PKMYT1 knockdown inhibits cholesterol biosynthesis and promotes the drug sensitivity of triple-negative breast cancer cells to atorvastatin.

Triple negative breast cancer (TNBC) as the most aggressive molecular subtype of breast cancer is characterized by high cancer cell proliferation and poor patient prognosis. Abnormal lipid metabolism contributes to the malignant process of cancers. Study observed significantly enhanced cholesterol biosynthesis in TNBC. However, the mechanisms underlying the abnormal increase of cholesterol biosynthesis in TNBC are still unclear. Hence, we identified a member of the serine/threonine protein kinase family PKMYT1 as a key driver of cholesterol synthesis in TNBC cells. Aberrantly high-expressed PKMYT1 in TNBC was indicative of unfavorable prognostic outcomes. In addition, PKMYT1 promoted sterol regulatory element-binding protein 2 (SREBP2)-mediated expression of enzymes related to cholesterol biosynthesis through activating the TNF/ TNF receptor-associated factor 1 (TRAF1)/AKT pathway. Notably, downregulation of PKMYT1 significantly inhibited the feedback upregulation of statin-mediated cholesterol biosynthesis, whereas knockdown of PKMYT1 promoted the drug sensitivity of atorvastatin in TNBC cells. Overall, our study revealed a novel function of PKMYT1 in TNBC cholesterol biosynthesis, providing a new target for targeting tumor metabolic reprogramming in the cancer.

Regulation of Microtubule Stability in Pulmonary Microvascular Endothelial Cells in Rats with Severe Acute Pancreatitis: Qingyi Decoction is a Potential CDK5 Inhibitor.

Purpose: Explore the therapeutic effects and regulatory mechanism of Qingyi Decoction (QYD) on severe acute pancreatitis (SAP) associated acute lung injury (ALI). Methods: We identified the constituents absorbed into the blood of QYD based on a network pharmacological strategy. The differentially expressed genes from the GEO database were screened to identify the critical targets of QYD treatment of SAP-ALI. The SAP-ALI rat model was constructed.Some methods were used to evaluate the efficacy and mechanism of QYD in treating SAP-ALI. LPS-stimulated pulmonary microvascular endothelial cell injury simulated the SAP-induced pulmonary endothelial injury model. We further observed the therapeutic effect of QYD and CDK5 plasmid transfection on endothelial cell injury. Results: 18 constituents were absorbed into the blood, and 764 targets were identified from QYD, 25 of which were considered core targets for treating SAP-ALI. CDK5 was identified as the most critical gene. The results of differential expression analysis showed that the mRNA expression level of CDK5 in the blood of SAP patients was significantly up-regulated compared with that of healthy people. Animal experiments have demonstrated that QYD can alleviate pancreatic and lung injury inflammatory response and reduce the upregulation of CDK5 in lung tissue. QYD or CDK5 inhibitors could decrease the expression of NFAT5 and GEF-H1, and increase the expression of ACE-tub in SAP rat lung tissue. Cell experiments proved that QYD could inhibit the expression of TNF-α and IL-6 induced by LPS. Immunofluorescence results suggested that QYD could alleviate the cytoskeleton damage of endothelial cells, and the mechanism might be related to the inhibition of CDK5-mediated activation of NFAT5, GEF-H1, and ACE-tub. Conclusion: CDK5 has been identified as a critical target for pulmonary endothelial injury of SAP-ALI. QYD may partially alleviate microtubule disassembly by targeting the CDK5/NFAT5/GEF-H1 signaling pathway, thus relieving SAP-induced pulmonary microvascular endothelial cell injury.

Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis.

The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.

Exploring the resistance mechanism of triple-negative breast cancer to paclitaxel through the scRNA-seq analysis.

