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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.

Schistosomiasis japonicum is a major zoonosis that seriously harms human health and affects social and economic development in China. The control of Oncomelania Hupensis, the only intermediate host of schistosome japonicum, is one of the integrated measures for schistosomiasis control in China. Acquiring updated elevation data of snail habitat environment, as well as it’s spatial analysis, play an important role for the risk evaluation and precise control of schistosomiasis transmission and prevalence. Currently, the elevation database of snail habitat environment in schistosomiasis epidemic areas has not been available in the world, which affects the development of research and application work regarding to snail control. Google Earth(GE) can provide massive information related to topography, geomorphology and ground objects of a region due to its indisputable advantages such as wide use, free charge and rapidly updating. In this paper, taking the Poyang lake region as a example, we extracted elevation data of snail-inhabited environment of the lake from GE and established a elevation correction regression model(CRM) for acquiring accurate geospatial elevations, so as to provide a decision-making reference for snail control and risk evaluation of schistosomiasis in China. We developed a GE Application Programming Interface(API) program to extract elevation data from GE, which was compared with the actual elevation data obtained from topographic map of the Poyang Lake bottom. Then, a correction regression model was established and evaluated by 3 index, Mean Absolute Error(MAE), Root Mean Squared Error(RMSE) and Index of Agreement(IOA) for the accuracy of the model. The elevation values extracted from GE in 15086 sample grid points of the lake ranged from 8.5 m to 24.8 m. After the sample points were divided randomly to three groups, the mean elevations of three groups were 13.49 m, 13.52 m and 13.65 m, respectively, with standard deviation ranged from 2.04–2.06. The mean elevation among three groups has no statistic difference (F = 1.536, P = 0.215). A elevation correction regression model was established as y = 6.228 + 0.485×. the evaluation results for the accuracy of the model showed that the MAE and RMSE before correction was 1.28 m and 3.95 m respectively, higher than that after correction, which were 0.74 and 1.30 m correspondingly. The IOA before correction (−0.40)was lower than that after correction(0.34). Google Earth can directly or indirectly get access to massive information related to topography, geomorphology and ground objects due to its indisputable advantages. However, it still needs to be converted into more reliable and accurate data by combining with pre-processing tools. This study used self-developed API program to extract elevation data from GE through precisely locating and improved the accuracy of elevation by using a correction regression model, which can provide reliable data sources for all kinds of spatial data researches and applications.

Expert weight determination is a critical issue in the design concept evaluation process, especially for complex products. However, this phase is often ignored by most decision makers. For the evaluation of complex product design concepts, experts are selected by clusters with different backgrounds. This work proposes a novel integrated two-layer method to determine expert weight under these circumstances. In the first layer, a hybrid model integrated by the entropy weight model and the Multiplicative analytical hierarchy process method is presented. In the second layer, a minimized variance model is applied to reach a consensus. Then the final expert weight is determined by the results of both layers. A real-life example of cruise ship cabin design evaluation is implemented to demonstrate the proposed expert weight determination method. To analyze the feasibility of the proposed method, weight determination with and without using experts is compared. The result shows the expert weight determination method is an effective approach to improve the accuracy of design concept evaluation.

Plant grafting has been practiced widely in horticulture and proved as a useful tool in science. However, the mechanisms of graft healing or graft incompatibility remain poorly understood. In this study, Litchi chinensis cv. ‘Jingganghongnuo’ homograft (‘J/J’) and ‘Jingganghongnuo’/‘zhuangyuanhong’ heterograft (‘J/Z’) as compatible and incompatible combination, respectively, was used to study transcriptional changes between incompatible and compatible graft during graft union formation. Anatomical observation indicated that three stages (2 h, 14 d and 21 d after grafting) were critical for graft union formation and selected for high-throughput sequencing. Results indicated 6060 DEGs were differentially expressed in the compatible combination and 5267 DEGs exhibiting in the incompatible one. KEGG pathway enrichment analysis revealed that DEGs were involved in metabolism, wound response, phenylpropanoid biosynthesis and plant hormone signal transduction. The expression of 9 DEGs annotated in auxin pathway was up-regulated in compatible combination than that in incompatible combination. The IAA concentration confirmed that the IAA might promote the graft compatibility. In addition, 13 DEGs related to lignin biosynthesis were differentially expressed during graft healing process. Overall, our results provide abundant sequence resources for studying mechanisms underlying graft compatibility and establish a platform for further studies of litchi and other evergreen fruit trees.

