Very-low-density lipoprotein receptor-enhanced lipid metabolism in pancreatic stellate cells promotes pancreatic fibrosis.

Lipoprotein disorder is a common feature of chronic pancreatitis (CP); however, the relationship between lipoprotein disorder and pancreatic fibrotic environment is unclear. Here, we investigated the occurrence and mechanism of pancreatic stellate cell (PSC) activation by lipoprotein metabolites and the subsequent regulation of type 2 immune responses, as well as the driving force of fibrotic aggressiveness in CP. Single-cell RNA sequencing revealed the heterogeneity of PSCs and identified very-low-density lipoprotein receptor (VLDLR)+ PSCs that were characterized by a higher lipid metabolism. VLDLR promoted intracellular lipid accumulation, followed by interleukin-33 (IL-33) expression and release in PSCs. PSC-derived IL-33 strongly induced pancreatic group 2 innate lymphoid cells (ILC2s) to trigger a type 2 immune response accompanied by the activation of PSCs, eventually leading to fibrosis during pancreatitis. Our findings indicate that VLDLR-enhanced lipoprotein metabolism in PSCs promotes pancreatic fibrosis and highlight a dominant role of IL-33 in this pro-fibrotic cascade.

Pancreatic STAT5 activation promotes KrasG12D-induced and inflammation-induced acinar-to-ductal metaplasia and pancreatic cancer.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear. DESIGN: We performed studies with LSL-Kras G12D; Ptf1a-Cre ERT (KCERT) mice or LSL-KrasG12D; LSL-Trp53R172H ; Pdx1-Cre (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice. RESULTS: The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1ß and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation. CONCLUSION: Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.

Porous Hydrogels for Immunomodulatory Applications.

Cancer immunotherapy relies on the insight that the immune system can be used to defend against malignant cells. The aim of cancer immunotherapy is to utilize, modulate, activate, and train the immune system to amplify antitumor T-cell immunity. In parallel, the immune system response to damaged tissue is also crucial in determining the success or failure of an implant. Due to their extracellular matrix mimetics and tunable chemical or physical performance, hydrogels are promising platforms for building immunomodulatory microenvironments for realizing cancer therapy and tissue regeneration. However, submicron or nanosized pore structures within hydrogels are not favorable for modulating immune cell function, such as cell invasion, migration, and immunophenotype. In contrast, hydrogels with a porous structure not only allow for nutrient transportation and metabolite discharge but also offer more space for realizing cell function. In this review, the design strategies and influencing factors of porous hydrogels for cancer therapy and tissue regeneration are first discussed. Second, the immunomodulatory effects and therapeutic outcomes of different porous hydrogels for cancer immunotherapy and tissue regeneration are highlighted. Beyond that, this review highlights the effects of pore size on immune function and potential signal transduction. Finally, the remaining challenges and perspectives of immunomodulatory porous hydrogels are discussed.

Characterizing Excited States of a Copper-Based Molecular Qubit Candidate with Correlated Electronic Structure Methods.

Molecular spins have a variety of potential advantages as qubits for quantum computation, such as tunability and well-understood design pathways through organometallic synthesis. Organometallic and heavy-metal-based molecular spin qubits can also exhibit rich electronic structures due to ligand field interactions and electron correlation. These features make consistent and reliable modeling of these species a considerable challenge for contemporary electronic structure techniques. Here, we elucidate the electronic structure of a Cu(II) complex analogous to a recently proposed room-temperature molecular spin qubit. Using active space methods to describe the electron correlation, we show the nuanced interaction between the metal d orbitals and ligand σ and π orbitals makes these systems challenging to model, both in terms of the delocalized spin density and the excited state ordering. We show that predicting the correct spin delocalization requires special consideration of the Cu d orbitals and that the excited state spectrum for the Cu(III) complex also requires the explicit inclusion of the π orbitals in the active space. These interactions are rather common in molecular spin qubit motifs and may play an important role in spin-decoherence processes. Our results may lend insight into future studies of the orbital interactions and electron delocalization of similar complexes.

