Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice.

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.

Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase.

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission.

Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418's inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma.

Prevalence, toxin-genotype distribution, and transmission of Clostridium perfringens from the breeding and milking process of dairy farms.

This study aimed to elucidate the distribution, transmission, and cross-contamination of Clostridium perfringens during the breeding and milking process from dairy farms. The prevalence of 22.3% (301/1351) yielded 494 C. perfringens isolates; all isolates were type A, except for one type D, and 69.8% (345/494) of the isolates carried atyp. cpb2 and only 0.6% (3/494) of the isolates carried cons. cpb2. C. perfringens detected throughout the whole process but without type F. 150 isolates were classified into 94 pulsed-field gel electrophoresis (PFGE) genotypes; among them, six clusters contained 34 PFGE genotypes with 58.0% isolates which revealed epidemic correlation and genetic diversity; four PFGE genotypes (PT57, PT9, PT61, and PT8) were the predominant genotypes. The isolates from different farms demonstrated high homology. Our study confirmed that C. perfringens demonstrated broad cross-contamination from nipples and hides of dairy cattle, followed by personnel and tools and air-introduced raw milk during the milking process. In conclusion, raw milk could serve as a medium for the transmission of C. perfringens, which could result in human food poisoning. Monitoring and controlling several points of cross-contamination during the milking process are essential as is implementing stringent hygiene measures to prevent further spread and reduce the risk of C. perfringens infection.

Activities of daily living predict periprocedural myocardial infarction and injury following percutaneous coronary intervention: a cross-sectional study.

BACKGROUND: In recent years, there has been growing interest in exploring the relationship between activities of daily living (ADL) and cardiovascular diseases. This retrospective cross-sectional study aimed to investigate the association of ADL measured by Barthel index (BI) with periprocedural myocardial infarction (PMI) and injury following percutaneous coronary intervention (PCI). METHODS: Enrolled patients were stratified into impaired and unimpaired ADL groups according to their BI scores. Logistic regressions were conducted to explore the association of ADL on admission with periprocedural myocardial injury and infarction. Restricted cubic spline (RCS) curve and subgroup analysis were also performed. RESULTS: Totally, 16.4% of patients suffered from PMI; the mean age was 65.8 ± 10.4 years old. RCS analysis showed that the morbidity of periprocedural myocardial infarction and injury showed a downward tendency with increasing BI scores. Multivariable logistic regression analysis demonstrated that impaired ADL was an independent risk factor for periprocedural myocardial infarction (OR = 1.190, 95% CI [1.041, 1.360], P = 0.011) and injury (OR = 1.131, 95% CI [1.017, 1.257], P = 0.023). Subgroup analysis showed that the association between ADL and PMI was founded in several subgroups, while the association between ADL and periprocedural myocardial injury was founded only in BMI ≥ 24 kg/m2 subgroup. CONCLUSION: Impaired ADL at hospital admission was an independent risk factor for periprocedural myocardial infarction and injury among patients following PCI.

Diastereoselective Cascade Cyclization of Diazoimides with Alkylidene Pyrazolones for Preparation of Pyrazole-Fused Oxa-Bridged Oxazocines.

Under the catalysis of Rh2(OAc)4 (10 mol%) and binapbisphosphine ligand (±)-L3 (20 mol%) in DCE at 80 °C, the cascade cyclization of diazoimides with alkylidenepyrazolones underwent stereoselectively (dr > 20:1), affording pyrazole-fused oxa-bridged oxazocines in reasonable chemical yields. The chemical structure and relative configuration of title products were firmly identified by X-ray diffraction analysis.

Developmental toxicity of TCBPA on the nervous and cardiovascular systems of zebrafish (Danio rerio): A combination of transcriptomic and metabolomics.

