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Objective: To evaluate the reliability of flow cytometry (FCM) for diagnosing lymphoma associated hemophagocytic syndrome (LAHS). Method: The clinical data in 57 patients with hemophagocytic lymphohistiocytosis (HLH)were retrospective analyzed at Peking University Shenzhen Hospital from July 2010 to July 2019. All patients were performed bone marrow FCM and bone marrow pathological examination before final diagnoses were made. The golden diagnosis criterion was based on clinical, biochemical and histopathological evidence, which was regarded as the standard to evaluate the sensitivity and specificity of FCM analysis in diagnosing LAHS. Results: Among 57 cases, 36 cases were eventually diagnosed with LAHS, including 15 B-cell lymphoma(14 diffuse large B-cell lymphoma, 1 B-cell lymphoma with reactive T-cell hyperplasia), 13 aggressive NK/T cell lymphoma/leukemia, 2 cases of gamma-delta T-cell lymphoma, 4 angioimmunoblastic T-cell lymphoma, 1 enteropathy-associated peripheral T-cell lymphoma and 1 anaplastic T-cell lymphoma. Lymphoma cells in bone marrow were detected in all patients by FCM except one ENTCL patient. The sensitivity and the specificity of FCM in LASH compared to bone marrow biopsy were 97.2%( P =0.014)and 90.5%( P =0.488) respectively. In the other 21 non-LAHS patients, T cell receptor Vβ (TCRVβ) rearrangement was detected in 2 patients with Epstein-Barr virus (EBV) associated primary HLH. Conclusions: FCM effectively detects lymphoma cells in bone marrow of lymphoma patients with LHL, suggesting that FCM could be an important indicator for the diagnosis of LAHS. FCM also has the advantage in differentiating LAHS from other HLH.

Objective: To investigate the effects and mechanisms of miR-146a on the proliferation, invasion, migration, apoptosis and cell cycle of esophageal squamous cell carcinoma cells. Methods: The expressions of miR-146a in 3 esophageal squamous carcinoma cell lines (Eca109, KYSE140, KYSE150) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MiR-146a mimics was transfected into Eca109 to up-regulate the expression of miR-146a. Effects of miR-146a on cell proliferation, invasion and migration were evaluated by cell counting kit 8 (CCK-8), Transwell assay and wound-healing assay, respectively. The cell apoptosis and cycle were assessed by flow cytometry (FCM). Finally, relevant bioinformatics techniques were used to predict the target gene of miR-146a. Dual luciferase reporter assay was used to identify the interaction of 3' terminal untranslated region (3' UTR) of miR-146a and its target gene, interleukin-1 receptor-associated kinase (IRAK1). RT-qPCR and western blot were used to detect the mRNA and protein expressions of IRAK1, respectively. Results: The relative expressions of miR-146a in 3 esophageal squamous cell carcinoma cells (Eca109, KYSE140, KYSE150) were 0.36±0.05, 0.16±0.06 and 0.09±0.02, respectively, all of which were significantly lower than 1±0.05 of normal esophageal epithelial cells (HEEC) ( P <0.01). The model of esophageal squamous cell carcinoma cells was constructed by transfecting miR-146a mimics into Eca109 cells. The results showed that the ability of absorbance value, the number of transmembrane cells (52±18), the reduced scratch distances at 48 hours and 72 hours after transfection [(25.29±0.77) μm, (30.66±0.91) μm] were significantly lower than those of the negative control group and blank control group (all P <0.01). The early apoptosis rate was (6.13±0.91)%, higher than (2.50±0.68)% of the negative control group ( P <0.01) and (1.70±0.20)% of blank control group ( P <0.01). The percentage of cells in G(1) phase [(44.74±6.76)%] was decreased while the G(2)/M phase [(41.88±2.88)%] was increased when compared with the negative control group and the blank control group ( P <0.05 and P <0.01, respectively). The results of dual luciferase reporter gene assay showed that luciferase activity in the group co-transfected with IRAK1-wild-type and miR-146a mimics was significantly lower than that in the control groups ( P <0.01). The results of RT-qPCR and western blot showed that the mRNA and protein expressions of IRAK1 in the co-transfected group were 1.02±0.28 and 1.00±0.05, respectively, both lower than those in the negative control group and the blank control group ( P <0.01). Conclusions: The expressions of miR-146a are decreased in the esophageal squamous cell lines, which plays a role as tumor suppressor gene. MiR-146a can inhibit the proliferation, invasion and migration of esophageal squamous cell cells, promote apoptosis, and block the cell cycle at G(2)/M stage. MiR-146a may mediate the malignant biological behavior of esophageal cancer cells through the regulation of IRAK1.

1. This study investigated the pattern of feather follicle morphogenesis and the expression of the Wnt/β-catenin signalling pathway in the skin of yellow-feathered broiler chick embryos during feather development, using haematoxylin and eosin (H&E) staining and Western blot assays, respectively. 2. The results showed that the skin displayed protrusions during embryonic days E7-E9, feather buds elongated during E10-E11 with anterior-posterior and proximal-distal asymmetries, and the epidermis invaginated to form the primary feather follicles (Pfs) at E12. At E13, the formation of the feather follicle and the epidermis at the base of the feather bud further invaginated into the dermis. By E15, Pf formation was essentially complete, and secondary feather follicles (Sfs) appeared. It was speculated that Pfs and Sfs developed independently and that Pfs occurred earlier than Sfs. 3. Quantitative measurements of Pf density reached a maximum at E15 and then decreased gradually. Sf density started to increase from E15. 4. Protein expression levels of β-catenin, TCF4, cyclin D1, and c-Myc were significantly increased during E8-E12 (P < 0.05) and then decreased from E13 to the day of hatching (DOH) (P < 0.05). The result of the β-catenin immunolocalisation signal intensity assay was consistent with the result of the Western blot assay. 5. Collectively, the results indicated that the Wnt/β-catenin signalling pathway is essential for promoting the development of feather follicles, especially during E7-E15.

This study was conducted to explore the regulatory role of methionine (Met) in feather follicle and feather development during the embryonic period of chicks. A total of 280 fertile eggs (40 eggs/group) were injected with 0, 5, 10, 20 mg of L-Met or DL-Met/per egg on embryonic day 9 (E9), and whole-body feather and skin tissues were collected on E15 and the day of hatching (DOH). The whole-body feather weight was determined to describe the feather growth, and the skin samples were subjected to hematoxylin and eosin staining and Western blotting for the evaluation of feather follicle development and the expressions of Wingless/Int (Wnt)/β-catenin signaling pathway proteins, respectively. The results showed that L- or DL-Met did not affect the embryo weight (P > 0.05), but increased the absolute and relative whole-body feather weights. Specifically, 5 and 10 mg of L-Met and 5, 10, and 20 mg of DL-Met significantly increased the absolute feather weight at E15 (P < 0.05), and 10 mg of L-Met and 5 and 10 mg of DL-Met significantly increased the absolute and relative feather weight on the DOH (P < 0.05). Moreover, a main effect analysis suggested that changes in the embryo and feather weights were related to the Met levels (P < 0.05) but not the Met source (P > 0.05). The levels of L- and DL-Met were quadratically correlated with the absolute and relative feather weights of chicks on the DOH (P < 0.05). Correspondingly, all doses of L- and DL-Met significantly increased the diameter and density of feather follicles on the DOH (P < 0.05), as well as the activity of Wnt/β-catenin on E15 and the DOH (P < 0.05). In conclusion, injection of either L- or DL-Met can improve feather follicle development by activating Wnt/β-catenin signaling, and thereby promoting feather growth; furthermore, no difference in feather growth was found between L- and DL-Met treatments. Our findings might provide a nutritional intervention for regulating feather growth in poultry production., (Copyright © 2020. Published by Elsevier Inc.)

Didymocarpus lobulatus , a new species endemic to Zhejiang province, eastern China, is described and illustrated with photographs. The new species is morphologically similar to D. heucherifolius , D. cortusifolius and D. salviiflorus in leaf morphology, but can be easily distinguished by a combination of characters, including the shape of bracts, calyx and calyx lobes., (Wen-Yuan Xie, Jia-Jun Zhou, Xin Hong, Fang Wen.)

