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Background: Aging is a global problem, and the ability assessment of the elderly plays an important role in the formulation of pension policies. It's necessary to evaluate the ability of the elderly in rural China to provide insights into future nursing care and policy making., Methods: The elderly in 20 rural villages were selected by convenience sampling. We used "Elderly Ability Evaluation Form" issued by the Ministry of Civil Affairs of China as survey tool. The characteristics and score differences of the elderly of different ability level were compared and analyzed. And logistic regression analyses were conducted to identify the potential risk factors for disability in the elderly., Results: A total of 2,878 elders were included, of which there were 1,916 elders with intact ability, 866 elders with mild disability, 42 elders with moderate disability, 54 elders with severe disability. The incidence of disability among respondents was 33.43%. There were significantly statistical differences in the dimensions of activities of daily living, mental state, perception and communication, and social participation among elders with intact ability, mild, moderate and severe disability (all P<0.05). The age, education level, marital status and living situations were all corrected to the scores on the activities of daily living, mental state, perception and communication, and social participation among elders (all P<0.05), and the elderly with age ≥75 years, illiteracy, unmarried and live alone had higher risk for disability (all P<0.05)., Conclusions: The current situation of the ability level of the elderly in rural China seems to be worrying, and it's necessary to establish a long-term nursing care system and aging policy to meet the needs of the elderly with regards to those potential influencing factors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-555). The authors have no conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Ochratoxin A (OTA) was reported to induce proximal tubules nephrotoxicity in humans and animals. However, the toxicity of OTA on glomeruli has rarely been studied. We investigated OTA-induced glomerular injury and the underlying mechanisms. Mice were intraperitoneally treated with OTA (0, 0.5, 1.5 and 2.5 mg/kg b.w.) on alternate day for 3 weeks. OTA exposure decreased the weight gain ratio, the kidney index and increased the levels of serum creatinine and blood urea nitrogen. It induced also fragmentation and atrophy in glomeruli, and increased the expression of TNF-α, IL-6, COX-2, TGF-β, α-SMA and vimentin in a dose-dependent manner. Human mesangial cells (HMC) were treated with OTA (0-8 μM) for 48 h. Treatment of HMC cells with OTA increased cell inhibition rate, up-regulated the expression of IL-6, TGF-β, α-SMA and vimentin in a dose-dependent manner. Additionally, it enhanced the phosphorylation of ERK1/2 and p65, degradation of IκB-α and translocation of p65 into the nucleus. OTA-induced toxicity was attenuated by NF-κB and ERK1/2 inhibitors. In conclusion, these results suggest that OTA exposure induces glomerular injury via activation of the ERK/NF-κB signaling pathway, and provide novel insights into the research of OTA induced nephrotoxicity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Metabolic syndrome (MS) is a powerful risk factor for cardiovascular and cerebrovascular diseases. Although lifestyle intervention reduces several of the symptoms of the syndrome and cardiovascular risks, the lifestyle intervention that yields the benefits is restrictive. Jinlida is a Chinese patent medicine that has shown activity in type 2 diabetes, which has been approved in China. Preclinical studies in Jinlida granules support an improved role of abnormal glucose and lipids metabolism as well as reducing weight. Here, we describe the protocol of an ongoing clinical trial investigating a new therapy for metabolic syndrome in patients with abnormal glucose metabolism. Methods: This study will enroll 880 subjects (aged 18-70 years) who have metabolic syndromes with abnormal glucose metabolism. All the participants in a double-blind, parallel, randomized, placebo-controlled trial, will receive Jinlida or placebo, orally, 9 g/time, three times daily for 2-4 years period on the basis of lifestyle intervention. The primary outcome measure (Incidence of type 2 diabetes) will be assessed during intervention cycles. Adverse events were monitored. All statistical tests will be performed using a two-sided test, and a p ≤ 0.05 (two-sided test) will be considered to be statistically significant results. Discussion: Results from this study will provide evidence on whether incorporating oral Jinlida granules treatment into lifestyle intervention can delay or inhibit the development of diabetes mellitus in metabolic syndrome subjects with abnormal glucose metabolism. Clinical trial registration: Registered at http://www.chictr.org.cn/enIndex.aspx. Trial registration number: ChiCTR1900023241., (Copyright © 2020 Jin, Hou, Han, Chang, Gao, Zhao, Zhao, An, Song, Piao, Lian, Xiao-lin and Jia.)

The integration of photochromic molecules into semiconducting polymer matrices via blending has recently attracted a great deal of attention, as it provides the means to reversibly modulate the output signal of electronic devices by using light as a remote control. However, the structural and electronic interactions between photochromic molecules and semiconducting polymers are far from being fully understood. Here we perform a comparative investigation by combining two photochromic diarylethene moieties possessing similar energy levels yet different propensity to aggregate with five prototypical polymer semiconductors exhibiting different energy levels and structural order, ranging from amorphous to semicrystalline. Our in-depth photochemical, structural, morphological, and electrical characterization reveals that the photoresponsive behavior of thin-film transistors including polymer/diarylethenes blends as the active layer is governed by a complex interplay between the relative position of the energy levels and the polymer matrix microstructure. By matching the energy levels and optimizing the molecular packing, high-performance optically switchable organic thin-film transistors were fabricated. These findings represent a major step forward in the fabrication of light-responsive organic devices.

Tamoxifen is widely used as a highly effective drug for treating estrogen‑receptor (ER) alpha‑positive breast cancer. However, tamoxifen resistance developed during cancer treatment remains a significant challenge. Tongue cancer resistance‑related protein1 (TCRP1), which is recognized as a novel drug target, is related to chemo‑resistance in human cancers, moreover, it is often overexpressed in various cancer cells, such as in lung cancer, breast cancer, and tongue cancer. However, the effects of TCRP1 on tamoxifen‑resistant breast cancer cells and tissues are far from clear. The present study revealed that TCRP1 induced tamoxifen resistance in breast cancer cells. Western blotting, quantitative real‑time polymerase chain reaction (RT‑PCR) and immunohistochemical staining were performed to detect the expression level of TCRP1 in vivo and in vitro between primary breast cancer tissues and tamoxifen‑resistant breast cancer tissues. The data revealed that the expression of TCRP1 was upregulated in the tamoxifen‑resistant breast cancer tissues and human breast cancer cell line, MCF‑7. Further study revealed that knocking down TCRP1 inhibited the growth of MCF‑7 cells with tamoxifen‑resistance (MCF7‑R cells) and induced cell apoptosis. Moreover, TCRP1 promoted serum‑ and glucocorticoid‑inducible kinase 1 (SGK1) activation via phosphorylation of phosphoinositide‑dependent kinase 1 (PDK1) in MCF7‑R cells. In addition, it was also observed that knocking down TCRP1 inhibited tumorigenesis of MCF‑7 cells in nude mice. In conclusion, these data indicated that TCRP1 could induce tamoxifen resistance by regulating the PDK1/SGK1 signaling pathway. Thus, TCRP1 could be explored as a promising candidate for treating tamoxifen‑resistant breast cancer in the future.

