Soft mechanical sensors for wearable and implantable applications.

Wearable and implantable sensing of biomechanical signals such as pressure, strain, shear, and vibration can enable a multitude of human-integrated applications, including on-skin monitoring of vital signs, motion tracking, monitoring of internal organ condition, restoration of lost/impaired mechanoreception, among many others. The mechanical conformability of such sensors to the human skin and tissue is critical to enhancing their biocompatibility and sensing accuracy. As such, in the recent decade, significant efforts have been made in the development of soft mechanical sensors. To satisfy the requirements of different wearable and implantable applications, such sensors have been imparted with various additional properties to make them better suited for the varied contexts of human-integrated applications. In this review, focusing on the four major types of soft mechanical sensors for pressure, strain, shear, and vibration, we discussed the recent material and device design innovations for achieving several important properties, including flexibility and stretchability, bioresorbability and biodegradability, self-healing properties, breathability, transparency, wireless communication capabilities, and high-density integration. We then went on to discuss the current research state of the use of such novel soft mechanical sensors in wearable and implantable applications, based on which future research needs were further discussed. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

Risk Factors for Urinary Tract Infection in Elderly Patients with Type 2 Diabetes: A Retrospective Cohort Study.

OBJECTIVE: The risk factors of urinary tract infection in elderly patients with type 2 diabetes were investigated. METHODS: A total of 72 elderly patients admitted to our hospital from December 2019 to September 2023 because of with type 2 diabetes were retrospectively included. They were divided into the observation group (n = 35) and control group (n = 37) according to whether they had urinary tract infection. The general clinical data, clinical characteristics and the distribution of pathogenic bacteria in the observation group were collected and analysed. Then, t-tests, chi-square tests, regression analysis and receiver operating characteristic curve analysis were conducted. RESULTS: Escherichia coli (E. coli) accounted for 51.43% of the pathogenic bacteria in the observation group, whereas Klebsiella pneumoniae (K. pneumoniae) accounted for 22.86%. The remaining pathogens accounted for 2.86% each. Differences in gender, course of disease, glycosylated haemoglobin and comorbid urinary calculi were found between the groups (p < 0.05); These factors were all risk factors for concurrent urinary infection, and the odds ratios were all >1. The obtained values for gender, disease course, glycosylated haemoglobin and comorbid urinary calculi were respectively 0.594, 0.654, 0.738 and 0.696 (area under the curve); 0.971, 0.714, 0.800 and 0.743 (sensitivity); 0.216, 0.595, 0.676 and 0.649 (specificity); And 0.188, 0.309, 0.476 and 0.392 (Youden index). CONCLUSIONS: Common pathogens in elderly people with type 2 diabetes and comorbid urinary tract infection are E. coli and K. pneumoniae. Risk factors include gender, disease duration, glycosylated haemoglobin and urinary stones. The prompt identification of pathogens and risk factors facilitates clinical treatment, reducing infection incidence.

TGF ß1 promotes the polarization of M2-type macrophages and activates PI3K/mTOR signaling pathway by inhibiting ISG20 to sensitize ovarian cancer to cisplatin.

The involvement of Interferon-stimulated exonuclease gene 20 (ISG20) has been reported in renal clear cell carcinoma, hepatocellular carcinoma, and cervical cancer. However, its role in ovarian cancer chemotherapy remains unclear. In this study, we conducted a comparative analysis of TGF-ß1 and ISG20 in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells and tissues using qRT-PCR and a tissue immunofluorescence analysis. We also investigated the impact of ISG20-targeted drugs (IFN-γ) and TGF-ß1 inhibitors on cisplatin response both in vivo and in vitro. Additionally, we assessed the effects of TGF-ß1 or ISG20 on the polarization of tumor-associated macrophages through flow cytometry and ELISA analysis. Our findings revealed that ISG20 expression was lower in cisplatin-resistant tissues compared to cisplatin-sensitive tissues; however, overexpression of ISG20 sensitized ovarian cancer to cisplatin treatment. Furthermore, activation of ISG20 expression with IFN-γ or TGF-ß1 inhibitors enhanced the sensitivity of ovarian cancer cells to cisplatin therapy. Notably, our results demonstrated that TGF-ß1 promoted M2-type macrophage polarization as well as PI3K/mTOR pathway activation by suppressing ISG20 expression both in vivo and in vitro. In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-ß1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer.