Objectives: Self-regulated learning has been proposed as a resource saving alternative for learning knot tying. However, this may be hindered by the Dunning-Kruger effect. A potential alternative is guided video reflection. The objectives of this study are to compare the performance and self-assessment abilities amongst medical students learning knot tying using either a traditional self-regulated approach versus guided video reflection., Design: This randomized, single-blinded, controlled trial used a pre-post-retention test design. All knot tying performances were video recorded and assessed nonsequentially by blinded evaluators using a modified Objective Structured Assessment of Technical Skills tool., Participants: This study recruited 31 first- and second-year medical students and 6 senior urology residents from Western University in Canada., Results: At baseline, the performances of the experts were significantly higher than the experimental groups (F 3,85  = 9.080, p < 0.001). After the intervention, there was a significant increase in the performance for both experimental groups compared to the pretest period (p < 0.001). The scores between the experimental groups were not significantly different (p = 0.338). The improved performances of both groups were sustained on retention testing (p < 0.001). The self-assessment abilities were accurate for both experimental groups at baseline. However, at the post-test period the accuracy was poor (interclass correlation 0.361) for the self-regulated group, while remaining moderately (interclass correlation 0.685) accurate for the reflection group., Conclusions: Students using guided video reflection were able to achieve competency and maintained their knot tying skills to the same degree as those who used the self-regulated approach. These results may be due to the positive effects of reflection on self-assessment abilities and subsequent improvement in goal setting for further practice., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective Hilar cholangiocarcinoma (HC) is invariably fatal without surgical resection. The primary aim of the current study was to determine the safety of variable surgical resections for patient with HC and their survival after surgical resection. In addition, prognostic factor for the overall survival was also evaluated. Methods The study included 59 consecutive patients who were newly diagnosed with HC and underwent surgical resections with curative intend between February 2009 and February 2017. Patients were followed up at 3-6 months intervals after hospital discharge. Postoperative complications and overall survival were determined. Associations of clinicopathologic and surgeon-related factors with overall survival were evaluated through univariate analysis and Cox regression analysis. Results Of patients with Bismuth and Corlette (B & C) type Ⅲ ( n =19) and Ⅳ ( n =25) HC lesions, 33 (55.9%) were treated with hilar resection combined with major liver resection (MLR), while the other 11 patients with type Ⅲ and Ⅳ, and those with type Ⅰ ( n =8) and Ⅱ ( n =7) HC lesions were treated with hilar resection. The overall surgical mortality was 5.1% and surgical morbidity was 35.6%. There was no statistical difference in the mortality between MLR group and hilar resection group (6.1% vs. 3.8%; X 2 =0.703, P =0.145). The median follow-up period was 18 months (range, 1-94 months). The 1-, 3-, 5-year survival rate was 59.3%, 36.5%, and 17.7%, respectively. The overall survival after resections was 18 months. In HC patients with B & C type Ⅲ and Ⅳ lesions, the median survival was 23 months for hilar resection with MLR and 8 months for hilar resection alone; the 1-, 3-, 5-year cumulative survival rate was 63.9%, 23.3%, and 15.5%, respectively for hilar resection with MLR, and 11.1%, 0, and 0, respectively for hilar resection alone, with significant differene observed ( HR , 9.902; 95% CI , 2.636-19.571, P =0.001). Four factors were independently associated with overall survival: preoperative serum Ca19-9 ( HR , 7.039; 95% CI , 2.803-17.678, P <0.001), histopathologic grade ( HR , 4.964; 95% CI , 1.046-23.552, P =0.044), surgical margins ( P =0.031), and AJCC staging ( P =0.015). Conclusions R0 resection is efficacious in surgical treatment of HC. MLR in combination with caudate lobe resection may increase the chance of R0 resection and improve survival of HC patients with B & C type Ⅲ and Ⅳ lesions. Preoperatively prepared for biliary drainage may ensure the safety of MLR in most HC patients. Novel adjuvant therapies are needed to improve the survival of HC patients with poor prognostic factors.

Avian feathers have robust growth and regeneration capability and serve as a useful model for decoding hair morphogenesis and other developmental studies. However, the molecular signaling involved in regulating the development of feather follicles is unclear. The purpose of this study was to investigate the role of the Wnt/β-catenin pathway in regulating feather morphogenesis in embryonic chicks through in ovo injection of different doses of Dickkopf-1 (DKK1, a specific inhibitor of the target of the Wnt/β-catenin pathway). A total of 120 fertilized embryo eggs were randomly divided into 4 treatments, including a noninjection group (control group) and groups injected with 100 μL of phosphate-buffered saline (PBS)/egg (PBS control group), 100 μL of PBS/egg containing 600-ng DKK1/egg (600-ng DKK1 group), and 100-μL PBS/egg containing 1,200-ng DKK1/egg (1,200-ng DKK1 group). Feathers and skin tissues were sampled on embryonic (E) day 15 and the day of hatching to examine the feather mass, diameter and density of feather follicles, and the protein expression of the Wnt/β-catenin pathway. The results showed that, compared with CON and PBS treatment, the injection of DKK1 into the yolk sac of chick embryos had no significant effect on the hatching rate and embryo weight (P > 0.05), while it significantly decreased the relative mass of feathers in the whole body (P < 0.05). The high dose of DKK1 (1,200-ng DKK1/egg) decreased the relative mass of feathers on the back, chest, belly, neck, wings, head, and legs, which was more obvious than that in the 600-ng DKK1 group, which presented a dose-dependent effect. In addition, DKK1 injection significantly downregulated the protein expression levels of β-catenin, transcription factor 4, Cyclin D1, and c-Myc (P < 0.05). The immunofluorescence result of β-catenin was consistent with the Western blotting assay results. Altogether, these observations suggested that the Wnt/β-catenin signaling pathway is involved in regulating feather follicle development and feather growth during the embryonic development of chicks., (Copyright © 2020. Published by Elsevier Inc.)

Feathers play a critical role in thermoregulation and directly influence poultry production. Poor feathering adversely affects living appearance and carcass quality, thus reducing profits. However, producers tend to ignore the importance of feather development and do not know the laws of feather growth and development. The objective of this study was to fit growth curves to describe the growth and development of feathers in yellow-feathered broilers during the embryonic and posthatching periods using different nonlinear functions (Gompertz, logistic and Bertalanffy). Feather mass and length were determined during the embryonic development and posthatching stages to identify which growth model most accurately described the feather growth pattern. The results showed that chick embryos began to grow feathers at approximately embryonic (E) day 10, and the feathers grew rapidly from E13 to E17. There was little change from E17 to the day of hatching (DOH). During the embryonic period, the Gompertz function (Y = 798.48e-203 431exp(-0.87t), Akaike's information criterion (AIC) = -0.950 × 103, Bayesian information criterion (BIC) = -0.711 × 103 and mean square error (MSE) = 559.308) provided the best fit for the feather growth curve compared with the other two functions. After hatching, feather mass and length changed little from the DOH to day (D) 14, increased rapidly from D21 to D91 and then grew slowly after D91. The first stage of feather molting occurred from 2 to 3 weeks of age when the down feathers were mostly shed and replaced with juvenile feathers, and the second stage occurred at approximately 13 to 15 weeks of age. The three nonlinear functions could overall fit the feather growth curve well, but the Bertalanffy model (Y = 116.88 × (1-0.86e-0.02t)3, AIC = 1.065 × 105, BIC = 1.077 × 105 and MSE = 11.308) showed the highest degree of fit among the models. Therefore, the Gompertz model exhibited the best goodness of fit for the feather growth curve during the embryonic development, while the Bertalanffy model was the most suitable model due to its accurate ability to predict the growth and development of feathers during the growth period, which is an important commercial characteristic of yellow-feathered chickens.

