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Background and aim Head and neck cancer patients are vulnerable to various psychological complications due to the effects of both cancer itself and cancer treatment on patients’ appearance and physical well-being. Nevertheless, few data have been obtained on effective psychosocial interventions that could protect this group of cancer patients’ psychological well-being. Therefore, this three-armed, parallel-group, double-blind, randomized control trial (RCT) aims to evaluate and compare the effects of acceptance and commitment therapy (ACT) and mindfulness-based stress reduction (MBSR) on positive psychology (such as posttraumatic growth [PTG], hope, and optimism), quality of life (QoL), and psychological complications (depression, anxiety, and experiential avoidance) among newly diagnosed head and neck cancer patients. Methods and analysis This RCT will target newly diagnosed head and neck cancer patients who have been treated only with surgery or who have not yet received any treatment. In total, 120 patients who meet all of the study’s inclusion criteria and none of its exclusion criteria will be randomly assigned into three groups—an ACT group, an MBSR group, and a treatment-as-usual control group—at a 1:1:1 allocation ratio. Participants in the two intervention groups (the ACT and MBSR groups) will undergo an eight-week group intervention program. During this program, each intervention will comprise eight modules based on ACT and MBSR, respectively. Outcome assessments will be performed across a three-point timeline, including before the intervention (t0), immediately after the psychosocial intervention at eight weeks (t1), and six months after the intervention (t2). The primary outcome that will be assessed during this RCT is PTG. Meanwhile, the secondary outcomes that will be evaluated in this study are such as QoL, hope, optimism, depression, anxiety, and experiential avoidance. Trial registration number NCT04800419 (ClinicalTrials.gov). Registered on March 16, 2021.

Drug-drug interaction (DDI) prediction has received considerable attention from industry and academia. Most existing methods predict DDIs from drug attributes or relationships with neighbors, which does not guarantee that informative drug embeddings for prediction will be obtained. To address this limitation, we propose a multitype drug interaction prediction method based on the deep fusion of drug features and topological relationships, abbreviated DM-DDI. The proposed method adopts a deep fusion strategy to combine drug features and topologies to learn representative drug embeddings for DDI prediction. Specifically, a deep neural network model is first used on the drug feature matrix to extract feature information, while a graph convolutional network model is employed to capture structural information from the adjacency matrix. Then, we adopt delivery operations that allow the two models to exchange information between layers, as well as an attention mechanism for a weighted fusion of the two learned embeddings before the output layer. Finally, the unified drug embeddings for the downstream task are obtained. We conducted extensive experiments on real-world datasets, the experimental results demonstrated that DM-DDI achieved more accurate prediction results than state-of-the-art baselines. Furthermore, in two tasks that are more similar to real-world scenarios, DM-DDI outperformed other prediction methods for unknown drugs.

Resource pulses are a common event in agro-ecosystems. A pot experiment was conducted to assess the effects of nitrogen (N) pulses and competition on the growth of an invasive weed, Amaranthus retroflexus, and a native crop, Glycine max. A. retroflexus and G. max were planted in pure culture with two individuals of one species in each pot and in mixed culture with one A. retroflexus and one G. max individual and subjected to three N pulse treatments. The N treatments included a no-peak treatment (NP) with N applied stably across the growing period, a single-peak treatment (SP) with only one N addition on the planting date, and a double-peak treatment (DP) with two N additions, one on the planting date and the other on the flowering date. N pulse significantly impacted biomass and height of the two species across the whole growing season. However, only the relative growth rate (RGR) of A. retroflexus was significantly affected by N pulse. A. retroflexus had the greatest biomass and height in the SP treatment at the first harvest, and in the DP treatment at the last three harvests. Pure culture G. max produced the greatest biomass in the DP treatment. In mixed culture, G. max produced the greatest biomass in the NP treatment. Biomass production of both species was significantly influenced by species combination, with higher biomass in mixed culture than in pure culture at most growth stages. Relative yield total (RYT) values were all greater than 1.0 at the last three harvests across the three N treatments, suggesting partial resource complementarity occurred when A. retroflexus is grown with G. max. These results indicate that A. retroflexus has a strong adaptive capacity to reduce interspecific competition, likely leading to its invasion of G. max cropland in China.

Endothelium lines the interior surface of vascular walls and regulates vascular tones. The endothelial cells sense and respond to chemical and mechanical stimuli in the circulation, and couple the stimulus signals to vascular smooth muscles, in which inward rectifier K+ currents (Kir) play an important role. Here we applied several complementary strategies to determine the Kir subunit in primarily cultured pulmonary arterial endothelial cells (PAECs) that was regulated by the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). In whole-cell voltage clamp, the Kir currents were sensitive to micromolar concentrations of extracellular Ba2+. In excised inside-out patches, an inward rectifier K+ current was observed with single-channel conductance 32.43 ± 0.45 pS and Popen 0.27 ± 0.04, which were consistent with known unitary conductance of Kir 2.1. RT-PCR and western blot results showed that expression of Kir 2.1 was significantly stronger than that of other subtypes in PAECs. Pharmacological analysis of the Kir currents demonstrated that insensitivity to intracellular ATP, pinacidil, glibenclamide, pH, GDP-β-S and choleratoxin suggested that currents weren't determined by KATP, Kir2.3, Kir2.4 and Kir3.x. The currents were strongly suppressed by exposure to CaMKII inhibitor W-7 and KN-62. The expression of Kir2.1 was inhibited by knocking down CaMKII. Consistently, vasodilation was suppressed by Ba2+, W-7 and KN-62 in isolated and perfused pulmonary arterial rings. These results suggest that the PAECs express an inward rectifier K+ current that is carried dominantly by Kir2.1, and this K+ channel appears to be targeted by CaMKII-dependent intracellular signaling systems.

