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This paper proposes a speech synthesis method based on unsupervisedly-learned fine-grained style representations, named word-level style variations (WSVs), in order to improve the naturalness of synthetic speech. The whole model contains a WSV extractor and a WSV predictor. The WSV extractor is jointly trained with a sequence-to-sequence (Seq2seq) synthesizer and learns a WSV vector from the mel-spectrogram of each prosodic word in the training set by extending the global style token (GST) framework. In contrast to GST weights which describe the global styles of utterances, WSVs operate at word-level and are expected to describe local style properties, such as stresses. Besides, Gumbel softmax is adopted and the extracted WSVs are close to one-hot vectors which facilitate the subsequent prediction task. The WSV predictor is a deterministic model which generates the sequence of WSV vectors from input text using an autoregressive LSTM network. In addition to phonetic information, e.g., phoneme sequences, Bidirectional Encoder Representation from Transformers (BERT) model is employed by the predictor to obtain the semantic descriptions of input text for better predicting the latent speech representation, i.e., WSVs. The WSV predictor is trained by considering both the accuracy of WSV prediction and the distortion of mel-spectrograms recovered from the predicted WSVs. Experimental results show that our proposed method can achieve better naturalness of synthetic speech than baseline Tacotron2, text-predicted global style token (TP-GST) and BERT-Tacotron2 models.

The development of linkage chemistry in the research area of covalent organic frameworks (COFs) is fundamentally important for creating robust structures with high crystallinity and diversified functionality. We reach herein a new level of complexity and controllability in linkage chemistry by achieving the first synthesis of fused-ring-linked COFs. A series of bicyclic pyrano[4,3

Butyrylcholinesterase (BuChE), the primary source of serum cholinesterase activity, is an indispensable biochemical marker for clinical diagnosis of liver function and organophosphorus poisoning. The requirement for bulky and expensive instruments represents a huge hindrance for point-of-care testing (POCT) of BuChE, especially in resource-limited settings. Herein, an easy-operated, economic, and portable photothermal (PT) biosensing platform for high-throughput BuChE detection was rationally designed. BuChE could "light up" the PT signal through in situ generation of Prussian blue (PB) by MIL-53 (Fe), which allowed us to translate biological signals into temperature signals. Such temperature change signals could be monitored at high throughput (six samples for a single measurement) by a miniature self-made integrated PT device via combining separable 96-well plates, a three-dimensional (3D) printed sample bracket, 808 nm lasers, and thermometers, satisfying the requirement for rapid on-site detection in a large batch with low cost. In addition, the large specific surface area, 3D network structure, and high porosity of MIL-53 (Fe) offered a beneficial platform for its reaction with enzymatic hydrolysate, resulting in high sensing sensitivity and low detection limit (0.3 U L-1), which was at least 20 000 times lower than the normal human serum BuChE activity. This facile, affordable, and broad applicability PT sensing platform provides a beneficial reference for the rational design of other disease diagnostic approaches suitable for POCT.

A novel moderately halophilic, filamentous actinobacterium, designated as XMNu-373T, was isolated from a saline–alkaline soil sample collected from the Mongolia Plateau, Dongwu County, Inner Mongolia Autonomous Region, PR China. The isolate grew optimally at 28‒37 °C, pH 7.0‒8.0 and with 2–5 % (w/v) NaCl. The substrate mycelia fragmented into rod-like elements, and the white aerial mycelia formed spore chains at maturity. The predominant menaquinone was MK-9(H4). The polar lipids were diphosphatidylglycerol, three unidentified phosphoglycolipids, an unidentified aminophospholipid, two phosphatidylinositol mannosides, four unidentified phospholipids, phosphatidylglycerol and two unidentified lipids. The major cellular fatty acids were iso-C16 : 0, anteiso-C17 : 0 and anteiso-C15 : 0. The genomic DNA G+C content was 66.2 mol%. It shared high 16S rRNA gene sequence similarities to Phytoactinopolyspora halotolerans YIM 96448T (96.1 %) and Phytoactinopolyspora endophytica EGI 60009T (96.0 %). Phylogenetic trees based on 16S rRNA gene sequences revealed that strain XMNu-373T resided in the clade of family Jiangellaceae , and it formed a monophyletic branch distinct from four other recognized type species in the subclade of the genus Phytoactinopolyspora . On the basis of polyphasic taxonomic evidence, strain XMNu-373T represents a novel species of the genus Phytoactinopolyspora , for which the name Phytoactinopolyspora mesophila sp. nov. is proposed. The type strain is XMNu-373T (=JCM 33740T=CGMCC 4.7654T).