Background: We assessed whether allograft rejection or failure can be predicted by an acute increase in C-peptide production from the transplanted pancreas., Methods: Patients with a minimum of 5 years of follow-up post simultaneous pancreas-kidney transplant were identified. C-peptide levels were obtained during clinic visits routinely. Graft failure was defined as return to dependence on insulin therapy or return to dialysis for pancreas and kidney grafts, respectively. Protocol kidney allograft biopsies were performed at 3 and 12 months. For-cause biopsies were also performed., Results: Acute rejections were detected in 11 patients on biopsy results of the renal allograft. C-peptide levels drawn prior to documented rejections were significantly higher in patients with acute rejection than patients with borderline or no rejection (P = .006). Receiver operating characteristics curves for C-peptide indicated greater accuracy in predicting rejection than simultaneously drawn serum creatinine or lipase., Conclusions: Higher C-peptide levels in simultaneous pancreas-kidney recipients is associated with acute rejection vs nonrejection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Muscle fat content and fatty acid composition play an important role in poultry flavor and taste. To investigate the effects of pioglitazone hydrochloride (PGZ) on growth performance and thigh muscle quality in yellow-feathered chickens, 360 female chickens were randomly divided into three groups and treated with three doses of PGZ (0, 7.5, and 15 mg kg -1 ) for 28 days. Each group had six replicates of 20 chickens., Results: The results showed that dietary supplementation with 15 mg kg -1 PGZ increased average daily feed intake (ADFI) and the average daily gain (ADG) from 0 to 14 days. Furthermore, the triglyceride (TG) level was decreased by 15 mg kg -1 PGZ, whereas the eviscerated yield was increased. The relative weight of the heart and kidneys showed a linear increase with dietary PGZ supplementation, and the drip loss of the thigh muscle was significantly decreased by 15 mg kg -1 PGZ supplementation. Moreover, a* value, intramuscular fat (IMF), and polyunsaturated fatty acids (PUFAs) showed a linear increase, and pH 24 h and drip loss showed a quadratic influence with the levels of PGZ supplementation. In particular, the PUFA proportion was increased by 7.63% and 9.14% in the 7.5 mg kg -1 PGZ and 15 mg kg -1 PGZ groups, respectively. Additionally, 15 mg kg -1 of PGZ increased the total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-P X ) activity., Conclusion: In summary, 15 mg kg -1 PGZ has substantial effects on growth performance and meat quality, particularly by decreasing drip loss and increasing IMF content, PUFA proportions, and antioxidant ability. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

The normal growth and regeneration of feathers is important for improving the welfare and economic value of poultry. Feather follicle stem cells are the basis for driving feather development and are regulated by various molecular signaling pathways in the feather follicle microenvironment. To date, the roles of the Wnt, Bone Morphogenetic Protein (BMP), Notch, and Sonic Hedgehog (SHH) signaling pathways in the regulation of feather growth and regeneration are among the best understood. While these pathways regulate feather morphogenesis in different stages, their dysregulation results in a low feather growth rate, poor quality of plumage, and depilation. Additionally, exogenous nutrient intervention can affect the feather follicle cycle, promote the formation of the feather shaft and feather branches, preventing plumage abnormalities. This review focuses on our understanding of the signaling pathways involved in the transcriptional control of feather morphogenesis and explores the impact of nutritional factors on feather growth and regeneration in poultry. This work may help to develop novel mechanisms by which follicle stem cells can be manipulated to produce superior plumage that enhances poultry carcass quality., (Copyright © 2020 Chen, Xie, Jiang, Wang, Yan and Gao.)

Metal(loid) resistance genes (MRGs) play important roles in conferring resistance to metal(loid)s in bacterial communities. How MRGs respond to bacterial succession during manure composting remains largely unknown. Metagenomics was used in the present study to investigate the compositional changes of MRGs, their candidate hosts and association with integrons during thermophilic composting of chicken manures. MRGs conferring resistance to 20 metal(loid)s were detected, and their diversity and abundance (normalized to the abundance of 16S rRNA genes) were significantly reduced during composting. MRGs associated with integron were exclusively observed in proteobacterial species. Class 1 integron likely played an important role in maintaining mercury-resistance mer operon genes in composts. Escherichia coli harbored the most abundant MRGs in the original composting material, whereas species of Actinobacteria and Bacilli became more important in carrying MRGs during the late phases. There were significant linear relationships between the relative abundance of some specific bacterial species (E. coli, Actinobacteria species and Enterococcus faecium) and the abundance of MRGs they potentially harbored. The succession of these bacteria contributed to an overall linear regression between the relative abundance of all predicted candidate hosts and the abundance of total MRGs. Our results suggest that the succession of bacterial community was the main driver of MRG dynamics during thermophilic composting., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Leucine (Leu) plays a critical regulatory role in protein synthesis, however, the effects and molecular mechanisms of Leu on crop milk protein in the domestic pigeons (Columba livia) are still unknown. Therefore, the study aimed to investigate the effects of dietary Leu supplementation on crop milk protein synthesis and the growth performance of squabs and the possible underlying mechanism. A total of 240 pairs of breeding pigeons (1102.3 ± 9.5 g/pair) were randomly assigned to 1 of 5 treatments, including a positive control (PC) diet that had adequate crude protein (crude protein, CP = 18%; Leu = 1.30%), a negative control (NC) diet that was low in CP (CP = 16%, Leu = 1.30%), and NC diets supplemented with Leu at 0.15%, 0.45%, or 1.05%. Compared with the NC diet, 0.15 to 0.45% Leu supplementation decreased BW loss and increased relative crop weight, crop thickness, and protein levels in the crop tissue and milk of breeding pigeons. However, dietary supplementation with 1.05% Leu inhibited ADFI in breeding pigeons. Dietary supplementation with 0.15 to 0.45% Leu decreased the mortality rate and increased the BW, eviscerated yield, and breast muscle yield of young squabs. The protein expression levels of the target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1), ribosomal protein S6 kinase (S6), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and eukaryotic translation initiation factor 4E (eIF4E) were upregulated in the crop tissue of breeding pigeons in PC, 0.15% and 0.45% Leu-supplemented groups. Collectively, these results indicated that 0.15 to 0.45% Leu supplementation could decrease BW loss, increase milk protein synthesis in the crop of breeding pigeons, and enhance the survival rate and growth performance of young squabs through the TOR signaling pathway., (© 2019 Poultry Science Association Inc.)

Microbial arsenic (As) methylation and demethylation are important components of the As biogeochemical cycle. Arsenic methylation is enhanced under flooded conditions in paddy soils, producing mainly phytotoxic dimethylarsenate (DMAs) that can cause rice straighthead disease, a physiological disorder occurring widely in some rice growing regions. The key microbial groups responsible for As methylation and demethylation in paddy soils are unknown. Three paddy soils were incubated under flooded conditions. DMAs initially accumulated in the soil porewater, followed by a rapid disappearance coinciding with the production of methane. The soil from a rice straighthead disease paddy field produced a much larger amount of DMAs than the other two soils. Using metabolic inhibition, quantification of functional gene transcripts, microbial enrichment cultures and 13 C-labeled DMAs, we show that sulfate-reducing bacteria (SRB) and methanogenic archaea are involved in As methylation and demethylation, respectively, controlling the dynamics of DMAs in paddy soils. We present a model of As biogeochemical cycle in paddy soils, linking the dynamics of changing soil redox potential with arsenite mobilization, arsenite methylation and subsequent demethylation driven by different microbial groups. The model provides a basis for controlling DMAs accumulation and incidence of straighthead disease in rice.