BACKGROUND: The triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer with high aggressiveness. Although paclitaxel-based chemotherapy scenario present the mainstay in TNBC treatment, paclitaxel resistance is still a striking obstacle for cancer cure. So it is imperative to probe new therapeutic targets through illustrating the mechanisms underlying paclitaxel chemoresistance. METHODS: The Single cell RNA sequencing (scRNA-seq) data of TNBC cells treated with paclitaxel at different points were downloaded from the Gene Expression Omnibus (GEO) database. The Seurat R package was used to filter and integrate the scRNA-seq expression matrix. Cells were further clustered by the FindClusters function, and the gene marker of each subset was defined by FindAllMarkers function. Then, the hallmark score of each cell was calculated by AUCell R package, the biological function of the highly expressed interest genes was analyzed by the DAVID database. Subsequently, we performed pseudotime analysis to explore the change patterns of drug resistance genes and SCENIC analysis to identify the key transcription factors (TFs). Finally, the inhibitors of which were also analyzed by the CTD database. RESULTS: We finally obtained 6 cell subsets from 2798 cells, which were marked as AKR1C3+, WNT7A+, FAM72B+, RERG+, IDO1+ and HEY1+HCC1143 cell subsets, among which the AKR1C3+, IDO1+ and HEY1+ cell subsets proportions increased with increasing treatment time, and then were regarded as paclitaxel resistance subsets. Hallmark score and pseudotime analysis showed that these paclitaxel resistance subsets were associated with the inflammatory response, virus and interferon response activation. In addition, the gene regulatory networks (GRNs) indicated that 3 key TFs (STAT1, CEBPB and IRF7) played vital role in promoting resistance development, and five common inhibitors targeted these TFs as potential combination therapies of paclitaxel were identified. CONCLUSION: In this study, we identified 3 paclitaxel resistance relevant IFs and their inhibitors, which offers essential molecular basis for paclitaxel resistance and beneficial guidance for the combination of paclitaxel in clinical TNBC therapy.

Emodin Ameliorates Severe Acute Pancreatitis-Associated Acute Lung Injury in Rats by Modulating Exosome-Specific miRNA Expression Profiles.

Background: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear. Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO. Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats. Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO.

Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.

BACKGROUND: In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood. OBJECTIVE: This study aimed to explore the potential mechanism of NMF for treating COVID-19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification. METHODS: The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification. RESULTS: Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity. CONCLUSION: Our findings provided theoretical grounds for NMF in the treatment of COVID19.

Integrated profiling identifies CACNG3 as a prognostic biomarker for patients with glioma.

Gliomas are the most common malignant primary brain tumors in adults with poor prognoses. The purpose of this study is to explore CACNG3 as a prognostic factor that is closely related to the progression and survival outcome of gliomas and to provide a potential new molecular target for the diagnosis and treatment of glioma patients. CACNG3 expression and related clinical data were collected from three major databases of The Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO). The CGGA dataset was used as a training set, and TCGA and GEO datasets obtained from the GEO database were used for validation. CACNG3 was expressed at low levels in the tumor group, and the overall survival (OS) in patients with low CACNG3 expression is shorter. Furthermore, CACNG3 expression was negatively associated with glioma grades, which was confirmed in the IHC results of clinical samples. The expression level of CACNG3 in the IDH1 wide-type group, 1p/19q non-codel group, and mesenchymal subtype group was significantly reduced, and the results showed that CACNG3 could serve as a biomarker for the mesenchymal molecular subtype. In addition, the univariate and multivariate analysis verified the prognostic value of CACNG3 in predicting the OS of gliomas of all grades. The results of functional annotation and pathway enrichment analysis of differently expressed genes(DEGs), showed that CACNG3 might affect the development of glioma by interfering with synaptic transmission. Moreover, temozolomide (TMZ), commonly used in the treatment of glioma, increased CACNG3 expression in a dose and time-dependent manner. Therefore, CACNG3 plays a vital role in the occurrence and development of gliomas and can serve as a potential biomarker for targeted therapy and further investigation in the future.

Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning.

Immunogenic cell death (ICD) is a form of programmed cell death with a strong sense of inflammatory detection, whose powerful situational awareness can cause the reactivation of aberrant immunity. However, the role of ICD in the pathogenesis of severe acute pancreatitis (SAP) has yet to be investigated. This study aims to explore the pivotal genes associated with ICD in SAP and how they relate to immune infiltration and short-chain fatty acids (SCFAs), in order to provide a theoretical foundation for further, in-depth mechanistic studies. We downloaded GSE194331 datasets from the Gene Expression Omnibus (GEO). The use of differentially expressed gene (DEG) analysis; weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis allowed us to identify a total of three ICD-related hub genes (LY96, BCL2, IFNGR1) in SAP. Furthermore, single sample gene set enrichment analysis (ssGSEA) demonstrated that hub genes are closely associated with the infiltration of specific immune cells, the activation of immune pathways and the metabolism of SCFAs (especially butyrate). These findings were validated through the analysis of gene expression patterns in both clinical patients and rat animal models of SAP. In conclusion, the first concept of ICD in the pathogenesis of SAP was proposed in our study. This has important implications for future investigations into the pro-inflammatory immune mechanisms mediated by damage-associated molecular patterns (DAMPs) in the late stages of SAP.

Clarifying the role of an unavailable distractor in human multiattribute choice.

