Effect of traditional Chinese medicine on metabolism disturbance in ischemic heart diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic heart diseases (IHD), characterized by metabolic dysregulation, contributes majorly to the global morbidity and mortality. Glucose, lipid and amino acid metabolism are critical energy production for cardiomyocytes, and disturbances of these metabolism lead to the cardiac injury. Traditional Chinese medicine (TCM), widely used for treating IHD, have been demonstrated to effectively and safely regulate the cardiac metabolism reprogramming. AIM OF THE REVIEW: This study discussed and analyzed the disturbed cardiac metabolism induced by IHD and development of formulas, extracts, single herb, bioactive compounds of TCM ameliorating IHD injury via metabolism regulation, with the aim of providing a basis for the development of clinical application of therapeutic strategies for TCM in IHD. MATERIALS AND METHODS: With "ischemic heart disease", "myocardial infarction", "myocardial ischemia", "metabolomics", "Chinese medicine", "herb", "extracts" "medicinal plants", "glucose", "lipid metabolism", "amino acid" as the main keywords, PubMed, Web of Science, and other online search engines were used for literature retrieval. RESULTS: IHD exhibits a close association with metabolism disorders, including but not limited to glycolysis, the TCA cycle, oxidative phosphorylation, branched-chain amino acids, fatty acid ß-oxidation, ketone body metabolism, sphingolipid and glycerol-phospholipid metabolism. The therapeutic potential of TCM lies in its ability to regulate these disturbed cardiac metabolisms. Additionally, the active ingredients of TCM have depicted wonderful effects in cardiac metabolism reprogramming in IHD. CONCLUSION: Drawing from the principles of TCM, we have pinpointed specific herbal remedies for the treatment of IHD, and leveraged advanced metabolomics technologies to uncover the effect of these TCMs on metabolomics alteration. In the future, further clinical experimental studies should be included to explore whether more TCM medicines can play a therapeutic role in IHD by reversing cardiac metabolism disorders; multi-omics would be conducted to explore more pathways and genes targeting such metabolism reprogramming by TCMs, and to seek more TCM therapies for IHD.

Association between programmed cell death ligand-1 expression in patients with cervical cancer and apparent diffusion coefficient values: a promising tool for patient´s immunotherapy selection.

OBJECTIVE: To investigate the associations between apparent diffusion coefficient (ADC) values extracted from three different region of interest (ROI) position approaches and programmed cell death ligand-1 (PD-L1) expression, and evaluate the performance of the nomogram established based on ADC values and clinicopathological parameters in predicting PD-L1 expression in cervical cancer (CC) patients. METHODS: Through retrospective recruitment, a training cohort of 683 CC patients was created, and a validation cohort of 332 CC patients was prospectively recruited. ROIs were delineated using three different methods to measure the mean ADC (ADCmean), single-section ADC (ADCss), and the minimum ADC of tumors (ADCmin). Logistic regression was employed to identify independent factors related to PD-L1 expression. A nomogram was drawn based on ADC values combined with clinicopathological features, its discrimination and calibration performances were estimated using the area under the curve (AUC) of receiver operating characteristic and calibration curve. The clinical benefits were evaluated by decision curve analysis. RESULTS: The ADCmin independently correlated with PD-L1 expression. The nomogram constructed with ADCmin and other independent clinicopathological-related factors: FIGO staging, pathological grade, parametrial invasion, and lymph node status demonstrated excellent diagnostic performance (AUC = 0.912 and 0.903, respectively), good calibration capacities, and greater net benefits compared to the clinicopathological model in both the training and validation cohorts. CONCLUSION: ADCmin independently correlated PD-L1 expression, and the nomogram established with ADCmin and clinicopathological independent prognostic factors had a strong predictive performance for PD-L1 expression, thereby serving as a promising tool for selecting cases eligible for immunotherapy. CLINICAL RELEVANCE STATEMENT: The minimum ADC can serve as a reliable imaging biomarker related to PD-L1 expression; the established nomogram combines the minimum ADC and clinicopathological factors that can assist clinical immunotherapy decisions.

Precise prediction of cerebrospinal fluid amyloid beta protein for early Alzheimer's disease detection using multimodal data.