Tibetan birds lay larger but fewer eggs in a clutch.

How do offspring size and number vary along elevational gradients? This is a striking but rarely addressed question in life-history evolution. Here we comparatively explore it using phylogenetically paired passerine birds of lowland China vs. the Tibetan plateau spanning an elevational range of 18-4500 m. Toward the Tibetan plateau, egg size increased, clutch size decreased and total clutch volume (= clutch size × egg size) did not change, when accounting for major confounding factors. Larger eggs and smaller clutches can be a response to harsh abiotic conditions at higher elevations and the corresponding reduction in food resources required for raising young, respectively. There was a negative correlation between egg size and clutch size after controlling for elevation effect on either trait, suggesting that the trade-off contributed to the expression of these two traits across elevations, given the lack of an elevational trend in total clutch volume. Tibetan birds had a shorter breeding season, prolonged incubation and nestling period than their lowland counterparts. While fewer clutches over the short breeding season may facilitate the increase in egg size, the concentration of annual reproductive investment did not seem to act on clutch size; despite the smaller clutches, hard environments may impose greater costs of parental care on Tibetan birds. The current research provides insight into the evolution of avian life histories across elevations.

Comparative efficacy of traditional conservative treatment and CT-guided local chemotherapy for mild spinal tuberculosis.

BACKGROUND: There are considerable differences in the treatment strategy for spinal tuberculosis, including conservative or surgical procedures. Conservative treatment is always suitable for most patients. This study aimed to compare the clinical efficacy of traditional conservative treatment with CT-guided local chemotherapy strategy of mild spinal tuberculosis. METHODS: This research retrospectively analysed 120 patients with spinal tuberculosis between January 2005 and January 2016 according to the diagnostic criteria of mild spinal tuberculosis. In total, 89 patients underwent traditional conservative treatment, 31 underwent CT-guided local chemotherapy. Clinical outcome, laboratory indexes, and radiological results were analysed to provide a clinical basis for the choice of mild spinal tuberculosis treatment. RESULTS: All cases achieved a clinical cure with 24 to 50 months followed up. Cobb angle of the two groups spinal tuberculosis segments was 6.25 ± 3.1100B0, 5.69 ± 2.5800B0 before treatment and 12.36 ± 6.3100B0, 14.87 ± 7.2600B0 after treatment, respectively. The VAS scores were significantly decreased post-treatment. At the 1 month follow-up, the VAS scores and erythrocyte sedimentation rate (ESR) were significantly differences between the two groups. The efficacy in the CT-guided local chemotherapy (Group B) was better than the traditional conservative treatment (Group A). But from the 3 months follow-up to the last follow-up, the VAS scores and ESR was no significant differences between the two groups and the average ESR decreased to normal. There was no evident kyphosis, symptoms or neurological deficits at the final follow-up. The paravertebral abscesses had disappeared, with no significant progression of local kyphosis, significant absorption and clear lesion edges, pain relief and normal ESR in the two groups. CONCLUSIONS: For mild spinal tuberculosis, traditional conservative treatment can achieve satisfactory results. The strategy combined with CT-guided local chemotherapy treatment is minimally invasive, beneficial for the drainage of paravertebral abscesses and pain relief.

Functional Characterization of Flavanone 3-Hydroxylase (F3H) and Its Role in Anthocyanin and Flavonoid Biosynthesis in Mulberry.

