Search

Objective: To evaluate the effect of far-infrared radiation on postpartum perineal pain and sexual function in primiparous women undergoing an episiotomy and 2nd degree perineal laceration., Materials and Methods: From May 2016 to May 2017, primiparous women with term pregnancies and vaginal deliveries with an episiotomy due to obstetric indications and 2nd degree perineal lacerations were invited to participate in this study. Women were randomly assigned into a far-infrared (FIR) group and a control group. Visual Analogue Scale (VAS) was used to evaluate the perineal pain immediately postpartum, and at 1 week and 6 weeks postpartum. Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire (PISQ-12) was used to evaluate sexual function at 6 weeks, 3 months and 6 months postpartum., Results: The data of the control group (n = 22) and FIR group (n = 18) were analyzed. Most of the women had minor perineal pain one week after delivery (1.1 ± 0.9 in control group vs 1.4 ± 1.5 in FIR group) and there was no significant difference between groups. The FIR group had a higher PISQ-12 total score at 3 months (35.4 ± 6.4 vs 34.7 ± 5.7) and 6 months (36.4 ± 5.6 vs 35.6 ± 5.7) postpartum compared with the control group but there was no statistically significant difference., Conclusion: Our study did not show any additional benefit of postpartum far-infrared radiation on primiparous women undergoing an episiotomy and 2nd degree perineal lacerations., (Copyright © 2018. Published by Elsevier B.V.)

Alzheimer's disease (AD) is considered to one of 10 key diseases leading to death in humans. AD is considered the main cause of brain degeneration, and will lead to dementia. It is beneficial for affected patients to be diagnosed with the disease at an early stage so that efforts to manage the patient can begin as soon as possible. Most existing protocols diagnose AD by way of magnetic resonance imaging (MRI). However, because the size of the images produced is large, existing techniques that employ MRI technology are expensive and time-consuming to perform. With this in mind, in the current study, AD is predicted instead by the use of a support vector machine (SVM) method based on gene-coding protein sequence information. In our proposed method, the frequency of two consecutive amino acids is used to describe the sequence information. The accuracy of the proposed method for identifying AD is 85.7%, which is demonstrated by the obtained experimental results. The experimental results also show that the sequence information of gene-coding proteins can be used to predict AD.

Aim: The aim of this study is to investigate the clinical features of graft dysfunction following living kidney transplantation and to assess its causes., Methods: We retrospectively analyzed a series of 366 living kidney transplantation indication biopsies with a clear etiology and diagnosis from July 2003 to June 2016 at our center. The classifications and diagnoses were performed based on clinical and pathological characteristics. All biopsies were evaluated according to the Banff 2007 schema., Results: Acute rejection (AR) occurred in 85 cases (22.0%), chronic rejection (CR) in 62 cases (16.1%), borderline rejection (BR) in 12 cases (3.1%), calcineurin inhibitor (CNI) toxicity damage in 41 cases (10.6%), BK virus-associated nephropathy (BKVAN) in 43 cases (11.1%), de novo or recurrent renal diseases in 134 cases (34.7%), and other causes in nine cases (2.3%); additionally, 20 cases had two simultaneous causes. The 80 cases with IgA nephropathy (IgAN) had the highest incidence (59.7%) of de novo or recurrent renal diseases. After a mean ± SD follow up of 3.7 ± 2.3 years, the 5-year graft cumulative survival rates of AR, CR, CNI toxicity, BKVAN, and de novo or recurrent renal diseases were 60.1%, 31.2%, 66.6%, 66.9%, and 67.1%, respectively., Conclusions: A biopsy is helpful for the diagnosis of graft dysfunction. De novo or recurrent renal disease, represented by IgAN, is a major cause of graft dysfunction following living kidney transplantation.

Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60⁻95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described.

Background: Risperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia., Methods: Ninety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups., Results: A total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group., Conclusions: Both risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ., Competing Interests: There are no conflicts of interest

The association between circulating saturated fatty acids (SFAs) and incident type 2 diabetes (T2D) is reported in Western populations with inconsistent results, while evidence from Asian populations is scarce. We aimed to examine the associations between erythrocyte SFAs and incident T2D in a Chinese population. Between 2008 and 2013, a total of 2683 participants, aged 40⁻75 years, free of diabetes were included in the present analyses. Incident T2D cases were ascertained during follow-up visits. Gas chromatography was used to measure erythrocyte fatty acids at baseline. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During 13,508 person years of follow-up, 216 T2D cases were identified. Compared with the first quartile, multivariable-adjusted HRs (95% CIs) of the fourth quartile were 1.20 (0.82⁻1.76; p = 0.242) for myristic acid (14-carbon tail, zero double bonds; 14:0), 0.69 (0.48⁻0.99; p = 0.080) for palmitic acid (16:0), 1.49 (1.02⁻2.19; p = 0.047) for stearic acid (18:0), 1.46 (1.00⁻2.12; p = 0.035) for arachidic acid (20:0), 1.48 (0.99⁻2.22; p = 0.061) for behenic acid (22:0), and 1.08 (0.74⁻1.56; p = 0.913) for lignoceric acid (24:0). Our findings indicate that individual erythrocyte SFAs are associated with T2D in different directions, with 18:0 and 20:0 SFAs positively associated with the risk, whereas no convincing inverse association for 16:0 SFAs., Competing Interests: The authors declare no conflicts of interest.

Systemic bacterial infections are prone to secondary Candida albicans super-infection. However, the molecular mechanisms involved remain poorly understood. In this study, a model comprising sublethal cecal ligation and puncture plus C. albicans intravenous injection was applied to mimic the situation in super-infection. Compared with mice without systemic bacterial infection, mice with systemic bacterial infection had lower antifungal gene expression (including Il1b, Tnf, Il6, Ifnb, Ifng, Cxcl1, and Ccr2) in monocytes and less inflammatory monocytes and neutrophils infiltrating into the kidney when challenged with C. albicans. Further, lentivirus-mediated Setdb2-knockout and overexpression experiments verified that Setdb2 levels in monocytes correlated negatively with antifungal gene expression and survival rates. Transcriptional repression was probably achieved by Setdb2 through H3 methylation at lysine 9 in promoter regions of these antifungal genes., (© 2018 John Wiley & Sons Ltd.)

It has been widely reported that ketamine rescues chronic stress-induced depression-like behavior, but the underlying cellular mechanisms of the rapid antidepressant actions of ketamine remain largely unclear. Both male and female Sprague-Dawley rats were used and received modified learned helplessness paradigm to induce depression-like behavior. Depression-like behavior was assayed and manipulated using forced swim tests, sucrose preference tests and pharmacological microinjection. We conducted whole-cell patch-clamp electrophysiological recordings in the midbrain ventrolateral periaqueductal gray (vlPAG) neurons. Surface and cytosolic glutamate receptor 1 (GluR1) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression were analyzed using Western blotting. Phosphorylated GluR1 expression was quantified using Western blotting analysis. The results showed that a single systemic administration of a ketamine metabolite (2R,6R)-hydroxynorketamine (2R,6R-HNK) rapidly rescued chronic stress-induced depression-like behavior and persisted for up to 21 days. Consistently, the chronic stress-induced diminished glutamatergic transmission and surface GluR1 expression in the vlPAG were also reversed by a single systemic injection of (2R,6R)-HNK. Furthermore, bath application of (2R,6R)-HNK increased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in the vlPAG. Further evidence for the antidepressant action of (2R,6R)-HNK is provided by the finding that microinjection of (2R,6R)-HNK into the vlPAG exhibited a rapid-acting and long-lasting antidepressant effect. This antidepressant effect of (2R,6R)-HNK was prevented by the intra-vlPAG microinjection of AMPA receptor antagonist CNQX. Together, the current results provide evidence that (2R,6R)-HNK rescues chronic stress-induced depression-like behavior with rapid-acting and long-lasting antidepressant effects through enhancement of AMPA receptor-mediated transmission in the vlPAG., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Extraskeletal osteosarcoma (ESOS) is a rare soft-tissue sarcoma that is treated with surgical resection, chemotherapy and radiotherapy; however, as it is now considered to be radiation resistance, it is associated with conflicting management principles and poor outcomes. A multimodality approach is currently used to treat ESOS, which entails the incorporation of multidrug chemotherapy and/or radiotherapy coupled with surgery to obtain the best outcome; however, there are many factors that influence the treatment effects and clinical outcomes of ESOS. In the present study, a case of an 81-year-old man who suffered from primary ESOS in the subcutaneous tissue of the right-hand side of the neck was reported. The patient was treated several times with partial resection and once with radiotherapy, and was still living following 3 years of follow-up. Thus, the present case report demonstrated that surgical resection and postoperative radiotherapy regimens may be favourable in the short term with a disease-free survival of ~15 months; however, patients are prone to relapse.