Alzheimer's disease (AD) constitutes a neurodegenerative disorder marked by a progressive decline in cognitive function and memory capacity. The accurate diagnosis of this condition predominantly relies on cerebrospinal fluid (CSF) markers, notwithstanding the associated burdens of pain and substantial financial costs endured by patients. This study encompasses subjects exhibiting varying degrees of cognitive impairment, encompassing individuals with subjective cognitive decline, mild cognitive impairment, and dementia, constituting a total sample size of 82 participants. The primary objective of this investigation is to explore the relationships among brain atrophy measurements derived from magnetic resonance imaging, atypical electroencephalography (EEG) patterns, behavioral assessment scales, and amyloid ß-protein (Aß) indicators. The findings of this research reveal that individuals displaying reduced Aß1-42/Aß-40 levels exhibit significant atrophy in the frontotemporal lobe, alongside irregularities in various parameters related to EEG frequency characteristics, signal complexity, inter-regional information exchange, and microstates. The study additionally endeavors to estimate Aß1-42/Aß-40 content through the application of a random forest algorithm, amalgamating structural data, electrophysiological features, and clinical scales, achieving a remarkable predictive precision of 91.6%. In summary, this study proposes a cost-effective methodology for acquiring CSF markers, thereby offering a valuable tool for the early detection of AD.

A novel spatiotemporal graph convolutional network framework for functional connectivity biomarkers identification of Alzheimer's disease.

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD. METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, firstly, we optimized the STGC-GCAM model to enhance classification accuracy. Secondly, we identified novel AD-associated biomarkers using the optimized model. Thirdly, we validated the imaging biomarkers using Kaplan-Meier analysis. Lastly, we performed correlation analysis and causal mediation analysis to confirm the physiological significance of the identified biomarkers. RESULTS: The STGC-GCAM model demonstrated great classification performance (The average area under the curve (AUC) values for different categories were: CN vs MCI = 0.98, CN vs AD = 0.95, MCI vs AD = 0.96, stable MCI vs progressive MCI = 0.79). Notably, the model identified specific brain regions, including the sensorimotor network (SMN), visual network (VN), and default mode network (DMN), as key differentiators between patients and CN individuals. These brain regions exhibited significant associations with the severity of cognitive impairment (p < 0.05). Moreover, the topological features of important brain regions demonstrated excellent predictive capability for the conversion from MCI to AD (Hazard ratio = 3.885, p < 0.001). Additionally, our findings revealed that the topological features of these brain regions mediated the impact of amyloid beta (Aß) deposition (bootstrapped average causal mediation effect: ß = -0.01 [-0.025, 0.00], p < 0.001) and brain glucose metabolism (bootstrapped average causal mediation effect: ß = -0.02 [-0.04, -0.001], p < 0.001) on cognitive status. CONCLUSIONS: This study presents the STGC-GCAM framework, which identifies FC biomarkers using a large multi-site fMRI dataset.

Human umbilical cord mesenchymal stem cells reverse depression in rats induced by chronic unpredictable mild stress combined with lipopolysaccharide.

BACKGROUND: Inflammation and oxidative stress are considered crucial to the pathogenesis of depression. Rat models of depression can be created by combined treatments of chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS). Behaviors associated with depression could be improved by treatment with mesenchymal stem cells (MSCs) owing to immunomodulatory functions of the cells. Therapeutic potentials of the MSCs to reverse pro-inflammatory cytokines, proteins, and metabolites were identified by transcriptomic, proteomic, and metabolomic analysis, respectively. METHODS: A depression model was established in male SD rats by 2 weeks of CUMS combined with LPS. The models were verified by behavioral tests, namely SPT, OFT, EPM, and qRT-PCR for pro-inflammatory cytokines. Such depressed rats were administered human umbilical cord MSCs (hUC-MSCs) via the tail vein once a week for 2 and 4 weeks. The homing capacity was confirmed by detection of the fluorescent dye on day 7 after the hUC-MSCs were labeled with CM-Dil and administered. The expression of GFAP in astrocytes serves as a biomarker of CNS disorders and IBA1 in microglia serves as a marker of microglia activation were detected by immunohistochemistry at 2 and 4 weeks after final administration of hUC-MSCs. At the same time, transcriptomics of rat hippocampal tissue, proteomic and metabolomic analysis of the serum from the normal, depressed, and treated rats were also compared. RESULTS: Reliable models of rat depression were successfully induced by treatments of CUMS combined with LPS. Rat depression behaviors, pro-inflammatory cytokines, and morphological disorders of the hippocampus associated with depression were reversed in 4 weeks by hUC-MSC treatment. hUC-MSCs could reach the hippocampus CA1 region through the blood circulation on day 7 after administration owing to the disruption of blood brain barrier (BBB) by microglial activation from depression. Differentiations of whole-genome expression, protein, and metabolite profiles between the normal and depression-modeled rats, which were analyzed by transcriptomic, proteomics, and metabolomics, further verified the high association with depression behaviors. CONCLUSIONS: Rat depression can be reversed or recovered by treatment with hUC-MSCs.

