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The phenomenon of stiffness hardening has detrimental influence on the natural frequency and the width of vibration isolation frequency bands, which significantly confines the development of quasi-zero-stiffness vibration isolators (QZSVIs). To overcome this restriction, the nonlinear mirrored-stiffness design method (NMSM) is proposed and its applicable condition is revealed. Based on the mechanism of stiffness hardening, a nonlinear spring (NS) is designed by the NMSM. NS possesses nonlinear restoring force and a mirror-image relationship with the targeted negatives stiffness. The mathematical model of the NS is established based on Heaviside function. Coupled QZSVIs (CQZSVIs) are constructed by a concave metastructure with multiple stiffness properties and the NS to validate the NMSM. A prototype of the CQZSVI is fabricated to prove the correctness of the theoretical analysis. The practical tests of the CQZSVI demonstrate an obvious QZS region where the restoring force remains approximately constant and the stiffness is almost invariable and close to zero. The results of sweep-frequency experiments show that the CQZSVI has a natural frequency of about 0.8 Hz and a broad effective vibration isolation region starting from about 1.1 Hz. Its transmissibility is about − 15 dB at 3 Hz and is about − 20 dB at 3.5 Hz. The NMSM successfully breaks through the bottleneck of the development of QZSVIs and produces a new approach for the construction of low-frequency vibration isolators. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) and glycolipid metabolism have been implicated in cognitive impairments and depression among Parkinson's disease (PD). However, the role of sex differences in this relationship remains elusive. This study aimed to investigate the potential sex differences in the link between serum BDNF levels, glycolipid metabolism and cognitive performance among depressive PD patients. PD patients comprising 108 individuals with depression and 108 without depression were recruited for this study. Cognitive function was assessed using the Montreal Cognitive Assessment Beijing version (MOCA-BJ). The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HAMD-17), while motor symptoms were evaluated using the Revised Hoehn and Yahr rating scale (H-Y) and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). Laboratory testing and enzyme-linked immunosorbent assay (ELISA) are used to measure serum levels of glycolipid metabolism and BDNF. Females showed superior performance in delayed recall (all p < 0.05), male PD patients exhibited higher scores in naming tasks compared to females in non-depression group. There was no sex differences in serum BDNF levels between depression and non-depression groups. Liner regression analysis indicated BDNF as an independent risk factor for language deficits in male PD patients with depression (p < 0.05), while cholesterol (CHOL) emerged as a cognitive influencing factor, particularly in delayed recall among male PD patients with depression (p < 0.05). Our study reveals extensive cognitive impairments in PD patients with depression. Moreover, BDNF and CHOL may contribute to the pathological mechanisms underlying cognitive deficits, particularly in male patients with depression. [ABSTRACT FROM AUTHOR]

Primary cilia are crucial for neurogenesis, and cilium-related genes are involved in the closure of neural tubes. Inositol polyphosphate-5-phosphatase (Inpp5e) was enriched in primary cilia and closely related to the occurrence of neural tube defects (NTDs). However, the role of Inpp5e in the development of NTDs is not well-known. To investigate whether Inpp5e gene is associated with the neural tube closure, we established a mouse model of NTDs by 5-fluorouracil (5-FU) exposure at gestational day 7.5 (GD7.5). The Inpp5e knockdown (Inpp5e-/-) mouse embryonic stem cells (mESCs) were produced by CRISPR/Cas9 system. The expressions of Inpp5e and other cilium-related genes including intraflagellar transport 80 (Ift80), McKusick-Kaufman syndrome (Mkks), and Kirsten rat sarcoma viral oncogene homolog (Kras) were determined, utilizing quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, PCR array, and immunofluorescence staining. The result showed that the incidence of NTDs was 37.10% (23 NTDs/62 total embryos) and significantly higher than that in the control group (P < 0.001). The neuroepithelial cells of neural tubes were obviously disarranged in NTD embryos. The mRNA and protein levels of Inpp5e, Ift80, Mkks, and Kras were significantly decreased in NTD embryonic brain tissues, compared to the control (P < 0.05). Knockdown of the Inpp5e (Inpp5e-/-) reduced the expressions of Ift80, Mkks, and Kras in mESCs. Furthermore, the levels of α-tubulin were significantly reduced in NTD embryonic neural tissue and Inpp5e-/- mESCs. These results suggested that maternal 5-FU exposure inhibited the expression of Inpp5e, which resulted in the downregulation of cilium-related genes (Ift80, Mkks, and Kras), leading to the impairment of primary cilium development, and ultimately disrupted the neural tube closure. [ABSTRACT FROM AUTHOR]

The exploitation of new green polymerization avenues for the effective synthesis of polymers by reversible-deactivation radical polymerization plays a critical role in pursuing the development of polymeric materials. In this work, serials of deep eutectic solvents (DES) with intermolecular-hydrogen-bonding interaction were constructed as catalysts and medium for actuating reversible complexation-mediated polymerization (RCMP) for the first time, yielding methacrylate polymers with high monomer conversion and narrow dispersion molecular weight in both water and oil systems. The mechanism and elementary reaction of RCMP were explored deeply, revealing that the complexation of initiator with DES to generate radicals was a ratecontrolling step and intermolecular-hydrogen-bond was primary factor to influence polymerization rate. Moreover, the insights of density functional theory calculations revealed that negative electrostatic potential ensured nucleophilic capacity. This investigation demonstrated the considerable potential of DES for RCMP, which is anticipated for other polymerization applications as a novel medium mode. [ABSTRACT FROM AUTHOR]