High-density genetic linkage maps are necessary for precisely mapping quantitative trait loci (QTLs) controlling grain shape and size in wheat. By applying the Infinium iSelect 9K SNP assay, we have constructed a high-density genetic linkage map with 269 F 8 recombinant inbred lines (RILs) developed between a Chinese cornerstone wheat breeding parental line Yanda1817 and a high-yielding line Beinong6. The map contains 2431 SNPs and 128 SSR & EST-SSR markers in a total coverage of 3213.2 cM with an average interval of 1.26 cM per marker. Eighty-eight QTLs for thousand-grain weight (TGW), grain length (GL), grain width (GW) and grain thickness (GT) were detected in nine ecological environments (Beijing, Shijiazhuang and Kaifeng) during five years between 2010-2014 by inclusive composite interval mapping (ICIM) (LOD ≥ 2.5). Among which, 17 QTLs for TGW were mapped on chromosomes 1A, 1B, 2A, 2B, 3A, 3B, 3D, 4A, 4D, 5A, 5B and 6B with phenotypic variations ranging from 2.62% to 12.08%. Four stable QTLs for TGW could be detected in five and seven environments, respectively. Thirty-two QTLs for GL were mapped on chromosomes 1B, 1D, 2A, 2B, 2D, 3B, 3D, 4A, 4B, 4D, 5A, 5B, 6B, 7A and 7B, with phenotypic variations ranging from 2.62% to 44.39%. QGl.cau-2A.2 can be detected in all the environments with the largest phenotypic variations, indicating that it is a major and stable QTL. For GW, 12 QTLs were identified with phenotypic variations range from 3.69% to 12.30%. We found 27 QTLs for GT with phenotypic variations ranged from 2.55% to 36.42%. In particular, QTL QGt.cau-5A.1 with phenotypic variations of 6.82-23.59% was detected in all the nine environments. Moreover, pleiotropic effects were detected for several QTL loci responsible for grain shape and size that could serve as target regions for fine mapping and marker assisted selection in wheat breeding programs.

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most important wheat diseases in the world. In this study, a single dominant powdery mildew resistance gene MlIW172 was identified in the IW172 wild emmer accession and mapped to the distal region of chromosome arm 7AL (bin7AL-16-0.86-0.90) via molecular marker analysis. MlIW172 was closely linked with the RFLP probe Xpsr680-derived STS marker Xmag2185 and the EST markers BE405531 and BE637476. This suggested that MlIW172 might be allelic to the Pm1 locus or a new locus closely linked to Pm1. By screening genomic BAC library of durum wheat cv. Langdon and 7AL-specific BAC library of hexaploid wheat cv. Chinese Spring, and after analyzing genome scaffolds of Triticum urartu containing the marker sequences, additional markers were developed to construct a fine genetic linkage map on the MlIW172 locus region and to delineate the resistance gene within a 0.48 cM interval. Comparative genetics analyses using ESTs and RFLP probe sequences flanking the MlIW172 region against other grass species revealed a general co-linearity in this region with the orthologous genomic regions of rice chromosome 6, Brachypodium chromosome 1, and sorghum chromosome 10. However, orthologous resistance gene-like RGA sequences were only present in wheat and Brachypodium. The BAC contigs and sequence scaffolds that we have developed provide a framework for the physical mapping and map-based cloning of MlIW172.

The tumor suppressor PTEN is now understood to regulate cellular processes at the cytoplasmic membrane, where it classically regulates PI3K signaling, as well as in the nucleus where multiple roles in controlling cell cycle and genome stability have been elucidated. Mechanisms that dictate nuclear import and, less extensively, nuclear export of PTEN have been described, however the relevance of these processes in disease states, particularly cancer, remain largely unknown. We investigated the impact of acid ceramidase on the nuclear-cytoplasmic trafficking of PTEN. Immunohistochemical analysis of a human prostate tissue microarray revealed that nuclear PTEN was lost in patients whose tumors had elevated acid ceramidase. We found that acid ceramidase promotes a reduction in nuclear PTEN that is dependent upon sphingosine 1-phosphate-mediated activation of Akt. We were further able to show that sphingosine 1-phosphate promotes formation of a complex between Crm1 and PTEN, and that leptomycin B prevents acid ceramidase and sphingosine 1-phosphate mediated loss of nuclear PTEN, suggesting an active exportin-mediated event. To investigate whether the tumor promoting aspects of acid ceramidase in prostate cancer depend upon its ability to export PTEN from the nucleus, we used enforced nuclear expression of PTEN to study docetaxel-induced apoptosis and cell killing, proliferation, and xenoengraftment. Interestingly, while acid ceramidase was able to protect cells expressing wild type PTEN from docetaxel, promote proliferation and xenoengraftment, acid ceramidase had no impact in cells expressing PTEN-NLS. These findings suggest that acid ceramidase, through sphingosine 1-phosphate, promotes nuclear export of PTEN as a means of promoting tumor formation, cell proliferation, and resistance to therapy.

