FAP Expression Dynamics and Role in Silicosis: Insights from Epidemiological and Experimental Models.

Prolonged exposure to free silica leads to the development of silicosis, wherein activated fibroblasts play a pivotal role in its pathogenesis and progression. Fibroblast Activation Protein (FAP), as a biomarker for activated fibroblasts, its expression pattern and role in key aspects of silicosis pathogenesis remain unclear. This study elucidated the expression pattern and function of FAP through population-based epidemiological investigations, establishment of mouse models of silicosis, and in vitro cellular models. Results indicated a significant elevation of FAP in plasma from silicosis patients and lung tissues from mouse models of silicosis. In the cellular model, we observed a sharp increase in FAP expression early in the differentiation process, which remained high expression. Inhibition of FAP suppressed fibroblast differentiation, while overexpression of FAP produced the opposite effect. Moreover, fibroblast-derived FAP can alter the phenotype and function of neighboring macrophages. In summary, we revealed a high expression pattern of FAP in silicosis and its potential mechanistic role in fibrosis, suggesting FAP as a potential therapeutic target for silicosis.

PELE scores: pelvic X-ray landmark detection with pelvis extraction and enhancement.

PURPOSE: Pelvic X-ray (PXR) is widely utilized in clinical decision-making associated with the pelvis, the lower part of the trunk that supports and balances the trunk. In particular, PXR-based landmark detection facilitates downstream analysis and computer-assisted diagnosis and treatment of pelvic diseases. Although PXR has the advantages of low radiation and reduced cost compared to computed tomography (CT), it characterizes the 2D pelvis-tissue superposition of 3D structures, which may affect the accuracy of landmark detection in some cases. However, the superposition nature of PXR is implicitly handled by existing deep learning-based landmark detection methods, which mainly design the deep network structures for better detection performances. Explicit handling of the superposition nature of PXR is rarely done. METHODS: In this paper, we explicitly focus on the superposition of X-ray images. Specifically, we propose a pelvis extraction (PELE) module that consists of a decomposition network, a domain adaptation network, and an enhancement module, which utilizes 3D prior anatomical knowledge in CT to guide and well isolate the pelvis from PXR, thereby eliminating the influence of soft tissue for landmark detection. The extracted pelvis image, after enhancement, is then used for landmark detection. RESULTS: We conduct an extensive evaluation based on two public and one private dataset, totaling 850 PXRs. The experimental results show that the proposed PELE module significantly improves the accuracy of PXRs landmark detection and achieves state-of-the-art performances in several benchmark metrics. CONCLUSION: The design of PELE module can improve the accuracy of different pelvic landmark detection baselines, which we believe is obviously conducive to the positioning and inspection of clinical landmarks and critical structures, thus better serving downstream tasks. Our project has been open-sourced at https://github.com/ECNUACRush/PELEscores .

Comparison of the clinical efficacy of orthokeratology and 0.01% atropine for retardation of myopia progression in myopic children.

OBJECTIVE: To compare the clinical efficacy of orthokeratology (ortho-k) and 0.01% atropine for retardation of myopia progression in myopic children. METHODS: This was a retrospective cohort study. A total of 282 patients, aged 8-17 years, were enrolled, including 100 children treated with ortho-k, 84 with 0.01% atropine, and 98 with single-vision spectacles. During the follow-up of 1 year, ortho-k wearers were examined at 1 day, 1 week, 1 month, 3 months after treatment, and thereafter every 3 months, while the others were examined every 3 months by measurements of uncorrected vision, intraocular pressure, refractive power, slit-lamp microscopy, corneal topography, and the lens fitting when necessary. The axial length was measured every 6 months. RESULTS: Patients with ortho-k had stable uncorrected vision after 1 month of lens wear, all reaching 0 logMAR. The annual axial elongation was 0.23 ± 0.19 mm, 0.22 ± 0.20 mm, and 0.39 ± 0.27 mm in the ortho-k, atropine, and spectacle groups, respectively, with significant difference (F = 23.251, P = 0.000). The axial length was delayed to increase by 41.03% and 43.59% within a year in patients with ortho-k and atropine, respectively, as compared to patients with spectacles (F = 0.006, P = 0.936). The elongation was ≤ 0.3 mm in 69.0% and 66.7% of patients in the two groups, respectively, versus 38.8% in the spectacle group (χ2 = 17.251, P = 0.000). During the follow-up, the rate of corneal staining was 11.0% and 2.0% in the ortho-k and spectacle groups, respectively (χ2 = 8.076, P = 0.003). The use of atropine did not increase corneal staining, but the incidence of related photophobia was 4.8%. No other serious complications were observed. CONCLUSION: Ortho-k lenses and 0.01% atropine can achieve similar efficacy of myopia retardation, which was significantly better than that obtained with single-vision spectacles, in myopic children. The risk of corneal staining after ortho-k wear may be slightly higher than that with spectacles, but could be well controlled.