Objective: To observe the relationship between the analgesic effect of balance acupuncture and functional changes in brain in patients with migraine without aura., Methods: A total of 40 cases of migraine without aura were equally randomized into a headache-acupoint group and a sham-acupoint group. When acupuncture given, a filiform needle was inserted into the headache-acupoint (the midpoint of the depression region anterior to the juncture of the first and second metatarsal bones on the dorsum of the foot) or the sham point (the midpoint of the depression region anterior to the juncture site between the 3 rd and 4 th metatarsal joints of the dorsum of the foot) about 25-40 mm deep and manipulated for a while till the patient experienced feelings of electric shock and numbness, then withdrawn immediately. The treatment was conducted once daily for 4 weeks. The visual analogue scale (VAS) was used to evaluate the severity of pain, and the regional homogeneity (ReHo) analysis of resting state functional magnetic resonance imaging (fMRI) was used to assess changes of the spontaneous brain activity., Results: After acupuncture, the analgesic effect of headache-acupoint was better than that of the sham-acupoint in both intervention stage and the follow-up stage ( P < 0.05), and was also stronger in the intervention stage than in the follow-up stage ( P <0.05). There was no significant difference in the analgesic effect between the intervention stage and the follow-up stage in the sham-acupoint group ( P >0.05). Compared with pre-intervention, 4-weeks' intervention at the headache-acupoint showed an increase of ReHo values in the anterior cingulate gyrus, anterior central gyrus, superior orbital frontal gyrus, insula, inferior lobule, left anterior cingulate gyrus, ventral lateral nucleus and ventral posteromedial nucleus of the thalamus, pontine nucleus, cerebellar tonsils and orbital frontal inferior gyrus of the brain ( P <0.05), and a decrease of ReHo values in the right brain bridge, central posterior gyrus, posterior cingulate gyrus, left central anterior gyrus, posterolateral nucleus of thalamus, and hippocampus ( P <0.05), separately. In the sham-acupoint group, the ReHo value was increased in the right tongue gyrus, the left anterior lobe, the anterior cingulate gyrus and the lower occipital gyrus of the brain ( P <0.05), and reduced in the left ventral posterolateral nucleus of the thalamus, separately ( P <0.05)., Conclusion: Balance acupuncture stimulation of headache acupoint has an analgesic effect in migraine patients without aura, which may be related to its effect in regulating resting state brain function of the limbic-system-dominated multiple brain regions.

The β2‑adrenergic receptor (β2‑AR, encoded by the ADRB2 gene) is a member of the G‑protein‑coupled receptor superfamily that can be stimulated by catecholamines. Studies in vivo and in vitro have confirmed that β‑blockers (β‑AR antagonists) exert antitumor effects on various tumors. Furthermore, ADRB2 single‑nucleotide polymorphisms (SNPs) have been identified to alter the expression and conformation of β2‑AR, which may alter the β‑blocker drug response. The aim of the present study was to investigate the effect of β‑blockers on triple‑negative breast cancer cells and determine whether ADRB2 SNPs affect the response to β‑blocker drugs. Propranolol and ICI 118,551 significantly inhibited the viability of MDA‑MB‑231 cells, arrested cell cycle progression at G0/G1 and S phase and induced cell apoptosis. Western blot analysis indicated that the phosphorylation levels of extracellular‑signal‑regulated kinase (ERK)1/2 and the expression levels of cyclo‑oxygenase 2 (COX‑2) were significantly decreased following β‑blocker treatment. Four haplotypes, which comprised ADRB2 SNPs rs1042713 and rs1042714, were transfected into 293 cells. After 24 and 48 h of transfection, ADRB2 mRNA expression was significantly decreased in mutant groups compared with the wild‑type group. The ADRB2 SNPs exerted no effect on cell viability, but did affect the drug response of ICI 118,551. Furthermore, ADRB2 SNPs also affected the regulatory function of ICI 118,551 on the ERK/COX‑2 signaling pathway. Collectively, propranolol and ICI 118,551 inhibited the viability of MDA‑MB‑231 cells by downregulating the ERK/COX‑2 signaling pathway and inducing apoptosis. The results of the present study indicated that SNPs rs1042713 and rs1042714 of ADRB2 affected the response to ICI 118,551, and the underlying molecular mechanism was elucidated.

Background and Objective: Insulin-like growth factor 1 (IGF1) gene three prime untranslated region (3'-UTR) polymorphisms have been reported to be associated with cancer risk. However, the conclusions of the relevant studies are not consistent. The present meta-analysis evaluates the relationship between IGF1 gene 3'-UTR polymorphisms (rs5742714, rs6214, and rs6220) and cancer risk., Methods: Articles regarding the relationship between IGF1 rs5742714, rs6214, and rs6220 polymorphisms and cancer risk were selected by searching the PubMed, Embase, and Web of Science databases before April 30, 2018. Altogether, we obtained 34 case-controlled studies from 20 articles, including 21,568 cases and 31,199 controls. The strength of associations was quantified using odds ratios (ORs) and the corresponding 95% confidence intervals (CIs)., Results: In the present meta-analysis, no significant associations were detected between rs5742714, rs6214, and rs6220 and overall cancer risk. Thus, in stratified analyses, we found that rs6214 was associated with a significantly reduced risk of breast cancer under the allele, heterozygote, and dominant models (A vs G: OR, 0.94, 95% CI,0.88-1.00, P = .044; GA vs GG: OR, 0.88, 95% CI, 0.80-0.97, P = .012; AA + GA vs GG: OR, 0.89, 95% CI, 0.81-0.97, P = .011), as well as pancreatic cancer under the recessive model (AA vs GA + GG: OR, 0.68, 95% CI,0.53-0.87, P = .003). Also, rs6220 was associated with a significantly increased risk of breast cancer under the homozygote model (GG vs AA: OR, 1.23, 95% CI, 1.02-1.48, P = .031). In addition, rs6220 was found to increase overall cancer risk among Caucasians under the allele model (G vs A: OR, 1.06, 95% CI, 1.00-1.13, P = .043)., Conclusions: In this meta-analysis, we investigated and reviewed the relationship between IGF1 gene 3'-UTR polymorphisms (rs5742714, rs6214, and rs6220) and cancer risk based on present epidemiological studies. Further studies are needed to draw more precise conclusions in the future.

Background: The rs1520220 polymorphism in the insulin-like growth factor 1 (IGF1) gene has been reported to affect cancer susceptibly in several studies. However, the results of the relevant studies are inconsistent. We conduct a current meta-analysis to investigate the association between rs1520220 and cancer susceptibly., Methods: Three databases (PubMed, Embase, and Web of Science) were searched for studies regarding the relationship between rs1520220 and cancer susceptibly. Odds ratios (ORs) and the related 95% confidence intervals (CIs) were employed to assess the strength of the associations. A stratified analysis was performed according to cancer type, ethnicity, and quality score, and when results were obtained from no fewer than two studies, these results were pooled., Results: There was no positive association between rs1520220 and overall cancer risk. However, the analysis stratified by ethnicity revealed that rs1520220 significantly increased cancer susceptibility in Asian populations (allele model OR = 1.10, 95%Cl = 1.00-1.21, p = 0.040; homozygote model OR = 1.22, 95%Cl = 1.01-1.47, p = 0.040; dominant model OR = 1.19, 95%Cl = 1.01-1.39, p = 0.033). No significantly association was detected in Caucasian populations. The analysis stratified by cancer type suggested that rs1520220 was not associated with susceptibility to breast cancer., Conclusions: The results of our meta-analysis demonstrate that the role of IGF1 rs1520220 in cancer susceptibility varies by ethnicity and cancer type and that rs1520220 increases cancer susceptibility in Asian populations.

Pickled mustard tuber (Brassica juncea var. tumida) belonging to Cruciferae, is a unique economic crop in China. Climate is an important factor affecting the distribution of pickled mustard tuber. Based on species presence data at 279 locations and 22 high-resolution environmental factor layers, we analyzed the potential planting area of pickled mustard tuber in Chongqing by MaxEnt model under the current conditions and the future distributions for the periods 2050s and 2070s under the climate change scenarios of RCP 2.6, RCP 4.5, RCP 6.0 and RCP 8.5 described in the Special Report on Emissions Scenarios (SRES) of IPCC (Intergovernmental Panel on Climate Change). The results showed that MaxEnt model was excellent in predicting its potential plan-ting area. The cumulative contributions of dominant factors reached as high as 81.7%, including precipitation of wettest month, temperature annual range, minimum temperature of coldest month, isothermality, mean diurnal range and average maximum temperature. The threshold of those factors was 173-183 mm, 27.2-28.3 ℃, 1.8-3.8 ℃, 22.5-24 ℃, 6.2-6.8 ℃ and 14.8-18.0 ℃, respectively. Under current condition, the optimum suitable areas of pickled mustard tuber, which amounted to 4.2%, were in the northeast, west and east of Fuling, the east and south of Changshou, the south and southeast of Dianjiang, the northwest and north of Fengdu, the southeast of Zhongxian, and a small part of Wulong and Nanchuan, while the proportion of moderately suitable areas was 6.3%. Under four climate change scenarios, the optimum suitable areas would drop to 2.7%, 3.8%, 3.1%, 3.2% and 3.1%, 3.7%, 3.5%, 2.9% for the periods 2050s and 2070s, respectively, while moderately suitable areas would rise gradually.

