Deep Self-Reconstruction Fusion Similarity Hashing for the Diagnosis of Alzheimer's Disease on Multi-Modal Data.

The pathogenesis of Alzheimer's disease (AD) is extremely intricate, which makes AD patients almost incurable. Recent studies have demonstrated that analyzing multi-modal data can offer a comprehensive perspective on the different stages of AD progression, which is beneficial for early diagnosis of AD. In this paper, we propose a deep self-reconstruction fusion similarity hashing (DS-FSH) method to effectively capture the AD-related biomarkers from the multi-modal data and leverage them to diagnose AD. Given that most existing methods ignore the topological structure of the data, a deep self-reconstruction model based on random walk graph regularization is designed to reconstruct the multi-modal data, thereby learning the nonlinear relationship between samples. Additionally, a fused similarity hash based on anchor graph is proposed to generate discriminative binary hash codes for multi-modal reconstructed data. This allows sample fused similarity to be effectively modeled by a fusion similarity matrix based on anchor graph while modal correlation can be approximated by Hamming distance. Especially, extracted features from the multi-modal data are classified using deep sparse autoencoders classifier. Finally, experiments conduct on the AD Neuroimaging Initiative database show that DS-FSH outperforms comparable methods of AD classification. To conclude, DS-FSH identifies multi-modal features closely associated with AD, which are expected to contribute significantly to understanding of the pathogenesis of AD.

Diagnosis-Guided Deep Subspace Clustering Association Study for Pathogenetic Markers Identification of Alzheimer's Disease Based on Comparative Atlases.

The roles of brain region activities and genotypic functions in the pathogenesis of Alzheimer's disease (AD) remain unclear. Meanwhile, current imaging genetics methods are difficult to identify potential pathogenetic markers by correlation analysis between brain network and genetic variation. To discover disease-related brain connectome from the specific brain structure and the fine-grained level, based on the Automated Anatomical Labeling (AAL) and human Brainnetome atlases, the functional brain network is first constructed for each subject. Specifically, the upper triangle elements of the functional connectivity matrix are extracted as connectivity features. The clustering coefficient and the average weighted node degree are developed to assess the significance of every brain area. Since the constructed brain network and genetic data are characterized by non-linearity, high-dimensionality, and few subjects, the deep subspace clustering algorithm is proposed to reconstruct the original data. Our multilayer neural network helps capture the non-linear manifolds, and subspace clustering learns pairwise affinities between samples. Moreover, most approaches in neuroimaging genetics are unsupervised learning, neglecting the diagnostic information related to diseases. We presented a label constraint with diagnostic status to instruct the imaging genetics correlation analysis. To this end, a diagnosis-guided deep subspace clustering association (DDSCA) method is developed to discover brain connectome and risk genetic factors by integrating genotypes with functional network phenotypes. Extensive experiments prove that DDSCA achieves superior performance to most association methods and effectively selects disease-relevant genetic markers and brain connectome at the coarse-grained and fine-grained levels.

Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology.

BACKGROUND: Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis, increase insulin secretion, and improve blood glucose tolerance. However, its mechanism of action in the treatment of diabetic cardiomyopathy (DCM) remains unclear, hindering research efforts aimed at developing drugs specifically for the treatment of DCM. AIM: To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment. METHODS: We explored various databases and software, including the Traditional Chinese Medicine Systems Pharmacology Database, Uniport, PubChem, GenCards, String, and Cytoscape, to identify the active components and targets of Jiawei Jiaotai Pill, and the disease targets in DCM. Protein-protein interaction network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM. Molecular docking of key active components and core targets was verified using AutoDock software. RESULTS: Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified. There were 100 common targets between the DCM and Jiawei Jiaotai Pills. Through this screening process, TNF, IL6, TP53, EGFR, INS, and other important targets were identified. These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase (MAPK) MAPK cascade, response to xenobiotic stimuli, response to hypoxia, positive regulation of gene expression, positive regulation of cell proliferation, negative regulation of the apoptotic process, and other biological processes. It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications, DCM, PI3K-Akt, interleukin-17, and MAPK signaling pathways. Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target. CONCLUSION: The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress, cardiomyocyte apoptosis and fibrosis, and maintaining metabolic homeostasis.