Autophagy is a cellular mechanism responsible for delivering protein aggregates or damaged organelles to lysosomes for degradation. It is also simultaneously a precise regulatory process, which is crucial for dealing with hunger, oxidative stress, and pathogen defense. Neutrophil Extracellular Traps (NETs), which form a part of a newly described bactericidal process, are reticular structures composed of a DNA backbone and multiple functional proteins, formed via a process known as NETosis. NETs exert their anti-infection activity by capturing pathogenic microorganisms, inhibiting their spread and inactivating virulence factors. However, NETs may also activate an immune response in non-infectious diseases, leading to tissue damage. Although the mechanism underlying this phenomenon is unclear, a large number of studies have suggested that autophagy may be involved. Autophagy-mediated NETs not only induce inflammation and tissue damage, but can also lead to cell senescence, malignant transformation, and cell death. Autophagy-dependent NETs also play a beneficial role in the hostwith respect to pathogen clearance and immune defense. Through careful review of the literature, we have found that the distinct roles of autophagy in NETosis may be dependent on the extent of autophagy and the specific manner in which it was induced. This article summarizes numerous recent studies, and reviews the role of autophagy-driven NETosis in various diseases, in the hope that this will lead to the development of more effective treatments., Competing Interests: Declaration of Competing Interest No potential conflicts of interest were disclosed by the authors., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Naphthalimides, such as amonafide and mitonafide in clinical trials, have been developed as antitumor agents for orthotopic tumor. However, the serious side effects in cancer patients limit their applications. Herein, a new class of polyamine-based naphthalimide conjugates 5a-5c , 7a-7b , and 11a-11b with and without the alkylation of the distant nitrogen in the polyamine chain were synthesized and the mechanism was determined. Compared with amonafide, dinitro-naphthalimide conjugate 5c with a 4,3-cyclopropyl motif preferentially accumulates in cancer cells and minimizes side effects in vitro and in vivo . More importantly, 5c at the dosage of as low as 3 mg/kg (57.97%) displays better antitumor effects than the positive control amonafide (53.27%) at 5 mg/kg in vivo . And a remarkably elevated antitumor activity and a reduced toxicity are also observed for 5c at 5 mg/kg (65.90%). The upregulated p53 and the apoptotic cells (73.50%) indicate that the mechanism of 5c to induce apoptosis may result from its enhanced DNA damage. Further investigation indicates that in addition to target DNA, 5c can modulate the polyamine homeostasis by upregulating polyamine oxidase (PAO) in a different way from that of amonafide. And also by targeting PTs overexpressed in most of cancer cells, 5c downregulates the contents of Put, Spd, and Spm, which are in favor of suppressing fast-growing tumor cells. Our study implies a promising strategy for naphthalimide conjugates to treat hepatic carcinoma with notable activities and reduced toxicities at a low dosage., (Copyright © 2020 Ma, Li, Li, Yue, Liu, Wang, Xi, Shi, Zhao, Ma, Liu, Guo, Liu, Hou, Wang, Wang, Tian and Xie.)

A completely water soluble azobenzene chemosensor 1 for selective detection of Hg2+ was synthesized. Taking advantage of the absorption changes corresponding to the transition moments polarized along the short axis of an azobenzene, 1 showed characteristic UV-Vis signal changes in the band around 240 nm for Hg2+ in wide pH ranges, which also showed good tolerance to various metal ions and photoirradiation. Upon addition of Hg2+ into the solution of 1, a favored formation of trans-1 was observed, which is attributed to an intramolecular coordination of the PEG chain and Nβ to Hg2+ confirmed by a control experiment test.

Ochratoxin A (OTA) is a potent nephrotoxin. Selenium (Se) is an essential micronutrient for humans and animals, and plays a key role in antioxidant defense. To date, little is known about the effect of Se on OTA-induced DNA damage. In this study, the protective effects of Se (from selenomethionine) against OTA-induced cytotoxicity and DNA damage were investigated by using PK15 cells as a model. The results showed that OTA at 4.0 μg/mL induced cytotoxicity and DNA damage. Se at 0.5, 1, 2 and 4 μM significantly blocked OTA-induced cytotoxicity and DNA damage. Furthermore, Se blocked the increases of DNMT1, DNMT3a and HDAC1 mRNA and protein expression, reversed the decreases of glutathione peroxidase 1 (GPx1) mRNA and protein expression, and promoted the increases of SOCS3 mRNA and protein expression induced by OTA. Overexpression of GPx1 by pcDNA3.1-GPx1 inhibited the OTA-induced DNMT1 expression, promoted OTA-induced SOCS3 expression, and prevented the OTA-induced cytotoxicity and DNA damage. In contrast, knock-down of GPx1 by using a GPx1-specific siRNA had the opposite effects. The results suggest that GPx1-mediated DNMT1 expression is involved in the blocking effects of selenium on OTA-induced cytotoxicity and DNA damage., Competing Interests: Declaration of competing interest We do not have any commercial associations that might create a conflict of interest in connection with this article., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cyclosporine A (CsA) extracted from the products of fungal fermentation is used to develop a chronic nephropathy model. However, it has numerous side effects. Ochratoxin A (OTA) is a mycotoxin that induces renal injury. We developed a chronic nephropathy model to lessen the side effects of CsA by administration of nontoxic dosage of OTA, and investigated the underlying mechanism. C57BL/10 wild-type mice, toll-like receptor 4 (TLR4) -/- mice, and HK-2 cells were used in this study. The nontoxic dosage (0.25 mg/kg, qod) of OTA could significantly decrease the dosage of CsA from 30 to 20 mg/kg per day, and combination of them induced chronic nephropathy model and alleviated the side effects of onefold CsA in vivo, including cardiotoxicity, hepatotoxicity, and immunosuppression. The nontoxic concentration (0.5 μg/ml) of OTA could significantly decrease the concentration of CsA from 10 to 6 μg/ml that induced cytotoxicity, oxidative stress, and nephrotoxicity in vitro. Nontoxic concentration of OTA and low dosage of CsA activated TLR4 and autophagy. These toxic effects induced by OTA and CsA could be reversed by knockdown of TLR4 and autophagy inhibitor 3-methyladenine in vitro. Furthermore, the renal injury and autophagy induced by OTA and CsA could be attenuated in TLR4 -/- mice. It suggested that a chronic nephropathy model had been successfully developed by administration of nontoxic concentration of OTA and low dosage of CsA via TLR4-mediated autophagy. The side effects of current model were significantly lesser than those of the previous model induced by onefold CsA. It provided a new tool for exploring the pathogenesis and treatment of chronic kidney disease.

Triple-negative breast cancer (TNBC) is a one of the subtypes of breast cancer which accounts for approximately 10-20% of all breast cancers. LncRNA XIST (XIST) is reported to be dysfunctional in numerous tumor types and is involved in the key pathways of cancer initiation, progression and metastasis. Thus, in the present study, we explored the detailed molecular mechanism of XIST in TNBC. XIST was down-regulated in TNBC tissues and cell lines. Overexpressed XIST inhibited cell proliferation, epithelial mesenchymal transition (EMT) and induced apoptosis in vitro as well as suppressed TNBC tumor growth in vivo . MicroRNA (miR)- 454 was up-regulated in TNBC tissues and cell lines. Knockdown of miR-454 inhibited TNBC progression by suppressing cell proliferation, EMT and inducing cell apoptosis. Moreover, miR-454 was predicted and confirmed to be a target of XIST, and rescue assay indicated that overexpressed miR-454 could reverse XIST restoration mediated-anti-tumor effects on TNBC cells. In conclusion, XIST interacts with miR-454 to inhibit cells proliferation, EMT and induce apoptosis in TNBC, indicating a promising treatment strategy for TNBC patients.