Heat treatment is widely applied in food processing, but its significant effects on flavor are often overlooked. This study explored how heat treatment impacts the flavor compounds of Antarctic krill. The volatile substances and flavor profiles of Antarctic krill post steaming or hot air drying were analyzed using headspace solid-phase microextraction, gas chromatography-mass spectrometry (HS-SPME-GC-MS), gas chromatography-ion mobility spectrometry (GC-IMS), and electronic tongue detection techniques. Free amino acids (FAAs) content, the main flavor precursors, were quantified and compared. The results showed that the FAAs content of SK was the lowest at 48.44 ± 2.10 mg/g db, while the FAAs content of HD_105 was the highest at 67.42 ± 1.77 mg/g db. Drying amplified the flavor intensity of umami and bitter amino acids, while steaming significantly increased the content of the sweet amino acid proline (p < 0.05). The electronic tongue discerned that drying had more pronounced effects than steaming on saltiness, umami, bitterness, and astringency. By combining the volatile organic compounds (VOCs) fingerprints with the results of the GC-MS analysis of five samples, it was observed that the richness in fat and aromatic taste of shrimp powder after hot air drying at 60℃ (HD_60) and 80℃ (HD_80) was enhanced. Krill dried at 105℃ (HD_105) predominantly exhibited a roasted flavor profile, while steamed krill (SK) displayed minimal alterations in volatile flavors. In summary, steaming increased the sweet amino acid content in krill, while drying enhanced krill's aroma characteristics. This study furnishes valuable insights for the subsequent processing and utilization of Antarctic krill to augment its flavor quality. [ABSTRACT FROM AUTHOR]

In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) is increasingly being recognized as a leading contributor to cognitive impairment in the elderly. However, there is a lack of effective preventative or therapeutic options for CSVD. In this exploratory study, we investigated the interplay between neuroinflammation and CSVD pathogenesis as well as the cognitive performance, focusing on NLRP3 signaling as a new therapeutic target. Spontaneously hypertensive stroke-prone (SHRSP) rats served as a CSVD model. We found that SHRSP rats showed decline in learning and memory abilities using morris water maze test. Activated NLRP3 signaling and an increased expression of the downstream pro-inflammatory factors, including IL (interleukin)-6 and tumor necrosis factor α were determined. We also observed a remarkable increase in the production of pyroptosis executive protein gasdermin D, and elevated astrocytic and microglial activation. In addition, we identify several neuropathological hallmarks of CSVD, including blood-brain barrier breakdown, white matter damage, and endothelial dysfunction. These results were in correlation with the activation of NLRP3 inflammasome. Thus, our findings reveal that the NLRP3-mediated inflammatory pathway could play a central role in the pathogenesis of CSVD, presenting a novel target for potential CSVD treatment. [ABSTRACT FROM AUTHOR]

Glucose disturbances are a common comorbidity of major depressive disorder (MDD) patients and have been extensively studied in the past. However, few studies have explored glucose disturbances in first-episode drug-naïve (FEDN) MDD patients. The purpose of this study was to examine the prevalence and risk factors of glucose disturbances in FEDN MDD patients to understand the relationship between MDD and glucose disturbances in the acute early phase and provide important implications for therapeutic interventions. Using a cross-sectional design, we recruited a total of 1718 MDD patients. We collected their socio-demographic information, clinical data, and blood glucose indicators.17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, psychotic symptoms, respectively. The prevalence of glucose disturbances in FEDN MDD patients was 13.6%. Depression, anxiety and psychotic symptoms, body mass index (BMI) levels and suicide attempts rates were higher in the group with glucose disorders than in the group without glucose disorders among patients with first-episode drug-naive MDD. Correlation analysis showed that glucose disturbances were associated with HAMD score, HAMA score, BMI, psychotic symptoms and suicide attempts. Furthermore, binary logistic regression showed that HAMD score and suicide attempts were independently associated with glucose disturbances in MDD patients. Our findings suggest that the prevalence of comorbid glucose disturbances is very high in FEDN MDD patients. Moreover, more severe depressive symptoms and higher suicide attempts are correlated with glucose disturbances in MDD FEDN patients in the early stage. [ABSTRACT FROM AUTHOR]

H-steel all-bolted connection steel frame structures with heat preservation and decoration composite wall boards were investigated and the seismic performances of three scaled specimens were studied. The failure modes, hysteresis curves, bearing capacity, ductility, energy dissipation capacity, stiffness degradation and strain distribution were discussed. The calculation method of structural theoretical internal force was presented. The results showed that the overall structural seismic performance was better, and the structural ductility met the demands of elastic-plastic inter-story drift angle for seismic design. The H-steel weak-axis connection structure obtained better energy dissipation capacity, and its bearing capacity and stiffness were slightly different from the strong-axis connection. The heat preservation and decoration performance of composite wallboard and the all-bolted connection of the steel frame realized prefabrication during the whole construction period. The plastic hinge of the steel beam can be moved outwards because of the L-angles, which effectively avoids stress concentration in joint areas and expands the plastic hinge range. The errors between the theoretical structural capacity calculated by the plastic analysis method and the test results were within 2.44%. In addition, structural failure mechanisms and bearing capacities were verified by the finite element (FE) analysis, and the effects of the main parameters on the structures were investigated. The FE verification results were the same as in the test. The research results provide theoretical support and technical guidance for the application of thermal insulation and decorative composite wall panels in H-shaped steel all-bolted steel frames. [ABSTRACT FROM AUTHOR]

