Intrinsic Elastomer with Remarkable Dielectric Constant via Elastification of Relaxor Ferroelectric Polymer.

High-dielectric-constant elastomers have always been playing a critical role in the development of wearable electronics for actuation, energy storage, and sensing; therefore, there is an urgent need for effective strategies to enhance dielectric constants. The present methods mainly involve adding inorganic or conductive fillers to the polymer elastomers, however, the addition of fillers will cause a series of problems, such as large dielectric loss, increased modulus, and deteriorating interface conditions. Here we investigate the elastification of relaxor ferroelectric polymers through slight crosslinking, aiming to obtain intrinsic elastomers with high dielectric constants. By crosslinking of the relaxor ferroelectric polymer P(VDF-TrFE-CFE) with a long soft chain crosslinker, we obtain a relaxor ferroelectric elastomer with an enhanced dielectric constant, twice that of the pristine relaxor ferroelectric polymer and surpassing all reported intrinsic elastomers. This elastomer maintains its high dielectric constant over a wide temperature range and exhibits robust mechanical fatigue resistance, chemical stability and thermal stability. Moreover, the ferroelectricity of the elastomer remains stable under strains up to 80%. Our study offers a simple and effective way to enhance the dielectric constant of intrinsic elastomers, thus facilitating advancements in soft robots, biosensors, and wearable electronics. This article is protected by copyright. All rights reserved.

Modified failproof physics-informed neural network framework for fast and accurate optical fiber transmission link modeling.

Physics-informed neural networks (PINNs) have recently emerged as an important and ground-breaking technique in scientific machine learning for numerous applications including in optical fiber communications. However, the vanilla/baseline version of PINNs is prone to fail under certain conditions because of the nature of the physics-based regularization term in its loss function. The use of this unique regularization technique results in a highly complex non-convex loss landscape when visualized. This leads to failure modes in PINN-based modeling. The baseline PINN works very well as an optical fiber model with relatively simple fiber parameters and for uncomplicated transmission tasks. Yet, it struggles when the modeling task becomes relatively complex, reaching very high error, for example, numerous modeling tasks/scenarios in soliton communication and soliton pulse development in special fibers such as erbium-doped dispersion compensating fibers. We implement two methods to circumvent the limitations caused by the physics-based regularization term to solve this problem, namely, the so-called scaffolding technique for PINN modeling and the progressive block learning PINN modeling strategy to solve the nonlinear Schrödinger equation (NLSE), which models pulse propagation in an optical fiber. This helps PINN learn more accurately the dynamics of pulse evolution and increases accuracy by two to three orders of magnitude. We show in addition that this error is not due to the depth or architecture of the neural network but a fundamental issue inherent to PINN by design. The results achieved indicate a considerable reduction in PINN error for complex modeling problems, with accuracy increasing by up to two orders of magnitude.

Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma (PRP).

BACKGROUND: Androgenic alopecia (AGA) is the most common type of hair loss in men, and there are many studies on the treatment of hair loss by platelet-rich plasma (PRP). The human scalp contains a huge microbiome, but its role in the process of hair loss remains unclear, and the relationship between PRP and the microbiome needs further study. Therefore, the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition. METHODS: We performed PRP treatment on 14 patients with AGA, observed their clinical efficacy, and collected scalp swab samples before and after treatment. The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification. RESULTS: The results showed that PRP was effective in the treatment of AGA patients, and the hair growth increased significantly. The results of relative abundance analysis of microbiota showed that after treatment, g_Cutibacterium increased and g_Staphylococcus decreased, which played a stable role in scalp microbiota. In addition, g_Lawsonella decreased, indicating that the scalp oil production decreased after treatment. CONCLUSIONS: The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

TRPV1 signaling of perirenal adipose tissue promotes DOCA-Salt-induced hypertension and kidney injury.