Insights into drought stress response mechanism of tobacco during seed germination by integrated analysis of transcriptome and metabolome.

Drought stress inhibits seed germination, plant growth and development of tobacco, and seriously affects the yield and quality of tobacco leaves. However, the molecular mechanism underlying tobacco drought stress response remains largely unknown. In this study, integrated analysis of transcriptome and metabolome was performed on the germinated seeds of a cultivated variety K326 and its EMS mutagenic mutant M28 with great drought tolerance. The result showed that drought stress inhibited seed germination of the both varieties, while the germination rate of M28 was faster than that of K326 under drought stress. Besides, the levels of phytohormone ABA, GA19, and zeatin were increased by drought stress in M28. Five vital pathways were identified through integrated transcriptomic and metabolomic analysis, including zeatin biosynthesis, aspartate and glutamate synthesis, phenylamine metabolism, glutathione metabolism, and phenylpropanoid synthesis. Furthermore, 20 key metabolites in the above pathways were selected for further analysis of gene modular-trait relationship, and then four highly correlated modules were found. Then analysis of gene expression network was carried out of Top30 hub gene of these four modules, and 9 key candidate genes were identified, including HSP70s, XTH16s, APX, PHI-1, 14-3-3, SCP, PPO. In conclusion, our study uncovered some key drought-responsive pathways and genes of tobacco during seeds germination, providing new insights into the regulatory mechanisms of tobacco drought stress response.

The trend of AIDS in China: A prediction and comparative analysis with G20 countries based on the Global Burden of Disease Study 2019.

Background: In China, AIDS has become the most severe notifiable infectious disease. The study aimed to analyse and predict the trend of AIDS in China and compared with Group of Twenty (G20) countries. Methods: We utilised incidence, mortality or disability-adjusted life years (DALY), age-standardised rates (ASR), average annual percentage changes (AAPC) to estimate the trend via GBD 2019. The Joinpoint regression analysis was applied to identify the most significant years of change. We explored the relationship between AAPC and social development index (SDI) or health care access and quality (HAQ), and predicted trends for the next 20 years. Results: The DALY in G20 increase of 340.42%, and 794.50% in China. The age-standardised DALY rate (ASDR) in G20 was 309.49 (95% uncertainty interval (UI) = 284.69, 350.58) in 2019, with an AAPC of 4.30. Among G20, the United States had the highest DALY in 1990, but it experienced a significant decline. In China, the ASDR was 98.15 (95% UI = 78.78, 119.58) with the 5th AAPC ranking. In term of gender, the incidence, mortality, DALY, and ASR of them in China and G20 were all higher in males. Furthermore, the gender gap in China had been widening. The most significant periods of ASDR increase in China were 1990-1995 and 2013-2016, and 1990-1994 in G20. The prediction for DALY indicated that high SDI countries were expected to exhibit a stable or declining trend, while low SDI countries showed an upward trend. China demonstrated a 57.66% increase in 2040 compared to 2019. Conclusions: AIDS continues to be a significant burden. In China, the ASIR exhibited a decline trend in certain age groups, while the ASMR and ASDR continued to increase, with a widening gender disparity. In addition, according to our predict results, some countries could not achieve the 2030 Agenda for Sustainable Development set by the UNAIDS. Therefore, it is necessary to establish more effective and targeted measures, as well as actively explore new treatment approaches.