Orostachys malacophylla (pall.) fisch extracts alleviate intestinal inflammation in Drosophila.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. AIM OF THE STUDY: We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. MATERIALS AND METHODS: Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. RESULTS: We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. CONCLUSIONS: In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.

Enabling continuous immune cell recirculation on a microfluidic array to study immunotherapeutic interactions in a recapitulated tumour microenvironment.

The effects of immunotherapeutics on interactions between immune and cancer cells are modulated by multiple components in the tumour microenvironment (TME), including endothelium and tumour stroma, which provide both a physical barrier and immunosuppressive stimuli. Herein, we report a recirculating chip to enable continuous immune cell recirculation through a microfluidic cell array to include these crucial players. This system consists of a three-layered cell array (µFCA) spatially emulating the TME, with tailored fluidic circuits establishing T cell recirculation. This platform enables the study of dynamics among the TME, immune cells in a circulatory system and cancer cell responses thereof. Through this system, we found that tumour endothelium hindered T cell infiltration into the reconstructed breast cancer tumour compartment. This negative effect was alleviated when treated with anti-human PD-L1 (programmed cell death ligand 1) antibody. Another key stromal component - cancer associated fibroblasts - attenuated T cell infiltration, compared against normal fibroblasts, and led to reduced apoptotic activity in cancer cells. These results confirm the capability of our tumour-on-a-chip system in identifying some key axes to target in overcoming barriers to immunotherapy by recapitulating immune cell interactions with the reconstructed TME. Our results also attest to the feasibility of scaling up this system for high-throughput cancer immunotherapeutic screening.

Real-time correlation of crystallization and segmental order in conjugated polymers.

Modulating the segmental order in the morphology of conjugated polymers is widely recognized as a crucial factor for achieving optimal electronic properties and mechanical deformability. However, it is worth noting that the segmental order is typically associated with the crystallization process, which can result in rigid and brittle long-range ordered crystalline domains. To precisely control the morphology, a comprehensive understanding of how highly anisotropic conjugated polymers form segmentally ordered structures with ongoing crystallization is essential, yet currently elusive. To fill this knowledge gap, we developed a novel approach with a combination of stage-type fast scanning calorimetry and micro-Raman spectroscopy to capture the series of specimens with a continuum in the polymer percent crystallinity and detect the segmental order in real-time. Through the investigation of conjugated polymers with different backbones and side-chain structures, we observed a generally existing phenomenon that the degree of segmental order saturates before the maximum crystallinity is achieved. This disparity allows the conjugated polymers to achieve good charge carrier mobility while retaining good segmental dynamic mobility through the tailored treatment. Moreover, the crystallization temperature to obtain optimal segmental order can be predicted based on Tg and Tm of conjugated polymers. This in-depth characterization study provides fundamental insights into the evolution of segmental order during crystallization, which can aid in designing and controlling the optoelectronic and mechanical properties of conjugated polymers.

Active oxygen species mediate the iron-promoting electrocatalysis of oxygen evolution reaction on metal oxyhydroxides.

Iron is an extraordinary promoter to impose nickel/cobalt (hydr)oxides as the most active oxygen evolution reaction catalysts, whereas the synergistic effect is actively debated. Here, we unveil that active oxygen species mediate a strong electrochemical interaction between iron oxides (FeOxHy) and the supporting metal oxyhydroxides. Our survey on the electrochemical behavior of nine supporting metal oxyhydroxides (M(O)OH) uncovers that FeOxHy synergistically promotes substrates that can produce active oxygen species exclusively. Tafel slopes correlate with the presence and kind of oxygen species. Moreover, the oxygen evolution reaction onset potentials of FeOxHy@M(O)OH coincide with the emerging potentials of active oxygen species, whereas large potential gaps are present for intact M(O)OH. Chemical probe experiments suggest that active oxygen species could act as proton acceptors and/or mediators for proton transfer and/or diffusion in cooperative catalysis. This discovery offers a new insight to understand the synergistic catalysis of Fe-based oxygen evolution reaction electrocatalysts.

