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We introduce an improved inert gas bubbling method for solvent deoxygenation, featuring a ventilation path alongside the inert gas inlet to enhance the efficiency and reproducibility. While essential for life, oxygen's reactivity can disrupt scientific and industrial processes by forming unwanted intermediates and deactivating catalysts, necessitating efficient deoxygenation methods. Traditional methods like freeze-pump-thaw (FPT) are effective but time-consuming, require stringent safety measures, and have potential limitations for use with aqueous and biological samples. Our enhanced inert gas bubbling method retains the simplicity and safety of conventional bubbling while achieving FPT-like deoxygenation efficiency, demonstrated by photoluminescence intensity and lifetime measurements in acetonitrile (ACN) and toluene (TOL). Simulations using a simplified kinetic model and the Stern-Volmer equation reveal that the added ventilation pathway reduces oxygen contamination in Ar gas bubbles, improving the deoxygenation efficiency. This method is widely applicable in academic and industrial fields, requiring consistent and efficient solvent deoxygenation., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background/aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis., Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased)., Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites., Conclusion: Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Backrground: Akkermansia muciniphila, a next-generation probiotic, is known as a cornerstone regulating the gut-organ axis in various diseases, but the underlying mechanism remains poorly understood. Here, we revealed the neuronal and antifibrotic effects of A. muciniphila on the gut-liver-brain axis in liver injury., Results: To investigate neurologic dysfunction and characteristic gut microbiotas, we performed a cirrhosis cohort (154 patients with or without hepatic encephalopathy) and a community cognition cohort (80 participants in one region for three years) and validated the existence of cognitive impairment in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic injury mouse model. The effects of the candidate strain on cognition were evaluated in animal models of liver injury. The expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors was accessed in patients with fibrosis (100 patients) according to the fibrosis grade and hepatic venous pressure gradient. The proportion of A. muciniphila decreased in populations with hepatic encephalopathy and cognitive dysfunction. Tissue staining techniques confirmed gut-liver-brain damage in liver injury, with drastic expression of BDNF and serotonin in the gut and brain. The administration of A. muciniphila significantly reduced tissue damage and improved cognitive dysfunction and the expression of BDNF and serotonin. Isolated vagus nerve staining showed a recovery of serotonin expression without affecting the dopamine pathway. Conversely, in liver tissue, the inhibition of injury through the suppression of serotonin receptor (5-hydroxytryptamine 2A and 2B) expression was confirmed. The severity of liver injury was correlated with the abundance of serotonin, BDNF, and A. muciniphila., Conclusions: A. muciniphila, a next-generation probiotic, is a therapeutic candidate for alleviating the symptoms of liver fibrosis and cognitive impairment., (© 2024. The Author(s).)

Despite many recent studies on non-alcoholic fatty liver disease (NAFLD) therapeutics, the optimal treatment has yet to be determined. In this unfinished project, we combined secondary metabolites (SMs) from the gut microbiota (GM) and Hordeum vulgare (HV) to investigate their combinatorial effects via network pharmacology (NP). Additionally, we analyzed GM or barley - signalling pathways - targets - metabolites (GBSTMs) in combinatorial perspectives (HV, and GM). A total of 31 key targets were analysed via a protein-protein interaction (PPI) network, and JUN was identified as the uppermost target in NAFLD. On a bubble plot, we revealed that apelin signalling pathway, which had the lowest enrichment factor antagonize NAFLD. Holistically, we scrutinized GBSTM to identify key components (GM, signalling pathways, targets, and metabolites) associated with the Apelin signalling pathway. Consequently, we found that the primary GMs ( Eubacterium limosum , Eggerthella sp. SDG-2 , Alistipes indistinctus YIT 12060 , Odoribacter laneus YIT 12061 , Paraprevotella clara YIT 11840 , Paraprevotella xylaniphila YIT 11841 ) to ameliorate NAFLD. The molecular docking test (MDT) suggested that tryptanthrin-JUN is an agonist, conversely, dihydroglycitein-HDAC5, 1,3-diphenylpropan-2-ol-NOS1, and (10[(Acetyloxy)methyl]-9-anthryl)methyl acetate-NOS2, which are antagonistic conformers in the apelin signalling pathway. Overall, these results suggest that combination therapy could be an effective strategy for treating NAFLD.

Alcoholic-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) show a high prevalence rate worldwide. As gut microbiota represents current state of ALD and MASLD via gut-liver axis, typical characteristics of gut microbiota can be used as a potential diagnostic marker in ALD and MASLD. Machine learning (ML) algorithms improve diagnostic performance in various diseases. Using gut microbiota-based ML algorithms, we evaluated the diagnostic index for ALD and MASLD. Fecal 16S rRNA sequencing data of 263 ALD (control, elevated liver enzyme [ELE], cirrhosis, and hepatocellular carcinoma [HCC]) and 201 MASLD (control and ELE) subjects were collected. For external validation, 126 ALD and 84 MASLD subjects were recruited. Four supervised ML algorithms (support vector machine, random forest, multilevel perceptron, and convolutional neural network) were used for classification with 20, 40, 60, and 80 features, in which three nonsupervised ML algorithms (independent component analysis, principal component analysis, linear discriminant analysis, and random projection) were used for feature reduction. A total of 52 combinations of ML algorithms for each pair of subgroups were performed with 60 hyperparameter variations and Stratified ShuffleSplit tenfold cross validation. The ML models of the convolutional neural network combined with principal component analysis achieved areas under the receiver operating characteristic curve (AUCs) > 0.90. In ALD, the diagnostic AUC values of the ML strategy (vs. control) were 0.94, 0.97, and 0.96 for ELE, cirrhosis, and liver cancer, respectively. The AUC value (vs. control) for MASLD (ELE) was 0.93. In the external validation, the AUC values of ALD and MASLD (vs control) were > 0.90 and 0.88, respectively. The gut microbiota-based ML strategy can be used for the diagnosis of ALD and MASLD.ClinicalTrials.gov NCT04339725., (© 2024. The Author(s).)

Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues. The resulting benefits in SNR are, however, balanced by significant risks associated with surgically removing these coils or with leaving them in place permanently. As an alternative, here the authors report classes of implantable inductor-capacitor circuits made entirely of bioresorbable organic and inorganic materials. Engineering choices for the designs of an inductor and a capacitor provide the ability to select the resonant frequency of the devices to meet MRI specifications (e.g., 200 MHz at 4.7 T MRI). Such devices enhance the SNR and improve the associated imaging capabilities. These simple, small bioelectronic systems function over clinically relevant time frames (up to 1 month) at physiological conditions and then disappear completely by natural mechanisms of bioresorption, thereby eliminating the need for surgical extraction. Imaging demonstrations in a nerve phantom and a human cadaver suggest that this technology has broad potential for post-surgical monitoring/evaluation of recovery processes., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays., Competing Interests: Competing interests statement:The authors declare no competing interest.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background and Aim: The prevalence and severity of alcoholic liver disease (ALD) are increasing. The incidence of alcohol-related cirrhosis has risen up to 2.5%. This study aimed to identify novel metabolite mechanisms involved in the development of ALD in patients. The use of gut microbiome-derived metabolites is increasing in targeted therapies. Identifying metabolic compounds is challenging due to the complex patterns that have long-term effects on ALD. We investigated the specific metabolite signatures in ALD patients., Methods: This study included 247 patients (heathy control, HC: n = 62, alcoholic fatty liver, AFL; n = 25, alcoholic hepatitis, AH; n = 80, and alcoholic cirrhosis, AC, n = 80) identified, and stool samples were collected. 16S rRNA sequencing and metabolomics were performed with MiSeq sequencer and liquid chromatography coupled to time-of-flight-mass spectrometry (LC-TOF-MS), respectively. The untargeted metabolites in AFL, AH, and AC samples were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Metabolic network classifiers were used to predict the pathway expression of the AFL, AH, and AC stages., Results: The relative abundance of Proteobacteria was increased and the abundance of Bacteroides was decreased in ALD samples (p = 0.001) compared with that in HC samples. Fusobacteria levels were higher in AH samples (p = 0.0001) than in HC samples. Untargeted metabolomics was applied to quantitatively screen 103 metabolites from each stool sample. Indole-3-propionic acid levels are significantly lower in AH and AC (vs. HC, p = 0.001). Indole-3-lactic acid (ILA: p = 0.04) levels were increased in AC samples. AC group showed an increase in indole-3-lactic acid (vs. HC, p = 0.040) level. Compared with that in HC samples, the levels of short-chain fatty acids (SCFAs: acetic acid, butyric acid, propionic acid, iso-butyric acid, and iso-valeric acid) and bile acids (lithocholic acids) were significantly decreased in AC. The pathways of linoleic acid metabolism, indole compounds, histidine metabolism, fatty acid degradation, and glutamate metabolism were closely associated with ALD metabolism., Conclusions: This study identified that microbial metabolic dysbiosis is associated with ALD-related metabolic dysfunction. The SCFAs, bile acids, and indole compounds were depleted during ALD progression., Clinical Trial: Clinicaltrials.gov, number NCT04339725., (© 2023. Asian Pacific Association for the Study of the Liver.)

Modern silicone-based epidermal electronics engineered for body temperature sensing represent a pivotal development in the quest for advancing preventive medicine and enhancing post-surgical monitoring. While these compact and highly flexible electronics empower real-time monitoring in dynamic environments, a noteworthy limitation is the challenge in regulating the infiltration or obstruction of heat from the external environment into the surface layers of these electronics. The study presents a cost-effective temperature sensing solution by embedding wireless electronics in a multi-layered elastomeric composite to meet the dual needs of enhanced thermal insulation for encapsulation in contact with air and improved thermal conductivity for the substrate in contact with the skin. The encapsulating composite benefits from the inclusion of hollow silica microspheres, which reduce the thermal conductivity by 40%, while non-spherical aluminum nitride enhances the thermal conductivity of the substrate by 370%. The addition of particles to the respective composites inevitably leads to an increase in modulus. Two composite elements are engineered to coexist while maintaining a matching low modulus of 3.4 MPa and a stretchability exceeding 30%, all without compromising the optimized thermal properties. Consecutive thermal, electrical, and mechanical characterization confirms the sensor's capacity for precise body temperature monitoring during a single day's lifespan, while also assessing the influence of behavioral factors on body temperature.

Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti-OB efficacy of the non-fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein-protein interaction (PPI), PAF-signaling pathways-targets-compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti-OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1-gamma-tocopherol, PPARA-fucosterol, PPARD-stigmasterol, (PPARG)-fucosterol, (NR1H3)-campesterol, and ILK-alpha-tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its prevalence has increased worldwide in recent years. Additionally, there is a close relationship between MASLD and gut microbiota-derived metabolites. However, the mechanisms of MASLD and its metabolites are still unclear. We demonstrated decreased indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in the feces of patients with hepatic steatosis compared to healthy controls. Here, IPA and IAA administration ameliorated hepatic steatosis and inflammation in an animal model of WD-induced MASLD by suppressing the NF-κB signaling pathway through a reduction in endotoxin levels and inactivation of macrophages. Bifidobacterium bifidum metabolizes tryptophan to produce IAA, and B. bifidum effectively prevents hepatic steatosis and inflammation through the production of IAA. Our study demonstrates that IPA and IAA derived from the gut microbiota have novel preventive or therapeutic potential for MASLD treatment.

