PCG-based exercise fatigue detection method using multi-scale feature fusion model.

Accurate detection of exercise fatigue based on physiological signals is vital for reasonable physical activity. Existing studies utilize widely Electrocardiogram (ECG) signals to achieve exercise monitoring. Nevertheless, ECG signals may be corrupted because of sweat or loose connection. As a non-invasive technique, Phonocardiogram (PCG) signals have a strong ability to reflect the Cardiovascular information, which is closely related to physical state. Therefore, a novel PCG-based detection method is proposed, where the feature fusion of deep learning features and linear features is the key technology of improving fatigue detection performance. Specifically, Short-Time Fourier Transform (STFT) is employed to convert 1D PCG signals into 2D images, and images are fed into the pre-trained convolutional neural network (VGG-16) for learning. Then, the fusion features are constructed by concatenating the VGG-16 output features and PCG linear features. Finally, the concatenated features are sent to Support Vector Machines (SVM) and Linear Discriminant Analysis (LDA) to distinguish six levels of exercise fatigue. The experimental results of two datasets show that the best performance of the proposed method achieves 91.47% and 99.00% accuracy, 91.49% and 99.09% F1-score, 90.99% and 99.07% sensitivity, which has comparable performance to an ECG-based system which is as gold standard (94.32% accuracy, 94.33% F1-score, 94.52% sensitivity).

[Mechanism of Panax notoginseng saponins in treating diabetic kidney disease based on network pharmacology and experimental verification].

This study aims to investigate the therapeutic effect and mechanism of Panax notoginseng saponins(PNS) on diabetic kidney disease(DKD) based on network pharmacology, molecular docking, animal experiments. Network pharmacology was employed to screen the potential targets, and STRING was employed to build the protein-protein interaction network. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out for the core targets screened out, and a ″components-targets-pathways″ visualization network was constructed to predict the potential mechanism of PNS in treating DKD. Five active ingredients were screened from PNS, the core targets of which for treating DKD were AKT1, STAT3, ESR1, HSP90AA1, MTOR, et al. The KEGG enrichment analysis showed that the pathways related to PNS for treating DKD included the pathway in cancer, chemical carcinogenesis-receptor activation, and PI3K-AKT signaling pathway. GO analysis revealed that protein binding, homologous protein binding, enzyme binding, and ATP binding were the main biological processes involved in the treatment of DKD with PNS. Male 6-week-old db/db mice were randomized into model, dapagliflozin, and low-dose and high-dose PNS groups, with 10 mice in each group. Ten 6-week-old db/m mice were used as the control group. Mice were administrated with corresponding drugs or distilled water(control and model groups) by gavage once a day for 8 weeks. The body weight, fasting blood glucose, kidney index, microalbuminuria, creatinine, microalbuminuria/creatinine ratio, and urea nitrogen content in the urine of mice were determined. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Masson staining were performed to observe the protective effect of PNS on the renal tissues in db/db mice. The results showed that PNS could significantly reduce the fasting blood glucose level and improve the renal damage in db/db mice. Western blot results showed that PNS down-regulated the protein levels of p-AKT1 and p-STAT3 and decreased the p-AKT1/AKT1 and p-STAT3/STAT3 ratios. In addition, high-dose PNS down-regulated the protein level of PIK3CA. In conclusion, PNS may exert the kidney-protecting effects in DKD by inhibiting STAT3 via the PI3K-AKT signaling pathway.

Value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of SLN in breast cancer.