Objective: To investigate the caring burden and its determinants of primary informal caregiver of patients with chronic wound. Approach: A prospective cross-sectional study of 132 pairs of chronic wound care recipients and their informal caregivers was included. The characteristics of patients and their informal caregivers as well as caregiver burden assessment by the caregiver burden inventory (CBI) were measured. Single factor analysis and multiple regression analysis were carried out to explore the independent determinants of caregiver burden on caring for patients with chronic wound. Results: Most of the caregivers were female with mean age of 54.57 ± 13.35 years, and 58.3% of the caregivers were adult children. The mean CBI score was 34.21 ± 9.69 at a medium level. The following variables increased the CBI scores of caregivers: long caring time per day for patients, powerlessness status of patients, insufficient self-efficacy, and social support of caregivers, the model was able to explain 67.5% of variance in caregiver burden ( F  = 47.167, p  = 0.000, R 2  = 0.675, adjusted R 2  = 0.660). Innovation: Caring burden of patients with chronic wound as a key consideration of patient-centered wound care has received relatively little attention. In this study we report the status of caring burden and reveal its determinants of primary informal caregiver of patients with chronic wound. Conclusion: Wound professionals are suggested to pay attention to the caregiver burden of patients with chronic wound and develop family-centered intervention support service system according to the determinants of caregiver burden to alleviate the caregiver burden., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No ghostwriters were involved in the preparation of this article.

Transgenic technology was developed to introduce transgenes into various organisms to validate gene function and add genetic variations >40 years ago. However, the identification of the transgene insertion position is still challenging in organisms with complex genomes. Here, we report a nanopore-based method to map the insertion position of a Ds transposable element originating in maize in the soybean genome. In this method, an oligo probe is used to capture the DNA fragments containing the Ds element from pooled DNA samples of transgenic soybean plants. The Ds element-enriched DNAs are then sequenced using the MinION-based platform of Nanopore. This method allowed us to rapidly map the Ds insertion positions in 51 transgenic soybean lines through a single sequencing run. This strategy is high throughput, convenient, reliable, and cost-efficient. The transgenic allele mapping protocol can be easily translated to other eukaryotes with complex genomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

The present study was conducted to evaluate the effects of zinc-enriched probiotics (ZnP) on growth performance, antioxidant status, immune function, related gene expression, and morphological characteristics of Wistar rats raised under high heat stress condition during summer. 36, 6-week-old male Wistar rats were randomly divided into three groups; fed with basal diet (control), basal diet with probiotics (P), and basal diet with zinc-enriched probiotics supplementation (ZnP, 100 mg/L), for 40 consecutive days. Blood samples were collected through intracardiac method on the last day of experiment and tissues were collected from liver, heart, and kidneys. The results revealed that both P and ZnP significantly ( P  < 0.05) enhanced growth performance. However, ZnP remarkably increased glutathione content, glutathione peroxidase, and superoxide dismutase activities but reduced malondialdehyde level in serum of the Wistar rats. The concentration of IL-2, IL-6, and IFN-γ was significantly ( P  < 0.05) increased with treatments of P and ZnP compared to control group while IL-10 was significantly ( P  < 0.05) decreased. Additionally, the expression of SOD1, SOD2, MT1, and MT2 genes was significantly ( P  < 0.05) up-regulated with the treatment of ZnP, but Hsp90 and Hsp70 heat shock genes were significantly ( P  < 0.05) down-regulated with the treatment of P and ZnP, respectively. Hematoxylin and Eosin staining showed that both P and ZnP supplementation treatments induced changes in villus height and intestinal wall thickness. In conclusion, zinc-enriched probiotics supplementation can improve the growth performance of Wistar rats under high ambient temperature through enhancing antioxidant status, immune function, related genes expression, and intestinal morphological characteristics. This product may serves as a potential nutritive supplement for Wistar rats under high heat stress conditions., Competing Interests: Conflict of interestThe authors declare no conflict of interest.

Soybean (Glycine max [L.] Merr.) is a commodity crop highly valued for its protein and oil content. The high percentage of polyunsaturated fatty acids in soybean oil results in low oxidative stability, which is a key parameter for usage in baking, high temperature frying applications, and affects shelf life of packaged products containing soybean oil. Introduction of a seed-specific expression cassette carrying the Arabidopsis transcription factor WRINKLED1 (AtWRI1) into soybean, led to seed oil with levels of palmitate up to approximately 20%. Stacking of the AtWRI1 transgenic allele with a transgenic locus harbouring the mangosteen steroyl-ACP thioesterase (GmFatA) resulted in oil with total saturates up to 30%. The creation of a triple stack in soybean, wherein the AtWRI1 and GmFatA alleles were combined with a FAD2-1 silencing allele led to the synthesis of an oil with 28% saturates and approximately 60% oleate. Constructs were then assembled that carry a dual FAD2-1 silencing element/GmFatA expression cassette, alone or combined with an AtWRI1 cassette. These plasmids are designated pPTN1289 and pPTN1301, respectively. Transgenic events carrying the T-DNA of pPTN1289 displayed an oil with stearate levels between 18% and 25%, and oleate in the upper 60%, with reduced palmitate (<5%). While soybean events harboring transgenic alleles of pPTN1301 had similar levels of stearic and oleate levels as that of the pPTRN1289 events, but with levels of palmitate closer to wild type. The modified fatty acid composition results in an oil with higher oxidative stability, and functionality attributes for end use in baking applications., (© 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

As the most toxic mycotoxin of all of the fungal toxins, aflatoxin B 1 (AFB 1 ) has carcinogenesis, heptotoxicity, and immunotoxicity. DNA methylation plays a critical role in gene expression regulation of the pathological process. However, the relationship between DNA methylation and AFB 1 -induced immunotoxicity was not yet reported. Therefore, the objectives of this study were to verify AFB 1 -induced immunotoxicity and investigate the potential role of the DNA methyltransferase (DNMT) family in AFB 1 -induced immunotoxicity and the pathway mechanism in 3D4/21 cells. The results showed that AFB 1 could induce cytotoxicity, apoptosis, pro-inflammatory cytokine expression, DNA damage, and oxidative stress and decrease phagocytotic capacity. Meanwhile, the levels of DNMT1 and DNMT3a were significantly increased in 0.04 and 0.08 μg/mL AFB 1 compared to the control. Inhibition of DNMT1 and DNMT3a by 5-Aza-2dc could reverse changes of the above parameters. Further, the JAK2/STAT3 pathway was significantly activated in 0.04 μg/mL AFB 1 . Inhibition of p-JAK2 and p-STAT3 by AG490 could alleviate AFB 1 -induced immunotoxicity. Moreover, inhibition of DNMT1 and DNMT3a by 5-Aza-2dc could suppress the phosphorylation of JAK2 and STAT3. Taken together, AFB 1 -induced immunotoxicity is related to the JAK2/STAT3 pathway mediated by DNMTs in 3D4/21 cells.

Ochratoxin A (OTA) is reported to induce nephrotoxicity and immunotoxicity in animals and humans. However, the underlying mechanism and the effects of OTA on DNA damage have not been reported until now. The present study aims to investigate OTA-induced cytotoxicity and DNA damage and the underlying mechanism in PK15 cells and PAMs. The results showed that OTA at 2.0-8.0 µg/mL for 24 h induced cytotoxicity and DNA damage in PK15 cells and PAMs as demonstrated by decreasing cell viabilities and mRNA levels of DNA repair genes (OGG1, NEIL1 and NEIL3), increasing LDH release, Annexin V staining cells, apoptotic nuclei and the accumulation of γ-H2AX foci. OTA at 2.0-8.0 µg/mL increased DNMT1 and SOCS3 mRNA expressions about 2-4 fold in PK15 cells or 1.3-2 fold in PAMs. OTA at 2.0-8.0 µg/mL increased DNMT1, SOCS3, JAK2 and STAT3 protein expressions in PK15 cells or PAMs. DNMT inhibitor (5-Aza-2-dc), promoted SOCS3 expression, inhibited JAK2 and STAT3 expression, alleviated cytotoxicity, apoptosis and DNA damage induced by OTA at 4.0 µg/mL in PK15 cells. While, in PAMs, 5-Aza-2-dc had no effects on SOCS3 expression induced by OTA at 4.0 µg/mL, but inhibited JAK2 and STAT3 expression, and alleviated cytotoxicity, apoptosis and DNA damage induced by OTA. JAK inhibitor (AG490) or STAT3-siRNA alleviated OTA-induced cytotoxicity and DNA damage in PK15 cells or PAMs. Taken together, nephrotoxicity instead of immunotoxicity of OTA is induced by targeting SOCS3 through DNMT1-mediated JAK2/STAT3 signaling pathway. These results provide a scientific and new explanation of the underlying mechanism of OTA-induced nephrotoxicity and immunotoxicity.