MLAM: Multi-Layer Attention Module for Radar Extrapolation Based on Spatiotemporal Sequence Neural Network.

Precipitation nowcasting is mainly achieved by the radar echo extrapolation method. Due to the timing characteristics of radar echo extrapolation, convolutional recurrent neural networks (ConvRNNs) have been used to solve the task. Most ConvRNNs have been proven to perform far better than traditional optical flow methods, but they still have fatal problems. These models lack differentiation in the prediction of echoes of different intensities, which leads to the omission of responses from regions with high intensities. Moreover, because it is difficult for these models to capture long-term feature dependencies among multiple echo maps, the extrapolation effect declines sharply over time. This paper proposes an embedded multi-layer attention module (MLAM) to address the shortcomings of ConvRNNs. Specifically, an MLAM mainly enhances attention to critical regions in echo images and the processing of long-term spatiotemporal features through the interaction between input and memory features in the current moment. Comprehensive experiments were conducted on the radar dataset HKO-7 provided by the Hong Kong Observatory and the radar dataset HMB provided by the Hunan Meteorological Bureau. Experiments show that ConvRNNs embedded with MLAMs achieve more advanced results than standard ConvRNNs.

Bioadhesive polymer semiconductors and transistors for intimate biointerfaces.

The use of bioelectronic devices relies on direct contact with soft biotissues. For transistor-type bioelectronic devices, the semiconductors that need to have direct interfacing with biotissues for effective signal transduction do not adhere well with wet tissues, thereby limiting the stability and conformability at the interface. We report a bioadhesive polymer semiconductor through a double-network structure formed by a bioadhesive brush polymer and a redox-active semiconducting polymer. The resulting semiconducting film can form rapid and strong adhesion with wet tissue surfaces together with high charge-carrier mobility of ~1 square centimeter per volt per second, high stretchability, and good biocompatibility. Further fabrication of a fully bioadhesive transistor sensor enabled us to produce high-quality and stable electrophysiological recordings on an isolated rat heart and in vivo rat muscles.

Achieving tissue-level softness on stretchable electronics through a generalizable soft interlayer design.

Soft and stretchable electronics have emerged as highly promising tools for biomedical diagnosis and biological studies, as they interface intimately with the human body and other biological systems. Most stretchable electronic materials and devices, however, still have Young's moduli orders of magnitude higher than soft bio-tissues, which limit their conformability and long-term biocompatibility. Here, we present a design strategy of soft interlayer for allowing the use of existing stretchable materials of relatively high moduli to versatilely realize stretchable devices with ultralow tissue-level moduli. We have demonstrated stretchable transistor arrays and active-matrix circuits with moduli below 10 kPa-over two orders of magnitude lower than the current state of the art. Benefiting from the increased conformability to irregular and dynamic surfaces, the ultrasoft device created with the soft interlayer design realizes electrophysiological recording on an isolated heart with high adaptability, spatial stability, and minimal influence on ventricle pressure. In vivo biocompatibility tests also demonstrate the benefit of suppressing foreign-body responses for long-term implantation. With its general applicability to diverse materials and devices, this soft-interlayer design overcomes the material-level limitation for imparting tissue-level softness to a variety of bioelectronic devices.

Under-Coordinated CoFe Layered Double Hydroxide Nanocages Derived from Nanoconfined Hydrolysis of Bimetal Organic Compounds for Efficient Electrocatalytic Water Oxidation.