PURPOSE: Thickness changes of corneal sub-layers after phacoemulsification were investigated by spectral domain ultra-high resolution optical coherence tomography (UHR-OCT). METHODS: The corneas (n = 26) of 26 age-related cataract surgery patients were studied. UHR-OCT was used to evaluate the thickness of Descemet's Endothelium Complex (DEC), stroma, Bowman's layer, epithelium, and full cornea at the center (CCT) before, one day after, and one week after surgery. Non-contact specular microscopy measured CCT, endothelial cell density, and morphology. RESULTS: The DEC, stroma, Bowman's layer, and epithelium were visualized by UHR-OCT. Before surgery, the DEC in all cases appeared as a translucent space between two smooth opaque lines. One day after surgery, the posterior corneal surfaces in half of the eyes were wavy and irregular. Compared to the baseline, one day after surgery the thickness increases of the DEC, stroma, and CCT were 4.3 ± 2.6 µm, 25.5 ± 24.9 µm, and 32.1 ± 26.6 µm, respectively (P < 0.001). The morphology of the DEC and the CCT recovered to baseline one week after surgery (P > 0.05), but endothelial cell density was 8.7% less than at baseline. There were no significant changes in Bowman's layer and epithelium after the operation. The pre-operative DEC thickness was positively correlated with the decreased endothelial cell density at 1 day after surgery (r = 0.55, P = 0.003). CONCLUSIONS: The DEC showed edematous thickening and different degrees of morphological changes after phacoemulsification. The DEC deformation and corneal edema recovered by one week after surgery, which indicated recovery of endothelial function. UHR-OCT is a useful tool to evaluate function of the DEC after phacoemulsification. Pre-operative DEC thickness may indicate the integrity of the endothelium and could be used for predicting endothelial cell loss after phacoemulsification.

Large ex situ collections require approaches for sampling manageable amounts of germplasm for in-depth characterization and use. We present here a large diversity survey in sorghum with 3367 accessions and 41 reference nuclear SSR markers. Of 19 alleles on average per locus, the largest numbers of alleles were concentrated in central and eastern Africa. Cultivated sorghum appeared structured according to geographic regions and race within region. A total of 13 groups of variable size were distinguished. The peripheral groups in western Africa, southern Africa and eastern Asia were the most homogeneous and clearly differentiated. Except for Kafir, there was little correspondence between races and marker-based groups. Bicolor, Caudatum, Durra and Guinea types were each dispersed in three groups or more. Races should therefore better be referred to as morphotypes. Wild and weedy accessions were very diverse and scattered among cultivated samples, reinforcing the idea that large gene-flow exists between the different compartments. Our study provides an entry to global sorghum germplasm collections. Our reference marker kit can serve to aggregate additional studies and enhance international collaboration. We propose a core reference set in order to facilitate integrated phenotyping experiments towards refined functional understanding of sorghum diversity.

The treatment of human hepatocellular carcinoma (HCC) cell lines with (+)-isocorydine, which was isolated and purified from Papaveraceae sp. plants, resulted in a growth inhibitory effect caused by the induction of G2/M phase cell cycle arrest and apoptosis. We report that isocorydine induces G2/M phase arrest by increasing cyclin B1 and p-CDK1 expression levels, which was caused by decreasing the expression and inhibiting the activation of Cdc25C. The phosphorylation levels of Chk1 and Chk2 were increased after ICD treatment. Furthermore, G2/M arrest induced by ICD can be disrupted by Chk1 siRNA but not by Chk2 siRNA. In addition, isocorydine treatment led to a decrease in the percentage of CD133(+) PLC/PRF/5 cells. Interestingly, isocorydine treatment dramatically decreased the tumorigenicity of SMMC-7721 and Huh7 cells. These findings indicate that isocorydine might be a potential therapeutic drug for the chemotherapeutic treatment of HCC.

We investigated the expression status of periostin in breast cancer stem cells and its clinical implications in order to lay a foundation for managing breast cancer. CD44+/CD24-/line- tumor cells (CSC) from clinical specimens were sorted using flow cytometry. Periostin expression status was detected in CSC cells and 1,086 breast cancer specimens by Western blot and immunohistochemistry staining, with the CSC ratio determined by immunofluorescence double staining. The relationship between the periostin protein and clinico-pathological parameters and prognosis was subsequently determined. As a result, CSC cells are more likely to generate new tumors in mice and cell microspheres that are deficient in NOD/SCID compared to the control group. Periostin protein was expressed higher in CSC cells compared to the control cells and was found to be related to CSC chemotherapy resistance. Moreover, periostin expression was found to be related to the CSC ratio in 1,086 breast cancer specimens (P = 0.001). In total, 334 (30.76%) of the 1,086 breast cases showed high periostin expression. After universal and Spearman regression correlation analysis, periostin was observed to be related to histological grade, CSC ratio, lymph node metastasis, tumor size, and triple-negative breast cancer (all P

