Involucrasin B Inhibits the Proliferation of Caco-2 Cells by Regulating the TGFß/SMAD2-3-4 Pathway.

(1) Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the second most common cause of cancer death. However, effective anti-CRC drugs are still lacking in clinical settings. This article investigated the anti-proliferative effect of involucrasin B on CRC Caco-2 cells. (2) Methods: This study employed a sulforhodamine B (SRB) method, colony formation experiments, flow cytometry, FastFUCCI assay, dual luciferase assay, and Western blot analysis for the investigation. (3) Results: The SRB method and colony formation experiments showed that involucrasin B exhibited an inhibitory effect on the Caco-2 cells cultured in vitro. Subsequently, the flow cytometry, FastFUCCI assay, and Western blotting results showed that involucrasin B induced cell cycle arrest in the G1 phase dose-dependently. Involucrasin B significantly enhanced the TGFß RII protein level and SMAD3 phosphorylation, thus inhibiting the expression of CDK4 and cyclin D1 and causing G1 cell cycle arrest. (4) Conclusion: This study shows that involucrasin B exerts its anti-proliferative effect by regulating the TGFß/SMAD2-3-4 pathway to cause G1 cycle arrest in Caco-2 cells.

Progress of research on aroma absorption mechanism and aroma fixation pathway of jasmine green tea.

This overview summarizes the latest research progress on the aroma absorption mechanism and aroma fixation pathway of jasmine green tea, and discusses in depth the aroma absorption mechanism of green tea, the aroma release mechanism of jasmine flowers, as well as the absorption and fixation mechanism of the aroma components of jasmine green tea in the process of scenting, to provide a theoretical basis for the improvement of the quality of jasmine green tea and the innovation of processing technology. It was found that the aroma absorption mechanism of jasmine green tea is mainly associated with both physical and chemical adsorption, aroma release in jasmine involves the phenylpropanoid/benzoin biosynthetic pathway, ß-glycosidase enzymes interpreting putative glycosidic groups, and heat shock proteins (HSPs) as molecular chaperones to prevent stress damage in postharvest flowers due to high temperatures and to promote the release of aroma components, and so forth. The preparation of aroma-protein nano-complexes, heat stress microcapsules, and the spraying of polymeric substances - ß-cyclodextrin are three examples of aroma-fixing pathways. This overview also summarizes the problems and future development trends of the current research and proposes the method of loading benzyl acetate, the main aroma component of jasmine, through konjac glucomannan (KGM)-based gel to solve the problem of volatile aroma and difficult-to-fix aroma, which provides a reference for the sustainable development of the jasmine green tea industry. © 2024 Society of Chemical Industry.

Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease.

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.

Super-enhancer-driven Sorting Nexin 5 expression promotes dopaminergic neuronal ferroptosis in Parkinson's disease models.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide. Recent studies revealed that the ferroptosis pathway is involved in the death process of dopaminergic neurons in PD. The aberrant endosomal sorting pathway, which results in aberrant iron level in eukaryotic cells, may serve a role in the ferroptosis pathway in PD condition. However, its specific molecular mechanisms remained unclear. In the present study, we performed chromatin immunoprecipitation (ChIP) assay, the rank ordering of super-enhancers (ROSE) algorithm, and RNA interference (RNAi) to explore the regulatory mechanism of PD-specific super-enhancer (SE) in the endosomal sorting pathway and ferroptosis pathway of 6-OHDA-lesioned rats and cells. The ChIP assay and ROSE algorithm results showed that there are specific SEs expression in 6-OHDA-lesioned SNc of PD rats, and the most significant expression gene is Sorting Nexin 5 (SNX5). SNX5 silencing by RNAi experiments significantly decreased the level of ferroptosis in 6-OHDA-lesioned PC12 cells, suggesting the correlation between the SNX5, ferroptosis, and PD. In conclusion, this study investigated the mechanism by which PD-specific SE driven SNX5 promoted the ferroptosis level in PD models. This study further improved the understanding of the mechanism of ferroptosis during PD injury and provided potential therapeutic targets and clinical diagnostic markers in PD condition.

Cystatin C is a potential predictor of unfavorable outcomes for cerebral ischemia with intravenous tissue plasminogen activator treatment: A multicenter prospective nested case-control study.