The neuropeptide natalisin (NTL) has been determined to play essential roles in reproduction in two Diptera and one Coleoptera species. Whether NTL has similar or even different functions in Lepidoptera remains to be determined. Here, we cloned the NTL transcript in the common cutworm moth Spodoptera litura. This transcript encodes a 438-amino acid protein. Twelve putative Sl-NTL neuropeptides were defined by cleavage sites. These NTL peptides share a DDPFWxxRamide C-terminal motif. The expressions of Sl-NTL is low during the egg and larval stages, which increased to a higher level during the pupal stage, and then reached the maximum during the adult stage. Moreover, the expression pattern during the pupal stage is similar between sexes while during the adult stage, it is dimorphic. To explore the function of Sl-NTL and assess its potential as a target for pest control, we knocked down the expression of Sl-NTL in both sexes by using bacteria-mediated RNAi. This technique significantly down regulated (reduced up to 83%) the expression of Sl-NTL in both sexes. Knocking down Sl-NTL expression did not significantly affect its development, survival and morphology but significantly reduced adults’ reproductive behavior (including female calling, male courtship, mating and remating patterns and rates) and reproductive output (offspring gain reduced more than 70%).

Gastric cancer (GC) ranks as the third leading cause of cancer-related mortality worldwide, and approximately 42% of all cases diagnosed each year worldwide are diagnosed in China. A large number of clinical applications have revealed that Trametes robiniophila Μurr. (Huaier) exhibits an anti-tumour effect. However, loss of the bioactive components of Huaier during the extraction procedure with water is unavoidable, and the underlying mechanism of the anti-cancer effect of Huaier remains poorly understood. In this study, we investigated the anti-cancer effect of Huaier n-butanol extract, which contained 51.4% total flavonoids, on HGC27, MGC803, and AGS human GC cell lines in vitro. At a low concentration, Huaier n-butanol extract inhibited the growth of these GC cell types, induced cell cycle arrest and reduced cell metastasis. Moreover, Huaier n-butanol extract suppressed the c-Myc-Bmi1 signalling pathway, and overexpression of Bmi1 reversed the effects of Huaier n-butanol extract on GC cells. Thus, our findings indicate that Huaier n-butanol extract suppresses the proliferation and metastasis of GC cells via a c-Myc-Bmi1-mediated approach, providing a new perspective for our understanding of the anti-tumour effects of Huaier. These results suggest that Huaier n-butanol extract could be an attractive therapeutic adjuvant for the treatment of human GC.

The Monte Carlo (MC) method is widely used to solve various problems in radiotherapy. There has been an impetus to accelerate MC simulation on GPUs whereas thread divergence remains a major issue for MC codes based on acceptance-rejection sampling. Inverse transform sampling has the potential to eliminate thread divergence but it is only implemented for photon transport. Here, we report a MC package Particle Transport in Media (PTM) to demonstrate the implementation of coupled photon-electron transport simulation using inverse transform sampling. Rayleigh scattering, Compton scattering, photo-electric effect and pair production are considered in an analogous manner for photon transport. Electron transport is simulated in a class II condensed history scheme, i.e., catastrophic inelastic scattering and Bremsstrahlung events are simulated explicitly while subthreshold interactions are subject to grouping. A random-hinge electron step correction algorithm and a modified PRESTA boundary crossing algorithm are employed to improve simulation accuracy. Benchmark studies against both EGSnrc simulations and experimental measurements are performed for various beams, phantoms and geometries. Gamma indices of the dose distributions are better than 99.6% for all the tested scenarios under the 2%/2 mm criteria. These results demonstrate the successful implementation of inverse transform sampling in coupled photon-electron transport simulation.