Brain-inspired neuromorphic computing systems, based on a crossbar array of two-terminal multilevel resistive random-access memory (RRAM), have attracted attention as promising technologies for processing large amounts of unstructured data. However, the low reliability and inferior conductance tunability of RRAM, caused by uncontrollable metal filament formation in the uneven switching medium, result in lower accuracy compared to the software neural network (SW-NN). In this work, we present a highly reliable CoO x -based multilevel RRAM with an optimized crystal size and density in the switching medium, providing a three-dimensional (3D) grain boundary (GB) network. This design enhances the reliability of the RRAM by improving the cycle-to-cycle endurance and device-to-device stability of the I-V characteristics with minimal variation. Furthermore, the designed 3D GB-channel RRAM (3D GB-RRAM) exhibits excellent conductance tunability, demonstrating high symmetricity (624), low nonlinearity (β LTP /β LTD ∼ 0.20/0.39), and a large dynamic range ( G max / G min ∼ 31.1). The cyclic stability of long-term potentiation and depression also exceeds 100 cycles (10 5 voltage pulses), and the relative standard deviation of G max / G min is only 2.9%. Leveraging these superior reliability and performance attributes, we propose a neuromorphic sensory system for finger motion tracking and hand gesture recognition as a potential elemental technology for the metaverse. This system consists of a stretchable double-layered photoacoustic strain sensor and a crossbar array neural network. We perform training and recognition tasks on ultrasonic patterns associated with finger motion and hand gestures, attaining a recognition accuracy of 97.9% and 97.4%, comparable to that of SW-NN (99.8% and 98.7%).

We intended to identify favourable metabolite(s) and pharmacological mechanism(s) of gut microbiota (GM) for liver regeneration (LR) through network pharmacology. We utilized the gutMGene database to obtain metabolites of GM, and targets associated with metabolites as well as LR-related targets were identified using public databases. Furthermore, we performed a molecular docking assay on the active metabolite(s) and target(s) to verify the network pharmacological concept. We mined a total of 208 metabolites in the gutMGene database and selected 668 targets from the SEA (1,256 targets) and STP (947 targets) databases. Finally, 13 targets were identified between 61 targets and the gutMGene database (243 targets). Protein-protein interaction network analysis showed that AKT1 is a hub target correlated with 12 additional targets. In this study, we describe the potential microbe from the microbiota ( E. coli ), chemokine signalling pathway, AKT1 and myricetin that accelerate LR, providing scientific evidence for further clinical trials.

We comprised metabolites of gut microbiota (GM; endogenous species) and dietary plant-derived natural flavonoids (DPDNFs; exogenous species) were known as potent effectors against non-alcoholic fatty liver disease (NAFLD) via network pharmacology (NP). The crucial targets against NAFLD were identified via GM and DPDNFs. The protein interaction (PPI), bubble chart and networks of GM or natural products- metabolites-targets-key signalling (GNMTK) pathway were described via R Package. Furthermore, the molecular docking test (MDT) to verify the affinity was performed between metabolite(s) and target(s) on a key signalling pathway. On the networks of GNMTK, Enterococcus sp. 45 , Escherichia sp.12 , Escherichia sp.33 and Bacterium MRG-PMF-1 as key microbiota; flavonoid-rich products as key natural resources; luteolin and myricetin as key metabolites (or dietary flavonoids); AKT Serine/Threonine Kinase 1 (AKT1), CF Transmembrane conductance Regulator (CFTR) and PhosphoInositide-3-Kinase, Regulatory subunit 1 (PIK3R1) as key targets are promising components to treat NAFLD, by suppressing cyclic Adenosine MonoPhosphate (cAMP) signalling pathway. This study shows that components (microbiota, metabolites, targets and a key signalling pathway) and DPDNFs can exert combinatorial pharmacological effects against NAFLD. Overall, the integrated pharmacological approach sheds light on the relationships between GM and DPDNFs.

The liver is rich in innate immune cells, such as natural killer (NK) cells, natural killer T cells, and Kupffer cells associated with the gut microbiome. These immune cells are dysfunctional owing to alcohol consumption. However, there is insufficient data on the association between immune cells and gut microbiome in alcoholic liver disease (ALD). Therefore, the purpose of this study was to evaluate the effects of probiotic strains on NK cells in ALD patients. In total, 125 human blood samples [control ( n  = 22), alcoholic hepatitis ( n  = 43), and alcoholic cirrhosis ( n  = 60]) were collected for flow cytometric analysis. C57BL/6J mice were divided into four groups (normal, EtOH-fed, and 2 EtOH+strain groups [ Phocaeicola dorei and Lactobacillus helveticus ]). Lymphocytes isolated from mouse livers were analyzed using flow cytometry. The frequency of NK cells increased in patients with alcoholic hepatitis and decreased in patients with alcoholic cirrhosis. The expression of NKp46, an NK cell-activating receptor, was decreased in patients with alcoholic hepatitis and increased in patients with alcoholic cirrhosis compared to that in the control group. The number of cytotoxic CD56dimCD16 + NK cells was significantly reduced in patients with alcoholic cirrhosis. We tested the effect of oral administration P. dorei and L. helveticus in EtOH-fed mice. P. dorei and L. helveticus improved liver inflammation and intestinal barrier damage caused by EtOH supply and increased NK cell activity. Therefore, these observations suggest that the gut microbiome may ameliorate ALD by regulating immune cells.

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays., (© 2023 Wiley-VCH GmbH.)