Presynaptic active zone proteins play a crucial role in regulating synaptic plasticity. Although the ubiquitin-proteasome system underlying the degradation of the presynaptic active zone protein is well established, the contribution of this machinery to regulating spinal plasticity during neuropathic pain development remains unclear. Here, using male Sprague Dawley rats, we demonstrated along with behavioral allodynia, neuropathic injury induced a marked elevation in the expression levels of an active zone protein Munc13-1 in the homogenate and synaptic plasma membrane of the ipsilateral dorsal horn. Moreover, nerve injury-increased Munc13-1 expression was associated with an increase in the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in ipsilateral dorsal horn neurons. This neuropathic injury-induced accumulation of Munc13-1 colocalized with synaptophysin but not homer1 in the dorsal horn. Focal knockdown of spinal Munc13-1 expression attenuated behavioral allodynia and the increased frequency, not the amplitude, of mEPSCs in neuropathic rats. Remarkably, neuropathic injury decreased spinal Fbxo45 expression, Fbxo45-Munc13-1 co-precipitation, and Munc13-1 ubiquitination in the ipsilateral dorsal horn. Conversely, focal knockdown of spinal Fbxo45 expression in naive animals resulted in behavioral allodynia in association with similar protein expression and ubiquitination in the dorsal horn as observed with neuropathic injury rats. Furthermore, both neuropathic insults and intrathecal injection of tumor necrosis factor-α (TNF-α) impeded spinal Fbxo45-dependent Munc13-1 ubiquitination, which was reversed by intrathecal TNF-α-neutralizing antibody. Our data revealed that spinal TNF-α impedes Fbxo45-dependent Munc13-1 ubiquitination that accumulates Munc13-1 in the presynaptic area and hence facilitates the synaptic excitability of nociceptive neurotransmission underlying neuropathic pain.

Trace detection of common pesticide residue is necessary to assure safety of fruit and vegetables, given that the potential health risk to consumers is attributed to the contamination of the sources. A simple, rapid and effective means of finding the residue is however required for household purposes. In recent years, the technique in association with surface-enhanced Raman scattering (SERS) has been well developed in particular for trace detection of target molecules. Herein, gold nanoparticles (Au NPs) were integrated with sol-gel spin-coated Zirconia nanofibers (ZrO₂ NFs) as a chemically stable substrate and used for SERS application. The morphologies of Au NPs/ZrO₂ NFs were adjusted by the precursor concentrations (&#95;X, X = 0.05⁻0.5 M) and the effect of SERS on Au NPs/ZrO₂ NFs&#95;X was evaluated by different Raman laser wavelengths using rhodamine 6G as the probe molecule at low concentrations. The target pesticides, phosmet (P1), carbaryl (C1), permethrin (P2) and cypermethrin (C2) were thereafter tested and analyzed. Au NPs/ZrO₂ NFs&#95;0.3 exhibited an enhancement factor of 2.1 × 10⁷, which could detect P1, C1, P2 and C2 at the concentrations down to 10 -8 , 10 -7 , 10 -7 and 10 -6 M, respectively. High selectivity to the organophosphates was also found. As the pesticides were dip-coated on an apple and then measured on the diluted juice containing sliced apple peels, the characteristic peaks of each pesticide could be clearly identified. It is thus promising to use NPs/ZrO₂ NFs&#95;0.3 as a novel SERS-active substrate for trace detection of pesticide residue upon, for example, fruits or vegetables.

Histone deacetylase 4 (HDAC4), which actively shuttles between the nucleus and cytoplasm, is an attractive candidate for a repressor mechanism in epigenetic modification. However, the potential role of HDAC4-dependent epigenetics in the neural plasticity underlying the development of inflammatory pain has not been well established. By injecting complete Freund's adjuvant (CFA) into the hind-paw of Sprague-Dawley rats (200-250 g), we found animals displayed behavioral hyperalgesia was accompanied with HDAC4 phosphorylation and cytoplasmic redistribution in the dorsal horn neurons. Cytoplasmic HDAC4 retention led to its uncoupling with the COX2 promoter, hence prompting spinal COX2 transcription and expression in the dorsal horn. Moreover, the GluN2B-bearing N-methyl-d-aspartate receptor (GluN2B-NMDAR)/calmodulin-dependent protein kinase II (CaMKII) acted as an upstream cascade to facilitate HDAC4 phosphorylation/redistribution-associated spinal COX2 expression after inflammatory insults. The results of this pilot study demonstrated that the development and/or maintenance of inflammatory pain involved the spinal HDAC4-dependent epigenetic mechanisms. Our findings open up a new avenue for the development of a novel medical strategy for the relief of inflammatory pain., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pure tone audiometry is a routine clinical examination used to identify hearing loss. A normal pure tone audiogram is usually taken as evidence of normal hearing. Auditory deficits detected in subjects with normal audiograms, such as poor sound discrimination and auditory perceptual disorders, are generally attributed to central problems. Does the pure tone audiogram truly reflect cochlear status? Recent evidence suggests that individuals with normal audiogram may still have reduced peripheral auditory responses but normal central responses, indicating that the pure tone audiometry may not detect some types of cochlear injuries. In the cochlea, the outer hair cells (OHCs), inner hair cells (IHCs), and the spiral ganglion neurons that synapse with IHCs are the 3 key cochlear components in transducing acoustical vibrations into the neural signals. This report reviews three types of cochlear damage identified in laboratory animals that may not lead to overt hearing loss. The first type of cochlear impairment, such as missing a certain proportion of IHCs without damage to OHCs, may reduce the cochlear output and elevate response threshold; however, the reduced peripheral auditory sensitivity may be restored along the auditory pathway via central gain enhancement. The second type of cochlear impairment, such as selective damage to the synapses of the high-threshold thin auditory nerve fibers (ANFs), reduces cochlear output at high stimulation levels with no effect on response threshold. In this case the reduced cochlear output may be compensated along the auditory pathway as well. The third type of cochlear impairment, such as missing a certain number of OHCs without damage to others, may not even affect cochlear function at all. These "hidden" cochlear impairments do not result in overt hearing loss, but they may increase the vulnerability of the cochlea to traumatic exposure and lead to disrupted central auditory processing.