Single-Dose Radial Extracorporeal Shock Wave Therapy Modulates Inflammation During Meniscal Tear Healing in the Avascular Zone.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) promotes tissue healing by modulating inflammation, which has implications for meniscal tear healing in the avascular zone. PURPOSE: To evaluate the effects of a single dose of radial ESWT on the healing process and inflammation of the meniscus and knee joints after meniscal tears in the avascular zone. STUDY DESIGN: Controlled laboratory study. METHODS: Avascular tears were induced in the medial meniscus (MM) of 72 Sprague-Dawley rats. One week postoperatively, the rats received a single session of radial ESWT with a Power+ handpiece (ESWT group; n = 36) or with a fake handpiece (sham-ESWT group; n = 36). The rats were then euthanized at 2, 4, or 8 weeks postoperatively. The MMs were harvested for analysis of healing (hematoxylin-eosin, safranin O-Fast Green, and collagen type 2 staining) and inflammation (interleukin [IL]-1ß and IL-6 staining). Lateral menisci and synovia were obtained to evaluate knee joint inflammation (enzyme-linked immunosorbent assay of IL-1ß and IL-6). Cartilage degeneration was assessed in the femurs and tibial plateaus using safranin O-Fast Green staining. RESULTS: The ESWT group showed significantly better meniscal healing scores than the sham-ESWT group at 4 (P = .0066) and 8 (P = .0050) weeks postoperatively. The IL-1ß level was significantly higher in the sham-ESWT group than in the ESWT group at 2 (MM: P = .0009; knee joint: P = .0160) and 8 (MM: P = .0399; knee joint: P = .0001) weeks. The IL-6 level was significantly lower in the sham-ESWT group than in the ESWT group at 2 (knee joint: P = .0184) and 4 (knee joint: P = .0247) weeks but higher at 8 weeks (MM: P = .0169; knee joint: P = .0038). The sham group had significantly higher osteoarthritis scores than the ESWT group at 4 (tibial plateau: P = .0157) and 8 (femur: P = .0048; tibial plateau: P = .0359) weeks. CONCLUSION: A single dose of radial ESWT promoted meniscal tear healing in the avascular zone, modulated inflammatory factors in the menisci and knee joints in rats, and alleviated cartilage degeneration. CLINICAL RELEVANCE: Radial ESWT can be considered a potential option for improving meniscal tear healing in the avascular zone because of its ability to modulate inflammation.

Integration of pharmacodynamics and metabolomics to reveal rhubarb anthraquinone protection against nonalcoholic fatty liver disease rat model.

OBJECTIVES: The objective of the present study was to investigate the effect of Rhubarb anthraquinone (RA) on a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) rat model, and explore potential biomarker and metabolic pathways by using the metabolomics method. MATERIALS AND METHODS: We established HFD rats as the NAFLD model. Forty Sprague-Dawley rats were randomly divided into a control group, model group, RA low-dose group, RA medium-dose group, and RA high-dose group, and evaluated the protective effect of RA on NAFLD by detecting biochemical indicators of serum and pathological changes of liver tissue. Investigating potential biomarkers and metabolic pathways connected with RA's protective effects against NAFLD by UHPLC-Q-TOF-MS untargeted metabolomics. RESULTS: The results showed that RA significantly reversed the increase of TG, TC, ALT, AST, and ALP (P < .05), the decrease of HDL-C (P < .05), and alleviated pathological conditions in NAFLD rats. Based on potential biomarker analysis, RA affected metabolic pathways such as fatty acids biosynthesis, bile acids biosynthesis, and pentose phosphate pathway, delaying the progression of NAFLD. CONCLUSION: RA improved blood lipid levels, liver function, and pathological conditions of NAFLD rats. Meanwhile, affected the metabolic pathways and regulated the synthesis of fatty acids and bile acids in NAFLD rats.

Diversity of Distoseptispora (Distoseptisporaceae) taxa on submerged decaying wood from the Red River in Yunnan, China.

The Red River Basin is located in the Indo-Burma biodiversity hotspot and is rich in lignicolous freshwater fungi, but no systematic research has been conducted. A systematic study on the species diversity of lignicolous freshwater fungi in the basin is ongoing. Seven distoseptispora-like specimens were collected from the Red River Basin in Yunnan. Phylogenetic analysis of ITS, LSU, tef1-α, and rpb2 genes and combined morphological data indicate that there are six distinct species of Distoseptispora, including two new species and four known species. Two new species were named D.suae and D.xinpingensis, and the four known species were D.bambusae, D.euseptata, D.obpyriformis and D.pachyconidia. This study provides detailed descriptions and illustrations of these six species and an updated phylogenetic backbone tree of Distoseptispora.

Lactobacillus johnsonii Improves Intestinal Barrier Function and Reduces Post-Weaning Diarrhea in Piglets: Involvement of the Endocannabinoid System.