A total of 187 lactic acid bacteria were isolated from four types of grains collected in South Korea. The bacterial strains were assigned as members of Levilactobacillus brevis, Latilactobacillus curvatus, Lactiplantibacillus plantarum, Lactococcus taiwanensis, Pediococcus pentosaceus, and Weissella paramesenteroides based on the closest similarity using 16S rRNA gene sequence analysis. The strains belonging to the same species were analyzed using RAPD-PCR, and one or two among strains showing the same band pattern were selected. Finally, 25 representative strains were selected for further functional study. Inhibitory effects of lipid accumulation were observed in the strains tested. Pediococcus pentosaceus K28, Levilactobacillus brevis RP21 and Lactiplantibacillus plantarum RP12 significantly reduced lipid accumulation and did not show cytotoxicity in C3H10T1/2 cells at treatment of 1-200 μg/mL. The three LAB strains decreased significantly expression of six adipogenic marker genes, PPARγ, C/EBPα, CD36, LPL, FAS and ACC, in C3H10T1/2 adipocytes. The three strains survived under strong acidity and bile salt conditions. The three strains showed adhesion to Caco-2 cells similar to a reference strain LGG. The resistance of the three strains to several antibiotics was also assessed. Strains RP12 and K28 were confirmed not to produce harmful enzymes based on API ZYM kit results. Based on these results, strains K28, RP21 and RP12 isolated from grains had the ability to inhibit adipogenesis in adipocytes and potentially be useful as probiotics., (© 2023. The Author(s).)

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system. These ultrathin and ultralight microneedle sensor arrays continuously and precisely monitored glucose concentration in the interstitial fluid with minimally invasive, pain-free, wound-free, and skin inflammation-free outcomes at various locations and thicknesses of the skin. Bioresorbability in the body without a need for device removal after use was a key characteristic of the microneedle glucose sensor. We demonstrated the potential long-term use of the bioresorbable device by applying the tether-free CGM system, thus confirming the successful detection of glucose levels based on changes in fluorescence intensity. In addition, this microneedle glucose sensor with a user-friendly designed home diagnosis system using mobile applications and portable accessories offers an advance in CGM and its applicability to other bioresorbable, wearable, and implantable monitoring device technology.

Aims: Nonalcoholic fatty liver disease (NAFLD) is becoming more common and severe. Individuals with NAFLD have an altered composition of gut- microbial metabolites. We used metabolomics profiling to identify microbial metabolites that could indicate gut-liver metabolic severity. Noninvasive biomarkers are required for NAFLD, especially for patients at high risk of disease progression., Main Methods: We compared the stool metabolomes, untargeted metabolomics, and clinical data of 80 patients. Patients with nonalcoholic fatty liver (NAFL: n = 16), nonalcoholic steatohepatitis (NASH: n = 26), and cirrhosis (n = 19) and healthy control individuals (HC: n = 19) were enrolled. The identified metabolites in NAFLD were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to time-of-flight-mass spectrometry (LC-TOF-MS) were used to analyze metabolites., Key Findings: Untargeted metabolomics was used to identify and quantify 103 metabolites. Principal component analysis (PCA) was used to assess the metabolic discrimination of NAFL, NASH, and cirrhosis. Short-chain fatty acids (SCFA) levels were significantly lower in NAFLD patients, including those of acetate (p = 0.03), butyrate (p = 0.0008), and propionate. The stool cholic acid (p = 0.001) level was significantly increased in NAFLD patients. Palmitoylcarnitine and l-carnitine levels were significantly increased in NASH and cirrhosis patients. The phenotypic expression of these metabolites was linked to β-oxidation., Significance: We demonstrated a distinct metabolome profile in NAFLD patients with NAFL, NASH, and cirrhosis. We also discovered that the expression of certain metabolites and metabolic pathways was linked to NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue globally, currently, the treatment of NAFLD lies still in the labyrinth. In the inchoate stage, the combinatorial application of food regimen and favorable gut microbiota (GM) are considered as an alternative therapeutic. Accordingly, we integrated secondary metabolites (SMs) from GM and Avena sativa (AS) known as potent dietary grain to identify the combinatorial efficacy through network pharmacology., Methods: We browsed the SMs of AS via Natural Product Activity & Species Source (NPASS) database and SMs of GM were retrieved by gutMGene database. Then, specific intersecting targets were identified from targets related to SMs of AS and GM. The final targets were selected on NAFLD-related targets, which was considered as crucial targets. The protein-protein interaction (PPI) networks and bubble chart analysis to identify a hub target and a key signaling pathway were conducted, respectively. In parallel, we analyzed the relationship of GM or AS─a key signaling pathway─targets─SMs (GASTM) by merging the five components via RPackage. We identified key SMs on a key signaling pathway via molecular docking assay (MDA). Finally, the identified key SMs were verified the physicochemical properties and toxicity in silico platform., Results: The final 16 targets were regarded as critical proteins against NAFLD, and Vascular Endothelial Growth Factor A (VEGFA) was a key target in PPI network analysis. The PI3K-Akt signaling pathway was the uppermost mechanism associated with VEGFA as an antagonistic mode. GASTM networks represented 122 nodes (60 GM, AS, PI3K-Akt signaling pathway, 4 targets, and 56 SMs) and 154 edges. The VEGFA-myricetin, or quercetin, GSK3B-myricetin, IL2-diosgenin complexes formed the most stable conformation, the three ligands were derived from GM. Conversely, NR4A1-vestitol formed stable conformation with the highest affinity, and the vestitol was obtained from AS. The given four SMs were no hurdles to develop into drugs devoid of its toxicity., Conclusion: In conclusion, we show that combinatorial application of AS and GM might be exerted to the potent synergistic effects against NAFLD, dampening PI3K-Akt signaling pathway. This work provides the importance of dietary strategy and beneficial GM on NAFLD, a data mining basis for further explicating the SMs and pharmacological mechanisms of combinatorial application (AS and GM) against NAFLD., (© 2023. The Author(s).)

