Combined intravenous and intra-arterial thrombolysis in hyperacute cerebral ischemia without significant corresponding vascular occlusion/stenosis: A Preliminary investigation.

Objective: In this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction. Methods: Patients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days. Results: Ninety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar (P > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P < 0.05). Asymptomatic hemorrhage rates were 8.7 % for the experimental group and 12.5 % for the control group, with no hemorrhage detected in other locations. Post-treatment median NIHSS scores were lower in the experimental group than in the control group (7 vs 9, P < 0.05), but short-term NIHSS scores were similar (P > 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P < 0.05). Conclusion: In patients with acute ischemic stroke with an onset time of ≤6 h and no major intracranial vessel occlusion, combining rt-PA intravenous thrombolysis with intra-arterial thrombolysis via a microcatheter might yield superior functional outcomes.

Ferroptosis and its implications in treating cognitive impairment caused by aging: A study on the mechanism of repetitive transcranial magnetic stimulation.

OBJECTIVE: Ferroptosis has been recognized as being closely associated with cognitive impairment. Research has established that Alzheimer's disease (AD)-associated proteins, such as amyloid precursor protein (APP) and phosphorylated tau, are involved in brain iron metabolism. These proteins are found in high concentrations within senile plaques and neurofibrillary tangles. Repetitive transcranial magnetic stimulation (rTMS) offers a non-pharmacological approach to AD treatment. This study aims to explore the potential therapeutic effects of rTMS on cognitive impairment through the modulation of the ferroptosis pathway, thereby laying both a theoretical and experimental groundwork for the application of rTMS in treating Alzheimer's disease. METHODS: The study utilized senescence-accelerated mouse prone 8 (SAMP8) mice to model brain aging-related cognitive impairment, with senescence-accelerated-mouse resistant 1 (SAMR1) mice acting as controls. The SAMP8 mice were subjected to high-frequency rTMS at 25 Hz for durations of 14 and 28 days. Cognitive function was evaluated using behavioral tests. Resting-state functional magnetic resonance imaging (rs-fMRI) assessed alterations in cerebral activity by measuring the fractional amplitude of low-frequency fluctuations (fALFF) of the blood oxygen level-dependent signal. Neuronal recovery post-rTMS in the SAMP8 model was examined via HE and Nissl staining. Immunohistochemistry was employed to detect the expression of APP and Phospho-Tau (Thr231). Oxidative stress markers were quantified using biochemical assay kits. ELISA methods were utilized to measure hippocampal levels of Fe2+ and Aß1-42. Finally, the expression of proteins related to the ferroptosis pathway was determined through western blot analysis. RESULTS: The findings indicate that 25 Hz rTMS enhances cognitive function and augments cerebral activity in SAMP8 model mice. Treatment with rTMS in these mice resulted in diminished oxidative stress and safeguarded neurons against damage. Additionally, iron accumulation was mitigated, and the expression of ferroptosis pathway proteins Gpx4, system Xc-, and Nrf2 was elevated. CONCLUSIONS: The Tau/APP-Fe-GPX4/system Xc-/Nrf2 pathway is implicated in the remedial effects of rTMS on cognitive dysfunction, offering a theoretical and experimental basis for employing rTMS in AD treatment.

Heat-induced agglomeration of water-soluble cod proteins toward gelled structures.

Cod proteins (CPs) have potential applications in designing desirable gel-based products, and this study aimed to unravel their heat-induced aggregation pattern and further probe the roles in protein gels. SDS-PAGE analysis indicated that high-precipitation-coefficient aggregates (HPCAs) of CPs aggregates were composed of considerable polymers of myosin heavy chains and actin, and their low-precipitation-coefficient aggregates (LPCAs) contained myosin light chains and tropomyosin. Studies from correlation analysis between the structure and aggregation kinetics revealed that the generation of ß-sheet and SS bonds were responsible for their spontaneous thermal aggregation induced by heating temperature and protein concentration, respectively. Additionally, as protein denaturation ratio increased, more and larger HPCAs were formed, which was evidenced driving the network formation of protein gels and resulting in higher storage modulus (G') values. These novel findings may be applicable to other animal proteins for better tailoring the manufacturing of muscle gel-based products.