The presence of uniformly small collagen fibrils in tendon repair is believed to play a major role in suboptimal tendon healing. Collagen V is significantly elevated in healing tendons and plays an important role in fibrillogenesis. The objective of this study was to investigate the effect of a particular chain of collagen V on the fibrillogenesis of Sprague-Dawley rat tenocytes, as well as the efficacy of Col V siRNA engineered tenocytes for tendon tissue engineering. RNA interference gene therapy and a scaffold free tissue engineered tendon model were employed. The results showed that scaffold free tissue engineered tendon had tissue-specific tendon structure. Down regulation of collagen V α1 or α2 chains by siRNAs (Col5α1 siRNA, Col5α2 siRNA) had different effects on collagen I and decorin gene expressions. Col5α1 siRNA treated tenocytes had smaller collagen fibrils with abnormal morphology; while those Col5α2 siRNA treated tenocytes had the same morphology as normal tenocytes. Furthermore, it was found that tendons formed by coculture of Col5α1 siRNA treated tenocytes with normal tenocytes at a proper ratio had larger collagen fibrils and relative normal contour. Conclusively, it was demonstrated that Col V siRNA engineered tenocytes improved tendon tissue regeneration. And an optimal level of collagen V is vital in regulating collagen fibrillogenesis. This may provide a basis for future development of novel cellular- and molecular biology-based therapeutics for tendon diseases.

FOXP1, known as a Forkhead-box (FOX) family protein, plays an important role in human tumorigenesis. However, the function and molecular mechanism of FOXP1 in pancreatic cancer (PC) remain unclear. Here, we report that PC patients with FOXP1 overexpression had a higher survival rate compared to patients with low- FOXP1 expression. Additionally, high expression of FOXP1 can markedly inhibit the growth of pancreatic cancer in vivo and in vitro, whereas low expression of FOXP1 effectively promoted the tumorigenesis. Mechanistically, FOXP1 could directly bind the IRF1 promoter, which triggered the transcriptional activity of IRF1. Taken together, FOXP1 suppressed PC growth via IRF1-dependent manner, serving as a potential prognostic biomarker for patients with PC.

With the development of convolutional neural networks, impressive success has been achieved in remote sensing image super-resolution. However, the performance of super-resolution reconstruction is unsatisfactory due to the lack of details in remote sensing images when compared to natural images. Therefore, this paper presents a novel multiscale convolutional sparse coding network (MCSCN) to carry out the remote sensing images SR reconstruction with rich details. The MCSCN, which consists of a multiscale convolutional sparse coding module (MCSCM) with dictionary convolution units, can improve the extraction of high frequency features. We can obtain more plentiful feature information by combining multiple sizes of sparse features. Finally, a layer based on sub-pixel convolution that combines global and local features takes as the reconstruction block. The experimental results show that the MCSCN gains an advantage over several existing state-of-the-art methods in terms of peak signal-to-noise ratio and structural similarity.

An easier assessment model would be helpful for high-throughput screening of Aeromonas virulence. The previous study indicated the potential of Tetrahymena as a permissive model to examine virulence of Aeromonas hydrophila. Here our aim was to assess virulence of Aeromonas spp. using two model hosts, a zebrafish assay and Tetrahymena-Aeromonas co-culture, and to examine whether data from the Tetrahymena thermophila model reflects infections in the well-established animal model. First, virulence of 39 Aeromonas strains was assessed by determining the 50% lethal dose (LD50) in zebrafish. LD50) values ranging from 1.3x10² to 3.0x107 indicated that these strains represent a high to moderate degree of virulence and could be useful to assess virulence in the Tetrahymena model. In Tetrahymena-Aeromonas co-culture, we evaluated the virulence of Aeromonas by detecting relative survival of Aeromonas and Tetrahymena. An Aeromonas isolate was considered virulent when its relative survival was greater than 60%, while the Aeromonas isolate was considered avirulent if its relative survival was below 40%. When relative survival of T. thermophila was lower than 40% after co-culture with an Aeromonas isolate, the bacterial strain was regarded as virulent. In contrast, the strain was classified as avirulent if relative survival of T. thermophila was greater than 50%. Encouragingly, data from the 39 Aeromonas strains showed good correlation in zebrafish and Tetrahymena-Aeromonas co-culture models. The results provide sufficient data to demonstrate that Tetrahymena can be a comparable alternative to zebrafish for determining the virulence of Aeromonas isolates. [ABSTRACT FROM AUTHOR]

Background: The IL4, IL13, and IL4 receptor a chain (IL4RA) genes are candidate genes for atopic diseases. We hypothesized that the polymorphisms in these genes are associated with persistent allergic rhinitis (PER). Objective: To investigate the association of the potential functional polymorphisms in IL4, IL13, and IL4RA with PER induced by house dust mites in a Chinese population. Methods: Using the TaqMan method, we genotyped six single nucleotide polymorphisms (SNPs) including C-590T in IL4, C- 1055T and Arg130Gln in IL13, and Ile50Val, Ser478Pro and Gln551Arg in IL4RA, in a case-control study of 265 patients with PER and 275 healthy controls. Results: We found that the CT/CC genotypes in IL4 C-590T were associated with a significantly decreased risk of mitesensitized PER [adjusted odds ratio (OR) = 0.64, 95% confidence interval (CI) 0.45-0.92], compared to the TT genotype. Furthermore, PER patients with CT/CC genotypes had significantly lower serum levels of total IgE than those with TT genotype (P = 0.001). However, there was no significant association of the IL13 and IL4RA polymorphisms with mitesensitized PER (P>0.05). Conclusions: Our results suggest that the C-590T polymorphism in IL4 may contribute to the susceptibility to mitesensitized PER in a Chinese population. [ABSTRACT FROM AUTHOR]