Pain is a complex sensory and affective experience. The current definition for pain relies on verbal reports in clinical settings and behavioral assays in animal models. These definitions can be subjective and do not take into consideration signals in the neural system. Local field potentials (LFPs) represent summed electrical currents from multiple neurons in a defined brain area. Although single neuronal spike activity has been shown to modulate the acute pain, it is not yet clear how ensemble activities in the form of LFPs can be used to decode the precise timing and intensity of pain. The anterior cingulate cortex (ACC) is known to play a role in the affective-aversive component of pain in human and animal studies. Few studies, however, have examined how neural activities in the ACC can be used to interpret or predict acute noxious inputs. Here, we recorded in vivo extracellular activity in the ACC from freely behaving rats after stimulus with non-noxious, low-intensity noxious, and high-intensity noxious stimuli, both in the absence and chronic pain. Using a supervised machine learning classifier with selected LFP features, we predicted the intensity and the onset of acute nociceptive signals with high degree of precision. These results suggest the potential to use LFPs to decode acute pain.

Pain is a complex sensory and affective experience. Through its anticipation, animals can learn to avoid pain. Much is known about passive avoidance during a painful event; however, less is known about active pain avoidance. The anterior cingulate cortex (ACC) is a critical hub for affective pain processing. However, there is currently no mechanism that links ACC activities at the cellular level with behavioral anticipation or avoidance. Here we asked whether distinct populations of neurons in the ACC can encode information for pain anticipation. We used tetrodes to record from ACC neurons during a conditioning assay to train rats to avoid pain. We found that in rats that successfully avoid acute pain episodes, neurons that responded to pain shifted their firing rates to an earlier time, whereas neurons that responded to the anticipation of pain increased their firing rates prior to noxious stimulation. Furthermore, we found a selected group of neurons that shifted their firing from a pain-tuned response to an anticipatory response. Unsupervised learning analysis of ensemble spike activity indicates that temporal spiking patterns of ACC neurons can indeed predict the onset of pain avoidance. These results suggest rate and temporal coding schemes in the ACC for pain avoidance.

Subclinical hypothyroidism (SHT) is a common disorder that may represent early thyroid dysfunction and is related to adverse cardiovascular events. However, myocardial injuries induced by SHT are difficult to detect. Our previous study demonstrated that the cardiac magnetic resonance (CMR) myocardial longitudinal relaxation time (T1) mapping technique is a useful tool for assessing diffuse myocardial injuries in overt hypothyroidism patients. This study was designed to detect whether diffuse myocardial injuries were present in SHT by using the T1 mapping technique. We found that SHT participants had significantly increased native T1 values within four segments of the left ventricle (all p p = 0.003) and were positively correlated with TSH (r = 0.489, p = 0.002). Furthermore, left ventricular diastolic function estimated by the peak filling rate (PFR) was significantly lower in patients with TSH levels ≥10 µIU/mL than that in the controls (p

Elsholtzia and its allied genera such as Collinsonia and Perilla (tribe Elsholtzieae, Lamiaceae) are an ecologically and economically important plant group consisting of ~71 species, with most species distributed in East and Southeast Asia, and several species in North America. Their phylogeny and historical biogeography resulting in a distant intercontinental disjunction are poorly understood. Here we use two nuclear (ETS, ITS) and five chloroplast (rbcL, matK, trnL-F, ycf1, ycf1-rps15) fragments to reconstruct the phylogeny, biogeographic history, and patterns of diversification of Elsholtzieae. The tribe Elsholtzieae is monophyletic and divided into five clades. The woody Elsholtzia species are nested within herbaceous ones and are inferred to have evolved from herbaceous ancestors. Molecular dating shows that the five major clades were established during the Eocene period, but most of the modern diversity did not originate until the Miocene. The divergence between the New World Collinsonia and the Old World Mosla-Keiskea-Perilla clade was dated to the mid-Miocene. Ancestral area reconstructions suggest that the tribe originated in East Asia, and then dispersed to Southeast Asia and North America. Overall, our findings highlight the important roles of the uplifts of the Qinghai-Tibetan Plateau (QTP) and climate changes from Middle Miocene onwards in promoting species diversification of Elsholtzieae.