Tethered and battery-powered devices that interface with neural tissues can restrict natural motions and prevent social interactions in animal models, thereby limiting the utility of these devices in behavioural neuroscience research. In this Review Article, we discuss recent progress in the development of miniaturized and ultralightweight devices as neuroengineering platforms that are wireless, battery-free and fully implantable, with capabilities that match or exceed those of wired or battery-powered alternatives. Such classes of advanced neural interfaces with optical, electrical or fluidic functionality can also combine recording and stimulation modalities for closed-loop applications in basic studies or in the practical treatment of abnormal physiological processes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Emerging evidences about gut-microbial modulation have been accumulated in the treatment of nonalcoholic fatty liver disease (NAFLD). We evaluated the effect of Bifidobacterium breve and Bifidobacterium longum on the NAFLD pathology and explore the molecular mechanisms based on multi-omics approaches. Human stool analysis [healthy subjects ( n  = 25) and NAFLD patients ( n  = 32)] was performed to select NAFLD-associated microbiota. Six-week-old male C57BL/6 J mice were fed a normal chow diet (NC), Western diet (WD), and WD with B. breve (BB) or B. longum (BL; 109 CFU/g) for 8 weeks. Liver/body weight ratio, histopathology, serum/tool analysis, 16S rRNA-sequencing, and metabolites were examined and compared. The BB and BL groups showed improved liver histology and function based on liver/body ratios (WD 7.07 ± 0.75, BB 5.27 ± 0.47, and BL 4.86 ± 0.57) and NAFLD activity scores (WD 5.00 ± 0.10, BB 1.89 ± 1.45, and BL 1.90 ± 0.99; p  < 0.05). Strain treatment showed ameliorative effects on gut barrier function. Metagenomic analysis showed treatment-specific changes in taxonomic composition. The community was mainly characterized by the significantly higher composition of the Bacteroidetes phylum among the NC and probiotic-feeding groups. Similarly, the gut metabolome was modulated by probiotics treatment. In particular, short-chain fatty acids and tryptophan metabolites were reverted to normal levels by probiotics, whereas bile acids were partially normalized to those of the NC group. The analysis of gene expression related to lipid and glucose metabolism as well as the immune response indicated the coordinative regulation of β-oxidation, lipogenesis, and systemic inflammation by probiotic treatment. BB and BL attenuate NAFLD by improving microbiome-associated factors of the gut-liver axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yoon, Yu, Min, Gupta, Won, Park, Han, Kim, Kim, Kim, Joung, Park, Ham, Lee and Suk.)

The progression and exacerbation of liver fibrosis are closely related to the gut microbiome. It is hypothesized that some probiotics may slow the progression of liver fibrosis. In human stool analysis [healthy group (n = 44) and cirrhosis group (n = 18)], difference in Lactobacillus genus between healthy group and cirrhosis group was observed. Based on human data, preventive and therapeutic effect of probiotics Lactobacillus lactis and L. rhamnosus was evaluated by using four mice fibrosis models. L. lactis and L. rhamnosus were supplied to 3,5-diethoxycarbonyl-1,4-dihydrocollidine or carbon tetrachloride-induced liver fibrosis C57BL/6 mouse model. Serum biochemical measurements, tissue staining, and mRNA expression in the liver were evaluated. The microbiome was analyzed in mouse cecal contents. In the mouse model, the effects of Lactobacillus in preventing and treating liver fibrosis were different for each microbe species. In case of L. lactis, all models showed preventive and therapeutic effects against liver fibrosis. In microbiome analysis in mouse models administered Lactobacillus, migration and changes in the ratio and composition of the gut microbial community were confirmed. L. lactis and L. rhamnosus showed preventive and therapeutic effects on the progression of liver fibrosis, suggesting that Lactobacillus intake may be a useful strategy for prevention and treatment., (© 2023. The Author(s), under exclusive licence to Microbiological Society of Korea.)

The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research., (© 2023. The Author(s).)

Abnormal formation of solid thrombus inside a blood vessel can cause thrombotic morbidity and mortality. This necessitates early stage diagnosis, which requires quantitative assessment with a small volume, for effective therapy with low risk to unwanted development of various diseases. We propose a micro-ultrasonic diagnosis using an all-optical ultrasound-based spectral sensing (AOUSS) technique for sensitive and quantitative characterization of early stage and whole blood coagulation. The AOUSS technique detects and analyzes minute viscoelastic variations of blood at a micro-ultrasonic spot (<100 μm) defined by laser-generated focused ultrasound (LGFU). This utilizes (1) a uniquely designed optical transducer configuration for frequency-spectral matching and wideband operation (6 dB widths: 7-32 MHz and d.c. ∼ 46 MHz, respectively) and (2) an empirical mode decomposition (EMD)-based signal process particularly adapted to nonstationary LGFU signals backscattered from the spot. An EMD-derived spectral analysis enables one to assess viscoelastic variations during the initiation of fibrin formation, which occurs at a very early stage of blood coagulation (1 min) with high sensitivity (frequency transition per storage modulus increment = 8.81 MHz/MPa). Our results exhibit strong agreement with those obtained by conventional rheometry (Pearson's R > 0.95), which are also confirmed by optical microscopy. The micro-ultrasonic and high-sensitivity detection of AOUSS poses a potential clinical significance, serving as a screening modality to diagnose early stage clot formation (e.g., as an indicator for hypercoagulation of blood) and stages of blood-to-clot transition to check a potential risk for development into thrombotic diseases.

In this work, we propose a vertical gate-all-around device architecture (GAA-FinFET) with the aim of simultaneously improving device performance as well as addressing the short channel effect (SCE). The GAA-FinFET was built using the technology computer-aided design (TCAD) simulation tool, and then, its electrical characteristics were quantitatively evaluated. The electrical characteristics of the GAA-FinFET were compared to those of conventional FinFET and nano-sheet FET (NSFET) at 7 nm or 5 nm nodes. When comparing the GAA-FinFET against the FinFET, it achieved not only better SCE characteristics, but also higher on-state drive current due to its gate-all-around device structure. This helps to improve the ratio of effective drive current to off-state leakage current (i.e., I eff /I off ) by ~30%, resulting in an improvement in DC device performance by ~10%. When comparing the GAA-FinFET against the NSFET, it exhibited SCE characteristics that were comparable or superior thanks to its improved sub-channel leakage suppression. It turned out that the proposed GAA-FinFET (compared to conventional FinFET at the 7 nm or 5 nm nodes, or even beyond) is an attractive option for improving device performance in terms of SCE and series resistance. Furthermore, it is expected that the device structure of GAA-FinFET is very similar to that of conventional FinFET, resulting in further improvement to its electrical characteristics as a result of its gate-all-around device structure without significant modification with respect to the processing steps for conventional FinFET.