Tetrachlorobisphenol A (TCBPA), a widely used halogenated flame retardant, is frequently detected in environmental compartments and human samples. However, unknown developmental toxicity and mechanisms limit the entire understanding of its effects. In this study, zebrafish (Danio rerio) embryos were exposed to various concentrations of TCBPA while a combination of transcriptomics, behavioral and biochemical analyzes as well as metabolomics were applied to decipher its toxic effects and the potential mechanisms. We found that TCBPA could interfere with nervous and cardiovascular development through focal adhesion and extracellular matrix-receptor (ECM-receptor) interaction pathways through transcriptomic analysis. Behavioral and biochemical analysis results indicated abnormal swimming behavior of zebrafish larvae. Morphological observations revealed that TCBPA could cause the loss of head blood vessels. Metabolomic analysis showed that arginine-related metabolic pathways were one of the main pathways leading to TCBPA developmental toxicity. Our study demonstrated that by using omics, TCBPA was shown to have neurological and cardiovascular developmental toxicity and the underlying mechanisms were uncovered and major pathways identified.

Synthesis of Renal-Clearable Multicolor Fluorescent Silicon Nanodots for Tumor Imaging and In Vivo H2O2 Profiling.

Fluorescent silicon nanodots have shown great prospects for bioimaging and biosensing applications. Although various fluorescent silicon-containing nanodots (SiNDs) have been developed, there are few reports about renal-clearable multicolor SiNDs. Herein, renal-clearable multicolor fluorescent SiNDs are synthesized by using silane molecules and organic dyes through a facile one-step hydrothermal method. The fluorescence of the resulting SiNDs can be tuned to blue (bSiNDs), green (gSiNDs), and red (rSiNDs) by simply changing the categories of silane reagents or dye molecules. The as-prepared SiNDs exhibit strong fluorescence with a quantum yield up to 72%, excellent photostability, and good biocompatibility with 12 h renal clearance rate as high as 86% ID. These properties enabled the SiNDs for tumor fluorescence imaging and H2O2 imaging in living cells and tissue through in situ reduction reaction-lighted fluorescence of the nanoprobe. Our results provide an invaluable methodology for the synthesis of renal-clearable multicolor SiNDs and their potential applications for fluorescence imaging and biomarker sensing. These SiNDs are also promising for various biological and biomedical applications.

Peroxydisulfate Activation and Singlet Oxygen Generation by Oxygen Vacancy for Degradation of Contaminants.

Oxygen vacancies (OVs) play a crucial role in the catalytic activity of metal-based catalysts; however, their activation mechanism toward peroxydisulfate (PDS) still lacks reasonable explanation. In this study, by taking bismuth bromide (BiOBr) as an example, we report an OV-mediated PDS activation process for degradation of bisphenol A (BPA) employing singlet oxygen (1O2) as the main reactive species under alkaline conditions. The experimental results show that the removal efficiency of BPA is proportional to the number of OVs and is highly related to the dosage of PDS and the catalyst. The surface OVs of BiOBr provide ideal sites for the inclusion of hydroxyl ions (HO-) to form BiIII-OH species, which are regarded as the major active sites for the adsorption and activation of PDS. Unexpectedly, the activation of PDS occurs through a nonradical mechanism mediated by 1O2, which is generated via multistep reactions, involving the formation of an intermediate superoxide radical (O2•-) and the redox cycle of Bi(III)/Bi(IV). This work is dedicated to the in-depth mechanism study into PDS activation over OV-rich BiOBr samples and provides a novel perspective for the activation of peroxides by defective materials in the absence of additional energy supply or aqueous transition metal ions.

Modeling pesticides toxicity to Sheepshead minnow using QSAR.

Nowadays, the environmental risk caused by the widespread use of pesticides and their ubiquitous residuals has received more and more attention in academia and regulatory agencies. Due to the large number of pesticides used in agriculture and their adverse effects on all living organisms and the numerous end-points, it is necessary to employ the in silico tools to quickly highlight hazardous pesticides. In this study, we have evaluated the toxicity of pesticides against Sheepshead minnow with the Quantitative Structure-Activity Relationship (QSAR) approach. The models for the specific-type (insecticides, herbicides and fungicides) as well as the general-type (combing all the specific-type pesticides and some microbicides, nematicides, etc.) pesticides were developed using the Genetic Algorithm and the Multiple Linear Regression method, subsequently validated with various metrics. The validation results suggested that the obtained models were highly robust, externally predictive and characterized by a broad applicability domain. Considering the modeling descriptors, the toxicity of pesticides would increase with the lipophilicity and decrease with the polarity and hydrophilicity. Most electrotopological state descriptors contribute negatively to the toxicity, while the influence of topological structure descriptors mainly depends on the physiochemical information they encode. The models proposed in this paper would be useful in filling the data gaps, prioritizing and then focusing experiments on more hazardous pesticides.

