Dominance complementation of parental heading date alleles of Hd1, Ghd7, DTH8, and PRR37 confers transgressive late maturation in hybrid rice.

Rice (Oryza sativa L.) is a short-day plant whose heading date is largely determined by photoperiod sensitivity (PS). Many parental lines used in hybrid rice breeding have weak PS, but their F1 progenies have strong PS and exhibit an undesirable transgressive late-maturing phenotype. However, the genetic basis for this phenomenon is unclear. Therefore, effective methods are needed for selecting parents to create F1 hybrid varieties with the desired PS. In this study, we used bulked segregant analysis with F1 Ningyou 1179 (strong PS) and its F2 population, and through analyzing both parental haplotypes and PS data for 918 hybrid rice varieties, to identify the genetic basis of transgressive late maturation which is dependent on dominance complementation effects of Hd1, Ghd7, DTH8, and PRR37 from both parents rather than from a single parental genotype. We designed a molecular marker-assisted selection system to identify the genotypes of Hd1, Ghd7, DTH8, and PRR37 in parental lines to predict PS in F1 plants prior to crossing. Furthermore, we used CRISPR/Cas9 technique to knock out Hd1 in Ning A (sterile line) and Ning B (maintainer line) and obtained an hd1-NY material with weak PS while retaining the elite agronomic traits of NY. Our findings clarified the genetic basis of transgressive late maturation in hybrid rice and developed effective methods for parental selection and gene editing to facilitate the breeding of hybrid varieties with the desired PS for improving their adaptability.

Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum.

BACKGROUND: Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. METHODS: The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC-MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. RESULTS: The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. CONCLUSION: We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

Photoperiod and temperature synergistically regulate heading date and regional adaptation in rice.

Plants must accurately integrate external environmental signals with their own development to initiate flowering at the appropriate time for reproductive success. Photoperiod and temperature are key external signals that determine flowering time; both are cyclical and periodic and they are closely related to regulate flowering. In this review, we describe photoperiod-sensitive genes that simultaneously respond to temperature signals in rice (Oryza sativa). We introduce the mechanisms by which photoperiod and temperature synergistically regulate heading date and regional adaptation in rice. We also discuss the prospects for designing different combinations of heading date genes and other cold tolerance or thermo-tolerance genes to help rice better adapt to changes in light and temperature via molecular breeding to enhance yield in the future.

TGFB1 stimulates the proliferation of quiescent oogonial stem cells in chicken.

In brief: Oogonial stem cells in the adult ovary can generate oocytes, but they are usually quiescent. TGFB1 is key in stimulating the proliferation of OSC, thereby ensuring the sustained reproductive potential in poultry species. Abstract: Oogonial stem cells (OSCs) are a type of germ stem cell present in the adult ovary. They have the ability to self-renew through mitosis and differentiate into oocytes through meiosis. We have previously identified a population of OSCs in the chicken ovary, but the underlying mechanisms controlling their activation and proliferation were unclear. In this study, we observed that OSCs showed robust proliferation when cultured on a layer of chicken embryo fibroblasts (CEF), suggesting that CEF may secrete certain crucial factors that activate OSC proliferation. We further detected TGFB1 as a potent signaling molecule to promote OSC proliferation. Additionally, we revealed the signaling pathways that play important roles downstream of TGFB1-induced OSC proliferation. These findings provide insights into the mechanisms underlying OSC proliferation in chickens and offer a foundation for future research on in situ activation of OSC proliferation in ovary and improvement of egg-laying performance in chickens.

Identification, characterisation and expression analysis of peanut sugar invertase genes reveal their vital roles in response to abiotic stress.

KEY MESSAGE: Sucrose invertase activity is positively related to osmotic and salt stress resistance in peanut. Sucrose invertases (INVs) have important functions in plant growth and response to environmental stresses. However, their biological roles in peanut are still not fully revealed. In this research, we identified 42 AhINV genes in the peanut genome. They were highly conserved and clustered into three groups with 24 segmental duplication events occurred under purifying selection. Transcriptional expression analysis exhibited that they were all ubiquitously expressed, and most of them were up-regulated by osmotic and salt stresses, with AhINV09, AhINV23 and AhINV19 showed the most significant up-regulation. Further physiochemical analysis showed that the resistance of peanut to osmotic and salt stress was positively related to the high sugar content and sucrose invertase activity. Our results provided fundamental information on the structure and evolutionary relationship of INV gene family in peanut and gave theoretical guideline for further functional study of AhINV genes in response to abiotic stress.

