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Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2’,3’-O-(2,4,6-trinitrophenyl)-adenosine 5’-triphosphate), a nonspecific P2X1–7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4–L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

In this study, we compared the concentrations of the heavy metals Cd, Cr, Cu, Zn, Ni, and Pb in the surface soils of urban parks in Wuhan, Hubei Province with those in the surface soils of urban parks worldwide. The soil contamination data were assessed using enrichment factors, and spatial analysis of heavy metals using inverse distance weighting and quantitative analysis of heavy metal sources with a positive definite matrix factor (PMF) receptor model. Further, a probabilistic health risk assessment of children and adults using Monte Carlo simulation was performed. The average Cd, Cr, Cu, Zn, Ni, and Pb concentrations in the surface soils of urban parks were 2.52, 58.74, 31.39, 186.28, 27.00, and 34.89 mg·kg−1, respectively, which exceeded the average soil background values in Hubei. From the inverse distance spatial interpolation map, heavy metal contamination was primarily observed to be present to the southwest of the main urban area. The PMF model resolved four sources: mixed traffic and industrial emission, natural, agricultural, and traffic sources, with relative contributions of 23.9%, 19.3%, 23.4%, and 33.4%, respectively. The Monte Carlo health risk evaluation model demonstrated negligible noncancer risks for both adult and child populations, whereas the health effects of Cd and Cr on children were a concern for cancer risks.

In this research, enrichment factor (EF) and pollution load index (PLI) were utilized to explore the contamination characteristics of toxic elements (TEs). The results exhibited that the study area was mainly moderately polluted, and the EF values of Cd, Zn, Pb, Cu and Sb were all > 1, which were cumulative. The concentrations of Cr, Cu, Zn and Pb increased with the decrease of dust particle size. The investigation results of chemical speciation and bioavailability of TEs showed that Zn had the highest bioavailability. Three sources of TEs were determined by positive matrix factorization (PMF), Pearson correlation analysis and geostatistical analyst, comprising factor 1 mixed sources of industrial and transportation activities (46.62%), factor 2 natural source (25.56%) and factor 3 mixed source of agricultural activities and the aging of park infrastructures (27.82%). Potential ecological risk (PER) and human health risk (HHR) based on PMF model were exploited to estimate PER and HHR of TEs from different sources. The PER value of TE in the park dust was 114, indicating that ecological risk in the study area was relatively high. Factor 1 contributed the most to PER, and the pollution of Cd was the most serious. There were no significant carcinogenic and non-carcinogenic risks for children and adults in the study area. And factor 3 was the biggest source of non-carcinogenic risk, As, Cr and Pb were the chief contributor to non-carcinogenic risk. The primary source of carcinogenic risk was factor 2, Cr was the cardinal cancer risk element.

In this research, enrichment factor (EF) and pollution load index (PLI) were utilized to estimate the features of enrichment and contamination of PTEs in farmland soil. Furthermore, combining the spatial distribution characteristics of potentially toxic elements (PTEs) and positive matrix factorization (PMF) to distinguish and quantify the sources of PTEs in farmland soil, and then the potential ecological risk (PER) and human health risk (HHR) model based on PMF are applied to quantify the ecological and human health risks from different sources. Taking Puning District as an example, four sources of PTEs in farmland soil were quantitatively allocated. For ecological risk, the study area is at moderate ecological hazard level, and industrial activities were the greatest contributor. The mean E_r^i of Hg were 69.82, reaching medium ecological risk level. For human health risks, both adults and children have no evident non-carcinogenic risk in the study area. And natural source was the largest contributor to non-carcinogenic risk, followed by agricultural activities. With regard to carcinogenic risk, tolerable risks of soil PTEs in the study area were limited not only for adults but also for children. Furthermore, compared with adults, the health risks of children, whether non-carcinogenic or carcinogenic, were higher than those of adults, and the trends in health risks for children and adults were similar. A comprehensive scheme combining source contribution and risk assessment is conducive to quantitatively assess ecological risks, health risks and priority pollution sources, thereupon provide effective suggestions for protecting human health and preventing and controlling pollution.

Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.

