Transcranial volumetric imaging using a conformal ultrasound patch.

Accurate and continuous monitoring of cerebral blood flow is valuable for clinical neurocritical care and fundamental neurovascular research. Transcranial Doppler (TCD) ultrasonography is a widely used non-invasive method for evaluating cerebral blood flow1, but the conventional rigid design severely limits the measurement accuracy of the complex three-dimensional (3D) vascular networks and the practicality for prolonged recording2. Here we report a conformal ultrasound patch for hands-free volumetric imaging and continuous monitoring of cerebral blood flow. The 2 MHz ultrasound waves reduce the attenuation and phase aberration caused by the skull, and the copper mesh shielding layer provides conformal contact to the skin while improving the signal-to-noise ratio by 5 dB. Ultrafast ultrasound imaging based on diverging waves can accurately render the circle of Willis in 3D and minimize human errors during examinations. Focused ultrasound waves allow the recording of blood flow spectra at selected locations continuously. The high accuracy of the conformal ultrasound patch was confirmed in comparison with a conventional TCD probe on 36 participants, showing a mean difference and standard deviation of difference as -1.51 ± 4.34 cm s-1, -0.84 ± 3.06 cm s-1 and -0.50 ± 2.55 cm s-1 for peak systolic velocity, mean flow velocity, and end diastolic velocity, respectively. The measurement success rate was 70.6%, compared with 75.3% for a conventional TCD probe. Furthermore, we demonstrate continuous blood flow spectra during different interventions and identify cascades of intracranial B waves during drowsiness within 4 h of recording.

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

A fully integrated wearable ultrasound system to monitor deep tissues in moving subjects.

Recent advances in wearable ultrasound technologies have demonstrated the potential for hands-free data acquisition, but technical barriers remain as these probes require wire connections, can lose track of moving targets and create data-interpretation challenges. Here we report a fully integrated autonomous wearable ultrasonic-system-on-patch (USoP). A miniaturized flexible control circuit is designed to interface with an ultrasound transducer array for signal pre-conditioning and wireless data communication. Machine learning is used to track moving tissue targets and assist the data interpretation. We demonstrate that the USoP allows continuous tracking of physiological signals from tissues as deep as 164 mm. On mobile subjects, the USoP can continuously monitor physiological signals, including central blood pressure, heart rate and cardiac output, for as long as 12 h. This result enables continuous autonomous surveillance of deep tissue signals toward the internet-of-medical-things.

CAZymes-associated method to explore glycans that mitigate DSS-induced colitis via targeting Bacteroides cellulosilyticus.

Improving Bacteroides cellulosilyticus abundance is a feasible approach to treating inflammatory bowel disease (IBD). Although B. cellulosilyticus is responsive to dietary components, untargeted manipulation cannot focus on target microbe and lead to an increase in harmful bacteria in the microbiota. Breakthroughs in methods for regulating specific microbes, but the protocols are expensive, time-consuming, and difficult to follow. Glycans based on microbial-carbohydrate-active enzymes (CAZymes) would provide a potential solution. We propose a method based on CAZymes to explore polysaccharides that target specific gut microbes and alleviate diseases. The designed polysaccharides (Arabinogalactan, AG) enrich the abundance of B. cellulosilyticus in single-strain co-cultures, fermentation in vitro, and mouse models in vivo. Supplementation with AG relieved mice from colitis and clinical symptoms. We reveal that AG directly alters B. cellulosilyticus level and cooperative microbes, resulting in remission of colitis. Our glycan design pipeline is a promising way to improve disease through the targeted enhancement of specific microbes.

Predicting Personalized Diets Based on Microbial Characteristics between Patients with Superficial Gastritis and Atrophic Gastritis.