Organic light-emitting transistors are pivotal components for emerging opto- and nanoelectronics applications, such as logic circuitries and smart displays. Within this technology sector, the integration of multiple functionalities in a single electronic device remains the key challenge. Here we show optically switchable organic light-emitting transistors fabricated through a judicious combination of light-emitting semiconductors and photochromic molecules. Irradiation of the solution-processed films at selected wavelengths enables the efficient and reversible tuning of charge transport and electroluminescence simultaneously, with a high degree of modulation (on/off ratios up to 500) in the three primary colours. Different emitting patterns can be written and erased through a non-invasive and mask-free process, on a length scale of a few micrometres in a single device, thereby rendering this technology potentially promising for optically gated highly integrated full-colour displays and active optical memory.

The airway vagal preganglionic neurons (AVPNs) in the external formation of the nucleus ambiguus (eNA) can be separated into inspiratory-activated AVPNs (IA-AVPNs) and inspiratory-inhibited AVPNs (II-AVPNs). IA-AVPNs are activated by excitatory presynaptic inputs during inspiratory bursts, but the composition and the roles of these excitatory inputs still remain obscure. II-AVPNs are inhibited by inhibitory presynaptic inputs but whether these inhibitory inputs are regulated by excitatory inputs is also unclear. In the current study, AVPNs were retrogradely fluorescent labeled. The IA-AVPNs were discriminated from II-AVPNs by their different synaptic inputs during inspiratory bursts. The excitatory inputs to IA-AVPNs and the presynaptic regulation of II-AVPNs were examined by whole-cell patch clamping. Topical application of 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) to the recorded IA-AVPNs almost abolished the tonic EPSCs during inspiratory intervals, inhibited the phasic excitatory currents during inspiratory bursts and attenuated the phasic inspiratory inward currents (PIICs) driven by central inspiratory activity. Blockade of α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) respectively inhibited PIICs in some IA-AVPNs. Carbenoxolone, a gap junction uncoupler, partly inhibited the PIICs of IA-AVPNs. Focal application of CNQX to the II-AVPNs significantly inhibited the frequency, peak amplitude and area of the phasic inspiratory outward currents (PIOCs). These findings demonstrated that glutamatergic non-NMDA receptors played a predominant role in the excitatory drive to the IA-AVPNs, and that α4β2, α7 nAChRs and gap junctions were also rhythmically activated by central inspiratory activity. Additionally, glycinergic neurons making inhibitory inputs to the II-AVPNs were pre-synaptically facilitated by excitatory glutamatergic synaptic inputs., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Graphene-based materials have recently attracted much attention due to their extraordinary physical and chemical properties, which make them attractive candidates for many technological applications in sensing, optoelectronics, catalysis, and energy storage. Their chemical functionalization is key to tuning their properties. Herein, a novel two-step synthetic approach, which enables a high degree of covalent functionalization of graphene oxide (GO) is devised, thereby making the facile attachment of various robust functional molecules possible. Such a process relies initially on the grafting of an ethylenediamine linker followed by a second step consisting of the condensation reaction between aldehyde and amine groups to form imine bonds. As test beds, two kinds of graphene-based functional systems, namely, porphyrin-modified GO and ferrocene-modified GO, are prepared. Such hybrid systems are characterized by various spectroscopic and microscopic techniques. The degree of functionalization is quantified as the attachment of one porphyrin or ferrocene unit to every 34 or 77 carbon atoms of the GO scaffold, respectively, which is much higher than that of values obtained upon using various established chemical approaches to functionalize GO, such as condensation, cycloaddition, or coupling reactions. For the first time, the reduced form of ferrocene-modified GO was employed as an electrode material in supercapacitors, showing a specific capacitance of 127 F g -1 at a current density of 1 A g -1 , with capacitance retention of about 93 % after 5000 cycles at the same current density; this demonstrates great potential for application in high-performance energy-storage devices., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ochratoxin A (OTA) could cause a variety of toxicological effects especially nephrotoxicity in animals and humans. Autophagy is a highly conserved metabolic process that plays an important role in the maintenance of cellular homeostasis under stress. However, the role of autophagy in OTA-induced nephrotoxicity is unknown. In the present study, we demonstrated that OTA treatment at 2.0-8.0 μM could increase cytotoxicity of PK-15 cells by inducing apoptosis as shown by the increased Annexin V/PI staining, increased caspase-3 and PARP cleavage and increased apoptotic nuclei. Meantime, autophagy was triggered when OTA was administrated, as indicated by markedly increased expressions of LC3-II, ATG5 and Beclin-1, accumulation of GFP-LC3 dots and increased double- or single-membrane vesicles. OTA treatment decreased p-AKT and p-mTOR activities, and OTA-induced autophagy was inhibited when insulin was applied. Furthermore, OTA treatments with autophagy inhibitors (3-methyladenine or chloroquine) or knockdown of autophagy-related genes (ATG5 or Beclin-1) resulted in significantly reduced autophagy level and enhanced cytotoxicity. In conclusion, OTA induces cytoprotective autophagy against its cytotoxicity and inactivation of AKT/mTOR axis plays a critical role in autophagy induction., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Hemodialysis (HD) patients are exposed to dysregulated fluid balance which can lead to overhydration. Poor sleep quality and excessive daytime sleepiness are particularly common in these patients, however the relationship between fluid status and sleep quality and daytime sleepiness has not yet been studied. Therefore, the aim of this study is to evaluate the correlations between fluid status and sleep quality and daytime sleepiness in HD patients., Method: This cross-sectional study included 115 HD patients and 30 healthy control subjects from the HD center of Shanghai Ninth People's Hospital. Fluid compartments [total body water (TBW)], extracellular water (ECW)] and overhydration index (OH) were analyzed by multifrequency bio-impedance (BCM). Overhydration was defined as OH/ECW≥7%. HD patients were divided into an overhydration group and non overhydration group according to OH/ECW. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (PSQI), and excessive daytime sleepiness was evaluated by the Epworth Sleepiness Scale (ESS)., Results: The prevalence rate of fluid overload in HD patients was 65.2%. Poor sleep quality (PSQI≥5) and excessive daytime sleepiness (ESS≥11) were significantly higher in HD patients compared with the healthy controls [6 (3, 10) vs.2.11 ± 1.59, p = 0.000; 3 (0, 6) vs.1.68 ± 1.07, p = 0.045]. Furthermore, the PSQI scores were higher in HD patients with overhydration (7.8 ± 4.5 vs. 4.8 ± 3.2, p = 0.000). The component scores 1, 2, 3 and 5 of the PSQI showed significant differences between the overhydration and non overhydration groups. The ESS scores did not show differences between the two groups (3.9 ± 4.1 vs. 3.3 ± 3.5, p = 0.508). OH was correlated with Systolic BP and Diastolic BP, and additionally was an independent predictor of poor sleep quality., Conclusion: Fluid overload is significantly linked with poor quality of sleep in HD patients, however there is no association with excessive daytime sleepiness. Our study provides new insight into possible treatment strategies. Future studies should examine the effects of optimizing fluid status on quality of sleep., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The airway vagal preganglionic neurons (AVPNs) providing projections to intrinsic tracheobronchial ganglia are considered to be crucial to modulation of airway resistance in physiological and pathological states. AVPNs classified into inspiratory-activated AVPNs (IA-AVPNs) and inspiratory-inhibited AVPNs (II-AVPNs) are regulated by thyrotropin-releasing hormone (TRH)-containing terminals. TRH causes a direct excitatory current and attenuates the phasic inspiratory glycinergic inputs in II-AVPNs, however, whether and how TRH influences IA-AVPNs remains unknown. In current study, TRH regulation of IA-AVPNs and its mechanisms involved were investigated. Using retrogradely fluorescent labeling method and electrophysiology techniques to identify IA-AVPNs in brainstem slices with rhythmic inspiratory hypoglossal bursts recorded by a suction electrode, the modulation of TRH was observed with patch-clamp technique. The findings demonstrate that under voltage clamp configuration, TRH (100 nM) caused a slow excitatory inward current, augmented the excitatory synaptic inputs, progressively suppressed the inhibitory synaptic inputs and elicited a distinctive electrical oscillatory pattern (OP). Such a current and an OP was independent of presynaptic inputs. Carbenoxolone (100 μM), a widely used gap junction inhibitor, fully suppressed the OP with persistence of TRH-induced excitatory slow inward current and augment of the excitatory synaptic inputs. Both tetrodotoxin (1 μM) and riluzole (20 μM) functioned to block the majority of the slow excitatory inward current and prevent the OP, respectively. Under current clamp recording, TRH caused a slowly developing depolarization and continuously progressive oscillatory firing pattern sensitive to TTX. TRH increased the firing frequency in response to injection of a square-wave current. The results suggest that TRH excited IA-AVPNs via the following multiple mechanisms: (1) TRH enhances the excitatory and depresses the inhibitory inputs; (2) TRH induces an excitatory postsynaptic slow inward current; (3) TRH evokes a distinctive OP mediated by gap junction.