It is still a high challenge to develop a simple, sensitive and portable approach for bioassay in strong scattering medium. Herein, a photoacoustic (PA) device is developed for the detection of alkaline phosphatase (ALP) in serum with silver nanoparticles (AgNPs) as signal probe, without any requirements for expensive equipment, professional operation and pre-processing of real samples. ALP as an important disease marker could catalyze the breakdown of sodium L-ascorbyl-2-phosphate (AAP) into ascorbic acid (AA), thereby reducing Ag+ to AgNPs. AgNPs could generate strong PA signal under the irradiation of modulated 638-nm laser due to their localized plasmon resonance, and detected by the self-made portable PA device. Under the optimized experimental conditions, the present PA device exhibits excellent photostability and reproducibility with the relative standard deviation (RSD) of 2.2% at the concentration of 25 U L−1 ALP. Linear calibration graph is obtained within 5–70 U L−1 for ALP, along with a detection limit of 1.1 U L−1. This portable PA device is applied to detect ALP in serum samples, providing satisfactory spiking recoveries and competitive analytical performances with the current techniques. The PA-based analytical strategy obviously opens up a new avenue to the detection of disease-correlated biomarker in practice.

Background. Tianxiangdan (TXD) is used in traditional Chinese medicine because of its therapeutic and preventive effects in the treatment of coronary heart disease. However, the underlying mechanism of TXD in coronary microvascular disease (CMD) remains unclear. Methods. A rat model of CMD was developed to study the mechanism of TXD activity. Sodium laurate was injected into the left ventricle of Sprague–Dawley rats to induce CMD. The rats were divided into six groups: a sham-operated (sham) group, an untreated CMD group, a low-dose TXD group (0.81 g·kg−1·d−1), a mid-dose TXD (TXD-M) group (1.62 g·kg−1·d−1), a high-dose TXD (TXD-H) group (3.24 g·kg−1·d−1), and a nicorandil (NCR) group (1.35 mg·kg−1·d−1). The effect of TXD on rats with CMD was observed after four weeks, and the mechanism of TXD in lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMECs) was explored through treatment with 50 μg/mL TXD. Results. Compared with the rats in the untreated CMD group, rats in the TXD-M and TXD-H groups showed higher left ventricular ejection fraction values, improved pathological structures, decreased expressions of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor-κB inhibitor α (IκBα) and phosphorylated p65, and increased expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 ( P < 0.05 ). These effects were more pronounced in the TXD-H group than in the TXD-M group. In vitro experiments showed that TXD treatment increased the viability of LPS-induced CMECs and decreased the expression of IL-1β, TNF-α, phosphorylated IκBα, and phosphorylated p65 ( P < 0.05 ). However, the effects of TXD on CMECs were markedly reversed upon treatment with ML385 (Nrf2 inhibitor). Conclusion. The results showed that TXD exerts a protective effect on rats with CMD and related inflammatory injuries, and its anti-inflammatory mechanism is related to the activation of Nrf2 signalling.

In this paper, we propose a method of learning deep and wide contextual representations for statistical parametric speech synthesis (SPSS) using BERT, a pre-trained language representation model. Traditional acoustic models in SPSS utilize phoneme sequences and prosody labels as input, and can not make full use of the deep linguistic representations of current and surrounding sentences. Therefore, this paper designs two context encoders, i.e., a sentence-window context encoder and a paragraph-level context encoder, to integrate the contextual representations extracted from multiple sentences by BERT into Tacotron2 via an extra attention module. The parameters of BERT are pre-trained and then fine-tuned together with other components in the model. Experimental results on the Blizzard Challenge 2019 dataset show that both context encoders can reduce the errors of acoustic feature prediction and improve the subjective performance of synthetic speech comparing with the baseline Tacotron2 model.

