ILD-GAP combined with the monocyte ratio could be a better prognostic prediction model than ILD-GAP in patients with interstitial lung diseases.

BACKGROUND: The ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis. METHODS: In patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models. RESULTS: A total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074). CONCLUSIONS: The ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

Alternative splicing of CsJAZ1 negatively regulates flavan-3-ol biosynthesis in tea plants.

Flavan-3-ols are abundant in the tea plant (Camellia sinensis) and confer tea with flavor and health benefits. We recently found that alternative splicing of genes is likely involved in the regulation of flavan-3-ol biosynthesis; however, the underlying regulatory mechanisms remain unknown. Here, we integrated metabolomics and transcriptomics to construct metabolite-gene networks in tea leaves, collected over five different months and from five spatial positions, and found positive correlations between endogenous jasmonic acid (JA), flavan-3-ols, and numerous transcripts. Transcriptome mining further identified CsJAZ1, which is negatively associated with flavan-3-ols formation and has three CsJAZ1 transcripts, one full-length (CsJAZ1-1), and two splice variants (CsJAZ1-2 and -3) that lacked 3' coding sequences, with CsJAZ1-3 also lacking the coding region for the Jas domain. Confocal microscopy showed that CsJAZ1-1 was localized to the nucleus, while CsJAZ1-2 and CsJAZ1-3 were present in both the nucleus and the cytosol. In the absence of JA, CsJAZ1-1 was bound to CsMYC2, a positive regulator of flavan-3-ol biosynthesis; CsJAZ1-2 functioned as an alternative enhancer of CsJAZ1-1 and an antagonist of CsJAZ1-1 in binding to CsMYC2; and CsJAZ1-3 did not interact with CsMYC2. In the presence of JA, CsJAZ1-3 interacted with CsJAZ1-1 and CsJAZ1-2 to form heterodimers that stabilized the CsJAZ1-1-CsMYC2 and CsJAZ1-2-CsMYC2 complexes, thereby repressing the transcription of four genes that act late in the flavan-3-ol biosynthetic pathway. These data indicate that the alternative splicing variants of CsJAZ1 coordinately regulate flavan-3-ol biosynthesis in the tea plant and improve our understanding of JA-mediated flavan-3-ol biosynthesis.

Regulation of biosynthesis of the main flavor-contributing metabolites in tea plant (Camellia sinensis): A review.

In the process of adapting to the environment, tea plants (Camellia sinensis) endow tea with unique flavor and health functions, which should be attributed to secondary metabolites, including catechins, L-theanine, caffeine and terpene volatiles. Since the content of these flavor-contributing metabolites are mainly determined by the growth of tea plant, it is very important to understand their alteration and regulation mechanisms. In the present work, we first summarize the distribution, change characteristics of the main flavor-contributing metabolites in different cultivars, organs and under environmental stresses of tea plant. Subsequently, we discuss the regulating mechanisms involved in the biosynthesis of these metabolites based on the existing evidence. Finally, we propose the remarks and perspectives on the future study relating flavor-contributing metabolites. This review would contribute to the acceleration of research on the characteristic secondary metabolites and the breeding programs in tea plants.

Healthcare costs attributable to abnormal weight in China: evidence based on a longitudinal study.

