Pan-transcriptomic analysis reveals alternative splicing control of cold tolerance in rice.

Plants have evolved complex mechanisms to adapt to harsh environmental conditions. Rice (Oryza sativa) is a staple food crop that is sensitive to low temperatures. However, its cold stress responses remain poorly understood, thus limiting possibilities for crop engineering to achieve greater cold tolerance. In this study, we constructed a rice pan-transcriptome and characterized its transcriptional regulatory landscape in response to cold stress. We performed Iso-Seq and RNA-Seq of 11 rice cultivars subjected to a time-course cold treatment. Our analyses revealed that alternative splicing-regulated gene expression plays a significant role in the cold stress response. Moreover, we identified CATALASE C (OsCATC) and Os03g0701200 as candidate genes for engineering enhanced cold tolerance. Importantly, we uncovered central roles for the 2 serine-arginine-rich proteins OsRS33 and OsRS2Z38 in cold tolerance. Our analysis of cold tolerance and resequencing data from a diverse collection of 165 rice cultivars suggested that OsRS2Z38 may be a key selection gene in japonica domestication for cold adaptation, associated with the adaptive evolution of rice. This study systematically investigated the distribution, dynamic changes, and regulatory mechanisms of alternative splicing in rice under cold stress. Overall, our work generates a rich resource with broad implications for understanding the genetic basis of cold response mechanisms in plants.

Gastrointestinal Characteristics of Constipation from the Perspectives of Microbiome and Metabolome.

BACKGROUND: Constipation is one of the most common gastrointestinal complaints. Yet, the underlying mechanisms of constipation remain to be explored deeply. Integration of microbiome and metabolome is powerful and promising to demonstrate characteristics of constipation. AIM OF STUDY: This study aimed to characterize intestinal microbiome and metabolome of constipation. In addition, this study revealed the correlations among behaviors, intestinal microbiota, and metabolites interrupted by constipation. METHODS: Firstly, the constipation model was successfully applied. At the macro level, the ability of learning, memory, locomotor activity, and the defecation index of rats with constipation-like phenotype were characterized. At the micro-level, 16S rRNA sequencing was applied to analyze the intestinal microbiota in rats with constipation-like phenotype. 1H nuclear magnetic resonance (NMR)-based metabolomics was employed to investigate the metabolic phenotype of constipation. In addition, we constructed a correlation network, intuitively showing the correlations among behaviors, intestinal microbiota, and metabolites. RESULTS: Constipation significantly attenuated the locomotor activity, memory recognition, and frequency of defecation of rats, while increased the time of defecation. Constipation significantly changed the diversity of intestinal microbial communities, which correspondingly involved in 5 functional pathways. Besides, 28 fecal metabolites were found to be associated with constipation, among which 14 metabolites were further screened that can be used to diagnose constipation. On top of this, associated networks intuitively showed the correlations among behaviors, intestinal microbiota, and metabolites. CONCLUSIONS: The current findings are significant in terms of not only laying a foundation for understanding characteristics of constipation, but also providing accurate diagnosis and treatments of constipation clinically.

Systematic evaluation and meta-analysis of the effects of major dietary patterns on cognitive function in healthy adults.

PURPOSE: Evidence shows diet promotes brain health. Combining foods and nutrients may have beneficial synergistic effects, but the effects on cognitive function interventions are inconsistent. So, a meta-analysis of RCTs was conducted to examine the specific effects on cognitive function. METHODS: We searched four databases from creation to April 2023. Eligible randomized controlled trials were identified. A random-effects meta-analysis was used to combine standardized mean differences (SMD) (95% confidence intervals [CI]), and homogeneity tests for a variance were calculated. RESULTS: A total of 19 studies involving 12,119 participants were included in this systematic review. The dietary intervention group had a positive effect on overall cognitive functioning compared to the control group (SMD = 0.14, 95% CI [0.08, 0.20], P < 0.00001). The dietary intervention improved executive function, processing speed and language skills (SMD = -0.10, 95% CI [-0.17,-0.04], P = 0.002, I2 = 0%), (SMD = -0.16, 95% CI [-0.23,-0.09], P < 0.00001, I2 = 0%), (SMD = 0.10, 95% CI [0.01, 0.20], P = 0.03, I2 = 0%). The dietary intervention had no effect on delayed memory and spatial ability (SMD = 0.04, 95% CI [-0.02, 0.09], P = 0.20, I2 = 0%), (SMD = 0.08, 95% CI [-0.01, 0.16], P = 0.08, I2 = 0%). CONCLUSION: The Mediterranean diet, a diet with restricted caloric intake, a diet incorporating aerobic exercise, a low-carbohydrate diet, and a healthy lifestyle diet (increased intake of fruits and vegetables, and weight and blood pressure management) appear to have positive effects on cognitively healthy adults, as reflected in their overall cognitive, processing speed, executive, and language functions. PROSPERO REGISTRATION NUMBER: CRD42023414704.

