A battery-less wireless implant for the continuous monitoring of vascular pressure, flow rate and temperature.

Devices for monitoring blood haemodynamics can guide the perioperative management of patients with cardiovascular disease. Current technologies for this purpose are constrained by wired connections to external electronics, and wireless alternatives are restricted to monitoring of either blood pressure or blood flow. Here we report the design aspects and performance parameters of an integrated wireless sensor capable of implantation in the heart or in a blood vessel for simultaneous measurements of pressure, flow rate and temperature in real time. The sensor is controlled via long-range communication through a subcutaneously implanted and wirelessly powered Bluetooth Low Energy system-on-a-chip. The device can be delivered via a minimally invasive transcatheter procedure or it can be mounted on a passive medical device such as a stent, as we show for the case of the pulmonary artery in a pig model and the aorta and left ventricle in a sheep model, where the device performs comparably to clinical tools for monitoring of blood flow and pressure. Battery-less and wireless devices such as these that integrate capabilities for flow, pressure and temperature sensing offer the potential for continuous monitoring of blood haemodynamics in patients.

Chemotaxis assay for evaluation of memory-like behavior in wild-type and Alzheimer's-disease-like C. elegans models.

Here, we present an olfactory-dependent chemotaxis assay for evaluating changes in memory-like behavior in both wild-type and Alzheimer's-disease-like C. elegans models. We describe steps for synchronizing and preparing C. elegans populations and for performing isoamyl alcohol conditioning during starvation and chemotaxis assaying. We then detail counting and quantification procedures. This protocol is applicable to mechanistic exploration and drug screening in neurodegenerative diseases and brain aging.

Implications of altered sirtuins in metabolic regulation and oral cancer.

Sirtuins (SIRTs 1-7) are a group of histone deacetylase enzymes with a wide range of enzyme activities that target a range of cellular proteins in the nucleus, cytoplasm, and mitochondria for posttranslational modifications by acetylation (SIRT1, 2, 3, and 5) or ADP ribosylation (SIRT4, 6, and 7). A variety of cellular functions, including mitochondrial functions and functions in energy homeostasis, metabolism, cancer, longevity and ageing, are regulated by sirtuins. Compromised sirtuin functions and/or alterations in the expression levels of sirtuins may lead to several pathological conditions and contribute significantly to alterations in metabolic phenotypes as well as oral carcinogenesis. Here, we describe the basic characteristics of seven mammalian sirtuins. This review also emphasizes the key molecular mechanisms of sirtuins in metabolic regulation and discusses the possible relationships of sirtuins with oral cancers. This review will provide novel insight into new therapeutic approaches targeting sirtuins that may potentially lead to effective strategies for combating oral malignancies.

Wireless, Soft Sensors of Skin Hydration with Designs Optimized for Rapid, Accurate Diagnostics of Dermatological Health.

Accurate measurements of skin hydration are of great interest to dermatological science and clinical practice. This parameter serves as a relevant surrogate of skin barrier function, a key representative benchmark for overall skin health. The skin hydration sensor (SHS) is a soft, skin-interfaced wireless system that exploits a thermal measurement method, as an alternative to conventional impedance-based hand-held probes. This study presents multiple strategies for maximizing the sensitivity and reliability of this previously reported SHS platform. An in-depth analysis of the thermal physics of the measurement process serves as the basis for structural optimizations of the electronics and the interface to the skin. Additional engineering advances eliminate variabilities associated with manual use of the device and with protocols for the measurement. The cumulative effect is an improvement in sensitivity by 135% and in repeatability by 36% over previously reported results. Pilot trials on more than 200 patients in a dermatology clinic validate the practical utility of the sensor for fast, reliable measurements.

High-speed, scanned laser structuring of multi-layered eco/bioresorbable materials for advanced electronic systems.

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin eco/bioresorbable materials of different types of semiconductors, dielectrics, and conductors on flexible substrates. Component-level demonstrations span passive and active devices, including diodes and field-effect transistors. Patterning these devices into interconnected layouts yields functional systems, as illustrated in examples that range from wireless implants as monitors of neural and cardiac activity, to thermal probes of microvascular flow, and multi-electrode arrays for biopotential sensing. These advances create important processing options for eco/bioresorbable materials and associated electronic systems, with immediate applicability across nearly all types of bioelectronic studies.

The effects of epigenetic modifications on bone remodeling in age-related osteoporosis.