BACKGROUND: Accurate sentinel lymph node (SLN) characterization is essential for breast cancer management, prompting advancements in imaging technologies such as contrast-enhanced ultrasound (CEUS) and sound touch quantification (STQ) to enhance diagnostic precision. OBJECTIVE: To explore the value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of sentinel lymph node (SLN) in breast cancer. METHODS: A total of 91 breast cancer patients (91 SLNs) admitted to the hospital from February 2022 to December 2023 were selected for this study. Among them, 26 patients with metastatic SLN confirmed by surgery and pathology were included in the metastatic SLN group, and 65 patients with non-metastatic SLN were included in the non-metastatic SLN group. Preoperative examination results of CEUS and STQ were retrospectively analyzed. The diagnostic efficacy of perfusion characteristics evaluated by CEUS and STQ parameters for the properties of SLN in breast cancer was analyzed using the receiver operating characteristics (ROC) curve. Statistical methods such as chi-square tests and logistic regression analysis were employed to analyze the data. RESULTS: Enhancement patterns differed significantly between the metastatic SLN and non-metastatic SLN groups (p< 0.05). ROC curve analysis indicated that CEUS perfusion characteristics had an AUC value of 0.823 for diagnosing SLN properties, with a sensitivity of 84.62% and specificity of 70.77% using type I as the critical value. Additionally, STQ measurement showed significantly higher values in the metastatic SLN group (44.18 ± 6.53 kPa) compared to the non-metastatic SLN group (34.69 ± 6.81 kPa) (t= 6.075, p< 0.001). The AUC value for STQ parameters in diagnosing metastatic SLN was 0.849, with a sensitivity of 73.08% and specificity of 92.31% using 42.40 kPa as the critical value. Though the AUC value of STQ measurement was higher than CEUS perfusion characteristics alone, the difference was not statistically significant (Z= 0.393, p= 0.695). Moreover, combining CEUS perfusion characteristics with STQ parameters yielded an AUC value of 0.815 for diagnosing SLN properties, showing no significant difference compared to diagnosis with CEUS or STQ parameters alone (Z= 0.149, 0.516, p= 0.882, 0.606). CONCLUSION: Combined use of perfusion characteristics evaluated by CEUS and STQ parameters can significantly improve the diagnostic specificity of SLN in breast cancer. It is worthy of clinical promotion.

Decade-long historical shifts in legacy and emerging per- and polyfluoroalkyl substances (PFAS) in surface sediments of China's marginal seas: Ongoing production and ecological risks.

Since the addition of perfluorooctane sulfonate (PFOS) to the Stockholm Convention in 2009, it became imperative to reassess the distribution and ecological risk of per- and polyfluoroalkyl substances (PFAS) in coastal sediments over the past decade as sediment records the history of pollutants from human activities. To achieve this, sediments were collected in 2009 and 2021 from China's coastal regions. Despite the consistent geographical pattern where the highest concentrations of ∑PFAS were found in the Yellow Sea, temporal changes have emerged. During the studied period, ∑PFAS levels experienced an increase in the East China Sea while concurrently witnessing a decrease in the South China Sea. Of significance, emerging PFAS compounds displayed not only rising concentrations but also a broader array, pointing towards their intensified production and utilization within China. Alarmingly, PFOS levels in sediments taken from the East China Sea maintained a consistently high ecological risk status over the last ten years. Significant correlations were found between long-chain PFAS and organic carbon content. Comparisons between datasets from 2009 to 2021 uncovered a shifting ecological risk landscape, with heightened concerns for PFOA in the East China Sea, while PFOS-associated risks appeared to diminish in the South China Sea-potentially reflecting the transition to alternative PFAS chemicals. The research reinforces the importance of continuous monitoring and emphasizes the urgent necessity for deeper exploration into the environmental implications and hazards posed by emerging PFAS.

Hypoxic Signal Transduction and Compensatory Mechanisms in the Neurovascular Unit.

Hypoxic hypoxia arises from an inadequate oxygen supply to the blood, resulting in reduced arterial oxygen partial pressure and a consequent decline in oxygen diffusion into tissue cells for utilization. This condition is characterized by diminished oxygen content in the blood, while the supply of other nutrients within the blood remains normal. The brain is particularly sensitive to oxygen deficiency, with varying degrees of hypoxic hypoxia resulting in different levels of neural functional disorder. Since the brain has a specific threshold range for the perception of hypoxic hypoxia, mild hypoxic hypoxia can trigger compensatory protective responses in the brain without affecting neural function. These hypoxic compensatory responses enable the maintenance of an adequate oxygen supply and energy substrates for neurons, thereby ensuring normal physiological functions. To further understand the hypoxic compensatory mechanisms of the central nervous system (CNS), this article explores the structural features of the brain's neurovascular unit model, hypoxic signal transduction, and compensatory mechanisms.