To compare the clinical effect between electroacupuncture (EA) at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery.Sixty patients with elective radical esophagectomy were randomly divided into a group A, a group B and a control group, 20 cases in each group. The patients in the group A were treated with injection of 20 mL 0.375% ropivacaine at epidural space 30 min before anesthesia induction, followed by normal anesthesia during operation; the patients in the group B were treated with 30 min EA at bilateral Neima point and Neiguan (PC 6) before anesthesia induction, followed by normal anesthesia during operation; the patients in the control group were treated with general anesthesia alone. Patient-controlled intravenous analgesia was applied for all the patients. The mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before acupuncture/epidural puncture (TThe MAP at TThe preemptive analgesia of EA at Neima point and Neiguan (PC 6) and epidural nerve block could both provide effective perioperative analgesia for thoracic surgery. The EA could better maintain intraoperative hemodynamics and has less physiological disturbance.

Real-time and rapid detection of various biomarkers in body fluids has important significance for early disease diagnosis, efficient monitoring of treatment, and evaluation of prognosis. However, traditional detection methods not only require bulky and costly instruments but also are not suitable for the analysis of heterogeneous samples (e.g., serum and urine), limiting their applications in point-of-care testing (POCT). Herein, an integrated photoacoustic (PA) device with a smartphone as the acoustic signal readout has been constructed, greatly reducing the volume and cost of the instrument, and providing a potential miniature platform for POCT of clinical samples. By exploiting the electron transfer product of 3,3',5,5'-tetramethylbenzidine (TMB) (i.e., TMB++) as the PA probe and hemin-graphene oxide (H-GO) complex as the peroxidase, quantitative analysis of uric acid was successfully performed by using only 30 μL of a sample solution. Due to the favorable stability of artificial enzymes, reaction reagents could be effectively embedded in agar gel to make a portable "test strip". Therefore, operators just need to drop clinical samples on the "test strip" for PA analysis, which is user friendly without requiring complex sample preparation steps. In addition, since the acoustic change mainly comes from the PA effect, it has a lower background signal than UV-vis and fluorescence analysis, greatly improving the analytical performance. The simplicity, low cost, and broad adaptability make this miniature PA device attractive for on-site detection, particularly in resource-limited settings.

Ileal J-pouch anal anastomosis (J-IPAA) is the standard approach for patients requiring restorative proctocolectomy due to familial adenomatous polyposis (FAP) or ulcerative colitis (UC). To obviate the risk of a J-tip leak, we modified the J-pouch with a D-pouch anal anastomosis (D-IPAA) designed to eliminate the ileal stump. The aim of our study was to evaluate the feasibility, safety and medium-term functional outcomes of D-IPAA. A retrospective comparison was made between D-IPAA and J-IPAA constructions after a restorative proctocolectomy. Clinical data were collated between October 2014–March 2018 recording operation duration, pouch construction time, pouch volume, intraoperative estimated blood loss, complication rates, readmissions and cumulative length of hospitalization. Continence was assessed at the final visit with the Wexner Cleveland Clinic Score along with the Cleveland Global Quality of Life (CGQL) scale. A total of 97 patients with FAP (n = 28) and UC (n = 69) who had J-IPAA (n = 54) or D-IPAA (n = 43) after proctocolectomy were identified. Patients were well matched with no differences noted in the intraoperative variables between the J- and D-pouch groups. The D-pouch construction time was shorter than that for a standard J-pouch. There was no difference in major or minor complications between groups. A pouch leak developed in each group: a cutaneous fistula from J tip leak in the J-IPAA group and a pouch-vaginal fistula from the IPAA the D-IPAA group. Clinical outcomes (the number of bowel movements) were equivalent in the two groups with the Wexner score significantly improving within each group up to 2.5 years and with improvement in the CGQL after surgery. The D-pouch construction is safe and feasible for patients with UC and FAP with good functional outcome over the medium term and the potential to reduce the risk of pouch leaks.

Cas12b/C2c1 is a newly identified class 2 CRISPR endonuclease that was recently engineered for targeted genome editing in mammals and rice. To explore the potential applications of the CRISPR-Cas12b system in the dicot Arabidopsis thaliana, we selected BvCas12b and BhCas12b v4 for analysis. We successfully used both endonucleases to induce mutations, perform multiplex genome editing, and create large deletions at multiple loci. No significant mutations were detected at potential off-target sites. Analysis of the insertion/deletion frequencies and patterns of mutants generated via targeted gene mutagenesis highlighted the potential utility of CRISPR-Cas12b systems for genome editing in Arabidopsis.