BACKGROUND: Denervation of renal or perirenal adipose tissue (PRAT) can reduce arterial blood pressure in various hypertensive experimental models. Trpv1 (transient receptor potential vanillin 1) channel is highly expressed in the renal sensory nerves and the dorsal root ganglias (DRGs) projected by PRAT. However, it is currently unclear whether Trpv1 in DRGs projected from PRAT can regulate renal hypertension. METHODS: We used resintoxin (RTX) to block the afferent sensory nerves of rat PRAT. We also constructed Trpv1-/- mice and Trpv1+/- mice or used the injection of AAV2-retro-shTrpv1 to detect the effects of Trpv1 knockout or knockdown of PRAT-projected DRGs on deoxycorticosterone acetate (DOCA)-Salt-induced hypertension and kidney injury. RESULTS: Blocking the afferent sensory nerves of PRAT with RTX can alleviate DOCA-Salt-induced hypertension and renal injury in rats. And this blockade reduces the expression of Trpv1 in the DRGs projected by PRAT. Injecting AAV2-retro-shTrpv1 into the PRAT of DOCA-Salt mice also achieved the same therapeutic effect. However, DOCA-Salt-induced hypertension and renal injury can be treated in Trpv1+/- mice but not alleviated or even worsened in Trpv1-/- mice, possibly because of compensatory increase of Trpv5 in DRG of Trpv1-/- mice. CONCLUSION: Reducing, rather than eliminating, Trpv1 in DRG from PRAT-projection can reduce blood pressure and kidney damage in DOCA-Salt in rats or mice. Trpv1 in PRAT-DRGs may serve as a therapeutic target for salt-sensitive hypertension and its renal complications.

Elastic Relaxor Ferroelectric by Thiol-ene Click Reaction.

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

Esculin targets TLR4 to protect against LPS-induced septic cardiomyopathy.

BACKGROUND: Esculin, a main active ingredient from Cortex fraxini, possesses biological activities such as anti-thrombosis, anti-inflammatory, and anti-oxidation effects. However, the effects of Esculin on septic cardiomyopathy remains unclear. This study aimed to explore the protective properties and mechanisms of Esculin in countering sepsis-induced cardiac trauma and dysfunction. METHODS AND RESULTS: In lipopolysaccharide (LPS)-induced mice model, Esculin could obviously improve heart injury and function. Esculin treatment also significantly reduced the production of inflammatory and apoptotic cells, the release of inflammatory cytokines, and the expression of oxidative stress-associated and apoptosis-associated markers in hearts compared to LPS injection alone. These results were consistent with those of in vitro experiments based on neonatal rat cardiomyocytes. Database analysis and molecular docking suggested that TLR4 was targeted by Esculin, as shown by stable hydrogen bonds formed between Esculin with VAL-308, ASN-307, CYS-280, CYS-304 and ASP-281 of TLR4. Esculin reversed LPS-induced upregulation of TLR4 and phosphorylation of NF-κB p65 in cardiomyocytes. The plasmid overexpressing TLR4 abolished the protective properties of Esculin in vitro. CONCLUSION: We concluded that Esculin could alleviate LPS-induced septic cardiomyopathy via binding to TLR4 to attenuate cardiomyocyte inflammation, oxidative stress and apoptosis.

High-Curie-Temperature Elastic Polymer Ferroelectric by Carbene Cross-Linking.

With the emergence of wearable electronics, ferroelectrics are poised to serve as key components for numerous potential applications. Currently, intrinsically elastic ferroelectrics featuring a network structure through a precise "slight cross-linking" approach have been realized. The resulting elastic ferroelectrics demonstrate a combination of stable ferroelectric properties and remarkable resilience under various strains. However, challenges arose as the cross-linking temperature was too high when integrating ferroelectrics with other functional materials, and the Curie temperature of this elastic ferroelectric was comparatively low. Addressing these challenges, we strategically chose a poly(vinylidene fluoride)-based copolymer with high vinylidene fluoride content to obtain a high Curie temperature while synthesizing a cross-linker with carbene intermediate for high reactivity to reduce the cross-linking temperature. At a relatively low temperature, we successfully fabricated elastic ferroelectrics through carbene cross-linking. The resulting elastic polymer ferroelectrics exhibit a higher Curie temperature and show a stable ferroelectric response under strains up to 50%. These materials hold significant potential for integration into wearable electronics.

Colquhounia root tablet in the treatment of idiopathic membranous nephropathy with subnephrotic proteinuria.

PURPOSE: Idiopathic membranous nephropathy (IMN) is the most frequent global cause of nephrotic syndrome in non-diabetic people. In clinical practice, An effective and mild treatment for IMN patients with subnephrotic proteinuria has been adopted. Colquhounia root tablet (CRT) is a traditional Chinese medicine that is widely used in China to treat glomerulopathies. In this study, the effectiveness and safety of CRT in the treatment of IMN with subnephrotic proteinuria have been determined by reviewing the clinical records of 44 patients with IMN. METHODS: Retrospective analysis of IMN patients with subnephrotic proteinuria treated with CRT in combination with ACEI/ARB or ACEI/ARB alone. The remission rate (complete or partial remission) was the main outcome observed, and proteinuria, estimated glomerular filtration rate (eGFR), serum albumin levels, and adverse effects were the secondary outcomes. RESULTS: This clinical trial included 44 patients, and the overall remission rates at months 6, 9, and 12 after treatment were 68.2% versus 27.3% (p = 0.016), 72.7% versus 36.4% (p = 0.015), and 77.3% versus 36.4% (p = 0.006) in the treatment and control groups, respectively. The application of CRT treatment was an independent predictor of proteinuria remission (p = 0.024). In addition, in patients who were positive for phospholipase A2 receptor (PLA2R) antibodies, the overall remission rate was higher in the treatment group than in the control group after 9 months of treatment (75% versus 23.08%, p = 0.017). CONCLUSION: This retrospective study illustrates that, based on supportive therapy, CRT could be effective in the treatment of IMN with subnephrotic proteinuria with a good safety profile at the same time.