BACKGROUND AND PURPOSE: The aim of this study was to explore whether cystatin C (CysC) could be used as a potential predictor of clinical outcomes in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA). METHODS: We performed an observational study including a retrospective analysis of data from 125 AIS patients with intravenous thrombolysis. General linear models were applied to compare CysC levels between groups with different outcomes; logistic regression analysis and receiver-operating characteristic curves were adopted to identify the association between CysC and the therapeutic effects. RESULTS: Compared with the "good and sustained benefit" (GSB) outcome group (defined as ≥4-point reduction in National Institutes of Health Stroke Scale or a score of 0-1 at 24 h and 7 days) and the "good functional outcome" (GFO) group (modified Rankin Scale score 0-2 at 90 days), serum CysC baseline levels were increased in the non-GSB and non-GFO groups. Logistic regression analysis found that CysC was an independent negative prognostic factor for GSB (odds ratio [OR] 0.010; p = 0.005) and GFO (OR 0.011; p = 0.021) after adjustment for potential influencing factors. Receiver-operating characteristic curves showed the CysC-involved combined models provided credible efficacy for predicting post-90-day favorable clinical outcome (area under the curve 0.86; p < 0.001). CONCLUSIONS: Elevated serum CysC is independently associated with unfavorable clinical outcomes after IV-tPA therapy in AIS. Our findings provide new insights into discovering potential mediators for neuropathological process or treatment in stroke.

Compound and heterozygous mutations of DSG2 identified by Whole Exome Sequencing in arrhythmogenic right ventricular cardiomyopathy/dysplasia with ventricular tachycardia.

BACKGROUNDS: This study was designed to identify the pathogenic mutations in two Chinese families of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) using the Whole Exome Sequencing (WES). METHODS AND RESULTS: The proband 1 (Family 1, II:1) and proband 2 (Family 2, II:1) underwent the WES of DNA from peripheral blood. The genes susceptible to arrhythmias and cardiomyopathies were analyzed and both the probands carried the same exonic mutation of DSG2 p.F531C (NM_001943, exon 11: c.T1592G). The proband 1 also carried the splicing mutation of DSG2 (NM_001943: exon 4:c.217-1G>T), and proband 2 carried the intronic mutation of DSG2 (NM_001943: exon 6: c.524-3C>G) that potentially influenced the splicing function predicted by Human Splicing Finder. The compound heterozygous mutations of the two probands inherited from their paternal and maternal side, respectively. The carriers with DSG2 p.F531C showed early abnormal electrocardiograms, characterized as the subclinical phenotype of ARVC/D. CONCLUSIONS: The DSG2 p.F531C was the main reason for ARVC/D. More severe phenotypes of ARVC/D occurred when coexisting with 217-1G>T or 524-3C>G mutation that potentially affecting the splicing function, as a compound heterozygous recessive inheritance.

Whole exome sequencing identified a pathogenic mutation in RYR2 in a Chinese family with unexplained sudden death.

OBJECTIVE: This study aimed to identify the pathogenic mutation in a Chinese family with unexplained sudden death (USD) or occasional syncope. MATERIALS AND METHODS: Whole exome sequencing and target capture sequencing were respectively conducted for two related patients. The genetic data was screened using the 1000 genomes project and SNP database (PubMed), and the identified mutations were assessed for predicted pathogenicity using the SIFT and Polyphen-2 algorithms. RESULTS: We identified a heterozygous mutation in the RYR2 gene at c.490C>T (p.P164S), highly conserved across all species, in three family members of USD, syncope and malignant ventricular tachycardias induced by treadmill exercise test, while another heterozygous de novo mutation in SCN5A at c.5576G>A p.R1859H was detected in one family member. Both variants were verified by Sanger sequencing. Importantly, RYR2 p.P164S is associated with the risk of sudden cardiac death, such as in catecholaminergic polymorphic ventricular tachycardia. CONCLUSIONS: A pathogenic mutation in RYR2 (p.P164S) is the likely cause of USD in a Chinese family associated with malignant ventricular arrhythmias. Whole exome and target capture sequencing can be useful for discovering the genetic causes of USD.

Some new traveling wave exact solutions of the (2+1)-dimensional Boiti-Leon-Pempinelli equations.