Mulberry (Morus spp., Moraceae) is an important economic crop plant and is rich in flavonoids and anthocyanidins in ripe fruits. Anthocyanins are glycosides of anthocyanidins. Flavanone 3-hydroxylase (F3H) catalyzes the conversion of naringenin into dihydroflavonols and is responsible for the biosynthesis of flavonols and anthocyanidins. In this study, MazsF3H was cloned and characterized from Morus atropurpurea var. Zhongshen 1. Conserved motif analysis based on alignment and phylogenetic analysis indicated that MazsF3H belonged to 2-oxoglutarate-dependent dioxygenase and MazsF3H clustered with F3Hs from other plants. MazsF3H was located in both nucleus and cytosol. MazsF3H was expressed in stems, leaves, stigmas and ovaries, except buds. F3H expression levels showed a positive and close relationship with anthocyanin content during the anthocyanin-rich fruit ripening process, while it showed a negative correlation with anthocyanin content in LvShenZi, whose fruits are white and would not experience anthocyanin accumulation during fruit ripening. Significantly different F3H expression levels were also found in different mulberry varieties that have quite different anthocyanin contents in ripe fruits. Overexpression MazsF3H in tobacco showed unexpected results, including decreased anthocyanin content. Down-regulation of F3H expression levels resulted in co-expression of the genes involved in anthocyanin biosynthesis and a significant decrease in anthocyanin content, but the change in total flavonoid content was subtle. Our results indicated that F3H may play quite different roles in different varieties that have quite different fruit colors. In addition, possible complex regulation of flavonoid biosynthesis should be further explored in some of the featured plant species.

Utilizing Plackett-Burman design and response surface analysis to optimize ultrasonic cleaning of pesticide residues from rape.

BACKGROUND: Pesticide residues in fruits and vegetables threaten food safety. Cleaning before eating is a usual way to remove pesticide residues, so it is very important to find the most efficient cleaning conditions for public health. However, many previous cleaning studies only focused on a single variable which required a large amount of time manpower and material resources. Plackett-Burman design (PBD) and response surface methodology can avoid the earlier-mentioned problems and have potential in studying the influence and interaction of multiple factors. In this study, the effect of five factors on the removal of triadimefon and boscalid from rape by ultrasonic washing was evaluated through PBD: pH of water, ultrasonic cleaning time, water temperature, initial residual concentration and volume of water. RESULTS: Temperature had a significant effect on the rate of triadimefon removal while the other four factors impacted boscalid removal greatly. A higher temperature was better for the removal rate of triadimefon. Under alkaline environment, when initial residual concentration and cleaning time increased with decreasing water volume, the removal rate of boscalid increased. Furthermore, the interactions among factors were obtained. The regression coefficients of fitting equations about triadimefon and boscalid were 0.9657 and 0.9738, respectively. CONCLUSION: Changing pH of water, cleaning time, water volume and temperature during the washing process of rape through PBD designed experiments represents a valid strategy for improving the removal rate of two pesticides residue. This study provides a reference for ultrasonic cleaning conditions by a sink dishwasher, which has a positive effect on food safety. © 2021 Society of Chemical Industry.

Quercetin suppresses pancreatic ductal adenocarcinoma progression via inhibition of SHH and TGF-ß/Smad signaling pathways.

Pancreatic ductal adenocarcinoma (PDA) is an aggressive type of malignant tumor with a poor prognosis and high mortality. Aberrant activation of hedgehog signaling plays a crucial role in the maintenance and progression of PDA. Here, we report that the dietary bioflavonoid quercetin has therapeutic potential for PDA by targeting sonic hedgehog (SHH) signaling. The effects of quercetin on the proliferation, apoptosis, migration, and invasion of pancreatic cancer cells (PCCs) and tumor growth and metastasis in PDA xenograft mouse models were evaluated. Additionally, SHH signaling activity was determined. Quercetin significantly inhibited PCC proliferation by downregulating c-Myc expression. In addition, quercetin suppressed epithelial-mesenchymal transition (EMT) by reducing TGF-ß1 level, which resulted in inhibition of PCC migration and invasion. Moreover, quercetin induced PCC apoptosis through mitochondrial and death receptor pathways. In nude mouse models, PDA growth and metastasis were reduced by quercetin treatment. Mechanically, quercetin exerts its therapeutic effects on PDA by decreasing SHH activity. Interestingly, quercetin-induced SHH inactivation is mainly dependent on Gli2, but not Gli1. Enhance SHH activity by recombinant Shh protein abolished the quercetin-mediated inhibition of PCC proliferation, migration, and invasion. Furthermore, Shh activated TGF-ß1/Smad2/3 signaling and promoted EMT by inducing the expression of Zeb2 and Snail1 that eventually resulted in a partial reversal of quercetin-mediated inhibition of PCC migration and invasion. We conclude that quercetin inhibited the growth, migration, and invasion and induced apoptosis of PCCs by antagonizing SHH and TGF-ß/Smad signaling pathways. Thus, quercetin may be a potential candidate for PDA treatment.