Catalase immobilization: Current knowledge, key insights, applications, and future prospects - A review.

Catalase (CAT), a ubiquitous enzyme in all oxygen-exposed organisms, effectively decomposes hydrogen peroxide (H2O2), a harmful by-product, into water and oxygen, mitigating oxidative stress and cellular damage, safeguarding cellular organelles and tissues. Therefore, CAT plays a crucial role in maintaining cellular homeostasis and function. Owing to its pivotal role, CAT has garnered considerable interest. However, many challenges arise when used, especially in multiple practical processes. "Immobilization", a widely-used technique, can help improve enzyme properties. CAT immobilization offers numerous advantages, including enhanced stability, reusability, and facilitated downstream processing. This review presents a comprehensive overview of CAT immobilization. It starts with discussing various immobilization mechanisms, support materials, advantages, drawbacks, and factors influencing the performance of immobilized CAT. Moreover, the review explores the application of the immobilized CAT in various industries and its prospects, highlighting its essential role in diverse fields and stimulating further research and investigation. Furthermore, the review highlights some of the world's leading companies in the field of the CAT industry and their substantial potential for economic contribution. This review aims to serve as a discerning, source of information for researchers seeking a comprehensive cutting-edge overview of this rapidly evolving field and have been overwhelmed by the size of publications.

Impact of Long Working Hours on Mental Health Status in Japan: Evidence from a National Representative Survey.

Using the 2010-2019 Comprehensive Survey of Living Conditions (CSLC) conducted in Japan, we examined the impact of long working hours on mental health in Japan while addressing the endogeneity issue arising from non-random selection bias. We assessed the variations in the effects of long working hours on mental health across different groups. The results show that first, individuals working longer hours (55 h or more per week) exhibited a higher likelihood of developing mental illness than those working regular hours or fewer hours. Second, the negative effect of long working hours on mental health is more pronounced among non-regular workers than among regular workers. Third, the effect of long working hours on mental health varies among different demographic groups, with a greater impact observed among women, managers, non-regular workers, employees in small- or large-sized firms, and those in smaller cities compared to their counterparts. Thus, to enhance worker productivity, the Japanese government should address the issue of long working hours to improve employees' mental well-being. Initiatives aimed at promoting work-life balance, family-friendly policies, and measures to ameliorate working conditions are expected to help mitigate the challenges associated with long working hours and mental health issues, especially among non-regular workers.

Unveiling the mechanisms of Moso bamboo's motor function and internal growth stress.

Bamboo, a renewable resource with rapid growth and an impressive height-to-diameter ratio, faces mechanical instability due to its slender structure. Despite this, bamboo maintains its posture without breaking in its battle against environmental and gravitational forces. But what drives this motor function in bamboo? This study subjected Moso bamboo (Phyllostachys edulis) to gravitational stimulation, compelling it to grow at a 45° angle instead of upright. Remarkably, the artificially inclined bamboo exhibited astonishing shape control and adjustment capabilities. The growth strain was detected at both macroscopic and microscopic levels, providing evidence for the presence of internal stress, namely growth stress. The high longitudinal tensile stress on the upper side, along with a significant asymmetry in stress distribution in tilted bamboo, plays a pivotal role in maintaining its mechanical stability. Drawing upon experimental findings, it can be deduced that the growth stress primarily originates from the broad layers of fiber cells. Bamboo could potentially regulate the magnitude of growth stress by modifying the number of fiber cell layers during its maturation process. Additionally, the microfibril angle and lignin disposition may decisively influence the generation of growth stress.