PURPOSE: As the population ages, there is an increased risk of fracture and morbidity diseases associated with aging, such as age-related osteoporosis and other bone diseases linked to aging skeletons. RESULTS: Several bone-related cells, including multipotent bone mesenchymal stem cells, osteoblasts that form bone tissue, and osteoclasts that break it down, are in symbiotic relationships throughout life. Growing evidence indicates that epigenetic modifications of cells caused by aging contribute to compromised bone remodeling and lead to osteoporosis. A number of epigenetic mechanisms are at play, including DNA/RNA modifications, histone modifications, microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), as well as chromatin remodeling. CONCLUSION: In this review, we summarized the epigenetic modifications of different bone-related cells during the development and progression of osteoporosis associated with aging. Additionally, we described a compensatory recovery mechanism under epigenetic regulation that may lead to new strategies for regulating bone remodeling in age-related osteoporosis.

Soft shape-programmable surfaces by fast electromagnetic actuation of liquid metal networks.

Low modulus materials that can shape-morph into different three-dimensional (3D) configurations in response to external stimuli have wide-ranging applications in flexible/stretchable electronics, surgical instruments, soft machines and soft robotics. This paper reports a shape-programmable system that exploits liquid metal microfluidic networks embedded in an elastomer matrix, with electromagnetic forms of actuation, to achieve a unique set of properties. Specifically, this materials structure is capable of fast, continuous morphing into a diverse set of continuous, complex 3D surfaces starting from a two-dimensional (2D) planar configuration, with fully reversible operation. Computational, multi-physics modeling methods and advanced 3D imaging techniques enable rapid, real-time transformations between target shapes. The liquid-solid phase transition of the liquid metal allows for shape fixation and reprogramming on demand. An unusual vibration insensitive, dynamic 3D display screen serves as an application example of this type of morphable surface.

A dynamically reprogrammable surface with self-evolving shape morphing.

Dynamic shape-morphing soft materials systems are ubiquitous in living organisms; they are also of rapidly increasing relevance to emerging technologies in soft machines1-3, flexible electronics4,5 and smart medicines6. Soft matter equipped with responsive components can switch between designed shapes or structures, but cannot support the types of dynamic morphing capabilities needed to reproduce natural, continuous processes of interest for many applications7-24. Challenges lie in the development of schemes to reprogram target shapes after fabrication, especially when complexities associated with the operating physics and disturbances from the environment can stop the use of deterministic theoretical models to guide inverse design and control strategies25-30. Here we present a mechanical metasurface constructed from a matrix of filamentary metal traces, driven by reprogrammable, distributed Lorentz forces that follow from the passage of electrical currents in the presence of a static magnetic field. The resulting system demonstrates complex, dynamic morphing capabilities with response times within 0.1 second. Implementing an in situ stereo-imaging feedback strategy with a digitally controlled actuation scheme guided by an optimization algorithm yields surfaces that can follow a self-evolving inverse design to morph into a wide range of three-dimensional target shapes with high precision, including an ability to morph against extrinsic or intrinsic perturbations. These concepts support a data-driven approach to the design of dynamic soft matter, with many unique characteristics.

Environmental determination of spring wheat yield in a climatic transition zone under global warming.

Understanding environmental determination of crop yield plays a critical role in agricultural. management in resource-limited areas. The climatic transition zone was a naturally ideal place to study. the relations between environmental factors and crop yield, due to its large annual variability of climatic factors and high speed of temperature increase under global warming. Our objectives were to identify the most critical environmental factor in determining spring wheat yield and analyze the convergence and divergence of water-yield relations for spring wheat in a typical climatic transition zone (semi-arid area). The study was conducted at two locations, Dingxi and Pengyang in Northwest China, with a long-term experiment (1987-2018) and two short-term irrigation experiments. Meanwhile, data of water use and spring wheat yield was collected from a series of previously published literature in the study area. The highest spring wheat yield was obtained under year pattern with higher soil water content at sowing (SWCS) and lower atmospheric dryness condition (ADC, the difference between reference evapotranspiration and precipitation during spring wheat growing season). SWCS was more important than precipitation during the growing season (PGS) in determining spring wheat yield in the study area. The relations between available water supply, water use, and spring wheat yield were convergence. However, SWCS had an impact on the relationship between yield and PGS and SWCS-yield relation was affected by ADC. We concluded that precipitation in 7 months before sowing was the dominant factor determining spring wheat yield in the climatic transition zone under global warming whereas the impact of high atmospheric evaporative demand resulted from the increasing temperature on crop yields and SWCS-yield relation must be taken into account for the analysis of environmental determination of spring wheat yield.

