Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway.

Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1ß. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.

Effect of electroacupuncture intervention on the spinal cord PPIA/NF-κB signaling pathway in mice with amyotrophic lateral sclerosis. / ç”µé’ˆå¯¹è‚ŒèŽç¼©ä¾§ç´¢ç¡¬åŒ–ç—‡å°é¼ è„Šé«“PPIA/NF-κB信号通路的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on motor function, expression of extracellular cyclophile A(PPIA) and PPIA/nuclear factor-κB (NF-κB) signaling pathway in spinal cord of amyotrophic la-teral sclerosis (ALS) mice, so as to explore the mechanism of EA intervention in regulating extracellular PPIA on neuroinflammation in ALS mice. METHODS: Thirty ALS-SOD1G93A mice with hSOD1-G93A gene were randomly divided into model, EA and Riluzole groups , with 10 mice in each group, and other 10 ALS-SOD1G93A negative mice were used as the blank group. EA was applied to bilateral "Yanglingquan"(GB34) and "Zusanli"(ST36) for 20 min once daily, 5 days a week for 2 weeks. In the Riluzole group, riluzole solution (30 mg·kg-1·d-1) was administrated intragastrically, and the treatment time was the same as that in the EA group.Rotating rod experiment and open field experiment were used to evaluate the changes in motor function of mice .The morphology of motor neurons in the anterior horn of spinal cord was observed by HE staining.The relative protein expression levels of PPIA, TDP-43 and NF-κB in the spinal cord were detected by Western blot.The positive expression level of TDP-43 in the spinal cord was detected by immunohistochemistry. The positive expression level of PPIA in spinal cord was marked by immunofluorescence. Serum PPIA content was determined by ELISA. RESULTS: Compared with the blank group, the time of rod dropping and the total distance of open field movement in the model group were shortened (P<0.01), the number of motor neurons in the anterior horn of the spinal cord was reduced, the cell morphology was incomplete, the cell body was atrophied, the protein expression and positive expression of TDP-43 were increased (P<0.01), the protein expressions of PPIA and NF-κB in the spinal cord were increased(P<0.01), the serum content of PPIA and immunofluorescence expression of PPIA in spinal cord were increased (P<0.01). Compared with the model group, the time of rod dropping and the total distance of open field movement of mice in the EA group and the Riluzole group were prolonged (P<0.05, P<0.01), and the injury of motor neuron in the anterior horn of the spinal cord was decreased, the protein expression and positive expression of TDP-43 in the spinal cord were decreased (P<0.05, P<0.01)；the relative expression levels of PPIA and NF-κB proteins were decreased (P<0.05, P<0.01), and the content of PPIA in serum and the immunofluorescence expression of PPIA in the spinal cord were decreased (P<0.05, P<0.01) in the EA group；the relative protein expression of NF-κB and fluorescence expression of PPIA in spinal cord of mice in the Riluzole group were decreased (P<0.05). CONCLUSIONS: EA intervention can improve motor function in ALS mice, and its mechanism may be related to the inhibition of PPIA/NF-κB signaling pathway by EA to alleviating neuroinflammatory response.

Irpex lacteus polysaccharide exhibits therapeutic potential for ovarian fibrosis in PCOS rats via the TGF-ß1/smad pathway.

Polycystic ovarian syndrome (PCOS) is one of the commonest endocrinopathies in childbearing women. The research was conducted to assess the impact of Irpex lacteus polysaccharide (ILP, 1000 mg/kg) on the letrozole (1 mg/kg)-induced PCOS model in female rats. Metformin (Met, 265 mg/kg) as the positive control. The study suggested that ILP restored the estrous cycle in rats with PCOS as well as lowered relative ovarian weight and body weight, in comparison to normal. Rats with PCOS showed improvement in ovarian structure and fibrosis when given ILP. ILP decreased the testosterone (T), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), luteinizing hormone (LH), homeostasis model assessment-insulin resistance (HOMA-IR), fasting blood glucose (FBG), and insulin (INS) levels and elevated the follicle-stimulating hormone (FSH) and estrogen (E2) levels in PCOS rats. In addition, ILP increased the content of superoxide dismutase (SOD) in serum and the antioxidant enzymes (Prdx3, Sod1, Gsr, Gsta4, Mgst1, Gpx3, Sod2 and Cat) expression levels in the ovaries and decreased the serum expression of malondialdehyde (MDA). In addition, ILP treatment slowed down the process of the fibrosis-associated TGF-ß1/Smad pathway and downregulated α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) levels in PCOS rats ovaries. According to these findings, ILP may be able to treat letrozole-induced PCOS in rats by ameliorating metabolic disturbances, sex hormone levels, oxidative stress, and ovarian fibrosis.

