Different color regulation mechanism in willow barks determined using integrated metabolomics and transcriptomics analyses.

BACKGROUND: The rich yellow-orange to vividly deep red bark of willow (Salix spp.) branches have high ornamental and economic value. However, the mechanism underlying the regulation of willow branch color remains unknown. Therefore, we performed metabolomics and transcriptomics analyses of purple, green, and red willow barks to elucidating the mechanisms regulating color development. RESULTS: Seven anthocyanins were isolated; pelargonidin, petunidin 3-O-rutinoside, and cyanin chloride were the most abundant in red bark, whereas pelargonin chloride was most abundant in purple bark. The green bark contained the highest level of malvidin; however, the malvidin level was not significantly higher than in the red bark. The purple bark contained the largest amount of canthaxanthin, a carotenoid pigment. The integrated pathways of flavonoid biosynthesis, carotenoid biosynthesis, and porphyrin and chlorophyll metabolism were constructed for the willow barks. Among the three barks, the expression of the structural genes ANS, ANR, and BZ1, which are involved in anthocyanin synthesis, was the highest in red bark, likely causing anthocyanin accumulation. The expression of CrtZ, which participates in the carotenoid pathway, was the highest in purple bark, likely leading to canthaxanthin accumulation. The high expression of DVR, POR, and CRD1 may be associated with green pigment synthesis in the chlorophyll biosynthesis pathway. CONCLUSIONS: Purple bark color is co-regulated by anthocyanins and carotenoids, whereas red bark is characterized by anthocyanin accumulation and chlorophyll degradation. The green pigment is regulated by maintaining chlorophyll synthesis. BZ1 and CrtZ are candidate genes regulating anthocyanin and canthaxanthin accumulation in red and purple barks respectively. Collectively, our results may facilitate the genetic breeding and cultivation of colorful willows with improved color and luster.

Comparison of two willow genotypes reveals potential roles of iron-regulated transporter 9 and heavy-metal ATPase 1 in cadmium accumulation and resistance in Salix suchowensis.

Willows (Salix spp.) are promising extractors of cadmium (Cd), with fast growth, high biomass production, and high Cd accumulation capacity. However, the molecular mechanisms underlying Cd uptake and detoxification are currently poorly understood. Analysis of the Cd uptake among 30 willow genotypes in hydroponic systems showed that the S. suchowensis and S. integra hybrids, Jw8-26 and Jw9-6, exhibited distinct Cd accumulation and resistance characteristics. Jw8-26 was a high Cd-accumulating and tolerant willow, while Jw9-6 was a low Cd-accumulating and relatively Cd-intolerant willow. Therefore, these two genotypes were ideal specimens for determining the molecular mechanisms of Cd uptake and detoxification. To identify relevant genes in Cd handling, the parent S. suchowensis was treated with Cd and RNA-seq analysis was performed. SsIRT, SsHMA, and SsGST, in addition to the transcription factors SsERF, SsMYB, and SsZAT were identified as being associated with Cd uptake and resistance. Because membrane-localised heavy metal transporters mediate Cd transfer to plant tissues, a total of 17 SsIRT and 12 SsHMA family members in S. suchowensis were identified. Subsequently, a thorough bioinformatics analysis of the SsIRT and SsHMA families was conducted, and their transcript levels were analysed in the roots of the two hybrids. The transcript levels of SsIRT9 in roots were positively correlated with the observed differences in Cd accumulation in Jw8-26 versus Jw9-6. Jw8-26 displayed higher SsIRT9 expression levels and higher Cd accumulation than Jw9-6; therefore, SsIRT9 may be involved in Cd uptake. Gene expression analysis also revealed that SsHMA1 was a candidate gene associated with Cd resistance. These results lay the foundation for understanding the molecular mechanism of Cd transfer and detoxification in willows, and provide guidance for the screening and breeding of high Cd-accumulating and tolerant willow genotypes via genetic engineering.

PSANet: Pyramid Splitting and Aggregation Network for 3D Object Detection in Point Cloud.