The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10-8). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative and neuropsychiatric disorders and WM-BAG genes for cancer therapy. GM-BAG displayed the most pronounced heritability enrichment in genetic variants within conserved regions. Oligodendrocytes and astrocytes, but not neurons, exhibited notable heritability enrichment in WM and FC-BAG, respectively. Mendelian randomization identified potential causal effects of several chronic diseases on brain aging, such as type 2 diabetes on GM-BAG and AD on WM-BAG. Our results provide insights into the genetics of human brain aging, with clinical implications for potential lifestyle and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Microstate analysis is a promising technique for analyzing high-density electroencephalographic data, but there are multiple questions about methodological best practices. Between and within individuals, microstates can differ both in terms of characteristic topographies and temporal dynamics, which leads to analytic challenges as the measurement of microstate dynamics is dependent on assumptions about their topographies. Here we focus on the analysis of group differences, using simulations seeded on real data from healthy control subjects to compare approaches that derive separate sets of maps within subgroups versus a single set of maps applied uniformly to the entire dataset. In the absence of true group differences in either microstate maps or temporal metrics, we found that using separate subgroup maps resulted in substantially inflated type I error rates. On the other hand, when groups truly differed in their microstate maps, analyses based on a single set of maps confounded topographic effects with differences in other derived metrics. We propose an approach to alleviate both classes of bias, based on a paired analysis of all subgroup maps. We illustrate the qualitative and quantitative impact of these issues in real data by comparing waking versus non-rapid eye movement sleep microstates. Overall, our results suggest that even subtle chance differences in microstate topography can have profound effects on derived microstate metrics and that future studies using microstate analysis should take steps to mitigate this large source of error. [ABSTRACT FROM AUTHOR]

Background: There is no optimal reconstruction method after proximal gastrectomy. The valvuloplastic esophagogastrostomy can reduce postoperative reflux esophagitis, but it is technically complex with a long operation time. The gastric tube anastomosis is technically simple, but the incidences of reflux esophagitis and anastomotic stricture are higher. Methods: We have devised a modified valvuloplastic esophagogastrostomy after laparoscopy-assisted proximal gastrectomy (LAPG), the arch-bridge anastomosis. After reviewing our prospectively maintained gastric cancer database, 43 patients who underwent LAPG from November 2021 to April 2023 were included in this cohort study, with 25 patients received the arch-bridge anastomosis and 18 patients received gastric tube anastomosis. The short-term outcomes were compared between the two groups to evaluate the efficacy of the arch-bridge anastomosis. Reporting was consistent with the STROCSS 2021 guideline. Results: The median operation time was 180 min in the arch-bridge group, significantly shorter than the gastric tube group (p = 0.003). In the arch-bridge group, none of the 25 patients experienced anastomotic leakage, while one patient (4%) experienced anastomotic stricture requiring endoscopic balloon dilation. The postoperative length of stay was shorter in the arch-bridge group (9 vs. 11, p = 0.034). None of the patients in the arch-bridge group experienced gastroesophageal reflux and used proton pump inhibitor (PPI), while four (22.2%) patients in the gastric tube group used PPI (p = 0.025). The incidence of reflux esophagitis (Los Angeles grade B or more severe) by endoscopy was lower in the arch-bridge group (0% vs. 25.0%). Conclusion: The arch-bridge anastomosis is a safe, time-saving, and feasible reconstruction method. It can reduce postoperative reflux and anastomotic stricture incidences in a selected cohort of patients undergoing laparoscopy-assisted proximal gastrectomy. [ABSTRACT FROM AUTHOR]

The accurate diagnosis of HFpEF is still challenging and controversial. In this study, we used 3D-DHM technology to compare the differences of cardiac structure and function between HFpEF patients and healthy controls, as well as the differences of two-dimensional and three-dimensional cardiac function in HFpEF patients. Echocardiography with 3D-DHM and conventional two-dimensional (2D) methods were applied to measure the volume and function parameters of left atrium and ventricle of patients with HFpEF and healthy controls. Significant differences of 3D cardiac function indexes including LVESV, 3D-LVEF, ESL, SV, CI, EDmass, LAVmax, LAVmin, LAEF, and LAVI were observed between patients with HFpEF and controls (P < 0.05). However, no significant difference of LVEDV and EDL were observed (P > 0.05). In addition, we found no significant between-group difference in 2D cardiac function indexes such as LVDD and 2D-LVEF (P > 0.05), but the LAD, LVSD, LVPW, IVS, E, E/A, and E/e ' were significantly different between groups (P < 0.05). There was no significant difference between 3D-LVEF and 2D-LVEF in the control group (P > 0.05), while 3D-LVEF in the HFpEF group was lower than 2D-LVEF(P < 0.05). Among the two-dimensional and three-dimensional parameters of HFpEF patients, the parameters related to diastolic function changed more significantly than those of the normal group, and the three-dimensional LVEF of HFpEF patients decreased. The three-dimensional cardiac function parameters analyzed by DHM can provide more information regarding myocardial mechanics. [ABSTRACT FROM AUTHOR]

The distribution of nerve veins in oral and maxillofacial region is very rich and connected with many parts of the body. Once the infection occurs behind the mouth and maxilla, the effects will be widespread. Therefore, this study aims to explore the application of light enhanced medical imaging technology based on computer diagnosis in the analysis of infection factors in oral and maxillofacial surgery to improve the ability of early diagnosis and accurate treatment. The oral and maxillofacial surgical infection was recorded by using light enhanced medical imaging. The clinical data of patients were collected and analyzed, and the images were processed by computer diagnostic technology. It was found that the relaxation factor λ was 0.5 and the number of iterations was 25 times to improve the accuracy. Studies have also shown that plasma fibrin has an advantage in predicting oral infections. This study demonstrated the potential application value of light enhanced medical imaging technology based on computer diagnosis in the analysis of infection factors in oral and maxillofacial surgery. This technique is helpful for early diagnosis and accurate treatment of oral and maxillofacial surgical infection, improving the treatment effect and quality of life of patients. Further research should also consider expanding the sample size and improving the accuracy of the analysis algorithm. [ABSTRACT FROM AUTHOR]

The theory of Formal Concept Analysis (FCA) finds diverse applications in fields like knowledge extraction, cognitive concept learning and data mining. The construction of a concept lattice significantly influences the effectiveness of formal concept analysis; hence, the development of high-performance algorithms for concept construction is crucial. In this paper, we introduce a novel algorithm called "Bit-Close" for formal concept construction. Bit-Close leverages bit representation and operations, fundamental to computer science, to enhance the In-Close algorithm. Furthermore, we explore the parallel method of Bit-Close. Our experimental results, obtained from multiple public and random datasets, demonstrate that Bit-Close outperforms In-Close by approximately 20% and is significantly better than other competing algorithms. [ABSTRACT FROM AUTHOR]