Decisions between two economic goods can be swayed by a third unavailable 'decoy' alternative, which does not compete for choice, notoriously violating the principles of rational choice theory. Although decoy effects typically depend on the decoy's position in a multiattribute choice space, recent studies using risky prospects (i.e., varying in reward and probability) reported a novel 'positive' decoy effect operating on a single value dimension: the higher the 'expected value' (EV) of an unavailable (distractor) prospect was, the easier the discrimination between two available target prospects became, especially when their expected-value difference was small. Here, we show that this unidimensional distractor effect affords alternative interpretations: it occurred because the distractor's EV covaried positively with the subjective utility difference between the two targets. Looking beyond this covariation, we report a modest 'negative' distractor effect operating on subjective utility, as well as classic multiattribute decoy effects. A normatively meaningful model (selective integration), in which subjective utilities are shaped by intra-attribute information distortion, reproduces the multiattribute decoy effects, and as an epiphenomenon, the negative unidimensional distractor effect. These findings clarify the modulatory role of an unavailable distracting option, shedding fresh light on the mechanisms that govern multiattribute decisions.

A Cartoon Version of Braden Scale to Assess the Risk of Pressure Injury: Content Validity and Interrater Reliability Study.

INTRODUCTION: The Braden Scale is widely used to assess the risk of pressure injury. However, the vague literal description of the items creates difficulties for bedside nurses and limits its sensitivity. To solve this problem, we developed a cartoon version of the Braden scale (CVBS) to improve the pressure injury risk assessment ability of bedside nurses. METHODS: The CVBS was constructed by two nurses, and the final version was determined through a two-round Delphi consultation. The scale's content validity was calculated based on expert ratings. A total of 265 patients were evaluated simultaneously with the CVBS by 119 bedside nurses and 46 wound care specialists; and 114 bedside nurses and the same 46 wound care specialists evaluated 239 patients with the original Braden scale (OBS). The interrater reliability between the two groups was calculated as Kappa value, and then the Kappa values of the two versions were compared. RESULTS: The content validity for the draft scale was not good enough. After modification, the indices of all the items in the final CVBS reached 1.00. The Kappa value of the OBS was 0.69 (95% CI 0.61-0.76); for each item, it ranged from 0.60 to 0.80. The interrater reliabilities of the CVBS were higher than those of the OBS, with an overall kappa value of 0.87 (95% CI 0.81-0.92) and a range of 0.77 to 0.93 for each item. The differences between the Kappa values of the CVBS and those of the OBS were all statistically significant. CONCLUSIONS: The CVBS had good validity and showed higher interrater reliability than the OBS, indicating that it may improve bedside nurses' ability to assess pressure injury risk.

Protective effect of endoplasmic reticulum stress inhibition on 5-fluorouracil-induced oral mucositis.

5-Fluorouracil (5-FU)-induced oral mucositis has a severe negative impact on the patient's quality of life. This study aimed to investigate the role of endoplasmic reticulum stress (ERS) in the occurrence of 5-FU-induced oral mucositis in vivo and in the clinic. In vivo, 5-FU-induced oral mucositis model mice showed a higher level of glucose-regulated protein 78 kD (GRP78, a marker of ERS) than control mice. The inhibition of ERS could effectively reduce 5-FU-induced oxidative stress, inflammatory factor mRNA and cell apoptosis. Moreover, inhibition of ERS significantly decreased the activation of nuclear factor kappa-B (NF-κB) in 5-FU-induced oral mucositis model mice following tissue damage reduction. In the clinic, 5-FU could increase cell apoptosis and cause oral mucosa damage while increasing the expression of the ERS marker genes GRP78 and C/EBP-homologous protein (CHOP). Our study found that 5-FU could induce severe ERS, upregulate the expression of GRP78 and CHOP, raise oxidative stress and increase the expression of inflammatory factors by activating the NF-κB pathway, thus causing cell apoptosis and finally leading to oral mucosal injury.

Efficacy and safety evaluation of bright light therapy in patients with post-stroke insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke insomnia (PSI) is a common and severe illness among the complications of stroke. Although there are plenty of drugs currently used for PSI treatment, they generate several side effects and other problems. Bright light therapy (BLT) is thought to be relatively safe and effective in treating PSI patients. Despite this, there is still a lack of systematic review on BLT in the treatment of PSI. Allowing for this, the aim of this study is to assess the efficacy and safety of BLT for PSI. METHODS: The meta-analysis and systematic review will perform a comprehensive electronic search for items fulfilling the required criteria in Web of Science, Google Scholar, Wan Fang database, MEDLINE, Baidu Scholar, PubMed, SinoMed, Embase, Chinese Biomedical Literature Database (CBM), China national knowledge infrastructure database (CNKI), Cochrane Library Central Register of Controlled Trials (CENTRAL), and Wei Pu database from establishment to January 1, 2022. We will select articles, collect data, and assess the methodology quality. And we will set the primary outcome and secondary outcomes in this research. RevMan 5.3 software will be used to analyze the data for this investigation. RESULTS: The work of this research will be published in peer-reviewed scientific journals. CONCLUSION: The aim of this study is to assess the efficacy and safety of BLT for PSI and present robust scientific evidence concerning BLT for PSI. REGISTRATION: INPLASY2021100065.