Many studies have reported that BRCA1 polymorphisms are associated with cancer risk, but the results remain controversial. The purpose of this meta-analysis is to evaluate the relationship between BRCA1 polymorphisms (rs799917, rs1799950, rs1799966, or rs16941) and cancer risk. Relevant studies were identified via a systematic search of the PubMed, Embase, and Web of Science databases up to July 31, 2017. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to examine the strength of the associations. Thirty-five studies published in 19 publications involving 28,094 cases and 50,657 controls were included in this meta-analysis. There was no obvious association between rs799917, rs1799966, or rs16941 polymorphisms and overall cancer risk in any genetic models. However, subgroup analyses revealed that the rs799917 polymorphism could decrease the risk of cervical cancer, esophageal squamous cell carcinoma (ESCC), gastric cancer, and non-Hodgkin lymphoma (NHL) among Asian populations in one or more genetic models and that rs16941 could increase overall cancer risk among Caucasian populations in the homozygote and recessive models. Our meta-analysis also indicated that rs1799950 could decrease the breast cancer (BC) risk among Caucasian populations in the homozygote and recessive models. In summary, our results suggest that BRCA1 polymorphisms may play an important role in the etiology of cancer. However, due to the limited number of studies, these findings should be confirmed by new studies with larger sample sizes that address various types of cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

In this work, a strategy of in-series combination of ultrasound-assisted extraction and online LC-GC/MS was constructed for effective separation and analysis of sucrose esters in tobacco. Sucrose esters were first extracted by ultrasound-assisted extraction with high efficiency and easyhandling. Online LC-GC/MS was then applied for sucrose ester clean-up and analysis. To better evaluate the effectiveness of this strategy, we limited our focus to five groups of sucrose ester isomers. Each group differed in mass from the next by 14 Da. The obtained coefficient of the calibration curve was 0.9986. Limit of detection (LOD) and limit of quantitation (LOQ) were 0.05 and 0.16 μg/ mL, respectively. The recovery was above 90% and the reproducibility was below 4%. This strategy was subsequently applied to the comparison of relative amounts of five groups of sucrose esters extracted from three different parts of aromatic tobacco. The satisfactory performance indicated that this strategy has great prospect for the rapid and high-throughput analysis of sucrose esters in tobacco.

Arsenic (As) biovolatilization is an important component of the global As biogeochemical cycle. Soils can emit various methylarsine gases, but the underlying microbial processes remain unclear. Here, we show that the addition of molybdate (Mo), an inhibitor of sulfate-reducing bacteria, greatly enhanced dimethylarsine evolution from dimethylarsenate [DMAs(V)] added to two paddy soils. Molybdate addition significantly affected the microbial community structure. The aerobic enrichment cultures from both soils volatilized substantial amounts of dimethylarsine from DMAs(V) in the presence of Mo, whereas the anaerobic enrichment cultures did not. A Bacillus strain (CZ-2) capable of reducing DMAs(V) to dimethylarsine was isolated from the aerobic enrichment culture, and its volatilization ability was enhanced by Mo. RNA-seq analysis identified 10 reductase genes upregulated by Mo. Addition of the reducing agent NADH increased dimethylarsine volatilization by strain CZ-2, suggesting that DMAs(V) reductase is an NADH-dependent enzyme. The strain could not methylate arsenite or convert monomethylarsenate and DMAs(V) to trimethylarsine. Our results show that dimethylarsine evolution from DMAs(V) is independent of the As methylation pathway and that Mo enhances dimethylarsine evolution from paddy soils by shifting the microbial community structure and enhancing the reduction of DMAs(V) to dimethylarsine, possibly through upregulating the expression of DMAs(V) reductase gene(s).

Objective: Early allograft dysfunction may be caused by several technical factors including vascular complications such as thrombosis, kinking, or extrinsic compression. Renal allograft compartment syndrome (RACS) is an unrecognized cause of early allograft dysfunction. This complication is characterized by increased pressure of the iliac fossa that reduces the blood supply to the graft with a potentially devastating consequence. The main objective when recognizing this condition is to create a tension-free muscle closure. Many approaches have been proposed involving mesh such as the mesh hood fascial closure technique. 1-4 PATIENT AND METHODS: We describe in the video an RACS during an operation. The recipient is a 23-year-old young man with a body mass index of 22, with renal failure secondary to chronic reflux. Past history of failure to peritoneal dialysis currently on hemodialysis. He received a living donor's kidney. After performing a standard anastomosis, his urine output was brisk. The fascia was then closed with no force, at which point he stopped making urine. A RACS was suspected; intraoperative examination and ultrasound showed no flow in the graft, with no signs of kinking. Immediately, reexploration was performed, showing the graft with abnormal color and turgor. After relieving the pressure, the graft returned to normal. The closure was redone with a large ellipsoid piece of polypropylene mesh draped loosely and without tension over the graft., Results: A Doppler ultrasound, after the skin closure was performed, showed good flow, and the postoperative course was unremarkable. There was minimal bulking in the right iliac area, making it cosmetically acceptable., Conclusion: RACS could be associated with a lack of compliance in the retroperitoneal cavity. 5 The RACS required a prompt intervention. The timely suspicion is a watershed in the prognosis of this rare pathology. We propose that mesh hood fascial closure is easy, effective, and a safe method to treat these complications., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Bombesin receptor-activated protein (BRAP) is highly expressed in human bronchial epithelial cells. Recent studies have shown that BRAP reduces oxidative stress, inhibits airway inflammation and suppresses nuclear factor kappaB (NF-κB) activity. Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases. Neutrophil elastase (NE) is a potent inducer of mucin5AC (MUC5AC), which is considered the predominant mucin secreted by human airway epithelial cells. Here, we hypothesize that BRAP may regulate NE-induced MUC5AC hypersecretion in a bronchial epithelial cell line (HBE16). We also investigated the underlying mechanism involved in the process. In this study, we found that BRAP was present in HBE16 human bronchial epithelial cells and was significantly increased by NE. Next, we found that the up-regulation of BRAP by pEGFP-N1-BRAP caused a significant decrease in the increased levels of MUC5AC expression, NF-κB activity, and the phosphorylation of extracellular signal-regulated kinases (ERK) and epidermal growth factor receptor (EGFR) induced by NE. Meanwhile, there was a significant decrease in ROS, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels when BRAP was up-regulated by pEGFP-N1-BRAP. Moreover, when cells were transfected with pEGFP-N1-BRAP and pretreated with NF-κB, ERK or EGFR inhibitors before the NE stimulation, there were further decreased in MUC5AC expression, NF-κB activity, and the phosphorylation of ERK and EGFR. These results suggest that BRAP plays an important role in airway inflammation and its overexpression may regulate NE-induced MUC5AC hypersecretion in HBE16 cells via the EGFR/ERK/NF-κB signaling pathway., (Copyright © 2017. Published by Elsevier Inc.)

Objective: To investigate whether Pi (Spleen) qi-deficiency affected psychological and neural responses in relevance to cognitive control., Methods: Pi qi-deficient and balanced participants were asked to perform the Stroop task, a classical cognitive control paradigm. In this paradigm, participants had to judge the color of the prompted word. The word's meaning indicated the color (the consistent condition) or not (the inconsistent condition), or were unrelated to the color (the neutral condition). Electroencephalograph (EEG) was recorded during the task., Results: Event-related potential (ERP) results showed that Pi qi-deficient individuals failed to exhibit a normal Stroop effect as Balanced individuals did, such as the accuracy differences between the consistent and the inconsistent conditions as well as the N450 effect (P>0.05). Meanwhile, Pi qi-deficient individuals displayed larger P2 and P3 amplitudes than balanced individuals did during performing the cognitive control task (P<0.05)., Conclusion: Pi qi-deficiency had psychological and neural basis at least in cognitive control aspect.

Glucocorticoids (GCs) are widely used for treating asthma, rheumatoid arthritis, nephrotic syndrome, acute lymphoblastic leukemia and other autoimmune diseases. However, in a subgroup of patients, failure to respond to GCs is known as GC resistance or GC insensitivity. This represents an important barrier to effective treatment and a clinical problem requiring an urgent solution. Genetic variation in the GC pathway is a significant factor in interindividual differences in GC treatment. This article reviews the pharmacogenetics of GCs in diverse diseases based on the GC pathway.