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and inflammation. Mitochondria regulate macrophage activation and innate immune responses in various inflammatory diseases, including cochlear inflammation. The distribution, number, and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions, including noise exposure, ototoxicity, and age-related degeneration. However, the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains unclear. Here, we summarize the major factors and mitochondrial signaling pathways (e.g., metabolism, mitochondrial reactive oxygen species, mitochondrial DNA, and the inflammasome) that influence macrophage activation in the innate immune response. In particular, we focus on the properties of cochlear macrophages, activated signaling pathways, and the secretion of inflammatory cytokines after acoustic injury. We hope this review will provide new perspectives and a basis for future research on cochlear inflammation. [ABSTRACT FROM AUTHOR]

This paper proposes a novel wake-induced vibration (WIV)-based energy harvesting system consisting of two bluff bodies. An inverted C-shaped bluff body is stationary installed at the upstream position to generate an interference wake street, and a cylinder bluff body equipped with a transducer is elastically suspended at the downstream position to harness WIV energy. The hydrodynamics and energy harvesting (EH) performance of the proposed system are investigated via experimental studies. The reduced velocity (U*) ranging from 2 to 14 (the corresponding Reynolds number ranging from 15100 to 106200) is considered in the present study. It is found that the wake generated by the inverted C-shaped bluff body significantly affects the EH performance. Enlarging the opening angle (α) of the C-shaped bluff body increases the vibration amplitude of the downstream cylinder, thereby increasing the harvested power. When the spacing (L) between two bluff bodies is two times the cylinder diameter (D), the wake-induced vibration (WIV) mode is observed, while the combined WIV and wake galloping (WG) mode occurs when α is 150°, and L equals 3D or 4D. The average drag coefficient becomes negative when L is 2D, 3D, or 4D. By carefully configuring a C-shaped bluff body, the wake generated by it can bring an augmenting effect on the vibration of the downstream EH cylinder. For example, the RMS power output of the proposed EH system reaches a maximum of 0.31 W at U* = 8 and L = 4D, which is 300% greater than that of its traditional counterpart. Furthermore, after a number of case studies, it is identified that the proposed EH system can achieve the best performance when α is 150° and L = 2D. [ABSTRACT FROM AUTHOR]

Accurate trajectory prediction of surrounding road users is the fundamental input for motion planning, which enables safe autonomous driving on public roads. In this paper, a safe motion planning approach is proposed based on the deep learning-based trajectory prediction method. To begin with, a trajectory prediction model is established based on the graph neural network (GNN) that is trained utilizing the INTERACTION dataset. Then, the validated trajectory prediction model is used to predict the future trajectories of surrounding road users, including pedestrians and vehicles. In addition, a GNN prediction model-enabled motion planner is developed based on the model predictive control technique. Furthermore, two driving scenarios are extracted from the INTERACTION dataset to validate and evaluate the effectiveness of the proposed motion planning approach, i.e., merging and roundabout scenarios. The results demonstrate that the proposed method can lower the risk and improve driving safety compared with the baseline method. [ABSTRACT FROM AUTHOR]

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients. A total of 163 PD patients aged 50–80 years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively. There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = – 0.002, t = − 2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = − 0.001, t = − 2.452, p = 0.017). LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall. [ABSTRACT FROM AUTHOR]

Current immunotherapy for prostate cancer is still in the stage of clinical trials. This delay is thought to be caused by an unclear regulatory mechanism of the immune microenvironment, which makes it impossible to distinguish patients suitable for immunotherapy. Cuprotosis may be related to the heterogeneity of immune microenvironment, which was regarded as a new copper-dependent cell death mode, was proposed, and gain attention. We explored for the first time the relationship between cuprotosis and the immune microenvironment of prostate cancer and constructed cuprotosis score. RNA sequencing data sets for prostate cancer were downloaded from public databases. Consensus clustering was applied to distinguish cuprotosis phenotype based on the expression of cuproptosis-related genes (CRGs) identified as prognostic factors. Genomic phenotypes of CRG clusters were depicted via consensus clustering. Cuprotosis score was established on the basis of differentially expressed genes (DEGs) identified as prognostic factors via principal component analysis. Cuprotosis score = the first principal component of prognostic factors + the second principal component of prognostic factors. The value of cuproptosis score in predicting prognosis and immunotherapy response was evaluated. PDHA1 (HR = 3.86, P < 0.001) and GLS (HR = 1.75, P = 0.018) were risk factors for prognosis of prostate cancer patients, while DBT (HR = 0.66, P = 0.048) was a favorable factor for prognosis of prostate cancer patients. CRG clusters had different prognosis and immune cell infiltration. So as gene clusters. Prostate cancer patients with low cuprotosis score showed better prognosis for biochemical relapse-free survival. Cuprotosis score is accompanied with high immune score and Gleason score. As cuprotosis genes, PDHA1, GLS, and DBT were identified as independent prognostic factors of prostate cancer. Cuprotosis score was established via principal component analysis of PDHA1, GLS, and DBT, which can be used as a predictor of prognosis and immunotherapy response of prostate cancer patients, and can characterize immune cells infiltration in tumors. Cuproptosis was involved in the regulation of immune microenvironment, which may depend on the effect of tricarboxylic acid cycle. Our study provided clues to reveal the relationship between copper death and immune microenvironment, highlighted the clinical significance of cuproptosis, and provided a reference for the development of personalized immunotherapy. [ABSTRACT FROM AUTHOR]