Corneal endothelial cells (CECs) are very important for the maintenance of corneal transparency. However, in vitro, CECs display limited proliferation and loss of phenotype via endothelial to mesenchymal transformation (EMT) and cellular senescence. In this study, we demonstrate that continuous supplementary nutrition using a perfusion culture bioreactor and three-dimensional (3D) spheroid culture can be used to improve CEC expansion in culture and to construct a tissue-engineered CEC layer. Compared with static culture, perfusion-derived CECs exhibited an increased proliferative ability as well as formed close cell-cell contact junctions and numerous surface microvilli. We also demonstrated that the CEC spheroid culture significantly down-regulated gene expression of the proliferation marker Ki67 and EMT-related markers Vimentin and α-SMA, whereas the gene expression level of the CEC marker ATP1A1 was significantly up-regulated. Furthermore, use of the perfusion system in conjunction with a spheroid culture on decellularized corneal scaffolds and collagen sheets promoted the generation of CEC monolayers as well as neo-synthesized ECM formation. This study also confirmed that a CEC spheroid culture on a curved collagen sheet with controlled physiological intraocular pressure could generate a CEC monolayer. Thus, our results show that the use of a perfusion system and 3D spheroid culture can promote CEC expansion and the construction of tissue-engineered corneal endothelial layers in vitro.

Optical spin splitting has a promising prospect in quantum information and precision metrology. Since it is typically small, many efforts have been devoted to its enhancement. However, the upper limit of optical spin splitting remains uninvestigated. Here, we investigate systematically the in-plane spin splitting of a Gaussian beam reflected from a glass-air interface and find that the spin splitting can be enhanced in three different incident angular ranges: around the Brewster angle, slightly smaller than and larger than the critical angle for total reflection. Within the first angular range, the reflected beam can undergo giant spin splitting but suffers from low energy reflectivity. In the second range, however, a large spin splitting and high energy reflectivity can be achieved simultaneously. The spin splitting becomes asymmetrical within the last angular range, and the displacement of one spin component can be up to half of incident beam waist w0/2. Of all the incident angles, the spin splitting reaches its maximum at Brewster angle. This maximum splitting increases with the refractive index of the “glass” prism, eventually approaching an upper limit of w0. These findings provide a deeper insight into the optical spin splitting phenomena and thereby facilitate the development of spin-based applications.

Pyramidal neurons in the rodent hippocampus exhibit spatial tuning during spatial navigation, and they are reactivated in specific temporal order during sharp-wave ripples observed in quiet wakefulness or slow wave sleep. However, analyzing representations of sleep-associated hippocampal ensemble spike activity remains a great challenge. In contrast to wake, during sleep there is a complete absence of animal behavior, and the ensemble spike activity is sparse (low occurrence) and fragmental in time. To examine important issues encountered in sleep data analysis, we constructed synthetic sleep-like hippocampal spike data (short epochs, sparse and sporadic firing, compressed timescale) for detailed investigations. Based upon two Bayesian population-decoding methods (one receptive field-based, and the other not), we systematically investigated their representation power and detection reliability. Notably, the receptive-field-free decoding method was found to be well-tuned for hippocampal ensemble spike data in slow wave sleep (SWS), even in the absence of prior behavioral measure or ground truth. Our results showed that in addition to the sample length, bin size, and firing rate, number of active hippocampal pyramidal neurons are critical for reliable representation of the space as well as for detection of spatiotemporal reactivated patterns in SWS or quiet wakefulness., Collaborative Research in Computational Neuroscience (Award IIS-1307645), United States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant N00014-10-1-0936), National Institutes of Health (U.S.) (Grant TR01-GM10498)

With the advance of the research on acoustic metamaterials, the limits of passive metamaterials have been observed, which prompts the studies concerning actively tunable metamaterials with adjustable characteristic frequency bands. In this work, we present a tunable acoustic metamaterial with double-negativity composed of periodical membranes and side holes, in which the double-negativity pass band can be controlled by an external direct-current voltage. The tension and stiffness of the periodically arranged membranes are actively controlled by electromagnets producing additional stresses, and thus, the transmission and phase velocity of the metamaterial can be adjusted by the driving voltage of the electromagnets. It is demonstrated that a tiny direct-current voltage of 6V can arise a shift of double-negativity pass band by 40% bandwidth, which exhibits that it is an easily controlled and highly tunable acoustic metamaterial, and furthermore, the metamaterial marginally causes electromagnetic interference to the surroundings.