Classification of exercise fatigue levels by multi-class SVM from ECG and HRV.

Among the various physiological signals, electrocardiogram (ECG) is a valid criterion for the classification of various exercise fatigue. In this study, we combine features extracted by deep neural networks with linear features from ECG and heart rate variability (HRV) for exercise fatigue classification. First, the ECG signals are converted into 2-D images by using the short-term Fourier transform (STFT), and image features are extracted by the visual geometry group (VGG) . The extracted image and linear features of ECG and HRV are sent to the different types of classifiers to distinguish distinct exercise fatigue level. To validate performance, the proposed methods are tested on (i) an open-source EPHNOGRAM dataset and (ii) a self-collected dataset (n = 51). The results reveal that the classification based on the concatenated features has the highest accuracy, and the calculation time of the system is also significantly reduced. This demonstrates that the proposed novel hybrid approach can be used to assist in improving the accuracy and timeliness of exercise fatigue classification in a real-time exercise environment. The experimental results show that the proposed method outperforms other recent state-of-the-art methods in terms of accuracy 96.90%, sensitivity 96.90%, F1-score of 0.9687 in EPHNOGRAM and accuracy 92.17%, sensitivity 92.63%, F1-score of 0.9213 in self-collected dataset.

[Determination of 12 prohibited veterinary drug residues in pig urine by ultra high performance liquid chromatography-tandem mass spectrometry].

A method was established for the simultaneous detection of 12 prohibited veterinary drugs, including ß2-receptor agonists, nitrofuran metabolites, nitroimidazoles, chlorpromazine, and chloramphenicol, in pig urine. The sample was pretreated by enzymolysis, acid hydrolysis/derivatization, and liquid-liquid extraction combined with solid-phase extraction. Detection was performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Ammonium acetate solution (0.2 mol/L, 4.5 mL) and ß-glucuronidase/aryl sulfatase (40 µL) were added to the sample, which was subsequently enzymolized at 37 ℃ for 2 h. Then, 1.5 mL of 1.0 mol/L hydrochloric acid solution and 100 µL of 0.1 mol/L o-nitrobenzaldehyde solution were added to the sample. The mixture was incubated at 37 ℃ for 16 h, and the analytes were extracted with 8 mL of ethyl acetate by liquid-liquid extraction. The lower aqueous phase obtained after extraction was extracted and purified using a mixed cation-exchange solid-phase extraction column. The extracts were combined, the extraction solution was blow-dried with nitrogen, and the residue was redissolved for determination. The samples were analyzed under multiple-reaction monitoring mode with both positive and negative electrospray ionization, and quantified using an isotope internal standard method. The correlation coefficients (r) of the 12 compounds were >0.99. The limits of detection (LODs) and quantification (LOQs) of chloramphenicol were 0.05 and 0.1 µg/L, respectively, and the LODs and LOQs of the other compounds were 0.25 and 0.5 µg/L, respectively. The mean recoveries and RSDs at 1, 2, and 10 times the LOQ were 83.6%-115.3% and 2.20%-12.34%, respectively. The proposed method has the advantages of high sensitivity, good stability, and accurate quantification; thus, it is suitable for the simultaneous determination of the 12 prohibited veterinary drug residues in pig urine.

A bimetallic peroxidase-mimicking nanozyme with antifouling property for construction of sensor array to identify phosphoproteins and diagnose cancers.

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.

The relationship between gastrointestinal symptoms in FGID patients and D-type personality and emotion regulation strategies.

This study examines the relationship between gastrointestinal symptoms in patients with functional gastrointestinal disorders (FGIDs) and type D personality traits, as well as emotion regulation strategies. Analyzing a diverse group of FGID patients, we uncover significant effects of gender and age on gastrointestinal symptoms. Negative Affectivity emerges as a key predictor, positively associated with symptom severity, whereas Social Inhibition correlates negatively with Abdominal Pain. Additionally, our findings suggest that the expressive suppression strategy predicts heightened gastrointestinal symptoms, whereas cognitive reappraisal predicts lower levels of certain symptoms. These findings provide valuable insights for precise diagnosis and tailored treatments of FGIDs. Further research is warranted to explore underlying mechanisms and inform evidence-based interventions.