Background: Prostatic oxidative stress (OS) is androgen-regulated and a key event in the development of prostate cancer (PC). Thus, reducing prostatic OS is an attractive target for PC prevention strategies. We sought to determine if the individual's prostatic OS status can be determined by examining the OS in surrogate androgen regulated tissues from the same host. Methodology/Principal Findings: Adult male rats were divided equally into three groups: (A-) underwent bilateral orchiectomy, (A+) received continuous testosterone supplementation or (C) were eugonadal. Serum testosterone, 8- hydroxy-2-deoxyguanosine (8-OHdG) and anti-oxidative capacity (AOC) were determined after 72 hrs and the prostate, salivary glands and the hair follicles' Dermal Papillary Cells (DPC) from each animal were harvested, embedded into tissue microarray and examined for the expression of 8-OHdG by immuno-staining. Multi-variate regression was used to analyze inter-individual differences in OS staining within each androgen group and if there was a correlation between serum testosterone, 8-OHdG or AOC and Prostatic OS in tissues of same host. At the group level, 8-OHdG staining intensity directly correlated with serum testosterone levels in all three target tissues (p>0.01, Mann-Whitney Test). Although different levels of prostatic OS were noted between rats with similar serum testosterone levels and similar systemic OS measurements (p<0.01), there were no intra-individual differences between the OS status of the prostate and DPC (p<0.05). Conclusions/Significance: The level of prostatic OS is correlated with the OS of hair follicles and salivary glands, but not systemic OS. Moreover, systemic AOC negatively correlates with both prostatic and hair follicle OS. This suggests that hair follicle and salivary gland OS can serve as surrogate markers for the efficiency of OS reduction. This has tremendous potential for the rational evaluation of patient response to prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Pertussis (whooping cough) caused by Bordetella pertussis (B.p), continues to be a serious public health threat. Vaccination is the most economical and effective strategy for preventing and controlling pertussis. However, few systematic investigations of actual human immune responses to pertussis vaccines have been performed. Therefore, we utilized a combination of two-dimensional electrophoresis (2-DE), immunoblotting, and mass spectrometry to reveal the entire antigenic proteome of whole-cell pertussis vaccine (WCV) targeted by the human immune system as a first step toward evaluating the repertoire of human humoral immune responses against WCV. Methodology/Principal Findings: Immunoproteomic profiling of total membrane enriched proteins and extracellular proteins of Chinese WCV strain 58003 identified a total of 30 immunoreactive proteins. Seven are known pertussis antigens including Pertactin, Serum resistance protein, chaperonin GroEL and two OMP porins. Sixteen have been documented to be immunogenic in other pathogens but not in B.p, and the immunogenicity of the last seven proteins was found for the first time. Furthermore, by comparison of the human and murine immunoproteomes of B.p, with the exception of four human immunoreactive proteins that were also reactive with mouse immune sera, a unique group of antigens including more than 20 novel immunoreactive proteins that uniquely reacted with human immune serum was confirmed. Conclusions/Significance: This study is the first time that the repertoire of human serum antibody responses against WCV was comprehensively investigated, and a small number of previously unidentified antigens of WCV were also found by means of the classic immunoproteomic strategy. Further research on these newly identified predominant antigens of B.p exclusively against humans will not only remarkably accelerate the development of diagnostic biomarkers and subunit vaccines but also provide detailed insight into human immunity mechanisms against WCV. In particular, this work highlights the heterogeneity of the B.p immunoreactivity patterns of the mouse model and the human host. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggested an association between diabetes and the risk of various geriatric conditions (i.e., cognitive impairment, dementia, depression, mobility impairment, disability, falls, and urinary incontinence). However, the magnitude and impact of diabetes on older adults have not been reviewed. Methodology/Principal Findings: MEDLINE and PSYCINFO databases were searched through November 2007 for published studies, supplemented by manual searches of bibliographies of key articles. Population-based, prospective cohort studies that reported risk of geriatric outcomes in relation to diabetes status at baseline were selected. Two authors independently extracted the data, including study population and follow-up duration, ascertainment of diabetes status at baseline, outcomes of interest and their ascertainment, adjusted covariates, measures of association, and brief results. Fifteen studies examined the association of DM with cognitive dysfunction. DM was associated with a faster decline in cognitive function among older adults. The pooled adjusted risk ratio (RR) for all dementia when persons with DM were compared to those without was 1.47 (95% CI, 1.25 to 1.73). Summary RRs for Alzheimer's disease and vascular dementia comparing persons with DM to those without were 1.39 (CI, 1.16 to 1.66) and 2.38 (CI, 1.79 to 3.18), respectively. Four of 5 studies found significant association of DM with faster mobility decline and incident disability. Two studies examined the association of diabetes with falls in older women. Both found statistically significant associations. Insulin users had higher RR for recurrent falls. One study for urinary incontinence in older women found statistically significant associations. Two studies for depression did not suggest that DM was an independent predictor of incident depression. Conclusions/Significance: Current evidence supports that DM is associated with increased risk for selected geriatric conditions. Clinicians should increase their awareness and provide appropriate care. Future research is required to elucidate the underlying pathological pathway. [ABSTRACT FROM AUTHOR]