Study on the antidepressive effects and mechanism of raw and fried Ziziphi Spinosae Semen via metabolomics and gut microbiota analysis.

Ziziphi Spinosae Semen (ZSS) and fried ZSS (FZSS) have been used for treating insomnia and depression in China. However, the potential influence of chemical variations on their efficacy remains unclear. This study demonstrated that compared with ZSS, FZSS exhibited an increase in the content of seven compounds, while the fatty oil content decreased. Both ZSS and FZSS exhibited antidepressive effects in a chronic unpredictable mild stress rat model, indicating a synergistic regulation of deficiencies in 5-hydroxytryptamine in the brain and the hyperactivation of severe peripheral inflammation. ZSS demonstrated a superior modulatory effect compared with FZSS, as indicated by integrated pharmacodynamic index, metabolic profile, and relative distance value. The potential mechanism underlying their antidepressive effects involved the modulation of gut microbiota structure to alleviate excessive inflammatory responses and imbalanced tryptophan metabolism. Correlation analysis indicated that the higher fatty oil contents should be comprehensively considered as the main reason for ZSS's superior antidepressive effects, achieved through the regulation of pyroglutamic acid levels.

Structural Characterization and Screening for Anti-inflammatory Activity of Polysaccharides with Different Molecular Weights from Astragali Radix.

Astragali Radix polysaccharides (APSs) exhibit a broad spectrum of biological activity, which is mainly related to immune regulation. At present, most available studies focus on total APSs or a certain component of APSs. However, systematic structural study and screening for the anti-inflammatory activity of polysaccharides with different molecular weights (MW) have yet to be conducted. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of APSs and its fractions. The results revealed that fraction APS-I had better anti-inflammatory effects than APS-II. After APS-I was hydrolyzed by trifluoroacetic acid (TFA), the resulting degradation products oligosaccharides were fully methylated. These derivatized oligosaccharides were further analyzed by MALDI-TOF-MS and UPLC-Q-Exactive-MS/MS. The results showed that APS-I was a hetero-polysaccharide with a molecular weight of about 2.0×106 Da, mainly consisting of glucose (46.8 %) and galactose (34.4 %). The degree of polymerization of Astragali Radix oligosaccharides (APOS) was 2-16. APOS were identified as 1,4-glucooligosaccharides and 1,4-galactooligosaccharides. The findings of this study lay the foundation for further elucidation of structure-function relationships of APSs and provide guidance for the development of anti-inflammatory drugs.

Stable Isotope Tracer Technique and Network Pharmacology to Reveal Antidepressant Targets and Active Components of Xiaoyao San.

In recent years, the research of mitochondrial dysfunction in depression has drawn the focus of researchers. Our research group previously found that Xiaoyao San (XYS) has improved the mitochondrial structure and the blocked tricarboxylic acid cycle (TCA cycle) in the hippocampal tissue of chronic unpredictable mild stress (CUMS) rats. However, the specific targets and active components of XYS remain unclear, and the potential to improve hippocampal mitochondrial TCA cycle disorder was also unexplored. In this research, a strategy to combine stable isotope-resolved metabolomics (SIRM), network pharmacology and transmission electron microscopy (TEM) was used to explore the potential, targets of action, and active components of XYS to improve hippocampal mitochondrial TCA cycle disorder of CUMS rats. The results of TEM showed that the ultrastructure of hippocampal mitochondria could be improved by XYS. A combination of SIRM and molecular docking showed that pyruvate carboxylase (PC), ATP citrate lyase (ACLK), glutamate dehydrogenase (GLDH), glutamate oxaloacetate transaminase (GOT) and pyruvate dehydrogenase (PDH) were targets of XYS to improve TCA cycle disorder. In addition, troxerutin was found to be the most potential active component of XYS to improve TCA cycle disorder. The above research results can provide new insights for the development of antidepressant drugs.