The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more importantly, key target(s) via a network pharmacology approach. First, we retrieved the metabolites related to gut microbes from the gutMGene database. Then, we performed a meta-analysis to identify metabolite-related targets via the similarity ensemble approach (SEA) and SwissTargetPrediction (STP), and obesity-related targets were identified by DisGeNET and OMIM databases. After selecting the overlapping targets, we adopted topological analysis to identify core targets against obesity. Furthermore, we employed the integrated networks to microbiota-substrate-metabolite-target (MSMT) via R Package. Finally, we performed a molecular docking test (MDT) to verify the binding affinity between metabolite(s) and target(s) with the Autodock 1.5.6 tool. Based on holistic viewpoints, we performed a filtering step to discover the core targets through topological analysis. Then, we implemented protein-protein interaction (PPI) networks with 342 overlapping target, another subnetwork was constructed with the top 30% degree centrality (DC), and the final core networks were obtained after screening the top 30% betweenness centrality (BC). The final core targets were IL6, AKT1, and ALB. We showed that the three core targets interacted with three other components via the MSMT network in alleviating obesity, i.e., four microbiota, two substrates, and six metabolites. The MDT confirmed that equol (postbiotics) converted from isoflavone (prebiotics) via Lactobacillus paracasei JS1 (probiotics) can bind the most stably on IL6 (target) compared with the other four metabolites (3-indolepropionic acid, trimethylamine oxide, butyrate, and acetate). In this study, we demonstrated that the promising substate (prebiotics), microbe (probiotics), metabolite (postbiotics), and target are suitable for obsesity treatment, providing a microbiome basis for further research.

Diet and lifestyle are crucial factors that influence the susceptibility of humans to nonalcoholic fatty liver disease (NAFLD). Personalized diet patterns chronically affect the composition and activity of microbiota in the human gut; consequently, nutrition-related dysbiosis exacerbates NAFLD via the gut-liver axis. Recent advances in diagnostic technology for gut microbes and microbiota-derived metabolites have led to advances in the diagnosis, treatment, and prognosis of NAFLD. Microbiota-derived metabolites, including tryptophan, short-chain fatty acid, fat, fructose, or bile acid, regulate the pathophysiology of NAFLD. The microbiota metabolize nutrients, and metabolites are closely related to the development of NAFLD. In this review, we discuss the influence of nutrients, gut microbes, their corresponding metabolites, and metabolism in the pathogenesis of NAFLD.

Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders. The link between the microbiota and the host plays a key role in the pathogenesis of HE. The link between the gut microbiome and disease can be positively utilized not only in the diagnosis area of HE but also in the treatment area. Probiotics and prebiotics aim to resolve gut dysbiosis and increase beneficial microbial taxa, while fecal microbiota transplantation aims to address gut dysbiosis through transplantation (FMT) of the gut microbiome from healthy donors. Antibiotics, such as rifaximin, aim to improve cognitive function and hyperammonemia by targeting harmful taxa. Current treatment regimens for HE have achieved some success in treatment by targeting the gut microbiota, however, are still accompanied by limitations and problems. A focused approach should be placed on the establishment of personalized trial designs and therapies for the improvement of future care. This narrative review identifies factors negatively influencing the gut-hepatic-brain axis leading to HE in cirrhosis and explores their relationship with the gut microbiome. We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy.

Alcohol consumption is a global healthcare problem. Chronic alcohol consumption generates a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, fibrosis, and cirrhosis. Alcoholic liver diseases (ALD) refer to liver damage and metabolomic changes caused by excessive alcohol intake. ALD present several clinical stages of severity found in liver metabolisms. With increased alcohol consumption, the gut microbiome promotes a leaky gut, metabolic dysfunction, oxidative stress, liver inflammation, and hepatocellular injury. Much attention has focused on ALD, such as alcoholic fatty liver (AFL), alcoholic steatohepatitis (ASH), alcoholic cirrhosis (AC), hepatocellular carcinoma (HCC), a partnership that reflects the metabolomic significance. Here, we report on the global function of inflammation, inhibition, oxidative stress, and reactive oxygen species (ROS) mechanisms in the liver biology framework. In this tutorial review, we hypothetically revisit therapeutic gut microbiota-derived alcoholic oxidative stress, liver inflammation, inflammatory cytokines, and metabolic regulation. We summarize the perspective of microbial therapy of genes, gut microbes, and metabolic role in ALD. The end stage is liver transplantation or death. This review may inspire a summary of the gut microbial genes, critical inflammatory molecules, oxidative stress, and metabolic routes, which will offer future promising therapeutic compounds in ALD.

Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the pathogenesis of ALD is strongly associated with metabolites of human microbiota. AFLD was the onset of disease among ALDs, the initial cause of which is alcohol consumption. Thus, we analyzed the significant metabolites of microbiota against AFLD via the network pharmacology concept. The metabolites from microbiota were retrieved by the gutMGene database; sequentially, AFLD targets were identified by public databases (DisGeNET, OMIM). The final targets were utilized for protein-protein interaction (PPI) networks and signaling pathway analyses. Then, we performed a molecular docking test (MDT) to verify the affinity between metabolite(s) and target(s) utilizing the Autodock 1.5.6 tool. From a holistic viewpoint, we integrated the relationships of microbiota-signaling pathways-targets-metabolites (MSTM) using the R Package. We identified the uppermost six key targets (TLR4, RELA, IL6, PPARG, COX-2, and CYP1A2) against AFLD. The PPI network analysis revealed that TLR4, RELA, IL6, PPARG, and COX-2 had equivalent degrees of value (4); however, CYP1A2 had no associations with the other targets. The bubble chart showed that the PI3K-Akt signaling pathway in nine signaling pathways might be the most significant mechanism with antagonistic functions in the treatment of AFLD. The MDT confirmed that Icaritin is a promising agent to bind stably to RELA (known as NF-Κb). In parallel, Bacterium MRG-PMF-1, the PI3K-Akt signaling pathway, RELA, and Icaritin were the most significant components against AFLD in MSTM networks. In conclusion, we showed that the Icaritin-RELA complex on the PI3K-Akt signaling pathway by bacterial MRG-PMF-1 might have promising therapeutic effects against AFLD, providing crucial evidence for further research.