Low concentrations of perfluorooctane sulfonate repress osteogenic and enhance adipogenic differentiation of human mesenchymal stem cells.

Humans are exposed to perfluorooctane sulfonate (PFOS) from sources of both continuing discharges and environmental legacies, and the health effects of low dose exposure remain unknown. We assessed the effects of PFOS at 0.2-200 nmol/L on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). PFOS affected hBMSCs differentiation in a nonmonotonic dose-response relationship, where the effects peaked at 100 nmol/L. PFOS repressed calcium deposition on day 14 of osteogenic differentiation. The molecular osteogenic biomarkers, osteopontin, osteonectin and osteocalcin, and the transcription factor ß-catenin, were also decreased on differentiation day 7. In hBMSCs co-treated by PFOS and WNT signaling agonist, LiCl, the osteogenic marker levels were higher than those treated by PFOS alone. Moreover, the osteogenic effect of PFOS was repressed by DKK1, the WNT signaling antagonist. PFOS additionally supported the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio. In contrast, PFOS enhanced adipogenesis in regard to lipid droplet formation and marker gene expression of PPARγ, CCAAT/enhancer-binding protein-α (C/EBPα), lipoprotein lipase and leptin. Microarray analysis identified 597 differentially expressed genes at p < .05 and log2 (fold change) > 0.3. These results demonstrated that PFOS repressed osteogenesis and enhanced adipogenesis, which could well explain the homeostatic imbalance seen in human bone associated with exposure to PFOS.

Influences of an Aluminum Covering Layer on the Performance of Cross-Like Hall Devices.

This work studies the effects of an aluminum covering on the performance of cross-like Hall devices. Four different Hall sensor structures of various sizes were designed and fabricated. The sensitivity and offset of the Hall sensors, two key points impacting their performance, were characterized using a self-built measurement system. The work analyzes the influences of the aluminum covering on those two aspects of the performance. The aluminum layer covering mainly leads to an eddy-current effect in an unstable magnetic field and an additional depletion region above the active region. Those two points have influences on the sensitivity and the offset voltage, respectively. The analysis guides the designer whether to choose covering with an aluminum layer the active region of the Hall sensor as a method to reduce the flicker noise and to improve the stability of the Hall sensor. Because Hall devices, as a reference element, always suffer from a large dispersion, improving their stability is a crucial issue.

Standardized Uptake Value on F-FDG PET/CT as a Prognostic Factor for Survival of Women with Malignant Uterine Tumors: A Meta-Analysis.

BACKGROUND: Malignant uterine tumors are crucial in the evaluation of prognosis and the determination of therapeutic strategy. AIM: This meta-analysis of the available literature aimed to investigate the prognostic value of standardized uptake value (SUV) on fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) in uterine malignancies before treatment. METHODS: The PubMed, MEDLINE and EMBASE databases (1990 to February 2014) were searched to identify studies evaluating SUV on 18F-FDG PET/CT as a prognostic tool for predicting long-term survival in patients with carcinomas of the uterus. The χ2 test and the I2 index were used to estimate heterogeneity among the trials selected in the meta-analysis. The combined hazard ratio was calculated by using a fixed- or random-effects model according to heterogeneity. RESULTS: Thirteen studies with a total of 1,196 patients were eligible for analysis. High pretreatment SUVmax was significantly associated with poorer event-free survival and overall survival, and the summarized hazard ratio was 3.33 (95% confidence interval 2.34-4.74) and 1.31 (95% confidence interval 1.03-1.67), respectively. CONCLUSION: The present evidence indicates that SUV on 18F-FDG PET/CT seems to be a valuable prognostic indicator for survival of patients with malignant uterine tumors. Given that 18F-FDG PET/CT can provide both morphologic and functional information, we suggest utilizing PET/CT and its quantitative marker in uterine malignancies before treatment. © 2015 S. Karger AG, Basel.