Perfluorooctanoic acid (PFOA) is widely used in household applications. High-dose exposure to PFOA has been associated with increased risks of infertility and premature ovarian insufficiency in woman. PFOA can alter hepatic gene expression by activating peroxisome proliferator-activated receptor α (PPARα). The present study investigated whether exposure to PFOA via PPARα activation alters the synthesis of hepatic fibroblast growth factor 21 (FGF21) to disturb female neuroendocrine and reproductive function. In the present study, we show that the oral administration of PFOA (2 or 5 mg kg-1 ) in adult female mice (PFOA mice) caused prolonged dioestrous, a reduction in the number of corpora lutea and decreased levels of hypothalamic gonadotrophin-releasing hormone, serum progesterone and luteinising hormone (LH). Exposure to PFOA decreased the expression of vasopressin in the suprachiasmatic nucleus (SCN) and kisspeptin in the anteroventral periventricular nucleus (AVPV) with deficits in preovulation or oestrogen-induced LH surge. PFOA via activation of PPARα increased dose-dependently hepatic FGF21 expression, leading to elevated serum and hypothalamic FGF21 concentrations. Treatment of PFOA mice with the PPARα antagonist GW6471 or the FGF21 inhibitor PD173074 rescued SCN vasopressin and AVPV-kisspeptin expression. Either administration of GW6471 and PD173074 or treatment with vasopressin and the G protein coupled receptor 54 agonist kisspeptin-10 in PFOA-mice was able to recover the regular oestrous cycle, ovulation ability, LH surge production and reproductive hormone levels. The present study provides in vivo evidence that exposure to PFOA (≥2 mg kg-1 ) in mice causes down-regulation of the kisspeptin-reproductive endocrine system by enhancing PPARα-mediated hepatic FGF21 expression. The liver-brain reproductive endocrine disorder caused by PFOA exposure may lead to prolonged dioestrous and ovulation failure.

Gliomas are responsible for the majority of deaths from primary brain tumours. Sevoflurane showed inhibition effects on the tumor progression in vitro. However, whether sevoflurane could affect the stemness of glioma stem cells (GSCs) and the potential molecular mechanism have not been well elucidated.Effects of sevoflurane on cell viability, proliferation and invasion ability of glioma cells as well as tumor growth in vivo were assessed. Sphere formation assay was performed to evaluate the effect of sevoflurane on the stemness of GSCs. Effects of sevoflurane on mitochondrial function was evaluated by intracellular/mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential. Expression levels of proliferation-related proteins, stemness markers and proteins in CaMKII/JNK cascade were measured by Western blot.Sevoflurane inhibited the viability, proliferation and invasion ability of glioma cells (U87MG and U373MG). Western blot showed that sevoflurane decreased the expression levels of proliferation and invasion-related proteins. Sphere formation ability of GSCs, expression levels of stemness markers and mitochondrial function were significantly suppressed by sevoflurane. Moreover, sevoflurane treatment significantly increased the CaThe present study demonstrated that sevoflurane inhibited glioma tumorigenesis and modulated the cancer stem cell-like properties and mitochondrial membrane potential via activation of Ca

We have synthesized a series of transition metal compounds [M(L)2(H2O)2] (M = Co (1), Ni (2), and Cu (3)) by using the 4-amino-1,2,4-triazole Schiff-base ligand via the hydrothermal methods. They are all mononuclear compounds with the octahedral geometry. Direct-current magnetic and HF-EPR measurements were combined to reveal the negative D values (–28.78 cm−1, –10.79 cm−1) of complexes 1 and 2, showing the easy-axis magnetic anisotropies of compounds 1 and 2. Applying a dc field of 800 Oe at 2.0 K, the slow magnetic relaxation effects were observed in compound 1, which is a remarkable feature of single-ion magnets.

As a new generation of amide-type local anesthetics (LAs), ropivacaine has been widely used for pain management in clinical settings. Increasing evidence has shown that administration of ropivacaine causes cytotoxic effects and apoptosis. However, the underlying molecular mechanisms still need to be elucidated. In the current study, our results indicated that ropivacaine treatment caused a significant induction of heme oxygenase-1 (HO-1) at both the mRNA and protein levels in human SHSY5Y cells. Levels of HO-1 mRNA and protein peaked at 1 h and 18 h, respectively, in response to ropivacaine treatment. Additionally, ropivacaine treatment enhanced HO-1 activity in a dose-dependent manner. Interestingly, we found that ropivacaine treatment induced phosphorylation of p38. Blockage of p38 phosphorylation with its specific inhibitor SB203580 or by transfection with p38 siRNA restrained ropivacaine-stimulated HO-1 expression. Additionally, we found that ropivacaine treatment promoted nuclear translocation of Nrf2 and amplified ARE promoter activity. Silencing of Nrf2 abolished ropivacaine-induced HO-1 expression. Notably, we found that inhibition of HO-1 activity promoted ropivacaine-induced production of reactive oxygen species (ROS), deletion of reduced glutathione (GSH), and release of lactate dehydrogenase (LDH), suggesting that induction of HO-1 by ropivacaine acted as a compensatory survival response against ropivacaine.

