Spatial Multi-Omics in Alzheimer's Disease: A Multi-Dimensional Approach to Understanding Pathology and Progression.

Alzheimer's Disease (AD) presents a complex neuropathological landscape characterized by hallmark amyloid plaques and neurofibrillary tangles, leading to progressive cognitive decline. Despite extensive research, the molecular intricacies contributing to AD pathogenesis are inadequately understood. While single-cell omics technology holds great promise for application in AD, particularly in deciphering the understanding of different cell types and analyzing rare cell types and transcriptomic expression changes, it is unable to provide spatial distribution information, which is crucial for understanding the pathological processes of AD. In contrast, spatial multi-omics research emerges as a promising and comprehensive approach to analyzing tissue cells, potentially better suited for addressing these issues in AD. This article focuses on the latest advancements in spatial multi-omics technology and compares various techniques. Additionally, we provide an overview of current spatial omics-based research results in AD. These technologies play a crucial role in facilitating new discoveries and advancing translational AD research in the future. Despite challenges such as balancing resolution, increasing throughput, and data analysis, the application of spatial multi-omics holds immense potential in revolutionizing our understanding of human disease processes and identifying new biomarkers and therapeutic targets, thereby potentially contributing to the advancement of AD research.

Impact of environmental variables on the distribution of phytoplankton communities in the Southern Yellow Sea.

To gain a comprehensive understanding of the seasonal variation in the structure of phytoplankton communities in the Southern Yellow Sea (SYS), two research expeditions were conducted from 12 to 24 in April 2019, and from 12 to 22 in October of 2019. During the spring season, the phytoplankton community within the SYS was primarily comprised of diatoms and dinoflagellates, while in autumn, diatoms and cyanobacteria dominated. Thalassiosira rotula and Paralia sulcata were the dominant species in both seasons. In spring, P. sulcata displayed no obvious correlation with any environmental parameter, while in autumn, it exhibited negative correlations with environmental factors. According to the cluster and multidimensional scaling analyses, the phytoplankton community was stratified into three distinct ecological provinces in the SYS: the Western Yellow Sea, the Yellow Sea basin, and the southern coastal region. The phytoplankton community composition was predominantly affected by seasonal fluctuations in temperature and nutrient levels. Notably, the Yellow Sea basin exhibited the lowest phytoplankton abundance, largely because of the impact of the Yellow Sea Cold Water Mass. Furthermore, the presence of cyanobacteria, particularly prevalent in the Yellow Sea basin, may have been facilitated by transport mechanisms associated with the Kuroshio current. Aggregated boosted tree (ABT) and Generalized Additive models (GAM) suggested that temperature, DIN, salinity, and DIP were significant parameters of phytoplankton abundance in SYS. Additionally, the N:P nutrient ratio was a key parameter in governing the structure of phytoplankton communities during both seasons.

Source apportionment and potential ecological risk assessment of heavy metals in soils on a large scale in China.

The properties and sources of soil heavy metals (Pb, Zn, Cu, Cd, As, Hg, Cr, and Ni) need to be comprehensively analyzed to take effective steps to control and reduce soil pollutants. In this research, 416 soil samples were collected on a large scale in China. Two receptor models (PCA/MLR and PMF) were utilized to identify pollutant sources and quantify the contributions. The means of soil heavy metals (Zn, Cu, As, Hg, Cr, and Ni) were lower than the corresponding screening values and intervention values. Cd was greater than the intervention value, while Pb was between the screening value and the intervention value. Source apportionments suggested that mine sources were the most polluted (64.28%), followed by traffic sources (38.98%), natural sources (11.41-39.58%), industrial sources (9.8-18.65%), and agricultural sources (2.79-14.51%). Compared to the PCA/MLR model, the PMF model had a better effect in evaluating soil heavy metal pollution. It gave corresponding weights according to the data concentration and its uncertainty, which made the result reasonable. The ecological risk assessment indicated that Cd posed a significant risk, while Hg caused a mild risk and the other six heavy metals posed a low risk. The spatial distribution of ecological risk suggested that severe risk points were mainly distributed in the central area, while high-risk points were distributed in the southern region. The SRI method was developed to link pollution sources and their potential ecological risks and indicated better applicability to the PMF model. The study findings could provide guidelines for monitoring the main sources and reducing the pollution of soil heavy metals.