We employ the complex method to obtain all meromorphic exact solutions of complex (2+1)-dimensional Boiti-Leon-Pempinelli equations (BLP system of equations). The idea introduced in this paper can be applied to other nonlinear evolution equations. Our results show that all rational and simply periodic traveling wave exact solutions of the equations (BLP) are solitary wave solutions, the complex method is simpler than other methods, and there exist some rational solutions ur,2 (z) and simply periodic solutions us,2-6(z) which are not only new but also not degenerated successively by the elliptic function solutions. We believe that this method should play an important role for finding exact solutions in the mathematical physics. For these new traveling wave solutions, we give some computer simulations to illustrate our main results.

Selective ensemble method for anomaly detection based on parallel learning.

Anomaly detection is a highly important task in the field of data analysis. Traditional anomaly detection approaches often strongly depend on data size, structure and features, while introducing the idea of ensemble into anomaly detection can greatly improve the generalization ability. Ensemble-based anomaly detection methods still face some challenges, however, such as data imbalance, time and space demand and the selection of base detectors. To this end, we propose a selective ensemble method for anomaly detection based on parallel learning (SEAD-PL). First, a differentiated stratified sampling method is designed to alleviate the problem of data imbalance. Then, a distributed parallel training frame is built to address the problem of excessive time and space consumption for base detector training. Finally, a clustering-based ensemble selection strategy is introduced to balance the accuracy and diversity of base detectors. Experiments are performed on six datasets, which demonstrate that the proposed method has obvious advantages over four selected methods.

Four sulfur-containing compounds with anti-colon cancer effect from marine-derived fungus Aspergillus terreus.

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.

Atractylodes lancea volatile oils target ADAR2-miR-181a-5p signaling to mesenchymal stem cell chondrogenic differentiation.

Atractylodeslancea Rhizoma (Rhizoma atractylodis [RA]) has long been recommended for the treatment of arthritis in traditional Chinese medicine, but its mechanism of action is still unclear. RA contains a large amount of Atractylodes lancea volatile oils (Atr). In this study, we investigated whether Atr can promote mesenchymal stem cells (MSCs) chondrogenic differentiation. The Atr were extracted from RA by steam distillation method, and the effect of Atr on MSCs was detected by the CCK8 assay. The optimal concentration of Atr for MSCs cultivation was 3 µg/ml. The differentially expressed miR-181a-5p was screened by miRNA microarray assay, and its mimics and inhibitors were transfected into MSCs. It was found that the inhibitor of miR-181a-5p could upregulate cartilage-specific genes such as SOX9, COL2A1, and ACAN. Meanwhile, we also found that the expression of gene editing enzyme ADAR2 was significantly increased in the chondrogenic differentiation of MSCs induced by Atr, and the bases of precursor sequence of miR-181a-5p were changed from A to G. After ADAR2 deletion, the expression of cartilage-specific genes was significantly down-regulated and the precursor sequence bases of miR-181a-5p were not changed. Bioinformatics analysis revealed that the predicted target gene of miR-181a-5p was yingyang1 (YY1), and the targeting relationship was verified by dual-luciferase reporter assay. After deleting YY1, the expression of cartilage-specific genes was significantly down-regulated. In conclusion, our study demonstrated that Atr can promote chondrogenic differentiation of MSC through regulation of the ADAR2-miR-181a-5p signaling pathway. This may provide a new insight into the possible mechanism of traditional Chinese medicine (Atr) in treating inflammatory joint diseases.

Mendelian randomization reveals association between retinal thickness and non-motor symptoms of Parkinson's disease.