Land applications of municipal sewage sludge may pose a risk of introducing antibiotic resistance genes (ARGs) from urban environments into agricultural systems. However, how the sewage sludge recycling and application method influence soil resistome and mobile genetic elements (MGEs) remains unclear. In the present study, high through-put quantitative PCR was conducted on the resistome of soils from a field experiment with past (between 1994 and 1997) and annual (since 1994) applications of five different sewage sludges. Total inputs of organic carbon were similar between the two modes of sludge applications. Intrinsic soil resistome, defined as the ARGs shared by the soils in the control and sludge-amended plots, consisted of genes conferring resistance to multidrug, β-lactam, Macrolide-Lincosamide-Streptogramin B (MLSB), tetracycline, vancomycin, and aminoglycoside, with multidrug resistance genes as the most abundant members. There was a strong correlation between the abundance of ARGs and MGE marker genes in soils. The composition and diversity of ARGs in the five sludges were substantially different from those in soils. Considerable proportions of ARGs and MGE marker genes in the sludges attenuated following the application, especially aminoglycoside and tetracycline resistance genes. Annual applications posed a more significant impact on the soil resistome, through both continued introduction and stimulation of the soil intrinsic ARGs. In addition, direct introduction of sludge-specific ARGs into soil was observed especially from ARG-rich sludge. These results provide a better insight into the characteristics of ARG dissemination from urban environment to the agricultural system through sewage sludge applications.

The over-use of antibiotics in animal husbandry in China and the concomitant enhanced selection of antibiotic resistance genes (ARGs) in animal manures are of serious concern. Thermophilic composting is an effective way of reducing hazards in organic wastes. However, its effectiveness in antibiotic degradation and ARG reduction in commercial operations remains unclear. In the present study, we determined the concentrations of 15 common veterinary antibiotics and the abundances of 213 ARGs and 10 marker genes for mobile genetic elements (MGEs) in commercial composts made from cattle, poultry and swine manures in Eastern China. High concentrations of fluoroquinolones were found in the poultry and swine composts, suggesting insufficient removal of these antibiotics by commercial thermophilic composting. Total ARGs in the cattle and poultry manures were as high as 1.9 and 5.5 copies per bacterial cell, respectively. After thermophilic composting, the ARG abundance in the mature compost decreased to 9.6% and 31.7% of that in the cattle and poultry manure, respectively. However, some ARGs (e.g. aadA, aadA2, qacEΔ1, tetL) and MGE marker genes (e.g. cintI-1, intI-1 and tnpA-04) were persistent with high abundance in the composts. The antibiotics that were detected at high levels in the composts (e.g. norfloxacin and ofloxacin) might have posed a selection pressure on ARGs. MGE marker genes were found to correlate closely with ARGs at the levels of individual gene, resistance class and total abundance, suggesting that MGEs and ARGs are closely associated in their persistence in the composts under antibiotic selection. Our research shows potential disseminations of antibiotics and ARGs via compost utilization., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The occurrence and mechanisms of autophagy induced by heat stress are not well known in lung cancer cells. Here, we have demonstrated that heat stress induces autophagy in A549 and NCI-H460 cells through morphological and biochemical analyses. The inhibition of autophagy by chloroquine, 3-methyladenine and Beclin 1 siRNA enhanced heat-induced apoptosis. Moreover, the combination of chloroquine and heat stress inhibited tumor growth and enhanced apoptosis in vivo experiments. In addition, heat-induced autophagy involved the ER stress pathway (PERK- or IRE1-dependent). Further, heat treatment led to the increased phosphorylation of AMPK and the decreased phosphorylation of mTOR in vitro and in vivo. Knockdown of GRP78 inhibited the AMPK-mTOR pathway, and the AMPK inhibitor compound C decreased heat-induced autophagy, suggesting that activation of ER stress was involved in autophagy induction and promotion of the AMPK-mTOR pathway. In conclusion, our data suggested that the heat treatment of lung cancer cells triggered protective autophagy, as mediated by ER stress. Thus, inhibition of autophagy can be a promising strategy to enhance hyperthermia in the treatment of lung cancer patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse neurodevelopmental outcomes in the child. Epigenetic alternations may play an essential role in the negative effects of PTSD. This study was aimed to investigate the possible epigenetic alterations of maternal PTSD, which underpins the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats were randomly grouped into PTSD and control groups. Open-field tests (OFTs), elevated pull maze (EPM) assays, gene expression profile chip tests, and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) were performed on the offsprings 30 days after birth. The results showed that PTSD offsprings had lower body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent assays showed that serotonin receptor (5-HT) and dopamine levels were significantly lower in PTSD offsprings than in control offsprings. In contrast, corticosterone levels were higher in the PTSD group than in the control group. In a comparison of the PTSD group versus the control group, 4,160 significantly differentially methylated loci containing 30,657 CpGs were identified; 2,487 genes, including 13 dysmethylated genes, were validated by gene expression profiling, showing a negative correlation between methylation and gene expression (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical and behavioral development of offsprings, and the underlying mechanism could contribute to changes in neurotransmitters and gene expression, owing to dysregulation of whole-genome methylation. These findings could support further clinical research on appropriate interventions for maternal PTSD to prevent methylation dysregulation and developmental retardation.

Objective: Metabolic syndrome (MetS) is associated with an increased risk of finding prostate cancer overall and high-grade disease on biopsy. This study sought to determine if MetS is associated with adverse final pathology and risk of overall recurrence in men undergoing radical prostatectomy (RP)., Methods: Men undergoing RP (2004-2013) were identified using our prospectively maintained institutional database. MetS was defined by ≥3 of 5 components (obesity, dysglycemia, hypertension, low high-density lipoprotein-cholesterol, and high triglycerides). Multivariable logistic regression models were created for prostate cancer grade and stage on final pathology. Kaplan-Meier and multivariable Cox regression analyses were performed to model overall recurrence, defined by biochemical recurrence (postoperative serum prostate-specific antigen ≥0.2 ng/mL) or use of salvage therapies., Results: Of 1939 men, 439 (22.6%) had MetS. MetS (≥3 vs. 0 components) was associated with an increased odds of Gleason 8-10 disease (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.32-4.67, P = .005) and extraprostatic disease (OR = 1.35, 95% CI = 1.02-1.80, P = .04). Decreased use of nerve-sparing in men with MetS was noted. In unadjusted analyses, MetS was associated with a significantly increased risk of receiving salvage therapy (hazard ratio [HR] = 1.38, 95% CI = 1.04-1.83, P = .03) and a near-significant increased overall recurrence risk (HR = 1.20, 95% CI = 0.94-1.53, P = .15). These associations were attenuated upon adjusting for disease-specific parameters (salvage therapy: HR = 1.03, 95% CI = 0.76-1.40, P = .87; overall recurrence: HR = 0.94, 95% CI = 0.72-1.21, P = .62)., Conclusion: MetS is associated with an increased odds of extraprostatic and high-grade disease on final RP pathology, which appears to drive an increased risk of needing salvage therapy after RP. However, with more aggressive resection, differences in failure-free outcomes were attenuated, suggesting that men with MetS should not be precluded from RP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cancer immunotherapy has primarily been focused on attacking tumor cells. However, given the close interaction between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), CAF-targeted strategies could also contribute to an integrated cancer immunotherapy. Fibroblast activation protein α (FAP α) is not detectible in normal tissues, but is overexpressed by CAFs and is the predominant component of the stroma in most types of cancer. FAP α has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. When all FAP α-expressing cells (stromal and cancerous) are destroyed, tumors rapidly die. Furthermore, a FAP α antibody, FAP α vaccine, and modified vaccine all inhibit tumor growth and prolong survival in mouse models, suggesting FAP α is an adaptive tumor-associated antigen. This review highlights the role of FAP α in tumor development, explores the relationship between FAP α and immune suppression in the TME, and discusses FAP α as a potential immunotherapeutic target., Competing Interests: No potential conflicts of interest were disclosed.