17-Hydroxybrevianamide N and Its N1-Methyl Derivative, Quinazolinones from a Soft-Coral-Derived Aspergillus sp. Fungus: 13S Enantiomers as the True Natural Products.

Under the guidance of MS/MS-based molecular networking and HPLC-UV, two new alkaloid racemates, (±)-17-hydroxybrevianamide N (1) and (±)-N1-methyl-17-hydroxybrevianamide N (2), featuring a rare o-hydroxyphenylalanine residue and an imide subunit, were isolated from a soft-coral-derived Aspergillus sp. fungus. The true natural products (+)-1 and (+)-2 were further monitored and obtained from the freshly prepared EtOAc extracts, while (-)-1 and (-)-2 are artifacts generated during extraction and purification processes. Simultaneously, the structures including absolute configurations of (+)-13S-1, (-)-13R-1, (+)-13S-2, and (-)-13R-2 were elucidated on the basis of comprehensive spectroscopic analysis, ECD calculations, and X-ray diffraction data. Interestingly, basic solution promotes the racemization of (+)-1 and (-)-1, whereas acidic solution suppresses the transformation. The current research was concerned with the true natural products and their artifacts, providing critical insight into the isolation and identification of natural products.

First Report of Powdery Mildew Caused by Podosphaera fusca on Helianthus tuberosus in China.

Helianthus tuberosus L. (Jerusalem artichoke) is an herbaceous perennial plant in the Asteraceae that is native to North America but introduced to China in the 17th century. The tubers of H. tuberosus are used as a vegetable, for the pharmaceutical production of inulin and as a source of ethanol biofuel, several B vitamins and minerals。From June to September 2009, severe powdery mildew infection was observed on H. tuberosus in a vegetable garden at Shangqiu Normal University, Shangqiu, China. Approximately 60% of leaves on individual plants were symptomatic, and almost 70% of the plants were infected. Initially, discrete powdery mildew colonies appeared on the upper surface of the leaves and on stems of the plants. Later, mycelial growth was amphigenous, thick, forming irregular white patches, covering the whole leaf surface. Eventually, leaves turned yellow, withered, and abscissed. Microscopic observations showed that conidia on infected leaves were ellipsoid-ovoid to barrel-shaped, with distinct fibrosin bodies visible in their cytoplasm, measuring 28 to 38 × 15 to 22 µm (n = 40). Conidiophores were unbranched, straight, 80 to 210 × 8 to 14 µm (n = 40) in size, and produced two to six immature conidia in chains with intercellular diaphragms. Foot cells of conidiophores were cylindrical and 45 to 65 µm × 8 to 14 µm (n = 40), with slight constrictions at basal septa, and followed by one to three short cells. Fungal hyphae were septate, branched, and flexuous to straight and 5 to 8 µm wide with indistinct to slightly nipple-shaped appressoria. These structures are typical of the genus Podosphaera, although chasmothecia were not observed. The sequence of ITS1-5.8s-ITS2 region of rDNA were amplified from conidia collected from infected leaves with universal primers ITS1F and ITS4 (White et al. 1990), sequenced and analyzed using the BLASTn search of GenBank. Amplicons were 603 bp (GQ927254) and exhibited 99.83% sequence identity with sequence of P. fusca from Cucurbita pepo (KJ698669) in Italy (Pirondi et al. 2015). The fungal species was identified as P. fusca (synonym P. xanthii ) by morphological characteristics and molecular analysis (Braun and Takamatsu 2000; Braun and Cook 2012). Pathogenicity tests were conducted by gently pressing the infected leaves onto leaves of six healthy H. tuberosus plants while six noninoculated plants served as controls. Plants were maintained in a greenhouse at 25 ± 2°C. Eight days after inoculation, symptoms similar to those observed under natural conditions developed on the inoculated leaves of H. tuberosus plants, whereas the control plants remained symptomless. The fungus on inoculated leaves was morphologically identical to that first observed in the field. P. fusca parasitizes a large number of asteraceous species including Euryops pectinatus (Saenz et al. 2000), Coreopsis lanceolata (Garibaldi et al. 2007), Cosmos caudatus (Siddiqui et al. 2011), Herba eupatorii (Ding et al. 2013) and etc. Powdery mildew caused by P. fusca has been reported on H. tuberosus in Russia (Farr and Rossman 2019). Golovinomyces ambrosiae was previously recorded on H. tuberosus in China (Huang et al. 2017; Radisek et al. 2018). This is the first report to our knowledge of powdery mildew P. fusca on H. tuberosus in China. It could cause significant yield losses and become a threat to production of H. tuberosus .