Small extracellular vesicle microRNAs in pediatric myasthenia gravis plasma and skeletal muscle.

BACKGROUND: The diagnosis of myasthenia gravis (MG) in children remains difficult. Circulating small extracellular vesicle (sEV)-derived miRNAs (sEV-miRNAs) have been recognized as biomarkers of various diseases and can be excreted by different cell types. These biomarker candidates also play a vital role in autoimmune diseases via intercellular communication. METHODS: In the present study, we used sEV isolation and purification methods to extract the plasma-derived sEV-miRNAs from children with MG and healthy controls. A small RNA sequencing analysis confirmed the miRNA expression features in plasma-derived sEVs from MG patients. The miRNA expression analysis in vitro was determined using microarray analysis. The enrichment and network analyses of altered sEV-miRNAs were performed using miRNA databases and Database for Annotation, Visualization, and Integrated Discovery website. Quantitative real-time polymerase chain reaction was performed for validation of sEV-miRNA. The diagnostic power of altered sEV-miRNAs was evaluated using receiver operating characteristic curve analyses. RESULTS: Twenty-four sEV-miRNAs with altered expression level were identified between groups by DESeq2 method. The miRNAs were extracted from the sEVs, which were isolated from human primary skeletal muscle cell culture treated with mAb198. The target genes and enriched pathways of sEV-miRNAs partially overlapped between cell supernatant and plasma samples. The significantly downregulated miR-143-3p was validated in quantitative real-time polymerase chain reaction analysis. CONCLUSIONS: For the first time, we report that plasma-derived sEV-miRNAs may act as novel circulating biomarkers and therapeutic targets in pediatric MG.

Effects of the core heading date genes Hd1, Ghd7, DTH8, and PRR37 on yield-related traits in rice.

KEY MESSAGE: We clarify the influence of the genotypes of the heading date genes Hd1, Ghd7, DTH8, and PRR37 and their combinations on yield-related traits and the functional differences between different haplotypes. Heading date is a key agronomic trait in rice (Oryza sativa L.) that determines yield and adaptability to different latitudes. Heading date 1 (Hd1), Grain number, plant height, and heading date 7 (Ghd7), Days to heading on chromosome 8 (DTH8), and PSEUDO-RESPONSE REGULATOR 37 (PRR37) are core rice genes controlling photoperiod sensitivity, and these genes have many haplotypes in rice cultivars. However, the effects of different haplotypes at these genes on yield-related traits in diverse rice materials remain poorly characterized. In this study, we knocked out Hd1, Ghd7, DTH8, or PRR37, alone or together, in indica and japonica varieties and systematically investigated the agronomic traits of each knockout line. Ghd7 and PRR37 increased the number of spikelets and improved yield, and this effect was enhanced with the Ghd7 DTH8 or Ghd7 PRR37 combination, but Hd1 negatively affected yield. We also identified a new weak functional Ghd7 allele containing a mutation that interferes with splicing. Furthermore, we determined that the promotion or inhibition of heading date by different PRR37 haplotypes is related to PRR37 expression levels, day length, and the genetic background. For rice breeding, a combination of functional alleles of Ghd7 and DTH8 or Ghd7 and PRR37 in the hd1 background can be used to increase yield. Our study clarifies the effects of heading date genes on yield-related traits and the functional differences among their different haplotypes, providing valuable information to identify and exploit elite haplotypes for heading date genes to breed high-yielding rice varieties.

Improving yield-related traits by editing the promoter of the heading date gene Ehd1 in rice.