CXCL14 as a Key Regulator of Neuronal Development: Insights from Its Receptor and Multi-Omics Analysis.

CXCL14 is not only involved in the immune process but is also closely related to neurodevelopment according to its molecular evolution. However, what role it plays in neurodevelopment remains unclear. In the present research, we found that, by crossbreeding CXCL14+/- and CXCL14-/- mice, the number of CXCL14-/- mice in their offspring was lower than the Mendelian frequency; CXCL14-/- mice had significantly fewer neurons in the external pyramidal layer of cortex than CXCL14+/- mice; and CXCL14 may be involved in synaptic plasticity, neuron projection, and chemical synaptic transmission based on analysis of human clinical transcriptome data. The expression of CXCL14 was highest at day 14.5 in the embryonic phase and after birth in the mRNA and protein levels. Therefore, we hypothesized that CXCL14 promotes the development of neurons in the somatic layer of the pyramidal cells of mice cortex on embryonic day 14.5. In order to further explore its mechanism, CXCR4 and CXCR7 were suggested as receptors by Membrane-Anchored Ligand and Receptor Yeast Two-Hybrid technology. Through metabolomic techniques, we inferred that CXCL14 promotes the development of neurons by regulating fatty acid anabolism and glycerophospholipid anabolism.

Cuproptosis-related LncRNA signatures as a prognostic model for head and neck squamous cell carcinoma.

Cuproptosis is a novel, distinct form of regulated cell death. However, little is known about the role of cuproptosis-related lncRNAs (CRlncRNAs) in head and neck squamous cell carcinoma (HNSCC). This study aimed to identify a CRlncRNAs signature, explore its prognostic value in HNSCC. RNA-seq data and relevant clinical data were downloaded from The Cancer Genome Atlas (TCGA) database, and cuproptosis-related genes were identified from a search of the relevant candidate-gene literature. Analysis of differentially expressed lncRNAs (DElncRNAs) was performed using the R package "edgeR". The intersection of the lncRNAs between DElncRNAs and CRlncRNAs was obtained using the R package "Venn Diagram". Univariate Cox regression was used to identify cuproptosis-related prognostic lncRNAs. LASSO-Cox method was used to narrow these cuproptosis-related prognostic lncRNAs and construct a prognostic model. Multiple statistical methods were used to evaluate the predictive ability of the model. Moreover, the relationships between the model and immune cell subpopulations, related functions and pathways and drug sensitivity were explored. Then, two risk groups were established according to the risk score calculated by the CRlncRNAs signature included three lncRNAs. In HNSCC patients, the risk score was a better predictor of survival than traditional clinicopathological features. In addition, significant differences in immune cells such as B cells, T cells and macrophages were observed between the two groups. Finally, the high-risk group had a lower IC50 for certain chemotherapeutic agents, such as cisplatin and cetuximab. This 3 CRlncRNAs signature is a powerful prognostic biomarker for predicting clinical outcomes and therapeutic responses in HNSCC patients.

Baicalein Attenuates Neuroinflammation in LPS-Treated BV-2 Cells by Inhibiting Glycolysis via STAT3/c-Myc Pathway.

More and more evidence shows that metabolic reprogramming is closely related to the occurrence of AD. The metabolic conversion of oxidative phosphorylation into glycolysis will aggravate microglia-mediated inflammation. It has been demonstrated that baicalein could inhibit neuroinflammation in LPS-treated BV-2 microglial cells, but whether the anti-neuroinflammatory mechanisms of baicalein were related to glycolysis is unclear. Our results depicted that baicalein significantly inhibited the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin 2 (PGE2) and tumor necrosis factor (TNF-α) in LPS-treated BV-2 cells. 1H-NMR metabolomics analysis showed that baicalein decreased the levels of lactic acid and pyruvate, and significantly regulated glycolytic pathway. Further study revealed that baicalein significantly inhibited the activities of glycolysis-related enzymes including hexokinase (HK), 6-phosphate kinase (6-PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and inhibited STAT3 phosphorylation and c-Myc expression. By using of STAT3 activator RO8191, we found that baicalein suppressed the increase of STAT3 phosphorylation and c-Myc expression triggered by RO8191, and inhibited the increased levels of 6-PFK, PK and LDH caused by RO8191. In conclusion, these results suggested that baicalein attenuated the neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through STAT3/c-Myc pathway.

Design, synthesis and biological evaluation of novel 3,4-dihydro-2H-[1,4]oxazino [2,3-f]quinazolin derivatives as EGFR-TKIs.

Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFRwt kinase (IC50 ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFRwt tyrosine kinase with IC50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC50) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents.

Prevalence and risk factors of anxious and depressive symptoms in first-trimester females and their partners: a study during the pandemic era of COVID-19 in China.

BACKGROUND: The pandemic of coronavirus disease 2019 lastingly affects public mental health. Many studies have described symptoms of anxiety and depression in pregnant women before the pandemic. However, the limited study focuses on the prevalence and risk factors of mood symptoms among first-trimester females and their partners during the pandemic in China, which was the aim of the study. METHODS: One hundred and sixty-nine first-trimester couples were enrolled. The Edinburgh Postnatal Depression Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item, Family Assessment Device-General Functioning (FAD-GF), and Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF) were applied. Data were mainly analyzed through logistic regression analysis. RESULTS: 17.75% and 5.92% of first-trimester females had depressive and anxious symptoms, respectively. Among partners, 11.83% and 9.47% had depressive and anxious symptoms, respectively. In females, higher scores of FAD-GF (OR = 5.46 and 13.09; P < 0.05) and lower scores of Q-LES-Q-SF (OR = 0.83 and 0.70; P < 0.01) were related to the risk of depressive and anxious symptoms. Higher scores of FAD-GF were associated with the risk of depressive and anxious symptoms in partners (OR = 3.95 and 6.89; P < 0.05). A history of smoking was also related to males' depressive symptoms (OR = 4.49; P < 0.05). CONCLUSION: This study prompted prominent mood symptoms during the pandemic. Family functioning, quality of life, and smoking history increased risks of mood symptoms among early pregnant families, which facilitated the updating of medical intervention. However, the current study did not explore interventions based on these findings.

Quality assessment of Astragali Radix based on pseudo-targeted metabolomics and chemometric approach.

Astragali Radix is widely used because of its dual use in medicine and food, and its quality evaluation is of great importance. In this study, a pseudo-targeted metabolomics approach based on scheduled multiple reaction monitoring was developed, and a total of 114 compounds with good linearity, sensitivity, and reproducibility were selected for relative quantification, and the chemical differences between Astragali Radix of different growth patterns were further compared by chemometric analysis. With the help of multivariate and univariate analysis, 26 differential compounds between wild/semi-wild Astragali Radix and cultivated Astragali Radix were determined. Then five marker compounds were screened out by lasso regression, and further verified by systematic clustering, random forest, support vector machine, and logistic regression. In addition, malonyl-substituted flavonoids showed relatively higher content in wild/semi-wild Astragali Radix. Thus, the malonyl substitution was characteristic for flavonoids in wild/semi-wild Astragali Radix. In conclusion, the application of pseudo-targeted metabolomics and various statistical methods could offer multi-dimensional information for the holistic quality evaluation of Astragali Radix.

Combining network pharmacology and experimental verification to reveal the mechanism of Chaigui granules in the treatment of depression through PI3K/Akt/mTOR signaling pathways.

INTRODUCTION: Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study. METHODS: Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus. RESULTS: The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3ß and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3ß and FoxO3a were upregulated. CONCLUSIONS: Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.

Rapid chemical characterization of Danggui Buxue decoction using processed Astragali Radix and Angelicae Sinensis Radix based on diagnostic ion and molecular network.

Danggui Buxue decoction (DBD), a classic prescription of traditional Chinese medicine (TCM) for invigorating qi and generating blood, contains honey-processed Astragali Radix (HAR) and wine-processed Angelicae Sinensis Radix (WDG) in its original prescription. In this study, the compositions of DBD, WDG, and HAR were characterized using ultra-high-performance liquid chromatography coupled with the quadrupole-time-of-flight tandem mass spectrometry technique in combination with molecular network and diagnostic ion strategies. Finally, 200 compounds were identified in DBD, 114 compounds were identified in WDG, and 180 compounds were identified in HAR; there were 48 common compounds in total. The results demonstrated that compatibility led to changes in the chemical composition of TCM, and the qualitative method used in this study provided an effective data processing strategy for the characterization of components and the database for the study of the compounding mechanism of TCM.

A strategy to explore the quality markers of Ziziphi Spinosae semen by combining metabolic in vivo study with network pharmacology.

Ziziphi Spinosae semen (ZSS), the dried and ripe seed of Ziziphus jujube Mill. var. spinosa (Bunge) Hu ex H. F. Chou, has been used as a sedative in China and other Asian countries for over a millennium. However, its quality markers (Q-markers) are not completely clear. In this study, Q-markers selected by a metabolic in vivo study combined with network pharmacology are proposed for ZSS quality control. An UHPLC (ultra-high-performance liquid chromatography)-Q-Orbitrap-MS method was developed to identify or tentatively assign 48 components including 21 flavonoid C-glycosides, 2 flavonoid O-glycosides, 11 dammarane triterpenoid saponins, 13 alkaloids, and 1 other, using a diagnostic product ion filtering strategy in ZSS. Subsequently, 147 metabolites detected from serum, urine, bile, and feces samples of para-chlorophenylalanine-induced insomnia rats treated with ZSS aqueous extracts could be linked to their respective parent compounds, including 27 prototypes. Meanwhile, three metabolic networks of flavonoids, saponins, and alkaloids are preliminarily established and potential metabolic pathways are investigated under the insomnia condition. Finally, 12 key bioactive components against insomnia including magnoflorine, caaverine, coclaurine, norisocorydine, genkwanin, juzinrine, apigenin, jujubogenin, kaempferol-3-O-rutinoside, jujuboside A, jujuboside B, and spinosin with the highest degree values in component-target-pathways network were selected as Q-markers for the quality control of ZSS.

Saikosaponins regulate bile acid excretion in mice liver and ileum by activating farnesoid X receptor and bile acid transporter.

Radix Bupleuri exerts effective hepatoprotective and cholagogic effects through its Saikosaponins (SSs) component. Therefore, we attempted to determine the mechanism of saikosaponins used to promote bile excretion by studying their effects on intrahepatic bile flow, focusing on the synthesis, transport, excretion, and metabolism of bile acids. C57BL/6N mice were continuously gavaged with saikosaponin a (SSa), saikosaponin b2 (SSb2 ), or saikosaponin D (SSd) (200 mg/kg) for 14 days. Liver and serum biochemical indices were determined using Enzyme-linked immunosorbent assay (ELISA) kits. In addition, an ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) was used to measure the levels of the 16 bile acids in the liver, gallbladder, and cecal contents. Furthermore, SSs pharmacokinetics and docking between SSs and farnesoid X receptor (FXR)-related proteins were analyzed to investigate the underlying molecular mechanisms. Administration of SSs and Radix Bupleuri alcohol extract (ESS) did not cause significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) levels. Saikosaponin-regulated changes in bile acid (BA) levels in the liver, gallbladder, and cecum were closely related to genes involved in BA synthesis, transport, and excretion in the liver. Pharmacokinetic studies indicated that SSs were characterized by rapid elimination (t1/2 as 0.68-2.47 h), absorption (Tmax as 0.47-0.78 h), and double peaks in the drug-time curves of SSa and SSb2 . A molecular docking study revealed that SSa, SSb2 , and SSd docked well with the 16 protein FXR molecules and target genes (<-5.2 kcal/mol). Collectively, saikosaponins may maintain BA homeostasis in mice by regulating FXR-related genes and transporters in the liver and intestine.

A Route for Investigating Psoriasis: From the Perspective of the Pathological Mechanisms and Therapeutic Strategies of Cancer.

Psoriasis is an incurable skin disease that develops in about two-thirds of patients before the age of 40 and requires lifelong treatment; its pathological mechanisms have not been fully elucidated. The core pathological process of psoriasis is epidermal thickening caused by the excessive proliferation of epidermal keratinocytes, which is similar to the key feature of cancer; the malignant proliferation of cancer cells causes tumor enlargement, suggesting that there is a certain degree of commonality between psoriasis and cancer. This article reviews the pathological mechanisms that are common to psoriasis and cancer, including the interaction between cell proliferation and an abnormal immune microenvironment, metabolic reprogramming, and epigenetic reprogramming. In addition, there are common therapeutic agents and drug targets between psoriasis and cancer. Thus, psoriasis and cancer share a common pathological mechanisms-drug targets-therapeutic agents framework. On this basis, it is proposed that investigating psoriasis from a cancer perspective is beneficial to enriching the research strategies related to psoriasis.

Correction: Gong et al. Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix. Molecules 2016, 21, 549.

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Microbiome and metabolome reveal the metabolic and microbial variations induced by depression and constipation.

BACKGROUND: Depressed patients are often accompanied with constipation symptoms, and vice versa. However, the underlying mechanisms of such a bidirectional correlation have remained elusive. We aim to reveal the possible correlations between depression and constipation from the perspectives of gut microbiome and plasma metabolome. METHODS: We constructed the depressed model and the constipated model of rats, respectively. First, we measured the locomotor activity status and the gastrointestinal functions of rats. And then, nuclear magnetic resonance plasma metabolomics was applied to reveal the shared and the unique metabolites of depression and constipation. In addition, 16 S ribosomal RNA gene sequencing was used to detect the impacts of constipation and depression on gut microbiota of rats. Finally, a multiscale and multifactorial network, that is, the 'phenotypes - differential metabolites - microbial biomarkers' integrated network, was constructed to visualise the mechanisms of connections between depression and constipation. RESULTS: We found that spontaneous locomotor activity and gastrointestinal functions of both depressed rats and constipated rats significantly decreased. Further, eight metabolites and 14 metabolites were associated depression and constipation, respectively. Among them, seven metabolites and four metabolic pathways were shared by constipation and depression, mainly perturbing energy metabolism and amino acid metabolism. Additionally, depression and constipation significantly disordered the functions and the compositions of gut microbiota of rats, and decreased the ratio of Firmicutes to Bacteroidetes. CONCLUSION: The current findings provide multiscale and multifactorial perspectives for understanding the correlations between depression and constipation, and demonstrate new mechanisms of comorbidity of depression and constipation.

Synthesis of Silver Nanoparticles from the Polysaccharide of Farfarae Flos and Uncovering Its Anticancer Mechanism Based on the Cell Metabolomic Approach.

In this study, the polysaccharide of Farfarae Flos (FFP) was utilized as a reducing agent to the green synthesis of FFP@AgNPs, and the anticancer activity was evaluated using the HT29 cells. The results showed that the FFP@AgNPs could significantly decrease proliferation ability, inhibit migration, and promote cell apoptosis of HT29 cells, which suggested that the FFP@AgNPs showed significant, strong cytotoxicity against HT29 cells. The cell metabolomic analysis coupled with the heatmap showed an obvious metabolome difference for the cells with and without FFP@AgNPs treatment, which was related to 51 differential metabolites. Four metabolic pathways were determined as the key pathways, and the representative functional metabolites and metabolic pathways were validated in vitro. Nicotinic acid (NA) was revealed as the key metabolite relating with the effect of FFP@AgNPs, and it was interesting that NA supplementation could inhibit the proliferation ability of HT29 cells in vitro, lead to mitochondrial dysfunction, reduce intracellular ATP, and damage the integrity of the cell membrane, which exhibited a similar effect as FFP@AgNPs. In conclusion, this study not only revealed the anticancer mechanism of FFP@AgNPs against the HT29 cells but also provided the important reference that NA shows a potential role in the development of a therapy for colorectal cancer.