Amelioration of Alzheimer's disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow.

A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer's disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-ß and tau pathologies, and improved the animals' memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational-experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.

Complex 3D microfluidic architectures formed by mechanically guided compressive buckling.

Microfluidic technologies have wide-ranging applications in chemical analysis systems, drug delivery platforms, and artificial vascular networks. This latter area is particularly relevant to 3D cell cultures, engineered tissues, and artificial organs, where volumetric capabilities in fluid distribution are essential. Existing schemes for fabricating 3D microfluidic structures are constrained in realizing desired layout designs, producing physiologically relevant microvascular structures, and/or integrating active electronic/optoelectronic/microelectromechanical components for sensing and actuation. This paper presents a guided assembly approach that bypasses these limitations to yield complex 3D microvascular structures from 2D precursors that exploit the full sophistication of 2D fabrication methods. The capabilities extend to feature sizes <5 µm, in extended arrays and with various embedded sensors and actuators, across wide ranges of overall dimensions, in a parallel, high-throughput process. Examples include 3D microvascular networks with sophisticated layouts, deterministically designed and constructed to expand the geometries and operating features of artificial vascular networks.

Direct-current generators based on conductive polymers for self-powered flexible devices.

Direct-current generators, especially those based on the Schottky contacts between conductive polymers and metal electrodes, are efficient in converting mechanical stimuli into electrical energy. In contrast to triboelectric and piezoelectric generators, direct-current generators readily produce direct-current outputs and high currents that are crucial for integrating multiple energy-harvesting units in large scale and driving some types of devices. We are focusing on the relationship between Schottky barrier height and performance, systematically investigating the effects of various conductive polymers and electrodes on the outputs by both theoretical simulation and experiments. Tailoring the Schottky barrier height between conductive polymers and metal electrodes is demonstrated a significant approach to design the new DC generators. The preparation method of electrochemical deposition endows the generators flexibility, the linear relationship of current/voltage output vs. strain applied on the generators, combined with the large outputs offer advantages for the generator to work as flexible sensors. Furthermore, a mechanosensation-active matrix array based on direct-current generator for the strain monitoring demonstrated its promising prospects in flexible electronics. The direct-current generators with improved performance could serve as a stream new blood for versatile sensory systems and human-machine interactive interfaces.

DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer's Disease.

DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB, respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM), and Werner syndrome (WS, with most cases caused by mutations in WRN). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD+), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer's disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.

Compliant 3D frameworks instrumented with strain sensors for characterization of millimeter-scale engineered muscle tissues.

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

Rapidly deployable and morphable 3D mesostructures with applications in multimodal biomedical devices.

Structures that significantly and rapidly change their shapes and sizes upon external stimuli have widespread applications in a diversity of areas. The ability to miniaturize these deployable and morphable structures is essential for applications in fields that require high-spatial resolution or minimal invasiveness, such as biomechanics sensing, surgery, and biopsy. Despite intensive studies on the actuation mechanisms and material/structure strategies, it remains challenging to realize deployable and morphable structures in high-performance inorganic materials at small scales (e.g., several millimeters, comparable to the feature size of many biological tissues). The difficulty in integrating actuation materials increases as the size scales down, and many types of actuation forces become too small compared to the structure rigidity at millimeter scales. Here, we present schemes of electromagnetic actuation and design strategies to overcome this challenge, by exploiting the mechanics-guided three-dimensional (3D) assembly to enable integration of current-carrying metallic or magnetic films into millimeter-scale structures that generate controlled Lorentz forces or magnetic forces under an external magnetic field. Tailored designs guided by quantitative modeling and developed scaling laws allow formation of low-rigidity 3D architectures that deform significantly, reversibly, and rapidly by remotely controlled electromagnetic actuation. Reconfigurable mesostructures with multiple stable states can be also achieved, in which distinct 3D configurations are maintained after removal of the magnetic field. Demonstration of a functional device that combines the deep and shallow sensing for simultaneous measurements of thermal conductivities in bilayer films suggests the promising potential of the proposed strategy toward multimodal sensing of biomedical signals.

Three-dimensional, multifunctional neural interfaces for cortical spheroids and engineered assembloids.