Distinct changes of taste quality and metabolite profile in different tomato varieties revealed by LC-MS metabolomics.

Breeding of tomato varieties based on phenotypic traits can potentially lead to a decline in taste and nutritional values, thereby impacting consumer acceptance. However, taste is an intrinsic characteristic of tomatoes. Its decoding requires the identification of crucial compounds and the associated metabolic pathways implicated in taste development and formation. In this study, the taste parameter differences of four tomato varieties were distinguished using an electronic tongue. The content of organic acids and free amino acids, which were closely associated with taste variations, was quantitatively analyzed. Several important taste metabolites and metabolic pathways were identified based on LC-MS metabolomics and enrichment analysis. Through correlation analysis, it was determined that there existed significant associations between the taste, compounds, and metabolites of tomato varieties with different phenotypes. This study could provide references and theoretical basis for tomato breeding, as well as the control and evaluation of taste and quality of tomato varieties.

Uncovering the differences in flavor volatiles of different colored foxtail millets based on gas chromatography-ion migration spectrometry and chemometrics.

The differences of volatile organic compounds in commercially available foxtail millets with different colors (black, green, white and yellow) were assayed through gas chromatography-ion migration spectrometry (GC-IMS) to explore their volatile flavor characteristics. Fifty-five volatile components were found in various colored foxtail millets, including 25 kinds of aldehydes (accounting for 39.19-48.69%), 10 ketones (25.36-32.37%), 15 alcohols (20.19-24.11%), 2 ethers (2.29-2.45%), 2 furans (1.49-2.95%) and 1 ester (0.27-0.39%). Aldehydes, alcohols and ketones were the chief volatiles in different colored foxtail millet, followed by furans, esters and ethers. These identified volatile flavor components in various colored foxtail millets obtained by GC-IMS could be well distinguished by principal components and cluster analysis. Meanwhile, a stable prediction model was fitted via partial least squares-discriminant analysis (PLS-DA), in which 17 kinds of differentially volatile components were screened out based on variable importance in projection (VIP>1). These findings might provide certain information for understanding the flavor traits of colored foxtail millets in future.

Insight into the relationship between metabolite dynamic changes and microorganisms of sea urchin (S. intermedius) gonads during storage.

Sea urchin gonads have high nutritional value and degenerate rapidly during storage. Previous assessment of the freshness of sea urchin gonads was based on experience without valid biochemical indicators. Thus, the current study is to find biochemical indicators representing the freshness of sea urchin gonads. Results showed that the dominant genera of sea urchin gonads were changed from Psychromonas, Ralstonia, and Roseimarinus to Aliivibrio, Psychrilyobacter, and Photobacterium. The differential metabolites of sea urchin gonads were mainly produced through amino acids metabolism. Among them, GC-TOF-MS based differential metabolites had the greatest enrichment in the valine, leucine and isoleucine biosynthesis pathway, while LC-MS based differential metabolites had the greatest enrichment in the alanine, aspartate and glutamate metabolism pathway. The growth of dominant genus (Aliivibrio) had a great influence on the production of differential metabolites. These results will provide valuable information for accurately judging the freshness and shelf life of sea urchin gonads.

Effects of sous vide cooking combined with ultrasound pretreatment on physicochemical properties and microbial communities of Russian sturgeon meat (Acipenser gueldenstaedti).