Ochratoxin A (OTA) is reported to induce nephrotoxicity in animals and humans. Porcine circovirus type 2 (PCV2) could induce porcine dermatitis and nephropathy syndrome. To date, little is known whether virus infection aggravates mycotoxin-induced toxicity. This work aimed to study the effects of PCV2 infection on OTA-induced nephrotoxicity and its mechanism in vivo and vitro. The results in vivo showed that PCV2 infection aggravated OTA-induced poor growth performance, nephrotoxicity, p38 phosphorylation and autophagy as demonstrated by Atg5, LC3 II and p62 protein expressions in kidney of pigs. The results in vitro indicated that PCV2 infection significantly aggravated OTA-induced nephrotoxicity as demonstrated by cell viabilities, annexin V/PI binding and caspase 3 activities, and induced p38 phosphorylation and autophagy in PK15 cells. p38 inhibitor decreased Atg5 and LC3 protein expression induced by PCV2 infection and OTA combined treatment. Adding autophagy inhibitor 3-MA or CQ alleviated the aggravating effects of PCV2 infection on OTA-induced nephrotoxicity. Atg5-specific siRNA eliminated the aggravating effects of PCV2 infection on OTA-induced nephrotoxicity. Taken together, these data indicate that in vivo and in vitro PCV2 infection aggravated OTA-induced nephrotoxicity via p38-mediated autophagy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Our previous studies showed that aflatoxin B1 (AFB1) and ochratoxin A (OTA) could trigger joint immune toxicity. Little is known about the combined effects of selenomethionine (SeMet) and N-acetylcysteine (NAC) on the joint toxicities of the two toxins. In this study, results showed that SeMet or NAC alone or in combination significantly alleviated the downswing of cell viability, glutathione production, and phagorytosis induced by AFB1 and OTA in porcine alveolar macrophages. The uptrend of lactate dehydrogenase activities, apoptosis, reactive oxygen species levels, and the relative mRNA of inflammatory cytokines triggered by the two toxins was decreased. Combination of them was more effective than single application. Knockdown of p38, c-JUN N-terminal kinase (JNK), or extracellular signal-regulated kinase (ERK) via use of the corresponding specific siRNA could alleviate the joint toxicities of AFB1 and OTA. However, the ERK but not p38 or JNK pathway was involved in the protection of SeMet and NAC against the immunotoxicity. In conclusion, combination of SeMet and NAC might be a new therapeutic orientation for preventing the joint toxicities induced by AFB1 and OTA.

Background: The chromosome-specific probe is a fundamental tool of chromosome painting and has been commonly applied in mammalian species. The technology, however, has not been widely applied in plants due to a lack of methodologies for probe development. Identification and labeling of a large number of oligonucleotides (oligos) specific to a single chromosome offers us an opportunity to establish chromosome-specific probes in plants. However, never before has whole chromosome painting been performed in rice., Results: We developed a pooled chromosome 9-specific probe in rice, which contains 25,000 oligos based on the genome sequence of a japonica rice (Oryza sativa L., AA, 2n = 2× = 24). Chromosome 9 was easily identified in both japonica and indica rice using this chromosome 9-painting probe. The probe was also successfully used to identify and characterize chromosome 9 in additional lines of O. sativa, a translocation line, two new aneuploids associated with chromosome 9 and a wild rice (Oryza eichingeri A. Peter, CC, 2n = 2× = 24)., Conclusion: The study reveals that a pool of oligos specific to a chromosome is a useful tool for chromosome painting in rice.

The co-contamination of cereals, grains, crops, and animal feeds by mycotoxins is a universal problem. Humans and animals are exposed to several mycotoxins simultaneously as evidenced by extensive studies on this topic. Yet, most studies have addressed the effects of mycotoxins individually. Aflatoxin B1 and ochratoxin A can induce immunotoxicity. However, it remains unclear whether a combination of these mycotoxins aggravates immunotoxicity and the potential mechanism underlying this effect. In this study, we used the cell line 3D4/21, swine alveolus macrophages and innate immune cell. The results showed that the percentage of cell inhibition, annexin V/PI-positive rates, and the expression of pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) significantly increased and the release of lactate dehydrogenase and phagocytotic index were significantly decreased at different concentrations of aflatoxin B1 and ochratoxin A combination when compared with control. The combination of aflatoxin B1 and ochratoxin A significantly decreased the production of GSH and increased reactive oxygen species level. However, N-acetylcysteine suppressed the oxidative stress and alleviated the immunotoxicity induced by the combination. The combination of aflatoxin B1 and ochratoxin A markedly enhanced the degradation of IκBa, the phosphorylation of nuclear factor kappa B (p65), and the translocation of activated nuclear factor kappa B (NF-κB) into the nuclei as demonstrated by western blotting and confocal laser scanning microscopy. These effects could be reversed by BAY 11-7082, a specific inhibitor of NF-κB. Taken together, a combination of aflatoxin B1 and ochratoxin A could aggravate immunotoxicity by activating the NF-κB signaling pathway., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.