Latest progress in low-intensity pulsed ultrasound for studying exosomes derived from stem/progenitor cells.

Stem cells have self-renewal, replication, and multidirectional differentiation potential, while progenitor cells are undifferentiated, pluripotent or specialized stem cells. Stem/progenitor cells secrete various factors, such as cytokines, exosomes, non-coding RNAs, and proteins, and have a wide range of applications in regenerative medicine. However, therapies based on stem cells and their secreted exosomes present limitations, such as insufficient source materials, mature differentiation, and low transplantation success rates, and methods addressing these problems are urgently required. Ultrasound is gaining increasing attention as an emerging technology. Low-intensity pulsed ultrasound (LIPUS) has mechanical, thermal, and cavitation effects and produces vibrational stimuli that can lead to a series of biochemical changes in organs, tissues, and cells, such as the release of extracellular bodies, cytokines, and other signals. These changes can alter the cellular microenvironment and affect biological behaviors, such as cell differentiation and proliferation. Here, we discuss the effects of LIPUS on the biological functions of stem/progenitor cells, exosomes, and non-coding RNAs, alterations involved in related pathways, various emerging applications, and future perspectives. We review the roles and mechanisms of LIPUS in stem/progenitor cells and exosomes with the aim of providing a deeper understanding of LIPUS and promoting research and development in this field.

[High-throughput screening of 54 alternative plasticizers in sesame oil using gas chromatography-quadrupole time-of-flight mass spectrometry].

Restrictions on the use of phthalates have led to the wide use of alternative plasticizers (APs) such as organophosphate, adipate, citrate, and sebacate. However, because plasticizers combine with polymers in plastic products via unstable noncovalent bonds, they can easily migrate out of these products, causing environmental pollution. In particular, their migration out of food packaging, containers, and other food-contact materials and into food has raised great concerns. Toxicological studies have shown that APs contain potentially toxic substances that can affect endocrine functions and cause neurotoxicity, genotoxicity, and other adverse effects. Thus, their potential risks to food should not be underestimated. Sesame oil is a necessity in daily cooking. The results of risk monitoring in recent years have indicated that sesame oil often contains phthalates in excess of the standard limits. However, the potential risks of APs in sesame oil have not yet been reported. Some common detection methods for APs include gas chromatography-mass spectrometry, gas chromatography-triple quadrupole mass spectrometry, and liquid chromatography-triple quadrupole mass spectrometry. Unfortunately, these methods use low-resolution mass spectrometry and are limited by the resolution, scan rate, and analysis mode. Gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) has the advantages of high resolution, sensitivity, and analysis speed. In full-scan mode, GC-Q-TOF/MS can accurately collect the full-spectrum mass number of target compounds with low content levels in complex substrates, thereby realizing efficient screening and quantitative analysis. It shows outstanding advantages in the trace analysis of pesticide residues and pollutants. Furthermore, it features strong qualitative and high screening abilities. Establishment of a personal compound database and library (PCDL) addresses limitations in the number of compounds that can be measured and enables the rapid identification of targets without the use of standard products. In addition, increasing the number of targets for synchronous screening enables the retrospective analysis of new targets. In this study, a method based on GC-Q-TOF/MS was developed for the determination of 54 APs in sesame oil. The samples were extracted with acetonitrile and purified using a PSA/silica solid-phase extraction column. The mass-spectral information of the samples was then collected by GC-Q-TOF/MS in full-scan mode, and the 54 APs were searched using an established high-resolution mass-spectrum database to simultaneously achieve the broad-spectrum screening, qualitative identification, and quantitative analysis of multiple targets. The effects of different extraction solvents and purification methods on sample extraction and purification were compared. The accuracy of the screening results was improved by optimizing the GC-separation conditions, quality-extraction window, retention-time deviation, and other screening parameters. The screening detection limits (SDLs) of the 54 APs ranged from 0.01 to 0.02 mg/kg; specifically, the SDL of 41 compounds was 0.01 mg/kg and that of 13 compounds were 0.02 mg/kg. The limits of quantification were in the range of 0.02-0.04 mg/kg. A total of 80 sesame-oil samples were rapidly screened using this method under optimal conditions. Five APs were identified from the 80 sesame-oil samples and quantitatively analyzed using the matrix-matched external-standard method. The results of this quantitative methodology showed that the five APs had good linear relationships in the range of 0.01-0.2 mg/L, with all correlation coefficients greater than 0.99. The accuracy and precision of the method were verified using a standard recovery test with blank sesame-oil samples. Under the three standard levels of 0.04, 0.08, and 0.2 mg/kg, the recoveries of the five APs ranged from 71.3% to 97.8%, and the relative standard deviations (RSDs) ranged from 0.4% to 6.1%(n=6). The developed method is fast, accurate, sensitive, and has high throughput. Thus, it can realize the efficient screening, qualitative identification, and quantitative analysis of the 54 APs in sesame oil and provides a potential solution for the monitoring of other contaminants in food.