Hierarchically structured bimetal hydroxides are promising for electrocatalytic oxygen evolution reaction (OER), yet synthetically challenging. Here, the nanoconfined hydrolysis of a hitherto unknown CoFe-bimetal-organic compound (b-MOC) is reported for the controllable synthesis of highly OER active nanostructures of CoFe layered double hydroxide (LDH). The nanoporous structures trigger the nanoconfined hydrolysis in the sacrificial b-MOC template, producing CoFe LDH core-shell octahedrons, nanoporous octahedrons, and hollow nanocages with abundant under-coordinated metal sites. The hollow nanocages of CoFe LDH demonstrate a remarkable turnover frequency (TOF) of 0.0505 s-1 for OER catalysis at an overpotential of 300 mV. It is durable in up to 50 h of electrolysis at step current densities of 10-100 mA cm-2 . Ex situ and in situ X-ray absorption spectroscopic analysis combined with theoretical calculations suggests that under-coordinated Co cations can bind with deprotonated Fe-OH motifs to form OER active Fe-O-Co dimmers in the electrochemical oxidation process, thereby contributing to the good catalytic activity. This work presents an efficient strategy for the synthesis of highly under-coordinated bimetal hydroxide nanostructures. The mechanistic understanding underscores the power of maximizing the amount of bimetal-dimer sites for efficient OER catalysis.

High-efficiency stretchable light-emitting polymers from thermally activated delayed fluorescence.

Stretchable light-emitting materials are the key components for realizing skin-like displays and optical biostimulation. All the stretchable emitters reported to date, to the best of our knowledge, have been based on electroluminescent polymers that only harness singlet excitons, limiting their theoretical quantum yield to 25%. Here we present a design concept for imparting stretchability onto electroluminescent polymers that can harness all the excitons through thermally activated delayed fluorescence, thereby reaching a near-unity theoretical quantum yield. We show that our design strategy of inserting flexible, linear units into a polymer backbone can substantially increase the mechanical stretchability without affecting the underlying electroluminescent processes. As a result, our synthesized polymer achieves a stretchability of 125%, with an external quantum efficiency of 10%. Furthermore, we demonstrate a fully stretchable organic light-emitting diode, confirming that the proposed stretchable thermally activated delayed fluorescence polymers provide a path towards simultaneously achieving desirable electroluminescent and mechanical characteristics, including high efficiency, brightness, switching speed and stretchability as well as low driving voltage.

A universal interface for plug-and-play assembly of stretchable devices.

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.

Entropy-Stabilized Multicomponent Porous Spinel Nanowires of NiFeXO4 (X = Fe, Ni, Al, Mo, Co, Cr) for Efficient and Durable Electrocatalytic Oxygen Evolution Reaction in Alkaline Medium.

Cost-effective electrochemical water splitting technology hinges on the development of efficient and durable catalysts for oxygen evolution reaction (OER). Spinel oxides (formula: AxB3-xO4) are structurally stable for real applications. Much effort has been devoted to improving the catalytic activity. Here, we report a eutectic dealloying strategy to activate the porous spinel NiFe2O4 nanowires with up to four metal cation substitutions. As-obtained spinel NiFeXO4 (X = Fe, Ni, Al, Mo, Co, Cr) delivers a benchmark current density of 10 mA·cm-2 at an overpotential of only 195 mV, outperforming most spinel phase OER electrocatalysts and comparable to the state-of-the-art NiFe hydroxides. It is stable for over 115 h of electrolysis. Aberration-corrected transmission electron microscopy, high-resolution electron energy loss spectroscopy, and atomic-scale strain mappings reveal that the multivalent cation substitutions result in substantial lattice distortion and significant electronic coupling of metal 3d and O 2p orbitals for increased covalency. Further theoretical calculations suggest that the NiFeXO4 are stabilized by the high configurational entropy, and their synergy favors the absorption of H2O molecules and lowers the adsorption energy barrier of the OOH* intermediate. The improved intrinsic activity together with the highly nanoporous structures contribute to the appealing apparent catalytic performances. The work demonstrates an effective approach for the synthesis of stable multicomponent spinel oxides and highlights the effectiveness of the multication substitution strategy for producing highly durable and active spinel catalysts, which meet multiplexed structure and superior property requirements in practical applications.

Anti- Toxoplasma gondii Properties of Ginseng polysaccharides and saponins.