Dysiarenone (1), a dimeric C 21 meroterpenoid featuring an unprecedented 2-oxaspiro[bicyclo[3.3.1]nonane-9,1'-cyclopentane] carbon skeleton, was isolated from the marine sponge Dysidea arenaria. The structure of 1 was determined by HRMS and NMR spectroscopic analyses coupled with ECD calculations. Dysiarenone showed inhibitory activities against COX-2 expression and the production of prostaglandin E 2 with an IC 50 value of 6.4 μM in LPS-stimulated RAW264.7 macrophages.

Furanosteroids, represented by wortmannin, viridin, and demethoxyviridin, are a special group of fungal-derived, highly oxygenated steroids featured by an extra furan ring. They are well-known nanomolar-potency inhibitors of phosphatidylinositol 3-kinase and widely used in biological studies. Despite their importance, the biosyntheses of these molecules are poorly understood. Here, we report the identification of the biosynthetic gene cluster for demethoxyviridin, consisting of 19 genes, and among them 15 biosynthetic genes, including six cytochrome P450 monooxygenase genes, are deleted. As a result, 14 biosynthetic intermediates are isolated, and the biosynthetic pathway for demethoxyviridin is elucidated. Notably, the pregnane side-chain cleavage requires three enzymes: flavin-dependent Baeyer-Villiger monooxygenase, esterase, and dehydrogenase, in sharp contrast to the single cytochrome P450-mediated process in mammalian cells. Structure-activity analyses of these obtained biosynthetic intermediates reveal that the 3-keto group, the C1β-OH, and the aromatic ring C are important for the inhibition of phosphatidylinositol 3-kinase.

Objective: To evaluate the efficacy and safety of different operation time for acute spinal cord injury(SCI) based on systematic review., Methods: PubMed database, EMBASE database, Cochrane Library, ISI Web of knowledge, CBM database, VIP database, CNKI database and Wanfang database were searched from their start year up to February 2017 for relevant randomized clinical trials on the treatment of acute spinal cord injury with different intervention times., Results: Four randomized clinical trials of total 156 cases were included. Early surgical intervention for the patients with incomplete spinal cord injury can improve the ASIA motor function score [MD=3.29, 95%CI(-7.90, 14.49), P =0.56] and overall Frankel score[ OR =7.65, 95%CI(2.69, 21.74), P =0.000 1]. There was no significant difference in the improvement of the overall Frankel score[ OR =4.88, 95%CI(0.74, 32.09), P =0.10] for the patients with complete spinal cord injury between the early surgery and delayed surgery group. There was no significant difference in hospitalization time[MD=-3.4, 95%CI(-8.12, 1.32), P =0.16], death rate [ OR =1.07, 95%CI(0.21, 5.56), P =0.93]and incidence of decubitus[ OR =1.07, 95%CI(0.17, 6.69), P =0.94] between the early surgery and delayed surgery group., Conclusions: Early surgical intervention can promote the nerve function recovery after spinal cord injury, whithout further incidence of complications, but random control trails with higher quality are still required for this conclusion., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

The aim of the present study was to explore the effects and mechanisms of insulin on mitochondrial oxidative stress in septic acute kidney injury (AKI). Male Sprague Dawley rats were divided randomly into four groups: Control group, sham surgery group, cecal ligation and puncture (CLP) group, and CLP plus insulin group. Blood specimens and kidney tissues were obtained at 12 and 24 h after surgery as separate experiments. Analyses of histology and indicators of renal injury [blood urea nitrogen (BUN) and serum creatinine (CRE) and neutrophil gelatinase-associated lipocalin (NGAL)], mitochondrial function [adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP)], oxidative stress [inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS) and nitric oxide (NO)], endogenous antioxidant systems [superoxide dismutase (SOD) and glutathione (GSH)] as well as the expression of uncoupling protein (UCP), PINK1 protein (a major mediator of mitophagy), PGC1α protein (a major regulator of mitochondrial biogenesis) were performed. Compared with CLP group, the CLP plus insulin group had milder histological damage, higher levels of ATP and MMP as well as lower levels of BUN, serum CRE and NGAL, intrarenal iNOS, mitochondrial ROS and total NO. Moreover, the CLP plus insulin group demonstrated increased expression of SOD2 and UCP2. In contrast, insulin administration suppressed mitophagy meanwhile did not upregulate total GSH and induce mitochondrial biogenesis following CLP. These findings indicated that the upregulation of SOD2 and UCP2 may be involved in insulin protecting against mitochondrial oxidative stress in septic AKI.

Objective: To investigate the application of ultrasound-guided continuous serratus plane block with patient-controlled analgesia on postoperation analgesia after thoracoscopic surgery, and influence on postoperative rehabilitation. Methods: Sixty patients scheduled for thoracoscopic surgery were randomly divided into two groups. PCNA group ( n =30) received ultrasound guided continuous serratus plane block with patient-controlled nerve analgesia, with continuous infusion of 0.2% ropivacaine and 30 ml of 0.3% ropivacaine for the first does. PCIA group( n =30) received patient-controlled intravenous analgesia, with continuous infusion of sufentanil. Postoperative visual analogue scale (VAS) and prince henry pain scale (PHPS) were recorded at 1 hour (T(1)), 4 hour (T(2)), 8 hour (T(3)), 24 hour (T(4)), 2 days (T(5)), 3 days (T(6)), 4 days (T(7)), before discharge (T(8)), 30 days (T(9)) after surgery. Adverse reactions and the time of postoperative first out-of-bed activity, passage of gas by anus, bowel movement, chest tube removal, discharge was also recorded. Results: The resting VAS score of T(3), T(4), T(5) in group PCNA and group PCIA were 0(0) vs 0(2.0), 0(0) vs 2.0(2.0), 0(0) vs 0(2.0), the resting VAS score was lower in group PCNA than in group PCIA ( Z =-2.524, -3.944, -3.652, P <0.05 or P <0.01). The upper arm activity VAS score of T(2), T(3), T(4), T(5), T(6), T(7) in group PCNA and group PCIA were 0(0) vs 0(2.0), 0(0) vs 2.0(2.5), 0(2.0) vs 2.0(2.0), 0(2.0) vs 2.0(2.0), 0(0) vs 2.0(2.0), 0(0) vs 0(2.0), the upper arm activity VAS score was lower in group PCNA compared with group PCIA ( Z =-2.984, -3.915, -4.484, -4.450, -3.422, -2.456, P <0.05 or P <0.01). The coughing VAS score T(3), T(4), T(5), T(6), T(7) in group PCNA and group PCIA were 2.0(2.0) vs 2.0(2.5), 2.0(2.5) vs 4.0(4.0), 2.0(2.5) vs 4.0(4.0), 2.0(2.0) vs 3.0(2.0), 2.0(2.0) vs 2.0(2.0), the coughing VAS score was lower in group PCNA compared with group PCIA ( Z =-3.432, -3.410, -2.643, -3.210, -2.746, P <0.05 or P <0.01). The PHPS score was significantly lower in group PCNA at T(3)[1.0(1.3) vs 2.0(2.0)], T(4)[1.0(2.0) vs 3.0(1.0)], T(5)[1.0(1.3) vs 2.0(1.3)], T(6)[1.0(1.3) vs 2.0(2.0)], T(7)[1.0(1.0) vs 1.0(2.0)] compared to group PCIA ( Z =-3.149, -3.662, -3.369, -3.681, -2.815, all P <0.01). And the time of out-of-bed activity, passage of gas by anus of the PCNA group were (20.0± 6.9)h, ( 16.0± 8.0)h, which was advanced more than PCIA group [(23.9± 7.1)h, (34.3± 13.2)h, t =-2.20, -6.47, all P <0.05]. Furthermore, PCNA group had better sleep quality from the 2nd night to the 4th night , and with lower adverse reactions (all P <0.05). Conclusion: The application of ultrasound-guided continuous serratus plane block after thoracoscopic surgery can reduce postoperative pain and enhance recovery after surgery.