Plasmonic nanosensor and pressure-induced transparency based on coupled resonator in a nanoscale system.

Plasmonic nanosensors and the dynamic control of light fields are of the utmost significance in the field of micro- and nano-optics. Here, our study successfully demonstrates a plasmonic nanosensor in a compact coupled resonator system and obtains the pressure-induced transparency phenomenon for the first time to our knowledge. The proposed structure consists of a groove and slot cavity coupled in the metal-insulator-metal waveguide, whose mechanical and optical characteristics are investigated in detail using the finite element method. Simulation results show that we construct a quantitative relationship among the resonator deformation quantity, the applied pressure variation, and the resonant wavelength offset by combining the mechanical and optical properties of the proposed system. The physical features contribute to highly efficient plasmonic nanosensors for refractive index and optical pressure sensing with sensitivity of 1800 nm/RIU and 7.4 nm/MPa, respectively. Furthermore, the light waves are coupled to each other in the resonators, which are detuned due to the presence of pressure, resulting in the pressure-induced transparency phenomenon. It is noteworthy to emphasize that, unlike previously published works, our numerical results take structural deformation-induced changes in optical properties into account, making them trustworthy and practical. The proposed structure introduces a novel, to the best of our knowledge, approach for the dynamic control of light fields and has special properties that can be utilized for the realization of various integrated components.

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury.

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwide1-6. Clinical studies have demonstrated that the severity of cardiac injury following myocardial infarction exhibits a circadian pattern, with larger infarct sizes and poorer outcomes in patients experiencing morning onset myocardial infarctions7-14. However, the molecular mechanisms that govern circadian variations of myocardial injury remain unclear. Here, we show that BMAL114-20, a core circadian transcription factor, orchestrates diurnal variability in myocardial injury. Unexpectedly, BMAL1 modulates circadian-dependent cardiac injury by forming a transcriptionally active heterodimer with a non-canonical partner, hypoxia-inducible factor 2 alpha (HIF2A)6,21-23, in a diurnal manner. Substantiating this finding, we determined the cryo-EM structure of the BMAL1/HIF2A/DNA complex, revealing a previously unknown capacity for structural rearrangement within BMAL1, which enables the crosstalk between circadian rhythms and hypoxia signaling. Furthermore, we identified amphiregulin (AREG) as a rhythmic transcriptional target of the BMAL1/HIF2A heterodimer, critical for regulating circadian variations of myocardial injury. Finally, pharmacologically targeting the BMAL1/HIF2A-AREG pathway provides effective cardioprotection, with maximum efficacy when aligned with the pathway's circadian trough. Our findings not only uncover a novel mechanism governing the circadian variations of myocardial injury but also pave the way for innovative circadian-based treatment strategies, potentially shifting current treatment paradigms for myocardial infarction.

Sestrin2 attenuates depressive-like behaviors and neuroinflammation in CUMS mice through inhibiting ferroptosis.

Sestrin2 (SESN2) is a stress-inducible protein and acts as a neuroprotective regulator. The present study aimed to explore the antidepressant activity of SESN2 and its relevant mechanism. Depression mouse model was established by chronic unpredictable mild stress (CUMS) for a successive 5 weeks. Behaviors tests were conducted to examine depressive-like behaviors including sugar preference test, tail suspension test and open field test. The expression of SESN2 and ferroptosis-related proteins was examined by western blot. The production of cytokines was measured by ELISA. Iron deposition was assessed using Prussian blue staining and Fe 2+ content was measured using commercial kits. Lipid peroxidation was evaluated by thiobarbituric acid reactive substances assay. BV-2 cells were treated with LPS to induce microglial activation, which was evaluated by the iba-1 level adopting immunofluorescence assay. The ferroptosis inducer Erastin was adopted for the pretreatment in BV-2 cells to conduct a rescue experiment. SESN2 was downregulated in CUMS-induced mice, and SESN2 overexpression dramatically ameliorated CUMS-induced depression-like behaviors. Meanwhile, SESN2 reduced the production of pro-inflammatory cytokines and iba-1 level in hippocampus of CUMS mice, as well as reducing iron deposition and lipid peroxidation, demonstrating that SESN2 reduced microglial activation, neuroinflammation and ferroptosis in CUMS mice. Similarly, SESN2 also restricted iba-1 level, pro-inflammatory cytokines production, and ferroptosis in LPS-induced BV-2 cells, which was partly reversed by additional treatment of Erastin. These findings suggest that SESN2 possesses potent antidepressant property through inhibiting ferroptosis and neuroinflammation.

