolites. For example, microbiota-derived Indoles via tryptophan metabolism prevented Aß accumulation and Tau hyperphosphorylation, restored synaptic plasticity, and then promoted the cognitive and behavioral ability of APP/PS1 mice. The imbalanced compositions of Indoles-producing bacteria with tryptophan deficiency were found in male APP/PS1 mice, but the molecular mechanisms remained unclear. Our current study revealed that Indoles (including indole, indole-3-acetic acid and indole-3-propionic acid) upregulated the production of aryl hydrocarbon receptor (AhR), inhibited the activation of the NF-κB signal pathway as well as the formation of the NLRP3 inflammasome, reduced the release of inflammatory cytokines, including TNF-α, IL-6, IL-1ß and IL-18, alleviating the inflammatory response of APP/PS1 mice. These findings demonstrated the roles of Indoles-producing bacteria in activating the AhR pathway to regulate neuroinflammation of AD through gut microbiota-derived Indoles, which implied a novel way for AD treatment.

Optical wavelength selective actuation of dye doped liquid crystalline elastomers by quasi-daylight.

We explore obtaining different photo responses of liquid crystalline elastomer (LCE) materials through modulating the optical wavelengths in order to promote the development of precise photocontrol on LCE actuators, and thus study the effect of light-absorbing dyes with different absorption bands on the selective actuation of LCE materials. The dye-doped LCEs were prepared by incorporating special visible absorber dyes into thiol-acrylate main chain LCE (MC-LCE) matrices. The dyes showed photo actuation performance to LCEs due to the photothermal effects. But, every dye-doped LCE could be effectively actuated by light irradiation whose wavelength was inside its absorption band, but could not be effectively actuated by the light whose wavelength was beyond its absorption band. Wavelength selective actuation effects, no matter actuating deformation or actuating force, could be remarkably demonstrated by these dye-doped LCEs through filtering the same quasi-daylight source to be different wavelength bands. Our work opens up a significant way for the precise and convenient photo actuation of LCE actuators, while expanding the utilization potential of quasi-daylight, and further natural sunlight.

Improving reliability for measuring ST deviation in suspected acute coronary syndrome.

BACKGROUND: Standard 12­lead ECG is used for diagnosis and risk stratification in suspected acute coronary syndrome (ACS) patients. Artifacts have significant impact on the measuring quality, which consequently affect the diagnostic decision. We used a signal quality indicator (SQI) to identify the ECG segments with lower artifact levels which we hypothesized would improve ST measurements. METHODS: The Staff III 12­lead ECG database was used with the ECG segments before balloon inflation (n = 185). SQI scores per second were calculated and a 10-s ECG segment with least noise and artifacts (Clean10) was identified for each minute of recording. The first 10 s of ECG recordings (First10) for each minute were selected as a reference. The Philips DXL™ algorithm was used to measure the ST levels at J-point, +20 ms, +40 ms, +60 ms, and + 80 ms after the J-point. Standard deviations (SDs) for the ST measurements for each of the 185 ECG records were calculated for the Clean10 and for the First10 across records. The resulting SDs for the Clean10 were compared with the SDs for the First10 using the Wilcoxon signed rank test. RESULTS: The results indicated that 1) The SDs for the Clean10 are lower than that of the First10; 2) The SDs for J+20 ms and J+40 ms are lowest among the 5 different measuring points although similar improvement for the Clean10 over the First10 is observed for J+60 ms and J+80 ms as well; 3) The improvement at the J-point was not as high as other ST measurements. CONCLUSIONS: The SQI is demonstrated as an efficient tool to identify the ECG segments with lower artifacts that produce more consistent and reliable ST measurement. The measurements at J+20 ms demonstrated the highest consistency among the five studied measuring points.