Precision Landing Test and Simulation of the Agricultural UAV on Apron.

Unmanned aerial vehicle (UAV) has been used to assist agricultural production. Precision landing control of UAV is critical for application of it in some specific areas such as greenhouses or livestock/poultry houses. For controlling UAV landing on a fixed or mobile apron/platform accurately, this study proposed an automatic method and tested it under three scenarios: (1) UAV landing at high operating altitude based on the GPS signal of the mobile apron; (2) UAV landing at low operating altitude based on the image recognition on the mobile apron; and (3) UAV landing progress control based on the fixed landing device and image detection to achieve a stable landing action. To verify the effectiveness of the proposed control method, apron at both stationary and mobile (e.g., 3 km/h moving speed) statuses were tested. Besides, a simulation was conducted for the UAV landing on a fixed apron by using a commercial poultry house as a model (135 L × 15 W × 3 H m). Results show that the average landing errors in high altitude and low altitude can be controlled within 6.78 cm and 13.29 cm, respectively. For the poultry house simulation, the landing errors were 6.22 ± 2.59 cm, 6.79 ± 3.26 cm, and 7.14 ± 2.41cm at the running speed of 2 km/h, 3 km/h, and 4 km/h, respectively. This study provides the basis for applying the UAV in agricultural facilities such as poultry or animal houses where requires a stricter landing control than open fields.

A Machine Vision-Based Method for Monitoring Broiler Chicken Floor Distribution.

The proper spatial distribution of chickens is an indication of a healthy flock. Routine inspections of broiler chicken floor distribution are done manually in commercial grow-out houses every day, which is labor intensive and time consuming. This task requires an efficient and automatic system that can monitor the chicken's floor distributions. In the current study, a machine vision-based method was developed and tested in an experimental broiler house. For the new method to recognize bird distribution in the images, the pen floor was virtually defined/divided into drinking, feeding, and rest/exercise zones. As broiler chickens grew, the images collected each day were analyzed separately to avoid biases caused by changes of body weight/size over time. About 7000 chicken areas/profiles were extracted from images collected from 18 to 35 days of age to build a BP neural network model for floor distribution analysis, and another 200 images were used to validate the model. The results showed that the identification accuracies of bird distribution in the drinking and feeding zones were 0.9419 and 0.9544, respectively. The correlation coefficient (R), mean square error (MSE), and mean absolute error (MAE) of the BP model were 0.996, 0.038, and 0.178, respectively, in our analysis of broiler distribution. Missed detections were mainly caused by interference with the equipment (e.g., the feeder hanging chain and water line); studies are ongoing to address these issues. This study provides the basis for devising a real-time evaluation tool to detect broiler chicken floor distribution and behavior in commercial facilities.

