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Experimental studies have demonstrated statin-induced toxicity for ovary and uterus. However, the safety of statins on the functions of ovary and uterus in real-world clinical settings remains unknown. The aim of this study was to identify ovary and uterus related adverse events (AEs) associated with statin use by analyzing data from FDA Adverse Event Reporting System (FAERS). We used OpenVigil 2.1 to query FAERS database. Ovary and uterus related AEs were defined by 383 Preferred Terms, which could be classified into ten aspects. Disproportionality analysis was performed to assess the association between AEs and statin use. Our results suggest that statin use may be associated with a series of ovary and uterus related AEs. These AEs are involved in ovarian cysts and neoplasms, uterine neoplasms, cervix neoplasms, uterine disorders (excl neoplasms), cervix disorders (excl neoplasms), endocrine disorders of gonadal function, menstrual cycle and uterine bleeding disorders, menopause related conditions, and sexual function disorders. Moreover, there are variabilities in the types and signal strengths of ovary and uterus related AEs across individual statins. According to our findings, the potential ovary and uterus related AEs of statins should attract enough attention and be closely monitored in future clinical practice.

Dual antiplatelet therapy (DAPT) reduced stroke risk in high-risk transient ischemic attack (TIA) patients assessed by ABCD2 score. Patients with positive diffusion-weighted imaging (DWI) were identified as imaging-based high-risk. The present study aims to investigate whether DAPT could reduce stroke risk in TIA with DWI positive. The study enrolled TIA patients within 72 h of onset from the prospective TIA database of the First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischemic stroke at 90-day. The relationship between DAPT and stroke was analyzed in a cox proportional hazards model. The Kaplan–Meier curves of TIA patients with DAPT and monotherapy were plotted. Total of 661 TIA patients were enrolled, 279 of whom were DWI positive and 281 used DAPT. The 90-day stroke risk was higher in patients used monotherapy than those used DAPT in TIA with positive DWI (23.7% vs. 13.4%, p = 0.029). DAPT was associated with reduced stroke risk in TIA patients with positive DWI (hazard ratio [HR] = 0.54; 95% confidence interval [CI], 0.30–0.97; p = 0.037). However, the benefit didn’t exist in TIA patients with negative DWI (HR = 0.43; 95% CI, 0.14–1.33; p = 0.142). Early use of DAPT reduced stroke risk in TIA patients with positive DWI.

Membrane fluidity, essential for cell functions, is obviously affected by copper, but the molecular mechanism is poorly understood. Here, we unexpectedly observed that a decrease in phospholipid (PL) bilayer fluidity caused by Cu2+ was more significant than those by Zn2+ and Ca2+, while a comparable reduction occurred in the last two ions. This finding disagrees with the placement in the periodic table of Cu just next to Zn and far from Ca. The physical nature was revealed to be an anomalous attraction between Cu+ cations, as well as the induced motif of two phospholipids coupled by Cu-Cu bond (PL-diCu-PL). Namely, upon Cu2+ ion binding to a negatively charged phosphate group of lipid, Cu2+ was reduced to Cu+. The attraction of the cations then caused one Cu+ ion simultaneously binding to two lipids and another Cu+, resulting in the formation of PL-diCu-PL structure. In contrast, this attraction cannot occur in the cases of Zn and Ca ions. Remarkably, besides lipids, the phosphate group also widely exists in other biological molecules, including DNA, RNA, ADP and ATP. Our findings thus provide a new view for understanding the biological functions of copper and the mechanism underlying copper-related diseases, as well as lipid assembly.

Nitrogen-fixing nodules, which are also major sites of sulfur assimilation, contribute significantly to the sulfur needs of whole soybean plants. Nodules are the predominant sites for cysteine accumulation and the activity of O-acetylserine(thiol)lyase (OASS) is central to the sulfur assimilation process in plants. Here, we examined the impact of overexpressing OASS on soybean nodulation and nodule metabolome. Overexpression of OASS did not affect the nodule number, but negatively impacted plant growth. HPLC measurement of antioxidant metabolites demonstrated that levels of cysteine, glutathione, and homoglutathione nearly doubled in OASS overexpressing nodules when compared to control nodules. Metabolite profiling by LC-MS and GC-MS demonstrated that several metabolites related to serine, aspartate, glutamate, and branched-chain amino acid pathways were significantly elevated in OASS overexpressing nodules. Striking differences were also observed in the flavonoid levels between the OASS overexpressing and control soybean nodules. Our results suggest that OASS overexpressing plants compensate for the increase in carbon requirement for sulfur assimilation by reducing the biosynthesis of some amino acids, and by replenishing the TCA cycle through fatty acid hydrolysis. These data may indicate that in OASS overexpressing soybean nodules there is a moderate decease in the supply of energy metabolites to the nodule, which is then compensated by the degradation of cellular components to meet the needs of the nodule energy metabolism.