BACKGROUND: The production of Russian sturgeon is expanding rapidly in China but it is necessary to adopt measures to extend the shelf life of sturgeon meat. Previous studies found that sous vide cooking (SVC) at 60 °C increased the protein and lipid oxidation. The addition of antioxidant substances reduced the acceptance of the product. The effect of combination SVC and ultrasound pretreatment was therefore investigated. RESULTS: Results showed that SVC at 50 °C combined with ultrasound effectively restrained the growth of total viable counts (TVC) in samples. Meanwhile, the main dominant genera changed from Pseudomonas to Carnobacterium and the number of microbial species decreased. The odor profile of Russian sturgeon meat was more stable and the lipoxygenase (LOX) activity decreased more rapidly after treating with SVC and ultrasound. Importantly, more stable protein aggregates were formed in samples treated by SVC 50 °C together with ultrasound pretreatment, so the protein and lipid oxidation were slowed during storage. Higher springiness values were obtained and the color of sturgeon meat was lighter under these conditions. CONCLUSION: The combination of SVC 50 °C and ultrasound pretreatment effectively inhibited the microbial growth of Russian sturgeon meat at lower oxidation levels. These findings theoretically support the preservation and development of sturgeon meat, and the application of SVC technology. © 2022 Society of Chemical Industry.

Ultra-thermostable soy protein particles prepared by combining preheating treatment with slightly alkaline pH.

The development of beverages with high protein concentrations has received considerable interest. Nevertheless, the unwanted protein aggregation and gelation of proteins caused by the pasteurization process are currently posing a significant obstacle. Herein, we describe a facile but robust approach to enhance the heat stability of soy proteins (SPs) by preheating at alkaline pH values. When the modified SPs were reheated at a concentration of 2% (w/v), the anti-aggregation properties of the modified SPs were confirmed without any further increase in the size of the particles. Even at concentrations as high as 20% (w/v), the modified protein suspensions preserved their flowability when reheated, whereas the control sample had already gelled at 10% (w/v) concentration. The fluorescence and circular dichroism (CD) spectra indicated that the structures of the modified SPs unfolded and their conformational integrity was diminished after modification. These changes contributed to the reduced unfolding of soy protein and the decreased exposure of active sites during reheating, which inhibited the cross-linking between soy protein molecules during reheating. Meanwhile, the increased surface charge also inhibited the secondary aggregation behavior, improving the thermal stability of protein particles. These findings show that preheating in combination with alkaline pH can be successfully applied to improve the thermal stability of soy proteins, providing a feasible technique and essential insights into the application of soy proteins in protein-enriched liquid systems.

Family Support and Hope among People with Substance Use Disorder in China: A Moderated Mediation Model.

Studies have shown that hope is an important protective factor. At present, few of the available studies on hope have been conducted on people undergoing compulsory rehabilitation. This study explores the mediating role of resilience between family support and hope, and whether relapse plays a moderating role between family support, resilience, and hope. A total of 647 people with substance use disorder completed surveys on Perceived Social Support from Family Scale, Connor-Davidson Resilience Scale, and Herth Hope Index. Structural equation modeling was used to examine the moderated mediation analysis. Family support not only has a direct effect on hope, but also has a significant indirect effect on hope through resilience. The indirect effect of family support on hope via resilience was significant among both the non-relapse group and relapse group; in addition, both the association between family support and resilience and the relation between resilience and hope were moderated by relapse experience. The results indicate that interventions targeting resilience might be an effective approach to improving hope among people with substance use disorder in China.

Detection of arrhythmia in 12-lead varied-length ECG using multi-branch signal fusion network.

Objective.Automatic detection of arrhythmia based on electrocardiogram (ECG) plays a critical role in early prevention and diagnosis of cardiovascular diseases. With the increase in widely available digital ECG data and the development of deep learning, multi-class arrhythmia classification based on automatic feature extraction of ECG has become increasingly attractive. However, the majority of studies cannot accept varied-length ECG signals and have limited performance in detecting multi-class arrhythmias.Approach.In this study, we propose a multi-branch signal fusion network (MBSF-Net) for multi-label classification of arrhythmia in 12-lead varied-length ECG. Our model utilizes the complementary power between different structures, which include Inception with depthwise separable convolution (DWS-Inception), spatial pyramid pooling (SPP) Layer, and multi-scale fusion Resnet (MSF-Resnet). The proposed method can extract features from each lead of 12-lead ECG recordings separately and then effectively fuse the features of each lead by integrating multiple convolution kernels with different receptive fields, which can achieve the information of complementation between different angles of the ECG signal. In particular, our model can accept 12-lead ECG signals of arbitrary length.Main results.The experimental results show that our model achieved an overall classification F1 score of 83.8% in the 12-lead ECG data of CPSC-2018. In addition, the F1 score of the MBSF-Net performed best among the MBF-Nets which are removed the SPP layer from MBSF-Net. In comparison with the latest ECG classification algorithms, the proposed model can be applied in varied-length signals and has an excellent performance, which not only can fully retain the integrity of the original signals, but also eliminates the cropping/padding signal beforehand when dealing with varied-length signal database.Significance.MBSF-Net provides an end-to-end multi-label classification model with outperfom performance, which allows detection of disease in varied-length signals without any additional cropping/padding. Moreover, our research is beneficial to the development of computer-aided diagnosis.