BACKGROUND: The prevalence of abnormal weight is on the rise, presenting serious health risks and socioeconomic problems. Nonetheless, there is a lack of studies on the medical cost savings that can be attained through the mitigation of abnormal weight. The aim of this study was to estimate the impact of abnormal weight on healthcare costs in China. METHODS: The study employed a 4-wave panel data from China Family Panel Studies (CFPS) between 2012 and 2018 (11,209 participants in each wave). Inpatient, non-inpatient and total healthcare costs were outcome variables. Abnormal weight is categorized based on body mass index (BMI). Initially, the two-part model was employed to investigate the impact of overweight/obesity and underweight on healthcare utilisation and costs, respectively. Subsequently, the estimated results were utilised to calculate the overweight/obesity attributable fraction (OAF) and the underweight attributable fraction (UAF). RESULTS: In 2018, healthcare costs per person for overweight and obese population were estimated to be $607.51 and $639.28, respectively, and the underweight population was $755.55. In comparison to people of normal weight, individuals who were overweight/obese (OR = 1.067, p < 0.05) was more likely to utilise healthcare services. Overweight/obesity attributable fraction (OAF) was 3.90% of total healthcare costs and 4.31% of non-inpatient costs. Overweight/obesity does not result in additional healthcare expenditures for young people but increases healthcare costs for middle-aged adults (OAF = 7.28%) and older adults (OAF = 6.48%). The non-inpatient cost of underweight population was significantly higher than that of normal weight population (ß = 0.060,p < 0.1), but the non-inpatient health service utilisation was not significantly affected. CONCLUSIONS: Abnormal weight imposes a huge economic burden on individuals, households and the society. Abnormal weight in Chinese adults significantly increased healthcare utilisation and costs, particular in non-inpatient care. It is recommended that government and relevant social agencies provide a better social environment to enhance individual self-perception and promote healthy weight.

Empirical validation of the information-motivation-behavioral skills model of gestational weight management behavior: a framework for intervention.

BACKGROUND: Unhealthy gestational weight gain is a modifiable risk factor for adverse maternal and child health. Appropriate and effective intervention strategies that focus on behavioral change or maintenance are critical in weight management during pregnancy. Our aim was to uncover the influencing factors and psychosocial mechanisms of gestational weight control behavior, and to construct a behavioral model suitable for intervention based on Information-Motivation-Behavioral skills (IMB) model. METHODS: A sample of 559 pregnant women from a municipal maternal and child healthcare facility in Jiangsu Province, China was enrolled in this cross-sectional empirical study. Partial least square structural equation modelling was used to verify the hypothesized model, and post hoc analyses was used to test the effect of parity and pre-pregnancy BMI on the model. RESULTS: The IMB model elements can predict gestational weight management (GWM) behavior well, with information being the most influential factor. As predicted, information affects GWM directly (ß = 0.325, p < 0.05) and indirectly (ß = 0.054, p < 0.05) through behavioral skills. Likewise, motivation has direct (ß = 0.461, p < 0.05) effects on GWM, and has indirect (ß = 0.071, p < 0.05) effects through behavioral skills. Behavioral skills have a direct impact (ß = 0.154, p < 0.05). The model had a goodness of fit (GOF = 0.421) and was robust when tested in subgroups of different parity or pre-pregnancy BMI. CONCLUSION: Findings from this study supported the predictions of the IMB model for GWM behavior, and identified its modifiable determinants. The tested behavior model for GWM can serve as a new validated intervention strategy in weight management among pregnant women.

Multi-omics analysis to visualize the dynamic roles of defense genes in the response of tea plants to gray blight.

Gray blight (GB) is one of the most destructive diseases of tea plants, causing considerable damage and productivity losses; however, the dynamic roles of defense genes during pathogen infection remain largely unclear. To explore the numerous molecular interactions associated with GB stress in tea plants, we employed transcriptome, sRNAome and degradome sequencing from 1 to 13 days post-inoculation (dpi) at 3-day intervals. The transcriptomics results showed that differentially expressed genes (DEGs) related to flavonoid synthesis, such as chalcone synthase (CHS) and phenylalanine ammonia-lyase (PAL), were particularly induced at 4 dpi. Consistent with this, the contents of catechins (especially gallocatechin), which are the dominant flavonoids in tea plants, also increased in the leaves of tea plants infected with GB. Combined analysis of the sRNAome and degradome revealed that microRNAs could mediate tea plant immunity by regulating DEG expression at the post-transcriptional level. Co-expression network analysis demonstrated that miR530b-ethylene responsive factor 96 (ERF96) and miRn211-thaumatin-like protein (TLP) play crucial roles in the response to GB. Accordingly, gene-specific antisense oligonucleotide assays suggested that suppressing ERF96 decreased the levels of reactive oxygen species (ROS), whereas suppressing TLP increased the levels of ROS. Furthermore, ERF96 was induced, but TLP was suppressed, in susceptible tea cultivars. Our results collectively demonstrate that ERF96 is a negative regulator and TLP is a positive regulator in the response of tea plants to GB. Taken together, our comprehensive integrated analysis reveals a dynamic regulatory network linked to GB stress in tea plants and provides candidate genes for improvement of tea plants.