Alterations of conjunctival microbiota associated with orthokeratology lens wearing in myopic children.

BACKGROUND: Orthokeratology (OK) lens wear increases the risk of bacterial infection, but little is known about the microbiota of the conjunctival sac in myopic children wearing OK lenses. This study aimed to investigate the changes of conjunctival microbiota in children after treatment with OK lenses using 16 S rDNA sequencing. METHODS: Twenty-eight myopic children who had been continuously wearing OK lenses for 12 to 13 months were enrolled in this prospective study. Twenty-two gender- and age-matched myopic children who had not worn OK lenses or discontinued OK lens wear at least 1 year ago were recruited as controls. Conjunctival swabs from each participant were collected for exploration of the microbiota profiles, targeting the V3-V4 regions of the 16 S rRNA gene by MiSeq sequencing. The differences in the microbial community structure and diversity were also compared between groups. RESULTS: The bacterial alpha diversity indices in the OK lens group were not different from those in the non-wearer group (P > 0.05, Wilcoxon test), while beta diversity examined using principle coordinate analysis of unweighted UniFrac divided the two groups into different clusters. Proteobacteria, Bacteroidetes, and Firmicutes were the abundant phyla in the conjunctival sac microbiota in both groups (P < 0.05, Mann-Whitney U test). Among children in the OK lens group, the Linear discriminant analysis Effect Size identified the compositional changes in OK lens-associated bacteria. Key functional genera such as Blautia, Parasutterella, and Muribaculum were enriched, whereas Brevundimonas, Acinetobacter, Proteus, and Agathobacter decreased significantly (P < 0.05, Mann-Whitney U test). Phylogenetic investigation of communities by reconstruction of unobserved states also showed altered bacterial metabolic pathways in OK lens-associated microbiota. Moreover, using receiver operating characteristic curves, Brevundimonas, Acinetobacter, Proteus, and Agathobacter alone (the area under the curve was all > 0.7500) or in combination (the area under the curve was 0.9058) were revealed to discriminate OK lens wearers from controls. CONCLUSIONS: The relative abundance of the microbial community in the conjunctival sac of myopic children can alter after OK lens wear. Brevundimonas, Acinetobacter, Proteus, and Agathobacter may be candidate biomarkers to distinguish between OK lens wearers and non-wearers.

Akkermansia muciniphila Protects Against Antibiotic-Associated Diarrhea in Mice.