Supraventricular ectopic beats and ventricular ectopic beats detection based on improved U-net.

Objective.Supraventricular ectopic beats (SVEB) or ventricular ectopic beats (VEB) are common arrhythmia with uncertain occurrence and morphological diversity, so realizing their automatic localization is of great significance in clinical diagnosis.Methods.We propose a modified U-net network: USV-net, it can simultaneously realize the automatic positioning of VEB and SVEB. The improvement consists of three parts: firstly, we reconstruct part of the convolutional layer in U-net using group convolution to reduce the expression of redundant features. Secondly, a plug-and-play multi-scale 2D deformable convolution module is designed to extract cross-channel features of different scales. Thirdly, in addition to conventional output of U-net, we also compress and output the bottom feature map of U-net, the dual-output is trained through Dice-loss to take into account the learning of high/low resolution features of the model. We used the MIT-BIH arrhythmia database for patient-specific training, and used Sensitivity, Positive prediction rate and F1-scores to evaluate the effectiveness of our method.Main Result.The F1-scores of SVEB and VEB achieve the best results compared with other studies in different testing records. It is worth noting that the F1-scores of SVEB and VEB reached 81.3 and 95.4 in the 24 testing records. Moreover, our method is also at the forefront in Sensitivity and Positive prediction rate.Significance.The method proposed in this paper has great potential in the detection of SVEB and VEB. We anticipate efficiency and accuracy of clinical detection of ectopic beats would be improved.

Ni-Catalyzed Enantioselective Benzylation of Secondary Phosphine Oxide.

A nickel-catalyzed benzylic substitution of secondary phosphine oxide was described, affording the dialkylated P-stereogenic tertiary phosphine oxides with high to excellent enantioselectivities. The reaction was performed under mild conditions with commercially available benzyl chlorides and bench stable secondary phosphine oxides, exhibiting broad functional group tolerance. It represented a practical example for the preparation of P-stereogenic phosphine compounds.

miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1.

We explore miR-150-5p in atherosclerosis (AS). The AS model was constructed using Apo E-/- mice with an injection of the miR-150-5p mimic or an inhibitor. Pathological characteristics were assessed using Oil red O staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expressions of microRNA-150-5p (miR-150-5p), STAT1, α-SMA (α-smooth muscle actin) and proliferating cell nuclear antigen (PCNA). Targetscan and dual-luciferase reporter assay were used to analyze the interaction between miR-150-5p and STAT1. The viability, migration, cell cycle and α-SMA and PCNA expressions in oxidized low-density lipoprotein (ox-LDL)-stimulated primary human aortic smooth muscle cells (ASMCs) were assessed using molecular experiments. miR-150-5p was reduced in both AS mice and ox-LDL-stimulated human aortic smooth muscle cells but STAT1 had the opposite effect. The miR-150-5p inhibitor alleviated the increase of lipid plaque and reduced collagen accumulation in the aortas during AS. Upregulation of α-SMA and PCNA was reversed by miR-150-5p upregulation. STAT1 was targeted by miR-150-5p, and overexpressed miR-150-5p weakened the ox-LDL-induced increase of viability and migration abilities and blocked cell cycle in ASMCs, but overexpressed STAT1 blocked the effect of the miR-150-5p mimic. This paper demonstrates that miR-150-5p has potential as a therapeutic target in AS, with plaque stabilization by regulating ASMC proliferation and migration via STAT1.