Performance comparison of cross-like Hall plates with different covering layers.

This paper studies the effects of the covering layers on the performance of a cross-like Hall plate. Three different structures of a cross-like Hall plate in various sizes are designed and analyzed. The Hall plate sensitivity and offset are characterized using a self-built measurement system. The effect of the P-type region over the active area on the current-related sensitivity is studied for different Hall plate designs. In addition, the correlation between the P-type covering layer and offset is analyzed. The best structure out of three designs is determined. Besides, a modified eight-resistor circuit model for the Hall plate is presented with improved accuracy by taking the offset into account.

Constructing Lysozyme Protective Layer via Conformational Transition for Aqueous Zn Batteries.

The practical applications for aqueous Zn ion batteries (ZIBs) are promising yet still impeded by the severe side reactions on Zn metal. Here, a lysozyme protective layer (LPL) is prepared on Zn metal surface by a simple and facile self-adsorption strategy. The LPL exhibits extremely strong adhesion on Zn metal to provide stable interface during long-term cycling. In addition, the self-adsorption strategy triggered by the hydrophobicity-induced aggregation effect endows the protective layer with a gap-free and compacted morphology which can reject free water for effective side reaction inhibition performance. More importantly, the lysozyme conformation is transformed from α-helix to ß-sheet structure before layer formation, thus abundant functional groups are exposed to interact with Zn2+ for electrical double layer (EDL) modification, desolvation energy decrease, and ion diffusion kinetics acceleration. Consequently, the LPL renders the symmetrical Zn battery with ultra-long cycling performance for more than 1200 h under high Zn depth of discharge (DOD) for 77.7%, and the Zn/Zn0.25V2O5 pouch cell with low N/P ratio of 2.1 at high Zn utilization of 48% for over 300 cycles. This study proposes a facile and low-cost method for constructing a stable protective layer of Zn metal for high Zn utilization aqueous devices.

Lead specifically declines tyrosine hydroxylase activity to induce the onset of Parkinson's disease through disrupting dopamine biosynthesis in fly models.

Parkinson's disease (PD) is one of the fastest-growing neurodegenerative diseases and has been linked to the exposure to numerous environmental neurotoxins. Although lead (Pb) exposure has been related to the development of PD, the molecular target of Pb to cause the onset of PD is insufficiently investigated. Herein, we explored the effects of Pb exposure on behavior, pathophysiology, and gene expression of wild-type (WT) fly (Drosophila melanogaster) by comparison with its PD model. After exposure to Pb, the WT flies showed PD-like locomotor impairments and selective loss of dopaminergic (DAergic) neurons, displaying similar phenotypes to fly PD model (PINK1). Transcriptomic analysis showed the similarity in gene expression profiles between Pb treatment WT flies and PINK1 mutant flies. Moreover, Pb exposure resulted in endogenous dopamine deficits in WT flies. Analyses of gene expression and enzyme activity confirmed that Pb exposure reduced tyrosine hydroxylase (TH) activity and led to failure of dopamine synthesis. Furthermore, molecular dynamics simulation confirmed that Pb was adsorbed by TH and subsequently inhibited the enzymatic activity. Exogenous injection of L-dopa and melatonin could partially rescue the pathological phenotypes of Pb-exposed flies and PD fly model. Antagonist injection of microRNA-133, which negatively regulated the expression of TH gene, ultimately rescued in the manifestation of PD phenotypes in flies. Involvement of TH overexpression mutants of fly strongly promoted the resistance to Pb exposure and rescued both behavior and the number of DAergic neurons. Therefore, our study elucidates the Pb molecular target in dopamine pathway and mechanism underlying the risks of Pb exposure on the occurrence of PD at environmentally-relevant concentrations.