Probiotics are used to prevent antibiotic-associated diarrhea (AAD) via the restoration of the gut microbiota. However, the precise effects of Akkermansia muciniphila (Akk), which is a promising probiotics, on AAD are unknown. Here, AAD models were established via the administration of lincomycin and ampicillin with or without pasteurized Akk or Amuc_1100 treatment. A diffusion test revealed that Akk was susceptible to the majority of the antibiotics, such as ampicillin. These effects were confirmed by the reduced Akk abundance in AAD model mice. Pasteurized Akk or Amuc_1100 significantly decreased the diarrhea status score and colon injury of AAD model mice. Additionally, these treatments significantly decreased the relative abundance of Citrobacter at genus level and reshaped the metabolic function of gut microbiota. Notably, pasteurized Akk or Amuc_1100 significantly changed the serum metabolome of AAD model mice. In addition, pasteurized Akk or Amuc_1100 suppressed intestinal inflammation by upregulating the expression of GPR109A and SLC5A8 and downregulating the expression of TNFα, IFNγ, IL1ß, and IL6. Furthermore, they enhanced water and electrolyte absorption by upregulating AQP4, SLC26A3, and NHE3. Pasteurized Akk or Amuc_1100 also restored intestinal barrier function by ameliorating the downregulation of ZO-1, OCLN, CLDN4, and Muc2 in AAD model mice. In summary, optimizing intestinal health with pasteurized Akk or Amuc_1100 may serve as an approach for preventing AAD.

HBV-infected hepatocellular carcinoma can be robustly classified into three clinically relevant subgroups by a novel analytical protocol.

Liver cancer is the third leading cause of cancer-related death worldwide, and hepatocellular carcinoma (HCC) accounts for a relatively large proportion of all primary liver malignancies. Among the several known risk factors, hepatitis B virus (HBV) infection is one of the important causes of HCC. In this study, we demonstrated that the HBV-infected HCC patients could be robustly classified into three clinically relevant subgroups, i.e. Cluster1, Cluster2 and Cluster3, based on consistent differentially expressed mRNAs and proteins, which showed better generalization. The proposed three subgroups showed different molecular characteristics, immune microenvironment and prognostic survival characteristics. The Cluster1 subgroup had near-normal levels of metabolism-related proteins, low proliferation activity and good immune infiltration, which were associated with its good liver function, smaller tumor size, good prognosis, low alpha-fetoprotein (AFP) levels and lower clinical stage. In contrast, the Cluster3 subgroup had the lowest levels of metabolism-related proteins, which corresponded with its severe liver dysfunction. Also, high proliferation activity and poor immune microenvironment in Cluster3 subgroup were associated with its poor prognosis, larger tumor size, high AFP levels, high incidence of tumor thrombus and higher clinical stage. The characteristics of the Cluster2 subgroup were between the Cluster1 and Cluster3 groups. In addition, MCM2-7, RFC2-5, MSH2, MSH6, SMC2, SMC4, NCPAG and TOP2A proteins were significantly upregulated in the Cluster3 subgroup. Meanwhile, abnormally high phosphorylation levels of these proteins were associated with high levels of DNA repair, telomere maintenance and proliferative features. Therefore, these proteins could be identified as potential diagnostic and prognostic markers. In general, our research provided a novel analytical protocol and insights for the robust classification, treatment and prevention of HBV-infected HCC.

Investigation of contrast visual acuity with rigid gas permeable contact lenses after penetrating Keratoplasty.

BACKGROUND: To investigate the effects of rigid gas permeable contact lens (RGP-CL) wear on contrast visual acuity in patients after penetrating keratoplasty. METHODS: Nineteen patients (19 eyes), aged 30.45 ± 5.83 years, who had received penetrating keratoplasty and were successfully fitted with RGP-CLs at our hospital from July 2017 to June 2018 were included. Contrast visual acuities at 100%, 25%, and 10% with spectacles and RGP-CLs were analyzed using the Chi-square test. The wavefront aberrations at the anterior surface of the cornea before and 1 month after RGP-CL wear were compared using the matched sample t-test. RESULTS: The mean best spectacle-corrected visual acuities were 0.390 ± 0.135 logMAR, 0.706 ± 0.182 logMAR, and 0.952 ± 0.223 logMAR at the 100%, 25%, and 10% contrast levels, respectively, which were significantly lower than the RGP-CL-corrected visions at the three levels (0.255 ± 0.133 logMAR, 0.488 ± 0.168 logMAR, and 0.737 ± 0.159 logMAR; all P < 0.001). The vision losses with RGP-CLs were 0.231 ± 0.099 logMAR and 0.466 ± 0.094 logMAR at the 25% and 10% contrast levels, respectively. The Zernike spherical aberration Z04 was reduced from 3.734 ± 1.061 µm to 2.622 ± 0.725 µm after wearing the RGP-CLs (P ≤ 0.001). The astigmatism parameters of Z- 22 and Z22 were also reduced from 3.761 ± 2.309 µm and 3.316 ± 2.147 µm to 2.637 ± 1.722 µm and 2.016 ± 1.184 µm, respectively (P < 0.05). CONCLUSION: For post-keratoplasty patients, RGP-CLs can help to improve visual performance, especially low contrast visual acuity. The improvement may be related to the reduction of corneal aberrations, mainly the spherical and astigmatism aberrations.