Retinal thickness is related to Parkinson's disease (PD), but its association with the severity of PD is still unclear. We conducted a Mendelian randomized (MR) study to explore the association between retinal thickness and PD. For the two-sample MR analysis, the summary statistics obtained from genome-wide association studies on the thickness of Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) were employed as exposure, while the summary statistics associated with PD were used as the outcome. The primary approach utilized was inverse variance weighted. To correct for multiple testing, the false discovery rate (FDR) was employed. For sensitivity analysis, an array of robust MR methods was utilized. We found genetically predicted significant association between reduced RNFL thickness and a reduced risk of constipation in PD (odds ratio [OR] = 0.854, 95% confidence interval [CI] (0.782, 0.933), P < 0.001, FDR-corrected P = 0.018). Genetically predicted reduced RNFL thickness was associated with a reduced Unified Parkinson's Disease Rating Scale total score (ß = -0.042, 95% CI (-0.079, 0.005), P = 0.025), and reduced GCIPL thickness was associated with a lower risk of constipation (OR = 0.901, 95% CI (0.821, 0.988), P = 0.027) but a higher risk of depression (OR = 1.103, 95% CI (1.016, 1.198), P = 0.020), insomnia (OR = 1.090, 95% CI (1.013, 1.172), P = 0.021), and rapid eye movement sleep behaviour disorder (RBD) (OR = 1.198, 95% CI (1.061, 1.352), P = 0.003). In conclusion, we identify an association between retinal thickness and non-motor symptoms (constipation, depression, insomnia and RBD) in PD, highlighting the potential of retinal thickness as a biomarker for PD nonmotor symptoms.

QEEG Signatures are Associated with Nonmotor Dysfunctions in Parkinson's Disease and Atypical Parkinsonism: An Integrative Analysis.

Parkinson's disease (PD) and atypical parkinsonism (AP), including progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), share similar nonmotor symptoms. Quantitative electroencephalography (QEEG) can be used to examine the nonmotor symptoms. This study aimed to characterize the patterns of QEEG and functional connectivity (FC) that differentiate PD from PSP or MSA, and explore the correlation between the differential QEEG indices and nonmotor dysfunctions in PD and AP. We enrolled 52 patients with PD, 31 with MSA, 22 with PSP, and 50 age-matched health controls to compare QEEG indices among specific brain regions. One-way analysis of variance was applied to assess QEEG indices between groups; Spearman's correlations were used to examine the relationship between QEEG indices and nonmotor symptoms scale (NMSS) and mini-mental state examination (MMSE). FCs using weighted phase lag index were compared between patients with PD and those with MSA/PSP. Patients with PSP revealed higher scores on the NMSS and lower MMSE scores than those with PD and MSA, with similar disease duration. The delta and theta powers revealed a significant increase in PSP, followed by PD and MSA. Patients with PD presented a significantly lower slow-to-fast ratio than those with PSP in the frontal region, while patients with PD presented significantly higher EEG-slowing indices than patients with MSA. The frontal slow-to-fast ratio showed a negative correlation with MMSE scores in patients with PD and PSP, and a positive correlation with NMSS in the perception and mood domain in patients with PSP but not in those with PD. Compared to PD, MSA presented enhanced FC in theta and delta bands in the posterior region, while PSP revealed decreased FC in the delta band within the frontal-temporal cortex. These findings suggest that QEEG might be a useful tool for evaluating the nonmotor dysfunctions in PD and AP. Our QEEG results suggested that with similar disease duration, the cortical neurodegenerative process was likely exacerbated in patients with PSP, followed by those with PD, and lastly in patients with MSA.

Non-linear association between Mediterranean diet and depressive symptom in U.S. adults: A cross-sectional study.

The Mediterranean diet (MED), a dietary pattern rich in fruits and vegetables, whole grains, legumes, nuts, fish, and olive oil, has anti-oxidative and anti-inflammatory effects. Although some data suggest that MED adherence is associated with decreased manifestation of depressive symptoms, it remains necessary to further analyze this apparent non-linear association as well as the influence of different factors on the relationship between MED and depression. Here, we investigated associations between the alternate MED (aMED) score and depressive symptom via multivariate logistic regression, weighted generalized additive (GAM) and two-step linear regression models, analyzing data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). The most important factor relevant to aMED score that contributed to the prevalence of depressive symptom was assessed using random forest. Furthermore, we examined whether the relationship between aMED score and depressive symptom differs by age, race, sex, socioeconomic variables, lifestyle- and health-related variables, and chronic medical conditions, via subgroup analyses. A total of 19,477 participants (20-80 years of age) were included in this cross-sectional study. In crude and adjusted (1-5) multivariate logistic regression models, increased aMED score was noted to associate with non-depressive status, as defined using the Patient Health Questionnaire-9 (P < 0.05). Data analyses via GAM and two-piecewise linear regression revealed a non-linear association between aMED and depressive symptom, which had an inflection point of 3. Random forest results revealed that vegetable score contributes greatest to the relationship between aMED and depressive symptom. Subgroup analyses revealed that aMED score is significantly negatively related with depressive symptom in most different populations (P < 0.05) with the exception of high annual income, diabetes, borderline blood glucose level and Parkinson's disease (PD) (P > 0.05). In conclusion, we observed a non-linear association between aMED score and depressive symptom. Further studies are needed to validate our results.

Sorting Nexin 5 Plays an Important Role in Promoting Ferroptosis in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly, which is related to brain iron metabolism disorders. Ferroptosis is a newly discovered iron-dependent programmed cell death mode, which has been considered an essential mechanism of PD pathogenesis in recent years. However, its underlying mechanisms have not been fully understood. In the present study, the PD rat model and PD cell model were induced by 6-hydroyxdopamine (6-OHDA). The results showed that the expression of Sorting Nexin 5 (SNX5) and the level of ferroptosis will increase after treatment with 6-OHDA. Consistent with these results, ferroptosis inducer erastin synergistically reduced the expression of glutathione peroxidase 4 (GPX4) and increased the expression of SNX5 in the PD cell model, while ferroptosis inhibitor ferrostatin-1 (Fer-1) inhibited the decrease of GPX4 and the increase of SNX5 in the PD cell model. Knockdown of SNX5 in PC-12 cells could reduce intracellular lipid peroxidation and accumulation of Fe2+ and significantly inhibit the occurrence of ferroptosis. In conclusion, the present study suggested that SNX5 promotes ferroptosis in the PD model, thus providing new insights and potential for research on the pharmacological targets of PD.

Ameliorating Effect on Glycolipid Metabolism of Spirulina Functional Formulation Combination from Traditional Chinese Medicine.

Insulin resistance is the major factor involved in the pathogenesis of type 2 diabetes. Although the oral drug metformin (MH) is widely used to reduce hyperglycemia, it is associated with adverse effects. Therefore, there is an urgent need to search for safe and natural foods that do not cause adverse effects as alternatives to commercial drugs. In this study, the active substances from Spirulina platensis, Grifola frondosa, Panax ginseng, and chromium-rich yeast were used to obtain Spirulina functional formulations (SFFs), and its therapeutic effects on mice with glycolipid metabolism disorder (GLD) were investigated. Results showed that SFFs not only improved glycolipid metabolism and reduced inflammation in mice with GLD but also showed good regenerative effects on the liver, jejunum, and cecum tissues. Moreover, SFFs could inhibit the growth of harmful microbes in the intestine and promote the proliferation of beneficial bacteria, thereby promoting the production of short-chain fatty acids and further regulating GLD. Additionally, SFFs significantly increased the expression of INS, INSR, IRS-1, PI3K, AKT-1, and GLUT-4 genes and significantly decreased that of GSK-3ß in the INS/PI3K/GLUT-4 signaling pathway. Therefore, the findings of this study suggest that SFFs can be further developed as a new class of therapeutic agents against GLD.

Sanghuangporus vaninii fruit body polysaccharide alleviates hyperglycemia and hyperlipidemia via modulating intestinal microflora in type 2 diabetic mice.

The disease of type 2 diabetes mellitus (T2DM) is principally induced by insufficient insulin secretion and insulin resistance. In the current study, Sanghuangporus vaninii fruit body polysaccharide (SVP) was prepared and structurally characterized. It was shown that the yield of SVP was 1.91%, and SVP mainly contains small molecular weight polysaccharides. Afterward, the hypoglycemic and hypolipidemic effects and the potential mechanism of SVP in T2DM mice were investigated. The results exhibited oral SVP could reverse the body weight loss, high levels of blood glucose, insulin resistance, hyperlipidemia, and inflammation in T2DM mice. Oral SVP increased fecal short-chain fatty acids (SCFAs) concentrations of T2DM mice. Additionally, 16S rRNA sequencing analysis illustrated that SVP can modulate the structure and function of intestinal microflora in T2DM mice, indicating as decreasing the levels of Firmicutes/Bacteroidetes, Flavonifractor, Odoribacter, and increasing the levels of Weissella, Alloprevotella, and Dubosiella. Additionally, the levels of predicted metabolic functions of Citrate cycle, GABAergic synapse, Insulin signaling pathway were increased, and those of Purine metabolism, Taurine and hypotaurine metabolism, and Starch and sucrose metabolism were decreased in intestinal microflora after SVP treatment. These findings demonstrate that SVP could potentially play hypoglycemic and hypolipidemic effects by regulating gut microflora and be a promising nutraceutical for ameliorating T2DM.