Air particulate pollution exposure associated with impaired cognition via microbiota gut-brain axis: an evidence from rural elderly female in northwest China.

This study aimed to reveal harm of exposure to indoor air pollution to cognitive function through "gut-brain-axis" among rural elderly residents. There were 120 participants recruited in rural villages of northwest China from December 2021 to February 2022. The cognitive level was assessed by eight-item ascertain dementia (AD) questionnaire, and indoor air pollution exposure was measured by air quality sensor. Inflammatory cytokines and oxidative stress-related index were detected in blood serum. Fecal samples were collected for gut microbiota analysis. The 120 participants were divided into impaired cognition (AD8) (81/67.5%) and cognition normal (NG) (39/32.5%). And there had more female in AD8 (FAD) (55/67.9%) than NG (FNG) (18/46.2%) (P = 0.003). Exposure of air pollution in FAD was higher than FNG (PM1, PM2.5, PM10, P < 0.001; NO2, P < 0.001; CO, P = 0.014; O3, P = 0.002). The risk of cognitive impairment increases 6.8%, 3.6%, 2.6%, 11%, and 2.4% in female for every 1 µg/m3 increased in exposure of PM1, PM2.5, PM10, NO2, and O3, separately. And GSH-Px and T-SOD in FAD were significantly lower than the FNG group (P = 0.011, P = 0.019). Gut microbiota in FAD is disordered with lower richness and diversity. Relative abundance of core bacteria Faecalibacterium (top 1 genus) in FAD was reduced (13.65% vs 19.81%, P = 0.0235), while Escherichia_Shigella and Akkermansia was increased. Correlation analysis showed Faecalibacterium was negatively correlated with age, and exposure of O3, PM1, PM2.5, and PM10; Akkermansia and Monoglobus were positively correlated with exposure of PM1, PM2.5 and PM10; Escherichia_Shigella was significantly positively correlated with NO2. Indoor air pollution exposure impaired cognitive function in elderly people, especially female, which may cause systemic inflammation, dysbiosis of the gut microbiota, and ultimately leading to early cognitive impairment through the gut-brain axis.

Ginsenoside Rg1 promotes ߭amyloid peptide degradation through inhibition of the ERK/PPARγ phosphorylation pathway in an Alzheimer's disease neuronal model.

ß-Amyloid peptide (Aß) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin-degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator-activated receptor γ (PPARγ), is able to proteolyze Aß. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aß production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, IDE, and whether it is able to promote Aß degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aß1-42, ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra- and extracellular Aß1-42 levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co-expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aß1-42 treatment, reduce the levels of intra- and extraneuronal Aß1-42 and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co-expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aß degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.

Transcriptomic and phenotype analysis revealed the role of rpoS in stress resistance and virulence of a novel ST3355 ESBL-producing hypervirulent Klebsiella pneumoniae isolate.