3D object detection in LiDAR point clouds has been extensively used in autonomous driving, intelligent robotics, and augmented reality. Although the one-stage 3D detector has satisfactory training and inference speed, there are still some performance problems due to insufficient utilization of bird's eye view (BEV) information. In this paper, a new backbone network is proposed to complete the cross-layer fusion of multi-scale BEV feature maps, which makes full use of various information for detection. Specifically, our proposed backbone network can be divided into a coarse branch and a fine branch. In the coarse branch, we use the pyramidal feature hierarchy (PFH) to generate multi-scale BEV feature maps, which retain the advantages of different levels and serves as the input of the fine branch. In the fine branch, our proposed pyramid splitting and aggregation (PSA) module deeply integrates different levels of multi-scale feature maps, thereby improving the expressive ability of the final features. Extensive experiments on the challenging KITTI-3D benchmark show that our method has better performance in both 3D and BEV object detection compared with some previous state-of-the-art methods. Experimental results with average precision (AP) prove the effectiveness of our network.

EPGNet: Enhanced Point Cloud Generation for 3D Object Detection.

Three-dimensional object detection from point cloud data is becoming more and more significant, especially for autonomous driving applications. However, it is difficult for lidar to obtain the complete structure of an object in a real scene due to its scanning characteristics. Although the existing methods have made great progress, most of them ignore the prior information of object structure, such as symmetry. So, in this paper, we use the symmetry of the object to complete the missing part in the point cloud and then detect it. Specifically, we propose a two-stage detection framework. In the first stage, we adopt an encoder-decoder structure to generate the symmetry points of the foreground points and make the symmetry points and the non-empty voxel centers form an enhanced point cloud. In the second stage, the enhanced point cloud is input into the baseline, which is an anchor-based region proposal network, to generate the detection results. Extensive experiments on the challenging KITTI benchmark show the effectiveness of our method, which has better performance on both 3D and BEV (bird's eye view) object detection compared with some previous state-of-the-art methods.

Androgen Receptor Is Inactivated and Degraded in Bladder Cancer Cells by Phenyl Glucosamine via miR-449a Restoration.

BACKGROUND Bladder cancer caused by exposure to aniline dyes, chronic cystitis, and smoking is detected in approximately 70 000 new cases annually. In the USA alone, it leads to 15 000 deaths every year. In the present study, we investigated the role of 3-((4'-amino-[1,1'-biphenyl]-4-yl)amino)-4-bromo-5-oxo-2,5-dihydrofuran-2-yl acetate (ABDHFA) in the inhibition of bladder cancer cell viability. MATERIAL AND METHODS Viability of cells was examined using MTT assay and distribution of cell cycle was assessed by flow cytometry. Expression of cyclin D1, androgen, prostate-specific antigen (PSA), and miR-449a was analyzed using Western blot and quantitative real-time polymerase chain reaction assays. RESULTS The results demonstrated that ABDHFA treatment inhibited viability of UMUC3 and TCCSUP AR-positive bladder cancer cells. ABDHFA treatment led to break-down of AR in UMUC3 and TCCSUP cells after 48 h in a dose-dependent manner. Up-regulation of miR-449a by lentivirus transfection down-regulated the AR signalling pathway. In UMUC3 and TCCSUP cells, ABDHFA treatment led to inhibition of mRNA and protein expression corresponding to AR. CONCLUSIONS In summary, the present study demonstrates that proliferation of AR-positive bladder carcinoma cells is markedly reduced by ABDHFA treatment through arrest of cell cycle and degradation of AR protein. Thus, ABDHFA, a novel compound, can be used for the treatment of bladder cancer.

The Utilization of a Coupled Electro-Thermal-Mechanical Model of High-Voltage Electric Pulse on Rock Fracture.

Our research proposes a unique coupled electro-thermal-mechanical model that takes electric breakdown and heterogeneity into account to show the mechanism of rock fracturing under high-voltage electropulses. Using finite element numerical software, the process of high voltage electrical pulse injection into the rock interior for breakdown is described, and the formation law of plasma channels during the electrical breakdown process is comprehensively analyzed in conjunction with the conductor particles present within the rock. On the basis of electrical, thermal, and mechanical theories, a coupled multi-physical field numerical model of rock failure under the action of high-voltage electrical pulses is developed, and a random distribution model is utilized to simulate the potential occurrence of conductor particles in the rock. Innovative numerical model indicates plasma channel creation in the rock-crushing process. Prior to the formation of the plasma channel, the temperature and stress are approximately 103 k and 10-2 MPa, respectively. Once the plasma channel is formed, the temperature and stress increase abruptly in a short time, with the temperature reaching 104 k and the stress reaching 103 MPa or higher. In addition, it is revealed that the breakdown field strength is the essential factor in plasma channel creation. The heterogeneity of the particles within the rock and the fluctuation in electrode settings are also significant variables influencing the creation of channels. The presented model contributes to a better understanding of the mechanism of rock fragmentation during high-voltage electrical pulses, which has substantial implications for oil exploration and mineral extraction.