Three-dimensional (3D), submillimeter-scale constructs of neural cells, known as cortical spheroids, are of rapidly growing importance in biological research because these systems reproduce complex features of the brain in vitro. Despite their great potential for studies of neurodevelopment and neurological disease modeling, 3D living objects cannot be studied easily using conventional approaches to neuromodulation, sensing, and manipulation. Here, we introduce classes of microfabricated 3D frameworks as compliant, multifunctional neural interfaces to spheroids and to assembloids. Electrical, optical, chemical, and thermal interfaces to cortical spheroids demonstrate some of the capabilities. Complex architectures and high-resolution features highlight the design versatility. Detailed studies of the spreading of coordinated bursting events across the surface of an isolated cortical spheroid and of the cascade of processes associated with formation and regrowth of bridging tissues across a pair of such spheroids represent two of the many opportunities in basic neuroscience research enabled by these platforms.

Synergistic effects of D-arginine, D-methionine and D-histidine against Porphyromonas gingivalis biofilms.

Porphyromonas gingivalis biofilms are implicated in the pathology of peri-implantitis and periodontitis. In this study, D-arginine (R), D-methionine (M), D-histidine (H), and a mixture of these D-amino acids (D-AAs) were investigated as an effective therapeutic strategy against P. gingivalis biofilms. The bacterial growth activity and minimum inhibitory concentrations were determined for each D-AA, along with the effects of the D-AAs mixture on biofilm development, morphology, structure, extracellular polysaccharides (EPS), cytotoxicity towards commensals, and bacterial structure. The D-AA mixture delayed the proliferation of P. gingivalis, changed its membrane structure, and decreased biofilm thickness and integrity, as compared with individual D-AAs. The EPS content increased with the concentration of D-AAs. The present study shows that a 4 mM RMH, triple D-AA mixture, enhanced deleterious effects on P. gingivalis biofilms without any cytotoxicity compared with individual D-AAs, thus providing a new strategy for the treatment of peri-implantitis and periodontitis.

Wireless, soft electronics for rapid, multisensor measurements of hydration levels in healthy and diseased skin.

Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.

The role of the microbiome in drug resistance in gastrointestinal cancers.

Introduction: The microbiota is recognized for its impact on both human health and disease. The human microbiota is made up of trillions of cells, including bacteria, viruses, and fungi. The largest population of microbes reside in the gut, prompting research for better understanding of the impact of gastrointestinal microbiota in different diseases. Evidence from numerous studies has pointed out the role of commensal microbes as key determinants of cancer pathogenesis. Moreover, gut microbiota may play an important role in chemoresistance; consequently, this knowledge might be important for novel strategies to improve anticancer treatment efficacy.Areas covered: We describe the role of microbiota in different gastrointestinal cancer types (esophageal, gastric, colorectal, hepatocellular and pancreatic-biliary tract cancers). Moreover, we analyzed the impact of the microbiota on resistance to anticancer therapies, and, lastly, we focused on possibilities of microbiota modulation to enhance anticancer therapy efficacy.Expert opinion: Increasing evidence shows that gut microbiota might influence resistance to anticancer treatment, including conventional chemotherapy, immunotherapy, radiotherapy, and surgery. Therefore, a better knowledge of gut microbiota and its interactions with anticancer drugs will enable us to develop novel anticancer treatment strategies and subsequently improve the cancer patients' outcome.

Reliable, low-cost, fully integrated hydration sensors for monitoring and diagnosis of inflammatory skin diseases in any environment.

Present-day dermatological diagnostic tools are expensive, time-consuming, require substantial operational expertise, and typically probe only the superficial layers of skin (~15 µm). We introduce a soft, battery-free, noninvasive, reusable skin hydration sensor (SHS) adherable to most of the body surface. The platform measures volumetric water content (up to ~1 mm in depth) and wirelessly transmits data to any near-field communication-compatible smartphone. The SHS is readily manufacturable, comprises unique powering and encapsulation strategies, and achieves high measurement precision (±5% volumetric water content) and resolution (±0.015°C skin surface temperature). Validation on n = 16 healthy/normal human participants reveals an average skin water content of ~63% across multiple body locations. Pilot studies on patients with atopic dermatitis (AD), psoriasis, urticaria, xerosis cutis, and rosacea highlight the diagnostic capability of the SHS (P AD = 0.0034) and its ability to study impact of topical treatments on skin diseases.