Viscosity is an indispensable micro-environmental parameter that affects the diffusion of matter and molecular activity in biological systems. Abnormal changes in viscosity levels are strongly associated with various human diseases, such as thrombosis, Alzheimer's disease, and the formation of malignant tumors. This paper reports a highly biocompatible xylan-based viscosity fluorescent probe (Xyl-V) for cell-level viscosity measurement. Xyl-V is constructed using non-toxic and biodegradable xylan (Xyl) in plant resources, combined with mitochondrial targeting and a near-infrared emission luminescent group. Under viscous conditions, the fluorescence of Xyl-V at 580 nm and 820 nm is very sensitive to viscosity changes, and the fluorescence intensity increases by 16 and 32 times with the increase in viscosity level, respectively. As the first xylan-based probe for viscosity detection, it has excellent selectivity, low toxicity, high biocompatibility, and superior detection performance in the living cell environment. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism. A systems-wide study of mice infected with SARS-CoV2 under ketogenic diet shows that this diet reprograms the transcriptional and metabolic response in animals following infection with improved health, reduced inflammation, and restored metabolism. [ABSTRACT FROM AUTHOR]

Purpose : Exposure to aggressive parenting is a well-established environmental risk factor for anxiety symptoms. Moreover, autonomic nervous system (ANS) activity, including activity in both parasympathetic and sympathetic nervous systems (PNS and SNS), may moderate the effects of aggressive parenting on anxiety. This study aims to examine the interactive effects of aggressive parenting and ANS activity (both PNS and SNS) in accounting for trait anxiety among emerging adults. Methods: Participants (n = 190, mean age = 19.29, 56% females) reported retrospectively on childhood aggressive parenting and trait anxiety. In addition, we measured resting respiratory sinus arrhythmia (RSA), an index of PNS, and resting skin conductance level (SCL), an index of SNS. Results: Regression analyses revealed that the three-way interaction between resting SCL, RSA, and aggressive parenting significantly accounted for trait anxiety. Simple slope analyses suggest that the relation between aggressive parenting and trait anxiety is stronger at lower conditional values of resting RSA and lower conditional values of resting SCL. Conclusion: Coinhibition, or relatively low activity across both systems, may exacerbate the link between aggressive parenting and trait anxiety. This study highlights the importance of considering the interaction effects of multiple physiological systems and environmental context on later psychological functioning. [ABSTRACT FROM AUTHOR]

The multi-chip parallel insulated gate bipolar transistor (IGBT) is the core device in large-capacity power electronic equipment, but its operational reliability is of considerable concern to industry. The application of IGBT online degradation state analysis technology can be beneficial to the improvement of system reliability. The failure mechanism of IGBT devices is discussed in this paper, and a technique for analyzing the degradation state of IGBT based on apparent junction temperature is proposed. First, the distortion consistency of the voltage rise time in various failures is discussed, and the junction temperature dependence of the voltage rise time is then demonstrated. Subsequently, an apparent junction temperature model based on the voltage rise time is established (the fitting accuracy is as high as 94.3%). From the high-frequency model in the switching process of the device, an online extraction technology of key parameters (e.g., voltage rise time) is developed. Finally, an experimental platform for IGBT degradation state estimation is established, and the feasibility of IGBT degradation state estimation based on apparent junction temperature is proved, especially the degradation of bonding-wire and the gate-oxide-layer. The experimental results show that the proposed IGBT degradation state estimation technique based on apparent junction temperature is a reliable online estimation method with non-contact, high accuracy, and comprehensiveness. [ABSTRACT FROM AUTHOR]

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50–80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50–59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50–59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70–80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression. [ABSTRACT FROM AUTHOR]

There have been many studies on the degradation of polyvinyl alcohol (PVA) by the Fenton-like method, but the narrow acid-base (pH) range, poor degradation effect, and time-consuming of the Fenton-like method limit its development. Therefore, to improve the shortcomings of the Fenton-like method, the study aimed to synthesize copper-manganese bimetal oxide loaded catalysts (MnCuO@γ-Al2O3) through the impregnation calcination method, and its potential to activate hydrogen peroxide (H2O2) for the degradation of PVA was evaluated. The X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer Emmett Teller (BET), energy dispersive spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) characterizations revealed the chemical composition, structure and morphology of the prepared MnCuO@γ-Al2O3, furthermore the synergistic mechanism was proposed. Results indicated that copper and manganese could successfully attach to γ-Al2O3 and reduce the specific surface area of γ-Al2O3, promoting the transformation of multivalent metals and the generation of oxygen vacancies. In addition, comparative experiments demonstrated that the PVA removal efficiency was significantly improved at the catalyst calcination temperature of 500 °C, reaction temperature of 70 °C, H2O2 dosage of 125 mL · L - 1 , and catalyst dosage of 625 mg · L - 1 and more than 96% of PVA was removed within 20 min in neutral conditions. Lastly, four catalyst cycle degradation experiments of PVA were carried out, and the degradation effect could reach more than 96% in a certain time. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) is one of the biggest threats to women's health. LncRNA HOTAIR is related to the recurrence and metastasis of BC. Whether HOTAIR can serve as an effective biomarker to distinguish BC patients with different prognosis need to be further studied. Methods: The miRNA and mRNA expression profile data of BC patients were downloaded from TCGA database. Univariate Cox regression was used to screen differential expression genes (DEGs). The miRcode database and miRWalk database were used to predict miRNA binding to HOTAIR and binding sites of miRNAs, respectively. Kaplan-Meier (KM) analysis was used to estimate the overall survival rate of BC patients. Finally, qRT-PCR and western blot were applied to evaluate the expression level of HOTAIR and mRNAs between BC cells and normal mammary cells. Results: The patients with high HOTAIR expression had poor prognosis in BC. Totally 10 genes correlated with BC prognosis were identified from 170 DEGs, among which PAX7, IYD, ZIC2, MS4A1, TPRXL, CD24, LHX1 were positively correlated with HOTAIR, while CHAD, NPY1R, TPRG1 were opposite. The levels of IYD, ZIC2, CD24 mRNA and protein were increased in BC tissues and BC cells. In BC cells, the levels of IYD, ZIC2 and CD24 mRNA and protein were significantly increased in HOTAIR overexpressed group. HOTAIR had the strongest interaction with hsa-miR-129-5p, followed by hsa-miR-107. Conclusion: HOTAIR regulated the expression of downstream genes by interacting with 8 miRNAs and ultimately affected the prognosis of BC patients. [ABSTRACT FROM AUTHOR]