Oyster peptide prevents the occurrence of exercise-hypogonadal male condition by improving the function of pituitary gonadal axis in male rats.

This study evaluates the protective role of oyster peptide (OP) on the occurrence of Exercise-Hypogonadal Male Condition. Male rats were given heavy-load swimming training and / or OP was supplemented for 6 consecutive weeks. After heavy-load training, sperm count, sperm viability and sperm motility in epididymis, testosterone in serum and testis, glutathione peroxidase (GSH-px) and androgen receptor (AR) in testis and mating times were remarkably decreased, malondialdehyde (MDA), capture latency and mating latency were significantly increased, mRNA expression of steroidogenic acute regulatory (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc) were obviously down-regulated, but serum follicle-stimulating hormone (FSH) and luteinising hormone (LH) were not statistically changed. Conversely, when OP was supplemented at heavy-load training, sperm count, sperm viability and sperm motility in epididymis, serum FSH, LH, testosterone, GSH-px, superoxide dismutase (SOD), testosterone, AR in testis and mating times were dramatically increased, while testicular MDA, capture latency and mating latency were significantly decreased, and mRNA expression of StAR, StARD7, P450scc and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) were significantly up-regulated. In conclusion, heavy-load training causes testicular spermatogenic and steroidogenic disorders by enhancing the generation of reactive oxygen species (ROS), which can be protected by the co-administration of OP by enhancing the function of pituitary gonad axis and lowering ROS generation.

Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo.

Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5-2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg(fli-1a: EGFP)y1. Timo AIII (0.5-4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment.

Revealing the spatiotemporal evolution pattern and convergence law of agricultural land transfer in China.

The transfer of land plays a crucial role in revitalizing land resources, acting as a catalyst for promoting the high-quality development of agriculture. The land transfer ratio is a crucial metric for assessing the progress of rural land transfer and the effective allocation of rural land resources. Thus, this study examines the rural land transfer ratio across 30 provinces in China from 2005 to 2020. The study explores the distribution characteristics of the ratio using the rank-size rule and trend surface analysis. The LISA space-time transition method is employed to analyze the spatial and temporal dynamics of the rural land transfer ratio and examine its convergence. The study aims to comprehensively analyze the spatial distribution characteristics and evolutionary patterns of rural land transfer in China, illustrating the convergence and influencing factors during the development process. The results indicate that: (1) The rural land transfer ratio in China is generally increasing, with a spatial pattern showing an upward trend from west to east and from north to south. The main spatial contrast is between the eastern and western regions, with a relatively minor distinction between the southern and northern regions. (2) The LISA space-time transition highlights a significant spatial locking effect in China's rural land transfer ratio, suggesting strong spatial integration in its evolution. (3) Clear indications of σ convergence, absolute ß convergence, and club convergence are evident in China's rural land transfer ratio. This suggests a gradual reduction in internal disparities among provinces and regions, where areas with higher land transfer ratios influence spatial spillover effects on adjacent lower areas. (4) Factors such as transportation infrastructure, irrigation, water conservancy construction, and farmers' per capita income collectively influence the spatial and temporal evolution of China's rural land transfer ratio, with dominant driving factors varying across different periods.

An arabinoxylan (AOP70-1) isolated from Alpinia oxyphylla alleviates neuroinflammation and neurotoxicity by TLR4/MyD88/NF-κB pathway.

Alpinia oxyphylla is famous for its neuroprotective and memory-improving effects. A crude polysaccharide AO70 from A. oxyphylla remarkably ameliorated neuroinflammation and cognitive dysfunction in Alzheimer's disease mice. This study aimed to explore the bioactive component of AO70 and its mechanism of action. A homogeneous polysaccharide (AOP70-1) rich in arabinose and xylose was purified from AO70, which was consisted of α-L-Araf-(1→, →5)-α-L-Araf-(1→, ß-D-Xylp-(1→,→2,4)-ß-D-Xylp-(1→, →2,3,4)-ß-D-Xylp-(1→, α-L-Rhap-(1→, α-D-Manp-(1→, →4)-α-D-Glcp-(1→, →4)-α-D-GlcpA-(1→, ß-D-Galp-(1→, →2)-α-D-Galp-(1→, →6)-α-D-Galp-(1 â†’ and →3,6)-α-D-Manp-(1 →. AOP70-1 (2.5, 5, 10 µM) significantly suppressed NO, IL-1ß, and TNF-α production in a concentration-dependent manner and inhibited the migration of BV2 microglia. AOP70-1 inhibited LPS-mediated activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), and nuclear factor kappa B (NF-κB). Moreover, AOP70-1 exerted neuroprotection on SH-SY5Y cells and primary neurons by reducing neuronal apoptosis (72 %, 44 %), alleviating ROS accumulation (63 %, 55 %), and improving mitochondrial membrane potential (63 %, 77 %). Overall, AOP70-1 is one of the major bioactive components in AO70 from A. oxyphylla, which has great potential in the prevention and treatment of neuroinflammation.