KEY MESSAGE: We developed an efficient promoter editing method to create different weak Ehd1 alleles in elite japonica rice variety ZJ8 with slightly delayed heading and improved yield for use in breeding. Heading date is an important agronomic trait of rice (Oryza sativa) that determines the planting areas and cultivation seasons of different varieties, thus affecting final yield. Early heading date 1 (Ehd1) is a major rice integrator gene in the regulatory network of heading date whose expression level is negatively correlated with heading date and grain yield. Some elite japonica varieties such as Zhongjia 8 (ZJ8) show very early heading with poor agronomic traits when planted in South China. This problem can be addressed by downregulating the expression of Ehd1. In this study, we analyzed the cis-regulatory elements in the Ehd1 promoter region. We then used CRISPR/Cas9-mediated editing to modify the Ehd1 promoter at multiple target sites in ZJ8. We rapidly identified homozygous allelic mutations in the T2 generation via long-read sequencing. We obtained several Ehd1 promoter mutants with different degrees of lower Ehd1 expression, delayed heading date, and improved yield-related traits. We developed an efficient promoter editing method to create different weak Ehd1 alleles for breeding selection. Using this method, a series of heading date materials from elite varieties can be created to expand the planting area of rice and improve grain yields.

Occurrence, Distribution, and Trophic Transfer of Pharmaceuticals and Personal Care Products in the Bohai Sea.

The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in environments has aroused global concerns; however, minimal information is available regarding their multimedia distribution, bioaccumulation, and trophic transfer in marine environments. Herein, we analyzed 77 representative PPCPs in samples of surface and bottom seawater, surface sediments, and benthic biota from the Bohai Sea. PPCPs were pervasively detected in seawater, sediments, and benthic biota, with antioxidants being the most abundant PPCPs. PPCP concentrations positively correlated between the surface and bottom water with a decreasing trend from the coast to the central oceans. Higher PPCP concentrations in sediment were found in the Yellow River estuary, and the variations in the physicochemical properties of PPCPs and sediment produced a different distribution pattern of PPCPs in sediment from seawater. The log Dow, but not log Kow, showed a linear and positive relationship with bioaccumulation and trophic magnification factors and a parabolic relationship with biota-sediment accumulation factors. The trophodynamics of miconazole and acetophenone are reported for the first time. This study provides novel insights into the multimedia distribution and biomagnification potential of PPCPs and suggests that log Dow is a better indicator of their bioaccumulation and trophic magnification.

Target gene mutations endowed cross-resistance to acetolactate synthase-inhibiting herbicides in wild Brassica juncea.

Wild Brassica juncea is a troublesome weed that infests wheat fields in China. Two suspected wild B. juncea populations (19-5 and 19-6) resistant to acetolactate synthase (ALS) inhibitors were collected from wheat fields in China. To clarify their resistance profiles and resistance mechanism, the resistance levels of populations 19-5 and 19-6 to ALS-inhibiting herbicides and their underlying target-site resistance mechanism were investigated. The results showed that the 19-5 population exhibited resistance to tribenuron-methyl, pyrithiobac­sodium and florasulam, while the 19-6 population was resistant to tribenuron-methyl, pyrithiobac­sodium, imazethapyr and florasulam. Using the homologous cloning method, two ALS genes were identified in wild B. juncea, with one gene (ALS1) encoding 652 amino acids and the other (ALS2) encoding 655 amino acids. Pro-197-Arg mutation on ALS2 and Trp-574-Leu mutation on ALS1, together with the combination of these two mutations in a single plant, were observed in both 19-5 and 19-6 populations. ALS2 enzymes carrying the Pro-197-Arg mutation were cross-resistant to tribenuron-methyl, pyrithiobac­sodium, imazerthapyr and florasulam, with resistance index (RI) values of 6.23, 32.81, 7.97 and 1162.50, respectively. Similarly, ALS1 enzymes with Trp-574-leu substitutions also displayed high resistance to these four herbicides (RI values ranging from 132.61 to 3375.00). In addition, the combination of Pro-197-Arg (ALS2) and Trp-574-Leu (ALS1) mutations increased the resistance level of the ALS enzyme to ALS inhibitors, with its RI values 3.83-214.19, 6.88-37.34, 1.91-31.82 and 2.03-5.90-fold higher than a single mutation for tribenuron-methyl, pyrithiobac­sodium, imazerthapyr and florasulam, respectively. Collectively, Pro-197-Arg mutation on ALS2, Trp-574-Leu mutation on ALS1 and the combination of Pro-197-Arg (ALS2) and Trp-574-Leu (ALS1) mutations in wild B. juncea could endow broad-spectrum resistance to ALS inhibitors, which might provide guides for establishing effective strategies to prevent or delay such resistance evolution in this weed.