Quantitative Data-Independent Acquisition Mass Spectrometry Proteomics and Weighted Correlation Network Analysis of Plasma Samples for the Discovery of Chronic Kidney Disease-Specific Atherosclerosis Risk Factors.

Chronic kidney disease (CKD) accelerates atherosclerosis. The mechanism of CKD-related atherosclerosis is complex, and CKD-specific risk factors may contribute to this process in addition to traditional risk factors such as hypertension, diabetes, and hypercholesterolemia. In the present study, to discover CKD-specific atherosclerosis risk factors, a total of 62 patients with different stages of kidney function were enrolled. All patients underwent coronary angiographies and the severity of coronary atherosclerosis was defined by the SYNTAX score. Patients were divided into different groups according to their kidney function levels and coronary atherosclerosis severity. Data-independent acquisition mass spectrometry was used to identify differentially expressed proteins (DEPs) in the plasma samples, and weighted correlation network analysis (WGCNA) was employed to identify significant protein modules and hub proteins related to CKD-specific atherosclerosis. The results showed that 10 DEPs associated with atherosclerosis were found in the comparative groups with modest and severe CKD. Through WGCNA, 1768 proteins were identified and 8 protein modules were established. Enrichment analyses of protein modules revealed functional clusters mainly associated with inflammation and the complement and coagulation cascade as atherosclerosis developed under CKD conditions. The results may help to better understand the mechanisms of CKD-related atherosclerosis and guide future research on developing treatments for CKD-related atherosclerosis.

Pan-Cancer Single-Cell Analysis Reveals the Core Factors and Pathway in Specific Cancer Stem Cells of Upper Gastrointestinal Cancer.

Upper gastrointestinal cancer (UGIC) is an aggressive carcinoma with increasing incidence and poor outcomes worldwide. Here, we collected 39,057 cells, and they were annotated into nine cell types. By clustering cancer stem cells (CSCs), we discovered the ubiquitous existence of sub-cluster CSCs in all UGICs, which is named upper gastrointestinal cancer stem cells (UGCSCs). The identification of UGCSC function is coincident with the carcinogen of UGICs. We compared the UGCSC expression profile with 215,291 single cells from six other cancers and discovered that UGCSCs are specific tumor stem cells in UGIC. Exploration of the expression network indicated that inflammatory genes (CXCL8, CXCL3, PIGR, and RNASE1) and Wnt pathway genes (GAST, REG1A, TFF3, and ZG16B) are upregulated in tumor stem cells of UGICs. These results suggest a new mechanism for carcinogenesis in UGIC: mucosa damage and repair caused by poor eating habits lead to chronic inflammation, and the persistent chronic inflammation triggers the Wnt pathway; ultimately, this process induces UGICs. These findings establish the core signal pathway that connects poor eating habits and UGIC. Our system provides deeper insights into UGIC carcinogens and a platform to promote gastrointestinal cancer diagnosis and therapy.

Low-Cost Al-Doped Layered Cathodes with Improved Electrochemical Performance for Rechargeable Sodium-Ion Batteries.