Wrist-ankle acupuncture combined with pain nursing for the treatment of urinary calculi with acute pain.

BACKGROUND: Urological calculi often cause renal colic, which is characterized by paroxysmal or persistent severe pain in the upper abdomen or lumbar region. Development of methods to quickly relieve these pain symptoms has garnered clinical attention. Wrist-ankle acupuncture is a type of floating acupuncture therapy administered at selected points in the carpal and ankle areas, and it has good pain-relieving effects. We used wrist-ankle acupuncture combined with pain nursing for pain intervention in patients with renal calculi to confirm its application and safety. AIM: To study the effect of wrist-ankle acupuncture combined with pain nursing in the treatment of urinary calculi with acute pain. METHODS: Eighty-two patients with urinary calculi with acute pain as the first symptom followed at our hospital from November 2019 to June 2021 were enrolled in the study and classified into two groups according to the odd and even numbers of the visit sequences, each with 41 cases. The control group received a routine nursing intervention and intramuscular injection of nonsteroidal anti-inflammatory drugs, whereas the observation group received pain management nursing and wrist-ankle acupuncture. Subsequently, the pain-relieving effect was compared between the two groups. RESULTS: The score on the visual analog scale (VAS) at 24, 48, and 72 h postintervention was decreased in both groups compared with the baseline data; moreover, the observation group scored significantly lower than the control group on the VAS at each time point after the intervention (P < 0.05). The clinical efficacy at 24 h postintervention was not significantly different between the two groups (P > 0.05). In turn, the pain recurrence rate at 72 h postintervention was lower in the observation group compared with the control group (P < 0.05). Finally, the nursing satisfaction rate in the observation group was significantly higher than that observed in the control group (P < 0.05). No serious adverse reactions occurred during the treatment and the safety of treatment was high in both groups. CONCLUSION: Wrist-ankle acupuncture combined with pain nursing for treating urolithiasis with acute pain effectively alleviated the degree of pain and reduced the recurrence rate, which was worthy of clinical application.

Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10.

Parthanatos is a type of programmed cell death dependent on hyper-activation of poly (ADP-ribose) polymerase 1 (PARP-1). SIRT1 is a highly conserved nuclear deacetylase and often acts as an inhibitor of parthanatos by deacetylation of PARP1. Our previous study showed that deoxypodophyllotoxin (DPT), a natural compound isolated from the traditional herb Anthriscus sylvestris, triggered glioma cell death via parthanatos. In this study, we investigated the role of SIRT1 in DPT-induced human glioma cell parthanatos. We showed that DPT (450 nmol/L) activated both PARP1 and SIRT1, and induced parthanatos in U87 and U251 glioma cells. Activation of SIRT1 with SRT2183 (10 µmol/L) enhanced, while inhibition of SIRT1 with EX527 (200 µmol/L) or knockdown of SIRT1 attenuated DPT-induced PARP1 activation and glioma cell death. We demonstrated that DPT (450 nmol/L) significantly decreased intracellular NAD+ levels in U87 and U251 cells. Further decrease of NAD+ levels with FK866 (100 µmol/L) aggravated, but supplement of NAD+ (0.5, 2 mmol/L) attenuated DPT-induced PARP1 activation. We found that NAD+ depletion enhanced PARP1 activation via two ways: one was aggravating ROS-dependent DNA DSBs by upregulation of NADPH oxidase 2 (NOX2); the other was reinforcing PARP1 acetylation via increase of N-acetyltransferase 10 (NAT10) expression. We found that SIRT1 activity was improved when being phosphorylated by JNK at Ser27, the activated SIRT1 in reverse aggravated JNK activation via upregulating ROS-related ASK1 signaling, thus forming a positive feedback between JNK and SIRT1. Taken together, SIRT1 activated by JNK contributed to DPT-induced human glioma cell parthanatos via initiation of NAD+ depletion-dependent upregulation of NOX2 and NAT10.