BACKGROUND: gastritis is a common stomach disease with a high global incidence and can potentially develop into gastric cancer. The treatment of gastritis focuses on medication or diets based on national guidelines. However, the specific diet that can alleviate gastritis remains largely unknown. METHODS: we propose a microbiota-directed dietary strategy that investigates potential food factors using microbial exogenous metabolites. Given the current lack of understanding of the repeatable characteristics of gastric microbiota, we conducted a meta-analysis to identify the features of gastric bacteria. Local samples were collected as validation cohorts. Furthermore, RevEcoR was employed to identify bacteria's exogenous metabolites, and FooDB was used to retrieve foods that can target specific bacteria. RESULTS: Bacteroides, Weissella, Actinomyces, Atopobium, Oribacterium, Peptostreptococcus, and Rothia were biomarkers between superficial gastritis (SG) and atrophic gastritis (AG) (AG_N) without H. pylori infection, whereas Bacillus, Actinomyces, Cutibacterium, Helicobacter, Novosphingobium, Pseudomonas, and Streptococcus were signatures between SG and AG (AG_P) with H. pylori infection. According to the exogenous metabolites, adenosyloobalamin, soybean, common wheat, dates, and barley were regarded as potential candidates for AG_N treatment, while gallate was regarded as a candidate for AG_P treatment. CONCLUSIONS: this study firstly profiled the gastric microbiota of AG and SG with or without H. pylori and provided a recommended diet for global AG according to exogenous metabolites.

Food and drug design for gut microbiota-directed regulation: Current experimental landscape and future innovation.

Most diets and medications enhance host health via microbiota-dependent ways, but it is in the present situation of untargeted regulation. Non-targeted regulation may lead to the ineffectiveness of dietary supplements or drug treatment. Microbiota-directed food, aiming to improve diseases by targeting specific microbes without affecting other bacteria, have been proposed to deal with this problem. However, there is currently no universally applicable method to explore such foods or drugs. In this review, thirty studies on recent efforts in microbiota directed diets and medications are summarized from various databases. The methods used to find new foods and medications are primarily divided into four groups depending on the experimental models: in vivo and in vitro, as well as predictions based on bioinformatics. We also discuss their implementation, interpretation, and respective limitations, and describe the present situation. We further put forward a framework for microbiota-directed foods and medicine according to above methods and other microbiome manipulation, which will spur precision medicine.

Stretchable ultrasonic arrays for the three-dimensional mapping of the modulus of deep tissue.

Serial assessment of the biomechanical properties of tissues can be used to aid the early detection and management of pathophysiological conditions, to track the evolution of lesions and to evaluate the progress of rehabilitation. However, current methods are invasive, can be used only for short-term measurements, or have insufficient penetration depth or spatial resolution. Here we describe a stretchable ultrasonic array for performing serial non-invasive elastographic measurements of tissues up to 4 cm beneath the skin at a spatial resolution of 0.5 mm. The array conforms to human skin and acoustically couples with it, allowing for accurate elastographic imaging, which we validated via magnetic resonance elastography. We used the device to map three-dimensional distributions of the Young's modulus of tissues ex vivo, to detect microstructural damage in the muscles of volunteers before the onset of soreness and to monitor the dynamic recovery process of muscle injuries during physiotherapies. The technology may facilitate the diagnosis and treatment of diseases affecting tissue biomechanics.

Skin-interfaced electronics: A promising and intelligent paradigm for personalized healthcare.

Skin-interfaced electronics (skintronics) have received considerable attention due to their thinness, skin-like mechanical softness, excellent conformability, and multifunctional integration. Current advancements in skintronics have enabled health monitoring and digital medicine. Particularly, skintronics offer a personalized platform for early-stage disease diagnosis and treatment. In this comprehensive review, we discuss (1) the state-of-the-art skintronic devices, (2) material selections and platform considerations of future skintronics toward intelligent healthcare, (3) device fabrication and system integrations of skintronics, (4) an overview of the skintronic platform for personalized healthcare applications, including biosensing as well as wound healing, sleep monitoring, the assessment of SARS-CoV-2, and the augmented reality-/virtual reality-enhanced human-machine interfaces, and (5) current challenges and future opportunities of skintronics and their potentials in clinical translation and commercialization. The field of skintronics will not only minimize physical and physiological mismatches with the skin but also shift the paradigm in intelligent and personalized healthcare and offer unprecedented promise to revolutionize conventional medical practices.