Anti-Oxidized Self-Assembly of Multilayered F-Mene/MXene/TPU Composite with Improved Environmental Stability and Pressure Sensing Performances.

MXenes, as emerging 2D sensing materials for next-generation electronics, have attracted tremendous attention owing to their extraordinary electrical conductivity, mechanical strength, and flexibility. However, challenges remain due to the weak stability in the oxygen environment and nonnegligible aggregation of layered MXenes, which severely affect the durability and sensing performances of the corresponding MXene-based pressure sensors, respectively. Here, in this work, we propose an easy-to-fabricate self-assembly strategy to prepare multilayered MXene composite films, where the first layer MXene is hydrogen-bond self-assembled on the electrospun thermoplastic urethane (TPU) fibers surface and the anti-oxidized functionalized-MXene (f-MXene) is subsequently adhered on the MXene layer by spontaneous electrostatic attraction. Remarkably, the f-MXene surface is functionalized with silanization reagents to form a hydrophobic protective layer, thus preventing the oxidation of the MXene-based pressure sensor during service. Simultaneously, the electrostatic self-assembled MXene and f-MXene successfully avoid the invalid stacking of MXene, leading to an improved pressure sensitivity. Moreover, the adopted electrospinning method can facilitate cyclic self-assembly and the formation of a hierarchical micro-nano porous structure of the multilayered f-MXene/MXene/TPU (M-fM2T) composite. The gradient pores can generate changes in the conductive pathways within a wide loading range, broadening the pressure detection range of the as-proposed multilayered f-MXene/MXene/TPU piezoresistive sensor (M-fM2TPS). Experimentally, these novel features endow our M-fM2TPS with an outstanding maximum sensitivity of 40.31 kPa-1 and an extensive sensing range of up to 120 kPa. Additionally, our M-fM2TPS exhibits excellent anti-oxidized properties for environmental stability and mechanical reliability for long-term use, which shows only ~0.8% fractional resistance changes after being placed in a natural environment for over 30 days and provides a reproducible loading-unloading pressure measurement for more than 1000 cycles. As a proof of concept, the M-fM2TPS is deployed to monitor human movements and radial artery pulse. Our anti-oxidized self-assembly strategy of multilayered MXene is expected to guide the future investigation of MXene-based advanced sensors with commercial values.

Magnoflorine attenuates Ang II-induced cardiac remodeling via promoting AMPK-regulated autophagy.

Background: Heart failure (HF) remains one of the most common events in the progression of hypertension. Magnoflorine (MNF) has been shown beneficial effects on the cardiovascular system. However, the action of MNF on angiotensin (Ang) II-induced cardiac remodeling and its underlying mechanisms have not yet been characterised. Here, we assessed the action of MNF in the development of hypertension-related HF. Methods: C57BL/6 male mice were subjected to Ang II through a micro-osmotic pump infusion continuously for 4 weeks to induce hypertensive HF. MNF (10 and 20 mg/kg) was administered in the final 2 weeks. Ang II content was measured by enzyme-linked immunosorbent assay (ELISA) kit. Values of ejection fraction (EF) and fractional shortening (FS) were detected using an ultrasound diagnostic instrument. The mRNA levels of hypertrophic and fibrotic genes were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Haematoxylin and eosin (H&E), wheat germ agglutinin (WGA), Masson trichrome, and Sirius Red staining were used to analyse pathologic changes in heart tissues. The expression levels of phosphorylated AMP-activated protein kinase (AMPK), light chain 3 microtubule associated protein II (LC3 II) to LC3 I, and p62 were detected by western blot assay. Results: MNF significantly improved cardiac dysfunction and the content of creatine kinase-MB without altering blood pressure in Ang II-challenged mice. MNF obviously corrected the phenotypes of cardiac hypertrophy and fibrosis, including the high mRNA levels of atrial natriuretic peptide (Anp), brain natriuretic peptide (Bnp), collagen1a (Col1a1), transforming growth factor beta (Tgfb1), enlarged myocardial areas, and increased positive areas of Masson trichrome and Sirius Red staining. In addition, MNF alleviated oxidative injury, reflected by the upregulation of glutathione and the downregulation of reactive oxygen species and malondialdehyde. The activation of AMPK was elevated accompanied by an increased level of autophagy by MNF in hypertensive heart tissues. The therapeutic action of MNF was confirmed in Ang II-challenged H9c2 cells. Specifically, the AMPK inhibitor could eliminate the autophagy pathway in which MNF is involved. Conclusions: MNF has benefits in hypertension-induced cardiac remodeling, which was partially associated with the improvement of oxidative stress via the mediation of the AMPK/autophagy axis.