Large-area large-grain CsPbCl3perovskite films by confined re-growth for violet photodetectors.

CsPbCl3perovskite is an attractive semiconductor material with characteristics such as a wide bandgap, high chemical stability, and excellent optoelectronic properties, which broaden its application prospects for ultraviolet (UV) and violet photodetectors (PDs). However, large-area CsPbCl3films with high coverage, large grains, and controllable thickness are still difficult to prepare by using the solution method due to the extremely low solubility of their precursors in conventional solvents. Herein, a water-assisted confined re-growth method is developed, and a CsPbCl3microcrystalline film with an area of 3 cm × 3 cm is grown, the thickness of which is controllable within a range of several microns. The as-prepared thin film exhibits a flat and smooth surface, large grains, and enhanced photoluminescence. Furthermore, the fabricated violet PDs based on the prepared CsPbCl3film show a high responsivity of 2.17 A W-1, external quantum efficiency of 664%, on/off ratio of 2.58 × 103, and good stability. This study provides a prospective solution for the growth of large-area, large-grain, and surface-smooth CsPbCl3films for high-performance UV and violet PDs.

Enhanced simultaneous partial nitrification and denitrification performance of aerobic granular sludge via tapered aeration in sequencing batch reactor for treating low strength and low COD/TN ratio municipal wastewater.

The aerobic granular sludge simultaneous partial nitrification, denitrification and phosphorus removal (AGS-SPNDPR) process was carried out via tapered aeration in sequencing batch reactor (SBR) for treating low strength and low COD/TN ratio municipal wastewater. The results showed that aerobic granular sludge was successfully cultivated with good sedimentation performance when treating the municipal wastewater. Meanwhile, the median granule size increased to 270 (R1) and 257 (R2) µm on day 80. The excellent removal performance of COD (92%) and NH4+-N (95%) were achieved under different aeration modes, while the higher TN removal efficiency (76%) was achieved by tapered aeration. The accumulation of NO2--N in R2 indicated that the tapered aeration was beneficial to achieve simultaneously partial nitrification and denitrification. Meanwhile, the high-efficiency phosphorus (95%) removal was realized via additional carbon source, and SPNDPR process was formed under tapered aeration. The bacterial community analysis indicated denitrifying glycogen-accumulating organisms (DGAOs) Candidatus_Competibacter and ammonia-oxidizing bacteria (AOB) Nitrosomonas were more effectively enriched via tapered aeration, while phosphorus-accumulating organisms (PAOs) Candidatus_Accumulibacter were effectively enriched under additional organic carbon. AOB, denitrifying bacteria and PAOs were simultaneously enriched by tapered aeration and additional carbon source, which was beneficial to nutrients removal. This study might be conducive to the application of AGS-SPNDPR system for treating low strength and low COD/TN ratio municipal wastewater under tapered aeration.

The GHG mitigation opportunity of sludge management in China.

Greenhouse gas (GHG) mitigation in wastewater treatment sector is indispensable in China's carbon neutral target. As an important component of wastewater system, sludge generation is rapidly increased with the acceleration of urbanization in China. It is crucial to investigate the carbon footprint of various sludge management strategies and quantify the potential optimization of GHG reduction effect at national scale. Therefore, this study conducted a comprehensive analysis of sludge distribution and GHG profiles of various sludge systems. The overall dry sludge generation in China is 12.15 Mt, with spatial resolution at city level. Different sludge treatment options were categorized into four types: energy recovery, nutrient recovery (e.g. phosphorus and nitrogen), material valorisation (e.g. brick, biochar) and conventional disposal. With various sludge treatment options, the GHG profile of annual sludge management in China ranges from -35.86 Mt/year to 57.11 Mt/year. The best GHG mitigation can be achieved through energy recovery by co-incineration system and the greatest reduction opportunity is concentrated in highly urbanized regions, such as Yangtze River Delta, Pearl River Delta, and Beijing-Tianjin-Hebei urban agglomerations.

Long noncoding RNA growth arrest-specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2.