To study the influence of fluid solid coupling erosion on the joints of gas pipelines, the Fluent DPM model was first used to conduct finite element analysis on several commonly used gas pipeline joints through gas-solid coupling numerical simulation. Secondly, the reasons for erosion of four-way joints and fish tail joints were studied, and the effects of fluid velocity, particle mass, and particle diameter on erosion were compared and analyzed. Finally, two optimization schemes were proposed for these two types of joints. The results show that fish tail joint is generally lower than that of the three-way channel structure. The erosion rate of the fish tail pipe is caused by the large angle between the inlet and outlet channels, which causes particles to directly impact the projection direction of the inlet channel. The erosion rate increases with the increase in velocity and increases with the increase in particle diameter. The use of a double lobe guide structure in the four-ways joint and fish tail joint not only effectively optimizes the internal flow channel, but also reduces wall erosion and avoids large flow velocity zones. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to synthesize insights from systems science approaches applied to domestic and gender-based violence. Methods: We conducted a systematic review of systems science studies (systems thinking, group model-building, agent-based modeling [ABM], system dynamics [SD] modeling, social network analysis [SNA], and network analysis [NA]) applied to domestic or gender-based violence, including victimization, perpetration, prevention, and community responses. We used blinded review to identify papers meeting our inclusion criteria (i.e., peer-reviewed journal article or published book chapter that described a systems science approach to domestic or gender-based violence, broadly defined) and assessed the quality and transparency of each study. Results: Our search yielded 1,841 studies, and 74 studies met our inclusion criteria (45 SNA, 12 NA, 8 ABM, and 3 SD). Although research aims varied across study types, the included studies highlighted social network influences on risks for domestic violence, clustering of risk factors and violence experiences, and potential targets for intervention. We assessed the quality of the included studies as moderate, though only a minority adhered to best practices in model development and dissemination, including stakeholder engagement and sharing of model code. Conclusions: Systems science approaches for the study of domestic and gender-based violence have shed light on the complex processes that characterize domestic violence and its broader context. Future research in this area should include greater dialogue between different types of systems science approaches, consideration of peer and family influences in the same models, and expanded use of best practices, including continued engagement of community stakeholders. [ABSTRACT FROM AUTHOR]

In order to achieve accurate fault diagnosis of rolling bearing under random noise, a new fault diagnosis method based on wavelet packet-variational mode decomposition (WP-VMD) and kernel extreme learning machine (KELM) optimized by particle swarm optimization (PSO) is proposed in this paper. Firstly, the time–frequency domain feature vectors of the original rolling bearing fault signals are effectively obtained by preprocessing of WMD and decomposition and reconstruction of VMD. Then, the extracted two-dimensional feature vector is input into the KELM neural network for fault identification, and combined with PSO, KELM parameters were optimized. The experimental results show that the proposed method can effectively diagnose the rolling bearing under random noise, with the features of fast speed, stable performance and high accuracy. By comparison, this paper obtains better accuracy and real-time performance with fewer features, which provides a simple and efficient solution for fault diagnosis of rolling bearings. [ABSTRACT FROM AUTHOR]

Inositol is closely related to the occurrence of neural tube defects (NTDs). Inositol 1, 3, 4-trisphosphate 5/6-kinase (ITPK1) gene encoded an essential regulatory enzyme ITPK1, which is involved in inositol metabolism and has a critical role in the development of neural tube and axial mesoderm. It had been reported that some polymorphisms of critical genes in inositol pathways, including ITPK1, were associated with NTDs in Chinese pregnant women; however, the association between fetus ITPK1 polymorphisms and NTDs had not been reported. In a high incidence of NTDs region of China, a case–control study was performed to evaluate the association between fetal ITPK1 polymorphisms and NTDs. The ITPK1 polymorphisms were genotyped by iPLEX® Gold assay. Inositol levels in fetus brain tissues were analyzed. Three genetic polymorphisms of fetus ITPK1's, including rs3818175, rs2295394, and rs4586354, were statistically associated with spina bifida (NTD subtypes). A higher risk of spina bifida was associated with genotype GG of rs3818175, genotype CC of rs4586354, and genotype TT of rs2295394 (OR = 2.66, 95% CI [1.17–6.05], P = 0.017; OR = 2.22, 95% CI [1.02–4.80], P = 0.041; and OR = 2.33, 95% CI [1.00–5.48], P = 0.047), when compared with the other wild-type genotypes CC, TT, and CC, respectively. Decreased brain inositol level was found in NTDs fetuses, compared to normal controls. Inositol levels were found to significantly decrease with rs2295394 (CC genotype), rs4586354 (TT genotype), and rs3818175 (GC genotype) (P < 0.05). The polymorphisms of fetus ITPK1 were associated with the incidence of NTDs and might be a genetic risk factor for spina bifida. [ABSTRACT FROM AUTHOR]