O3-NaNi0.25Fe0.5Mn0.25O2 layered oxide is considered one of the most promising cathode candidates for sodium-ion batteries because of its advantages, such as its large capacity and low cost. However, the practical application of this material is limited by its poor cyclic stability and insufficient rate capability. Here, a strategy to substitute the Fe3+ in NaNi0.25Fe0.5Mn0.25O2 with Al3+ is adopted to address these issues. The substitution of Fe3+ with Al3+ enhances the framework stability and phase transition reversibility of the parent NaNi0.25Fe0.5Mn0.25O2 material by forming a stronger TM-O bond, which improves the cycling stability. Moreover, partial Al3+ substitution increases the interslab distance, providing a spacious path for Na+ diffusion and resulting in fast diffusion kinetics, which lead to improved rate capability. Consequently, the target NaNi0.25Fe0.5-xAlxMn0.25O2 sample with optimal x = 0.045 exhibits a remarkable electrochemical performance in a Na-ion cell with a large reversible capacity of 131.7 mA h g-1, a stable retention of approximately 81.6% after cycling at 1C for 100 cycles, and a rate performance of 81.3 mA h g-1 at 10C. This method might pave the way for novel means of improving the electrochemical properties of layered transitional-metal oxides and provide insightful guidance for the design of low-cost cathode materials.

A Rational Biphasic Tailoring Strategy Enabling High-Performance Layered Cathodes for Sodium-Ion Batteries.

Layered oxide cathodes usually exhibit high compositional diversity, thus providing controllable electrochemical performance for Na-ion batteries. These abundant components lead to complicated structural chemistry, closely affecting the stacking preference, phase transition and Na+ kinetics. With this perspective, we explore the thermodynamically stable phase diagram of various P2/O3 composites based on a rational biphasic tailoring strategy. Then a specific P2/O3 composite is investigated and compared with its monophasic counterparts. A highly reversible structural evolution of P2/O3-P2/O3/P3-P2/P3-P2/Z/O3'-Z/O3' based on the Ni2+ /Ni3.5+ , Fe3+ /Fe4+ and Mn3.8+ /Mn4+ redox couples upon sequential Na extraction/insertion is revealed. The reduced structural strain at the phase boundary alleviates the phase transition and decreases the lattice mismatch during cycling, endowing the biphasic electrode a large reversible capacity of 144 mAh g-1 with the energy density approaching 514 Wh kg-1 .

Epigenetic Changes and Functions in Pneumoconiosis.

Pneumoconiosis is one of the most common occupational diseases in the world, and specific treatment methods of pneumoconiosis are lacking at present, so it carries great social and economic burdens. Pneumoconiosis, coronavirus disease 2019, and idiopathic pulmonary fibrosis all have similar typical pathological changes-pulmonary fibrosis. Pulmonary fibrosis is a chronic lung disease characterized by excessive deposition of the extracellular matrix and remodeling of the lung tissue structure. Clarifying the pathogenesis of pneumoconiosis plays an important guiding role in its treatment. The occurrence and development of pneumoconiosis are accompanied by epigenetic factors (e.g., DNA methylation and noncoding RNA) changes, which in turn can promote or inhibit the process of pneumoconiosis. Here, we summarize epigenetic changes and functions in the several kinds of evidence classification (epidemiological investigation, in vivo, and in vitro experiments) and main types of cells (macrophages, fibroblasts, and alveolar epithelial cells) to provide some clues for finding specific therapeutic targets for pneumoconiosis and even for pulmonary fibrosis.

A meta-learning approach to improving radiation response prediction in cancers.