Nakagami statistics-based photoacoustic spectroscopy used for label-free assessment of bone tissue.

Quick identification of abnormal molecular metabolism of bone tissues is challenging. Photoacoustic (PA) spectroscopy techniques have great potential in molecular imaging. However, most of them are amplitude-dependent and easily affected by the light deposition, especially for bone tissues with high optical scattering. In this Letter, we propose a Nakagami statistics-based PA spectroscopy (NSPS) method for characterizing molecules in bone tissues. We indicate that the NSPS curve can intelligently identify changes in the content of molecules in bone tissues, with a high disturbance-resisting ability. The NSPS has remarkable potential for use in the early and rapid detection of bone diseases.

A wearable cardiac ultrasound imager.

Continuous imaging of cardiac functions is highly desirable for the assessment of long-term cardiovascular health, detection of acute cardiac dysfunction and clinical management of critically ill or surgical patients1-4. However, conventional non-invasive approaches to image the cardiac function cannot provide continuous measurements owing to device bulkiness5-11, and existing wearable cardiac devices can only capture signals on the skin12-16. Here we report a wearable ultrasonic device for continuous, real-time and direct cardiac function assessment. We introduce innovations in device design and material fabrication that improve the mechanical coupling between the device and human skin, allowing the left ventricle to be examined from different views during motion. We also develop a deep learning model that automatically extracts the left ventricular volume from the continuous image recording, yielding waveforms of key cardiac performance indices such as stroke volume, cardiac output and ejection fraction. This technology enables dynamic wearable monitoring of cardiac performance with substantially improved accuracy in various environments.

The regulatory effects of specific polyphenols on Akkermansia are dependent on uridine.

We examined the microbial regulatory capacity of four polyphenols with different structure in healthy mice and explore the mechanism according to exogenous metabolites and microbial metabolites. Oral administration of four polyphenols, including caffeic acid (CA), procyanidin (PA), puerarin (Pue), and resveratrol (Res), did not lead to metabolic disorder in healthy mice. Gut microbiota analysis revealed that CA, PA, and Pue administration significantly enhanced the abundance of Akkermansia and Ruminococcaceae UCG-014 while Res supplement mainly promoted the growth of Lactobacillus and Bacteroides. Furthermore, correlation analysis and exogenous metabolite prediction revealed that the effects of polyphenols, including CA, PA, and Pue, on Akkermansia have strong relationship with uridine while the regulation of Res on microbiota might be dependent on the decrease on petroselinic acid. These investigations considerably suggest the importance of exploration of exogenous metabolites and reveal the similarity of effects of polyphenols on microbiota and metabolites.

A Breathable, Passive-Cooling, Non-Inflammatory, and Biodegradable Aerogel Electronic Skin for Wearable Physical-Electrophysiological-Chemical Analysis.

Real-time monitoring of human health can be significantly improved by designing novel electronic skin (E-skin) platforms that mimic the characteristics and sensitivity of human skin. A high-quality E-skin platform that can simultaneously monitor multiple physiological and metabolic biomarkers without introducing skin discomfort or irritation is an unmet medical need. Conventional E-skins are either monofunctional or made from elastomeric films that do not include key synergistic features of natural skin, such as multi-sensing, breathability, and thermal management capabilities in a single patch. Herein, a biocompatible and biodegradable E-skin patch based on flexible gelatin methacryloyl aerogel (FGA) for non-invasive and continuous monitoring of multiple biomarkers of interest is engineered and demonstrated. Taking advantage of cryogenic temperature treatment and slow polymerization, FGA is fabricated with a highly interconnected porous structure that displays good flexibility, passive-cooling capabilities, and ultra-lightweight properties that make it comfortable to wear for long periods of time. It also provides numerous permeable capillary channels for thermal-moisture transfer, ensuring its excellent breathability. Therefore, the engineered FGA-based E-skin can simultaneously monitor body temperature, hydration, and biopotentials via electrophysiological sensors and detect glucose, lactate, and alcohol levels via electrochemical sensors. This work offers a previously unexplored materials strategy for next-generation E-skin platforms with superior practicality.