Shh-Gli2-Runx2 inhibits vascular calcification.

BACKGROUND: In patients with chronic kidney disease (CKD), vascular calcification (VC) is common and is associated with a higher risk of all-cause mortality. Shh, one ligand for Hedgehog (Hh) signaling, participates in osteogenesis and several cardiovascular diseases. However, it remains unclear whether Shh is implicated in the development of VC. METHODS: Inorganic phosphorus 2.6 mM was used to induce vascular smooth muscle cells (VSMCs) calcification. Mice were fed with adenine diet supplement with 1.2% phosphorus to induce VC. RESULTS: Shh was decreased in VSMCs exposed to inorganic phosphorus, calcified arteries in mice fed with an adenine diet, as well as radial arteries from patients with CKD presenting VC. Overexpression of Shh inhibited VSMCs ostosteoblastic differentiation and calcification, whereas its silencing accelerated these processes. Likewise, mice treated with smoothened agonist (SAG; Hh signaling agonist) showed alleviated VC, and mice treated with cyclopamine (CPN; Hh signaling antagonist) exhibited severe VC. Additionally, overexpression of Gli2 significantly reversed the pro-calcification effect of Shh silencing on VSMCs, suggesting that Shh inhibited VC via Gli2. Mechanistically, Gli2 interacted with Runx2 and promoted its ubiquitin proteasomal degradation, therefore protecting against VC. Of interest, the pro-degradation effect of Gli2 on Runx2 was independent of Smurf1 and Cullin4B. CONCLUSIONS: Our study provided deeper insight to the pathogenesis of VC, and Shh might be a novel potential target for VC treatment.

Hollow-microsphere-integrated optofluidic immunochip for myocardial infarction biomarker microanalysis.

This work developed an optofluidic immunochip that uses whispering gallery mode with fiber laser enhancement, for the rapid detection of a key biomarker cardiac troponin I for acute myocardial infarction (AMI). The immunochip adopted an innovative design, using perforated hollow glass microspheres (HGMS) as carriers, with antibodies immobilized on the inner surface of the HGMS, thereby achieving ultra-low sample consumption. The performance of the immunochip was improved by fiber laser, including spectral width compression to 0.019 nm, optical signal-to-noise ratio amplification to 63.17 dB, and an enhancement in the limit of detection to 5 pg/mL. Moreover, this immunochip can provide results within 15 min, making it highly suitable for early AMI risk management. Compared to the standard electrochemiluminescence detection method, although some differences exist in the results of the immunochip due to the principle of detection and differences in antibody affinity, its positive reference value can be calculated as 0.0754 ng/mL, with a successful recognition rate of 88% for positive patients. The immunosensor is integrated on a polydimethylsiloxane substrate, with a compact size suitable for use in point-of-care devices and AMI self-screening, as well as rapid disease screening and microanalysis of various biomarkers, offering new possibilities for applications in these fields.

Simultaneous bond-selective deuterium-based isotopic labeling sensing with disposable ultra-miniature CARS fiber probe.

Deuterium-based isotopic labeling is an important technique for tracking cellular metabolism with the Raman signals analysis of low-wavenumber (LW) C-D bonds and high-wavenumber (HW) C-H bonds. We propose and demonstrate a disposable ultra-miniature fiber probe to detect LW and HW coherent anti-Stokes Raman scattering (CARS) spectra for deuterated compounds simultaneously and bond-selectively sensing. The 10.78 µm diameter disposable fiber probe, comprised of focusing taper as fiber probe head and time-domain walk-off eliminating fiber section with designed length, realizes wide-frequency-interval dual Stokes pulse delivering and focusing. The fiber probe enables quantitative concentration determination with resolution down to 11 mM. The chemical vibration modes of LW region C-D bonds and HW region C-H bonds of the mixture samples of organic compounds and their deuterated counterparts in a simulated cell are simultaneously excited and characterized. The CARS disposable fiber probe introduces a promising handle for in vivo biochemical detection based on isotopic labeling sensing.