PURPOSE: Predicting the efficacy of radiotherapy in individual patients has drawn widespread attention, but the limited sample size remains a bottleneck for utilizing high-dimensional multi-omics data to guide personalized radiotherapy. We hypothesize the recently developed meta-learning framework could address this limitation. METHODS AND MATERIALS: By combining gene expression, DNA methylation, and clinical data of 806 patients who had received radiotherapy from The Cancer Genome Atlas (TCGA), we applied the Model-Agnostic Meta-Learning (MAML) framework to tasks consisting of pan-cancer data, to obtain the best initial parameters of a neural network for a specific cancer with smaller number of samples. The performance of meta-learning framework was compared with four traditional machine learning methods based on two training schemes, and tested on Cancer Cell Line Encyclopedia (CCLE) and Chinese Glioma Genome Atlas (CGGA) datasets. Moreover, biological significance of the models was investigated by survival analysis and feature interpretation. RESULTS: The mean AUC (Area under the ROC Curve) [95% confidence interval] of our models across nine cancer types was 0.702 [0.691-0.713], which improved by 0.166 on average over other the four machine learning methods on two training schemes. Our models performed significantly better (p < 0.05) in seven cancer types and performed comparable to the other predictors in the rest of two cancer types. The more pan-cancer samples were used to transfer meta-knowledge, the greater the performance improved (p < 0.05). The predicted response scores that our models generated were negatively correlated with cell radiosensitivity index in four cancer types (p < 0.05), while not statistically significant in the other three cancer types. Moreover, the predicted response scores were shown to be prognostic factors in seven cancer types and eight potential radiosensitivity-related genes were identified. CONCLUSIONS: For the first time, we established the meta-learning approach to improving individual radiation response prediction by transferring common knowledge from pan-cancer data with MAML framework. The results demonstrated the superiority, generalizability, and biological significance of our approach.

Is adiposity associated with objectively measured physical activity and sedentary behaviors in older adults?

BACKGROUND: Many older adults in the U.S. do not achieve the recommended amount of physical activity (PA) to fully realize a myriad of health benefits. Adiposity is one of those important correlates of PA and sedentary behaviors. However, the full extent to which adiposity is associated with PA and stationary time (STA) is uncertain. Therefore, we examined the association of adiposity with objectively measured PA and STA in black and white older adults. METHODS: We conducted a cross-sectional study of older adults enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study 2003-2007 who participated in an ancillary accelerometer study 2009-2013. Assessment of body mass index (BMI) and waist circumference (WC) was completed during an in-home visit in the parent study. PA was measured by Actical™ accelerometers, which provided estimates of moderate-to-vigorous-intensity PA (MVPA), light-intensity PA (LPA), and STA for 4-7 consecutive days. Data from accelerometers were standardized to square root percentages of total wear time per day (SqrtMVPA%, SqrtLPA%, and SqrtSTA%). Interactions were tested for BMI and WC by race and sex, separately. RESULTS: Data were available for 7873 participants (69.8 ± 8.7 yr, 54.2% women, 31.5% African American). In mixed linear regression models, significant interactions existed in BMI by race and sex for the SqrtMVPA%, WC by race and sex for the SqrtMVPA% and the SqrtLPA% model(p < 0.05). No interaction was significant for the logistic model of meeting the PA guideline or not. In subgroup analyses, BMI was inversely associated with SqrtMVPA%, SqrtLPA%, and positively related to SqrtSTA% in black women, white men and white women after adjustments. Similar patterns were observed between WC and SqrtMVPA%, SqrtLPA%, and SqrtSTA% in all groups, respectively. However, BMI was not associated with SqrtMVPA% in black men. Those with higher BMI or WC were less likely to meet the PA guideline in all groups. CONCLUSIONS: Adiposity was inversely associated with higher levels of MVPA/LPA and positively associated with higher levels of STA among black and white older adults. Prevention efforts aimed at promoting weight control may be beneficial to prevent physical inactivity and sedentary lifestyle among older adults.

Mortality trends of bladder cancer in China from 1991 to 2015: an age-period-cohort analysis.