Objective: To evaluate the association between preeclampsia and three single nucleotide polymorphisms (rs13405728 in LHCGR gene; rs13429458 in THADA gene, and rs2479106 in DENND1A gene) whi...

Emulsified isoflurane (EIso) has a protective effect against ischemia/reperfusion (I/R) injury in animal models. However, the protective effects of EIso on global cerebral I/R injury remain unclear. The present study aimed to investigate whether EIso postconditioning was able to improve survival and neurological outcomes in a rat model of cardiac arrest (CA). Rats were randomly divided into five groups, namely the control, EIso-2ml, EIso-4ml, isoflurane (Iso) and emulsion (E) groups. All rats were resuscitated by a standardized method following 6 min of asphyxia. Furthermore, all interventions were administered immediately following the return of spontaneous circulation (ROSC). The animal survival was recorded daily, and evaluations of behavioral and brain morphology were assessed at 1 and 7 days after ROSC. The results showed that EIso treatment increased the survival rate 7 days after ROSC, with a 41.7% 7-day survival in the EIso-2ml group, 66.7% in the EIso-4ml group and 50% in the Iso group compared with 33.3% survival in the control and E groups. Moreover, the neural deficit score and memory function were improved in the EIso-4ml group, and this treatment also ameliorated brain hippocampal cell injury and apoptosis. In addition, a better brain protective effect was observed in the EIso-4ml group compared with the EIso-2ml, Iso and E groups. In summary, the data of the present study suggest that EIso postconditioning improved the survival and neurological outcomes following CA in a dose-dependent manner.

Emulsified isoflurane (EIso), when introduced following cardiopulmonary resuscitation (CPR), significantly improves survival and neurological outcomes in a rat model of cardiac arrest (CA). The present study aimed to examine whether EIso combined with therapeutic hypothermia (TH) confers an additive neuroprotective effect. Adult male Sprague-Dawley rats that were subjected to return of spontaneous circulation (ROSC) after a 6-min asphyxia-induced CA were randomized to five groups: Sham group, control group under normothermic conditions, EIso group (4 ml/kg for 30 min under normothermic conditions), TH group (33°C for 2 h), and EIso plus TH group. Survival conditions and neurological outcomes were evaluated at 1 day and 7 days after ROSC. Animal survival rate at 7 days after ROSC was 30.7% in the CPR group, 60% in the EIso group, 63.6% in the TH group and 72.7% in the EIso plus TH group. EIso, TH and EIso plus TH yielded significant improvements in survival rates, neural deficit score and cognitive function, and ameliorated hippocampal CA1 region cell injury and apoptosis at 1 day and 7 days after ROSC compared with the CPR group. Combined therapy of EIso and TH was superior to EIso or TH alone, suggesting that combined EIso and TH treatment results in significant improvements in survival and neurological outcomes, and was more effective than independent EIso or TH treatment.

Characterized by wide frequency coverage, high power transmission and high sensitivity reception for the microwave remote sensing satellite, ninety-seven percent of the satellite devices cannot satisfy their standards or requirements in the receiving frequency band of payload, and the electromagnetic environment of the satellite is complicated. This paper mainly discusses the system level EMC design technology, including inhibiting the interference path, controlling the unexpected radiation emission of satellite products, and improving the shielding performance of cabin plates, to solve the interference problem, leading to a good electromagnetic compatibility for the satellite.