Objective: To evaluate the effects of an internet-platform exergame cycling programme on cardiovascular fitness of youth with cerebral palsy (CP)., Methods: In this pilot prospective case series, eight youth with bilateral spastic CP, Gross Motor Functional Classification System (GMFCS) level III, completed a six-week exergame programme. Outcomes were obtained at baseline and post-intervention. The primary outcome measure was the GMFCS III-specific shuttle run test (SRT-III). Secondary outcomes included health-related quality of life (HQL) as measured by the KIDSCREEN-52 questionnaire, six-minute walk test, Wingate arm cranking test and anthropomorphic measurements., Results: There were significant improvements in the SRT-III (t = -2.5, p = 0.04, d = 0.88) post-intervention. There were no significant changes in secondary outcomes., Conclusion: An exergame cycling programme may lead to improvement in cardiovascular fitness in youth with CP. This study was limited by small sample size and lack of a comparison group. Future research is warranted.

An acidic tumor microenvironment exists widely in solid tumors. However, the detailed mechanism of cell survival under acidic stress remains unclear. The aim of this study is to clarify whether acid-induced autophagy exists and to determine the function and mechanism of autophagy in lung cancer cells. We have found that acute low pH stimulated autophagy by increasing LC3-positive punctate vesicles, increasing LC3 II expression levels and reducing p62 protein levels. Additionally, autophagy was inhibited by the addition of Baf or knockdown of Beclin 1, and cell apoptosis was increased markedly. In mouse tumors, the expression of cleaved caspase3 and p62 was enhanced by oral treatment with sodium bicarbonate, which can raise the intratumoral pH. Furthermore, the protein levels of ER stress markers, including p-PERK, p-eIF2α, CHOP, XBP-1s and GRP78, were also increased in response to acidic pH. The antioxidant NAC, which reduces ROS accumulation, alleviated acid-mediated ER stress and autophagy, and knocking down GRP78 reduced autophagy activation under acidic conditions, which suggests that autophagy was induced by acidic pH through ER stress. Taken together, these results indicate that the acidic microenvironment in non-small cell lung cancer cells promotes autophagy by increasing ROS-ER stress, which serves as a survival adaption in this setting., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Arsenite [As (III)] oxidation can be accelerated by bacterial catalysis, but the effects of the accelerated oxidation on arsenic toxicity and translocation in rice plants are poorly understood. Herein we investigated how an arsenite-oxidizing bacterium, namely Brevibacillus laterosporus, influences As (III) toxicity and translocation in rice plants. Rice seedlings of four cultivars, namely Guangyou Ming 118 (GM), Teyou Hang II (TH), Shanyou 63 (SY) and Minghui 63 (MH), inoculated with or without the bacterium were grown hydroponically with As (III) to investigate its effects on arsenic toxicity and translocation in the plants. Percentages of As (III) oxidation in the solutions with the bacterium (100%) were all significantly higher than those without (30-72%). The addition of the bacterium significantly decreased As (III) concentrations in SY root, GM root and shoot, while increased the As (III) concentrations in the shoot of SY, MH and TH and in the root of MH. Furthermore, the As (III) concentrations in the root and shoot of SY were both the lowest among the treatments with the bacterium. On the other hand, its addition significantly alleviated the As (III) toxicity on four rice cultivars. Among the treatments amended with B. laterosporus, the bacterium showed the best remediation on SY seedlings, with respect to the subdued As (III) toxicity and decreased As (III) concentration in its roots. These results indicated that As (III) oxidation accelerated by B. laterosporus could be an effective method to alleviate As (III) toxicity on rice seedlings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Fibroblast activation protein α (FAPα) is a potential target for cancer therapy. However, elimination of FAPα+ fibroblasts activates secretion of IFN-γ and TNF-α. IFN-γ can in turn induce expression indolamine-2,3-dioxygenase (IDO), thereby contributing to immunosuppression, while TNF-α can induce EMT. These two reactive effects would limit the efficacy of a tumor vaccine. We found that curcumin can inhibit IDO expression and TNF-α-induced EMT. Moreover, FAPαc vaccine and CpG combined with curcumin lavage inhibited tumor growth and prolonged the survival of mice implanted with melanoma cells. The combination of FAPαc vaccine, CpG and curcumin stimulated FAPα antibody production and CD8+ T cell-mediated killing of FAPα-expressing stromal cells without adverse reactive effects. We suggest a combination of curcumin and FAPαc vaccine for melanoma therapy.

The phyllosphere of floating macrophytes in paddy soil ecosystems, a unique habitat, may support large microbial communities but remains largely unknown. We took Wolffia australiana as a representative floating plant and investigated its phyllosphere bacterial community and the underlying driving forces of community modulation in paddy soil ecosystems using Illumina HiSeq 2000 platform-based 16S rRNA gene sequence analysis. The results showed that the phyllosphere of W. australiana harbored considerably rich communities of bacteria, with Proteobacteria and Bacteroidetes as the predominant phyla. The core microbiome in the phyllosphere contained genera such as Acidovorax, Asticcacaulis, Methylibium, and Methylophilus. Complexity of the phyllosphere bacterial communities in terms of class number and α-diversity was reduced compared to those in corresponding water and soil. Furthermore, the bacterial communities exhibited structures significantly different from those in water and soil. These findings and the following redundancy analysis (RDA) suggest that species sorting played an important role in the recruitment of bacterial species in the phyllosphere. The compositional structures of the phyllosphere bacterial communities were modulated predominantly by water physicochemical properties, while the initial soil bacterial communities had limited impact. Taken together, the findings from this study reveal the diversity and uniqueness of the phyllosphere bacterial communities associated with the floating macrophytes in paddy soil environments., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Residues 221-239 of rubella virus E1 glycoprotein contain antibody neutralization domains, and the solvent-exposed charged amino acids at the binding interface may be crucial for binding ability. However, the role of charged amino acid residues on the E1 epitope in peptide-antibody binding is unknown. To investigate the role of single amino acid substitutions on the important neutralizing epitope, biolayer interferometry and serological tests were performed. There are three charged residues in the neutralizing epitope: D229, R237, and H238. Substitution of D229 for amino acid A had no influence on the binding activity of the antibody to the peptide. However, substitutions of R237 or H238 for charged amino acid H or R were found to abolish the binding activity. Furthermore, substitution of an uncharged amino acid Q236 for a charged amino acid D was found to reduce the binding activity significantly. Thus, R237 and H238 are key amino acids in the rubella virus E1 neutralization epitope.

Speciation is a key determinant in the toxicity, behavior, and fate of arsenic (As) in the environment. However, little is known about the transformation of As species mediated by floating macrophytes and the phyllosphere bacteria in aquatic and wetland environment. In this study, Wolffia australiana, a rootless floating duckweed, was cultured with (W+B) or without (W-B) phyllosphere bacteria to investigate its ability in arsenite (As(III)) oxidation. Results showed that sterile W. australiana did not oxidize As(III) in the growth medium or in plant tissue, whereas W. australiana with phyllpsphere bacteria displayed substantial As(III) oxidation in the medium. Quantitative PCR of As redox-related functional genes revealed the dominance of the arsenite oxidase (aioA) gene in the phyllosphere bacterial community. These results demonstrate that the phyllosphere bacteria were responsible for the As(III) oxidation in the W+B system. The rapid oxidation of As(III) by the phyllosphere bacterial community may suppress As accumulation in plant tissues under phosphate rich conditions. The aioA gene library showed that the majority of the phyllosphere arsenite-oxidizing bacteria related either closely to unidentified bacteria found in paddy environments or distantly to known arsenite-oxidizing bacteria. Our research suggests a previously overlooked diversity of arsenite-oxidizing bacteria in the phyllosphere of aquatic macrophytes which may have a substantial impact on As biogeochemistry in water environments, warranting further exploration.