PURPOSE: The effects of age, period, and cohort on mortality rates of bladder cancer in China remained vague. This study aimed to analyze the secular trends of bladder cancer mortality in China and estimate the independent effects of age, period, and cohort. METHODS: Data for bladder cancer mortality from 1991 to 2015 was obtained from the WHO Mortality Database and China Health Statistical Yearbook. The age-period-cohort model was used to estimate the effect of age, period, and cohort. The intrinsic estimator method was used to solve the nonidentification problem of collinearity among age, period, and cohort. RESULTS: The age-standardized mortality rates of total residents (2.33-1.87/100,000), male (3.45-2.89/100,000), and female (1.24-0.82/100,000) showed decreasing trends, which was more obvious in males than in females. Age effects increased consistently with age in all age groups (coefficients: -2.02 to 1.91 in the total population, -2.06 to 2.02 in males and -2.04 to 1.81 in females). Cohort effects decreased overall (coefficients: 0.96 to -1.62 in the total population, 1.11 to -1.66 in males and 0.78 to -1.46 in females). Period effects were not found in China. CONCLUSION: Although a decreasing mortality was observed, the bladder cancer burden in China will likely increase in the next few years due to population aging, environmental pollution, and food safety. The findings suggested that preventive measures should be taken corresponding to the changes in age-and cohort-related factors in the population.

The protein elicitor Hrip1 enhances resistance to insects and early bolting and flowering in Arabidopsis thaliana.

The elicitor Hrip1 isolated from necrotrophic fungus Alternaria tenuissima, could induce systemic acquired resistance in tobacco to enhance resistance to tobacco mosaic virus. In the present study, we found that the transgenic lines of Hrip1-overexpression in wild type (WT) Arabidopsis thaliana were more resistant to Spodoptera exigua and were early bolting and flowering than the WT. A profiling of transcription assay using digital gene expression profiling was used for transgenic and WT Arabidopsis thaliana. Differentially expressed genes including 40 upregulated and three downregulated genes were identified. In transgenic lines of Hrip1-overexpression, three genes related to jasmonate (JA) biosynthesis were significantly upregulated, and the JA level was found to be higher than WT. Two GDSL family members (GLIP1 and GLIP4) and pathogen-related gene, which participated in pathogen defense action, were upregulated in the transgenic line of Hrip1-overexpression. Thus, Hrip1 is involved in affecting the flower bolting time and regulating endogenous JA biosynthesis and regulatory network to enhance resistance to insect.

Polymer translocation through a hairy channel mimicking the inner plug of a nuclear pore complex.

A microscopic transport model of a polymer translocating through a nuclear pore complex (NPC) is presented based on self-consistent field theory (SCFT), with the NPC and its nucleoporins mimicked by a hairy channel. Multiple cell environment effects (electrolyte effect, excluded volume effect, NPC drag effect, and hydrophobic effect) are all considered in this hairy channel model. The influence of various parameters (polymer chain length, length of NPC, strength of hydrophobic effect, and excluded volume effect) on translocation time is studied through theoretical analysis and numerical calculation. Numerical simulation results show that an area of low nucleoporin number density exists in the NPC, which facilitates the translocation of the polymer. The results also show that the translocation time curves with increasing NPC length and polymer charge number are concave. In addition, there are critical values for NPC length and polymer charge number for which the translocation time has a minimal value. The translocation time decreases with the increasing strength of the hydrophobic effect and excluded volume effect.

Multivariate analysis of genome-wide data to identify potential pleiotropic genes for five major psychiatric disorders using MetaCCA.

BACKGROUND: Genome-wide association studies have been extensively applied in identifying SNP associated with major psychiatric disorders. However, the SNPs identified by the prevailing univariate approach only explain a small percentage of the genetic variance of traits, and the extensive data have shown the major psychiatric disorders have common biological mechanisms and the overlapping pathophysiological pathways. METHODS: We applied the genetic pleiotropy-informed metaCCA method on summary statistics data from the Psychiatric Genomics Consortium Cross-Disorder Group to examine the overlapping genetic relations between the five major psychiatric disorders. Furthermore, to refine all genes, we performed gene-based association analyses for the five disorders respectively using VEGAS2. Gene enrichment analysis was applied to explore the potential functional significance of the identified genes. RESULTS: After metaCCA analysis, 1147 SNPs reached the Bonferroni corrected threshold (p < 1.06 × 10-6) in the univariate SNP-multivariate phenotype analysis, and 246 genes with a significance threshold (p < 3.85 × 10-6) were identified as potentially pleiotropic genes in the multivariate SNP-multivariate phenotype analysis. By screening the results of gene-based p-values, we identified 37 putative pleiotropic genes which achieved significance threshold in metaCCA analyses and were also associated with at least one disorder in the VEGAS2 analyses. LIMITATIONS: Alternative approaches and experimental studies may be applied to check whether novel genes could still be identified/substantiated with these methods. CONCLUSIONS: The metaCCA method identified novel variants associated with psychiatric disorders by effectively incorporating information from different GWAS datasets. Our analyses may provide insights for some common therapeutic approaches of these five major psychiatric disorders based on the pleiotropic genes and common mechanisms identified.