Two-stage ECG signal denoising based on deep convolutional network.

Background.An electrocardiogram (ECG) is an effective and non-invasive indicator for the detection and prevention of arrhythmia. ECG signals are susceptible to noise contamination, which can lead to errors in ECG interpretation. Therefore, ECG pretreatment is important for accurate analysis.Methods.The ECG data used are from CPSC2018, and the noise signal is from MIT-BIH Noise Stress Test Database. In the experiment, the signal-to-noise ratio (SNR), the root mean square error (RMSE), and the correlation coefficientPare used to evaluate the performance of the network. The method proposed is divided into two stages. In the first stage, a Ude-net model is designed for ECG signal denoising to eliminate noise. The DR-net model in the second stage is used to reconstruct the ECG signal and to correct the waveform distortion caused by noise removal in the first stage. In this paper, the Ude-net and the DR-net are constructed by the convolution method to achieve end-to-end mapping from noisy ECG signals to clean ECG signals.Result.In SNR, RMSE andPindicators, Ude-net + DR-net proposed in this paper can achieve the best performance compared with the other five schemes (FCN, U-net etc). In the three data sets, SNR can be increased by 11.61 dB, 13.71 dB and 14.40 dB and RMSE can be reduced by 10.46 × 10-2, 21.55 × 10-2and 15.98 × 10-2.Conclusions.Despite the contradictory results, the proposed two-stages method can achieve both the elimination of noise and the preservation of effective details to a large extent of the signals. The proposed method has good application prospects in clinical practice.

Changes in the digestion properties and protein conformation of sturgeon myofibrillar protein treated by low temperature vacuum heating during in vitro digestion.

The digestion properties of sturgeon myofibrillar protein (MF) treated by low temperature vacuum heating (LTVH) at different processing temperatures (50, 60 and 70 °C) and times (15 and 30 min) were studied and compared with those of sturgeon MF treated by traditional cooking (TC). The results showed that as the temperature and time increased, the protein digestibility decreased, whereas the particle size and protein aggregation increased. It was observed that the band intensity of myosin heavy chain and myosin heavy chain 7 weakened; however, the band intensity of actin showed little change. MALDI-TOF-MS analysis revealed that the digested products of the samples treated by LTVH had a larger proportion of 750-1000 Da peptides than those treated by TC, which was consistent with the trend of the number of unique peptides identified in each group. Fourier transmission infrared (FT-IR) spectroscopy showed that the contents of α-helices and ß-sheets exhibited negative and positive correlations with the temperature, respectively. Overall, compared to TC, LTVH can relieve the heat stress of protein conformation, reduce protein aggregation to improve the accessibility of the protein to digestive protease, and increase digestibility.

A novel method to reduce false alarms in ECG diagnostic systems: capture and quantification of noisy signals.

Objective. Muscle artifacts (MA) and electrode motion artifacts (EMA) in electrocardiogram (ECG) signals lead to a large number of false alarms from cardiac diagnostic systems. To reduce false alarms, it is necessary to improve the performance of the diagnostic algorithm in noisy environments by removing excessively noisy signals. However, existing methods focus on signal quality assessment and contain too many artificial features. Here, we present a novel method to flexibly eliminate noisy signals without any artificial features.Approach. Our method contains an improved lightweight deep neural network (DNN) to capture the signal portions damaged by EMA and MA, uses the sample entropy to quantize noisy portions, and discards those portions that exceed a defined threshold. Our method was tested in conjunction with Pan-Tompkins (PT), Filter Bank (FB), and 'UNSW' R-peak detection algorithms along with two heartbeat classification algorithms on datasets synthesized from the MIT-BIH Noise Stress Test Database, the China Physiological Signal Challenge 2018 Database and the MIT-BIH Arrhythmia Database.Main results. For PT R-peak detection algorithms, the sensitivity (Se) increased noticeably from 89.01% to 99.42% in the synthesized datasets with a signal-to-noise ratio of 6 dB. With the same datasets, the Se of the FB algorithm increased about 9.29%, and a 3.64% increase occurred in the Se of the 'UNSW' algorithm. For heartbeat classification algorithms, the overall F1-score increased about 6% in the synthesized one-heartbeat datasets. It is the first study to utilize a DNN to capture noisy segments of the ECG signal.Significance. Too many false alarms can cause alarm fatigue. Our method can be utilized as the preprocessing before signal analysis, thereby reducing false alarms from the ECG diagnostic systems.