Aquaporins, evaporative water loss and thermoregulation in heat-acclimated Mongolian gerbils (Meriones unguiculatus).

Evaporative water loss is an essential strategy to maintain stable body temperature in heat-exposed rodents. However, the thermoregulatory role and adjustment of evaporative heat loss capacity is unclear during prolonged heat exposure. Here, we studied the role of evaporative water loss in thermoregulation in Mongolian gerbils during heat acclimation. After 3 weeks of heat acclimation, gerbils exhibited a lower body temperature than the controls, and no difference in evaporative losses of water from the lung or saliva spreading compared with the controls. Heat acclimation did not alter the expression of aquaporin-1 and aquaporin-5 in the lungs and the expression of aquaporin-5 in the salivary glands. The expression of aquaporin-2 in the kidneys was kept stable, while the expression of aquaporin-1 in the kidneys was down-regulated. In addition, resting metabolic rate and non-shivering thermogenesis of heat-acclimated gerbils were reduced to 51% and 55% of the control group, respectively. Taken together, heat-acclimated Mongolian gerbils can reduce the metabolic thermogenesis without enhancing the evaporative water loss capacity for thermoregulation.

Residue behavior and removal of iprodione in garlic, green garlic, and garlic shoot.

BACKGROUND: Iprodione is considered to be an endocrine-disturbing pesticide, which could harm consumers. The garlic crop has three edible parts: the garlic, the green garlic, and the garlic shoot, which correspond to different stages of its growth. In this study, iprodione residue dissipation and distribution in these three edible parts were investigated, and dietary risk was evaluated. RESULTS: Iprodione residues were present in these samples in the following order: green garlic > garlic shoot > > garlic. The dissipation of iprodione in green garlic was slow with a half-life of 5.82-19.25 days. A very high RQchronic value of 207.35-407.30% suggested that the residual iprodione in green garlic had an unacceptable level of risk. Iprodione residue was significantly eliminated (59-90%) by an alkaline solution. The order for removing iprodione by soaking was the alkaline solutions (0.5% and 2% NaHCO3 ) > the acidic solutions (5% and 10% of vinegar) ≈ the neutral solutions (the 1% and 2% of table salt) > tap water. Processing factors (PFs) were <1, indicating that processing could decrease the iprodione residue level. CONCLUSION: This work could contribute to establishing maximum residue limits (MRLs) for iprodione in garlic, green garlic, and garlic shoots, and could provide guidance on the safe and appropriate use of iprodione in the garlic crop. © 2020 Society of Chemical Industry.

The DNA methylation profile of non-coding RNAs improves prognosis prediction for pancreatic adenocarcinoma.