Aumolertinib-based comprehensive treatment for an uncommon site of EGFR exon 20 insertion mutations with multiple metastases non-small cell lung cancer: a case report.

EGFR exon 20 insertion mutation is a rare mutation subtype of EGFR mutations, with no approved treatment in China so far. The clinical treatments of advanced EGFR exon 20 insertion mutations in non-small cell lung cancer (NSCLC) are mainly based on EGFR-TKI, chemotherapy, ICI, and other therapies. However, the efficacy is not satisfactory. Aumolertinib is the third-generation EGFR-TKI independently developed in China, which has shown excellent efficacy and safety in phase 2 and 3 clinical trials. This study aimed to share a case of applying aumolertinib as the core combined with other treatments for a patient with multiple metastases in NSCLC with an uncommon site of EGFR exon 20 insertion mutations. The comprehensive treatment benefited the patient in terms of 10 months of progression-free survival and a significant improvement in quality of life. We discussed whether we could further explore the potential of aumolertinib in treating EGFR exon 20 insertion mutations through this case report.

Genome Sequence Data of Leptosphaerulina arachidicola, a Causal Agent of Peanut Scorch Spot in China.

Peanut scorch spot caused by Leptosphaerulina arachidicola is one of the most severe leaf diseases of peanut that causes significant yield loss. Here, we report the first high-quality genome sequence of L. arachidicola JB313 isolated from an infected peanut leaf in China. The genome size is 47.66 Mb, consisting of 65 scaffolds (N50 length = 1.58 Mb) with a G+C content of 49.05%. The information in this report will provide a reference genome for future studies on the peanut scorch spot pathogen in peanut.

Exploration of public stereotypes of supply-and-demand characteristics of recycled water infrastructure - Evidence from an event-related potential experiment in Xi'an, China.

There is a growing consensus that recycled water, as an alternative and renewable water source, can serve as a vital water supply to alleviate water scarcity problem and in support of water resilience. Accordingly, recycled water infrastructure investment has seen a significant growth in recent years in many regions of the world. However, previous studies found the perceptions of public, the main end user, toward using recycled water for potable or non-potable purposes remain negatively stereotyped. The negative stereotypes led to public rejections to the construction and operation of recycled water infrastructure. Traditionally, public perceptions of recycled water uses are captured through self-reporting interview or survey techniques. To gain a more accurate measurement of the implicit public stereotypes toward recycled water uses, this study employed an event-related potential (ERPs) technique to collect neurophysiological responses with participants and presented a few research findings. Firstly, the negative stereotypes of recycled water still exist. Secondly, the degree of human contact impacts the negative stereotypes of participants toward recycled water uses more significantly on the supply side (referring to the whole supply chain of recycled water) rather than on the demand side (referring to the potential consumers of recycled water) Third, knowledge level significantly impacts the negative stereotypes of participants toward recycled water uses that have close human contact, at both supply and demand sides, and shows a more significant impact on the supply side. The findings of study contributed to the literature through creatively dividing the negative stereotypes of recycled water into the "supply-side" and the "demand-side" ones, and meanwhile have managerial implication for policymaking and scheme implementation in the area.

Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma.

Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28-2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46-5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19-3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy.

Potentiometric Sensor Based on Carbon Paste Electrode for Monitoring Total Residual Chlorine in Electrolytically-Treated Ballast Water.

A new potentiometric sensor based on modified carbon paste electrode (CPE) was prepared for the sensitive and selective detection of total residual chlorine (TRC) in simulated electrolytically-treated ballast water (BW). The modified CPE was prepared using ferrocene (Fc) as the sensing species and paraffin oil as the binder. It is revealed that the addition of Fc can significantly shorten the response time and improve the reproducibility, selectivity, and stability of the sensor. The open circuit potential of the Fc-CPE is in linear proportion to the logarithm of TRC within the TRC concentration range from 1 mg∙dm-3 to 15 mg∙dm-3. In addition, the Fc-CPE sensor exhibits good selectivity to TRC over a wide concentration range of the possible co-exiting interference ions in seawater. The Fc-CPE electrode can be used as a convenient and reliable sensor for the continuous monitoring of TRC during the electrolytic treatment of BW.