Genome-Wide Identification of the Pectate Lyase Gene Family in Potato and Expression Analysis under Salt Stress.

Pectin is a structural polysaccharide and a major component of plant cell walls. Pectate lyases are a class of enzymes that degrade demethylated pectin by cleaving the α-1,4-glycosidic bond, and they play an important role in plant growth and development. Currently, little is known about the PL gene family members and their involvement in salt stress in potato. In this study, we utilized bioinformatics to identify members of the potato pectate lyase gene family and analyzed their gene and amino acid sequence characteristics. The results showed that a total of 27 members of the pectate lyase gene family were identified in potato. Phylogenetic tree analysis revealed that these genes were divided into eight groups. Analysis of their promoters indicated that several members' promoter regions contained a significant number of hormone and stress response elements. Further, we found that several members responded positively to salt treatment under single salt and mixed salt stress. Since StPL18 exhibited a consistent expression pattern under both single and mixed salt stress conditions, its subcellular localization was determined. The results indicated that StPL18 is localized in the endoplasmic reticulum membrane. The results will establish a foundation for analyzing the functions of potato pectate lyase family members and their expression under salt stress.

Qiangxinyin formula protects against isoproterenol-induced cardiac hypertrophy.

Heart failure is a life-threatening cardiovascular disease and characterized by cardiac hypertrophy, inflammation and fibrosis. The traditional Chinese medicine formula Qiangxinyin (QXY) is effective for the treatment of heart failure while the underlying mechanism is not clear. This study aims to identify the active ingredients of QXY and explore its mechanisms protecting against cardiac hypertrophy. We found that QXY significantly protected against isoproterenol (ISO)-induced cardiac hypertrophy and dysfunction in zebrafish. Eight compounds, including benzoylmesaconine (BMA), atractylenolide I (ATL I), icariin (ICA), quercitrin (QUE), psoralen (PRN), kaempferol (KMP), ferulic acid (FA) and protocatechuic acid (PCA) were identified from QXY. PRN, KMP and icaritin (ICT), an active pharmaceutical ingredient of ICA, prevented ISO-induced cardiac hypertrophy and dysfunction in zebrafish. In H9c2 cardiomyocyte treated with ISO, QXY significantly blocked the calcium influx, reduced intracellular lipid peroxidative product MDA, stimulated ATP production and increased mitochondrial membrane potential. QXY also inhibited ISO-induced cardiomyocyte hypertrophy and cytoskeleton reorganization. Mechanistically, QXY enhanced the phosphorylation of Smad family member 2 (SMAD2) and myosin phosphatase target subunit-1 (MYPT1), and suppressed the phosphorylation of myosin light chain (MLC). In conclusion, PRN, KMP and ICA are the main active ingredients of QXY that protect against ISO-induced cardiac hypertrophy and dysfunction largely via the blockage of calcium influx and inhibition of mitochondrial dysfunction as well as cytoskeleton reorganization.

Analysis of the multi-media environmental behavior of polycyclic aromatic hydrocarbons (PAHs) within Haizhou Bay using a fugacity model.

In this study, we aimed to quantify the transport and fate of PAHs in different environmental phases (air, seawater, soil, sediment and fish), verify application of the Level III fugacity model in a bay simulation, and understand the transport and fate of PAHs in the bay environment on a macroscopic scale. The simulated average concentrations of ∑16PAH in the air and soil (23.8 ng/m3 and 1080.91 ng/g, respectively), which is as a background reference data for the Haizhou Bay. In addition, the soil (307 t), fish (29.4 t), and sediment (9.72 t) phases were found to be important reservoirs in the Haizhou Bay. Emissions from road vehicles (658 t) accounted for the largest share of PAH emissions in the area, and atmospheric deposition contributed most to the input of PAHs to the polluted area in the region. Whereas the contribution of river runoff input was small, and degradation loss was the main output pathway.