Diabetic nephropathy (DN) is a frequently occurred microvascular complication associated with type I and type II diabetes mellitus. The participation of long noncoding RNAs (lncRNAs) in diabetes-related microvascular complications has been reported extensively. We attempted to unveil the possible regulatory mechanism of lncRNA growth arrest-specific transcript 5 (GAS5) and matrix metalloproteinase 9 (MMP9), an important inflammatory protein, in the progression of DN. A rat DN model was induced by streptozocin (STZ). The low expression of GAS5 and high expression of MMP9 in DN rats with DN was then determined by RT-qPCR and western blot analysis, and lentivirus-mediated GAS5 overexpression was shown to ameliorate STZ-induced renal interstitial fibrosis (RIF) and inflammatory reaction in the kidney of DN rats. Moreover, MMP9 was found to be upregulated in STZ-induced DN, while MMP9 silencing induced by lentivirus expressing shRNA against MMP9 reduced RIF and suppressed inflammation in the kidney of DN rats. RIP, RNA pull-down, and ChIP assays demonstrated that GAS5 downregulated MMP9 via recruiting enhancer of zeste homolog 2 (EZH2) in the promoter region of MMP9. Overall, our study reveals that GAS5 downregulates MMP9 expression through recruiting EZH2 to MMP9 promoter region and alleviates the progression of renal fibrosis in DN rats, which sheds new light on the therapeutic potential of GAS5-targeted therapies in combating that disease.

miR-194-Loaded Gelatin Nanospheres Target MEF2C to Suppress Muscle Atrophy in a Mechanical Unloading Model.

Muscle atrophy usually occurs under mechanical unloading, which increases the risk of injury to reduce the functionality of the moving system, while there is still no effective therapy until now. It was found that miR-194 was significantly downregulated in a muscle atrophy model, and its target protein was the myocyte enhancer factor 2C (MEF2C). miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid drug to treat muscle atrophy, whereas miRNA was unstable in vivo, limiting its application as a therapeutic drug. A gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA here. Exogenous miR-194 was loaded in GNs and injected into the muscle atrophy model. It demonstrated that the muscle fiber cross-sectional area, in situ muscle contractile properties, and myogenic markers were increased significantly after treatment. It proposed miR-194 loaded in GNs as an effective treatment for muscle atrophy by promoting muscle differentiation and inhibiting ubiquitin ligase activity. Moreover, the developed miRNA delivery system, taking advantage of its tunable composition, degradation rate, and capacity to load various drug molecules with high dosage, is considered a promising platform to achieve precise treatment of muscle atrophy-related diseases.

Efficacy and safety of different ticagrelor regimens versus clopidogrel in patients with coronary artery disease: a retrospective multicenter study (SUPERIOR).

Current guidelines favor dual anti-platelet therapy with ticagrelor 90 mg BID (T90BID) over clopidogrel 75 mg QD (C75QD) in addition to aspirin for acute coronary syndrome. However, an increased risk of ticagrelor-related adverse events prompted the evaluation of low-dose regimens. This study (NCT03381742) retrospectively analyzed the data from 11 hospitals on 3,043 patients with coronary artery disease, who received C75QD, T90BID, ticagrelor 45 mg BID (T45BID), or ticagrelor 90 mg QD (T90QD). Compared with C75QD, both T45BID and T90QD showed significantly higher inhibition of platelet aggregation (P < .0001) and lower platelet-fibrin clot strength (P < .0001) induced by adenosine diphosphate. Furthermore, compared with T90BID, two low-dose regimens had a much lower minor bleeding rate and a significantly higher proportion of patients within the therapeutic window for P2Y12 receptor reactivity. There were no significant differences between T45BID and T90QD in the trough plasma concentrations of ticagrelor and its active metabolite. Similar efficacy and safety outcomes were observed in the propensity score-matched analysis. In conclusion, the low-dose ticagrelor regimen, either T45BID or T90QD, may provide a more attractive benefit-risk profile than C75QD or T90BID.

Transcriptomic analyses reveal a systemic defense role of the uninfested adjacent leaf in tea plant (Camellia sinensis) attacked by tea geometrids (Ectropis obliqua).