[High-throughput screening of multi-pesticide residues in animal-derived foods by QuEChERS-online gel permeation chromatography-gas chromatography-tandem mass spectrometry].

Improvements in living standards have led to an increase in the consumption of animal-derived foods. Pesticides may be used illegally during animal breeding as well as meat production and processing for pest control and preservation. Pesticides applied to crops may also be enriched in animal tissues through the food chain, thereby increasing the risk of pesticide residue accumulation in muscles and visceral tissues and endangering human health. China has stipulated maximum residue limits for pesticide residues in livestock and poultry meat and their viscera. Many other major developed countries and organizations, including the European Union, Codex Alimentarius Commission, and Japan, have also set maximum residue limits for these residues (0.005-10, 0.004-10, and 0.001-10 mg/kg, respectively). Research on pretreatment technologies for pesticide residue detection in plant-derived foods is widely available, but insufficient attention has been paid to animal-derived foods. Thus, high-throughput detection technologies for pesticide residues in animal-derived foods are limited. The impurities that can interfere with the detection process for plant-derived foods mainly include organic acids, polar pigments, and other small molecular compounds; by contrast, the matrix of animal-derived foods is much more complex. Macromolecular proteins, fats, small molecular amino acids, organic acids, and phospholipids can interfere with the detection of pesticide residues in animal-derived foods. Thus, selecting the appropriate pretreatment and purification technology is of great importance. In this study, the QuEChERS technique was combined with online gel permeation chromatography-gas chromatography-tandem mass spectrometry (GPC-GC-MS/MS) to determine 196 pesticide residues in animal-derived foods. The samples were extracted with acetonitrile, purified using the QuEChERS technique coupled with online GPC, detected by GC-MS/MS, determined in multiple reaction monitoring mode (MRM), and quantified using the external standard method. The effects of the extraction solvent and purification agent type on the extraction efficiency and matrix removal of the method were optimized. The purification effect of online GPC on the sample solution was investigated. The optimal distillate receiving time was obtained by studying the recoveries of the target substances and matrix effects over different distillate receiving periods to achieve the effective introduction of target substances and efficient matrix removal. Further, the advantages of the QuEChERS technique combined with online GPC were evaluated. The matrix effects of 196 pesticides were assessed; ten pesticide residues showed moderate matrix effects, while four pesticide residues showed strong matrix effects. A matrix-matched standard solution was used for quantification. The 196 pesticides showed good linearity in the range of 0.005-0.2 mg/L, with correlation coefficients greater than 0.996. The limits of detection and quantification were 0.002 and 0.005 mg/kg, respectively. The recoveries of 196 pesticides at spiked levels of 0.01, 0.05, and 0.20 mg/kg were 65.3%-126.2%, with relative standard deviations (RSDs) of 0.7%-5.7%. The proposed method is rapid, accurate, and sensitive; thus, it is suitable for the high-throughput screening and detection of multiple pesticide residues in animal-derived foods.

Restraint stress induced anxiety and sleep in mice.

In humans and animals, exposure to changes in internal or external environments causes acute stress, which changes sleep and enhances neurochemical, neuroendocrine, and sympathetic activities. Repeated stress responses play an essential role in the pathogenesis of psychiatric diseases and sleep disorders. However, the underlying mechanism of sleep changes and anxiety disorders in response to acute stress is not well established. In the current study, the effects of restraint stress (RS) on anxiety and sleep-wake cycles in mice were investigated. We found that after RS, the mice showed anxiety-like behavior after RS manipulation and increased the amounts of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in the dark period. The increase in sleep time was mainly due to the increased number of episodes of NREM and REM sleep during the dark period. In addition, the mice showed an elevation of the EEG power spectrum of both NREM and REM sleep 2 h after RS manipulation. There was a significant reduction in the EEG power spectrum of both NREM and REM sleep during the darkperiod in the RS condition. The expression of the c-Fos protein was significantly increased in the parabrachial nucleus, bed nucleus of the stria terminalis, central amygdala, and paraventricular hypothalamus by RS manipulation. Altogether, the findings from the present study indicated that neural circuits from the parabrachial nucleus might regulate anxiety and sleep responses to acute stress, and suggest a potential therapeutic target for RS induced anxiety and sleep alterations.