Assessment of the capability of cadmium accumulation and translocation among 31 willows: four patterns of willow biomass variation response to cadmium.

Cadmium (Cd) pollution threatens food security and the environment. Willow species (Salix, Salicaceae) exhibit a remarkable potential to restore Cd-polluted sites due to their high biomass production and high Cd accumulation capacities. This study examined the Cd accumulation and tolerance in 31 genotypes of shrub willow in hydroponic conditions at varying Cd levels (0 µM Cd, 5 µM Cd, and 20 µM Cd). The root, stem, and leaf biomass of 31 shrub willow genotypes showed significant differences to Cd exposure. Among 31 willow genotypes, four patterns of biomass variation response to Cd were identified: insensitive to Cd; growth inhibition due to excessive Cd supply (high Cd inhibition); low Cd causing inhibited growth, whereas high Cd leading to increased biomass (U-shape); and growth increment with excessive Cd exposure (high Cd induction). The genotypes belonging to the "insensitive to Cd" and/or "high Cd induction" were candidates for the utilization of phytoremediation. Based on the analysis of Cd accumulation of 31 shrub willow genotypes at high and low Cd levels, genotypes 2372, 51-3, and 1052 obtained from a cross between S. albertii and S. argyracea grew well and accumulated relatively more Cd levels than other genotypes. In addition, for Cd-treated seedlings, root Cd accumulation was positively correlated with shoot Cd accumulation and total Cd uptake, demonstrating that Cd accumulation in roots could serve as a biomarker for evaluating the Cd extraction capacity of willows, especially in hydroponics screening. The results of this study screened out willow genotypes with high Cd uptake and translocation capacities, which will provide valuable approaches for restoring Cd-contaminated soils with willows.

Role of semaphorin 7a signaling in transforming growth factor ß1-induced lung fibrosis and scleroderma-related interstitial lung disease.

OBJECTIVE: Semaphorin 7a regulates transforming growth factor ß1 (TGFß1)-induced fibrosis. This study was undertaken to test the hypothesis that semaphorin 7a exerts its profibrotic effects in part by promoting the tissue accumulation of CD45+ fibrocytes. METHODS: A murine model of pulmonary fibrosis in which an inducible, bioactive form of the human TGFß1 gene is overexpressed in the lung was used. Fibrosis and fibrocytes were evaluated in TGFß1-transgenic mice in which the semaphorin 7a locus had been disrupted. The effect of replacement or deletion of semaphorin 7a on bone marrow-derived cells was ascertained using bone marrow transplantation. The role of the semaphorin 7a receptor ß1 integrin was assessed using neutralizing antibodies. The applicability of these findings to TGFß1-driven fibrosis in humans was examined in patients with scleroderma-related interstitial lung disease (ILD). RESULTS: The appearance of fibrocytes in the lungs of TGFß1-transgenic mice required semaphorin 7a. Replacement of semaphorin 7a on bone marrow-derived cells restored lung fibrosis and fibrocytes. Immunoneutralization of ß1 integrin reduced pulmonary fibrocytes and fibrosis. Peripheral blood mononuclear cells (PBMCs) from patients with scleroderma-related ILD showed increased levels of messenger RNA for semaphorin 7a and its receptors, with semaphorin 7a located on collagen-producing fibrocytes and CD19+ lymphocytes. Peripheral blood fibrocyte outgrowth was enhanced in these patients. Stimulation of normal human PBMCs with recombinant semaphorin 7a enhanced fibrocyte differentiation; these effects were attenuated by ß1 integrin neutralization. CONCLUSION: Our findings indicate that interventions that reduce semaphorin 7a expression or prevent the semaphorin 7a-ß1 integrin interaction may ameliorate TGFß1-driven or fibrocyte-associated autoimmune fibroses.