Ochratoxin A (OTA) as a fungal metabolite is reported to induce cytotoxicity and apoptosis through the mechanism of oxidative stress. Oxidative stress could induce the epigenetic enzymes modifications. However, whether epigenetic enzymes modifications are involved in OTA-induced cytotoxicity and apoptosis has not been reported until now. Therefore, the objectives of this study were to verify OTA-induced cytotoxicity and apoptosis and to investigate the potential role of epigenetic enzymes in OTA-induced cytotoxicity and apoptosis in PK15 cells. The results demonstrated that OTA at 4 μg/ml treatment for 12 h and 24 h induced cytotoxicity and apoptosis as demonstrated by decreasing cell viability, increasing LDH release, Annexin V/PI staining, Bcl-2/Bax mRNA ratio and apoptotic nuclei in PK15 cells. OTA treatment up-regulated ROS production and down-regulated GSH levels. In addition, OTA treatment activated the epigenetics related enzymes DNA methyltransferase 1 (DNMT1) and Histone deacetylase 1 (HDAC1). Adding DNMT1 inhibitor (5-Aza-2dc) or HDAC1 inhibitor (LBH589) depressed the up-regulation of DNMT1 or HDAC1 expression, the decreases of GSH levels and increases of ROS production induced by OTA, respectively. Furthermore, inhibition of DNMT1 or HDAC1 by their inhibitor reversed the decreases of cell viability and increases of LDH activity and apoptosis induced by OTA, respectively. In conclusion, the observed effects indicate that the critical modulation of DNMT1 and HDAC1 is related to OTA-induced cytotoxicity and apoptosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Vesicular stomatitis virus (VSV) and rabies and Chandipura viruses belong to the Rhabdovirus family. VSV is a common laboratory virus to study viral evolution and host immune responses to viral infection, and recombinant VSV-based vectors have been widely used for viral oncolysis, vaccination, and gene therapy. Although the tropism of VSV is broad, and its envelope glycoprotein G is often used for pseudotyping other viruses, the host cellular components involved in VSV infection remain unclear. Here, we demonstrate that the host protein leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is essential for VSV and VSV-G pseudotyped lentivirus (VSVG-LV) to infect susceptible cells. Accordingly, Lgr4-deficient mice had dramatically decreased VSV levels in the olfactory bulb. Furthermore, Lgr4 knockdown in RAW 264.7 cells also significantly suppressed VSV infection, and Lgr4 overexpression in RAW 264.7 cells enhanced VSV infection. Interestingly, only VSV infection relied on Lgr4, whereas infections with Newcastle disease virus, influenza A virus (A/WSN/33), and herpes simplex virus were unaffected by Lgr4 status. Of note, assays of virus entry, cell ELISA, immunoprecipitation, and surface plasmon resonance indicated that VSV bound susceptible cells via the Lgr4 extracellular domain. Pretreating cells with an Lgr4 antibody, soluble LGR4 extracellular domain, or R-spondin 1 blocked VSV infection by competitively inhibiting VSV binding to Lgr4. Taken together, the identification of Lgr4 as a VSV-specific host factor provides important insights into understanding VSV entry and its pathogenesis and lays the foundation for VSV-based gene therapy and viral oncolytic therapeutics., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin and immunotoxin in animals and humans. This research was conducted to evaluate whether endoplasmic reticulum (ER) stress, MAPK signaling pathway and autophagy were induced by OTA in kidney and spleen of pigs. Twenty-seven crossbred pigs randomly allocated to 3 groups were fed for 42 days ad libitum a basal diet without (Con group, 0.00 μg OTA/kg) and with supplementation of OTA at 400 (OTA-L group) and 800 μg/kg (OTA-H group). From each group, 6 pigs were randomly selected for blood collection on days 0, 21, and 42 and 3 pigs were randomly selected for tissue collection on day 42. The results showed that OTA at 400 and 800 μg/kg diets significantly increased OTA concentrations in serum and kidney and spleen induced the histopathological lesions of kidney and spleen, decreased TCR-stimulated T lymphocyte viabilities and IL-2 concentration, increased TNF-α concentration, and decreased T-AOC levels. OTA increased glucose regulated protein 78, p38, and ERK1/2 phosphorylation, and LC3 II and Atg5 protein expression in kidney and spleen of pigs. These results provide new insights into the relationship between OTA and ER stress, p38 and ERK1/2 MAPK signaling pathway and autophagy in pigs., (© 2017 Wiley Periodicals, Inc.)

Ochratoxin A (OTA) is reported to be a potent nephrotoxin and immunotoxin in animals and humans. However, the mechanisms underlying OTA toxicity have not been clearly determined until now. Toxicity of OTA and its mechanism was investigated in PK15 cells and in porcine primary splenocytes. The results showed that OTA at 2.0-8.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in PK 15 cells. OTA at 0.5-4.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in porcine primary splenocytes. In addition, OTA induced p38 and ERK1/2 phosphorylation both in PK15 cells and porcine primary splenocytes. Knock-down of p38 instead of ERK by their specific siRNA significantly eliminated the nephrotoxicity induced by OTA. Contrary, knock-down of ERK1/2 instead of p38 by their specific siRNA significantly eliminated the immunotoxicity induced by OTA. The observed effects indicate that OTA induced nephrotoxicity by p38 signaling pathway in PK15 cells and immunotoxicity by ERK signaling pathway in porcine primary splenocytes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To analyze the changes and characteristics of respiratory tract bacteria in Hebei 3A Hospital, and to provide new rationale for clinical diagnosis and treatment., Methods: A single-center retrospective analysis was conducted. 7 497 patients with respiratory tract infection admitted to Hebei Chest Hospital from January 2013 to December 2016 were enrolled. Deep sputum was collected, and the bacterial cultures and susceptibility analysis was conducted in sputum and upper respiratory secretions were collected by fiberoptic bronchoscopy., Results: A total of 7 497 patients with respiratory tract infection were enrolled in the study, and 11 909 strains of 13 kinds of dominant pathogens were isolated. The dominant pathogens for respiratory tract infection were Monilia albican (23.7%), Klebsiella pneumoniae (12.9%), Pseudomonas aeruginosa (11.6%), Escherichia coli (9.5%), Candida glabrata (9.1%), Acinetobacter baumanii (7.9%), Aspergillus (6.7%), Stenotrophomonas maltophilia (4.5%), coagulase negative Staphylococcus (3.7%) and some species of Pseudomonas (3.7%), Staphylococcus aureus (3.0%), Aerobacter cloacae (1.9%), and Candida tropicalis (1.8%). A total of 6 198 strains of 7 kinds of Gram negative (G - ) bacilli infection dominant pathogens accounts for 52.0% of all infections, Klebsiella pneumonia (24.8%), Pseudomonas aeruginosa (22.3%), Escherichia coli (18.2%) and Acinetobacter baumanii (15.3%) were the main pathogens, and increased year by year. Susceptibility analysis showed that the preferred antibiotics for G - bacteria were carbapenems, followed by risperidone, sulbactam, cefepime, amikacin, and the third generation of cephalosporins. A total of 798 strains of 2 kinds of Gram positive (G + ) bacilli infection dominant pathogens accounted for 6.7% of all infections, were coagulase negative Staphylococcus (54.8%) and Staphylococcus aureus (45.2%), each had changed little by year. Susceptibility analysis showed that G + bacteria were sensitive to glycopeptides, followed by cefoxitin, cotrimoxazole, the tetracyclines, quinolones, azithromycin, erythromycin and so on. The advantages of 4 species of fungi were 4 913 strains, accounted for all of the 41.3% strains, with 57.5% of Candida albicans, and the trend was increasing year by year. Susceptibility analysis results showed that the antifungal susceptibility of dominant fungi were higher., Conclusions: G - bacilli is still the main source of infection, and showed an upward trend year by year. Fungal infection rate cannot be ignored, and we must pay attention to fungal infection incentives. We should strengthen the rational use of antibiotics.