New anti- Toxoplasma gondii agents are in demand due to the emergence of high toxicity. Ginseng polysaccharides and saponins can be used to treat the replication of Toxoplasma gondii in an attempt to determine whether the medicinal uses of ginseng are supported by pharmacological effects. Anti- Toxoplasma gondii activities of ginseng polysaccharides and saponins were examined in vitro and in vivo. The findings are the survival time and rate of Toxoplasma gondii infected mice after the intake of the total polysaccharides and saponins increased compared to untreated control mice. The survival rate of mice treated with ginseng saponins was the highest at 83.3%, the phenomenon of splenomegaly of mice was decreased especially ( p < 0.05) treated with ginseng polysaccharides. Accordingly, ginseng polysaccharides and saponins have a potential application in anti-Toxoplasma gondii treatments.

Synthesis, Characterization and Biological Evaluation of Benzothiazole-Isoquinoline Derivative.

Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression.

Identifying the geometric catalytic active sites of crystalline cobalt oxyhydroxides for oxygen evolution reaction.

Unraveling the precise location and nature of active sites is of paramount significance for the understanding of the catalytic mechanism and the rational design of efficient electrocatalysts. Here, we use well-defined crystalline cobalt oxyhydroxides CoOOH nanorods and nanosheets as model catalysts to investigate the geometric catalytic active sites. The morphology-dependent analysis reveals a ~50 times higher specific activity of CoOOH nanorods than that of CoOOH nanosheets. Furthermore, we disclose a linear correlation of catalytic activities with their lateral surface areas, suggesting that the active sites are exclusively located at lateral facets rather than basal facets. Theoretical calculations show that the coordinatively unsaturated cobalt sites of lateral facets upshift the O 2p-band center closer to the Fermi level, thereby enhancing the covalency of Co-O bonds to yield the reactivity. This work elucidates the geometrical catalytic active sites and enlightens the design strategy of surface engineering for efficient OER catalysts.

Anti-Toxoplasma gondii agent isolated from Orostachys malacophylla (Pallas) Fischer.

Botanical medicinal plants have aroused our interest to deal with Toxoplasmosis which can causes serious public health problems. Nipagic acid, gallic acid, ethyl gallate, phloretic acid, protocatechuic acid, methyl p-coumarate, arbutin, and homoprotocatechuic acid are first isolated from Orostachys malacophylla (Pallas) Fischer, their inhibition rate, survival rate, biochemical and viscera index are evaluated using gastric epithelia strain-1(GES-1). Among them, arbutin can effectively prolong the survival time of mice acutely infected with T. gondii, and exhibit the same curative effect as Spiramycin (Spi) group in terms of the glutathione (GSH) and malondialdehyde (MDA) content, alleviate hepatomegaly and splenomegaly. Structure-activity relationship (SAR) and molecular docking implies that phenolic hydroxyl group would be preferred for improvement of activity. In a summary, arbutin is a potential anti-T. gondii candidate for clinical application.

Synergistic Hybrid Electrocatalysts of Platinum Alloy and Single-Atom Platinum for an Efficient and Durable Oxygen Reduction Reaction.

Pt single-atom materials possess an ideal atom economy but suffer from limited intrinsic activity and side reaction of producing H2O2 in catalyzing the oxygen reduction reaction (ORR); platinum alloys have higher intrinsic activity but weak stability. Here, we demonstrate that anchoring platinum alloys on single-atom Pt-decorated carbon (Pt-SAC) surmounts their inherent deficiencies, thereby enabling a complete four-electron ORR pathway catalysis with high efficiency and durability. Pt3Co@Pt-SAC demonstrates an exceptional mass and specific activities 1 order of magnitude higher than those of commercial Pt/C. They are durable throughout 50000 cycles, showing only a 10 mV decay in half-wave potential. An in situ Raman analysis and theoretical calculations reveal that Pt3Co core nanocrystals modulate electron structures of the adjacent Pt single atoms to facilitate the intermediate absorption for fast kinetics. The superior durability is attributed to the shielding effect of the Pt-SAC coating, which significantly mitigates the dissolution of Pt3Co cores. The hybridizing strategy might promote the development of highly active and durable ORR catalysts.