Immobilization of engineered E. coli cells for asymmetric reduction of methyl acetoacetate to methyl-(R)-3-hydroxybutyrate.

The efficient asymmetric bio-synthesis of chiral ß-hydroxy esters is of great importance for industrial production. In this work, a simple and productive engineered E.coli cell-immobilized strategy was applied for the asymmetric reduction of MAA to (R)-HBME with high enantioselectivity. Compared with the corresponding inactivated free cells, the alginate-immobilized cells remained 45% of initial activity at 50 â„ƒ and 65% after reuse of 10 times. After 60 days of storage at 4 â„ƒ, the immobilized cells maintained more than 80% relative activity. Immobilization contributed significantly to the improvement of thermal stability, pH tolerance, storage stability and operation stability without affecting the yield of product. The immobilized recombinant E. coli cell had absolute enantioselectivity for the asymmetric reduction of MAA to (R)-HBME with e.e. > 99.9%. Therefore, microbial cell immobilization is a perspective approach in asymmetric synthesis of chiral ß-hydroxy esters for industrial applications.

Clinicopathologic factors linked to oncologic outcomes for renal cell carcinoma with sarcomatoid dedifferentiation: A PRISMA-compliant systematic review and meta-analysis.

Background: There are still differences in the prognostic factors of renal cell carcinoma with sarcomatoid dedifferentiation (sRCC). The aim of this study was to evaluate important predictors of survival in patients with sRCC. Patients and methods: A comprehensive search of PubMed, Embase, and Cochrane Library was conducted to identify eligible studies. The endpoints embraced overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Hazard ratios (HRs) and related 95% confidence intervals (CIs) were extracted. Results: A total of 13 studies were included for analyses. The pooled results showed that high European Cooperative Oncology Group performance score (HR 2.39, 95% CI 1.32-4.30; P = 0.004), high T stage (HR 2.18, 95% CI 1.66-2.86; P < 0.001), positive lymph node (HR 1.54, 95% CI 1.40-1.69; P < 0.001), distant metastasis (HR 2.52, 95% CI 1.99-3.21; P < 0.001), lung metastases (HR 1.45, 95% CI 1.16-1.80; P < 0.001), liver metastases (HR 1.71, 95% CI 1.30-2.25; P < 0.001), tumor necrosis (HR 1.78, 95% CI 1.14-2.80; P = 0.010), and percentage sarcomatoid ≥50% (HR 2.35, 95% CI 1.57-3.52; P < 0.001) were associated with unfavorable OS. Positive lymph node (HR 1.57, 95% CI 1.33-1.85; P < 0.001) and high neutrophil to lymphocyte ratio (HR 1.16, 95% CI 1.04-1.29; P = 0.008) were associated with unfavorable CSS. High T stage (HR 1.93 95% CI 1.44-2.58; P < 0.001) was associated with unfavorable progression-free survival. Conclusions: A meta-analysis of available data identified important prognostic factors for CSS, OS, and PFS of sRCC, which should be systematically evaluated for patient counseling, risk stratification, and treatment selection. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=249449.

Mechanism Analysis of Rock Failure Process under High-Voltage Electropulse: Analytical Solution and Simulation.

This work aims to investigate and analyse the mechanism of rock failure under high-voltage electropulses in order to evaluate and increase the efficiency of high-voltage pulse technology in geological well drilling, tunnel boring, and other geotechnical engineering applications. To this end, this paper discusses the equivalent circuit of electric pulse rock breaking, the model of shock wave in electro channel plasma, and, particularly, the model of rock failure in order to disclose the rock failure process when exposed to high-voltage electropulse. This article uses granite as an example to present an analytical approach for predicting the mechanical behaviour of high-voltage electropulses and to analyse the damage that occurs. A numerical model based on equivalent circuit, shock wave model, and elasto-brittle failure criterion is developed for granite under electropulse to further examine the granite failure process. Under the conditions described in this study, and using granite as an example, the granite is impacted by a discharge device (Marx generator) with an initial voltage U0 that is 10 kV and a capacitance F that is 5 µF before it begins to degrade at about 40 µs after discharge, with the current reaching its peak at approximately 50 µs. The shock wave pressure then attains a peak at about 70 µs. Dense short cracks form around granite and the dominant cracks grow to an average length of about 20 cm at around 200 µs. The crack width dcr is predicted to be approximately 1.6 mm. This study detects dense cracks in a few centimetres surrounding the borehole, while around seven dominant cracks expand outward. The distribution of the length of the dominating cracks can be inhomogeneous because of the spatial heterogeneity of granite's tensile strength, however the heterogeneity has an insignificant effect on the crack growth rate, total cracked area, or the number of main cracks. The mechanism of rock failure under electropulse can be well supported by the findings of numerical simulations and analytical studies.