Background: Repetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ., Methods: One hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group., Results: Compared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05)., Conclusions: Based on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.

Two pairs of enantiomeric phthalide trimers [(-)/(+) triligustilides A (1a/1b) and (-)/(+) triligustilides B (2a/2b)] with complex polycyclic skeletons simultaneously possessing bridged, fused, and spiro ring systems were isolated from Angelica sinensis, together with two pairs of new phthalide dimers. The biogenetic pathways of new phthalides were proposed, and their bioactivities were also evaluated. This is the first time optically pure polymeric phthalides have been obtained from racemates, and their absolute configurations are reported.

Age-related hearing loss, which affects roughly 35% of those over the age of 70, is the second most common disorder among the elderly. The severity of age related hearing loss may actually be worse if assessments are made under more realistic conditions, such as communicating in noise. Emerging data from humans and animal models suggest that damage to the inner hair cells and/or type I neurons, that relay sound information to the brain may contribute to hearing deficits in a noisy background. Data obtained from carboplatin-treated chinchillas suggest that tone-in-noise thresholds are a sensitive and frequency dependent method of detecting damage to the IHC/type I system. Therefore, tone detection thresholds measured in broadband noise may provide an efficient method of detecting the deficits in specific frequency regions. Preliminary data obtained in elderly subject with normal thresholds in quiet compared to young subjects illustrate the importance of repeating these measurements in broadband noise because thresholds in noise were worse for our elderly subjects than young subjects, even though both groups had similar hearing thresholds in quiet. N-acetyl cysteine supplementation which protects against inner hair cell loss in animal models, may represent a viable therapy for protecting the inner hair cell/type I neurons., Competing Interests: Declaration of Interest: The authors report no conflicts of interest

The mechanisms underlying chronic stress-induced dysfunction of glutamatergic transmission that contribute to helplessness-associated depressive disorder are unknown. We investigated the relationship of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and stress, and the neuroplastic changes of stress-induced depression-like behavior in the ventrolateral periaqueductal gray (vlPAG). We conducted whole-cell patch-clamp electrophysiological recordings in the vlPAG neurons. Depression-like behavior was assayed using tail suspension test and sucrose preference test. Surface and cytosolic glutamate receptor 1 (GluR1) AMPA receptor expression was analyzed using western blotting. Phosphorylated GluR1 expression was quantified using western blotting and immunohistochemical analysis. Unpredictable inescapable foot shock stress caused reduction in glutamatergic transmission originating from both presynaptic and postsynaptic loci in the vlPAG that was associated with behavioral despair and anhedonia in chronic stress-induced depression. Pharmacological inhibition of GluR1 function in the vlPAG caused depression-like behavior. Diminished glutamatergic transmission was due to reduced glutamate release presynaptically and enhanced GluR1-endocytosis from the cell surface postsynaptically. Chronic stress-induced neuroplastic changes and maladaptive behavior were reversed and mimicked by administration of glucocorticoid receptor (GR) antagonist and agonist, respectively. However, chronic stress did not affect γ-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission in the vlPAG. These results demonstrate that depression-like behavior is associated with remarkable reduction in glutamatergic, but not GABAergic, transmission in the vlPAG. These neuroplastic changes and maladaptive behavior are attributed to GR-dependent mechanisms. As reduced GluR1-associated responses in the vlPAG contribute to chronic stress-induced neuroplastic changes, this cellular mechanism may be a critical component in the pathogenesis of stress-associated neuropsychiatric disorders.

Four new phenylisotertronic acids (1a/1b, 2a, and 3a) were isolated from a TCM endophytic fungal strain Phyllosticta sp. J13-2-12Y obtained from the leaves of Acorus tatarinowii, along with two known ones (2b and 3b). Compounds 1-3 all existed as mixtures of enantiomers, and their corresponding optically pure enantiomers were successfully isolated by chiral HPLC. The structures of isolated compounds were determined by comprehensive spectroscopic analyses and X-ray diffraction. Their absolute configurations were determined by ECD experiments and quantum chemical calculations. In addition, the antimicrobial activities and the cytotoxicities of these three pairs of optically pure enantiomers (1a/1b, 2a/2b, and 3a/3b) had been evaluated., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine the dose-response relationship of ropivacaine for epidural block in early herpes zoster by CT guided. Methods: From January 2015 to February 2017, according to the principle of completely random digital table, 80 patients with early herpes zoster who were prepared for epidural block were divided into 4 groups(each group 20 patients): in group A the concentration of ropivacaine was 0.08%, in group B was 0.10%, in group C was 0.12% and in group D was 0.14%.Under CT guidance, epidural puncture was performed in the relevant section, mixing liquid 5.0 ml (with 10% iodohydrin)were injected into epidural gap.CT scan showed that the mixing liquid covered the relevant spinal nerve segmental.The numeric rating scale(NRS) values before treatment and at 30 minutes, the incidence of adverse reactions were recorded, and the treatment were evaluated. The response to ropivacaine for epidural block in early herpes zoster was defined as positive when the NRS values was less than or equal to one.The ED(50), ED(95) and 95% confidence interval ( CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were calculated by probit analysis. Results: The NRS values before treatment were 5.00(4.00, 6.00), 5.00(4.25, 6.00), 5.50(5.00, 6.00) and 5.00(4.00, 6.00), the difference was no significant( Z =2.576, P =0.462). The NRS values at 30 minutes decreased and the effective rate of the treatment increased(χ(2)=8.371, P =0.004), following ropivacaine dose gradient increasing, they were 1.50(1.00, 2.00), 1.00(1.00, 2.00), 0.50(0.00, 1.00) and 0.00(0.00, 1.00), the difference was statistically significant ( Z =17.421, P =0.001). There was one case in group C and four cases in group D were hypoesthesia, others were no significant adverse reactions occurred. The ED(50) and ED(95) (95% CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were 0.078%(0.015%-0.095%)and 0.157%(0.133%-0.271%), respectively. Conclusion: Ropivacaine for epidural block in early herpes zoster guided by CT is effective for neuropathic pain, with no significant adverse reactions.