Study question Does endothelin-1 (ET-1) promote human oocyte maturation and by what mechanism? Summary answer Addition of ET-1 to the medium in which human germinal vesicle (GV)-stage immature oocytes are cultured enhances the GV breakdown (GVBD) rate; the resumption of meiosis may be initiated by ET-1 downregulating the expression of connexin-26 (Cx26) in cumulus cells via endothelin receptor type B (ETRB), leading to decreased cAMP levels in the oocyte. What is known already The paracrine factor ET-1 is secreted by ovarian somatic cells in pre-ovulatory follicles and regulates oocyte maturation in mice. Connexins, or gap junction proteins, form intercellular membrane channels that play important roles in the resumption of meiosis. Study design, size, duration This laboratory study was conducted over a 1-year period. The effects of ET-1 on meiotic resumption were evaluated in human GV-stage cumulus-oocyte complexes (COCs; 70 oocytes/group). The transcriptome profiles of ET-1-treated or untreated cumulus cells were compared to explore the possible mechanisms by which ET-1 may regulate oocyte maturation. Participants/materials, setting, methods The ET-1, ETRA and ETRB expression levels in human cumulus cells from oocytes at different stages of maturation were evaluated using real-time quantitative PCR. Human GV-stage COCs collected from patients undergoing IVF at a university-affiliated infertility centre were cultured with or without ET-1, and cumulus cells were subsequently denuded using hyaluronidase and cultured in α-MEM. A GeneChip® Human Transcriptome Array was applied to explore differences in the whole-genome transcriptome profiles of cumulus cells treated with or without ET-1. Real-time quantitative PCR and Western blotting were used respectively to examine Cx26 mRNA and protein levels in cumulus cells. Changes in cAMP levels in both oocytes and cumulus cells after ET-1 treatment were measured using an enzyme-linked immunosorbent assay. Main results and the role of chance Cumulus cells from MII-stage oocytes exhibited upregulated ET-1 expression, compared to those from GV-stage oocytes. The addition of ET-1 to the culture medium enhanced the GVBD rate of cumulus cell-enclosed human oocytes. Whole-genome transcriptome microarray analyses revealed significantly downregulated Cx26 expression in cumulus cells after ET-1 treatment, and this action was blocked by an ETRB antagonist. The involvement of Cx26 was further supported by the finding that ET-1 treatment led to decreased cAMP levels in oocytes but increased cAMP levels in cumulus cells. Large scale data Microarray data are published in the GEO database (GSE97684). Limitations, reasons for caution The heterogeneity of human COCs collected from patients undergoing IVF might affect the maturation results in vitro. Although we focused on the effects of ET-1 on human oocyte maturation in the present study, mammalian oocyte maturation is a complicated process involving many endocrine and paracrine factors. Wider implications of the findings Our present study suggests that in vitro, human GV-stage oocyte maturation could be enhanced by adding ET-1 to the culture medium. In the present study, we explored the molecular mechanisms by which ET-1 initiates the resumption of meiosis and demonstrated that ET-1 promotes oocyte maturation by downregulating the expression of the gap junction protein Cx26 in cumulus cells. These results expand our understanding of the molecular mechanisms underlying mammalian oocyte maturation and provide a basis for better in-vitro maturation strategies. Study funding and competing interests This work was supported by grants from the China Natural Science Foundation (Grant Nos. 81170567 and 81370761). The authors declare that they have no conflicts of interest associated with this manuscript.

Schizophrenia is a severe psychiatric disorder with complex clinical manifestations and its aetiological factors remain unclear. During the past decade, the oligodendrocyte-related myelin dysfunction was proposed as a hypothesis for schizophrenia, supported initially by a series of neuroimaging studies and genetic evidence. Recently, the effects of antipsychotics on myelination and oligodendroglial lineage development and their underlying molecular mechanisms were evaluated. Data from those studies suggest that the antipsychotics-resulting improvement in myelin/oligodendrocyte-related dysfunction may contribute, at least in part, to their therapeutic effect on schizophrenia. Importantly, these findings may provide the basis for a new insight into the therapeutic strategy by targeting the oligodendroglia lineage cells against schizophrenia.