Identification of differentially accumulated proteins involved in regulating independent and combined osmosis and cadmium stress response in Brachypodium seedling roots.

In this study, we aimed to identify differentially accumulated proteins (DAPs) involved in PEG mock osmotic stress, cadmium (Cd2+) stress, and their combined stress responses in Brachypodium distachyon seedling roots. The results showed that combined PEG and Cd2+ stresses had more significant effects on Brachypodium seedling root growth, physiological traits, and ultrastructures when compared with each individual stress. Totally, 106 DAPs were identified that are responsive to individual and combined stresses in roots. These DAPs were mainly involved in energy metabolism, detoxification and stress defense and protein metabolism. Principal component analysis revealed that DAPs from Cd2+ and combined stress treatments were grouped closer than those from osmotic stress treatment, indicating that Cd2+ and combined stresses had more severe influences on the root proteome than osmotic stress alone. Protein-protein interaction analyses highlighted a 14-3-3 centered sub-network that synergistically responded to osmotic and Cd2+ stresses and their combined stresses. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 14 key DAP genes revealed that most genes showed consistency between transcriptional and translational expression patterns. A putative pathway of proteome metabolic changes in Brachypodium seedling roots under different stresses was proposed, which revealed a complicated synergetic responsive network of plant roots to adverse environments.

Integrated physiological and proteomic analysis reveals underlying response and defense mechanisms of Brachypodium distachyon seedling leaves under osmotic stress, cadmium and their combined stresses.

Drought stress, a major abiotic stress, commonly occurs in metal-contaminated environments and affects crop growth and yield. In this study, we performed the first integrated phenotypic, physiological, and proteomic analysis of Brachypodium distachyon L. seedling leaves under polyethylene glycol (PEG) mock osmotic stress, cadmium (Cd2+), and their combined stresses. Combined osmotic and Cd2+ stress had more significant effects than each individual stress on seedling growth, and the physiological traits and ultrastructures of leaves. Totally 117 differentially accumulated protein (DAP) spots detected by two-dimensional difference gel electrophoresis (2D-DIGE) were identified, and representing 89 unique proteins under individual and combined stresses. These DAPs were involved in photosynthesis/respiration (34%), energy and carbon metabolism (21%), stress/defense/detoxification (13%), protein folding and degradation (12%), and amino acid metabolism (7%). Principal component analysis (PCA) revealed that DAPs from the Cd2+ and combined stresses grouped much closer than those from osmotic stress, indicating Cd2+ and combined stresses resulted in more changes to the leaf proteome than osmotic stress alone. Protein-protein interaction analyses showed that a 14-3-3 centered sub-network could play important roles in responses to abiotic stresses. An overview pathway of proteome metabolic changes in Bd21 seedling leaves under combined stresses is proposed, representing a synergistic responsive network and underlying response and defense mechanisms. SIGNIFICANCE: Drought stress is one of the major abiotic stresses, which commonly occurs in metal-contaminated environments, and affects crop growth and yield performance. We performed the first integrated phenotypic, physiological and proteomic analysis of Brachypodium distachyon L. seedling leaves under drought (PEG), cadmium (Cd2+) and their combined stresses.