Highly sensitive and label-free detection of biotin using a liquid crystal-based optofluidic biosensor.

A liquid crystal (LC)-based optofluidic whispering gallery mode (WGM) resonator has been applied as a biosensor to detect biotin. Immobilized streptavidin (SA) act as protein molecules and specifically bind to biotin through strong non-covalent interaction, which can interfere with the orientation of LCs by decreasing the vertical anchoring force of the alignment layer in which the WGM spectral wavelength shift is monitored as a sensing parameter. Due to the double magnification of the LC molecular orientation transition and the resonance of the WGM, the detection limit for SA can reach 1.25 fM (4.7 × 10-13 g/ml). The measurable concentration of biotin and the wavelength shift of the WGM spectrum have an excellent linearity in the range of 0 to 0.1 pg/ml, which can achieve ultra-low detection limit (0.4 fM), i.e., seven orders of magnitude improvement over conventional polarized optical microscope (POM) method. The proposed optofluidic biosensor is highly reproducible and can be used as an ultrasensitive real-time monitoring biosensor, which will open the door for applications to other receptor and ligand models.

Another thread to uncover the aging mystery of white tea: Focusing on the natural nanoparticles in tea infusion.

Aged white tea (WT) has promising medicinal potential, but how to accurately identify aged white tea is still a difficult problem. Inspired by tea cream, the relationship between the characteristics of nanoparticles in tea infusion and aging time was studied. The results showed that with the increase of aging time, the particle size of white tea nanoparticles (WTNs) decreased gradually. Microscopic images showed that the surface structure of WTNs was changed in three aspects: the waxy layer, the cuticle layer and the palisade tissue. Additional in vitro modeling demonstrated a strong correlation between nanoparticle size and protein and tea polyphenol content. The correlation between nanoparticle sizes and aging time was further verified in aged Pu'er raw tea. Starting with the tea infusion's nanoparticles, this study showed that the aging time of WT would impact the nanoparticles' properties, offering a unique way to determine the aging period of WT.

Achievable information rate optimization in C-band optical fiber communication system.

Optical fiber communication networks play an important role in the global telecommunication network. However, nonlinear effects in the optical fiber and transceiver noise greatly limit the performance of fiber communication systems. In this paper, the product of mutual information (MI) and communication bandwidth is used as the metric of the achievable information rate (AIR). The MI loss caused by the transceiver is also considered in this work, and the bit-wise MI, generalized mutual information (GMI), is used to calculate the AIR. This loss is more significant in the use of higher-order modulation formats. The AIR analysis is carried out in the QPSK, 16QAM, 64QAM and 256QAM modulation formats for the communication systems with different communication bandwidths and transmission distances based on the enhanced Gaussian noise (EGN) model. The paper provides suggestions for the selection of the optimal modulation format in different transmission scenarios.

Hedgehog signaling is a potential therapeutic target for vascular calcification.

BACKGROUND: Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling plays a crucial role in physiological bone mineralization and is associated with several cardiovascular diseases. However, the molecular changes underlying VC is ill defined and it remains unclear whether Hh signaling intervention affects VC. METHODS: We constructed human primary vascular smooth muscle cell (VSMC) calcification model and performed RNA sequencing. Alizarin red staining and calcium content assay were conducted to identify the occurrence of VC. Three different R packages were applied to determine differentially expressed genes (DEGs). Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out to explore the biological roles of DEGs. qRT-PCR assay was then applied to validate the expression of key genes. By using Connectivity Map (CMAP) analysis, several small molecular drugs targeting these key genes were obtained, including SAG (Hedgehog signaling activator) and cyclopamine (CPN) (Hedgehog signaling inhibitor), which were subsequently used to treat VSMC. RESULTS: Obvious Alizarin red staining and increased calcium content identified the occurrence of VC. By integrating results from three R packages, we totally obtained 166 DEGs (86 up-regulated and 80 down-regulated), which were significantly enriched in ossification, osteoblast differentiation, and Hh signaling. PPI network analysis identified 10 key genes and CMAP analysis predicted several small molecular drugs targeting these key genes including chlorphenamine, isoeugenol, CPN and phenazopyridine. Notably, our in vitro experiment showed that SAG markedly alleviated VSMC calcification, whereas CPN significantly exacerbated VC. CONCLUSIONS: Our research provided deeper insight to the pathogenesis of VC and indicated that targeting Hh signaling pathway may represent a potential and effective therapy for VC.

Ginkgolide A targets forkhead box O1 to protect against lipopolysaccharide-induced septic cardiomyopathy.