A photoacoustic patch for three-dimensional imaging of hemoglobin and core temperature.

Electronic patches, based on various mechanisms, allow continuous and noninvasive monitoring of biomolecules on the skin surface. However, to date, such devices are unable to sense biomolecules in deep tissues, which have a stronger and faster correlation with the human physiological status than those on the skin surface. Here, we demonstrate a photoacoustic patch for three-dimensional (3D) mapping of hemoglobin in deep tissues. This photoacoustic patch integrates an array of ultrasonic transducers and vertical-cavity surface-emitting laser (VCSEL) diodes on a common soft substrate. The high-power VCSEL diodes can generate laser pulses that penetrate >2 cm into biological tissues and activate hemoglobin molecules to generate acoustic waves, which can be collected by the transducers for 3D imaging of the hemoglobin with a high spatial resolution. Additionally, the photoacoustic signal amplitude and temperature have a linear relationship, which allows 3D mapping of core temperatures with high accuracy and fast response. With access to biomolecules in deep tissues, this technology adds unprecedented capabilities to wearable electronics and thus holds significant implications for various applications in both basic research and clinical practice.

Antioxidant and anti-aging activities of Laminaria japonica polysaccharide in Caenorhabditis elegans based on metabonomic analysis.

In this study, Laminaria japonica polysaccharide (LJP) was measured in vitro against three antioxidant indicators: DPPH, ABTS, and hydroxyl. In vivo, LJP investigated thermal tolerance, H2O2-induced oxidative stress tolerance, and lipofuscin in Caenorhabditis elegans (C. elegans). Following that, after LJP treatment, the effects and underlying mechanisms were investigated at the mRNA and metabolite levels. We discovered the free radical scavenging activity of LJP. The thermal tolerance of C. elegans improved significantly, lowering levels of malondialdehyde, lipofuscin, and reactive oxygen species. Upregulation of Glp-1, Daf-16, Skn-1, and Sod-3 expression and downregulation of Age-1 and Daf-2 expression increased the ability to resist oxidative stress. Metabolomic analysis revealed that LJP promoted alanine, aspartate, and glutamate metabolism, the TCA cycle, butanoate metabolism, and the FOXO signaling pathway expression, resulting in significant changes in (R)-3-hydroxybutyric acid, palmitic acid, L-glutamic acid, L-malic acid, and oleic acid. The present study shows that LJP, as a functional food, has the potential to boost antioxidant capacity and delay aging.

Advances in fucoxanthin chemistry and management of neurodegenerative diseases.

BACKGROUND: Neurodegenerative diseases are chronic, currently incurable, diseases of the elderly, which are characterized by protein misfolding and neuronal damage. Fucoxanthin, derived from marine brown algae, presents a promising candidate for the development of effective therapeutic strategies. HYPOTHESIS AND PURPOSE: The relationship between neurodegenerative disease management and fucoxanthin has not yet been clarified. This study focuses on the fundamental mechanisms and targets of fucoxanthin in Alzheimer's and Parkinson's disease management, showing that communication between the brain and the gut contributes to neurodegenerative diseases and early diagnosis of ophthalmic diseases. This paper also presents, new insights for future therapeutic directions based on the integrated application of artificial intelligence. CONCLUSION: Fucoxanthin primarily binds to amyloid fibrils with spreading properties such as Aß, tau, and α-synuclein to reduce their accumulation levels, alleviate inflammatory factors, and restore mitochondrial membranes to prevent oxidative stress via Nrf2 and Akt signaling pathways, involving reduction of specific secretases. In addition, fucoxanthin may serve as a preventive diagnosis for neurodegenerative diseases through ophthalmic disorders. It can modulate gut microbes and has potential for the alleviation and treatment of neurodegenerative diseases.

Metabolomics and biochemical insights on the regulation of aging-related diabetes by a low-molecular-weight polysaccharide from green microalga Chlorella pyrenoidosa.