PurposeCisplatin resistance is still a serious problem in the clinic. However, the underlying mechanism remains unknown. In our study, we investigated cisplatin resistance by using the cisplatin-resistant cell line HCT116R.MethodsThe HCT116 cell line, a colon cancer cell line, was purchased. Cell viability was determined using CCK-8 Assay Kit. The gene expression levels of MIR4435-2HG, Nrf2, and HO-1, and caspase activity were determined using qRT-PCR and Caspase 3 Assay Kit, respectively.ResultsIn this study, we found that the levels of the lncRNA MIR4435-2HG were dramatically increased in the cisplatin-resistant cell line HCT116R. Knockdown of MIR4435-2HG in HCT116R cells significantly restored the sensitivity to cisplatin, inhibited cell proliferation and promoted cell apoptosis. Furthermore, Nrf2 and HO-1 mRNA levels, as critical molecules in the oxidative stress pathway, were inhibited by siRNAs targeting MIR4435-2HG, suggesting that MIR4435-2HG-mediated cisplatin resistance occurs through the Nrf2/HO-1 pathway.ConclusionOur findings demonstrate that the lncRNA MIR4435-2HG is a main factor driving the cisplatin resistance of HCT116 cells.

The neurocognitive basis of the effect of long-term high altitude exposure on conflict control is unclear. Event related potentials (ERPs) were recorded in a flanker task to investigate the influence of high altitude on conflict control in the high-altitude group (who had lived at high altitude for three years but were born at low altitude) and the low-altitude group (living in low altitude only). Although altitude effect was not significant at the behavioral level, ERPs showed cognitive conflict modulation. The interaction between group and trial type was significant: P3 amplitude was greater in the low-altitude group than in the high-altitude group in the incongruent trial. This result suggests that long-term exposure to high altitude affects conflict control in the conflict-resolving stage, and that attentional resources are decreased to resist the conflict control in the high-altitude group.

Endothelial cells (ECs) lining the blood vessels serve a variety of functions and play a central role in the homeostasis of the circulatory system. Since the ductus arteriosus (DA) has different arterial characteristics from its connecting vessels, we hypothesized that ECs of the DA exhibited a unique gene profile involved in the regulation of DA-specific morphology and function. Using a fluorescence-activated cell sorter, we isolated ECs from pooled tissues from the DA or the descending aorta of Wistar rat fetuses at full-term of gestation (F group) or neonates 30 minutes after birth (N group). Using anti-CD31 and anti-CD45 antibodies as cell surface markers for ECs and hematopoietic derived cells, respectively, cDNAs from the CD31-positive and CD45-negative cells were hybridized to the Affymetrix GeneChip® Rat Gene 1.0 ST Array. Among 26,469 gene-level probe sets, 82 genes in the F group and 81 genes in the N group were expressed at higher levels in DA ECs than in aortic ECs (p2.0). In addition to well-known endothelium-enriched genes such as Tgfb2 and Vegfa, novel DA endothelium-dominant genes including Slc38a1, Capn6, and Lrat were discovered. Enrichment analysis using GeneGo MetaCore software showed that DA endothelium-related biological processes were involved in morphogenesis and development. We identified many overlapping genes in each process including neural crest-related genes (Hoxa1, Hoxa4, and Hand2, etc) and the second heart field-related genes (Tbx1, Isl1, and Fgf10, etc). Moreover, we found that regulation of epithelial-to-mesenchymal transition, cell adhesion, and retinol metabolism are the active pathways involved in the network via potential interactions with many of the identified genes to form DA-specific endothelia. In conclusion, the present study uncovered several significant differences of the transcriptional profile between the DA and aortic ECs. Newly identified DA endothelium-dominant genes may play an important role in DA-specific functional and morphologic characteristics.

Agaricus bisporus is widely consumed on the world market. The easy browning of mushroom surface is one of the most intuitive factors affecting consumer purchase. A certain cognition on browning mechanism has been made after years of research. At present, people slow down the browning of mushrooms mainly by improving preservation methods. In addition, breeding is also a reliable way. In the production practice, we have identified some browning-resistant varieties, and we selected a browning-resistant variety to compare with an ordinary variety to reveal the resistance mechanism. Using transcriptomics and metabolomics, the differences in gene expression and metabolite levels were revealed, respectively. The results showed that differentially expressed genes (DEGs) like AbPPO4, AbPPO3 and AbPPO2 were differently expressed and these DEGs were involved in many pathways related to browning. The expression of AbPPO expression play an important role in the browning of A. bisporus and multiple PPO family members are involved in the regulation of browning. However, the resistance to browning cannot be judged only by the expression level of AbPPOs. For metabolomics, most of the different metabolites were organic acids. These organic acids had a higher level in anti-browning (BT) than easy-browning varieties (BS), although the profile was very heterogeneous. On the contrary, the content of trehalose in BS was significantly higher than that in BT. Higher organic acids decreased pH and further inhibited PPO activity. In addition, the BS had a higher content of trehalose, which might play roles in maintaining PPO activity. The difference of browning resistance between BS and BT is mainly due to the differential regulation mechanism of PPO.