Difference in the adhesion of Bifidobacterium breve to lotus seed resistant starch is attributable to its structural performance conferred by the preparation method.

Resistant starch (RS) is a kind of important carbon source for colonic microorganisms. Its structure-function relationship is helpful to understand the mechanism of dietary nutrition in the body. In this paper, lotus seed resistant starches (LRS) prepared by microwave-power method (MP-LRS3-1 and MP-LRS3-2) and water-bath method (WB-LRS3-1 and WB-LRS3-2) were used to determine the structural changes and establish their nutritional interactions with Bifidobacterium breve. The results showed that four types all formed scale- and gully-like surface microstructures, B-type crystal structures, and lightly variable double helix structures. However, greater diffraction peak intensity was observed of MP-LRS3 at 18° and 19° compared with WB-LRS3, and higher crystallinity and tighter double helix were detected in MP-LRS3-1 than others. Meanwhile, MP-LRS3-1 showed the most effective proliferation promoting capability and highest adhesion value to B. breve. It might be related to specific surface microstructure and crystallinity differences of LRS caused by different preparing methods. There was also a positive correlation between the adhesion and the ability to promote proliferation, and it could be speculated this structural difference makes MP-LRS3-1 having highest adhesion ability and the most proliferative effect. This result can provide theoretical bases for improving the metabolism and probiotic action of RS.

Chronic Cerebral Hypoperfusion Aggravates Parkinson's Disease Dementia-Like Symptoms and Pathology in 6-OHDA-Lesioned Rat through Interfering with Sphingolipid Metabolism.

Chronic cerebral hypoperfusion (CCH) is a cardinal risk factor for Parkinson's disease dementia (PDD), but this potential causality lacks mechanistic evidence. We selected bilateral common carotid artery occlusion (BCCAO) to simulate chronic cerebral hypoperfusion in the rat model of PD induced by typical neurotoxin 6-hydroxy dopamine (6-OHDA). Four weeks after unilateral injection of 6-OHDA into the medial forebrain bundle, rats underwent BCCAO. Male Sprague-Dawley rats were divided into five groups of ten, including sham, PD+BCCAO 2 weeks, PD+BCCAO 1 week, PD, and BCCAO 2 weeks. Then, open field test (OFT) and Morris water maze test (MWM) were used to assess the PDD-like symptoms in rats. Also, the pathological manifestations and mechanisms of BCCAO impairing cognitive functions have been explored via hematoxylin-eosin staining, Nissl staining, immunohistochemistry, immunofluorescence, RNA sequencing analysis, lipidomics, and quantitative real-time polymerase chain reaction. In this study, we found that CCH could aggravate PDD-like cognitive symptoms (i.e., learning memory and spatial cognition) and PDD-like pathology (higher expression of α-Syn and Aß in prefrontal cortex and striatum). Moreover, a potential relationship between differentially expressed mRNAs and lipid metabolism was revealed by RNA sequencing analysis. Lipidomics showed that CCH could affect the intensity of 5 lipids, including sphingomyelin (SM 9:0;2O/26:2; SM 8:1;2O/25:0; and SM 8:0;2O/28:4), cardiolipin, lysophosphatidylcholine, cholesteryl ester, and triacylglycerol. Interestingly, the KEGG pathway analysis of both RNA sequencing analysis and lipidomics suggested that CCH leaded to learning impairment by affecting sphingolipid metabolism. Finally, we found that CCH disrupts the sphingolipid metabolism by affecting the mRNA expression of SMPD1 and SMS2, leading to the accumulation of sphingomyelin in the prefrontal cortex. In summary, CCH, an independent exacerbating reason for impairment in learning and memory within the pathopoiesis of PD, aggravates Parkinson's disease dementia-like symptoms and pathology in 6-OHDA-lesioned rat through interfering with sphingolipid metabolism.