Outcomes of present-on-admission pressure injuries at discharge and potential prognostic factors: A historical cohort study in China.

BACKGROUND: The prevalence of present-on-admission pressure injuries (POA-PIs) is much higher than hospital-acquired pressure injuries (HAPIs). But scant attention has been paid to POA-PIs, especially the healing rate and potential prognostic factors. OBJECTIVE: To describe the characteristics of POA-PIs at admission and the outcomes of POA-PIs at discharge, and to explore potential prognostic factors of POA-PIs wound healing. METHODS: This study analyzed electronic health records (EHRs) for 838 POA-PIs among 586 patients from a Chinese tertiary hospital in 2018. The outcomes of POA-PIs were identified into four categories by comparing POA-PIs' wound area and exudation amount scores at admission and discharge: deteriorating, stable, improving, and healed. The generalized estimating equation (GEE) was carried out to screen the prognostic factors of POA-PIs wound healing. RESULTS: Among this population, 66.38% of the patients were male, 44.03% patients had a Braden Score less than 12 and the median of the Charlson comorbidity index was 5. The most common location of POA-PI wounds was the sacrum and the most common stage of them was Stage II. Nearly half of wounds (45.78%) were larger than 15 cm2, 26.61% were deeper than 0.5 cm, and 61.81% of the wounds were painful. When the patients were discharged, 29.71% wounds were healed, 36.16% were in improving status, 25.78% kept stable, and 8.35% wounds were in deteriorating status. Wound depth was the only independent prognostic factor for POA-PIs wound healing. CONCLUSIONS: The healing rate of POA-PIs is quite low, and the only independent prognostic factor of POA-PIs was wound depth.

Removal of gaseous elemental mercury by hydrogen chloride non-thermal plasma modified biochar.

Hydrogen chloride (HCl) non-thermal plasma was applied to introduce Cl active sites on biochar prepared from sorghum straw in this study. Surface modified biochar was then placed in flue gas with typical components to investigate its elemental mercury (Hg0) capture ability. To elucidate the adsorption mechanism & binding properties, samples were characterized by N2 adsorption, scanning electron microscopy with energy dispersive spectrometer (SEM-EDS) and X-ray absorption near edge structure (XANES) analysis of Hg LIII-edge, Cl K-edge and S K-edge. Experimental results showed that HCl plasma modification successfully increased Cl active sites on biochar and greatly increased its mercury removal efficiency. Both HCl treatments (w/without plasma involvement) altered biochar's surface structure and layered structure generated. XANES spectra revealed that adsorbed-Hg on HCl-treated biochars mainly in the form of Hg+. Gaseous Hg0 was believed to heterogeneously react with chlorinated sites through electron-transfer and formed Hg2Cl2 compounds. With the presence of NO or SO2 in the system, adsorbed mercury existed on biochar mainly as Hg+. SO2 competed and inhibited the adsorption of Hg0; while NO promoted Hg0 removal capacity by increasing the active sites and enhancing the adsorption kinetics of adjacent Cl-containing sites.

Study on the effects of oxygen-containing functional groups on Hg0 adsorption in simulated flue gas by XAFS and XPS analysis.

The effect of physicochemical properties of activated carbon on adsorption of elemental mercury (Hg0) was investigated on a series of modified activated carbons. Heat treatment and benzoic acid impregnation were conducted to vary the oxygen functional groups on carbon surface. Hg0 adsorption experiments were run in a fixed-bed reactor at 140 °C. Surface characteristics of carbon samples were studied by N2 adsorption, Boehm titration, X-ray photoelectron spectroscopy (XPS) and X-ray absorption fine structure (XAFS), respectively. The predominant mechanism of Hg0 removal was the formation of chemical bonds between Hg and various functional groups. Both XPS and XAFS analysis revealed that mercury bound on carbon surface was mainly in oxidation state. Under N2 atmosphere, the absorbed Hg was found as Hg2+, and coordinated to O atom. With the existence of HCl in simulated flue gas, Hg0 was bonded on Cl sites and HgCl2 was assumed to be the dominated form.