A Semi-Analytical Solution for Shock Wave Pressure and Radius of Soil Plastic Zone Induced by Lightning Strikes.

A semi-analytical solution for forecasting the soil behavior induced by lightning strikes is of great engineering significance to calculate the radius of the soil plastic zone. In this paper, a simplified two-stage method is employed to solve the shock wave pressure and the radius of the soil plastic zone. The solution is verified against experimental data. Using the present model, the major factors dominating the shock wave pressure and the radius of the soil plastic zone are investigated. The results show that (1) the radius of the soil plastic zone (rp) induced by lightning decreases monotonically with cohesion (c) and internal friction angle (φ), while c has a better effect on soil properties than φ does; (2) increasing the initial radius of the plasma channel (ri0) can reduce the pressure (P) and increasing ri0 has a nonnegligible effect on rp; with ri0 increasing by 100%, the radius of the soil plastic zone increases by 47.9-59.7%; (3) the plasma channel length (L) has a significant influence on P and rp, especially when L is at a relatively low level; (4) the rp induced by lightning decreases exponentially with attenuation coefficient (a); (5) the wavefront time is a major factor while the half-value time is a minor factor for the shock wave pressure induced by plasma explosives.

Prognostic Role of Pretreatment C-Reactive Protein to Albumin Ratio in Urological Cancers: A Systematic Review and Meta-Analysis.

Background: To investigate the potential prognostic role of C-reactive protein to albumin ratio (CAR) in patients with urinary cancers, including renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PC). Methods: We searched and screened literatures with PubMed, Embase, Cochrane Library, and Web of Science in January 2022. We applied combined hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the associations. Results: Thirteen studies including 2,941 cases were analyzed in our study. Merged results indicated that highly pretreated CAR was associated with inferior overall survival (HR 2.21, 95% CI 1.86-2.62, p < 0.001) and progression-free survival (HR 1.85, 95% CI 1.36-2.52, p < 0.001) for urinary cancers. In a subgroup analysis of OS by tumor type, CAR can be a predictor in RCC (HR 2.10, 95% CI 1.72-2.56), BC (HR 3.35, 95% CI 1.94-5.80), and PC (HR 2.20, 95% CI 1.43-3.37). In a subgroup analysis of PFS by tumor type, CAR can be a predictor in BC (HR 1.76, 95% CI 1.03-3.02), and RCC (HR 1.90, 95% CI 1.25-2.89). The reliability and robustness of results were confirmed. Conclusions: High pretreated CAR was effective predictor of poor survival in patients with urinary cancers and can act as prognostic factor for these cases. Systematic Review Registration: PROSPERO (CRD42022306414).

Comparison of outcomes between laparoscopic and robot-assisted partial nephrectomy for complex renal tumors: RENAL score ≥7 or maximum tumor size >4 cm.