Ginkgolide A (GA), a main terpenoid extracted from Ginkgo biloba, possesses biological activities such as anti-inflammatory, anti-tumor, and liver protection. However, the inhibitory effects of GA on septic cardiomyopathy remain unclear. This study aimed to explore the effects and mechanisms of GA in countering sepsis-induced cardiac dysfunction and injury. In lipopolysaccharide (LPS)-induced mouse model, GA alleviated mitochondrial injury and cardiac dysfunction. GA also significantly reduced the production of inflammatory and apoptotic cells, the release of inflammatory indicators, and the expression of oxidative stress-associated and apoptosis-associated markers, but increased the expression of pivotal antioxidant enzymes in hearts from LPS group. These results were consistent with those of in vitro experiments based on H9C2 cells. Database analysis and molecular docking suggested that FoxO1 was targeted by GA, as shown by stable hydrogen bonds formed between GA with SER-39 and ASN-29 of FoxO1. GA reversed LPS-induced downregulation of nucleus FoxO1 and upregulation of p-FoxO1 in H9C2 cells. FoxO1 knockdown abolished the protective properties of GA in vitro. KLF15, TXN2, NOTCH1, and XBP1, as the downstream genes of FoxO1, also exerted protective effects. We concluded that GA could alleviate LPS-induced septic cardiomyopathy via binding to FoxO1 to attenuate cardiomyocyte inflammation, oxidative stress, and apoptosis.

Optimally Configured Optical Fiber Near-Field Enhanced Plasmonic Resonance Immunoprobe for the Detection of Alpha-Fetoprotein.

The detection of trace biomarkers is an important supplementary approach for early screening and diagnoses of tumors. An optical fiber near-field enhanced plasmonic resonance immunoprobe is developed for the detection of the hepatocellular carcinoma biomarker, i.e., the alpha-fetoprotein. Generic principles based on dispersion models and finite element analysis (FEA) models are developed to realize the optimized configuration of spectral characteristics of the immunoprobe. Dispersion models provide theoretical guidance for the design of the multilayer sensing structure from the perspective of the ray optics theory. FEA models provide theoretical guidance for the selection of coating materials from the perspective of the self-defined dielectric constant ratio, i.e., the ratio of the real part to the imaginary part. The optimized configuration of the antibody coupling further improves the biosensing performance of the immunoprobe. The limit of detection (LOD) can reach down to 0.01 ng mL-1 , which is one order of magnitude lower than those relevant reported works. Such a low LOD can more effectively avoid the accuracy degradation of detection results due to measurement errors. Human serum samples have also been detected, with the good precision achieved. This work shows promising prospects in applications of label-free, low-cost, rapid, and convenient early screening of tumors.

Autonomous Microlasers for Profiling Extracellular Vesicles from Cancer Spheroids.

Self-propelled micro/nanomotors are emergent intelligent sensors for analyzing extracellular biomarkers in circulating biological fluids. Conventional luminescent motors are often masked by a highly dynamic and scattered environment, creating challenges to characterize biomarkers or subtle binding dynamics. Here we introduce a strategy to amplify subtle signals by coupling strong light-matter interactions on micromotors. A smart whispering-gallery-mode microlaser that can self-propel and analyze extracellular biomarkers is demonstrated through a liquid crystal microdroplet. Lasing spectral responses induced by cavity energy transfer were employed to reflect the abundance of protein biomarkers, generating exclusive molecular labels for cellular profiling of exosomes derived from 3D multicellular cancer spheroids. Finally, a microfluidic biosystem with different tumor-derived exosomes was employed to elaborate its sensing capability in complex environments. The proposed autonomous microlaser exhibits a promising method for both fundamental biological science and applications in drug screening, phenotyping, and organ-on-chip applications.

Wideband Multichannel Nyquist-Spaced Long-Haul Optical Transmission Influenced by Enhanced Equalization Phase Noise.

Enhanced equalization phase noise (EEPN), generated from the uncompensated dispersion experienced by laser phase noises, can cause serious damage to the transmission quality of optical fiber systems. In this work, the performance of a wideband Nyquist-spaced long-haul nonlinear optical fiber communication systems suffering from EEPN is investigated and discussed through split-step numerical simulations and analytical models based on the perturbation analysis, in the cases of digital nonlinearity compensation (NLC) and electronic dispersion compensation (EDC). The efficiency and the accuracy of the analytical models were validated via simulations, considering the different symbol rates and modulation formats. The performance of the C-band transmission was comprehensively studied based on the model. Our results reveal that the growth of symbol rates and transmission distances aggravates the distortions in the C-band system.