Effects of Aerobic Exercise Combined with Oyster Peptide Supplement on the Formation of CTX-induced Late-Onset Hypogonadism in Male Rats.

The purpose of this study is to investigate the effect of aerobic exercise (AE) training and/or oyster peptide (OP) supplementation on the formation of late-onset hypogonadism (LOH). AE training and/or OP supplement was performed during Cytoxan (CTX)-induced LOH formation in male SD rats for 6 consecutive weeks. Low dose of CTX could decrease mating times, the levels of luteinizing hormone (LH), total testosterone (TT), free testosterone (FT) in serum and TT, androgen receptor (AR), androgen binding protein (ABP), and glutathione peroxidase (GSH-Px) in testicle, but increase capture latency, mating latency, and malondialdehyde, and downregulate the mRNA expression of steroidogenic acute regulatory (StAR), P450 cholesterol side chain cleavage enzyme (P450scc), and StAR-related lipid transfer domain 7 (StARD7) in testicle. Every change was altered by AE training combined with OP supplement significantly, except for serum LH. Moreover, the effect of AE training combined with OP supplement was better than that of AE training on serum TT, FSH, testicular TT, mating latency, capture times, and mating times. AE training combined with OP supplement during CTX-induced LOH formation can prevent the LOH development by enhancing pituitary-gonads axis's function and reducing testicular oxidative stress to promote testosterone synthesis and spermatogenesis.

Isolation, Characterization, and Antioxidant Activity of Melanin from Auricularia auricula (Agaricomycetes).

The cell wall of Auricularia auricula fruit bodies is extremely tough, making it difficult to dissolve the melanin using the traditional preparation method. To investigate the efficient preparation of melanin and its resistance to oxidative stress, this paper first used ultrasound-assisted alkaline cellulase to optimize the optimal wall-breaking parameters through a Box-Behnken design based on a single-factor experiment. After optimization, the yield of melanin from A. auricula reached 3.201 ± 0.018%. Then, different types and different proportions of deep eutectic solvents (DES) were used for further extraction. When choline chloride and urea were selected and the ratio was 1:2, the melanin yield was up to 25.99% ± 2.36%. Scanning electron microscope (SEM) images showed that the melanin was amorphous mass with no crystal structure. X-ray photoelectron spectroscopy (XPS) analysis revealed that the melanin was mainly composed of C (5.38%), O (15.69%) and N (30.29%), as was the typical composition of eumelanin. The melanin had a concentration-dependent relationship with both ABTS+ and hydroxyl radical scavenging ability; at the concentration of 0.5 mg/mL, it significantly prolonged Caenorhabditis elegans survival under hydrogen peroxide and methyl viologen stress and increased the glutathione level and enzyme (total superoxide dismutase and catalase) activities in vivo compared with the negative control (P < 0.05), indicating that the melanin enhances oxidative stress resistance in C. elegans.

Clinical outcomes and characteristics of patients with TP53-mutated myelodysplastic syndromes.

OBJECTIVE: To explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS). METHODS: A total of 74 de novo primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence in-situ hybridization. RESULTS: Patients were divided into two cohorts, the TP53-mutated type (TP53Mut) group (n = 19) and TP53 wild type (TP53WT) group (n = 55). Compared with the TP53WT group, patients in the TP53Mut group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, P < 0.001), with 5q- karyotype (64.70% vs. 38.5%, P < 0.001), complex karyotype(CK) (64.70% vs. 38.5%, P < 0.001), HR-MDS (94.7% vs. 61.8%, P = 0.008), and acute myelogenous leukemia (AML) transformation (26.3% vs. 12.7%, P < 0.001). Interestingly, patients in the TP53Mut group had lower median MCV than the TP53WT group (94.40 fl vs. 101.90 fl, P = 0.008). Furthermore, MCV = 100 fl as cutoff, and found that MCV ≤ 100 fl was more common in the TP53Mut group (73.7% vs. 38.2%, P < 0.001). After 1-4 courses of HMA ± chemotherapy, the overall response rate of the TP53Mut group was higher than the TP53WT group (83.3% vs. 71.4%, P = 0.012). With the median follow-up 12.0 months (1-46 months), the results show that the median OS and leukemia-free survival (LFS) of TP53Mut group was significantly shorter than the TP53WT group (P = 0.0018; P = 0.0310). Results of multivariate Cox proportional hazard analyses show TP53 mutation was an independent prognostic factor for the OS (HR 2.724, 95%CI 1.099-6.750, P = 0.030). CONCLUSION: TP53-mutated primary MDS patients were associated with higher frequency of cytogenetic abnormalities, with 5q- karyotype, CK, AML transformation, higher risk IPSS-R, lower MCV and sensitive to HMA treatment, but worse survival.