BACKGROUND: Compelling lines of evidence indicate that DNA methylation of non-coding RNAs (ncRNAs) plays critical roles in various tumour progression. In addition, the differential methylation of ncRNAs can predict prognosis of patients. However, little is known about the clear relationship between DNA methylation profile of ncRNAs and the prognosis of pancreatic adenocarcinoma (PAC) patients. METHODS: The data of DNA methylation, RNA-seq, miRNA-seq and clinical features of PAC patients were collected from TCGA database. The DNA methylation profile was obtained using the Infinium HumanMethylation450 BeadChip array. LASSO regression was performed to construct two methylation-based classifiers. The risk score of methylation-based classifiers was calculated for each patient, and the accuracy of the classifiers in predicting overall survival (OS) was examined by ROC curve analysis. In addition, Cox regression models were utilized to assess whether clinical variables and the classifiers were independent prognostic factors for OS. The targets of miRNA and the genes co-expressed with lncRNA were identified with DIANA microT-CDS and the Multi-Experiment Matrix (MEM), respectively. Moreover, DAVID Bioinformatics Resources were applied to analyse the functional enrichment of these targets and co-expressed genes. RESULTS: A total of 4004 CpG sites of miRNA and 11,259 CpG sites of lncRNA were screened. Among these CpG sites, 8 CpG sites of miRNA and 7 CpG sites of lncRNA were found with regression coefficients. By multiplying the sum of methylation degrees of the selected CpGs with these coefficients, two methylation-based classifiers were constructed. The classifiers have shown good performance in predicting the survival rate of PAC patients at varying follow-up times. Interestingly, both of these two classifiers were predominant and independent factors for OS. Furthermore, functional enrichment analysis demonstrated that aberrantly methylated miRNAs and lncRNAs are related to calcium ion transmembrane transport and MAPK, Ras and calcium signalling pathways. CONCLUSION: In the present study, we identified two methylation-based classifiers of ncRNA associated with OS in PAC patients through a comprehensive analysis of miRNA and lncRNA profiles. We are the first group to demonstrate a relationship between the aberrant DNA methylation of ncRNAs and the prognosis of PAC, and this relationship would contribute to individualized PAC therapy.

Epithelial and interstitial Notch1 activity contributes to the myofibroblastic phenotype and fibrosis.

BACKGROUND: Notch1 signalling is a stem-cell-related pathway that is essential for embryonic development, tissue regeneration and organogenesis. However, the role of Notch1 in the formation of myofibroblasts and fibrosis in kidneys following injury remains unknown. METHODS: The activity of Notch1 signalling was evaluated in fibrotic kidneys in CKD patients and in ureteral obstructive models in vivo and in cultured fibroblasts and TECs in vitro. In addition, the crosstalk of Notch1 with TGF-ß1/Smad2/3 signalling was also investigated. RESULTS: Notch1 activity was elevated in fibrotic kidneys of rat models and patients with chronic kidney disease (CKD). Further study revealed that epithelial and interstitial Notch1 activity correlated with an α-SMA-positive myofibroblastic phenotype. In vitro, injury stimulated epithelial Notch1 activation and epithelial-mesenchymal transition (EMT), resulting in matrix deposition in tubular epithelial cells (TECs). Additionally, interstitial Notch1 activation in association with fibroblast-myofibroblast differentiation (FMD) in fibroblasts mediated a myofibroblastic phenotype. These TGF-ß1/Smad2/3-dependent phenotypic transitions were abolished by Notch1 knockdown or a specific antagonist, DAPT, and were exacerbated by Notch1 overexpression or an activator Jagged-1-Fc chimaera protein. Interestingly, as a major driving force behind the EMT and FMD, TGF-ß1, also induced epithelial and interstitial Notch1 activity, indicating that TGF-ß1 may engage in crosstalk with Notch1 signalling to trigger fibrogenesis. CONCLUSION: These findings suggest that epithelial and interstitial Notch1 activation in kidneys following injury contributes to the myofibroblastic phenotype and fibrosis through the EMT in TECs and to the FMD in fibroblasts by targeting downstream TGF-ß1/Smad2/3 signalling.

Toward facile broadband photodetectors based on self-assembled ZnO nanobridge/rubrene heterointerface.

ZnO nanowire photodetectors have attracted much attention due to their excellent optoelectronic performance. However, operating speed remains a challenge, and scalability is also impeded by uncontrolled transfer methods and sophisticated fabrication process. In this paper, we have fabricated an excellent ZnO nanobridge ultraviolet photodetector array by using a simple one-step method. The faster photoresponse speed and a broader response wavelength (from UV to visible range) have been achieved by constructing a type-II ZnO/rubrene heterointerface. Performance enhancement is believed to arise from the well-matching band alignment and highly efficient separation of photogenerated electron-hole pairs at the heterointerface. Our strategy provides a simple and promising route to develop cost-effective and highly sensitive UV-vis photodetectors.