To get a more detailed understanding of the interaction between tea plant (Camellia sinensis) and tea geometrids (Ectropis obliqua), transcriptomic profile in undamaged adjacent leaf (TGL) of tea geometrids fed local leaves (LL) was investigated for the first time. Here, approximately 245 million clean reads contained 39.39 Gb of sequence data were obtained from TGL. Further analysis revealed that systemic response was induced in TGL after tea geometrids feeding on LL, although the defense response was weaker than that in LL. The differentially expressed genes (DEGs) identification analysis showed little overlap of DEGs between TGL and LL. Comparative transcriptome analysis suggested that JA signal regulated resistant pathway was induced in LL; whereas primary metabolism pathway was activated in TGL in response to tea geometrids feeding. This study reveals a novel resistance mechanism of TGL to tea geometrids feeding.

Effects of Light Intensity and Spectral Composition on the Transcriptome Profiles of Leaves in Shade Grown Tea Plants (Camellia sinensis L.) and Regulatory Network of Flavonoid Biosynthesis.

Black net shade treatment attenuates flavonoid biosynthesis in tea plants, while the effect of light quality is still unclear. We investigated the flavonoid and transcriptome profiles of tea leaves under different light conditions, using black nets with different shade percentages, blue, yellow and red nets to alter the light intensity and light spectral composition in the fields. Flavonol glycosides are more sensitive to light intensity than catechins, with a reduction percentage of total flavonol glycosides up to 79.6% compared with 38.7% of total catechins under shade treatment. A total of 29,292 unigenes were identified, and the KEGG result indicated that flavonoid biosynthesis was regulated by both light intensity and light spectral composition while phytohormone signal transduction was modulated under blue net shade treatment. PAL, CHS, and F3H were transcriptionally downregulated with light intensity. Co-expression analysis showed the expressions of key transcription factors MYB12, MYB86, C1, MYB4, KTN80.4, and light signal perception and signaling genes (UVR8, HY5) had correlations with the contents of certain flavonoids (p < 0.05). The level of abscisic acid in tea leaves was elevated under shade treatment, with a negative correlation with TFG content (p < 0.05). This work provides a potential route of changing light intensity and spectral composition in the field to alter the compositions of flavor substances in tea leaves and regulate plant growth, which is instructive to the production of summer/autumn tea and matcha.

Comprehensive profiling of alternative splicing landscape during cold acclimation in tea plant.

BACKGROUND: Alternative splicing (AS) may generate multiple mRNA splicing isoforms from a single mRNA precursor using different splicing sites, leading to enhanced diversity of transcripts and proteins. AS has been implicated in cold acclimation by affecting gene expression in various ways, yet little information is known about how AS influences cold responses in tea plant (Camellia sinensis). RESULTS: In this study, the AS transcriptional landscape was characterized in the tea plant genome using high-throughput RNA-seq during cold acclimation. We found that more than 41% (14,103) of genes underwent AS events. We summarize the possible existence of 11 types of AS events, including the four common types of intron retention (IR), exon skipping (ES), alternative 5' splice site (A5SS), and alternative 3' splice site (A3SS); of these, IR was the major type in all samples. The number of AS events increased rapidly during cold treatment, but decreased significantly following de-acclimation (DA). It is notable that the number of differential AS genes gradually increased during cold acclimation, and these genes were enriched in pathways relating to oxidoreductase activity and sugar metabolism during acclimation and de-acclimation. Remarkably, the AS isoforms of bHLH transcription factors showed higher expression levels than their full-length ones during cold acclimation. Interestingly, the expression pattern of some AS transcripts of raffinose and sucrose synthase genes were significantly correlated with sugar contents. CONCLUSION: Our findings demonstrated that changes in AS numbers and transcript expression may contribute to rapid changes in gene expression and metabolite profile during cold acclimation, suggesting that AS events play an important regulatory role in response to cold acclimation in tea plant.

Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer.

Breast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration-dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen-induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration-resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.

Integrated transcriptomics and metabolomics analysis of catechins, caffeine and theanine biosynthesis in tea plant (Camellia sinensis) over the course of seasons.