Authenticity and species identification of Fritillariae cirrhosae: a data fusion method combining electronic nose, electronic tongue, electronic eye and near infrared spectroscopy.

This paper focuses on determining the authenticity and identifying the species of Fritillariae cirrhosae using electronic nose, electronic tongue, and electronic eye sensors, near infrared and mid-level data fusion. 80 batches of Fritillariae cirrhosae and its counterfeits (including several batches of Fritillaria unibracteata Hsiao et K.C. Hsia, Fritillaria przewalskii Maxim, Fritillaria delavayi Franch and Fritillaria ussuriensis Maxim) were initially identified by Chinese medicine specialists and by criteria in the 2020 edition of Chinese Pharmacopoeia. After obtaining the information from several sensors we constructed single-source PLS-DA models for authenticity identification and single-source PCA-DA models for species identification. We selected variables of interest by VIP value and Wilk's lambda value, and we subsequently constructed the three-source fusion model of intelligent senses and the four-source fusion model of intelligent senses and near-infrared spectroscopy. We then explained and analyzed the four-source fusion models based on the sensitive substances detected by key sensors. The accuracies of single-source authenticity PLS-DA identification models based on electronic nose, electronic eye, electronic tongue sensors and near-infrared were respectively 96.25%, 91.25%, 97.50% and 97.50%. The accuracies of single-source PCA-DA species identification models were respectively 85%, 71.25%, 97.50% and 97.50%. After three-source data fusion, the accuracy of the authenticity identification of the PLS-DA identification model was 97.50% and the accuracy of the species identification of the PCA-DA model was 95%. After four-source data fusion, the accuracy of the authenticity of the PLS-DA identification model was 98.75% and the accuracy of the species identification of the PCA-DA model was 97.50%. In terms of authenticity identification, four-source data fusion can improve the performance of the model, while for the identification of the species the four-source data fusion failed to optimize the performance of the model. We conclude that electronic nose, electronic tongue, electronic eye data and near-infrared spectroscopy combined with data fusion and chemometrics methods can identify the authenticity and determine the species of Fritillariae cirrhosae. Our model explanation and analysis can help other researchers identify key quality factors for sample identification. This study aims to provide a reference method for the quality evaluation of Chinese herbs.

Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501).

Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD.

Characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-FDG PET/computed tomography and HRCT.

PURPOSE: To assess the characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) and high-resolution computed tomography (HRCT). MATERIAL AND METHODS: This was a retrospective study with 20 cases in the fibrotic-foci-like lung adenocarcinoma group; the control group was old fibrotic-foci of the lung with 20 cases. The following 18 F-FDG PET/CT and HRCT features were evaluated: the maximum standardized uptake value (SUVmax); the tumor-to-background ratios of SUVmax (TBRmax); the long-to-short diameter ratio (L/S); anatomic location; location type; internal characteristics; marginal characteristics and surrounding structures. In the fibrotic-foci-like lung adenocarcinoma group, a comparison of 18 F-FDG uptake between the metastatic group ( n  = 10) and the non-metastatic group ( n  = 10) was performed. Finally, the comparison of diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma between 18 F-FDG PET/CT and HRCT was performed. RESULTS: The SUVmax [2.6 (1.7-7.9) vs. 1.0 (0.7-1.4)], TBRmax [2.9 (2.1-9.9) vs. 1.3 (1.2- 1.7)], L/S [2.4 (1.7-3.8) vs. 4.0 (3.2-6.3)], ground-glass opacity (GGO) [13/20 (65.0%) vs. 4/20 (20.0%)], and vessel convergence [7/20 (35.0%) vs. 1/20 (5.0%)] were found to be statistically significant differences between the fibrotic-foci-like lung adenocarcinoma group and the old fibrotic-foci group ( P  < 0.05). SUVmax [7.9 (4.7-8.8) vs. 1.7 (1.2-2.2)] and TBRmax [9.9 (6.5-11.0) vs. 2.1 (1.6-2.9)] were found to be statistically significant differences between the metastatic group and the non-metastatic group ( P  < 0.05). 18 F-FDG PET/CT showed the higher diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma than HRCT [95.0% (19/20) vs. 65.0% (13/20), P  < 0.05]. CONCLUSION: The specific characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-FDG PET/CT and HRCT were high 18 F-FDG uptake, GGO, and vessel convergence, which could be distinguished from old fibrotic-foci of the lung.