Cervical cancer is one of the most common malignancies of the female reproductive system. Therefore, it is critical to investigate the molecular mechanisms involved in the development and progression of cervical cancer. In this study, we stimulated cervical cancer cells with 5-aza-2'-deoxycytidine (5-Aza-dC) and found that this treatment inhibited cell proliferation and induced apoptosis; additionally, methylation of p16 and O-6-methylguanine-DNA methyltransferase (MGMT) was reversed, although their expression was suppressed. 5-Aza-dC inhibited E6 and E7 expression and up-regulated p53, p21, and Rb expression. Cells transfected with siRNAs targeting p16 and MGMT as well as cells stimulated with 5-Aza-dC were arrested in S phase, and the expression of p53, p21, and Rb was up-regulated more significantly. However, when cells were stimulated with 5-Aza-dC after transfection with siRNAs targeting p16 and MGMT, proliferation decreased significantly, and the percentage of cells in the sub-G1 peak and in S phase was significantly increased, suggesting a marked increase in apoptosis. But E6 and E7 overexpression could rescue the observed effects in proliferation. Furthermore, X-ray radiation caused cells to arrest in G2/M phase, but cells transfected with p16- and MGMT-targeted siRNAs followed by X-ray radiation exhibited a significant decrease in proliferation and were shifted toward the sub-G1 peak, also indicating enhanced apoptosis. In addition, the effects of 5-Aza-dC and X-ray radiation were most pronounced when MGMT expression was down-regulated. Therefore, down-regulation of p16 and MGMT expression enhances the anti-proliferative effects of 5-Aza-dC and X-ray radiation. This discovery may provide novel ideas for the treatment of cervical cancer., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: This is part of a three-year study designed to evaluate the natural history of lower urinary tract symptoms in local community residents aged 40 years and above in central Taiwan. We evaluated the prevalence of overactive bladder (OAB) and voiding dysfunction (VD) in female residents using validated questionnaires., Materials and Methods: A structured questionnaire containing groups of different questionnaires was translated into Chinese and each one was validated separately. A trained research assistant interviewed the participants and assisted in filling in the questionnaires. Residents were recorded to have OAB if the total OABSS score was≧4. Urge urinary incontinence (UUI) was defined as urine leakage preceded by the feeling of urgency which is slightly or more distressful. VD was defined as feeling of difficulty in emptying the bladder which is slightly or more distressful., Results: A total of 2411 community residents aged 40 years and above who completed all the questionnaires in the initial survey were recruited, of which 1469(60.9%) were women. The prevalence of OAB, UUI and VD were 33.1%, 26.8% and 28.3% respectively in the female community residents. Age≧60 (OR, 1.5; 95%CI, 1.1-2.0), menopause (OR1.4; 95% CI, 1.0-1.9) and a history of diabetes mellitus (OR, 1.8; 95% CI, 1.2-2.8) were the risk factors for OAB. Age≧60 (OR, 1.4; 95%CI, 1.0-1.9), BMI ≧25 (OR, 1.3; 95% CI, 1.0-1.7) and instrument deliveries (OR, 1.5; 95% CI, 1.0-2.1) were the risk factors for VD., Conclusion: Our results imply that the prevalence of overactive bladder and voiding difficulty are high in female community residents aged ≧ 40 years in central Taiwan., (Copyright © 2017. Published by Elsevier B.V.)

A new α-pyrone, nocapyrone S (1), together with five known compounds (2-6), were isolated from the deep-sea actinomycete Nocardiopsis dassonvillei subsp. dassonvillei DSM 43111(T). Their structures were determined by spectroscopic analyses. The absolute configuration of 1 was established by quantum approaches. Cytotoxic activity of 1 was evaluated against K562, MCF-7, SGC7901, A375, Hela, and HepG2 cell lines.

Background: Using dexmedetomidine (Dex) as a sedative agent may benefit the clinical outcomes of post-surgery patients. We reviewed randomized controlled trials (RCTs) to assess whether use of a Dex could improve the outcomes in post-surgery critically ill adults., Methods: We searched Medline, Embase, PubMed, and the Cochrane databases for RCTs comparing Dex with propofol or a placebo in post-operative patients, all included RCTs should be published in English before Jul 2016. Citations meeting inclusion criteria were full screened, and trial available data were abstracted independently and the Cochrane risk of bias tool was used for quality assessment., Results: Sixteen RCTs involving 2568 patients were subject to this meta-analysis. The use of a Dex sedative regimen was associated with a reduce delirium prevalence [odd ratio (OR):0.33, 95% confidence intervals (CI): 0.24-0.45, I 2 = 5%, P <0.001], a shorter the length of ICU stay [mean difference (MD): -0.60, 95%CI: -0.69 to -0.50, I 2 =40%, P <0.001] and the length of hospital stay [MD: -0.68, 95%CI: -1.21 to -0.16, I 2 =0%, P =0.01]. However, using of Dex could not shorter the duration of mechanical ventilation [MD: -10.18. 95%CI: -31.08-10.72, I 2 =99%, P =0.34], but could shorter the time to extubation in post-surgery patients [MD: -47.46, 95%CI: -84.63-10.67, I 2 =98%, P =0.01]., Conclusion: The use of a Dex sedative regimen was associated with a reduce delirium prevalence, a shorter the length of ICU and hospital stay, and a shorter time to extubation in post-surgery critical ill patients., Competing Interests: Conflict of interest The authors have declared that they were no competing interests.

Eight new (1a/1b, 2a, 3a, 4a/4b, and 5a/5b) and seven known (2b, 3b, and 6-10) asarone-derived phenylpropanoids, a known asarone-derived lignan (12), and four known lignan analogues (11 and 13-15) were isolated from the rhizome of Acorus tatarinowii Schott. The structures were elucidated via comprehensive spectroscopic analyses, modified Mosher's method, and quantum chemical calculations. Compounds 1-8 were present as enantiomers, and 1-5 were successfully resolved via chiral-phase HPLC. Compounds 1a/1b were the first cases of asarone-derived phenylpropanoids with an isopropyl C-3 side-chain tethered to a benzene core from nature. Hypoglycemic, antioxidant, and AChE inhibitory activities of 1-15 were assessed by the α-glucosidase inhibitory, ORAC, DPPH radical scavenging, and AChE inhibitory assays, respectively. All compounds except 3a showed α-glucosidase inhibitory activity. Compound 3b has the highest α-glucosidase inhibitory effect with an IC 50 of 80.6 μM (positive drug acarbose IC 50 of 442.4 μM). In the antioxidant assays, compounds 13-15 exhibited ORAC and DPPH radical scavenging activities. The results of the AChE inhibitory assay indicated that all compounds exhibited weak AChE inhibitory activities.

Long persistent phosphorescence is generally known as a phenomenon involving carrier traps induced by defects or impurities in crystals. In this paper, phosphorescence sustained for tens of minutes was found in intentionally undoped ZnO and it was proposed to be a universal phenomenon in wide bandgap semiconductors upon satisfying several conditions. A new model was built to understand this attractive phenomenon within the framework of the traditional trapping-detrapping model but it was modified by considering the free electrons in the conduction band as a significant contributor to the long persistent phosphorescence besides the electrons trapped by shallow donors. This model, explicitly expressed as I(t) ∝ [1 + M(1 - Fe -γt ) -2 ]e -γt , is not only capable of giving a quantitative description of the non-exponential decay of phosphorescence in a wide temperature range but also enables one to determine the depth of shallow donors in semiconductors. The participation of free electrons in phosphorescence was further confirmed by another carefully designed experiment. Thus, this study may represent significant progress in understanding phosphorescence.

Houttuynoid M (1), a new houttuynoid, and the related known compound houttuynoid A (2) were isolated from Houttuynia cordata. Their structures were defined using NMR data analysis, HR-MS n experiment, and chemical derivatization. Houttuynoid M is the first example of a houttuynoid with a bis-houttuynin chain tethered to a flavonoid core. A putative biosynthetic pathway of houttuynoid M (1) is proposed. The anti-herpes simplex virus (anti-HSV) activities of 1 and 2 (IC 50 values of 17.72 and 12.42 μM, respectively) were evaluated using a plaque formation assay with acyclovir as the positive control.

Fusidane-type antibiotics represented by helvolic acid, fusidic acid and cephalosporin P 1 are a class of bacteriostatic agents, which have drawn renewed attention because they have no cross-resistance to commonly used antibiotics. However, their biosynthesis is poorly understood. Here, we perform a stepwise introduction of the nine genes from the proposed gene cluster for helvolic acid into Aspergillus oryzae NSAR1, which enables us to isolate helvolic acid (~20 mg L -1 ) and its 21 derivatives. Anti-Staphylococcus aureus assay reveals that the antibacterial activity of three intermediates is even stronger than that of helvolic acid. Notably, we observe an unusual C-4 demethylation process mediated by a promiscuous short-chain dehydrogenase/reductase (HelC) and a cytochrome P450 enzyme (HelB1), which is distinct from the common sterol biosynthesis. These studies have set the stage for using biosynthetic approaches to expand chemical diversity of fusidane-type antibiotics.

Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity. In addition, enhanced Tet1 expression, Tet1-metabotropic glutamate receptor subtype 5 (mGluR5) promoter coupling, demethylation at the mGluR5 promoter, and mGluR5 expression in dorsal horn neurons were observed. Rats subjected to spinal nerve ligation and intraplantar complete Freund's adjuvant injection displayed tactile allodynia and behavioral hyperalgesia associated with similar changes in the dorsal horn. Notably, intrathecal melatonin injection reversed the protein expression, protein-promoter coupling, promoter demethylation, and pain hypersensitivity induced by Tet1 gene transfer, spinal nerve ligation, and intraplantar complete Freund's adjuvant injection. All the effects caused by melatonin were blocked by pretreatment with a MT2 receptor-selective antagonist. In conclusion, melatonin relieves pain by impeding Tet1-dependent demethylation of mGluR5 in dorsal horn neurons through the MT2 receptor. Our findings link melatonin/MT2 signaling to Tet1-dependent epigenetic demethylation of nociceptive genes for the first time and suggest melatonin as a promising therapy for the treatment of pain., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Phyllomeroterpenoids A-C (1-3), multi-biosynthetic pathway derived meroterpenoids from amino acid/pentose phosphate/terpenoid pathways, were isolated from the TCM endophytic fungus Phyllosticta sp. J13-2-12Y, together with six biosynthetically related compounds (4-9). All structures were determined by extensive spectroscopic analysis, chemical derivatization, and ECD experiments. A plausible biosynthetic pathway of 1-3 was proposed. In addition, the antimicrobial activities of all isolated compounds were evaluated against Staphylococcus aureus 209P (bacterium) and Candida albicans FIM709 (fungus).

Background: To determine if there are clinical and urodynamic (UD) differences between female overactive bladder (OAB) patients with bladder oversensitivity (BO) and detrusor overactivity (DO) via a much lower filling rate., Methods: In total, 205 patients with OAB symptoms were recruited for this study. During filling cystometry, the bladder was filled at a more "physiological" rate of 20 ml/min. All patients underwent a complete urogynecological evaluation including detailed history, physical examination, urinalysis, pad test for quantification of urine leakage, 3-day frequency-volume chart (FVC) documentation, and completion of a UD study., Results: The overall incidence of BO was 34.2% and that of DO was 65.8%. The first desire to void (FDV) in patients with BO and DO were at filling of 117.47 ± 21.68 ml and 135.23 ± 22.88 ml, respectively (p < 0.05). Maximal cystometric capacities (MCC) in patients with BO and DO were recorded at 259.44 ± 33.87 ml and 265.32 ± 44.05 ml (p > 0.05). A receiver operating characteristic (ROC) curve was used to find the cut-off values of FDV for sensitivity and specificity in patients diagnosed with DO. Area under the curve (AUC) was 0.702 (p < 0.005, 95% confidence interval: 0.626-0.779) if FDV was determined as more than 127 ml. Patients with BO experienced significantly increased daytime urinary frequency and nocturia symptoms (<0.05). Patients with DO had a significantly higher prevalence of urgent urinary incontinence (p < 0.05). In this study, a higher FDV and higher body mass index (BMI) were correlating factors for OAB patients with DO after multiple logistic regression analysis., Conclusion: Patients with BO seemed to be on a different spectrum compared to those with DO and also had different symptom-specific and associative factors. It was also found that FDV could be good predictive indicator for detecting DO at a low filling rate., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

A new asarone-derived racemate (1) was isolated from the rhizome of Acorus tatarinowii. The structure of 1 was established by comprehensive spectroscopic analyses, and it was successfully resolved by chiral HPLC, demonstrating that it is racemic. The absolute configurations of 1a [(-)-acortatarone A] and 1b [(+)-acortatarone A] were determined using quantum chemical calculations. Compounds 1a and 1b were the first cases of asarone derivatives with the 5,7-dialkyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one core. The α-glucosidase inhibitory and acetylcholinesterase (AChE) inhibitory activities of 1 were evaluated, and it exhibited α-glucosidase inhibitory activity with potency close to that of the positive control (acarbose)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Prolonged low-level noise exposure alters loudness perception in humans, presumably by decreasing the gain of the central auditory system. Here we test the central gain hypothesis by measuring the acute and chronic physiologic changes at the level of the cochlea and inferior colliculus (IC) after a 75-dB SPL, 10-20-kHz noise exposure for 5weeks. The compound action potential (CAP) and summating potential (SP) were used to assess the functional status of the cochlea and 16 channel electrodes were used to measure the local field potentials (LFP) and multi-unit spike discharge rates (SDR) from the IC immediately after and one-week post-exposure. Measurements obtained immediately post-exposure demonstrated a significant reduction in supra-threshold CAP amplitudes. In contrast to the periphery, sound-evoked activity in the IC was enhanced in a frequency-dependent manner consistent with models of enhanced central gain. Surprisingly, one-week post-exposure supra-threshold responses from the cochlea had not only recovered, but were significantly larger than normal, and thresholds were significantly better than controls. Moreover, sound-evoked hyperactivity in the IC was sustained within the noise exposure frequency band but suppressed at higher frequencies. When response amplitudes representing the neural output of the cochlea and IC activity at one-week post exposure were compared with control animal responses, a central attenuation phenomenon becomes evident, which may play a key role in understanding why low-level noise can sometimes ameliorate tinnitus and hyperacusis percepts., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Filamentous fungi represent an invaluable source of pharmaceutically active compounds. The development of versatile methods to genetically manipulate filamentous fungi is of great value for improving the low yields of bioactive metabolites and expanding chemical diversity. The CRISPR-Cas9-based system has become a common platform for genome editing in a variety of organisms. However, recent application of this technology in filamentous fungi is limited to model strains, a versatile method for efficient gene disruption in different fungi is lacking. Here, we investigated the utility of the CRISPR-Cas9 system in a less-studied fungus Nodulisporium sp. (No. 65-12-7-1), and we have developed an efficient CRISPR-Cas9-based gene disruption strategy by simultaneous transformation of in vitro transcriptional gRNA and the linear maker gene cassette into the Cas9-expressing fungi. We found that the linear marker gene cassette could not only allow for selection of transformants, but also significantly enhance the gene disruption efficiency by inserting itself into the Cas9 cut site. Moreover, the above approach also demonstrated its efficiency in two other phylogenetically distinct strains Aspergillus oryzae NSAR1 and Sporormiella minima (No. 40-1-4-1) from two different classes of Ascomycota. These results suggested that a versatile CRISPR-Cas9-based gene disruption method in filamentous fungi was established.

Four unusual meroterpenoids, dysivillosins A-D (1-4), were isolated from an organic extract of the marine sponge Dysidea villosa collected from the South China Sea. Their planar structures were determined by 1D and 2D NMR and HRESIMS techniques, while the relative and absolute configurations were elucidated by NOESY experiments and comparison between the calculated and experimental ECD spectra. To the best of our knowledge, dysivillosins A-D are the first examples of terpene-polyketide-pyridine hybrid metabolites from the nature. Anti-allergic activity evaluation showed that compounds 1-4 potently inhibited the release of β-hexosaminidase, a marker of degranulation, in a dose-dependent manner with IC 50 values of 8.2-19.9 μM. Additionally, the four meroterpenoids could downregulate the production of lipid mediator leukotrienes B 4 (LTB 4 ) and pro-inflammatory cytokine interleukin-4 (IL-4) in the antigen-stimulated RBL-2H3 mast cells. Further biological investigations revealed that dysivillosin A (1) could suppress the phosphorylation of Syk and PLCγ1 in IgE/FcɛRI/Syk signaling pathway, which resulted in the inhibition of degranulation and the downregulation of LTB 4 and IL-4 production in mast cells.