In this paper we demonstrate strain-dependent photoacoustic (PA) characteristics of free-standing nanocomposite transmitters that are made of carbon nanotubes (CNT) and candle soot nanoparticles (CSNP) with an elastomeric polymer matrix. We analyzed and compared PA output performances of these transmitters which are prepared first on glass substrates and then in a delaminated free-standing form for strain-dependent characterization. This confirms that the nanocomposite transmitters with lower concentration of nanoparticles exhibit more flexible and stretchable property in terms of Young's modulus in a range of 4.08-10.57 kPa. Then, a dynamic endurance test was performed revealing that both types of transmitters are reliable with pressure amplitude variation as low as 8-15% over 100-800 stretching cycles for a strain level of 5-28% with dynamic endurance in range of 0.28-2.8%. Then, after 2000 cycles, the transmitters showed pressure amplitude variation of 6-29% (dynamic endurance range of 0.21-1.03%) at a fixed strain level of 28%. This suggests that the free-standing nanocomposite transmitters can be used as a strain sensor under a variety of environments providing robustness under repeated stretching cycles.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a significant health threat globally, and has attracted growing concern in the research field of liver diseases. NAFLD comprises multifarious fatty degenerative disorders in the liver, including simple steatosis, steatohepatitis and fibrosis. The fundamental pathophysiology of NAFLD is complex and multifactor-driven. In addition to viruses, metabolic syndrome and alcohol, evidence has recently indicated that the microbiome is related to the development and progression of NAFLD. In this review, we summarize the possible microbiota-based therapeutic approaches and highlight the importance of establishing the diagnosis of NAFLD through the different spectra of the disease via the gut-liver axis.

Over the past decade, scientific evidence for the properties, functions, and beneficial effects of probiotics for humans has continued to accumulate. Interest in the use of probiotics for humans has increased tremendously. Among various microorganisms, probiotics using bacteria have been widely studied and commercialized, and, among them, Lactobacillus is representative. This genus contains about 300 species of bacteria (recently differentiated into 23 genera) and countless strains have been reported. They improved a wide range of diseases including liver disease, gastrointestinal diseases, respiratory diseases, and autoimmune diseases. Here, we intend to discuss in depth the genus Lactobacillus as a representative probiotic for chronic liver diseases.

We demonstrate a variable-focus optoacoustic lens (VFOL) by pneumatically controlling a flexible polymer nano-composite membrane, which can produce laser-generated focused ultrasound (LGFU) with a high peak amplitude (>30 MPa) and a tight focal dimension (several hundred μm) over a wide dynamic range of focus variation (>20 mm) together with a long focal length up to 60 mm, each of which is widest and longest among optoacoustic lenses developed so far. Two different designs in lens dimension have been fabricated and characterized: VFOL-L with a 40-mm diameter and VFOL-S with 10 mm. VFOL-L exhibits a wide dynamic range of focal length variation from 38.52 to 60.39 mm with a center frequency near ~ 10 MHz, which is proper for practical long-range applications with several-cm depth. In comparison, VFOL-S covers a focal variation range from 6.75 to 11.1 mm with ~ 14 MHz, producing a relatively higher-pressure amplitude, which allows the inception of acoustic cavitation at an impedance-mismatched boundary. The nano-composite membrane of VFOL is actuated from a planar to deeply curved shape by externally injecting liquid into the VFOL, resulting in a focal gain up to 255 and a positive peak pressure of > 30 MPa in the VFOL-L case. The minimum-geometrical f-number as low as 0.963 is achieved at the shortest focal length (38.52 mm) with 6-dB lateral and axial spot dimensions of 304 μm and 2.86 mm, respectively. We expect that the proposed VFOL-based LGFU with a high peak pressure, a wide dynamic axial range, and a tight focal dimension are suitably applied for depth-dependent characterization of tissues and shockwave treatment, taking advantages of optoacoustic pulses as input with inherent broadband high-frequency characteristics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by hepatic accumulation of excess lipids. T cells are commonly classified into various subsets based on their surface markers including T cell receptors, type of antigen presentation and pathophysiological functions. Several studies have implicated various T cell subsets and natural killer (NK) cells in the progression of NAFLD. While NK cells are mainly components of the innate hepatic immune system, the majority of T cell subsets can be part of both the adaptive and innate systems. Several studies have reported that various stages of NAFLD are accompanied by the accumulation of distinct T cell subsets and NK cells with different functions and phenotypes observed usually resulting in proinflammatory effects. More importantly, the overall stimulation of the intrahepatic T cell subsets is directly influenced by the homeostasis of the gut microbiota. Similarly, NK cells have been found to accumulate in the liver in response to pathogens and tumors. In this review, we discussed the nature and pathophysiological roles of T cell subsets including γδ T cells, NKT cells, Mucosal-associated invariant T (MAIT) cells as well as NK cells in NAFLD.