Sodium tanshinone IIA sulfonate protects against hyperhomocysteine-induced vascular endothelial injury via activation of NNMT/SIRT1-mediated NRF2/HO-1 and AKT/MAPKs signaling in human umbilical vascular endothelial cells.

Homocysteine (Hcy) is one of the independent risk factors of cardiovascular disease. Sodium tanshinone IIA sulfonate (STS) is a hydrophilic derivate of tanshinone IIA which is the main active constitute of Chinese Materia Medica Salviae Miltiorrhizae Radix et Rhizoma, and exhibits multiple pharmacological activities. However, whether STS could prevent from Hcy-induced endothelial cell injury is unknown. We found that STS dramatically reversed Hcy-induced cell death concentration dependently in human umbilical vascular endothelial cells (HUVECs). STS ameliorated the endothelial cell cycle progression, proliferation and cell migratory function impaired by Hcy, which might be co-related to the inhibition of intracellular oxidative stress and mitochondrial dysfunction. STS also elevated the phosphorylation of AKT and MAPKs and protein expression of sirtuin1 (SIRT1), NRF2 and HO-1 which were suppressed by Hcy. The protective effect of STS against Hcy-induced endothelial cell toxicity was partially attenuated by PI3K, AKT, MEK, ERK, SIRT1, NRF2 and HO-1 inhibitors. Besides, knockdown of SIRT1 by its siRNA dramatically decreased the endothelial protective effect of STS accompanied with suppression of SIRT1, NRF2, HO-1 and phosphorylated AKT. The activation of AKT or NRF2 partially reversed SIRT1-knockdown impaired cyto-protective effect of STS against Hcy-induced cell injury. Furthermore, STS prevented from Hcy-induced intracellular nicotinamide N-methyltransferase (NNMT) reduction along with elevation of intracellular methylnicotinamide (MNA), and MNA enhanced STS protecting against Hcy induced endothelial death. Knockdown of NNMT reduced the protective effect of STS against Hcy induced endothelial cell injury. Collectively, STS presented potent endothelial protective effect against Hcy and the underlying molecular mechanisms were involved in the suppression of intracellular oxidative stress and mitochondria dysfunction by activation of AKT/MAPKs, SIRT1/NRF2/HO-1 and NNMT/MNA signaling pathways.

circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer.

BACKGROUND: Circular RNAs (circRNAs) are associated with cisplatin resistance in gastric cancer (GC). This study aims to explore the role of circRNA AKT serine/threonine kinase 3 (circ_AKT3) in the resistance of GC to cisplatin. METHODS: 42 sensitive and 23 resistant GC patients were recruited for tissue collection. The cisplatin-resistant GC cells MKN-7/DDP and HGC-27/DDP were used for in vitro study. circ_AKT3, microRNA-206 (miR-206) and protein tyrosine phosphatase non-receptor type 14 (PTPN14) levels were detected via quantitative reverse transcription real-time PCR (qPCR) and Western blot. Cisplatin resistance was assessed by detecting P-glycoprotein (P-gp) level, half maximal inhibitory concentration (IC50) of cisplatin and cell apoptosis. The target relationship between miR-206 and circ_AKT3 or PTPN14 was analyzed via dual-luciferase reporter and RNA pull-down assays. The role of circ_AKT3 in vivo was assessed using xenograft model. RESULTS: circ_AKT3 level was increased, but miR-206 was declined in cisplatin-resistant GC tissues and cells. circ_AKT3 knockdown or miR-206 overexpression decreased the level of P-gp and IC50 of cisplatin and increased apoptosis of MKN-7/DDP and HGC-27/DDP cells. Additionally, circ_AKT3 targeted miR-206, and regulated cisplatin resistance by interacting with miR-206. PTPN14 was regulated by circ_AKT3 through miR-206 as a bridge. Also, circ_AKT3 knockdown decreased xenograft tumor growth. CONCLUSION: circ_AKT3 knockdown suppressed cisplatin resistance using miR-206/PTPN14 axis in cisplatin-resistant GC cells.

Polycyclic aromatic hydrocarbons in seawater, surface sediment, and marine organisms of Haizhou Bay in Yellow Sea, China: Distribution, source apportionment, and health risk assessment.

The pollution status of polycyclic aromatic hydrocarbons (PAHs) in seawater, surface sediment, and marine organisms was investigated in Haizhou Bay, which is a traditional marine fish farming region in China. The total concentrations of PAHs in seawater, surface sediment, and marine organisms were 12.4-40.3 ng/L (average 24.8 ng/L), 183.2-496.6 ng/g (average 293.5 ng/g), and 228.1-679.9 ng/g (average 392.6 ng/g), respectively. Source analysis results showed that the PAH sources for seawater and marine organisms were coal and biomass combustion (66.53%), petroleum (28.94%), and traffic (4.52%), while those for the surface sediment were traffic (48.14%), coal and biomass combustion (40.56%). The lifetime cancer risk increment (ILCR) values of marine organisms in the Haizhou Bay were less than 10-6, indicating no carcinogenic risk. In the future, this study can be used as a reference to understand the distribution and interrelation of PAHs in other semi-enclosed bays in the world.

Tribulus terrestris L. extract ameliorates atherosclerosis by inhibition of vascular smooth muscle cell proliferation in ApoE-/- mice and A7r5 cells via suppression of Akt/MEK/ERK signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS) is one of major threatens of death worldwide, and vascular smooth muscle cell (VSMC) proliferation is an important characteristic in the progression of AS. Tribulus terrestris L. is a well-known Chinese Materia Medica for treating skin pruritus, vertigo and cardiovascular diseases in traditional Chinese medicine. However, its anti-AS activity and inhibition effect on VSMC proliferation are not fully elucidated. AIMS: We hypothesize that the furostanol saponins enriched extract (FSEE) of T. terrestris L. presents anti-AS effect by inhibition of VSMC proliferation. The molecular action mechanism underlying the anti-VSMC proliferation effect of FSEE is also investigated. MATERIALS AND METHODS: Apolipoprotein-E deficient (ApoE-/-) mice and rat thoracic smooth muscle cell A7r5 were employed as the in vivo and in vitro models respectively to evaluate the anti- AS and VSMC proliferation effects of FSEE. In ApoE-/- mice, the amounts of total cholesterol, triglyceride, low density lipoprotein and high density lipoprotein in serum were measured by commercially available kits. The size of atherosclerotic plaque was observed by hematoxylin & eosin staining. The protein expressions of α-smooth muscle actin (α-SMA) and osteopontin (OPN) in the plaque were examined by immunohistochemistry. In A7r5 cells, the cell viability and proliferation were tested by MTT and Real Time Cell Analysis assays. The cell migration was evaluated by wound healing assay. Propidium iodide staining followed by flow cytometry was used to analyze the cell cycle progression. The expression of intracellular total and phosphorylated proteins including protein kinase B (Akt) and mitogen-activated protein kinases (MAPKs), such as mitogen-activated extracellular signal-regulated kinase (MEK), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), were detected by western blotting analysis. RESULTS: FSEE significantly reduced the area of atherosclerotic plaque in high-fat diet-fed ApoE-/- mice. And FSEE increased the protein expression level of α-SMA and decreased the level of OPN in atherosclerotic plaque, which revealed the inhibition of VSMC phenotype switching and proliferation. In A7r5 cells, FSEE suppressed fetal bovine serum (FBS) or oxidized low density lipoprotein (oxLDL)-triggered VSMC proliferation and migration in a concentration dependent manner. FSEE protected against the elevation of cell numbers in S phase induced by FBS or oxLDL and the reduction of cell numbers in G0/G1 phase induced by oxLDL. Moreover, the phosphorylation of Akt and MAPKs including MEK, ERK and JNK could be facilitated by FBS or oxLDL, while co-treatment of FSEE attenuated the phosphorylation of Akt induced by oxLDL as well as the phosphorylation of MEK and ERK induced by FBS. In addition, (25R)-terrestrinin B (JL-6), which was the main ingredient of FSEE, and its potential active pharmaceutical ingredients tigogenin (Tigo) and hecogenin (Heco) also significantly attenuated FBS or oxLDL-induced VSMC proliferation in A7r5 cells. CONCLUSION: FSEE presents potent anti- AS and VSMC proliferation activities and the underlying mechanism is likely to the suppression of Akt/MEK/ERK signaling. The active components of FSEE are JL-6 and its potential active pharmaceutical ingredients Tigo and Heco. So, FSEE and its active compounds may be potential therapeutic drug candidates for AS.

Pollution status of polycyclic aromatic hydrocarbons in surface sediments off the Jiangsu coastal zone, East China: A case study of Rudong.

In the current study, 16 congeners of PAHs were measured in 32 surface sediment samples to determine their pollution status in the Jiangsu coastal zone, East China. The total concentrations of the 16 PAHs ranged from 2.2 to 46.6 ng g-1 with an average of 8.36 ng g-1 in surface sediments and were significantly lower than those of PAHs in other coastal areas of China. The spatial distribution of PAHs revealed an increasing trend from nearshore to offshore, controlled by the regional sedimentary dynamic environment. Diagnostic ratios and positive matrix factorization demonstrated that petroleum, industries, biomass and coal combustion, and marine and vehicular traffic sources contributed to 28.9%, 25.5%, 24.7%, and 20.9% of the total PAHs, respectively. Risk assessment suggested that the carcinogenic risks were <1 × 10-4 for all age groups in the area, indicating that long-term seafood consumption does not pose a significant cancer risk in this area.

Comparative study between two bleeding grading systems of immune thrombocytopenia purpura.

OBJECTIVE: To explore the relationship between platelet count and bleeding score in immune thrombocytopenia purpura (ITP) and compare the clinical practicability of two bleeding grading systems with adult patients with ITP. METHODS: A total of 204 patients were retrospectively analyzed with the ITP bleeding scale (IBLS) and the ITP bleeding assessment tool (version 2016) (ITP-2016). The correlation between the two bleeding score systems and the relations among the platelet counts were respectively analyzed. RESULTS: (1) There is a linear relationship between platelet count and bleeding score, no matter which scoring system it is based on (rs = -0.429, p < 0.001; rs = -0.331, p < 0.001, the analysis of the number of sites of Grade 1/2 bleeding were done; and rs = -0.466, p < 0.05, the analysis between platelet count and bleeding score by ITP-2016 respectively). (2) Platelet count and bleeding scores are negatively correlated in those with extremely low platelet counts ( < 10*109/L). The number of sites of Grade 2 bleeding and the ITP-2016 scores are negatively correlated with platelet counts (rs = -0.15 and rs = -0.244, p < 0.05, respectively). Significantly, there is no correlation between the platelet count and bleeding scores when the platelet count is more than 10*109/L. (3) It takes less time to score with ITP-2016 than IBLS (z = -3.825, P < 0.001). CONCLUSIONS: There is good responsiveness, strong assessment consistency, close correlation between ITP-2016 and IBLS. ITP-2016 takes less time-consuming in clinical application. It can be used as an effective tool of condition judgement, risk assessment and efficacy evaluation of patients with ITP.

Similarities and Differences: A Comparative Review of the Molecular Mechanisms and Effectors of NAFLD and AFLD.

Non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are the most prevalent metabolic liver diseases globally. Due to the complex pathogenic mechanisms of NAFLD and AFLD, no specific drugs were approved at present. Lipid accumulation, oxidative stress, insulin resistance, inflammation, and dietary habits are all closely related to the pathogenesis of NAFLD and AFLD. However, the mechanism that promotes disease progression has not been fully elucidated. Meanwhile, the gut microbiota and their metabolites also play an important role in the pathogenesis and development of NAFLD and AFLD. This article comparatively reviewed the shared and specific signaling pathways, clinical trials, and potential intervention effectors of NAFLD and AFLD, revealing their similarities and differences. By comparing the shared and specific molecular regulatory mechanisms, this paper provides mutual reference strategies for preventing and treating NAFLD, AFLD, and related metabolic diseases. Furthermore, it provides enlightenment for discovering novel therapies of safe and effective drugs targeting the metabolic liver disease.