Photoacoustic (PA) effect has been widely applied in many fields, e.g., physics, chemistry and biomedicine. Herein, a miniaturized PA device is developed by integrating laser source, photo chopper, PA cell, microphone, and laptop for point-of-care testing in bioassay. With glucose assay as model, a piece of paper strip preloading chitosan, starch-potassium iodide (KI) and glucose oxidase (GOD) as lab-on-paper is employed for loading sample prior to PA detection. In the presence of glucose, the product generated on the paper strip would give rise to a strong PA signal in the PA cell under the irradiation of frequency-modulated laser at 520 nm via laptop readout. With a sample volume of 20 μL, a detection limit of 0.03 mM is obtained for glucose assay, along with a linear range of 0.08–1 mM. The accuracy and practicability of the present PA device is well demonstrated by detecting glucose in whole blood. Differing from the conventional PA instrument, the present PA device is really small in bulk with competitive sensitivity and excellent stability, offering a promising tool for point-of-care testing in bioassay.

In this paper, we introduce the Variational Autoencoder (VAE) to an end-to-end speech synthesis model, to learn the latent representation of speaking styles in an unsupervised manner. The style representation learned through VAE shows good properties such as disentangling, scaling, and combination, which makes it easy for style control. Style transfer can be achieved in this framework by first inferring style representation through the recognition network of VAE, then feeding it into TTS network to guide the style in synthesizing speech. To avoid Kullback-Leibler (KL) divergence collapse in training, several techniques are adopted. Finally, the proposed model shows good performance of style control and outperforms Global Style Token (GST) model in ABX preference tests on style transfer., Paper accepted by ICASSP 2019

Aims Gliomas are responsible for the majority of deaths from primary brain tumours. Sevoflurane showed inhibition effects on the tumor progression in vitro. However, whether sevoflurane could affect the stemness of glioma stem cells (GSCs) and the potential molecular mechanism have not been well elucidated. Main methods Effects of sevoflurane on cell viability, proliferation and invasion ability of glioma cells as well as tumor growth in vivo were assessed. Sphere formation assay was performed to evaluate the effect of sevoflurane on the stemness of GSCs. Effects of sevoflurane on mitochondrial function was evaluated by intracellular/mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential. Expression levels of proliferation-related proteins, stemness markers and proteins in CaMKII/JNK cascade were measured by Western blot. Key findings Sevoflurane inhibited the viability, proliferation and invasion ability of glioma cells (U87MG and U373MG). Western blot showed that sevoflurane decreased the expression levels of proliferation and invasion-related proteins. Sphere formation ability of GSCs, expression levels of stemness markers and mitochondrial function were significantly suppressed by sevoflurane. Moreover, sevoflurane treatment significantly increased the Ca2+ concentration and stimulated phosphorylation of CaMKII, JNK and IRS1. Ca2+ chelator BAPTA-AM combined with sevoflurane synergistically inhibited colony forming ability and the expression levels of proliferation-related proteins and stemness markers. In addition, the in vivo study further confirmed that sevoflurane inhibited tumor growth via Ca2+-dependent CaMKII/JNK cascade. Significance The present study demonstrated that sevoflurane inhibited glioma tumorigenesis and modulated the cancer stem cell-like properties and mitochondrial membrane potential via activation of Ca2+-dependent CaMKII/JNK cascade.

Background and aims Oxidative stress-induced endothelial dysfunction is considered to exert a vital role in the development of atherosclerotic coronary heart disease (CHD). NRF2 is a key transcriptional factor against oxidative stress through activation of multiple ARE-mediated genes. Z-Lig is derived from the Ligusticum species with antitumor, anti-inflammation and neuroprotection activities. However, the antioxidant potentials of Z-Lig on endothelial dysfunction and atherosclerosis have not been well elucidated. Therefore, in the present work, we appraise the cytoprotective property and anti-atherosclerosis effect of Z-Lig. Methods Potential NRF2 activators were screened and verified by luciferase reporter gene assay. The protein and mRNA levels of NRF2 and ARE-mediated genes, and GSH/GSSG level in EA.hy926 cells treated with Z-Lig were detected. The cytoprotective property of Z-Lig was assessed in the tert-butyl hydroperoxide (t-BHP)-evoked oxidative stress model. Cell viability and reactive oxygen species (ROS) levels in EA.hy926 cells were determined. An atherosclerosis model induced by HFD was used to determine the anti-atherosclerosis effect of Z-Lig in HFD-fed Ldlr-deficient mice. Results In vitro, 100 μM Z-Lig upregulated expressions of NRF2 and ARE-driven genes, promoted accumulation of nuclear NRF2 and unbound NRF2- KEAP1 complex in EA.hy926 cells. Furthermore, Z-Lig alleviated oxidative stress and cell injury caused by t-BHP via stimulation of the NRF2/ARE pathway. In vivo, intervention with 20 mg/kg Z-Lig markedly restrained atherosclerosis progression, including attenuation of HFD-induced atherosclerotic plaque formation, alleviation of lipid peroxidation and increase in antioxidant enzyme activity in aortas of HFD-fed Ldlr −/− mice. The chemopreventive effects of Z-Lig might be associated with the activation of NRF2 and ARE-driven genes. Conclusions The present study suggested that Z-Lig is an effective NRF2 activator, which can protect vascular endothelial cells from oxidative stress and rescue HFD-induced atherosclerosis.