Introduction: An extended-spectrum beta-lactamase (ESBL)-hypervirulent Klebsiella pneumoniae (HvKP) strain HKE9 was isolated from the blood in an outpatient. Methods: The effect of the global regulatory factor RpoS on antimicrobial resistance, pathogenicity, and environmental adaptability was elucidated. Results: HKE9 is a novel ST3355 (K20/O2a) hypervirulent strain with a positive string test and resistant to cephems except cefotetan. It has a genome size of 5.6M, including two plasmids. CTX-M-15 was found in plasmid 2, and only ompk37 was found in the chromosome. HKE9 could produce bacterial siderophores, and genes of enterobactin, yersiniabactin, aerobactin, and salmochelin have been retrieved in the genome. As a global regulatory factor, knockout of rpoS did not change antimicrobial resistance or hemolytic phenotype while increasing the virulence to Galleria mellonella larvae and showing higher viscosity. Moreover, rpoS knockout can increase bacterial competitiveness and cell adhesion ability. Interestingly, HKE9-M-rpoS decreased resistance to acidic pH, high osmotic pressure, heat shock, and ultraviolet and became sensitive to disinfectants (H2O2, alcohol, and sodium hypochlorite). Although there were 13 Type 6 secretion system (T6SS) core genes divided into two segments with tle1 between segments in the chromosome, transcriptomic analysis showed that rpoS negatively regulated T4SS located on plasmid 2, type 1, and type 3 fimbriae and positively regulate genes responsible for acidic response, hyperosmotic pressure, heat shock, oxidative stress, alcohol and hypochlorous acid metabolism, and quorum sensing. Discussion: Here, this novel ST3355 ESBL-HvKP strain HKE9 may spread via various clonal types. The important regulation effect of rpoS is the enhanced tolerance and resistance to environmental stress and disinfectants, which may be at the cost of reducing virulence and regulated by T4SS.

Maximum intensity projection based on high frame rate contrast-enhanced ultrasound for the differentiation of breast tumors.

Objective: We explored the role of maximum intensity projection (MIP) based on high frame rate contrast-enhanced ultrasound (H-CEUS) for the differentiation of breast tumors. Methods: MIP imaging was performed in patients with breast tumors who underwent H-CEUS examinations. The microvasculature morphology of breast tumors was assessed. The receiver operating characteristic curve was plotted to evaluate the diagnostic performance of MIP. Results: Forty-three breast tumors were finally analyzed, consisting of 19 benign and 24 malignant tumors. For the ≤30-s and >30-s phases, dot-, line-, or branch-like patterns were significantly more common in benign tumors. A tree-like pattern was only present in the benign tumors. A crab claw-like pattern was significantly more common in the malignant tumors. Among the tumors with crab claw-like patterns, three cases of malignant tumors had multiple parallel small spiculated vessels. There were significant differences in the microvasculature morphology for the ≤30-s and >30-s phases between the benign and malignant tumors (all p < 0.001). The area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the ≤30-s phase were all higher than those of the >30-s phase for the classification of breast tumors. Conclusion: MIP based on H-CEUS can be used for the differentiation of breast tumors, and the ≤30-s phase had a better diagnostic value. Multiple parallel small spiculated vessels were a new finding, which could provide new insight for the subsequent study of breast tumors.

Tunable electromagnetically induced absorption based on coupled-resonators in a compact plasmonic system.

Electromagnetically induced absorption (EIA) exhibits abnormal dispersion and novel fast-light features, making it a crucial aspect of nanophotonics. Here, the EIA phenomenon is numerically predicted in a compact plasmonic waveguide system by introducing a slot resonator above a square cavity. Simulation results reveal that the EIA response can be easily tuned by altering the structure's parameters, and double EIA valleys can be observed with an additional slot resonator. Furthermore, the investigated structures demonstrate a fast-light effect with an optical delay of ∼ -1.0 ps as a result of aberrant dispersion at the EIA valley, which enable promising applications in the on-chip fast-light area. Finally, a plasmonic nanosensor with a sensitivity of ∼1200 nm/RIU and figure of merit of ∼16600 is achieved based on Fano resonance. The special features of our suggested structure are applicable in realization of various integrated components for the development of multifunctional high-performance nano-photonic devices.