Brown adipose tissue plays thermoregulatory role within the thermoneutral zone in Mongolian gerbils (Meriones unguiculatus).

Brown adipose tissue (BAT) plays an important role in thermoregulation and many metabolic processes in small mammals, especially in cold adaptation. However, in warm adaptation, ambient temperature cannot directly activate BAT by sympathetic nervous system. Mongolian gerbils exhibit a wider thermoneutral zone (26.5-38.9 °C). We hypothesized that BAT atrophied near the lower critical temperature and further atrophied near the upper critical temperature. Male gerbils were acclimated to 23 °C, 27 °C or 37 °C, respectively, for 3 weeks. Results showed that regulatory non-shivering thermogenesis did not change in gerbils acclimated to 27 °C compared with 23 °C group, whereas it was reduced by 43.5% in gerbils acclimated to 37 °C. Bigger lipid droplet in BAT was observed in gerbils acclimated to 27 °C and 37 °C compared with 23 °C group, while the expression of uncoupling protein 1 and tyrosine hydroxylase was only reduced in gerbils acclimated to 37 °C. Further, thermoneutral acclimation did not change BAT thermogenesis by down-regulation of peroxisome proliferator-activated receptor gamma coactivator-1α, PR domain containing 16, peroxisome proliferator-activated receptor-α or peroxisome proliferator activated receptor-γ gene expression in BAT. In addition, body temperature was reduced in gerbils acclimated to 37 °C compared with 23 °C group, which was associated with a decreased resting metabolic rate and regulatory non-shivering thermogenesis. In conclusion, BAT does not atrophy near the lower critical temperature, whereas it atrophies near the upper critical temperature, suggesting that BAT may play thermoregulatory role within the TNZ in Mongolian gerbils.

Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin mediated hippocampal neuroapoptosis in aged rats.

BACKGROUND: Calcineurin (CaN) having a high expression in hippocampal neurons is closely related to apoptosis. Pretreatment with nimodipine can lower the apoptosis rate of hippocampal neuron to reduce the incidence of postoperative cognitive dysfunction (POCD). However, the relationship between cerebral protective effect of pretreatment with nimodipine and CaN is controversial in the literature. The aim of this study is to evaluate the relationship between neuroprotective effect of nimodipine and CaN on POCD in aged rats. METHODS: Ninety-six 18-month-old male Sprague-Dawley rats were randomly assigned into 4 groups (n = 24 each): control group (Group C), nimodipine group (Group N), surgery group (Group S) and nimodipine + surgery group (Group N + S). In Group N and Group N + S, nimodipine 1 mg/kg was intraperitoneally injected, while the equal volume of normal saline was given instead in Group S. 30 min later, Group N and Group C inhaled pure oxygen for 2 h, and Group S and N + S inhaled 3% sevoflurane for 2 h when exploratory laparotomy was performed. Morris water maze test was performed on 1 day before operation and 1, 3 and 7 days after operation. After the end of Morris water maze test at 1 day before operation and 1 and 7 days after operation, 8 rats were sacrificed, brains were removed and hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons, cytoplasmic calcium ([Ca2+]i), and hippocampal CaN and caspase-3 expression. RESULTS: Compared with the 1st day before operation, the escape latency, apoptosis rate, [Ca2+]i, expression of CaN and caspase-3 increased significantly, but the frequency of crossing the original platform decreased dramatically in Group S and N + S(P<0.05). In addition, the escape latency, apoptosis rate, [Ca2+]i, and expression of CaN and caspase-3 decreased markedly, but the frequency of crossing the original platform increased significantly in Group N + S as compared with Group S (P<0.05). CONCLUSIONS: Pretreatment with nimodipine reduces the incidence of POCD by decreasing CaN mediated hippocampal neuroapoptosis in aged rats.