Causal Inference in the Multisensory Brain.

When combining information across different senses, humans need to flexibly select cues of a common origin while avoiding distraction from irrelevant inputs. The brain could solve this challenge using a hierarchical principle by deriving rapidly a fused sensory estimate for computational expediency and, later and if required, filtering out irrelevant signals based on the inferred sensory cause(s). Analyzing time- and source-resolved human magnetoencephalographic data, we unveil a systematic spatiotemporal cascade of the relevant computations, starting with early segregated unisensory representations, continuing with sensory fusion in parietal-temporal regions, and culminating as causal inference in the frontal lobe. Our results reconcile previous computational accounts of multisensory perception by showing that prefrontal cortex guides flexible integrative behavior based on candidate representations established in sensory and association cortices, thereby framing multisensory integration in the generalized context of adaptive behavior.

Melamine negatively affects testosterone synthesis in mice.

Several studies have found that melamine causes damage to the testes, epididymis and sperm. However, few studies have investigated the effect of melamine on the synthesis of testosterone, which plays an import role in testicular development and spermatogenesis. In present study, mice were orally administrated with 2, 10 or 50mg/kg of melamine for 28days. In these groups, various abnormalities were observed including disruption of the seminiferous tubule structure, an increased necrotic germ cells and sperm abnormalities, and a reduced sperm count. Melamine exposure also decreased the level of serum testosterone and levels of testicular StAR, P450scc and 17ß-HSD. In addition, melamine exposure reduced the number of Leydig cells. Taken together, these results indicate that melamine exposure reduces the level of testosterone through down-regulation of StAR and testosterone synthetic enzyme expression and also a decreased number of Leydig cells. This may further affect testicular development and lead to sperm damage.

Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid.

Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17ß-HSD I, and 17ß-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats.

The dominance of haptics over audition in controlling wrist velocity during striking movements.

Skilled interactions with sounding objects, such as drumming, rely on resolving the uncertainty in the acoustical and tactual feedback signals generated by vibrating objects. Uncertainty may arise from mis-estimation of the objects' geometry-independent mechanical properties, such as surface stiffness. How multisensory information feeds back into the fine-tuning of sound-generating actions remains unexplored. Participants (percussionists, non-percussion musicians, or non-musicians) held a stylus and learned to control their wrist velocity while repeatedly striking a virtual sounding object whose surface stiffness was under computer control. Sensory feedback was manipulated by perturbing the surface stiffness specified by audition and haptics in a congruent or incongruent manner. The compensatory changes in striking velocity were measured as the motor effects of the sensory perturbations, and sensory dominance was quantified by the asymmetry of congruency effects across audition and haptics. A pronounced dominance of haptics over audition suggested a superior utility of somatosensation developed through long-term experience with object exploration. Large interindividual differences in the motor effects of haptic perturbation potentially arose from a differential reliance on the type of tactual prediction error for which participants tend to compensate: vibrotactile force versus object deformation. Musical experience did not have much of an effect beyond a slightly greater reliance on object deformation in mallet percussionists. The bias toward haptics in the presence of crossmodal perturbations was greater when participants appeared to rely on object deformation feedback, suggesting a weaker association between haptically sensed object deformation and the acoustical structure of concomitant sound during everyday experience of actions upon objects.

Occurrence of 13 veterinary drugs in animal manure-amended soils in Eastern China.

The occurrence of 13 veterinary drugs were studied in soil fertilized with animal manures in Eastern China. The 69 soil samples were obtained from twenty-three vegetable fields in 2009 and analysed for selected veterinary drugs by HPLC-MS/MS at soil depths of 0-20, 20-40 and 40-60 cm, and two additional samples were re-analysed from an earlier study from November 2011. Results showed that animal wastes, especially those from poultry farms, were one of pollution sources of veterinary drugs in soil. The detection frequency of veterinary drugs in soil was 83%, 91% and 87% in the three soil depths, respectively. The detection rates for the five classes of drugs in soils followed the rank order cyromazine > tetracyclines > sulfonamides > fluoroquinolones > florfenicol. Veterinary drugs were detected in soil layers at 20-40 and 40-60 cm depth to a greater extent than at 0-20 cm depth. The results of the same point in years 2009 and 2011 indicated that veterinary drugs accumulate easily and persist in the deeper soil. In addition, residue levels of veterinary drugs in soil were related to the animal species the manure was derived from. Overall, the predominance of tetracyclines in sampled soils underscored the need to regulate their veterinary use in order to improve the management and treatment of associated releases.