INTRODUCTION: We reviewed current studies and performed a meta-analysis to compare outcomes between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) treating complex renal tumors (RENAL score ≥7 or maximum clinical tumor size >4 cm). EVIDENCE ACQUISITION: Using the databases of PubMed, Embase, and the Cochrane Library, a comprehensive literature search was performed in April, 2020. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model. Publication bias was evaluated by funnel plots. EVIDENCE SYNTHESIS: Ten observational studies including 5193 patients (LPN: 1574; RAPN: 3619) were included. There was no significant difference between the two groups regarding conversion to open (P=0.07) surgery, all complications (P=0.12), grade 1-2 complications (P=0.10), grade 3-5 complications (P=0.93), operative time (P=0.94), estimated blood loss (P=0.17). Patients undergoing LPN had a significant higher rate of conversion to radical (OR=4.33; 95% CI: 2.01-9.33; P<0.001), a longer ischemia time (IT, P<0.001; WMD=3.02 min; 95% CI: 1.67 to 4.36), a longer length of stay (LOS, P<0.001; WMD=0.67 days; 95% CI: 0.35 to 0.99), a lower rate of positive surgical margin (P=0.03; OR=0.71; 95% CI: 0.53 to 0.96), a greater eGFR decline (P<0.001; WMD=2.41 mL/min/1.73 m2; 95% CI: 1.22 to 3.60), a higher rate of CKD upstaging (P<0.001; OR=2.44; 95% CI: 1.54 to 3.87). No obvious publication bias was observed. CONCLUSIONS: For complex renal tumors, RAPN is more favorable than LPN in terms of lower rate of conversion to radical surgery, shorter IT, shorter LOS, less eGFR decline, and lower rate of CKD upstaging. Methodological limitations of observational studies should be taken into account in interpreting these results.

The complete chloroplast genome of Ulmus parvifolia, an important landscaping tree.

Ulmus parvifolia is a promising tree species for landscaping. In this study, the complete genome of U. parvifolia was reported using next-generation sequencing technology. The chloroplast genome was a circular double-stranded DNA molecule with 159,182 bp in length. It contained a large single copy (LSC) region of 87,838 bp, a small single copy (SSC) region of 18,750 bp, and two inverted repeat (IRa and IRb) regions of 26,297 bp each, which exhibited a typical quadripartite structure. A total of 133 genes were identified, including 84 protein-coding genes, 41 tRNA genes, and eight rRNA genes. The overall GC content in the chloroplast genome was 35.59%. Phylogenetic analysis indicated that U. parvifolia, as a representative of Sect. Microptelea within the Ulmus genus, is sister to the species of Sect. Ulmus.

Prognostic Role of Serum Lactate Dehydrogenase in Patients With Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

Background: To investigate the potential prognostic role of serum lactate dehydrogenase (LDH) in patients with urothelial carcinoma (UC) using the method of systematic review and meta-analysis. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies up to February 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the relationship. Results: A total of 14 studies including 4,009 patients with UC were incorporated. The results showed that a high pretreatment serum LDH was associated with an inferior overall survival (OS, HR 1.61, 95% CI 1.39-1.87, p < 0.001), cancer-specific survival (CSS, HR 1.41, 95% CI 1.05-1.90, p = 0.022), and disease-free survival (DFS, HR 1.64, 95% CI 1.04-2.59, p = 0.034) in UC. Subgroup analyses identified that a high pretreatment serum LDH was associated with a poor OS (HR 1.97, 95% CI 1.02-3.81, p = 0.042) and DFS (HR 1.64, 95% CI 1.04-2.59, p = 0.034) in upper tract urothelial carcinoma, a short OS (HR 1.71, 95% CI 1.37-2.15, p < 0.001) in urothelial carcinoma of bladder. Conclusion: Our findings indicated that a high level of pretreatment serum LDH was associated with inferior OS, CSS, and DFS in patients with UC. This biomarker can be an important factor incorporated into the prognostic models for UC.

Physiological and Anatomical Differences and Differentially Expressed Genes Reveal Yellow Leaf Coloration in Shumard Oak.

Shumard oak (Quercus shumardii Buckley) is a traditional foliage plant, but little is known about its regulatory mechanism of yellow leaf coloration. Here, the yellow leaf variety of Q. shumardii named 'Zhongshan Hongjincai' (identified as 'ZH' throughout this work) and a green leaf variety named 'Shumard oak No. 23' (identified as 'SO' throughout this work) were compared. 'ZH' had lower chlorophyll content and higher carotenoid content; photosynthetic characteristics and chlorophyll fluorescence parameters were also lower. Moreover, the mesophyll cells of 'ZH' showed reduced number of chloroplasts and some structural damage. In addition, transcriptomic analysis identified 39,962 differentially expressed genes, and their expression levels were randomly verified. Expressions of chlorophyll biosynthesis-related glumly-tRNA reductase gene and Mg-chelatase gene were decreased, while pheophorbide a oxygenase gene associated with chlorophyll degradation was up-regulated in 'ZH'. Simultaneously, carotenoid isomerase gene, z-carotene desaturase gene, violaxanthin de-epoxidase gene and zeaxanthin epoxidase gene involved in carotenoid biosynthesis were up-regulated in 'ZH'. These gene expression changes were accompanied by decreased chlorophyll content and enhanced carotenoid accumulation in 'ZH'. Consequently, changes in the ratio of carotenoids to chlorophyll could be driving the yellow leaf coloration in Q. shumardii.