This paper investigates the methods to detect and classify marmoset vocalizations automatically using a large data set of marmoset vocalizations and deep learning techniques. For vocalization detection, neural networks-based methods, including deep neural network (DNN) and recurrent neural network with long short-term memory units, are designed and compared against a conventional rule-based detection method. For vocalization classification, three different classification algorithms are compared, including a support vector machine (SVM), DNN, and long short-term memory recurrent neural networks (LSTM-RNNs). A 1500-min audio data set containing recordings from four pairs of marmoset twins and manual annotations is employed for experiments. Two test sets are built according to whether the test samples are produced by the marmosets in the training set (test set I) or not (test set II). Experimental results show that the LSTM-RNN-based detection method outperformed others and achieved 0.92% and 1.67% frame error rate on these two test sets. Furthermore, the deep learning models obtained higher classification accuracy than the SVM model, which was 95.60% and 91.67% on the two test sets, respectively.

In this paper, we investigate the performance of using different excitation parameters for WaveNet-based neural vocoders by experiments. The neural vocoders based on WaveNet models have been proposed recently and achieved high quality of reconstructed speech. In these vocoders, spectral features and excitation parameters are used as local conditions of WaveNet models to predict the distribution of waveform samples. In our experiments, F0s, pulse trains, and LPC residual signals are utilized to represent excitation parameters separately or jointly. When using pulse trains and LPC residual signals, additional dilated causal convolution blocks are adopted to derive the condition vectors. Experimental results show that the vocoders conditioned on LPC residual signals can achieve better temporal accuracy of waveform modeling and prediction than using F0s and pulse trains as excitation parameters. These results imply the deficiency of only using F0s as excitation parameters and other parameters that can provide more detailed description of excitations should be explored in future work.

Water samples were collected in summer, autumn, winter, and spring in Beihai Lake for the analysis of water quality and microbial community structure. It was found that the water quality in summer and autumn was worse than in winter and spring, and TN and TP were the most important factors affecting the water quality. The microbial community structure was investigated using MiSeq high-throughput sequencing. It was found that the phyla Cyanobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes were abundant in all the samples, whereas their relative abundances differed among the four seasons. In summer and autumn, the microbial diversities were higher, and the phylum Cyanobacteria was most abundant, with the genus

Neovascular glaucoma is an ophthalmic disease and a potentially blinding secondary glaucoma caused by the formation of abnormal new blood vessels on the iris, which can prevent the normal drainage of water from the anterior segment of the eye. Evidence from China has suggested that puerarin benefits many diseases including myocardial infarction, stable angina, cerebral ischemia and glaucoma in a clinical setting. In the present study, the aim was to investigate the efficacies of puerarin on neovascular glaucoma in a mouse model. The molecular mechanism of puerarin‑mediated treatment for neovascular glaucoma was also investigated both in vitro and in vivo. Inflammatory responses in mice with neovascular glaucoma were analyzed by western blotting. Oxidative stress levels were investigated following treatment with puerarin in a mouse model of neovascular glaucoma. The results indicated that puerarin markedly improved growth of vascular endothelial cells. The present study reported that puerarin treatment markedly decreased interleukin (IL)‑1β, IL‑17A and tumor necrosis factor‑α expression levels in mice with neovascular glaucoma. It was found that puerarin significantly decreased oxidative stress levels by reducing reactive oxygen species, superoxide dismutase and malondialdehyde levels, as well as neuronal nitric oxide synthase (NOS) and inducible NOS expression levels. Results indicated that expression levels of pigment epithelium‑derived growth factor were significantly inhibited following treatment with puerarin. Mechanism analysis demonstrated that treatment with puerarin effectively inhibited nuclear factor (NF)‑κB activity and its target protein levels p65, inhibitor of NF‑κB kinase subunit β and inhibitor of NF‑κB kinase subunit α in vascular endothelial cells. Increasing endothelial‑derived growth factor (EDGF) expression levels could stimulate NF‑κB activity and abolish the inhibitory effects of puerarin. An animal study reported that puerarin treatment presented therapeutic effects for mice with neovascular glaucoma. Numbers of new vessels in iris were recovered to normal following puerarin treatment. In conclusion, these results indicated that puerarin treatment can inhibit inflammatory responses and oxidative stress, platelet‑derived growth factor (PDGF) expression and NF‑κB activity, suggesting puerarin may be a potential agent for the treatment of neovascular glaucoma through PDGF‑induced NF‑κB signaling pathway.