This is the first meta-analysis of the pooled prevalence of insomnia in the general population of China. A systematic literature search was conducted via the following databases: PubMed, PsycINFO, EMBASE and Chinese databases (China National Knowledge Interne (CNKI), WanFang Data and SinoMed). Statistical analyses were performed using the Comprehensive Meta-Analysis program. A total of 17 studies with 115,988 participants met the inclusion criteria for the analysis. The pooled prevalence of insomnia in China was 15.0% (95% Confidence interval [CI]: 12.1%-18.5%). No significant difference was found in the prevalence between genders or across time period. The pooled prevalence of insomnia in population with a mean age of 43.7 years and older (11.6%; 95% CI: 7.5%-17.6%) was significantly lower than in those with a mean age younger than 43.7 years (20.4%; 95% CI: 14.2%-28.2%). The prevalence of insomnia was significantly affected by the type of assessment tools (Q = 14.1, P = 0.001). The general population prevalence of insomnia in China is lower than those reported in Western countries but similar to those in Asian countries. Younger Chinese adults appear to suffer from more insomnia than older adults. TRIAL REGISTRATION:CRD 42016043620.

Previous genetic studies of Atlantic swordfish (Xiphias gladius L.) revealed significant differentiation among Mediterranean, North Atlantic and South Atlantic populations using both mitochondrial and nuclear DNA data. However, limitations in geographic sampling coverage, and the use of single loci, precluded an accurate placement of boundaries and of estimates of admixture. In this study, we present multilocus analyses of 26 single nucleotide polymorphisms (SNPs) within 10 nuclear genes to estimate population differentiation and admixture based on the characterization of 774 individuals representing North Atlantic, South Atlantic, and Mediterranean swordfish populations. Pairwise FST values, AMOVA, PCoA, and Bayesian individual assignments support the differentiation of swordfish inhabiting these three basins, but not the current placement of the boundaries that separate them. Specifically, the range of the South Atlantic population extends beyond 5°N management boundary to 20°N-25°N from 45°W. Likewise the Mediterranean population extends beyond the current management boundary at the Strait of Gibraltar to approximately 10°W. Further, admixture zones, characterized by asymmetric contributions of adjacent populations within samples, are confined to the Northeast Atlantic. While South Atlantic and Mediterranean migrants were identified within these Northeast Atlantic admixture zones no North Atlantic migrants were identified respectively in these two neighboring basins. Owing to both, the characterization of larger number of loci and a more ample spatial sampling coverage, it was possible to provide a finer resolution of the boundaries separating Atlantic swordfish populations than previous studies. Finally, the patterns of population structure and admixture are discussed in the light of the reproductive biology, the known patterns of dispersal, and oceanographic features that may act as barriers to gene flow to Atlantic swordfish.

As recent studies have described an association between vitamin D and allergic rhinitis, we hypothesized that vitamin D pathway-related genes may be candidate genes for susceptibility to allergic rhinitis. Thus, we sought to evaluate whether polymorphisms in the vitamin D receptor (VDR) and CYP2R1 genes are associated with mite-sensitized persistent allergic rhinitis (PER) in a Han Chinese population. A hospital-based case-control study consisting of 519 patients with mite-sensitized PER and 447 healthy controls was conducted. Five single nucleotide polymorphisms (SNPs) in VDR and CYP2R1 were selected for genotyping. The genotype and allele frequencies of rs9729, rs2228570, rs1544410, and rs731236 in VDR as well as rs2060793 in CYP2R1 were not significantly associated with susceptibility to mite-sensitized PER. After stratification analyses, however, both the CT and CT/TT genotypes of rs2228570 in VDR exhibited a significantly decreased risk (CT: adjusted odds ratio (OR)=0.58, 95% confidence intervals (CI)=0.37-0.91;adjusted OR=0.61, 95% CI=0.40-0.93) of mite-sensitized PER, while the AA genotype of rs2060793 in CYP2R1 exhibited a significantly increased risk (adjusted OR=1.85, 95% CI=1.03-3.34) of PER in the age subgroup of