Anti-depressant-like effects of rannasangpei and its active ingredient crocin-1 on chronic unpredictable mild stress mice.

Major depressive disorder is one of the most common neuropsychiatric diseases and it is a global public health problem that leads to disabilities. Currently, there is a growing need to explore novel strategy to cure major depressive disorder due to the limitation of available treatments. Rannasangpei (RSNP) is a traditional Tibetan medicine which acts as a therapeutic agent in various acute or chronic diseases, including cardiovascular diseases and neurodegenerative diseases. Crocin-1 a coloring ingredient of saffron which exhibited anti-oxidative and anti-inflammatory properties. Here, we aimed to illustrate whether RSNP and its active ingredient crocin-1 rescue depressive-like phenotypes in chronic unpredictable mild stress (CUMS) induced mouse model of depression. Our results showed that peripheral administration of RSNP or crocin-1 ameliorated the depressive-like behaviors in CUMS-treated mice, as demonstrated by the forced swimming test and tail suspension test. Furthermore, RSNP or crocin-1 treatment reduced oxidative stress in the peripheral blood and hippocampus of the CUMS-treated mice. Additionally, the dysregulated immune system response, as demonstrated by the increased expression of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6) and the decreased expression of the anti-inflammatory factor-interleukin-10 in the prefrontal cortex and/or hippocampus of CUMS-treated mice, were at least partially restored by RSNP or crocin-1 treatment. RSNP or crocin-1 also restored apoptotic protein marker (Bcl-2 and Bax) levels in the prefrontal cortex and hippocampus of the CUMS-treated mice. Moreover, our data indicated that RSNP or crocin-1 increased astrocyte number and brain-derived neurotrophic factor levels in the hippocampus of CUMS-treated mice after RSNP or crocin-1 administration. Taken together, our study for the first time revealed an anti-depressant effect of RSNP and its active ingredient crocin-1 in a mouse model of depression, with involvement of oxidative stress, inflammatory response and apoptotic pathway.

Circulating monocyte-platelet aggregates with different monocyte subsets and their association with disease severity in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is usually considered an immune inflammatory disease. Interaction between platelets and monocytes is associated with immune inflammation. Cross-talk between platelets and monocytes is reflected by formation monocyte-platelet aggregates (MPAs). This study aims to test MPAs and MPAs with the different monocyte subsets to evaluate their association with disease severity in CKD. METHODS: Forty-four hospitalized patients with CKD and twenty healthy volunteers were enrolled. The proportion of MPAs and MPAs with the different monocyte subsets were tested by flow cytometry. RESULTS: The proportion of circulating MPAs in all patients with CKD were significantly higher than those of healthy controls (p<0.001). A higher proportion of MPAs with classical monocytes (CM) was found in CKD4-5 patients (p=0.007), while another higher proportion of MPAs with non-classical monocytes (NCM) was found CKD2-3 patients (p<0.001). The proportion of MPAs with intermediate monocytes (IM) in CKD 4-5 group was significantly higher in comparison to CKD2-3 group and healthy controls (p<0.001). Circulating MPAs were found to be correlated with serum creatinine (r=0.538, p<0.001) and eGFR (r=-0.864, p<0.001). The AUC for MPAs with IM was 0.942 (95% CI 0.890-0.994, p<0.001). CONCLUSIONS: Study results highlight the interplay between platelets and inflammatory monocytes in CKD. There are alterations in circulating MPAs and MPAs with the different monocyte subsets in CKD patients compared to controls which change with CKD severity. The MPAs may have an important role in the development of CKD or as a predictive marker for monitoring disease severity.