Plasma metabolic profiling reveals that crude and processed Polygonatum cyrtonema hua extract ameliorates myocardial ischemia-induced damage by regulating branched-chain amino acid and energy metabolism.

Polygonatum cyrtonema Hua and its processed products have demonstrated cardio-protective effects, though the underlying mechanisms remain unclear. In this study, plasma metabolic profiling and pattern recognition were employed to explore the cardio-protective mechanisms of both crude and processed P. cyrtonema in a myocardial ischemia model induced by ligation, using gas chromatography-mass spectrometry. Post-modeling, plasma levels of creatine kinase-MB, lactate dehydrogenase, troponin T, and malondialdehyde were significantly elevated but were notably reduced after treatment. Conversely, plasma levels of glutathione peroxidase and superoxide dismutase, which were significantly decreased post-modeling, were restored following treatment. Hematoxylin-eosin (HE) and Masson staining revealed that both crude and processed P. cyrtonema effectively reduced inflammatory infiltration and fibrosis in cardiac tissue. Metabolic profiling identified 34 differential endogenous metabolites in the treatment groups, with 19 confirmed using standard compounds. The linear correlation coefficients (R2) for these standards ranged from 0.9960 to 0.9996, indicating high accuracy. The method exhibited excellent precision and repeatability, with relative standard deviation (RSD) values below 8.57%. Recovery rates were between 95.02% and 105.15%, and the stability of the standard compounds was confirmed after three freeze-thaw cycles, with RSD values under 4.42%. Both crude and processed P. cyrtonema were found to alleviate myocardial ischemia symptoms by regulating branched-chain amino acid metabolism and energy metabolism. These findings provide a solid foundation for the potential clinical use of this herb and its processed products in treating heart disease.

A liquid metal-embedded 3D interconnected-porous TPU/MXene composite with improved capacitive sensitivity and pressure detection range.

Flexible capacitive sensors are widely deployed in wearable smart electronics. Substantial studies have been devoted to constructing characteristic material architectures to improve their electromechanical sensing performance by facilitating the change of the electrode layer spacing. However, the air gaps introduced by the designed material architectures are easily squeezed when subjected to high-pressure loads, resulting in a limited increase in sensitivity over a wide range. To overcome this limitation, in this work, we embed the liquid metal (LM) in the internally interconnected porous structure of a flexible composite foam to fabricate a flexible and high-performance capacitive sensor. Different from the conventional conductive elements filled composite, the incompressible feature of the embedded fluidic LM leads to significantly improved mechanical stability of the composite foam to withstand high pressure loadings, resulting in a wider pressure sensing range from 10 Pa to 260 kPa for our capacitive composite sensor. Simultaneously, the metal conductivity and liquid ductility of the embedded LM endow the as-fabricated capacitive sensor with outstanding mechanical flexibility and pressure sensitivity (up to 1.91 kPa-1). Meanwhile, the LM-embedded interconnected-porous thermoplastic polyurethane/MXene composite sensor also shows excellent reliability over 4000 long-period load cycles, and the response times are merely 60 ms and 110 ms for the loading and unloading processes, respectively. To highlight their advantages in various applications, the as-proposed capacitive sensors are demonstrated to detect human movements and monitor biophysical heart-rate signals. It is believed that our finding could extend the material framework of flexible capacitive sensors and offer new possibilities and solutions in the development of the next-generation wearable electronics.