Medical assistance in dying in Canada: A scoping review on the concept of suffering.

OBJECTIVES: Medical Assistance in Dying (MAiD) has been legal in Canada since June 2016. A person can receive MAiD if their suffering cannot be relieved under conditions that they consider acceptable. Informed consent requires that the person requesting MAiD has received all the information needed to make their decision; that is, medical diagnosis and prognosis, available treatments including palliative care. The evaluation of unbearable suffering is known to be challenging as suffering is often psychological, existential, and social in nature. While interventions to relieve suffering exist, it is unclear how suffering is assessed and addressed in the literature on MAiD practice. No scoping review exists on the topic in Canada. The aim of this study was to understand how the concept of suffering was approached within the Canadian MAiD grey (GL) and scientific (peer-reviewed) literature (SL), specifically: 1- How suffering is defined and assessed in the context of MAiD in Canada and 2- Which interventions in response to suffering are recommended within the process of obtaining informed consent for MAiD and throughout the process of MAiD itself. METHODS: A scoping review was conducted based on PRISMA-SR guidelines. SL articles (N = 1027) were identified from a review of 6 databases and GL documents (N = 537) were obtained from the provinces of Quebec, Ontario and British Columbia. Documents were analyzed using NVivo with coding by two-raters and continuous team discussions. RESULTS: A multidimensional definition of suffering, akin to the concept of total pain, is used. The assessment of suffering is based upon patients' reports. Tools to aid in the assessment are not comprehensively covered. Specific interventions to address suffering were often focused on active listening and the management of physical symptoms. No specific interventions were mentioned and there was no reference to clinical practice guidelines in the grey literature to address other components of suffering. The use of a multidisciplinary approach is suggested without specifying the nature of involvement. CONCLUSIONS: Our review indicates that published guidelines of MAID assessments could include clearer structure around the assessment and management of suffering, with suggestions of tools that may help clarify types of suffering and reference to clinical practice guidelines and interventions to holistically attend to patient suffering with an attention on non-physical symptoms. Guidelines would benefit from clearer explanations of how members of an interdisciplinary teams could be coherently coordinated.

Difference Between Posterior Monteggia Fractures and Posterior Fracture-Dislocation of Proximal Ulna in Adults.

OBJECTIVE: To figure out the difference between patients with posterior Monteggia fractures which were concomitant with proximal radioulnar joint (PRUJ) dislocation and posterior fracture-dislocation of the proximal ulna that were not concomitant with PRUJ. METHODS: From January 2016 to January 2019, 37 consecutive adult patients who had posterior fracture-dislocation of proximal ulna (no PRUJ dislocation, n = 16) and posterior Monteggia fractures (PRUJ dislocation, n = 21) were included. All patients had intraoperative fluoroscopy, computed tomography (CT) scans, and standard radiography (anteroposterior view and lateral view). The mechanism of injury, the cases with open fracture, sustained multiple injuries and classification of fracture was recorded. The clinical details of the patients such as the final range of motion (ROM) and the Broberg-Morrey scores were described. RESULTS: Patients with PRUJ dislocation (ten type A, five type B, and six type D) and those without concomitant PRUJ dislocation (fifteen type A and one type C) exhibited an obvious difference according to the classifications of Jupiter et al. (P = 0.010). Ninety-five percent of patients who had PRUJ dislocation were accompanied by a metaphyseal fracture, while only 50% of the patients who did not have PRUJ dislocation were accompanied by a metaphyseal fracture (P = 0.002). Meanwhile, 16 of 20 metaphyseal fractures had more than one fragment in the group of dislocations, but five of eight metaphyseal fractures were comminuted in the control group. The two groups exhibited an obvious difference (P = 0.009). The 21 patients who sustained a radioulnar dislocation had less mean arc of flexion, pronation, and Broberg-Morrey scores were significantly less than the patients of the control group (flexion: 117.38 ± 14.46 vs 127.50 ± 13.416, P = 0.035; pronation: 59.76 ± 11.88 vs 67.50 ± 6.58, P = 0.017; Broberg-Morrey: 80.48 ± 12.17 vs 88.19 ± 10.28, P = 0.040). CONCLUSIONS: Patients suffering posterior Monteggia fractures had more metaphyseal fractures, more comminuted fractures of the metaphysis, and worse ultimate ulnohumeral motion than patients of posterior fracture-dislocation of proximal ulna.

Enhanced charge transport via d(δ)-p(π) conjugation in Mo2-integrated single-molecule junctions.