Microgravity induces observed bone loss in space flight and reduced osteogenesis of bone mesenchymal stem cells (BMSCs) partly contributes to this phenomenon. Abnormal regulation or functioning of the actin cytoskeleton induced by microgravity may cause the inhibited osteogenesis of BMSCs, but the underlying mechanism remains obscure. In this study, we demonstrated that actin cytoskeletal changes regulate nuclear aggregation of the transcriptional coactivator with PDZ-binding motif (TAZ), which is indispensable for osteogenesis of bone mesenchymal stem cells (BMSCs). Moreover, we utilized a clinostat to model simulated microgravity (SMG) and demonstrated that SMG obviously depolymerized F-actin and hindered TAZ nuclear translocation. Interestingly, stabilizing the actin cytoskeleton induced by Jasplakinolide (Jasp) significantly rescued TAZ nuclear translocation and recovered the osteogenic differentiation of BMSCs in SMG, independently of large tumor suppressor 1(LATS1, an upstream kinase of TAZ). Furthermore, lysophosphatidic acid (LPA) also significantly recovered the osteogenic differentiation of BMSCs in SMG through the F-actin-TAZ pathway. Taken together, we propose that the depolymerized actin cytoskeleton inhibits osteogenic differentiation of BMSCs through impeding nuclear aggregation of TAZ, which provides a novel connection between F-actin cytoskeleton and osteogenesis of BMSCs and has important implications in bone loss caused by microgravity.

High efficient and sustainable utilization of water-based lubricant is essential for saving energy. In this paper, a kind of layered double hydroxide (LDH) nanoplatelets is synthesized and well dispersed in water due to the surface modification with oleylamine. The excellent tribological properties of the oleylamine-modified Ni-Al LDH (NiAl-LDH/OAm) nanoplatelets as water-based lubricant additives are evaluated by the tribological tests in an aqueous environment. The modified LDH nanoplatelets are found to not only reduce the friction but also enhance the wear resistance, compared with the water-based cutting fluid and lubricants containing other particle additives. By adding 0.5 wt% LDH nanoplatelets, under 1.5 GPa initial contact pressure, the friction coefficient, scar diameter, depth and width of the wear track dramatically decrease by 83.1%, 43.2%, 88.5% and 59.5%, respectively. It is considered that the sufficiently small size and the excellent dispersion of NiAl-LDH/OAm nanoplatelets in water are the key factors, so as to make them enter the contact area, form a lubricating film and prevent direct collision of asperity peaks. Our investigations demonstrate that the LDH nanoplatelet as a water-based lubricant additive has a great potential value in industrial application.

Creatine kinase (CK) helps maintain homeostasis of intracellular ATP level by catalyzing the reversible phosphotransfer between ATP and phosphocreatine. In humans, there are two cytosolic CK isoforms, the muscle-type (M) and the brain-type (B), which frequently function as homodimers (hMMCK and hBBCK). Interestingly, these isoenzymes exhibit significantly different thermostabilities, despite high similarity in amino acid sequences and tertiary structures. In order to investigate the mechanism of this phenomenon, in this work, we first used domain swapping and site-directed mutagenesis to search for the key residues responsible for the isoenzyme-specific thermostability. Strikingly, the difference in thermostability was found to principally arise from one single residue substitution at position 36 (Pro in hBBCK vs. Leu in hMMCK). We then engaged the molecular dynamics simulations to study the molecular mechanism. The calculations imply that the P36L substitution introduces additional local interactions around residue 36 and thus further stabilizes the dimer interface through a complex interaction network, which rationalizes the observation that hMMCK is more resistant to thermal inactivation than hBBCK. We finally confirmed this molecular explanation through thermal inactivation assays on Asp36 mutants that were proposed to devastate the local interactions and thus the dimer associations in both isoenzymes.