Transcriptome and Gene Editing Analyses Reveal MOF1a Defect Alters the Expression of Genes Associated with Tapetum Development and Chromosome Behavior at Meiosis Stage Resulting in Low Pollen Fertility of Tetraploid Rice.

Autotetraploid rice is a useful rice germplasm for polyploid rice breeding. However, low fertility limits its commercial production. A neo-tetraploid rice with high fertility was developed from the progenies of crossing between autotetraploid lines by our research group. Our previous study showed that a myeloblastosis (MYB) transcription factor, MOF1, might be associated with the pollen development in tetraploid rice. However, little information is available about its role in pollen development in tetraploid rice. Here, we identified a new haplotype of MOF1 from neo-tetraploid rice and marked it as MOF1a. Transcriptome and qRT-PCR analysis demonstrated that MOF1a highly expressed in anthers, and displayed differential expression in neo-tetraploid rice compared to tetraploid rice line with low pollen fertility. The mutant (mof1a) of MOF1a, which was generated by CRISPR/Cas9 knockout in neo-tetraploid rice, showed low pollen fertility, and also exhibited abnormal tapetum and middle layer development, and defective chromosome behaviors during meiosis. A total of 13 tapetal related genes were found to be up-regulated in meiotic anthers of MOF1a compared with wild type plants by RNA-seq analysis, including CYP703A3, PTC1, and OsABCG26, which had been demonstrated to affect tapetal development. Moreover, 335 meiosis-related genes displayed differential expression patterns at same stage, including nine important meiosis-related genes, such as metallothionein OsMT1a. These results demonstrated that MOF1a plays an important role in pollen development and provides a foundation for understanding the molecular mechanism underlying MOF1a in reproduction of tetraploid rice.

Antiviral effects of Shuanghuanglian injection powder against influenza A virus H5N1 in vitro and in vivo.

The current study was to identify a protective role of Shuanghuanglian (SHL) injection powder in vitro and in vivo after H5N1 viral infection. Immunofluorescent staining was used to determine the susceptibility of rat intestinal mucosa microvascular endothelial cells (RIM-MVECs) to the H5N1 virus. Viral replication of RIM-MVECs was measured by transmission electron microscopy (TEM) a hemagglutination assay and real-time quantitative PCR. H5N1 virally infected RIM-MVECs, and BALB/c mice were treated with SHL to investigate its therapeutic effect. Animal survival and the weight of H5N1 virally infected BALB/c mice after SHL treatment was noted, and histology and real-time PCR applied to mouse lungs were used to confirm the anti-H5N1 viral effects of SHL. RIM-MVECs supported replication of the H5N1 virus in vitro. SHL treatment reduced viral titers in H5N1 virally infected RIM-MVECs and mouse lungs. SHL -treated mice survived compared to controls. Mild pathological changes, reduced inflammatory cell infiltration and fewer viral antigens were observed in the lungs of SHL-treated mice at days 3 and 6 post-infection. In conclusion, SHL may have the antiviral activity against the H5N1 virus infection by inhibiting viral replication and alleviating lung injury.

Therapeutic Targeting of RNA Polymerase I With the Small-Molecule CX-5461 for Prevention of Arterial Injury-Induced Neointimal Hyperplasia.