Laser-generated focused ultrasound (LGFU) is an emerging modality for cavitation-based therapy. However, focal pressure amplitudes by LGFU alone to achieve pulsed cavitation are often lacking as a treatment depth increases. This requires a higher pressure from a transmitter surface and more laser energies that even approach to a damage threshold of transmitter. To mitigate the requirement for LGFU-induced cavitation, we propose LGFU configurations with a locally heated focal zone using an additional high-intensity focused ultrasound (HIFU) transmitter. After confirming heat-induced cavitation enhancement using two separate transmitters, we then developed a stacked hybrid optoacoustic-piezoelectric transmitter, which is a unique configuration made by coating an optoacoustic layer directly onto a piezoelectric substrate. This shared curvature design has great practical advantage without requiring the complex alignment of two focal zones. Moreover, this enabled the amplification of cavitation bubble density by 18.5-fold compared to the LGFU operation alone. Finally, the feasibility of tissue fragmentation was confirmed through a tissue-mimicking gel, using the combination of LGFU and HIFU (not via a stacked structure). We expect that the stacked transmitter can be effectively used for stronger and faster tissue fragmentation than the LGFU transmitter alone.

Soft grippers that incorporate functional materials are important in the development of mechanically compliant and multifunctional interfaces for both sensing and stimulating soft objects and organisms. In particular, the capability for firm and delicate grasping of soft cells and organs without mechanical damage is essential to identify the condition of and monitor meaningful biosignals from objects. Here, we report a millimeter-scale soft gripper based on a shape memory polymer that enables manipulating a heavy object (payload-to-weight ratio up to 6400) and grasping organisms at the micro/milliscale. The silver nanowires and crack-based strain sensor embedded in this soft gripper enable simultaneous measurement of the temperature and pressure on grasped objects and offer temperature and mechanical stimuli for the grasped object. We validate our miniaturized soft gripper by demonstrating that it can grasp a snail egg while simultaneously applying a moderate temperature stimulation to induce hatching process and monitor the heart rate of a newborn snail. The results present the potential for widespread utility of soft grippers in the area of biomedical engineering, especially in the development of conditional or closed-loop interfacing with microscale biotissues and organisms.

Effects of Latilactobacillus sakei ADM14 on changes in lipid metabolism and fecal microbiota composition were studied in high-fat diet (HFD) mouse model. The mice were divided into three groups: normal diet (ND), high-fat diet (HD), and HFD plus L. sakei ADM14 (HDA). Oral administration of L. sakei ADM14 daily for 10weeks decreased body weight gain, fat tissue mass, and liver weight in mice and reduced the size of histologically stained liver adipocytes. In addition, serum total cholesterol, triglycerides, and blood glucose decreased significantly. Latilactobacillus sakei ADM14 regulated the expression of genes related to lipid metabolism in epididymal adipose tissue and liver and induced changes in the composition of fecal microbiota, thereby improving energy harvests and changing metabolic disorder-related taxa. A significant decrease ( p <0.05) in the Firmicutes to Bacteroidetes ratio was found in the HDA group compared to the HD group, particularly due to the difference in the relative abundance of the Bacteroidetes between the two groups over 10weeks. Differences in proportions of some taxa reported to have correlation with obesity were also found between HD and HDA groups. These results suggest that L. sakei ADM14 can have a positive effect on metabolic disorders such as obesity and fatty liver through effective regulation of host lipid metabolism and gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Won, Seo, Kwon, Park and Yoon.)

Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide. NAFLD is a term that involves a variety of conditions such as fatty liver, steatohepatitis, or fibrosis. Gut microbiota and its products have been extensively studied because of a close relation between NAFLD and microbiota in pathogenesis. In the progression of NAFLD, various microbiota-related molecular and cellular mechanisms, including dysbiosis, leaky bowel, endotoxin, bile acids enterohepatic circulation, metabolites, or alcohol-producing microbiota, are involved. Currently, diagnosis and treatment techniques using these mechanisms are being developed. In this review, we will introduce the microbiota-related mechanisms in the progression of NAFLD and future directions will be discussed.

Large, distributed collections of miniaturized, wireless electronic devices 1,2 may form the basis of future systems for environmental monitoring 3 , population surveillance 4 , disease management 5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds 6 -we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures 7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings., (© 2021. The Author(s).)

Implantable deep brain stimulation (DBS) systems are utilized for clinical treatment of diseases such as Parkinson's disease and chronic pain. However, long-term efficacy of DBS is limited, and chronic neuroplastic changes and associated therapeutic mechanisms are not well understood. Fundamental and mechanistic investigation, typically accomplished in small animal models, is difficult because of the need for chronic stimulators that currently require either frequent handling of test subjects to charge battery-powered systems or specialized setups to manage tethers that restrict experimental paradigms and compromise insight. To overcome these challenges, we demonstrate a fully implantable, wireless, battery-free platform that allows for chronic DBS in rodents with the capability to control stimulation parameters digitally in real time. The devices are able to provide stimulation over a wide range of frequencies with biphasic pulses and constant voltage control via low-impedance, surface-engineered platinum electrodes. The devices utilize off-the-shelf components and feature the ability to customize electrodes to enable broad utility and rapid dissemination. Efficacy of the system is demonstrated with a readout of stimulation-evoked neural activity in vivo and chronic stimulation of the medial forebrain bundle in freely moving rats to evoke characteristic head motion for over 36 days., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021, corrected publication 2021.)

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut-liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions.

Evaluating the biomechanics of soft tissues at depths well below their surface, and at high precision and in real time, would open up diagnostic opportunities. Here, we report the development and application of miniaturized electromagnetic devices, each integrating a vibratory actuator and a soft strain-sensing sheet, for dynamically measuring the Young's modulus of skin and of other soft tissues at depths of approximately 1-8 mm, depending on the particular design of the sensor. We experimentally and computationally established the operational principles of the devices and evaluated their performance with a range of synthetic and biological materials and with human skin in healthy volunteers. Arrays of devices can be used to spatially map elastic moduli and to profile the modulus depth-wise. As an example of practical medical utility, we show that the devices can be used to accurately locate lesions associated with psoriasis. Compact electronic devices for the rapid and precise mechanical characterization of living tissues could be used to monitor and diagnose a range of health disorders., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)