In this paper, a new kind of oil-soluble ultrathin MoS2 nanosheets is prepared through a one-pot process. A superior extreme pressure property, which has not been attained with other nano-additives, is discovered when the nanosheets are used as lubricant additives. The as-synthesized MoS2 nanosheet is only a few atomic layers thick and tens of nanometers wide and it is surface-modified with oleylamine so it can be well dispersed in oil or lubricant without adscititious dispersants or surfactants. By adding 1 wt% ultrathin MoS2 nanosheets, at the temperature of 120 °C, the highest load liquid paraffin can bear is tremendously improved from less than 50 N to more than 2000 N. Based on the tribological tests and analysis of the wear scar, a lubrication mechanism is proposed. It is believed that the good dispersion and the ultrathin shape of the nanosheets ensure that they can enter the contact area of the opposite sliding surfaces and act like a protective film to prevent direct contact and seizure between them. This work enriches the investigation of ultrathin MoS2 and has potential application in the mechanical industry.

Some natural product leads of drugs (NPLDs) have been found to congregate in the chemical space. The extent, detailed patterns and mechanisms of this congregation phenomenon have not been fully investigated and their usefulness for NPLD discovery needs to be more extensively tested. In this work, we generated and evaluated the distribution patterns of 442 NPLDs of 749 pre-2013 approved and 263 clinical trial small molecule drugs in the chemical space represented by the molecular scaffold and fingerprint trees of 137,836 non-redundant natural products. In the molecular scaffold trees, 62.7% approved and 37.4% clinical trial NPLDs congregate in 62 drug-productive scaffolds/scaffold-branches. In the molecular fingerprint tree, 82.5% approved and 63.0% clinical trial NPLDs are clustered in 60 drug-productive clusters (DCs) partly due to their preferential binding to 45 privileged target-site classes. The distribution patterns of the NPLDs are distinguished from those of the bioactive natural products. 11.7% of the NPLDs in these DCs have remote-similarity relationship with the nearest NPLD in their own DC. The majority of the new NPLDs emerge from preexisting DCs. The usefulness of the derived knowledge for NPLD discovery was demonstrated by the recognition of the new NPLDs of 2013–2014 approved drugs.

In this paper, we report our experimental study on directly coupling a micro/nano fiber (MNOF) ring with a side-polished fiber(SPF). As a result of the study, the behavior of an add-drop filter was observed. The demonstrated add-drop filter explored the wavelength dependence of light coupling between a MNOF ring and a SPF. The characteristics of the filter and its performance dependence on the MNOF ring diameter were investigated experimentally. The investigation resulted in an empirically obtained ring diameter that showed relatively good filter performance. Since light coupling between a (MNOF) and a conventional single mode fiber has remained a challenge in the photonic integration community, the present study may provide an alternative way to couple light between a MNOF device and a conventional single mode fiber based device or system. The hybridization approach that uses a SPF as a platform to integrate a MNOF device may enable the realization of other all-fiber optical hybrid devices.

Ediacara fossils are central to our understanding of animal evolution on the eve of the Cambrian explosion, because some of them likely represent stem-group marine animals. However, some of the iconic Ediacara fossils have also been interpreted as terrestrial lichens or microbial colonies. Our ability to test these hypotheses is limited by a taphonomic bias that most Ediacara fossils are preserved in sandstones and siltstones. Here we report several iconic Ediacara fossils and an annulated tubular fossil (reconstructed as an erect epibenthic organism with uniserial arranged modular units), from marine limestone of the 551–541 Ma Dengying Formation in South China. These fossils significantly expand the ecological ranges of several key Ediacara taxa and support that they are marine organisms rather than terrestrial lichens or microbial colonies. Their close association with abundant bilaterian burrows also indicates that they could tolerate and may have survived moderate levels of bioturbation.