Herein, by combining the merits of nanotechnology and fuzzy logic theory, we develop a simple, label-free, and general strategy based on an organic dye-graphene hybrid system for fluorescence intelligent sensing of G-quadruplexes (G4) formation, hydroxyl radical (HO∙), and Fe(2+) in vitro. By exploiting acridine orange (AO) dyes-graphene as a nanofilter and nanoswitch and the ability of graphene to interact with DNA with different structures, our approach can efficiently distinguish, quantitatively detect target analytes. In vitro assays with G4DNA demonstrated increases in fluorescence intensity of the AO-rGO system with a linear range of 16-338 nM and a detection limit as low as 2.0 nM. The requenched fluorescence of the G4TBA-AO-rGO system has a non-linear response to Fenton reagent. But this requenching reduces the fluorescence intensity in a manner proportional to the logarithm to the base 10 of the concentration of Fenton reagent in the range of 0.1-100 μM and 100-2000 μM, respectively. Furthermore, we develop a novel and intelligent sensing method based on fuzzy logic which mimics human reasoning, solves complex and non-linear problems, and transforms the numerical output into the language description output for potential application in biochemical systems, environmental monitoring systems, and molecular-level fuzzy logic computing system., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: Pain in children with cerebral palsy (CP) is underrecognized, undertreated, and negatively affects quality of life. Communication challenges and multiple pain etiologies complicate diagnosis and treatment. The primary objectives of this study were to determine the impact of pain on activities and to identify the common physician-identified causes of pain in children and youth ages 3 to 19 years across all levels of severity of CP., Methods: The study design was cross-sectional, whereby children/youth aged 3 to 19 years and their families were consecutively recruited. The primary caregivers were asked to complete a one-time questionnaire, including the Health Utilities Index 3 pain subset, about the presence and characteristics of pain. The treating physician was asked to identify the presence of pain and provide a clinical diagnosis for the pain, if applicable., Results: The response rate was 92%. Of 252 participants, 54.8% reported some pain on the Health Utilities Index 3, with 24.4% of the caregivers reporting that their child experienced pain that affected some level of activities in the preceding 2 weeks. Physicians reported pain in 38.7% and identified hip dislocation/subluxation, dystonia, and constipation as the most frequent causes of pain., Conclusions: One-quarter of our sample experienced pain that limited activities and participation. Clinicians should be aware that hip subluxation/dislocation and dystonia were the most common causes of pain in children/youth with CP in this study. Potential causes of pain should be identified and addressed early to mitigate the negative impact of pain on quality of life.

This experiment was undertaken to examine the effect of beak trimming stress on the growth performance and immune system, and to consider possible roles of γ-aminobutyric acid (GABA) in this stress response. Results showed that body weight, feed intake and relative spleen weight were significantly increased by GABA at 80 mg/kg (P < 0.05) under beak trimming stress, whereas the relative organ weights of the bursa of fabricius and thymus were not significantly affected (P > 0.05). Adrenocorticotropic hormone concentration in serum was highest for chicks fed the GABA-deficient water and was significantly decreased by the supplement of GABA at days 1, 3 and 5 after beak trimming (P < 0.05). The supplement of GABA significantly increased the proportions of CD4(+) and CD8(+) lymphocytes, especially at the dose of 60 mg/kg (P < 0.05). The levels of interleukin (IL)-1β, lipopolysaccharide-induced tumor necrosis factor-α and IL-6 in serum were significantly decreased by GABA at 80 mg/kg (P < 0.05). All the three cytokines expressed in the spleen were significantly decreased by GABA at 80 mg/kg when birds were under beak trimming stress (P < 0.05). It is concluded that beak trimming suppressed the immune response of chicks, whereas the immune response of chicks could be improved by GABA supplementation., (© 2012 Japanese Society of Animal Science.)

Cadmium (Cd) pollution around the world is a serious issue demanding acceptable solutions, one of which is phytoremediation that is both cost-effective and eco-friendly. Removal of Cd from contaminated water using plants with high growth rates and sufficient Cd accumulation abilities could be an appropriate choice. Here, we investigated a potential Cd accumulator, Wolffia, a rootless duckweed with high growth rate. Cd uptake, accumulation, tolerance, and phytofiltration ability by Wolffia globosa were examined. Furthermore, the effects of arsenic (As) on Cd uptake and phytofiltration by W. globosa were also studied. Cd uptake kinetics showed a linear pattern and a hyperbolic pattern without a plateau in lower (0-2 microM) and higher (0-200 microM) Cd concentration ranges, respectively, suggesting rapid Cd uptake by W. globosa Cd accumulation ability by W. globosa was higher at Cd concentrations < 10 microM than at >10 microM. All the five species of Wolffia exposed to I microM Cd for 5 days accumulated > 500 mg Cd kg(-1) DW. Ten gram fresh W. globosa could diminish almost all the Cd (2 microM) in a 200 mL solution. This enormous accumulation ability was mostly due to passive adsorption of Cd by the apoplast. Arsenic had no significant effect on Cd uptake and phytofiltration. The fresh fronds also showed a great As extracting ability. The results indicated that Wolffia is a strong Cd accumulator and has great Cd phytoremediation potential. Therefore, this plant can be used in fresh aquatic environments co-contaminated by low-levels of Cd and As.

A new room-temperature phosphorescence (RTP) mercury ions sensor has been developed based on cetyltrimethylammonium bromide-capped Mn-doped ZnS quantum dots (CTAB/Mn-ZnS QDs) and label-free thymine (T)-rich aptamer. The formed T-Hg(2+)-T dsDNA can linearly quench the RTP of Mn-ZnS QDs through electron transfer and aggregation effect, and give a detection limit of 1.5 nM.

Coupling T base with Hg(2+) to form stable T-Hg(2+)-T complexes represents a new direction in detection of Hg(2+). Here a graphene oxide (GO)-based fluorescence Hg(2+) analysis using DNA duplexes of poly(dT) that allows rapid, sensitive, and selective detection is first reported. The Hg(2+)-induced T(15)-(Hg(2+))(n)-T(15) duplexes make T(15) unable to hybridize with its complementary A(15) labelled with 6'-carboxyfluorescein (FAM-A(15)), which has low fluorescence in the presence of GO. On the contrary, when T(15) hybridizes with FAM-A(15) to form double-stranded DNA because of the absence of Hg(2+), the fluorescence largely remains in the presence of GO. A linear range from 10 nM to 2.0 μM (R(2) = 0.9963) and a detection limit of 0.5 nM for Hg(2+) were obtained under optimal experimental conditions. Other metal ions, such as Al(3+), Ag(+), Ca(2+), Ba(2+), Mg(2+), Zn(2+), Mn(2+), Co(2+), Pb(2+), Ni(2+), Cu(2+), Cd(2+), Cr(3+), Fe(2+), and Fe(3+), had no significant effect on Hg(2+) detection. Moreover, the sensing system was used for the determination of Hg(2+) in river water samples with satisfactory results.

The rootless duckweed Wolffia globosa can accumulate and tolerate relatively large amounts of arsenic (As); however, the underlying mechanisms were unknown. W. globosa was exposed to different concentrations of arsenate with or without l-buthionine sulphoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. Free thiol compounds and As(III)-thiol complexes were identified and quantified using HPLC - high resolution ICP-MS - accurate mass ESI-MS. Without BSO, 74% of the As accumulated in the duckweed was complexed with phytochelatins (PCs), with As(III)-PC(4) and As(III)-PC(3) being the main species. BSO was taken up by the duckweed and partly deaminated. The BSO treatment completely suppressed the synthesis of PCs and the formation of As(III)-PC complexes, and also inhibited the reduction of arsenate to arsenite. BSO markedly decreased both As accumulation and As tolerance in W. globosa. The results demonstrate an important role of PCs in detoxifying As and enabling As accumulation in W. globosa., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Our previous study identified Threonine 161 (Thr-161), located in the second intracellular loop of the δ-opioid receptor (DOR), as the only consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund's adjuvant (CFA)-induced inflammatory pain and morphine tolerance., Methods: Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain., Results: Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. Intrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased inflammatory hypersensitivity, and inhibited DOR- but not µ-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain., Conclusion: Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr-161 attenuates morphine tolerance.

In the presence of graphene oxide, upon formation of cytosine-Ag-cytosine the fluorescence wavelength of FAM-labeled DNA exhibited a red shift, and its intensity significantly increased. A novel fluorescent DNA sensor for Ag(+) and cysteine detection, and a dual-output fluorescent DNA INHIBIT logic gate are designed., (This journal is © The Royal Society of Chemistry 2012)