A trans-dimolybdenum nicotinate (m-Mo2) complex and its isonicotinate isomer (p-Mo2) were synthesized and characterized crystallographically, and their single-molecule charge transport properties were investigated using the STM break junction (STM-BJ) technique. With a quadruply bonded Mo2 complex unit integrated into molecular backbones, the single-molecule conductance for complex molecules was increased by more than one order of magnitude compared with that of the organic π-conjugated analogues 1,4-bis(4-pyridyl)benzene (p-Ph) and 1,4-bis(3-pyridyl)benzene (m-Ph). More interestingly, unlike m-Ph, m-Mo2 with meta connected pyridyl anchors presents larger conductance than that of p-Mo2 with two para connected pyridyl groups. DFT-based transmission calculations revealed that the significant conductance enhancement of Mo2 molecules originates from the largely reduced HOMO-LUMO gap, and the unique d(δ)-p(π) conjugation between the Mo2 unit and the pyridine rings gives rise to a delocalized electronic structure that endows the Mo2 molecules with an unexpected high conductance.

Determination of the degree of PEGylation of protein bioconjugates using data from proton nuclear magnetic resonance spectroscopy.

The average number of methoxy poly(ethylene glycol) (mPEG) chains grafted to a protein - also known as the degree of PEGylation - is a fundamental parameter for characterizing a bioconjugate. The degree of PEGylation is typically determined by chromatographic or electrophoretic methods, which are subject to certain biases. This contribution describes an analytical approach alongside technical precautions for quantitatively determining the degree of PEGylation of protein bioconjugates by 1H NMR spectroscopy. An accompanying dataset, corresponding to the raw 1H NMR spectra of thirteen bioconjugates with different degrees of PEGylation and different mPEG molecular weights, is provided for the reader to become familiar with the analysis. The exemplary bioconjugate system used in this Data article is the enzyme glutamate dehydrogenase (GDH) modified with multiple copies of mPEG (0.5-20 kDa). These bioconjugates correspond to those discussed in-depth in the article "Mechanisms of activity loss for a multi-PEGylated protein by experiment and simulation" by Zaghmi et al., 2019 The described approach to calculate degree of PEGylation is quantitative, applicable to other proteins, and can be adapted to other types of polymers.

Surface-enhanced Raman spectroscopy: bottlenecks and future directions.

In this feature article, we discuss in detail developmental bottleneck issues in Raman spectroscopy in its early stages and surface-enhanced Raman spectroscopy (SERS) in the past four decades. We divide SERS research into two different directions with different targets. Fundamental research is extending the limits of SERS to single-molecule, sub-nanometer resolution and femtosecond processes. In contrast, practical research is expanding the range of applications with the aim of providing versatile analytical tools for surface, materials, life, environmental, forensic and food sciences and also commercial instruments for use in daily life. In the second direction there have continually been many complex bottlenecks to be overcome. We attempt to enumerate the key issues in detail and also describe the achievements made to overcome the bottlenecks. In the last, but not least important part, we discuss the remaining bottlenecks and possible strategies for overcoming them to enable SERS to be an even more powerful and versatile technique.

Plasmonic photoluminescence for recovering native chemical information from surface-enhanced Raman scattering.

Surface-enhanced Raman scattering (SERS) spectroscopy has attracted tremendous interests as a highly sensitive label-free tool. The local field produced by the excitation of localized surface plasmon resonances (LSPRs) dominates the overall enhancement of SERS. Such an electromagnetic enhancement is unfortunately accompanied by a strong modification in the relative intensity of the original Raman spectra, which highly distorts spectral features providing chemical information. Here we propose a robust method to retrieve the fingerprint of intrinsic chemical information from the SERS spectra. The method is established based on the finding that the SERS background originates from the LSPR-modulated photoluminescence, which contains the local field information shared also by SERS. We validate this concept of retrieval of intrinsic fingerprint information in well controlled single metallic nanoantennas of varying aspect ratios. We further demonstrate its unambiguity and generality in more complicated systems of tip-enhanced Raman spectroscopy (TERS) and SERS of silver nanoaggregates.

[Identifying Factors Associated with Visits to Doctors using a Multilevel Zero-inflated Poisson Model].

OBJECTIVE: To determine factors influencing patient visits to doctors using a multilevel zero-inflated Poisson model with count data with excessive zero. METHODS: The data in relation to rural health services collected in Sichuan Province as part of the Fifth National Health Service Survey (2013) were used in this study. A multilevel random intercept zero-inflated Poisson model was established to identify factors associated with visits to doctors in two weeks. RESULTS: The logistic regression showed that gender, age and presence of chronic diseases were the main factors associated with the likelihood of visiting doctors in two weeks. The Poisson regression revealed that travel time to the nearest medical facility, ethnicity, marital status and educational attainment were associated with numbers of visits to doctors in two weeks. CONCLUSION: Rural residents with a high level of education, unmarried, and living close to medical facility are more likely to visit doctors than others. The multilevel zero-inflated Poisson model can be used for analyzing data with zero extra.