Objectives To explore whether transcutaneous electrical acupoint stimulation (TEAS) can improve the outcomes of in vitro fertilization (IVF). Design A prospective, randomized and controlled study. Setting IVF center in a university hospital. Participants Four hundred and eighty-one infertile patients with bilateral tubal blockage who were referred for IVF. Patients were randomized into four groups. Intervention TEAS was administered for 30 min, respectively at 24 h before TVOR and 2 h before ET. The acupoints included SP10 (Xuehai, bilateral), SP8 (Diji, bilateral), LR3 (Taichong, bilateral), ST36 (Zusanli, bilateral), EX-CA1 (Zigong, bilateral), RN4 (Guanyuan), PC6 (Neiguan, bilateral) and RN12 (Zhongwan). Based on different frequencies of TEAS, patients were grouped into a TEAS-2 Hz group, a TEAS-100 Hz group and a TEAS-2/100 Hz group. Patients in the control group only received routine IVF treatment and no TEAS were applied on them. Primary and secondary outcome measures The number of mature oocytes, normally fertilized oocytes and good-quality embryos were used to evaluate oocyte developmental competence of the patients. Data of clinical pregnancy rate (CPR), implantation rate (IR) and live birth rate (LBR) were also obtained. The levels of neuropeptide Y (NPY), transforming growth factor alpha and granulocyte colony-stimulating factor in the follicular fluids were measured with enzyme-linked immunosorbent assay (ELISA). Results No significant differences were found between the control, TEAS-2 Hz, TEAS-100 Hz and TEAS-2/100 Hz groups on the numbers of metaphase II oocytes, normally fertilized zygotes, early cleavage embryos or good quality embryos (P>0.05). However, the CPR, IR and LBR of the TEAS-2/100 Hz group were significantly higher than those of the other groups, respectively (P

An ionic-liquid-like copolymer was used to stabilize the platinum nanoclusters in ionic liquids. Catalytic performance was tested by the selective hydrogenation of o-chloronitrobenzene. Platinum catalysts Pt-I (5.1 nm) and Pt-II (1.7 nm) both exhibited excellent activity and selectivity for the reaction and were recycled with the activity and selectivity preserved. An unprecedented total turnover number (>25,900) was obtained on the Pt-II catalyst. Infrared spectroscopy, transmission electron microscopy, X-ray diffraction characterizations, and density functional theory calculations were used to study the catalysts.

Rhodium nanoparticles stabilized by the ionic-liq.-like copolymer N-Vinyl-2-pyrrolidone-1-vinyl-3-butylimidazolium chloride-1-vinyl-3-ethylimidazolium bromide copolymer were used to catalyze the hydrogenation of benzene and other arenes in ILs. The nanoparticle catalysts can endure forcing conditions (75 °C, 40 bar H2), resulting in high reaction rates and high conversions compared with other nanoparticles that operate in ILs. The hydrogenation of benzene attained record total turnovers of 20,000, and the products were easily sepd. without being contaminated by the catalysts. Other substrates, including alkyl-substituted arenes, phenol, 4-n-propylphenol, 4-methoxylphenol, and phenyl-methanol, were studied and in most cases were found to afford partially hydrogenated products in addn. to cyclohexanes. In-depth investigations on reaction optimization, including characterization of copolymers, TEM, and an IR spectroscopic study of nanocatalysts, were carried out.

To investigate the changes and of serum cardiotrophin I (cTN I) and cystatin C in preeclampsia clinical significance thereof.Peripheral blood samples were collected from 40 women with preeclampsia, aged 29 (18 - 39), with the medium gestational age of 35 weeks, and 40 age- and gestational age-matched controls. Serum cTN I and cystatin C were determined with ELISA and serum levels of creatinine kinase, creatinine, and uric acid were assayed by automatic biochemical analyzer. Comparison was made between the 2 groups.The serum cTn I of the preeclampsia group was 0.59 microg/L +/- 0.42 microg/L, significantly higher than that of the control group (0.09 microg/L +/- 0.22 microg/L P0.001), and the serum cystatin C of the preeclampsia group was 1.64 mg/L +/- 0.47 mg/L, significantly higher than that of the control group (1.08 mg/L +/- 0.19 mg/L, P0.001). And the serum cardiotrophin I and cystatin C concentrations of the patients with severe preeclampsia were 0.66 microg/L +/- 0.40 microg/L and 1.72 mg/L +/- 0.46 mg/L respectively, both significantly higher than those of the patients with mild preeclampsia (0.17 microg/L +/- 0.26 microg/L and 1.21 mg/L +/- 0.37 mg/L respectively, P0.001 and 0.05 respectively).Serum cTn I and cystatin C levels are elevated in preeclampsia and the elevation is associated with the severity of preeclampsia, suggesting that serum concentrations of cTn I and cystatin C are useful markers in the early diagnosis of cardiac and renal injury in patients of preeclampsia.