Probiotic intervention is a well-established approach for replacing antibiotics in the management of weaning piglet diarrhea, which involves a large number of complex systems interacting with the gut microbiota, including the endocannabinoid system; nevertheless, the specific role of the endocannabinoid system mediated by probiotics in the piglet intestine has rarely been studied. In this study, we used antibiotics (ampicillin) to perturb the intestinal microbiota of piglets. This resulted in that the gene expression of the intestinal endocannabinoid system was reprogrammed and the abundance of probiotic Lactobacillus johnsonii in the colon was lowered. Moreover, the abundance of Lactobacillus johnsonii was positively correlated with colonic endocannabinoid system components (chiefly diacylglycerol lipase beta) via correlation analysis. Subsequently, we administered another batch of piglets with Lactobacillus johnsonii. Interestingly, dietary Lactobacillus johnsonii effectively alleviated the diarrhea ratio in weaning piglets, accompanied by improvements in intestinal development and motility. Notably, Lactobacillus johnsonii administration enhanced the intestinal barrier function of piglets as evidenced by a higher expression of tight junction protein ZO-1, which might be associated with the increased level in colonic diacylglycerol lipase beta. Taken together, the dietary Lactobacillus johnsonii-mediated reprogramming of the endocannabinoid system might function as a promising target for improving the intestinal health of piglets.

Phillygenin Inhibits TGF-ß1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/ß-catenin Pathways.

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C21H24O6) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-ß1 (TGF-ß1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-ß1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-ß1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/ß-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.

An ensemble learning model for continuous cognition assessment based on resting-state EEG.

One critical manifestation of neurological deterioration is the sign of cognitive decline. Causes of cognitive decline include but are not limited to: aging, cerebrovascular disease, Alzheimer's disease, and trauma. Currently, the primary tool used to examine cognitive decline is scale. However, scale examination has drawbacks such as its clinician subjectivity and inconsistent results. This study attempted to use resting-state EEG to construct a cognitive assessment model that is capable of providing a more scientific and robust evaluation on cognition levels. In this study, 75 healthy subjects, 99 patients with Mild Cognitive Impairment (MCI), and 78 patients with dementia were involved. Their resting-state EEG signals were collected twice, and the recording devices varied. By matching these EEG and traditional scale results, the proposed cognition assessment model was trained based on Adaptive Boosting (AdaBoost) and Support Vector Machines (SVM) methods, mapping subjects' cognitive levels to a 0-100 test score with a mean error of 4.82 (<5%). This study is the first to establish a continuous evaluation model of cognitive decline on a large sample dataset. Its cross-device usability also suggests universality and robustness of this EEG model, offering a more reliable and affordable way to assess cognitive decline for clinical diagnosis and treatment as well. Furthermore, the interpretability of features involved may further contribute to the early diagnosis and superior treatment evaluation of Alzheimer's disease.

Structural stabilities and natural half-metallic properties of OsXCoSi (X=Ti, Zr, Hf) quaternary Heusler alloys series first-principles calculations.

Based on first-principles calculation of density functional theory, this study investigates the structural stability, magnetic properties, and electronic properties of the three different phases (i.e. type 1, type 2, and type 3) of OsXCoSi (X=Ti, Zr, Hf) in a new quaternary Heusler alloy series. The corresponding equilibrium lattice constants of each type are optimized, and the change of formation enthalpy and elastic constant phonon spectrum show that the OsXCoSi (X=Ti, Zr, Hf) alloy is thermodynamically, dynamically and mechanically stable. Furthermore, the bonding features of each phase are discussed. It is found that all type 1 structures of OsXCoSi (X=Ti, Zr, Hf) exhibit natural half-metallicity (HM) in equilibrium lattice constant, and their equilibrium lattice constants in the ground state were determined to be 5.909 Å for OsTiCoSi, 6.155 Å for OsZrCoSi, and 6.100 Å for OsHfCoSi. Meanwhile, by testing the alloy under different pressures, the range of the integer magnetic moment non-equilibrium lattice constants for the three alloys OsTiCoSi, OsZrCoSi, and OsHfCoSi are 5.710 Š∼ 6.329 Å, 5.696 Š∼ 6.1557 Å and 5.716 Š∼6.1009 Å, respectively, which is wide and is more close to the practical application for spin-polarized materials. In addition, its magnetic moment is consistent with the values given by the Slater-Pauling rule. Furthermore, the forming of the HM gap is examined by analysing the total and partial density of states, energy bands of alloy's electronic property, with respect to the calculated results. What's more, special attention is paid to the differences of the properties for series Heusler alloys. It is found that the electronics properties distinction is mainly based on valence electron changes. However, the lattice constants are susceptible to size of a nucleus.