Sugar O-methylation is a ubiquitous modification in natural products and plays diverse roles. This realization has inspired many attempts to search for novel methyltransferases. Chalcomycins are a group of 16-membered macrolides containing two methylated sugars that require three methyltransferases for their biosynthesis. Here, we identified that AlmCII, a sugar O-methyltransferase belonging to the TylF family that was previously only known to methylate sugars with a 4'-hydroxy group, can methylate a 4',6'-dideoxysugar during the biosynthesis of chalcomycins. An in vitro enzymatic assay revealed that AlmCII is divalent metal-dependent with an optimal pH of 8.0 and optimal temperature of 42 °C. Moreover, the 3'-O-demethylated chalcomycins exhibit less than 6 % of the antibacterial activity of their parent compounds. This is the first report demonstrating that a TylF family O-methyltransferase can use a 4'-deoxy sugar as a substrate and highlighting the importance of this methylation for the antibacterial activity of chalcomycins., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chronic tinnitus and hyperacusis often develop with age-related hearing loss presumably due to aberrant neural activity in the central auditory system (CAS) induced by cochlear pathologies. However, the full spectrum of physiological changes that occur in the CAS as a result age-related hearing loss are still poorly understood. To address this issue, neurophysiological measures were obtained from the cochlea and the inferior colliculus (IC) of 2, 6 and 12 month old C57BL/6J mice, a mouse model for early age-related hearing loss. Thresholds of the compound action potentials (CAP) in 6 and 12 month old mice were significantly higher than in 2 month old mice. The sound driven and spontaneous firing rates of IC neurons, recorded with 16 channel electrodes, revealed mean IC thresholds of 22.8 ± 6.5 dB (n = 167) at 2 months, 37.9 ± 6.2 dB (n = 132) at 6 months and 47.1 ± 15.3 dB (n = 151) at 12 months of age consistent with the rise in CAP thresholds. The characteristic frequencies (CF) of IC neurons ranged from 3 to 32 kHz in 2 month old mice; the upper CF ranged decreased to 26 kHz and 16 kHz in 6 and 12 month old mice respectively. The percentage of IC neurons with CFs between 8 and 12 kHz increased from 36.5% in 2 month old mice, to 48.8% and 76.2% in 6 and 12 month old mice, respectively, suggesting a downshift of IC CFs due to the high-frequency hearing loss. The average spontaneous firing rate (SFRs) of all recorded neurons in 2 month old mice was 3.2 ± 2.5 Hz (n = 167). For 6 and 12 month old mice, the SFRs of low CF neurons (<8 kHz) was maintained at 3-6 spikes/s; whereas SFRs of IC neurons with CFs > 8 kHz increased to 13.0 ± 15.4 (n = 68) Hz at 6 months of age and then declined to 4.8 ± 7.4 (n = 110) spikes/s at 12 months of age. In addition, sound-evoked activity at suprathreshold levels at 6 months of age was much higher than at 2 and 12 months of age. To evaluate the behavioral consequences of sound evoked hyperactivity in the IC, the amplitude of the acoustic startle reflex was measured at 4, 8 and 16 kHz using narrow band noise bursts. Acoustic startle reflex amplitudes in 6 and 12 month old mice (n = 4) were significantly larger than 2 month old mice (n = 4) at 4 and 8 kHz, but not 16 kHz. The enhanced reflex amplitudes suggest that high-intensity, low-frequency sounds are perceived as louder than normal in 6 and 12 month old mice compared to 2 month olds. The increased spontaneous activity, particularly at 6 months, may be related to tinnitus whereas the increase in sound-evoked activity and startle reflex amplitudes may be related to hyperacusis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Tinnitus and hyperacusis are common and potentially serious hearing disorders associated with noise-, age- or drug-induced hearing loss. Accumulating evidence suggests that tinnitus and hyperacusis are linked to excessive neural activity in a distributed brain network that not only includes the central auditory pathway, but also brain regions involved in arousal, emotion, stress and motor control. Here we examine electrophysiological changes in two novel non-auditory areas implicated in tinnitus and hyperacusis: the caudal pontine reticular nucleus (PnC), involved in arousal, and the paraflocculus lobe of the cerebellum (PFL), implicated in head-eye coordination and gating tinnitus and we measure the changes in corticosterone stress hormone levels. Using the salicylate-induced model of tinnitus and hyperacusis, we found that long-latency (>10 ms) sound-evoked response components in both the brain regions were significantly enhanced after salicylate administration, while the short-latency responses were reduced, likely reflecting cochlear hearing loss. These results are consistent with the central gain model of tinnitus and hyperacusis, which proposes that these disorders arise from the amplification of neural activity in central auditory pathway plus other regions linked to arousal, emotion, tinnitus gating and motor control. Finally, we demonstrate that salicylate results in an increase in corticosterone level in a dose-dependent manner consistent with the notion that stress may interact with hearing loss in tinnitus and hyperacusis development. This increased stress response has the potential to have wide-ranging effects on the central nervous system and may therefore contribute to brain-wide changes in neural activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Six new sesquiterpenoids, namely nardosinanones J-N and nardoaristolone C, were isolated from the rhizomes and roots of Nardostachys chinensis Batal. Their structures were determined by interpretation of spectroscopic data (HR-ESI-MS, 1D and 2D NMR). A combination of X-ray crystal diffraction, ECD calculation, and Mosher ester methods was employed to determine the absolute configuration of the isolated compounds. Compounds 1-2, 4-6 were evaluated anti-inflammatory activities in LPS-stimulated RAW264.7 macrophages. The results showed that compound 5 obviously inhibited LPS-induced iNOS and COX-2 protein expression compared to single LPS stimulation, which indicated the potential effect to medicate anti-inflammatory., (Copyright © 2017. Published by Elsevier B.V.)

The many-body expansion (MBE) method is the basis of many fragment-based methods and is widely applied to the computation of large molecular systems. To reach linear-scaling computation, a cutoff must be used to discard those subsystems with long interfragment distances. However, this leads to a discontinuous potential energy surface (PES) that would cause various problems in geometry optimizations and molecular dynamics simulations. To solve this problem, we present a generalized-switch-function (GSF) approach to smooth the PES computed by the MBE method with the use of a cutoff distance. The GSFs are naturally normalized and are permutation invariant. This approach can be applied to adaptively computing any order of many-body correction energies with multilevel computational methods and is a dynamic subsystem approach. We have applied the two versions of our method, GSF-MBE(m)/L 1 and GSF-MBE(m)/(L 1 :L 2 :L 3 ), to water clusters. Thorough tests show that our method can indeed give smooth potential-energy surface and is linear scaling but without losing much accuracy for very large water clusters with appropriately chosen cutoff distances.