Taxol has been extensively used as an antineoplastic drug to treat human gastric cancer. However, the acquired drug resistance invariably develops and greatly limits the therapeutic efficacy of Taxol. Identification of the underlying resistance mechanisms may inform the development of new therapies of gastric cancers to Taxol treatment. Here we report that upregulation of Mcl-1 (Myeloid cell leukemia-1) confers acquired resistance to Taxol in human gastric cancer. Mcl-1 is shown to be stabilized in Taxol -resistant gastric cancer cells because of the hyper-activation of the PI3K/Akt signaling pathway. The increased Mcl-1 prevents of the permeabilization of the outer mitochondrial membrane, thereby blocking the Taxol-induced apoptosis. Furthermore, inhibition of Mcl-1 or PI3K/Akt pathway significantly reversed the resistant phenotype of Taxol-resistant human gastric cancer cells. Taken together, our findings broaden the view of PI3K/Akt pathway as an important regulator in Taxol acquired resistance, and implicate Mcl-1 as a specific therapeutic target for the treatment of Taxol-resistant human gastric cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Background: To explore the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) approach on cancer-related fatigue (CRF) in non-small cell lung cancer (NSCLC) chemotherapy patients., Methods: A total of 162 participants who treated with gemcitabine combined with platinum-based drugs (GP chemotherapy) were randomly assigned to three groups: Control (Group A, n=56), Sham TEAS (Group B, n=49), and TEAS (Group C, n=57). The following acupoints were used in this study: Qihai (CV6), Keshu (UB17), and Zusanli (ST36). The Revised Piper Fatigue Scale (RPFS) were used to measure CRF on the day before chemotherapy (P1), days 8 (P2) and 28 (P3) separately. The Differences among three groups were analyzed., Results: At the 28th day, the outcomes of the fatigue scores for Group C, Group B and Group A were 2.06±0.90, 2.80±1.34, 3.00±1.29 respectively. There were significantly different among three groups (F=9.784, P<0.01). At the 28th day, the outcomes of the affective fatigue (F=8.161, P<0.01), sensory fatigue (F=3.06, P=0.05) and cognitive fatigue (F=8.06, P<0.01) for Group C, Group B and Group A were significantly different among three groups., Conclusions: Chemotherapy may increase the fatigue from P1 to P2 and P3 in NSCLC patients. And TEAS could help to relived CRF, especially at P3., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium. Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. Recently, we reported that low doses of OTA promoted PCV2 replication in vitro and in vivo, but the underlying mechanism needed further investigation. The present studies further confirmed OTA-induced PCV2 replication promotion as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. Our studies also showed that OTA induced autophagy in PK-15 cells, as assessed by the markedly increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II, autophagy-related protein 5 (ATG5), and Beclin-1 and the accumulation of green fluorescent protein (GFP)-LC3 dots. OTA induced complete autophagic flux, which was detected by monitoring p62 degradation and LC3-II turnover using immunoblotting. Inhibition of autophagy by 3-methylademine (3-MA) and chloroquine (CQ) significantly attenuated OTA-induced PCV2 replication promotion. The observed phenomenon was further confirmed by the knock-down of ATG5 or Beclin-1 by specific siRNA. Further studies showed that N-acetyl-L-cysteine (NAC), an ROS scavenger could block autophagy induced by OTA, indicating that ROS may be involved in the regulation of OTA-induced autophagy. Furthermore, we observed significant increases in OTA concentrations in lung, spleen, kidney, liver and inguinal lymph nodes (ILN) and bronchial lymph nodes (BLN) of pigs fed 75 and 150 μg/kg OTA compared with controls in vivo. Administration of 75 μg/kg OTA significantly increased PCV2 replication and autophagy in the lung, spleen, kidney and BLN of pigs. Taken together, it could be concluded that OTA-induced autophagy in vitro and in vivo promotes PCV2 replication.

Background: To investigate the effect of percutaneous electrical stimulation on chemotherapy-induced bone marrow suppression in patients with lung cancer., Methods: From December 2014 to August 2015, one hundred ninety-one non-small cell lung cancer patients with chemotherapy naive were randomly divided into control group, medication group, and transcutaneous electrical acupoint stimulation (TEAS) group. Patients with the control group received routine nursing care, the medication group was treated by oral administration of prophylactic agents, and TEAS group received electrical stimulation of acupoints including Dazhui (DU14), Geshu (BL17), Zusanli (ST36), Sanyinjiao (SP6), and Hegu (LI4). The primary end point was the blood routine indexes and secondary end point was the degree of comfort., Results: The white blood cell in the TEAS group was significantly higher than the control group on day 8 and day 14 (P<0.05). The platelet count in the TEAS group was significantly higher than control group on day 5, day 8 and day 11 (P<0.05). The comfort score in the TEAS group was significantly higher than control group on day 8 (P<0.05)., Conclusions: Percutaneous electrical stimulation of acupoints could prevent chemotherapy-induced bone marrow suppression in lung cancer patients and ensure a smooth continuation of chemotherapy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Immune checkpoint inhibitors that block the PD-1/PD-L1 signaling pathway have been used to treat a wide variety of cancers. Although results have been promising, significant inter-individual and inter-tumor variability has been observed. It is believed that better clinical outcome could be achieved if the treatment was individually designed based on the functional status of the PD-1/PD-L1 signaling and the cellular immunity. In this study, we analyzed the mRNA expression of PD-1 and other immunomodulatory genes in peripheral blood from cancer patients, and immunomodulatory gene expression during radiotherapy and immunomodulation therapy with cytokines. Our results show that the PD-1 mRNA expression is significantly increased in peripheral blood in cancer patients. Anti-cancer treatments can significantly modulate the PD-1 expression, but this is largely dependent on the initial immune status. Moreover, the PD-1 expression on peripheral lymphocytes can be immunoactivation-derived. These results suggest that the regulation and expression pattern of PD-1/PD-L1 signal is complicated which will influence the effect of blockade of the PD-1/PD-L1 signaling pathway for cancer treatment. Through combined analysis of PD-1, CTLA-4, and other immune markers in peripheral blood, we may accurately evaluate the functional status of PD-1/PD-L1 signaling and cellular immunity, thereby providing clues for guiding anti-PD-1 or anti-PD-L1 treatment., Competing Interests: CONFLICTS OF INTEREST All authors have no potential conflicts of interest.

Aims: Present study was performed to examine whether ADH was implicated in psychological stress asthma and to explore the underlying molecular mechanism., Methods: We not only examined ADH levels in the cerebrospinal fluid (CSF) via radioimmunoassay, but also measured ADH receptor (ADHR) expression in airway-related vagal preganglionic neurons (AVPNs) through real-time PCR in all experimental mice. Western blotting was performed to evaluate the relationship between ADH and PKA/PKC in psychological stress asthma. Finally, the role of PKA/PKC in psychological stress asthma was analyzed., Results: Marked asthma exacerbations were noted owing to significantly elevated levels of ADH and ADHR after psychological stress induction as compared to OVA alone (asthma group). ADHR antagonists (SR-49095 or SR-121463A) dramatically lowered higher protein levels of PKAα and PKCα induced by psychological stress as compared to OVA alone, suggesting the correlation between ADH and PKA/PKC in psychological stress asthma. KT-5720 (PKA inhibitor) and Go-7874 (PKC inhibitor) further directly revealed the involvement of PKA/PKC in psychological stress asthma. Some notable changes were also noted after employing PKA and PKC inhibitors in psychological stress asthma, including reduced asthmatic inflammation (lower eosinophil peroxidase (EPO) activity, myeloperoxidase (MPO) activity, immunoglobulin E (IgE) level, and histamine release), substantial decrements in inflammatory cell counts (eosinophils and lymphocytes), and decreased cytokine secretion (IL-6, IL-10, and IFN-γ), indicating the involvement of PKA/PKC in asthma exacerbations induced by psychological stress., Conclusion: Our results strongly suggested that ADH participated in psychological stress-induced asthma exacerbations via PKA/PKC signal pathway in AVPNs., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