OBJECTIVE: RNA polymerase I (Pol I)-dependent rRNA synthesis is a determinant factor in ribosome biogenesis and thus cell proliferation. The importance of dysregulated Pol I activity in cardiovascular disease, however, has not been recognized. Here, we tested the hypothesis that specific inhibition of Pol I might prevent arterial injury-induced neointimal hyperplasia. APPROACH AND RESULTS: CX-5461 is a novel selective Pol I inhibitor. Using this tool, we demonstrated that local inhibition of Pol I blocked balloon injury-induced neointima formation in rat carotid arteries in vivo. Neointimal development was associated with augmented rDNA transcriptional activity as evidenced by the increased phosphorylation of upstream binding factor-1. The beneficial effect of CX-5461 was mainly mediated by inducing G2/M cell cycle arrest of proliferating smooth muscle cells without obvious apoptosis. CX-5461 did not induce p53 stabilization but increased p53 phosphorylation and acetylation and activated the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATR) pathway. Inhibition of ATR, but not of ataxia telangiectasia mutated, abolished the cytostatic effect of CX-5461 and p53 phosphorylation. In addition, inhibition of p53 or knockdown of the p53 target GADD45 mimicked the effect of ATR inhibition. In vivo experiments showed that the levels of phospho-p53 and acetyl-p53, and activity of the ataxia telangiectasia mutated/ATR pathway were all augmented in CX-5461-treated vessels. CONCLUSIONS: Pol I can be therapeutically targeted to inhibit the growth of neointima, supporting that Pol I is a novel biological target for preventing arterial restenosis. Mechanistically, Pol I inhibition elicited G2/M cell cycle arrest in smooth muscle cells via activation of the ATR-p53 axis.

NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD.

BACKGROUND: Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is suggested as the consequence of emphysematous destruction of vascular bed and hypoxia of pulmonary microenvironment, mechanisms underpinning its pathogenesis however remain elusive. The dysregulated expression of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases and superoxide generation by pulmonary vasculatures have significant implications in the hypoxia-induced PH. METHODS: In this study, the involvement of NADPH oxidase subunit 4 (NOX4) in pulmonary arteriolar remodeling of PH in COPD was investigated by ascertaining the morphological alteration of pulmonary arteries and pulmonary blood flow using cardiac magnetic resonance imaging (cMRI), and the expression and correlation of NOX4 with pulmonary vascular remodeling and pulmonary functions in COPD lungs. RESULTS: Results demonstrated that an augmented expression of NOX4 was correlated with the increased volume of pulmonary vascular wall in COPD lung. While the volume of distal pulmonary arteries was inversely correlated with pulmonary functions, despite it was positively associated with the main pulmonary artery distensibility, right ventricular myocardial mass end-systolic and right ventricular myocardial mass end-diastolic in COPD. In addition, an increased malondialdehyde and a decreased superoxide dismutase were observed in sera of COPD patients. Mechanistically, the abundance of NOX4 and production of reactive oxygen species (ROS) in pulmonary artery smooth muscle cells could be dynamically induced by transforming growth factor-beta (TGF-ß), which in turn led pulmonary arteriolar remodeling in COPD lungs. CONCLUSION: These results suggest that the NOX4-derived ROS production may play a key role in the development of PH in COPD by promoting distal pulmonary vascular remodeling.

Early adventitial activation characterized by NADPH oxidase expression and neovascularization in an aortic transplantation model.

Increasing evidence has suggested that arterial adventitia may contribute to pathological vessel remodeling by producing reactive oxygen species and promoting neovascularization. However, these processes have not been studied yet in transplantation-induced vascular pathologies. We characterized the dynamic changes in NADPH oxidase expression and adventitial angiogenic response in a model of allograft aortic transplantation. The thoracic aorta from Fischer 344 rats were transplanted into the abdominal aorta of Lewis rats. Graft specimens were collected on days 0.5, 3, 7, and 14 for morphometry, immunohistochemistry, immunofluorescence staining, and quantitative PCR tests. Following transplantation, adventitial thickening was found as early as day 3, while neointima was observed from day 7. As compared to normal adventitial tissue, the expression levels of NADPH oxidase subunits gp91phox and p47phox in graft adventitia were elevated from day 3 and further increased up to day 14. Immunohistochemistry staining showed that infiltrating macrophages appeared to be a major source of NADPH oxidase expression. Increases in NADPH oxidase expression were also detected in fibroblasts isolated from the graft adventitia. Gene silencing of p47phox significantly suppressed proliferation and migration of the graft fibroblast cells. We also showed that adventitial thickening was accompanied by increased adventitial neovascularization; at day 14, there was a positive correlation between the density of adventitial microvessels and the neointimal thickness. Transplantation injury induces NADPH oxidase expression and neovascularization in the adventitia, raising the possibility that the activated adventitia may represent a target site for prevention of transplantation-induced transplant vasculopathy.