Endogenous IL-11 signaling is essential in Th2- and IL-13-induced inflammation and mucus production.

IL-11 and IL-11 receptor (R)alpha are induced by Th2 cytokines. However, the role(s) of endogenous IL-11 in antigen-induced Th2 inflammation has not been fully defined. We hypothesized that IL-11, signaling via IL-11Ralpha, plays an important role in aeroallergen-induced Th2 inflammation and mucus metaplasia. To test this hypothesis, we compared the responses induced by the aeroallergen ovalbumin (OVA) in wild-type (WT) and IL-11Ralpha-null mutant mice. We also generated and defined the effects of an antagonistic IL-11 mutein on pulmonary Th2 responses. Increased levels of IgE, eosinophilic tissue and bronchoalveolar lavage (BAL) inflammation, IL-13 production, and increased mucus production and secretion were noted in OVA-sensitized and -challenged WT mice. These responses were at least partially IL-11 dependent because each was decreased in mice with null mutations of IL-11Ralpha. Importantly, the administration of the IL-11 mutein to OVA-sensitized mice before aerosol antigen challenge also caused a significant decrease in OVA-induced inflammation, mucus responses, and IL-13 production. Intraperitoneal administration of the mutein to lung-specific IL-13-overexpressing transgenic mice also reduced BAL inflammation and airway mucus elaboration. These studies demonstrate that endogenous IL-11R signaling plays an important role in antigen-induced sensitization, eosinophilic inflammation, and airway mucus production. They also demonstrate that Th2 and IL-13 responses can be regulated by interventions that manipulate IL-11 signaling in the murine lung.

Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema.

Th1 inflammation and remodeling characterized by tissue destruction frequently coexist in human diseases. To further understand the mechanisms of these responses, we defined the role(s) of CCR5 in the pathogenesis of IFN-gamma-induced inflammation and remodeling in a murine emphysema model. IFN-gamma was a potent stimulator of the CCR5 ligands macrophage inflammatory protein-1alpha/CCL-3 (MIP-1alpha/CCL-3), MIP-1beta/CCL-4, and RANTES/CCL-5, among others. Antibody neutralization or null mutation of CCR5 decreased IFN-gamma-induced inflammation, DNA injury, apoptosis, and alveolar remodeling. These interventions decreased the expression of select chemokines, including CCR5 ligands and MMP-9, and increased levels of secretory leukocyte protease inhibitor. They also decreased the expression and/or activation of Fas, FasL, TNF, caspase-3, -8, and -9, Bid, and Bax. In accordance with these findings, cigarette smoke induced pulmonary inflammation, DNA injury, apoptosis, and emphysema via an IFN-gamma-dependent pathway(s), and a null mutation of CCR5 decreased these responses. These studies demonstrate that IFN-gamma is a potent stimulator of CC and CXC chemokines and highlight the importance of CCR5 in the pathogenesis of IFN-gamma-induced and cigarette smoke-induced inflammation, tissue remodeling, and emphysema. They also demonstrate that CCR5 is required for optimal IFN-gamma stimulation of its own ligands, other chemokines, MMPs, caspases, and cell death regulators and the inhibition of antiproteases.

Bcl-2-related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury.

Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O(2) caused TUNEL(+) cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O(2). In A1-null mice, IL-11-induced protection, survival advantage, and Bcl-2 and Bcl-xl induction were significantly decreased. VEGF also conferred protection via an A1-dependent mechanism. In vitro hyperoxia also stimulated A1, and A1 overexpression inhibited oxidant-induced epithelial cell apoptosis and necrosis. A1 is an important regulator of oxidant-induced lung injury, apoptosis, necrosis, and Bcl-2 and Bcl-xl gene expression and a critical mediator of IL-11- and VEGF-induced cytoprotection.