Triclosan (TCS), as a broad spectrum antibacterial agent, is commonly utilized in personal care and household products. Maternal urinary TCS level has been associated with changes in birth weight of infants. We in the present study investigated whether exposure of mice to 8 mg/kg TCS from gestational day (GD) 6 to GD14 alters prenatal and postnatal growth and development, and metabolic phenotypes in male and female offspring (TCS-offspring). Compared with control offspring, body weight in postnatal day (PND) 1 male or female TCS-offspring was reduced, but body weight gain was faster within postnatal 5 days. PND30 and PND60 TCS-offspring showed overweight with increases in visceral fat and adipocyte size. PND60 TCS-offspring displayed delayed glucose clearance and insulin resistance. PND30 TCS-offspring showed an increase in food intake without the changes in the oxygen consumption and respiratory exchange ratio (RER). The expression levels of proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH) and single-minded 1 (SIM1) in hypothalamus arcuate nucleus (ARC) and paraventricular nucleus (PVN), respectively, were significantly reduced in PND30 TCS-offspring compared to controls. The hypermethylation of CpG sites at the POMC promoter was observed in PND30 TCS-offspring, while the concentration of serum leptin was elevated and the level of STAT3 phosphorylation in ARC had no significant difference from control. This study demonstrates that TCS exposure during early/mid-gestation through the hypermethylation of the POMC promoter reduces the expression of anorexigenic neuropeptides to cause the postnatal hyperphagic obesity, leading to metabolic syndrome in adulthood.

Sevoflurane, an inhaled ether general anesthetic agent, exerts a variety of neurotoxic effects, including oxidative stress, mitochondrial dysfunction, and neuronal apoptosis. However, the underlying molecular mechanisms remain to be elucidated. DJ-1 is a protein that exerts neuroprotective effects against different kinds of stress through multiple pathways. This study aimed to investigate the neuroprotective effects of DJ-1 against sevoflurane-induced neurotoxicity. Here, we found that sevoflurane treatment significantly increased DJ-1 expression in human neuroblastoma M17 cells in a dose-dependent manner at both the mRNA and protein levels. Interestingly, we found that overexpression of wild-type (WT) DJ-1 prevented sevoflurane-induced generation of reactive oxygen species (ROS) and nitric oxide (NO), deletion of reduced GSH, reduction of adenosine triphosphate (ATP), and mitochondrial membrane potential. Interestingly, we found that WT DJ-1 could inhibit sevoflurane-induced apoptosis by modulating the mitochondrial pathway. However, its “loss of function” mutation DJ-1(L166P) exacerbated sevoflurane-induced neurotoxicity in M17 cells. Our findings suggest that WT DJ-1 protects neuronal cells against sevoflurane-induced neurotoxicity.

The aim of this study was to investigate the effects of L-carnitine (LC) on follicular survival and ovarian function following cryopreservation-thawing and autotransplantation of ovarian tissues. ICR mice were divided into three groups: control; saline group (cryopreservation+autograft+saline); and LC group (cryopreservation+autograft+L-carnitine). The ovarian tissues from control group, saline group, and LC group were histological assessed. There were no significant differences in the percentage of morphologically normal primordial follicles between the LC group and the saline group. After 28 days of autotransplantation, apoptosis rates, plasma malondialdehyde (MDA), progesterone (P4) and estradiol (E2) concentrations, and follicular densities of grafts were evaluated. Apoptosis rate and the concentration of MDA in the LC group were significantly lower than those in the saline group. The concentration of E2 and follicular densities of grafts in LC group were significantly higher than that in saline group. LC inhibits follicle apoptosis and increases follicular survival and function of ovarian graft.