Changes in food quality and microbial composition of Russian sturgeon (Acipenser gueldenstaedti) fillets treated with low temperature vacuum heating method during storage at 4 °C.

Russian sturgeon is a high-quality cultured fish and traditional heating methods may lead to deterioration of its food quality. This study aimed to evaluate the food quality and microbial composition of sturgeon fillets by low temperature vacuum heating (LTVH) and storage at 4 °C. The treatments varied in temperature (50, 60, and 70 °C) and duration (15 and 30 min); samples treated by traditional heating (100 °C, 15 min) methods were included as controls. We found that LTVH could reduce the values of lightness (L*), yellowness (b*), and pH and increase the values of redness (a*), chewiness, and hardness, to promote food quality. The biogenic amine content declined with the increase in heating temperature and time, the histamine of most concern was low at the end of storage, the values of LTVH70-30 and TC was 33.12 ± 1.25 and 30.39 ± 0.86 mg/kg. The total viable count (TVC) and biogenic amines showed the same trend, and the finial TVC values of LTVH60-30, LTVH70-15, LTVH70-30 and TC were 6.72 ± 0.17, 6.33 ± 0.18, 6.18 ± 0.08 and 5.93 ± 0.16 log CFU/g, which did not exceed the limit value (7 log CFU/g), indicating that the biosafety risk was reduced. According to the high-throughput sequencing results, the microbial composition of LTVH samples showed a lesser abundance pseudomonads than that found in the control. Thus, LTVH technology could be used as an alternative to traditional heating treatment.

Effect of low-temperature vacuum heating on physicochemical properties of sturgeon (Acipenser gueldenstaedti) fillets.

BACKGROUND: Sturgeon is popular for its nutritious value and its taste. However, sturgeon fillets are traditionally heated in 100 °C boiling water, resulting in unfavorable taste and with a negative effect on the quality. This study considered the effect of combinations of vacuum and low-temperature treatments (LTVH groups) on sturgeon fillets compared with the traditional heat treatment (TC groups). RESULTS: The results show that the LTVH groups had lower cooking-loss rates. All LTVH fillets were changed to a white color, and appeared 'done', as did the TC fillets. The LTVH and TC methods gave rise to significant differences in texture: the springiness of the LTVH groups decreased with heating time, and decreased rapidly in the TC groups (P < 0.05); hardness and chewiness increased with time and temperature in the LTVH groups, but decreased in the TC groups. More compact and denser gaps were observed in LTVH70 groups and TC groups. Less protein and lipid oxidation was evident in LTVH groups, including more myofibril protein solubility; there was less protein aggregation, fewer thiobarbituric acid reactive substance, and Schiff base. CONCLUSION: Vacuum and low-temperature treated sturgeon fillets can be served as a good alternative. This treatment caused slight tissue damage and less proteolysis and lipid oxidation, which is beneficial for the quality of aquatic products.

Selective Ortho Thiolation Enabled by Tuning the Ancillary Ligand in Palladium/Norbornene Catalysis.

Site-selective introduction of a sulfur group into aromatic compounds is essential and useful in organic, material, and pharmaceutical chemistry. A palladium/norbornene-catalyzed chemoselective ortho thiolation of aryl halides was reported. The selectivity of reductive elimination for C(Ar)-SR bond formation was well controlled by tuning the ancillary ligand in the aryl-NBE palladacycle Pd(IV) intermediate. The reaction showcased good substrate scope: both S-alkyl and S-aryl thiosulfonates were compatible.