BACKGROUND: The ADAM33 gene has been identified as a potentially important asthma candidate gene and polymorphisms in this gene have been shown to be associated with asthma and seasonal allergic rhinitis. OBJECTIVE: To assess whether the ADAM33 polymorphisms are associated with persistent allergic rhinitis (PER) due to house dust mites in a Chinese population. METHODS: In a hospital-based case-control study of 515 patients with mite-sensitized PER and 495 healthy controls, we genotyped seven single nucleotide polymorphisms (SNPs) in ADAM33. Serum levels of eosinophil cationic protein, total IgE and allergen-specific IgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae were measured by the ImmunoCAP assays. RESULTS: In the single-locus analysis, three polymorphisms, rs3918392 (F1), rs528557 (S2) and rs2787093, were significantly associated with mite-sensitized PER. SNP S2 was associated with significantly increased risk both of asthmatic and nonasthmatic mite-sensitized PER. In the combined genotypes analysis, individuals with 2-4 risk alleles had a significantly higher risk of mite-sensitized PER (adjusted OR = 1.99, 95% CI = 1.50-2.62) than those with 0-1 risk alleles. Haplotype-based association analysis revealed that the ACAGCCT haplotype might have potential to protect against mite-sensitized PER (adjusted OR = 0.67; 95% CI = 0.49-0.90). CONCLUSIONS: Polymorphisms in the ADAM33 gene may contribute to susceptibility of mite-sensitized PER in this Chinese population.

The SNF1/AMPK pathway has a central role in response to nutrient stress in yeast and mammals. Previous studies on SNF1 function in phytopathogenic fungi mostly focused on the catalytic subunit Snf1 and its contribution to the derepression of cell wall degrading enzymes (CWDEs). However, the MoSnf1 in Magnaporthe oryzae was reported not to be involved in CWDEs regulation. The mechanism how MoSnf1 functions as a virulence determinant remains unclear. In this report, we demonstrate that MoSnf1 retains the ability to respond to nutrient-free environment via its participation in peroxisomal maintenance and lipid metabolism. Observation of GFP-tagged peroxisomal targeting signal-1 (PTS1) revealed that the peroxisomes of ΔMosnf1 were enlarged in mycelia and tended to be degraded before conidial germination, leading to the sharp decline of peroxisomal amount during appressorial development, which might impart the mutant great retard in lipid droplets mobilization and degradation. Consequently, ΔMosnf1 exhibited inability to maintain normal appressorial cell wall porosity and turgor pressure, which are key players in epidermal infection process. Exogenous glucose could partially restore the appressorial function and virulence of ΔMosnf1. Toward a further understanding of SNF1 pathway, the β-subunit MoSip2, γ-subunit MoSnf4, and two putative Snf1-activating kinases, MoSak1 and MoTos3, were additionally identified and characterized. Here we show the null mutants ΔMosip2 and ΔMosnf4 performed multiple disorders as ΔMosnf1 did, suggesting the complex integrity is essential for M. oryzae SNF1 kinase function. And the upstream kinases, MoSak1 and MoTos3, play unequal roles in SNF1 activation with a clear preference to MoSak1 over MoTos3. Meanwhile, the mutant lacking both of them exhibited a severe phenotype comparable to ΔMosnf1, uncovering a cooperative relationship between MoSak1 and MoTos3. Taken together, our data indicate that the SNF1 pathway is required for fungal development and facilitates pathogenicity by its contribution to peroxisomal maintenance and lipid metabolism in M. oryzae.

Streptococcus agalactiae, long recognized as a mammalian pathogen, is an emerging concern with regard to fish. In this study, we used a mouse model and in vitro cell infection to evaluate the pathogenetic characteristics of S. agalactiae GD201008-001, isolated from tilapia in China. This bacterium was found to be highly virulent and capable of inducing brain damage by migrating into the brain by crossing the blood-brain barrier (BBB). The phagocytosis assays indicated that this bacterium could be internalized by murine macrophages and survive intracellularly for more than 24 h, inducing injury to macrophages. Further, selective capture of transcribed sequences (SCOTS) was used to investigate microbial gene expression associated with intracellular survival. This positive cDNA selection technique identified 60 distinct genes that could be characterized into 6 functional categories. More than 50% of the differentially expressed genes were involved in metabolic adaptation. Some genes have previously been described as associated with virulence in other bacteria, and four showed no significant similarities to any other previously described genes. This study constitutes the first step in further gene expression analyses that will lead to a better understanding of the molecular mechanisms used by S. agalactiae to survive in macrophages and to cross the BBB.

Streptococcussuis serotype 2 (SS 2) is an important zoonotic pathogen that has caused two major infectious outbreaks of streptococcal toxic shock syndrome (STSS) in China. A novel gene located in the 89K pathogenicity island (PAI) encoding a putative hemolysin-III-related protein (Hhly3) has been previously characterized. In this study, the SS2 deletion mutant of the exogenous gene hhly3 was constructed by homologous recombination. This protein was found to exhibit cytolytic activity, and hemolytic activity of the hhly3 gene knockout mutant (Δhhly3) was significantly lower than that in the wild-type strain ZY05719. In addition, qRT-PCR revealed that Hhly3 played an important role in the expression of the secreted hemolysin SLY, which may be the key reason for the decreased hemolytic activity. Consequently, compared with the WT strain, the infection and pathogenicity of Δhhly3 was also decreased, as evidenced by in vitro bacterial growth in whole blood and by the in vivo zebrafish test, suggesting that hhly3 is a novel exogenous hemolysis-related gene in SS2 strains.

Epstein-Barr virus (EBV) infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma.The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR) and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival.Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92-1.68]). In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL) (HR = 1.84, 95% CI: 1.02-3.34), but not with survival of patients with Hodgkin disease (HD) (HR = 1.03, 95% CI: 0.74-1.44). In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value.This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression.