No-reflow after recanalization in ischemic stroke: From pathomechanisms to therapeutic strategies.

Endovascular reperfusion therapy is the primary strategy for acute ischemic stroke. No-reflow is a common phenomenon, which is defined as the failure of microcirculatory reperfusion despite clot removal by thrombolysis or mechanical embolization. It has been reported that up to 25% of ischemic strokes suffer from no-reflow, which strongly contributes to an increased risk of poor clinical outcomes. No-reflow is associated with functional and structural alterations of cerebrovascular microcirculation, and the injury to the microcirculation seriously hinders the neural functional recovery following macrovascular reperfusion. Accumulated evidence indicates that pathology of no-reflow is linked to adhesion, aggregation, and rolling of blood components along the endothelium, capillary stagnation with neutrophils, astrocytes end-feet, and endothelial cell edema, pericyte contraction, and vasoconstriction. Prevention or treatment strategies aim to alleviate or reverse these pathological changes, including targeted therapies such as cilostazol, adhesion molecule blocking antibodies, peroxisome proliferator-activated receptors (PPARs) activator, adenosine, pericyte regulators, as well as adjunctive therapies, such as extracorporeal counterpulsation, ischemic preconditioning, and alternative or complementary therapies. Herein, we provide an overview of pathomechanisms, predictive factors, diagnosis, and intervention strategies for no-reflow, and attempt to convey a new perspective on the clinical management of no-reflow post-ischemic stroke.

The Potential of Berberine to Target Telocytes in Rabbit Heart.

A brand-new class of interstitial cells, called telocytes, has been detected in the heart. Telocytes can connect and transmit signals to almost all cardiomyocytes; this is highly interrelated with the occurrence and development of heart diseases. Modern studies have shown that berberine has a therapeutic effect on cardiovascular health. However, berberine's mechanism of action on the cardiovascular system through cardiac telocytes is unclear. Interestingly, 5 µm of berberine remarkably decreased the concentration of intracellular calcium and membrane depolarization in cultured telocytes, upregulated the expression of CX43 and ß-catenin, and downregulated the expressions of TRPV4 and TRPV1. Here, telocytes were identified in the vascular adventitia and intima, endocardium, myocardium, adventitia, and heart valves. Moreover, telocytes were broadly dispersed around cardiac vessels and interacted directly through gap junctions and indirectly through extracellular vesicles. Together, cardiac telocytes interact with berberine and then deliver drug information to the heart. Telocytes may be an essential cellular target for drug therapy of the cardiovascular system.

Nanoplasmonic biosensors for multicolor visual analysis of acetylcholinesterase activity and drug inhibitor screening in point-of-care testing.

The monitoring of acetylcholinesterase (AChE) activity and the screening of its inhibitors are significance of the diagnosis and drug therapy of nervous diseases. A metal ions-mediated signal amplification strategy was developed for the highly sensitive and multicolor assay of AChE activity and visually screening its drug inhibitors. After the specific reaction between AChE and acetylthiocholine (ATCh), the hydrolysis product thiocholine (TCh) can directly and decompose the α-FeOOH nanorods (NRs) to release amounts of Fe2+, which was regarded as Fenton reagent to efficiently catalyze H2O2 to produce ·OH. Then, the as-formed ·OH can further largely shorten the gold nanobipyramids (Au NBPs), generating a series of palpable color variations. The linear range for AChE activity was 0.01-500.0 U/L with the limit of detection as low as 0.0074 U/L. The vivid visual effects could be easily distinguished for the multicolor assay of AChE activity by naked eye in visible light. To achieve the point-of-care testing, Au NBPs were further assembled on polymeric electrospun nanofibrous films (ENFs) surface as test strips for the easy-to-use test of AChE activity by RGB values with a smartphone. Fascinatingly, this proposed strategy can be used for the visual screening AChE inhibitors or non-inhibitors. Comparing with the clinical drugs (rivastigmine tartrate, and donepezil), some natural alkaloids such as evodiamine, caffeine, camptothecin, and berberine hydrochloride were selected as inhibitor modes to confirm the drug screening capability of this method. This proposed strategy may have great potential in the other disease-related enzymatic biomarkers assay and the rapid screening of drug therapy.

Naotaifang III Protects Against Cerebral Ischemia Injury Through LPS/TLR4 Signaling Pathway in the Microbiota-Gut-Brain Axis.

Background: Ischemic stroke (IS) is a leading cause of mortality worldwide. Naotaifang III is a new Chinese herbal formula to treat IS. Previous studies have shown that Astragali Radix, Puerariae Lobatae Radix, Chuanxiong Rhizoma, and Rhei Radix Et Rhizoma in Naotaifang III were able to regulate the imbalance of intestinal microbiota during cerebral ischemia injury. Methods: Rats were randomly divided into sham operation group, normal control group, middle cerebral artery occlusion (MCAO) group, intestinal microbiota imbalance MCAO group, Naotaifang III group, and normal bacteria transplantation group, with 15 rats in each group. Then, neurological function scores and cerebral infarction volume were detected; haematoxylin and eosin staining and Golgi silver staining were used to observe morphological changes in brain tissue. Meanwhile, the lipopolysaccharide (LPS) and cerebral cortex interleukin (IL)-1ß were detected by enzyme-linked immunosorbent assay (ELISA); the expressions of Toll-like receptor (TLR)-4 and nuclear factor kappa-B (NF-κB) proteins were detected by immunofluorescence and Western blot. The cecal flora was detected by 16S rDNA. The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1ß, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis. In summary, Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis. Results: The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1ß, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis. Conclusion: Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis.

Relationship between the circulating N-terminal pro B-type natriuretic peptide and the risk of carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a CSCD-TCM plus study in China.

OBJECTIVE: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a marker for heart failure in patients with coronary heart disease (CHD) and associated with glycemic abnormalities. Studies on the association and diagnostic value of NT-proBNP in carotid plaques (CAP) in patients with CHD are limited. METHODS: The relationships between NT-proBNP and the risk of CAP in different glucose metabolic states, sexes, and age categories were also examined using 5,093 patients diagnosed with CHD. The NT-proBNP tertiles were used to divide patients into three groups in which the NT-proBNP levels, blood glucose levels, the occurrence of CAP, and the number and nature of CAP were measured using normoglycemic (NG), prediabetes (Pre-DM), and diabetes mellitus (DM) glucose metabolic statuses. Logistic regression analyses were used to compare the relationship between NT-proBNP and the risk of CAP occurrence and the number and nature of CAP. The diagnostic value of NT-proBNP for CAP risk was measured using receiver operating characteristic (ROC) curves. RESULTS: We found a 37% relative increase in the correlation between changes in NT-proBNP per standard deviation (SD) and the incidence of CAP. After adjusting for potential confounders, NT-proBNP at the T3 level was found to be associated with an increased CAP odds ratio (OR) when T1 was used as the reference. This relationship was also present in males, patients aged > 60 years, or both pre-DM and DM states. NT-proBNP was more likely to present as hypoechoic plaques at T1 and as mixed plaques at T3. We also measured the diagnostic accuracy of CAP for NT-proBNP in patients with CHD, with an AUC value of 0.627(95% CI 0.592-0.631), sensitivity of 50.7%, and specificity of 68.0%. CONCLUSION: An increase in NT-proBNP was significantly associated with the risk of CAP in patients with CHD, especially in males and patients aged > 60 years, and exhibited specific characteristics under different glucose metabolism states. Trial registration The study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Approval number TJUTCM-EC20210007) and certified by the Chinese Clinical Trials Registry on April 4, 2022 (Registration number ChiCTR2200058296) and March 25, 2022 by ClinicalTrials.gov (registration number NCT05309343).

Chemoproteomics reveals Sofalcone inhibits the inflammatory response of Caco-2 cells by covalently targeting HMGB1.

Sofalcone (Sof), a synthetic analog of sophoradin, is a type of natural phenol derived from the traditional medicinal herb Sophora subprostrata, with potent anti-inflammatory activity. However, the mechanisms of action of Sof for treating intestinal-associated inflammation are not well known. In this work, we identified high mobility group box 1 (HMGB1) as the key covalent target of Sof for the anti-inflammatory activity in the human colonic epithelial cells through quantitative chemoproteomics profiling.

Research on the evolution law of hot spots in the field of coal seam hydraulic fracturing based on bibliometric analysis: review from a new scientific perspective.

As an unconventional natural gas, the calorific value of coal seam gas (CSG) is equivalent to that of natural gas. It is a high-quality, clean, and efficient green low-carbon energy source. Coal seam hydraulic fracturing is an important permeability enhancement measure in the process of CSG drainage. In order to further understand the overall research progress in the field of coal seam hydraulic fracturing, the Web of Science (WOS) database is used as a sample source, and the bibliometric analysis of the literature is carried out by CiteSpace software. The visual knowledge maps of the number of publications, the research countries, institutions, and keyword clustering are drawn. The research shows that it has gone through two stages of slow development and rapid growth in terms of time distribution. In terms of cooperation networks, the main active countries include China, the USA, Australia, Russia, and Canada, composed of China University of Mining and Technology, Chongqing University, Henan Polytechnic University, and China University of Petroleum as the core research institutions. Taking keywords as the theme, the coal seam hydraulic fracturing research field mainly involves high-frequency keywords such as hydraulic fracturing, permeability, model, and numerical simulation. The hotspot evolution law and frontier development trend of keywords with time are analyzed and obtained. On this basis, from a new perspective, the "scientific research landscape map" in the field of coal seam hydraulic fracturing is outlined, in order to provide a scientific reference for the research in this field.

Methodological and reporting quality evaluation of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury: a systematic review.

Buyang Huanwu decoction, a classic traditional Chinese prescription, has been used to prevent and treat stroke for hundreds of years. An increasing number of the laboratory research on Buyang Huanwu decoction used in treating cerebral ischemia-reperfusion injury have been published recently. However, the problem of methodological and reporting quality of some studies is lack of assessment. This study aims to evaluate the methodological and reporting quality of the research on Buyang Huanwu decoction against experimental cerebral ischemia-reperfusion injury. A comprehensive search on six databases was performed. Two researchers independently screened the literature considering the eligibility criteria. Methodological and reporting quality of the included studies were evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guideline. Forty-five studies met the inclusion criteria. No study achieved a decent overall rating in using the SYRCLE tool (percentage of items with "low risk" ≥ 50%). Of the 22 items on the SYRCLE tool, only 7 items (31.82%) were rated as "low risk" in more than 50% of the included studies. Of the 39 items of ARRIVE guideline, 14 (35.9%) items were rated as "yes" in more than 50% of the included studies. The methodological and reporting quality of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury was substandard, which needed to be further improved. The limitations should be addressed when planning similar studies in the future. Additionally, these findings provided evidence-based guidance for future preclinical studies evaluating the efficacy of Buyang Huanwu decoction in the treatment of cerebral ischemia-reperfusion injury.

Therapeutic potential of plant iridoids in depression: a review.

CONTEXT: Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. OBJECTIVE: The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication. METHODS: The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with in vivo or in vitro experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plant-derived iridoids for depression. RESULTS: Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression. DISCUSSION AND CONCLUSIONS: Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.

[Relative molecular mass distribution and monosaccharide composition of polysaccharides in Polygonatum kingianum var.grandifolium].

Polygonatum kingianum var.grandifolium, different from most Polygonatum species in biological characteristics, sprouts and blooms in spring and autumn, respectively, and it is evergreen in winter.It is difficult to learn from the patterns of other Polygonatum plants because the chemical composition in P.kingianum var.grandifolium changes with phenology, which consequently restricts the production of high-quality medicinal and eatable substances.Samples of P.kingianum var.grandifolium in different months and ages collected from Xiushan, Chongqing were analyzed for polysaccharide content, polysaccharide relative molecular mass, and mono-saccharide composition by anthrone-sulfuric acid colorimetric assay, high-performance gel-permeation chromatography, and trimethylsilane(TMS) derivatization prior to GC-MS.The results showed that the polysaccharide content and composition in the rhizome of P.kingianum var.grandifolium were closely related to the growth period.New shoot sprouting promoted the accumulation of polysaccharides, and flowering and fruiting consumed polysaccharides.The highest polysaccharide content was found in April, reaching 134.04 mg·g~(-1).Polysaccharides in P.kingianum var.grandifolium were divided into five fractions according to the weight-average M_W, i.e., P1(2.02×10~7), P2(5.09×10~6), P3(1.37×10~6), P4(4.73×10~5), and P5(5.11×10~3), and P5 had the highest content.In terms of monosaccharide composition, polysaccharides were mainly composed of fructose, glucose, galactose, mannose, xylose, and arabinose with the average molar ratio of 1.31∶1.00∶0.90∶0.53∶0.22∶0.21.The results of the study provide a scientific basis for the precise harvesting and resource utilization of P.kingianum var.grandifolium.

[Polygonati Rhizoma: a crop with potential of being consumed as food and medicine].

As revealed by the investigation on the name change, biological characteristics, artificial cultivation, and edible history of Polygonatum kingianum var. grandifolium, it was described as a variation pattern of P. kingianum in the Chinese version of Flora of China(1978) and as a variant of P. kingianum in the revised English version of the Flora of China(2000). P. kingianum var. grandifolium, long been consumed as food by local folks, has been widely cultivated in its natural distribution area and circulated as Polygonati Rhizoma in the market. The important biological properties of P. kingianum var. grandifolium make it possess a great potential of being consumed as both medicine and food. The shoots of P. kingianum var. grandifolium sprout immediately out of the ground after seed germination and a new seedling will be formed at the same year, implying that its seedling cultivation period is at least two years shorter than that of P. cyrtonema. It can sprout more than twice a year, and the adult plants always remain evergreen, thereby obtaining higher biomass. Its rhizome biomass can be more than one time higher than that of P. cyrtonema. With reference to the diploid P. cyrtonema, flow cytometry revealed the polyploid and aneuploid forms in natural populations, which were tall and light-adapted with large underground rhizome. It can grow normally under the forest canopy and in the open field. Furthermore, P. kingianum var. grandifolium has important theoretical values for the study of ploidy variation, bud dormancy mechanism, etc.

An Integrated Analysis of Network Pharmacology and Experimental Validation to Reveal the Mechanism of Chinese Medicine Formula Naotaifang in Treating Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a crucial factor leading to a poor prognosis for ischemic stroke patients. As a novel Chinese medicine formula, Naotaifang (NTF) was proven to exhibit a neuroprotective effect against ischemic stroke, clinically, and to alleviate CIRI in animals. However, the mechanisms underlying the beneficial effect have not been fully elucidated. METHODS: In this study, we combined a network pharmacology approach and an in vivo experiment to explore the specific effects and underlying mechanisms of NTF in the treatment of ischemia-reperfusion injury. A research strategy based on network pharmacology, combining target prediction, network construction, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking was used to predict the targets of NTF in treating the ischemic stroke and CIRI. On the other hand, we used HPLC and HRMS to identify biologically active components of NTF. Middle cerebral artery occlusion models in rats were utilized to evaluate the effect and the underlying mechanisms of NTF against CIRI after ischemic stroke. RESULTS: Network pharmacology analysis revealed 43 potential targets and 14 signaling pathways for the treatment of NTF against CIRI after ischemic stroke. Functional enrichment analysis showed that a STAT3/PI3K/AKT signaling pathway serves as the target for in vivo experimental study validation. The results of animal experiments showed that NTF significantly alleviated CIRI by decreasing neurological score, infarct volume, numbers of apoptotic neuronal cells, increasing density of dendritic spines and survival of neurons. Furthermore, NTF could increase the expression of p-STAT3, PI3K, p-AKT. In addition, the detection of apoptosis-related factors showed that the NTF could raise the expression of Bcl-2 and reduce the expression of Bax. CONCLUSION: This network pharmacological and experimental study indicated that NTF, as a therapeutic candidate for the management of CIRI following ischemic stroke, may exert a protective effect through the STAT3/PI3K/AKT signaling pathway.

Effect of High-Fat Diet on the Intestinal Flora in Letrozole-Induced Polycystic Ovary Syndrome Rats.

AIM: The aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with intestinal flora dysbiosis in a rat model. We compared the changes in the intestinal flora of letrozole-induced rats fed with HFD or normal chow, to explore the effects of HFD and letrozole independently and synergistically on the intestinal flora. METHODS: Five-week-old female Sprague Dawley (SD) rats were divided into four groups: control (C) group fed with regular diet; L1 group administered with letrozole and fed with regular diet; L2 group received letrozole and fed with HFD; and HFD group fed with HFD. At the end of the experiment, ovarian morphology, hormones, metabolism, oxidative stress, and inflammatory status of all rats were studied. 16S rDNA high-throughput sequencing was used to profile microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. RESULTS: Compared to the C group, the increased plasma fasting insulin and glucose, HOMA-IR, triglyceride, testosterone, and malondialdehyde were significantly higher in the L2 group, while high-density lipoprotein cholesterol was significantly lower in the L1 group and L2 group. The indices of Chao1 and the Abundance-based Coverage Estimator (ACE) (α-diversity) in the L2 and HFD groups were significantly lower than that in the C group. Bray-Curtis dissimilarity based principal coordinate analysis (PCoA) plots and analysis of similarities (ANOSIM) test showed obvious separations between the L2 group and C group, between the HFD group and C group, and between the L2 and HFD groups. At the phylum level, Firmicutes and ratio of Firmicutes and Bacteroidetes (F/B ratio) were increased in the L2 group; Bacteroidetes was decreased in the L2 and HFD groups. No significant differences in bacterial abundance between the C group and L1 group were observed at the phylum level. Based on linear discriminant analysis (LDA) effect size (LEfSe) analysis, the bacterial genera (the relative abundance > 0.1%, LDA > 3, p < 0.05) were selected as candidate bacterial signatures. They showed that the abundance of Vibrio was significantly increased in the L1 group; Bacteroides and Phascolarctobacterium were enriched in the HFD group, and Bacteroides, Phascolarctobacterium, Blautia, Parabacteroides, Akkermansia [Ruminococcus]_torques_group, and Anaerotruncus were enriched in the L2 group. CONCLUSION: The effect of letrozole on intestinal flora was not significant as HFD. HFD could destroy the balance of intestinal flora and aggravate the intestinal flora dysbiosis in PCOS. Letrozole-induced rats fed with HFD have many characteristics like human PCOS, including some metabolic disorders and intestinal flora dysbiosis. The dysbiosis was characterized by an increased Firmicutes/Bacteroidetes ratio, an expansion of Firmicutes, a contraction of Bacteroidetes, and the decreased microbial richness. Beta-diversity also showed significant differences in intestinal microflora, compared with control rats.

The effect of vitamin D on the occurrence and development of colorectal cancer: a systematic review and meta-analysis.

PURPOSE: There has been a lot of controversies about the correlation between vitamin D and colorectal cancer (CRC). In this meta-analysis, we purposed to explore the relationship between vitamin D and the incidence of CRC/the prognosis of CRC. METHODS: A systematic search for articles in databases (Pubmed, Web of Science, EBSCO and Cochrane Library) was terminated in April 2020. The primary outcomes were the incidence rate of CRC and the long-term survival of patients with CRC. RESULTS: According to the estimated pooled OR from 21 eligible studies, covering 904,152 people, the use of vitamin D was inversely associated with the incidence of CRC [OR = 0.87, (0.82-0.92)]. Among the four studies included in this meta-analysis, covering 7486 patients, compared the overall survival (OS) of CRC between the vitamin D users and the non-users. Based on the estimated pooled HR, vitamin D potentially improved the long-term survival of CRC patients [HR = 0.91, (0.83-0.98)]. CONCLUSION: This meta-analysis demonstrates that vitamin D not only has a positive impact on the incidence of CRC from either the dietary or supplemental sources but also benefits clinical outcomes and improves the long-term survival of CRC patients. However, further studies are recommended to clarify the above phenomena.

Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial.

BACKGROUND: Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial. OBJECTIVE: To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. METHODS: This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months. RESULTS: Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p < 0.001). Leukocyte TL was significantly higher, while serum 8-OXO-dG, OGG1mRNA, and P16INK4amRNA revealed greater decreases in the vitamin D group over the placebo group (p < 0.001). According to mixed-model repeated-measures ANOVA analysis, vitamin D group showed a significant enhancement in the FSIQ score for 12 months compared with the control (estimate value = 5.132, p < 0.001). CONCLUSION: Vitamin D supplementation for 12 months appears to improve cognitive function through reducing oxidative stress regulated by increased TL in order adults with MCI. Vitamin D may be a promising public health strategy to prevent cognitive decline.

Mussel-inspired "built-up" surface chemistry for combining nitric oxide catalytic and vascular cell selective properties.

Specific selectivity of vascular cells and antithrombogenicity are crucial factors for the long-term success of vascular implants. In this work, a novel concept of mussel-inspired "built-up" surface chemistry realized by sequential stacking of a copper-dopamine network basement, followed by a polydopamine layer is introduced to facilitate the combination of nitric oxide (NO) catalysis and vascular cell selectivity. The resultant "built-up" film allowed easy manipulation of the content of copper ions and the density of catechol/quinone groups, facilitating the multifunctional surface engineering of vascular devices. For example, the chelated copper ions in the copper-dopamine network endow a functionalized vascular stent with a durable release of NO via catalytic decomposition of endogenous S-nitrosothiol. Meanwhile, the catechol/quinone groups on the film surface allow the facile, secondary grafting of the REDV peptide to develop a selectivity for vascular cells, as a supplement to the functions of NO. As a result, the functionalized vascular stent perfectly combines the functions of NO and REDV, showing excellent antithrombotic properties and competitive selectivity toward the endothelial cells over the smooth muscle cells, hence impressively promotes re-endothelialization and improves anti-restenosis in vivo. Therefore, the first mussel-inspired "built-up" surface chemistry can be a promising candidate for the engineering of multifunctional surfaces.

Strengthened thalamoparietal functional connectivity in patients with hemifacial spasm: a cross-sectional resting-state fMRI study.

OBJECTIVE: In spite of the well-known importance of thalamus in hemifacial spasm (HFS), the thalamic resting-state networks in HFS is still rarely mentioned. This study aimed to investigate resting-state functional connectivity (FC) of the thalamus in HFS patients and examine its association with clinical measures. METHODS: 25 HFS patients and 28 matched healthy controls underwent functional MRI at rest. Using the left and right thalamus as seed regions respectively, we compared the thalamic resting-state networks between patient and control groups using two independent sample t-test. RESULTS: Compared with controls, HFS patients exhibited strengthened bilateral thalamus-seeded FC with the parietal cortex. Enhanced FC between right thalamus and left somatosensory association cortex was linked to worse motor disturbance, and the increased right thalamus-right supramarginal gyrus connection were correlated with improvement of affective symptoms. CONCLUSION: Our findings indicate that the right thalamus-left somatosensory association cortex hyperconnectivity may represent the underlying neuroplasticity related to sensorimotor dysfunction. In addition, the upregulated FC between the right thalamus and right supramarginal gyrus in HFS, is part of the thalamo-default mode network pathway involved in emotional adaptation. ADVANCES IN KNOWLEDGE: This study provides new insights on the integrative role of thalamo-parietal connectivity, which participates in differential neural circuitry as a mechanism underlying motor and emotional functions in HFS patients.

Chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species.

The chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species were studied. The contents of total phenolic and 10 phenolic compounds were highest in Juniperus rigida Sieb.et Zucc., of which catechin and cumaric acid were the predominant phenolic compounds, but were lowest in Juniperus sibirica Burgsd. GC-MS analysis showed the highest contents of essential oils were in J. rigida (92.61%), followed by Juniperus formosana Hayata (87.30%) and J. sibirica (84.89%). The a-pinene was the most dominant compound in J. rigida (23.99%) and J. formosana (9.71%), however, it has not been detected in J. sibirica. Ethanol extracts showed the higher radical scavenging capacity in ABTS, FRAP and DPPH assays than essential oils. The essential oils and ethanol extracts of J.sibirica showed the strong antibacterial activity against Salmonella typhimurium and Escherichia coli. Three Juniperus species showed certain acetylcholinesterase and butyrylcholinesterase inhibitions and J. formosana showed better cholinesterase inhibitory.

Termipaniculatones A-F, chalcone-flavonone heterodimers from Terminthia paniculata, and their protective effects on hyperuricemia and acute gouty arthritis.

Terminthia paniculata (Sanyeqi) is widely used for treating inflammation and rheumatic arthritis in the folk areas of Yunnan province, China. Its total extract was first revealed with xanthine oxidase (XO) inhibitory activity in vitro and anti-hyperuricemic effect in vivo. Bioassay-guided separation on Fr. A5 yielded six chalcone-flavonone heterodimers, termipaniculatones A-F. Their structures were elucidated based on extensive spectroscopic analyses involving HRESIMS, 1D and 2D NMR, UV, IR and [α]D, and the absolute configuration of termipaniculatone F was verified by ECD calculation. Termipaniculatones A and E showed obvious XO inhibitory activity with IC50 values of 55.6 and 89.5 µM, respectively, which took effects via a mix-type mode. A molecular modeling study revealed that termipaniculatone A was well located into the active site of XO by interacting with Glu802, Arg880, Thr1010 and Val1011 residues. Termipaniculatone A showed anti-hyperuricemic effects by decreasing serum uric acid levels and inhibiting XO activity in both serum and liver on potassium oxonate (PO)-induced hyperuricemia mice, and anti-inflammatory activity through alleviating paw swelling on monosodium urate (MSU)-induced mice, at the concentration of 20 mg/kg. This is the first time to reveal the anti-hyperuricemic and anti-acute gouty arthritis potency of T. paniculata and the characteristic biflavonoids as active constituents, which provides valuable information for searching new XO inhibitors from natural sources.