Protective mechanism of Paeonol on central nervous system.

Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug components from natural plants and the study of their mechanism are a research idea different from chemical synthetic medicines. Paeonol is the main active component of traditional Chinese medicine Paeonia lactiflora Pall. It widely exists in many medicinal plants and has pharmacological effects such as anti-atherosclerosis, antiplatelet aggregation, anti-oxidation, and anti-inflammatory, which keeps generally used in the treatment of cardiovascular and cerebrovascular diseases. Based on the therapeutic effects of Paeonol for cardiovascular and cerebrovascular diseases, this article reviewed the pharmacological effects of Paeonol in Alzheimer's disease, Parkinson's disease, stroke, epilepsy, diabetes encephalopathy, and other neurological diseases, providing a reference for the research of the mechanism of Paeonol in central nervous system diseases.

Gentianine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibition of TLR4/NLRP3-mediated pyroptosis.

OBJECTIVES: Ulcerative colitis (UC) is a common inflammatory bowel disorder. Gentiana scabra Bunge is a traditional medicinal plant that is used to treat a variety of diseases. Studies have shown that gentianine (GTN) from Gentiana scabra inhibits the development of inflammatory diseases. The purpose of this study was to investigate the effect and possible mechanism of action of GTN on UC in mice. METHODS: An animal model of UC was established using dextran sulfate sodium (DSS). Mice were administered intraperitoneally with GTN (12.5, 25, or 50 mg/kg/day) for seven days. Body weight and disease activity index (DAI) were monitored daily during GTN administration. Colon length, pathological changes, and myeloperoxidase (MPO) activity were measured following GTN administration. The signalling pathways regulated by GTN were analysed using machine learning. HT-29 cells were used to verify the effect and mechanism of action of GTN on UC in vitro. RESULTS: GTN suppressed weight loss, shortened colon length, alleviated colon injury, and reduced the DAI score and MPO activity of mice with UC in a dose-dependent manner. Further analysis showed that GTN inhibited the NOD-like receptor (NLR) signalling pathway. GTN markedly decreased the levels of NLR signalling pathway-related proteins. Moreover, GTN decreased the levels of pyroptosis-related proteins, IL-1ß and IL-18. The in vitro data were consistent with those of animal experiments. Furthermore, TLR4 and NLRP3 overexpression eliminated the protective effects of GTN in HT-29 cells. CONCLUSION: Gentianine alleviated DSS-induced UC by inhibiting TLR4/NLRP3-mediated pyroptosis.

Natural and anthropogenic controls on environmental change during the Holocene based on a multi-proxy record obtained from subalpine peatland in southern China.

The interactions between past climate, human activity and environmental change in subtropical mountainous areas are poorly understood due to the lack of reliable records in South China. In this study, the evolution of the East Asian summer monsoon (EASM) during the Holocene, and the interactions between regional human activity and environmental change, were studied using multi-proxy records from a subalpine peat core recovered from South China. The chronology of this peat core has been well-constrained by 10 AMS 14C dates of peat stems. A series of proxy indicators, including carbon isotopes (δ13C), loss on ignition (LOI), magnetic susceptibility (MS), the chemical index of alteration (CIA), and geochemical elements from the Shiwangutian (SWGT) peatland were used to reconstruct the palaeohydrological changes during the Holocene. Regional moisture levels showed a generally arid-wet-arid pattern, and three phases of climatic change were detected as follows. 1) Between 11,600 and 9000 cal yr BP, the EASM was weak and a relatively dry climate developed. 2) Between 9000 and 4000 cal yr BP, the prevalence of humid climatic conditions was associated with a strong summer monsoon. 3) After 4000 cal yr BP, the climate shifted to relatively dry conditions. Further comparisons and analysis suggested that solar insolation, migration of the Intertropical Convergence Zone (ITCZ), and El Niño-Southern Oscillation (ENSO) activity played an important role in determining the variations in Holocene EASM intensity. In addition, the increase in both MS and heavy metal concentrations over the last 1000 years is consistent with an increase in the population of Hunan Province. Therefore, it can be inferred that population growth and the associated expansion of cropland and mining led to an increase in soil erosion and metal tool use. These findings suggest that the impact of human activity generally outweighed the natural climatic controls on the environment and landscape in the mountainous region of southern China over the last 1000 years.