Ovarian cancer is the second leading cause of deaths among gynecologic cancers in the world. Approximately 90% of women with ovarian cancer reported having symptoms long before a diagnosis was made. Literature shows that recurrence should be predicted with regard to their personal risk factors and the clinical symptoms of this devastating cancer. In this study, ensemble learning and five data mining approaches, including support vector machine (SVM), C5.0, extreme learning machine (ELM), multivariate adaptive regression splines (MARS), and random forest (RF), were integrated to rank the importance of risk factors and diagnose the recurrence of ovarian cancer. The medical records and pathologic status were extracted from the Chung Shan Medical University Hospital Tumor Registry. Experimental results illustrated that the integrated C5.0 model is a superior approach in predicting the recurrence of ovarian cancer. Moreover, the classification accuracies of C5.0, ELM, MARS, RF, and SVM indeed increased after using the selected important risk factors as predictors. Our findings suggest that The International Federation of Gynecology and Obstetrics (FIGO), Pathologic M, Age, and Pathologic T were the four most critical risk factors for ovarian cancer recurrence. In summary, the above information can support the important influence of personality and clinical symptom representations on all phases of guide interventions, with the complexities of multiple symptoms associated with ovarian cancer in all phases of the recurrent trajectory., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Researches have suggested Mediterranean diet might lower the risk of chronic diseases, but data on skeletal muscle mass (SMM) are limited. This community-based cross-sectional study examined the association between the alternate Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40-75 years in Guangzhou, China. General information and habitual dietary information were assessed in face-to-face interviews conducted during 2008-2010 and 3 years later. The aMDS was calculated by summing the dichotomous points for the items of higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the whole body, limbs, arms and legs were measured using dual-energy X-ray absorptiometry during 2011-2013. After adjusting for potential covariates, higher aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2, kg/m2) at all of the studied sites in males (all P trend<0·05). The multiple covariate-adjusted SMI means were 2·70 % (whole body), 2·65 % (limbs), 2·50 % (arms) and 2·70 % (legs) higher in the high (v. low) category aMDS in males (all P<0·05). In females, the corresponding values were 1·35 % (P trend=0·03), 1·05, 0·52 and 1·20 %, (P trend>0·05). Age-stratified analyses showed that the favourable associations tended to be more pronounced in the younger subjects aged less than the medians of 59·2 and 62·2 years in females and males (P interaction>0·10). In conclusion, the aMDS shows protective associations with SMM in Chinese adults, particularly in male and younger subjects.

High dose of salicylate, the active ingredient in aspirin, has long been known to induce transient hearing loss, tinnitus and hyperacusis making it a powerful experimental tool. These salicylate-induced perceptual disturbances are associated with a massive reduction in the neural output of the cochlea. Paradoxically, the diminished neural output of the cochlea is accompanied by a dramatic increase in sound-evoked activity in the auditory cortex (AC) and several other parts of the central nervous system. Exactly where the increase in neural activity begins and builds up along the central auditory pathway are not fully understood. To address this issue, we measured sound-evoked neural activity in the cochlea, cochlear nucleus (CN), inferior colliculus (IC), and AC before and after administering a high dose of sodium salicylate (SS, 300 mg/kg). The SS-treatment abolished low-level sound-evoked responses along the auditory pathway resulting in a 20-30 dB threshold shift. While the neural output of the cochlea was substantially reduced at high intensities, the neural responses in the CN were only slightly reduced; those in the IC were nearly normal or slightly enhanced while those in the AC considerably enhanced, indicative of a progress increase in central gain. The SS-induced increase in central response in the IC and AC was frequency-dependent with the greatest increase occurring in the mid-frequency range the putative pitch of SS-induced tinnitus. This frequency-dependent hyperactivity appeared to result from shifts in the frequency receptive fields (FRF) such that the response areas of many FRF shifted/expanded toward the mid-frequencies. Our results suggest that the SS-induced threshold shift originates in the cochlea. In contrast, enhanced central gain is not localized to one region, but progressively builds up at successively higher stage of the auditory pathway either through a loss of inhibition and/or increased excitation., (Copyright © 2016. Published by Elsevier B.V.)

This cross-sectional study investigated the association between the modified 2006 American Heart Association Diet and Lifestyle Recommendations (AHA-DLR) and bone mineral density in Chinese adults. We found that better adherence to the AHA-DLR associated with higher bone mineral density (BMD) at multiple sites., Introduction: Accumulating evidence shows that cardiovascular disease (CVD) and osteoporosis are associated with each other, yet little research has focused on whether strategies to reduce CVD risk could also benefit bone health. We aimed to assess the association between adherence to the modified 2006 American Heart Association Diet and Lifestyle Recommendations (AHA-DLR) and BMD in Chinese adults., Methods: We included 2092 women and 1051 men aged 40-75 years in this community-based cross-sectional study. Dietary information was assessed using a 79-item food frequency survey through face-to-face interviews at baseline (2008-2010) and 3 years later (2011-2013). Adherence to the AHA-DLR was assessed using modified diet and lifestyle scores (American Heart Association Diet and Lifestyle Score (AHA-DLS)) adjusted for bone health. BMD for the whole body, lumbar spine, total hip, femur neck, and trochanter sites was measured using dual-energy X-ray absorptiometry in 2011-2013., Results: After adjusting for potential covariates, greater adherence to the modified AHA-DLS was positively and dose-dependently associated with BMD. The mean BMD was 1.93-3.11% higher in quartile 4 (vs. 1) (all p values <0.01) at multiple sites. Five-unit increases in the modified AHA-DLS score were associated with 4.20-6.07, 4.44-8.51, and 3.36-4.67 mg/cm 2 increases in BMD at multiple sites for the total subjects, males, and females, respectively (all p values <0.01)., Conclusions: Better adherence to the AHA-DLR shows protective associations with BMD at multiple sites in the middle-aged and elderly Chinese population.

UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/hydroxymethylation are unknown. Here we show that in mice, UHRF2 is more abundantly expressed in the brain and a few other tissues. Uhrf2 knock-out mice are viable and fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, the Uhrf2 null mice exhibit a reduction of 5hmC in the brain, including the cortex and hippocampus. Furthermore, the Uhrf2 null mice exhibit a partial impairment in spatial memory acquisition and retention. Consistent with the phenotype, gene expression profiling uncovers a role for UHRF2 in regulating neuron-related gene expression. Finally, we provide evidence that UHRF2 binds 5hmC in cells but does not appear to affect the TET1 enzymatic activity. Together, our study supports UHRF2 as a bona fide 5hmC reader and further demonstrates a role for 5hmC in neuronal function., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

The joint effect of sodium and potassium on bone health remains uncertain. We examined the associations between urinary excretion of sodium, potassium, and their ratio and bone mineral density (BMD), and reported an inverse association between urinary sodium-to-potassium ratio and BMD in women, but not in men., Introduction: Several studies have suggested that a higher sodium or lower potassium intake is associated with poor bone health. However, few studies have examined their joint effects. We examined the associations of urinary excretion of sodium, potassium, and the sodium-to-potassium ratio with BMD in Chinese adults., Methods: This community-based, cross-sectional study included 2202 women and 1063 men (40-75 years) in Guangzhou, China. The BMD of the whole body, lumbar spine, and hip sites were measured by dual-energy x-ray absorptiometry. The concentrations of sodium, potassium, and creatinine of the fasting morning first-void urine sample were measured, and creatinine-adjusted values were then used for further analyses. General information was collected via face-to-face interviews., Results: For women, after multivariable adjustment, the urinary sodium-to-potassium ratio was inversely associated with BMD at the whole body, total hip, trochanter, and intertrochanter (all p trend <0.05). The mean BMD differences between extreme quartiles ranged from 1.50 to 2.98 % at these sites (all p < 0.05). Similar, but less significant, associations were observed for urinary sodium/creatinine, for which the only significant difference was found at the trochanter (2.00 %, p = 0.016). We did not find any significant associations of BMD with urinary potassium in women and with urinary sodium/creatinine, potassium/creatinine, or their ratio in men., Conclusion: Our findings suggest that the urinary sodium-to-potassium ratio, but not individual creatinine-adjusted values of sodium or potassium, is a good predictor of BMD in women, but not in men.