Chemotherapeutic agents such as methotrexate (MTX), raltitrexed (RTX), 5-fluorouracil (5-FU), hydroxyurea (HU), and retinoic acid (RA), and valproic acid (VPA), an antiepileptic drug, all can cause malformations in the developing central nervous system (CNS), such as neural tube defects (NTDs). However, the common pathogenic mechanisms remain unclear. This study aimed to explore the mechanisms of NTDs caused by MTX, RTX, 5-FU, HU, RA, and VPA (MRFHRV), based on network pharmacology and molecular biology experiments. The MRFHRV targets were integrated with disease targets, to find the potential molecules related to MRFHRV-induced NTDs. Protein–protein interaction analysis and molecular docking were performed to analyze these common targets. Utilizing the kyoto encyclopedia of genes and genomes (KEGG) signaling pathways, we analyzed and searched the possible causative pathogenic mechanisms by crucial targets and the signaling pathway. Results showed that MRFHRV induced NTDs through several key targets (including TP53, MAPK1, HSP90AA1, ESR1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN) and multiple signaling pathways such as PI3K/Akt pathway, suggesting that abnormal proliferation and differentiation could be critical pathogenic contributors in NTDs induced by MRFHRV. These results were further validated by CCK8 assay in mouse embryonic stem cells and GFAP staining in embryonic brain tissue. This study indicated that chemotherapeutic and antiepileptic agents induced NTDs might through predicted targets TP53, MAPK1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN and multiple signaling pathways. More caution was required for the clinical administration for women with childbearing potential and pregnant. [ABSTRACT FROM AUTHOR]

Childhood family stress (CFS) exacerbates risk for physical health problems across the lifespan. Health risks associated with CFS are particularly relevant for women who tend to endorse more CFS than men. Importantly, some evidence suggests that individuals may vary in their susceptibility to CFS. Parasympathetic activity, which helps to regulate automatic bodily activity (e.g., breathing, digestion), has been proposed to represent a marker of plasticity to environmental exposure. However, no research to date has tested whether parasympathetic activity may modulate the impact of early adversity on health. We examined whether parasympathetic activity would moderate the link between CFS and health complaints in a sample of 68 undergraduate women (Mean age = 19.44). Participants self-reported CFS and health complaints. Parasympathetic activity was indexed using high-frequency heart rate variability (HF-HRV) and was evaluated by measuring changes in HF-HRV in response to and following a laboratory-based stress induction. Multiple regression analyses indicated that CFS was significantly associated with more health complaints. Further, HF-HRV in response to stress and during recovery relative to baseline significantly moderated relationship between CFS and health complaints. Specifically, more CFS was significantly associated with more health complaints among women who showed mean or greater decreases in HF-HRV in response to stress. Additionally, lower levels of CFS were associated with fewer health complaints among women who showed mean or greater HF-HRV during recovery relative to baseline. Findings highlight the importance of parasympathetic activity in modulating stress-health links. [ABSTRACT FROM AUTHOR]

Strain parameters on speckle tracking echocardiography (STE) have been proposed as effective indexes for evaluating right ventricular (RV) function. This pilot study investigated the role of STE-derived strain parameters in assessing global and regional RV myocardial mechanical changes in patients with acute pulmonary embolism (PE) before and after thrombolytic therapy. In this case–control study, a total of 73 PE patients, 34 with pulmonary hypertension (PH) and 39 without PH, who underwent thrombolytic therapy were included. Healthy volunteers were included as controls. The peak longitudinal systolic strain (PLSS) and time to PLSS (TTP) for the global and regional RV were analyzed by STE software immediately before and 14 days after thrombolytic therapy. Changes in STE-derived strain parameters and conventional ultrasound parameters were compared. PLSS and TTP decreased before treatment in PE patients compared with measurements in the control group, particularly in those with PH. Also, the strain parameters decreased more significantly for the free wall than for the septum wall (P < 0.05). Moreover, the RV diastolic diameter (RVDD) and RV/left ventricular (LV) diameter ratio increased, while RV fraction shortening (RVFS), RV fractional area change (RVFAC), tricuspid regurgitation pressure gradient (TRPG), and tricuspid annular peak systolic excursion (TAPSE) decreased (P < 0.05). The global strain parameters for the RV were positively correlated with RVDD and RV/LV diameter ratio, but negatively correlated with RVFS, RVFAC, TRPG, and TAPSE (P < 0.05). After treatment, the strain parameters differed significantly between PE patients with PH and controls but did not differ between PE patients without PH and controls. STE-derived parameters are effective for detecting changes in global and regional RV function in PE patients with or without acute PH. [ABSTRACT FROM AUTHOR]

Human emotions are integral to daily tasks, and driving is now a typical daily task. Creating a multi-modal human emotion dataset in driving tasks is an essential step in human emotion studies. we conducted three experiments to collect multimodal psychological, physiological and behavioural dataset for human emotions (PPB-Emo). In Experiment I, 27 participants were recruited, the in-depth interview method was employed to explore the driver's viewpoints on driving scenarios that induce different emotions. For Experiment II, 409 participants were recruited, a questionnaire survey was conducted to obtain driving scenarios information that induces human drivers to produce specific emotions, and the results were used as the basis for selecting video-audio stimulus materials. In Experiment III, 40 participants were recruited, and the psychological data and physiological data, as well as their behavioural data were collected of all participants in 280 times driving tasks. The PPB-Emo dataset will largely support the analysis of human emotion in driving tasks. Moreover, The PPB-Emo dataset will also benefit human emotion research in other daily tasks. Measurement(s) electroencephalogram measurement • driving behaviour measurement • face expression, body gesture and road scenario measurement • emotion and persionality Technology Type(s) electroencephalography (EEG) • driving simulator • visual observation method • self-reported scale [ABSTRACT FROM AUTHOR]