Corollas (or perianths), considered to contribute to pollinator attraction during anthesis, persist after anthesis in many plants. However, their post-floral function has been little investigated within a cost-benefit framework. We explored the adaptive significance of corolla retention after anthesis for reproduction in Fritillaria delavayi, a perennial herb endemic to the alpine areas of the Hengduan Mountains, southwestern China. We examined whether the persistent corollas enhance reproductive success during seed development. Persistent corollas increased fruit temperature on sunny days, and greatly decreased the intensity of ultraviolet-B/C (UV-B/C) radiation reaching fruits. When corollas were removed immediately after pollination, fecundity and progeny quality were adversely affected. Measurements of flower mass and size showed no further corolla growth during fruiting, and respiration and transpiration tests demonstrated that both respiration rate and transpiration rate of corollas were much lower during fruiting than during flowering, indicating a slight additional resource investment in corolla retention after anthesis. Thus, seed production by F. delavayi may be facilitated by corolla retention during seed development at only a small physiological cost. We conclude that corolla retention may be an adaptive strategy that enhances female reproductive success by having a protective role for ripening seeds in the harsh conditions at high elevation.

To determine whether positive or negative DWI TIA patients could get benefits from HST we conducted a cohort study which data from the prospective, hospital-based, TIA database of the First Affiliated Hospital of Zhengzhou University. The end-point was 7-day and 90-day incidence of stroke. Cox proportional hazard regression models were used to analyze the association between end-points and high-intensity statin treatment in TIA patients with positive and negative DWI. A total of 987 eligible TIA patients were analyzed. The stroke risk of patients with positive DWI was about a four-fold increase compared to that with negative DWI (7 d, 10.9 versus 1.8, p

Herein, we demonstrate the contribution of the oxygen-deficiencies on the bipolar resistance switching (RS) properties of amorphous-YFe0.5Cr0.5O3−d (a-YFCO) films. The a-YFCO films were prepared under various oxygen pressures to tune the concentration of oxygen-deficiencies in the films. The XPS data verify that the oxygen-deficiencies increase with decreasing oxygen pressure. The RS property becomes more pronounced with more oxygen-deficiencies in a-YFCO films. Based on the Ohmic conduction measurements in the low resistance state, we confirm that the RS mechanism is related to the migration of oxygen-deficiencies. The enhanced RS and long retention in a-YFCO suggest a great potential for applications in nonvolatile memory devices.

A prerequisite for the evolutionary stability of pollinating seed-consuming mutualisms is that each partner benefits from the association. However, few studies of such mutualism have considered the benefit gained by the pollinators. Here, we determined how the pollinating seed-predators ensure the provisioning of their offspring in the recently discovered mutualism between Rheum nobile and Bradysia flies. The correlation between flower fate and fly oviposition was examined. Floral traits and patterns of variation in fruit abortion and fly oviposition were investigated to determine whether female flies exhibit preferences for particular flowers when laying eggs. Indole-3-acetic acid (IAA) was quantified to determine whether female flies manipulate host physiology. Flowers that flies oviposited on had a significantly lower probability of fruit abortion compared with intact flowers. Females did not exhibit oviposition preference for any of the floral traits examined. There was no significant correlation between fruit abortion and fly oviposition in terms of either flower position or timing of flowering. IAA concentrations in oviposited flowers were significantly higher than in intact flowers. Our results suggest that oviposition by the mutualistic seed-consuming pollinator Bradysia sp., greatly reduces the probability of fruit abortion of its host, R. nobile; this may be attributed to the manipulation of host physiology through regulating IAA levels.

The precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain. Unilateral intra-plantar supplementation of proBDNF by injecting exogenous proBDNF or ectopic overexpression resulted in pain hypersensitivity and induced spinal phosphorylated extracellular signal-regulated kinase activation. Exogenous proBDNF injection induced the infiltration of inflammatory cells and the activation of proinflammatory cytokines, suggesting that inflammatory reaction contributed to the pro-algesic effect of proBDNF. Finally, we generated monoclonal anti-proBDNF antibody that could biologically block proBDNF. Administration of monoclonal Ab-proBDNF attenuated various types of inflammatory pain and surgical pain. Thus, peripheral proBDNF is a potential pain mediator and anti-proBDNF pretreatment may alleviate the development of inflammatory pain.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (PST), is one of the most destructive diseases and can cause severe yield losses in many regions of the world. Because of the large size and complexity of wheat genome, it is difficult to study the molecular mechanism of interaction between wheat and PST. Brachypodium distachyon has become a model system for temperate grasses’ functional genomics research. The phenotypic evaluation showed that the response of Brachypodium distachyon to PST was nonhost resistance (NHR), which allowed us to present this plant-pathogen system as a model to explore the immune response and the molecular mechanism underlying wheat and PST. Here we reported the generation of about 7,000 T-DNA insertion lines based on a highly efficient Agrobacterium-mediated transformation system. Hundreds of mutants either more susceptible or more resistant to PST than that of the wild type Bd21 were obtained. The three putative target genes, Bradi5g17540, BdMYB102 and Bradi5g11590, of three T-DNA insertion mutants could be involved in NHR of Brachypodium distachyon to wheat stripe rust. The systemic pathologic study of this T-DNA mutants would broaden our knowledge of NHR, and assist in breeding wheat cultivars with durable resistance.

The pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) is currently unclear. However, inflammation has been suggested to play an important role in BPS/IC. JNK downstream signaling plays an important role in numerous chronic inflammatory diseases. However, studies of the JNK pathway in BPS/IC are limited. In this study, we investigated the role of the JNK pathway in human BPS/IC and rat protamine sulfate (PS)-induced cystitis and examined the effect of the selective JNK inhibitor SP600125 on rat bladder cystitis. In our study, we demonstrated that the JNK signaling pathway was activated (the expression of JNK, c-Jun, p-JNK, p-c-Jun, IL-6 and TNF-α were significantly increasing in BPS/IC compared to the non-BPS/IC patients) and resulted in inflammation in human BPS/IC. Further animal models showed that the JNK pathway played an important role in the pathogenesis of cystitis. JNK inhibitors, SP600125, effectively inhibited the expression of p-JNK, p-c-Jun, IL-6 and TNF-α. The inhibition of these pathways had a protective effect on PS-induced rat cystitis by significantly decreasing histological score and mast cell count and improving bladder micturition function (micturition frequency significantly decreasing and bladder capacity significantly increasing). Therefore, JNK inhibition could be used as a potential treatment for BPS/IC.

Sensitive optical imaging of active biomolecules in the living organism requires both a molecular probe specifically responsive to the target and a high-contrast approach to remove the background interference from autofluorescence and light scatterings. Here, a responsive probe for ascorbic acid (vitamin C) has been developed by conjugating two nitroxide radicals with a long-lived luminescent europium complex. The nitroxide radical withholds the probe on its “off” state (barely luminescent), until the presence of vitamin C will switch on the probe by forming its hydroxylamine derivative. The probe showed a linear response to vitamin C concentration with a detection limit of 9.1 nM, two orders of magnitude lower than that achieved using electrochemical methods. Time-gated luminescence microscopy (TGLM) method has further enabled real-time, specific and background-free monitoring of cellular uptake or endogenous production of vitamin C and mapping of vitamin C in living Daphnia magna. This work suggests a rational design of lanthanide complexes for background-free small animal imaging of biologically functional molecules.

Aluminum electrolytic capacitors (AECs) are widely used for alternating current (ac) line-filtering. However, their bulky size is becoming more and more incompatible with the rapid development of portable electronics. Here we report a scalable process to fabricate miniaturized graphene-based ac line-filters on flexible substrates at room temperature. In this work, graphene oxide (GO) is reduced by patterned metal interdigits at room temperature and used directly as the electrode material. The as-fabricated device shows a phase angle of −75.4° at 120 Hz with a specific capacitance of 316 µF/cm2 and a RC time constant of 0.35 ms. In addition, it retains 97.2% of the initial capacitance after 10000 charge/discharge cycles. These outstanding performance characteristics of our device demonstrate its promising to replace the conventional AECs for ac line filtering.

By understanding the growth mechanism of nanomaterials, the morphological features of nanostructures can be rationally controlled, thereby achieving the desired physical properties for specific applications. Herein, the growth habits of aluminum nitride (AlN) nanostructures and single crystals synthesized by an ultrahigh-temperature, catalyst-free, physical vapor transport process were investigated by transmission electron microscopy. The detailed structural characterizations strongly suggested that the growth of AlN nanostructures including AlN nanowires and nanohelixes follow a sequential and periodic rotation in the growth direction, which is independent of the size and shape of the material. Based on these experimental observations, an helical growth mechanism that may originate from the coeffect of the polar-surface and dislocation-driven growth is proposed, which offers a new insight into the related growth kinetics of low-dimensional AlN structures and will enable the rational design and synthesis of novel AlN nanostructures. Further, with the increase of temperature, the growth process of AlN grains followed the helical growth model.