Background: In conventional Chinese culture, awareness of a malignant disease is believed to increase a patient's psychological pressure, leading to anxiety or depression. But this notion is in conflict with the patient's right to receive information about their own disease., Methods: This study is to investigate whether disclosure of diagnosis increases the level of anxiety or depression in patients diagnosed with lung cancer. Seventy patients who underwent lung resection and diagnosed with lung cancer postoperatively were divided into two groups-the disclosed group (n=35) and the undisclosed group (n=35), depending on the awareness of their diagnosis, as decided by their consigned family members. All patients were asked to fill in a form to evaluate their level of anxiety and depression before discharge., Results: Disclosure of diagnosis did not affect the degree of anxiety or depression in patients with lung cancer (P>0.05). Age ≤50, relatively more advanced stage (stage II as compared with stage I) of disease, extensive surgery and major postoperative complication were risk factors of anxiety (P<0.05). Major postoperative complication was the only risk factor of depression (P<0.05)., Conclusions: Disclosure of diagnosis to patients with lung cancer does not induce or aggravate anxiety or depression in modern Chinese population. Factors such as complications, age, stage of disease and extent of surgery do have psychological impacts on patient with lung cancer., Competing Interests: The authors have no conflicts of interest to declare.

C23 is an abundant and multi-functional protein, which plays an important role in various biological processes, including ribosome biogenesis and maturation, cell cycle checkpoints and transcriptional regulation [1, 2]. However, the role of C23 in controlling tumorigenesis has not been well defined. Here we report that C23 is highly expressed in cancer cells and the elevated expression of C23 facilitates cancer cell proliferation in vitro and tumor xenograft growth in vivo. Notably, C23 binds to p53 through its GAR domain and suppresses the transcriptional activity of p53 under DNA damage and hypoxia. Moreover, the GAR domain is critical for C23-mediated tumor cell proliferation both in vitro and in vivo. Our findings reveal a novel role of C23 in tumorigenesis and suggest that C23 may represent a potential therapeutic target for treating malignancy., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate the effects of electric acupoint stimulation on gastrointestinal hormones and motility among geriatric postoperative patients with gastrointestinal tumors, and to explore an efficient and noninvasive method for postoperative recovery of bowel functions., Methods: Forty patients were randomly and evenly assigned into a regular nursing care group (RNC) and an acupoint electric stimulation group (AES). Patients in the RNC group received regular nursing care and patients in the AES group received regular nursing care plus electric stimulation of acupoints. The serum levels of gastrin (GAS), motilin (MOT), and cholecystokinin (CCK), and an electrogastrogram (EGG) of all the patients were evaluated on the first, third, and fifth day after surgery. The time to first flatus after surgery and the number of patients with side effects such as abdominal pain, abdominal distention, and diarrhea were recorded., Results: There were significant differences between the two groups in GAS, MOT, EGG, time to first flatus, abdominal pain, abdominal distention, and diarrhea (P < 0.05)., Conclusion: Electric stimulation on acupoints could increase levels of GAS and MOT, promote the recovery of gastrointestinal functions, and decrease complications among postoperative senile patients with gastrointestinal tumors.

Objective: In this study, a modified LC-MS/MS method was used to determine plasma ambroxol concentration and thereby examine the bioequivalence of two ambroxol medications among healthy Chinese male volunteers., Methods: The study used a single-dose, randomized, open-label design principle and calculated pharmacokinetic parameters for the comparison of the two formulations., Results: Administration of a single oral dose of either the test drug or reference drug was found to be safe in healthy subjects. No severe, serious, or life-threatening clinical or drug-related side effects were reported during the study. The majority of clinical laboratory test results were within the normal range or not clinically significant. The pharmacokinetic parameters for ambroxol oral tablets and ambroxol orally disintegrating tablets were comparable. For the comparison of the two formulations, the 90% confidence intervals for the log-transformed pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-inf) fell within the bioequivalence< acceptance criteria (80-125%)., Conclusions: The ambroxol oral tablets were bioequivalent to ambroxol orally-disintegrating tablets in healthy human adult male volunteers, under fasting conditions.

Multifunctional carbon-based nanomaterials offer routes towards the realization of smart and high-performing (opto)electronic (nano)devices, sensors and logic gates. Meanwhile photochromic molecules exhibit reversible transformation between two forms, induced by the absorption of electromagnetic radiation. By combining carbon-based nanomaterials with photochromic molecules, one can achieve reversible changes in geometrical structure, electronic properties and nanoscale mechanics triggering by light. This thus enables a reversible modulation of numerous physical and chemical properties of the carbon-based nanomaterials towards the fabrication of cognitive devices. This review examines the state of the art with respect to these responsive materials, and seeks to identify future directions for investigation.

The novel concept of amphiphilic molecular motors that self-assemble into responsive supramolecular nanotubes in water is presented. The dynamic function of the molecular motor units inside the supramolecular assemblies was studied using UV-vis absorption spectroscopy and cryo-transmission electron microscopy (cryo-TEM) microscopy. Reorganization between distinct, well-defined nanotubes and vesicles can be reversibly induced by light, going through the rotation cycle of the motor, i.e. driven by alternate photochemical and thermal isomerization steps in the system. This is the first example in which a molecular rotary motor shows self-assembly in an aqueous medium with full retention of its functionality, paving the way to increasingly complex, highly dynamic artificial nanosystems in water.

Crop improvement is a never ending process. With a transgenesis approach, it is not inconceivable to envision a continuous addition of new transgenes to existing cultivars. Previously, we described a recombinase-directed gene stacking method in tobacco (Hou et al., Mol Plant 7:1756-1765, 2014). Being able to stack DNA to a previous location ensures that the number of genetic loci does not increase with each new round of transgene addition. Whereas the previous demonstration was conducted through polyethylene glycol to mediate uptake of DNA into tobacco protoplasts, we now describe protocols for using biolistic transformation to stack DNA in tobacco and rice.

The leptotene-zygotene transition is a major step in meiotic progression during which pairing between homologous chromosomes is initiated and double strand breaks occur. OsAM1, a homologue of maize AM1 and Arabidopsis SWI1, encodes a protein with a coiled-coil domain in its central region that is required for the leptotene-zygotene transition during rice meiosis. To gain more insight into the role of OsAM1 in rice meiosis and identify additional meiosis-specific genes, we characterized the transcriptomes of young panicles of Osam1 mutant and wild-type rice plants using RNA-Seq combined with bioinformatic and statistical analyses. As a result, a total of 25,750 and 28,455 genes were expressed in young panicles of wild-type and Osam1 mutant plants, respectively, and 4,400 differentially expressed genes (DEGs; log2 Ratio ≥ 1, FDR ≤ 0.05) were identified. Of these DEGs, four known rice meiosis-specific genes were detected, and 22 new putative meiosis-related genes were found by mapping these DEGs to reference biological pathways in the KEGG database. We identified eight additional well-conserved OsAM1-responsive rice meiotic genes by comparing our RNA-Seq data with known meiotic genes in Arabidopsis and fission yeast.