Globally, aging and diabetes are considered prevalent threats to human health. Chlorella pyrenoidosa polysaccharide (CPP) is a natural active ingredient with multiple health benefits including antioxidant and hypolipidemic activities. In this study, the aging-related diabetic (AD) mice model was established to investigate the underlying hypoglycemic and antioxidant mechanisms of CPP. It improved superoxide dismutase, catalase (CAT), glutathione peroxidase (GSH-px), and malondialdehyde activities in liver and insulin secretion. CAT and GSH-px activity in the brain increased after CPP administration. In addition, through histopathological examinations, it was evident that injuries in the liver, brain, jejunum, and pancreas were restored by CPP. This restoration was likely mediated via the activation of glucagon-like peptide-1 receptor/FOXO-1 (forkhead box O1) pathway concurrent with the inhibition of interleukin-6 receptor/FOXO-1 pathway. Furthermore, metabolomics and correlation analysis revealed that CPP possibly relived AD through changes in insulin levels and declined oxidative stress as regulated by phenylpyruvic acid. These findings suggested that CPP exerted antioxidant and hypoglycemic roles in an AD mice model, thereby providing a sound scientific foundation for further development and utilization of CPP.

Fucosylated oligosaccharide Lacto-N-fucopentaose I ameliorates enterovirus 71 infection by inhibiting apoptosis.

Enterovirus 71 (EV71) is the main cause of hand, foot and mouth disease that results in high rates of severe diseases in small children. Lacto-N-fucopentaose I (LNFPI) can inhibit pathogen invasion and regulate intestinal flora. However, whether LNFPI inhibits EV71 infection remains unknown. In this study, we examined the effect and mechanism of LNFPI against EV71. LNFPI reduced capsid protein VP1 to block virus adsorption, inhibited cyclin E transcription and promoted CDK2 expression in EV71-induced human rhabdomyosarcoma cells, thereby causing virus-induced S phase arrest and inhibiting death receptor and mitochondria-induced apoptosis. The effects of LNFPI on apoptosis were further confirmed in Caenorhabditis elegans. The correlation analysis revealed that LNFPI inhibited cell apoptosis by reducing the abundance of Sphingomonas, Stenotrophomonas and Achromatic, which are associated with pro-apoptotic genes in C. elegans, and by increasing the abundance of Micromonospora, which is related to apoptotic inhibition. These findings lead to further recommendations for LNFPI supplementation in infant formula, as it could offer antiviral benefits to formula-fed infants.

Bi-Needle PELD with Intra-Discal Irrigation Technique for the Management of Lumbar Disc Herniation.

BACKGROUND: Lumbar disc herniation (LDH) is the most common cause of sciatica. Percutaneous endoscopic discectomy (PELD) is indicated when conservative treatments fail, which has been proved effective. During conventional PELD, ruptured discs and loose fragments inside discs are removed as much as possible to guarantee a lower reherniation rate, but it inevitably would lead to deterioration of disc degeneration and loss of disc height after PELD. Ensuring sufficient decompression while alleviating the post-operation disc degeneration process is still a clinical problem. OBJECTIVE: To evaluate the imaging and clinical outcomes of bi-needle PELD with intradiscal irrigation technique for the treatment of lumbar disc herniation (LDH). STUDY DESIGN: Multicenter retrospective cohort study. SETTING: Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China. METHODS: A total of 48 patients who underwent bi-needle PELD (B-PELD) or conventional-PELD (C-PELD) for LDH in our 2 spine centers were included in this study. There were 26 cases in the C-PELD group (male 12 cases, female 14 cases) with an average age of 34.6 ± 6.8 years. And there were 22 patients in the B-PELD group (male 10 cases, female 12 cases) with an average age of 35.1 ± 6.4 years. The difference in postoperative disc degeneration (Pfirrmann grades, disc-vertebra height ratios [D-V H ratios]), visual analog scale (VAS) of low back pain, and reoperation rates were compared between the 2 groups. RESULTS: There was no significant difference in gender, age, disease duration, and surgical level between the 2 groups (P > 0.05). The postoperative VAS of back pain was 2.31 ± 0.53 for the C-PELD group and 0.63 ± 0.74 for the B-PELD group; the difference was significant (P = 0.013). The difference between the preoperative and postoperative D-V H ratios in the C-PELD group was significant (P < 0.0001), while it was not significant in the B-PELD group (P = 0.6708). The difference between the loss of D-V H ratios after surgery was significant between the 2 groups (P = 0.0003). The loss of D-V H ratios was higher in the C-PELD group. The difference between the preoperative and postoperative Pfirrmann grades in the B-PELD group was not significant (P = 0.7261); however, it was significant in the C-PELD group (P = 0.0012). The reoperation rate in the C-PELD group was 7.7%, and the reoperation rate in the B-PELD group was 4.5%; the difference was not significant (P = 1). LIMITATIONS: This study employed a retrospective design, and its inherent selection bias and limited statistical power should be considered. CONCLUSIONS: Bi-needle technique with saline irrigation maneuver showed a significant advantage of restoration of disc height and amelioration of disc degeneration compared to conventional PELD surgery.