Fibroblast Growth Factor 2 Levels in Patients with Major Depressive Disorder: A Meta-analysis.

Fibroblast growth factor 2 (FGF2) plays an essential role in neurogenesis, oxidative stress, and emotional behavior. However, the evidence regarding the role of FGF2 in the pathophysiology of depression remains limited and inconclusive. We conducted a systematic review and meta-analysis to investigate peripheral blood FGF2 levels in patients with depression and healthy controls. The PubMed and Web of Science databases were used to identify relevant articles for systematic retrieval. Eight studies involving 310 patients with depression and 268 healthy controls were included in this meta-analysis. A random-effects meta-analysis showed no difference in peripheral blood fibroblast growth factor 2 (FGF2) levels between patients with depression and HC (Hedges' g = - 0.288, 95% CI = - 0.828 to 0.253, P = 0.297), but there was heterogeneity (Q = 55.719, df = 7, I2 = 87.437, P = 0.000). Subgroup analysis showed no statistically significant differences in the blood (serum/ plasma) and assay (ELISA/ no ELISA) FGF2 levels between all patients with depression and controls; however, there was heterogeneity. The meta-regression analysis showed that age, sex, sample size, depression severity, and publication year did not affect the results. Patients with different subtypes may have mild-to-severe symptoms or a different course of the disease, affecting neurotrophic factor levels. We could not obtain sufficient data from different studies to control for variables. Although the relationship between our findings and the pathophysiology of depression and the role of FGF2 in disease development remains to be determined, FGF2 may be a potential biomarker for depression.

Identification of Bletilla striata and related decoction pieces: a data fusion method combining electronic nose, electronic tongue, electronic eye, and high-performance liquid chromatography data.

Introduction: We here describe a new method for distinguishing authentic Bletilla striata from similar decoctions (namely, Gastrodia elata, Polygonatum odoratum, and Bletilla ochracea schltr). Methods: Preliminary identification and analysis of four types of decoction pieces were conducted following the Chinese Pharmacopoeia and local standards. Intelligent sensory data were then collected using an electronic nose, an electronic tongue, and an electronic eye, and chromatography data were obtained via high-performance liquid chromatography (HPLC). Partial least squares discriminant analysis (PLS-DA), support vector machines (SVM), and back propagation neural network (BP-NN) models were built using each set of single-source data for authenticity identification (binary classification of B. striata vs. other samples) and for species determination (multi-class sample identification). Features were extracted from all datasets using an unsupervised approach [principal component analysis (PCA)] and a supervised approach (PLS-DA). Mid-level data fusion was then used to combine features from the four datasets and the effects of feature extraction methods on model performance were compared. Results and Discussion: Gas chromatography-ion mobility spectrometry (GC-IMS) showed significant differences in the types and abundances of volatile organic compounds between the four sample types. In authenticity determination, the PLS-DA and SVM models based on fused latent variables (LVs) performed the best, with 100% accuracy in both the calibration and validation sets. In species identification, the PLS-DA model built with fused principal components (PCs) or fused LVs had the best performance, with 100% accuracy in the calibration set and just one misclassification in the validation set. In the PLS-DA and SVM authenticity identification models, fused LVs performed better than fused PCs. Model analysis was used to identify PCs that strongly contributed to accurate sample classification, and a PC factor loading matrix was used to assess the correlation between PCs and the original variables. This study serves as a reference for future efforts to accurately evaluate the quality of Chinese medicine decoction pieces, promoting medicinal formulation safety.

Copper-Catalyzed Difluoroalkylation Reaction.

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.

The peroxins BcPex8, BcPex10, and BcPex12 are required for the development and pathogenicity of Botrytis cinerea.

Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially, Botrytis cinerea. The homologs of Pex8, Pex10, and Pex12 in B. cinerea were functionally characterized in this work using gene disruption strategies. Compared with the wild-type strain (WT), the Δbcpex8, Δbcpex10, and Δbcpex12 mutants exhibited significant reduction in melanin production, fatty acid utilization, and decreased tolerance to high osmotic pressure and reactive oxygen species (ROS). The mycelial growth and conidiation of were significantly inhibited in Δbcpex8, Δbcpex10, and Δbcpex12 strains. The mycelial growth rates of Δbcpex8, Δbcpex10, and Δbcpex12 were reduced by 32, 35, and 34%, respectively, compared with WT and ectopic transformant (ET), and the conidiation was reduced by approximately 89, 27, and 88%, respectively. The conidial germination, germ tube elongation, and the formation of initiate infection structures (IFSs) were also reduced by the deletion of the genes. The pathogenicity was tested on the leaves of tobacco and strawberry, and fruits of tomato. On the leaves of tobacco and strawberry, the Δbcpex8, Δbcpex10, and Δbcpex12 mutants could not induce necrotic lesions, and the lesions on tomato fruits infected with the mutants were significantly reduced than those of the wide type. The results indicated that BcPEX8, BcPEX10, and BcPEX12 are indispensable for the development and pathogenicity of B. cinerea.

Sodium oligomannate combined with rivastigmine may improve cerebral blood flow and cognitive impairment following CAR-T cell therapy: A case report.

Chimeric antigen receptor-T (CAR-T) cell therapy is a breakthrough for B-cell hematological malignancies but is commonly associated with cytokine release syndrome and neurotoxicity and is occasionally complicated by neurological symptoms, such as cognitive disturbances. Currently, no effective treatments for CAR-T therapy-related cognitive impairment are available. Here, we present a 22-year-old patient with cognitive impairment who was treated with CAR-T cells as a salvage therapy for Burkitt lymphoma. One month after CAR-T cell infusion, he experienced memory loss that mainly manifested as forgetting recent-onset events. Two months of rehabilitation and hyperbaric oxygen therapy failed to provide clinical improvement. Subsequently, the patient improved with oral oxiracetam for 5 months. However, after 10 months of withdrawal, he showed significantly worse memory decline. Then, he began to take sodium oligomannate (22 February 2021). Follow-up testing at 6 and 12 months revealed maintenance of memory gains with sodium oligomannate alone or in combination with rivastigmine. Our case shows that CAR-T therapy may compromise cognitive function and that sodium oligomannate may have partial efficacy in restoring cognitive performance and activities of daily living. This may provide insights for further applications of sodium oligomannate for neurological symptoms, especially cognitive deficits following CAR-T cell therapy.

[Cell metabolomics study of ginkgo flavone aglycone combined with doxorubicin against liver cancer in synergy].

Ultra-high-performance liquid chromatography-Q exactive orbitrap tandem mass spectrometry(UHPLC-QEOrbitrap-MS/MS) was used to explore the inhibitory effect and mechanism of ginkgo flavone aglycone(GA) combined with doxorubicin(DOX) on H22 cells. The effects of different concentrations of GA and DOX on the viability of H22 cells were investigated, and combination index(CI) was used to evaluate the effects. In the experiments, control(CON) group, DOX group, GA group, and combined GA and DOX(GDOX) group were constructed. Then the metabolomics strategy was employed to explore the metabolic markers that were significantly changed after combination therapy on the basis of single medication treatment, and by analyzing their biological significance, the effect and mechanism of the anti-tumor effect of GA combined with DOX were explained. The results revealed that when 30 µg·mL~(-1) GA and 0.5 µmol·L~(-1) DOX was determined as the co-administration concentration, the CI value was 0.808, indicating that the combination of GA and DOX had a synergistic anti-tumor effect. Metabolomics analysis identified 23 metabolic markers, including L-arginine, L-tyrosine and L-valine, mostly amino acids. Compared with the CON group, 22 and 17 metabolic markers were significantly down-regulated after DOX treatment and GA treatment, respectively. Compared with the DOX and GA groups, the treatment of GA combined with DOX further down-regulated the levels of these metabolic markers in liver cancer, which might contribute to the synergistic effect of the two. Five key metabolic pathways were found in pathway enrichment analysis, including glutathione metabolism, phenylalanine metabolism, arginine and proline metabolism, ß-alanine metabolism, and valine, leucine and isoleucine degradation. These findings demonstrated that the combination of GA and DOX remarkably inhibited the viability of H22 cells and exerted a synergistic anti-tumor effect. The mechanism might be related to the influence of the energy supply of tumor cells by interfering with the metabolism of various amino acids.