Quantitative correlation between defect density and heterogeneous electron transfer rate of single layer graphene.

Improving electrochemical activity of graphene is crucial for its various applications, which requires delicate control over its geometric and electronic structures. We demonstrate that precise control of the density of vacancy defects, introduced by Ar(+) irradiation, can improve and finely tune the heterogeneous electron transfer (HET) rate of graphene. For reliable comparisons, we made patterns with different defect densities on a same single layer graphene sheet, which allows us to correlate defect density (via Raman spectroscopy) with HET rate (via scanning electrochemical microscopy) of graphene quantitatively, under exactly the same experimental conditions. By balancing the defect induced increase of density of states (DOS) and decrease of conductivity, the optimal HET rate is attained at a moderate defect density, which is in a critical state; that is, the whole graphene sheet becomes electronically activated and, meanwhile, maintains structural integrity. The improved electrochemical activity can be understood by a high DOS near the Fermi level of defective graphene, as revealed by ab initio simulation, which enlarges the overlap between the electronic states of graphene and the redox couple. The results are valuable to promote the performance of graphene-based electrochemical devices. Furthermore, our findings may serve as a guide to tailor the structure and properties of graphene and other ultrathin two-dimensional materials through defect density engineering.

Chaihu-Shugan-San, an oriental herbal preparation, for the treatment of chronic gastritis: a meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic gastritis is a very common disease of the digestive tract. Although herbal preparation Chaihu-Shugan-San (CSS) has been widely used as an alternative treatment for chronic gastritis in East Asia, its effectiveness is not verified. The purpose of this meta-analysis is to evaluate the effectiveness of CSS in treating various types of chronic gastritis. MATERIALS AND METHODS: Retrospective review of pertinent literature via Embase, China National Knowledge Infrastructure database, Wanfang Data, Vip Information and the Cochrane Library search using the keywords "Chaihushugan" or "Chaihu Shugan" or "Chai Hu Shu Gan" or "Chaihu Shu Gan". Twenty-one trials were identified including 2572 patients (1384 in CSS group and 1188 in chemotherapy group). Each trial was independently reviewed by two assessors. RESULTS: The risk ratios of bile reflux gastritis, chronic superficial gastritis, chronic atrophic gastritis, and chronic erosive gastritis in the CSS-treated and chemotherapy groups were 1.30, 1.20, 1.24, and 1.48, respectively. CSS had more therapeutic effect in various types of chronic gastritis patients for improving clinical response compared with the chemotherapy group. Of the 21 trials administrating CSS to patients, no adverse event was reported. CONCLUSIONS: CSS was more effective compared to chemotherapy in the treatment of chronic gastritis and no serious side-effects were identified. However, the evidence is insufficient because of the low methodological quality of the included trials. More full-scale, randomized, double-blind, placebo-controlled clinical trials are recommended to further evaluate the therapeutic benefit of CSS.

Growth of adlayer graphene on Cu studied by carbon isotope labeling.

The growth of bilayer and multilayer graphene on copper foils was studied by isotopic labeling of the methane precursor. Isotope-labeled graphene films were characterized by micro-Raman mapping and time-of-flight secondary ion mass spectrometry. Our investigation shows that during growth at high temperature, the adlayers formed simultaneously and beneath the top, continuous layer of graphene and the Cu substrate. Additionally, the adlayers share the same nucleation center and all adlayers nucleating in one place have the same edge termination. These results suggest that adlayer growth proceeds by catalytic decomposition of methane (or CH(x), x < 4) trapped in a "nano-chemical vapor deposition" chamber between the first layer and the substrate. On the basis of these results, submillimeter bilayer graphene was synthesized by applying a much lower growth rate.

Conductance histogram evolution of an EC-MCBJ fabricated Au atomic point contact.

This work presents a study of Au conductance quantization based on a combined electrochemical deposition and mechanically controllable break junction (MCBJ) method. We describe the microfabrication process and discuss improved features of our microchip structure compared to the previous one. The improved structure prolongs the available life of the microchip and also increases the success rate of the MCBJ experiment. Stepwise changes in the current were observed at the last stage of atomic point contact breakdown and conductance histograms were constructed. The evolution of 1G0 peak height in conductance histograms was used to investigate the probability of formation of an atomic point contact. It has been shown that the success rate in forming an atomic point contact can be improved by decreasing the stretching speed and the degree that the two electrodes are brought into contact. The repeated breakdown and formation over thousands of cycles led to a distinctive increase of 1G0 peak height in the conductance histograms, and this increased probability of forming a single atomic point contact is discussed.