Treponema primitia α1-2-fucosyltransferase-catalyzed one-pot multienzyme synthesis of fucosylated oligosaccharide lacto-N-fucopentaose I with antiviral activity against enterovirus 71.

Fucosylated oligosaccharides have important biological functions as well as an excellent antiviral activity. A novel α 1-2-fucosyltransferase (α 2FT) from Treponema primitia (Tp2FT) was cloned and expressed in Escherichia coli BL21(DE3) and purified as an N-His6-tagged fusion protein (His6-Tp2FT). Mass spectrometry was carried out to identify the products of enzymatic reaction. The Tp2FT exhibited strict acceptor substrate specificity for type 1 structure (Galß1-3GlcNAc)-containing glycans. It might be a promising emzyme for the chemo-enzymatic synthesis of lacto-N-fucopentaose I (LNFP I), which is one of the important fucosylated oligosaccharides. In this study, different in vitro experiments were used to study the biological activities of LNFP I. It could reduce the concentrations of inflammatory cytokines and effectively inhibit the synthesis of enterovirus 71 proliferation. LNFP I was an inhibitor of enterovirus 71 in the early stages of infection, it can used in infant nutrition and might provide a new drug for hand foot mouth disease.

Effects of alkaloid-rich extracts obtained from Grifola frondosa on gut microbiota and glucose homeostasis in rats.

Grifola frondosa (GF), also known as maitake (a type of mushroom), has been widely used as a food item and it exhibits various health-beneficial hypoglycemic activities. Rats fed with a fat/high-sucrose-based diet were used to determine the hypoglycemic activity of 95% and 55% GF ethanol extracts (labeled as GF95 and GF55, respectively). The activity was determined by monitoring the fasting blood glucose level. Oral glucose tolerance tests were conducted, and the levels of alanine aminotransferase and aspartate aminotransferase were studied to study the hypoglycemic activity. The HPLC-ESI-TOF-MS technique was used to analyze the samples, and the results revealed that alkaloids were present in abundance in GF95 and GF55. It was also observed that GF55 contained some organic acids and GF95 contained extra small amounts of phenoloid. The levels of intestinal microbiota were analyzed, and the results from transcriptome analysis indicated that GF55 reduced the relative abundance of Romboutsia and affected RT-Db1, thereby improving the extent of glucose metabolism achieved. GF95 downregulated the mRNA level of Socs1 by increasing the levels of Oscillibacter, Butyricimonas, Barnesiella, Turicibacter, Methanosphaera, Asaccharobacter, Globicatella, Bifidobacterium, Allobaculum, and Romboutsia. The expression of Pik3rl was upregulated when the levels of Ruminococcus and Saccharibacteria increased. The hypoglycemic activity was induced under these conditions. The obtained data indicated that the efficiency of GF95 to control glucose levels was higher than the efficiency of GF55. This suggested that GF95 can be potentially used to protect against hyperglycemia.