Depressive symptoms and abnormal glycolipid metabolisms are common in patients with Parkinson's disease (PD), but their relationship has not been fully reported. It is not clear whether glycolipid impairments lead to poor cognitive and motor function, and aggravate depressive symptoms. Therefore, we aimed to explore the relationships between glycolipid variables, cognition, motor and depressive symptoms in PD patients cross-sectionally. Two hundred ten PD patients were recruited. Glycolipid parameters and Uric acid (UA) were measured. Depressive symptoms, cognitive function and motor symptoms were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MOCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III). Depressive PD patients had significantly worse motor symptoms and higher levels of fasting plasma glucose (FPG) than those in non-depressive patients (F = 24.145, P < 0.001). Further, logistic regression analysis indicated that UPDRS-III (OR = 1.039, 95% CI 1.019–1.057, P = 0.044), FPG (OR = 1.447, 95% CI 1.050–1.994, P = 0.024) were independently associated with depression. In PD patients without depression, UA (β = − 0.068, t = − 2.913, P = 0.005) and cholesterol (CHOL) (β = − 3.941, t = − 2.518, P = 0.014) were independent predictors of the UPDRS-III score; in addition, UPDRS-III score was negatively associated with MOCA score (β = − 0.092, t = − 2.791, P = 0.007). FPG levels and motor symptoms were related to depressive symptoms in PD patients. Further, in non-depressive PD patients, UA and CHOL showed putative biomarkers of motor symptoms. [ABSTRACT FROM AUTHOR]

The use of insecticides remains important in managing pest insects. Over the years, many insects manifested physiological and behavioral modifications resulting in reduced efficacy of insecticides targeted against them. Emerging evidence suggests that bacterial symbionts could modulate susceptibility of host insects against insecticides. Here, we explore the influence of host microbiota in affecting the susceptibility of insect host against different insecticides in the blood-sucking bed bug, Cimex hemipterus. Rifampicin antibiotic treatment resulted in increased susceptibility to fenitrothion and imidacloprid, but not against deltamethrin. Meanwhile, the host fitness parameters measured in the present study were not significantly affected by rifampicin treatment, suggesting the role of bacterial symbionts influencing susceptibility against the insecticides. 16S metagenomics sequencing revealed a drastic shift in the composition of several bacterial taxa following rifampicin treatment. The highly abundant Alphaproteobacteria (Wolbachia > 90%) and Gammaproteobacteria (Yersinia > 6%) in control bed bugs were significantly suppressed and replaced by Actinobacteria, Bacilli, and Betaproteobacteria in the rifampicin treated F1 bed bugs, suggesting possibilities of Wolbachia mediating insecticide susceptibility in C. hemipterus. However, no significant changes in the total esterase, GST, and P450 activities were observed following rifampicin treatment, indicating yet unknown bacterial mechanisms explaining the observed phenomena. Re-inoculation of microbial content from control individuals regained the tolerance of rifampicin treated bed bugs to imidacloprid and fenitrothion. This study provides a foundation for a symbiont-mediated mechanism in influencing insecticide susceptibility that was previously unknown to bed bugs. [ABSTRACT FROM AUTHOR]

Pruning of Juglans mandshurica produces many branches, which are potentially a rich source of juglone although they are usually discarded as waste. Herein, we describe a water-in-oil microemulsion-based microwave-assisted extraction (MBMAE) method to isolate the juglone found in waste branches from J. mandshurica. In our experiment, J. mandshurica waste branch powder was added to the MBMAE system. Using the optimized microemulsion system comprising Tween 80:n-propanol:n-hexane:water at 27:13.5:4.5:55 (w/w/w/w), and a pH of 5.6, at an operating temperature of 40 °C, operating time of 63 s, and operating power of 400 W, the juglone yield was 4.58 mg/g from a ratio of microemulsion to branch power of 20:1 (mL/g). The juglone extraction yield using the MBMAE method was 1.86- and 6.65-fold better than that obtained from microwave-assisted extraction by ethanol (Ethanol-MAE) and heat reflux extraction by ethanol (Ethanol-HRE), respectively. The MBMAE method may be useful as an alternative to traditional extraction methods to isolate juglone. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) have been shown to promote stroke recovery, however, the underlying mechanisms are not well understood. In this study naïve rats were intravenously injected with syngeneic BMSCs to screen for potential differences in brain metabolite spectrum versus vehicle-treated controls by capillary electrophoresis-mass spectrometry. A total of 65 metabolites were significantly changed after BMSC treatment. Among them, 5-oxoproline, an intermediate in the biosynthesis of the endogenous glutathione (GSH), was increased. To confirm the obtained results and investigate the metabolic pathways, BMSCs were injected into rats 24 h after middle cerebral artery occlusion (MCAO). Rats receiving vehicle solution and sham-operated animals served as controls. High performance liquid chromatography, reverse transcription-quantitative polymerase chain reaction, and Western blotting revealed that intravenous BMSC application increased the levels of 5-oxoproline and GSH in MCAO rats, as well as the expression of key enzymes involved in GSH synthesis including, gamma-glutamylcyclotransferase and gamma-glutamylcysteine ligase. Subsequent clinical investigation confirmed that acute ischemic stroke patients had higher plasma 5-oxoproline and GSH levels than age- and sex-matched non-stroke controls. The optimal cutoff value for 5-oxoproline diagnosing acute ischemic stroke (≤ 7d) was 3.127 µg/mL (sensitivity, 63.4 %; specificity, 81.2 %) determined by receiver characteristic operator curve. The area under the curve was 0.782 (95 % confidence interval: 0.718–0.845). Our findings indicate that BMSCs play a protective role in ischemic stroke through upregulation of GSH and 5-oxoproline is a potential biomarker for acute ischemic stroke. Ischemic stroke causes oxidative stress and induction of endogenous, glutathione-dependent anti-oxidative mechanisms. 5-oxoproline, an important metabolite in glutathione biosynthesis, could serve as a biomarker of acute ischemic stroke. Moreover, intravenous bone marrow mesenchymal stem cell (BMSC) treatment after experimental stroke upregulates the expression of key enzymes involved in glutathione synthesis, which results in better antioxidative defense and improved stroke outcome. [ABSTRACT FROM AUTHOR]