Interfacial engineering of Ti3C2-TiO2 MXenes by managing surface oxidation behavior for enhanced sonodynamic therapy.

As a kind of reactive oxygen species (ROS) mediated therapy, sonodynamic therapy (SDT) has attracted great interest in cancer therapy. However, highly efficient and biocompatible sonosensitizers are urgently required to improve the therapeutic efficiency of SDT. In this work, Ti3C2-TiO2 MXenes were controllably synthesized as good sonosensitizers through interface engineering by regulating the dissolved oxygen concentration of the aqueous solution. The as-prepared Ar-Ti3C2-TiO2 MXene possessed a narrow band gap of 2.37 eV with promoted charge carrier transformation and efficient electron-hole separation. Compared with pure TiO2 sonosensitizers, the Ar-Ti3C2-TiO2 MXene displayed higher US-triggered reactive oxygen species (ROS) generation efficiency. In addition, the structurally maintained Ar-Ti3C2-TiO2 possessed good photothermal conversion efficiency and the laser irradiation could greatly improve the electron-hole pair separation efficiency to further increase the ROS generation capability. After modification with arginyl-glycyl-aspartic (RGD) peptide, the Ar-Ti3C2-TiO2-RGD could efficiently accumulate in the tumor sites and achieve effective PTT enhanced SDT to eliminate tumors after intravenous injection without causing appreciable long-term toxicity. Therefore, this work presented a new way to construct safe sonosensitizers for enhanced SDT and the as-prepared Ar-Ti3C2-TiO2-RGD displayed good potential for further clinical translation. STATEMENT OF SIGNIFICANCE: To achieve superior tumor treatment, the nanosized TiO2/Ti3C2 heterostructure was controllably synthesized through interface engineering by regulating the dissolved oxygen concentration of the aqueous solution using inert gas. The oxidation-optimized Ar-Ti3C2-TiO2 MXene possessed good sonodynamic performance with a narrow band gap of 2.37 eV and good photothermal conversion efficiency of 47.3% with structurally maintained Ti3C2 MXene. Additionally, the laser irradiation could greatly improve the electron-hole pair separation efficiency to further boost sonodynamic performance of Ar-Ti3C2-TiO2 MXene. Encouragingly, the Ar-Ti3C2-TiO2-RGD could efficiently accumulate in the tumor sites and achieve effective PTT enhanced SDT to eliminate tumors.

Comparative Pharmacokinetic Study of Rhubarb Anthraquinones in Normal and Nonalcoholic Fatty Liver Disease Rats.

BACKGROUND AND OBJECTIVES: Rhubarb anthraquinones contain five main components, that is, rhein, emodin, aloe-emodin, chrysophanol, and physcion, which demonstrate good therapeutic effects on nonalcoholic fatty liver disease (NAFLD). However, research on its pharmacokinetics in NAFLD remains lacking. This study aimed to investigate the pharmacokinetic differences of rhubarb anthraquinones in normal and NAFLD rats. METHODS: This study developed an NAFLD rat model by high-fat diet feeding for 6 weeks. Normal and NAFLD groups were orally administered different rhubarb anthraquinones doses (37.5, 75, and 150 mg/kg). The concentration of the rhein, emodin, aloe-emodin, chrysophanol, and physcion in plasma was determined by high-performance liquid chromatography-ultraviolet. RESULTS: The results revealed significant differences in pharmacokinetic behavior between normal and NAFLD rats. Compared with normal rats, NAFLD rats demonstrated significantly increased maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0 → ∞) of rhubarb anthraquinones (P < 0.05), as well as significantly prolonged time to reach maximum plasma concentration (Tmax), terminal elimination half-life (t1/2), and mean residence time (MRT) of rhubarb anthraquinones (P < 0.05). CONCLUSIONS: This study indicates significant differences in the pharmacokinetics of rhubarb anthraquinones between the physiological and NAFLD states of rats. Rhubarb anthraquinone demonstrated a longer retention time and slower absorption rate in NAFLD rats and exhibited higher bioavailability and peak concentration. This finding provides important information for guiding the clinical use of rhubarb anthraquinones under pathological conditions.