BACKGROUND: Catechins, caffeine, and theanine as three important metabolites in the tea leaves play essential roles in the formation of specific taste and shows potential health benefits to humans. However, the knowledge on the dynamic changes of these metabolites content over seasons, as well as the candidate regulatory factors, remains largely undetermined. RESULTS: An integrated transcriptomic and metabolomic approach was used to analyze the dynamic changes of three mainly metabolites including catechins, caffeine, and theanine, and to explore the potential influencing factors associated with these dynamic changes over the course of seasons. We found that the catechins abundance was higher in Summer than that in Spring and Autumn, and the theanine abundance was significantly higher in Spring than that in Summer and Autumn, whereas caffeine exhibited no significant changes over three seasons. Transcriptomics analysis suggested that genes in photosynthesis pathway were significantly down-regulated which might in linkage to the formation of different phenotypes and metabolites content in the tea leaves of varied seasons. Fifty-six copies of nine genes in catechins biosynthesis, 30 copies of 10 genes in caffeine biosynthesis, and 12 copies of six genes in theanine biosynthesis were detected. The correlative analysis further presented that eight genes can be regulated by transcription factors, and highly correlated with the changes of metabolites abundance in tea-leaves. CONCLUSION: Sunshine intensity as a key factor can affect photosynthesis of tea plants, further affect the expression of major Transcription factors (TFs) and structural genes in, and finally resulted in the various amounts of catechins, caffeine and theaine in tea-leaves over three seasons. These findings provide new insights into abundance and influencing factors of metabolites of tea in different seasons, and further our understanding in the formation of flavor, nutrition and medicinal function.

microRNA-206 overexpression inhibits epithelial-mesenchymal transition and glomerulosclerosis in rats with chronic kidney disease by inhibiting JAK/STAT signaling pathway.

Chronic kidney disease (CKD) is a traumatic disease with significant psychic consequences to the patient's overall physical condition. microRNA-206 (miR-206) has been reported to play an essential role in the development of various diseases. The purpose of the present study is to investigate the effect of miR-206 through the JAK/STAT signaling pathway on epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and glomerulosclerosis in rats with CKD. The targeting relationship between miR-206 and ANXA1 was verified. To explore the role of miR-206 in CKD, the model of CKD rats was established to detect glomerular sclerosis index (GSI), contents of interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-ß1), and expression of type IV collagen. Moreover, to further determine the roles of both miR-206 and the JAK/STAT signaling pathway in CKD, the gain- and loss-of function approaches were performed with the expression of ANXA1, α-SMA, E-cadherin, vimentin, N-cadherin, and the JAK/STAT signaling pathway-related genes detected. miR-206 negatively targeted ANXA1. Overexpressed miR-206 inhibited the degeneration and interstitial fibrosis of renal tubular epithelial cells, decreased GSI of rats, and the expression of type IV collagen, TGF-ß1 and IL-6. Overexpressed miR-206 inhibited the degeneration of renal tubular epithelial cells, the expression of ANXA1, α-SMA, TGF-ß1, p-STAT3, STAT3, p-STAT1, STAT1, p-JAK2, and JAK2, while promoted the expression of E-cadherin. Taken together the results, miR-206 inhibits EMT of renal tubular epithelial cells and glomerulosclerosis by inactivating the JAK/STAT signaling pathway via ANXA1 in CKD.

Characterization and Alternative Splicing Profiles of the Lipoxygenase Gene Family in Tea Plant (Camellia sinensis).

Oxylipins, including jasmonic acid (JA) and volatiles, are important for signaling in plants, and these are formed by the lipoxygenase (LOX) enzyme family. There is a large gap in understanding of the underlying molecular basis of their roles in tea plants. Here, we identified 11 CsLOX genes from the tea plant (Camellia sinensis), and characterized their phylogeny, gene structure and protein features into three subclasses. We then examined their enzymatic activities, LOX expression and alternative splicing of transcripts during development and in response to abiotic or biotic stresses in tea plants. In vitro expressed protein assays showed that the CsLOX2, 3 and 9 enzymatically function to produce 9/13-HPOT, 13-HPOT and 9-HPOT, respectively. CsLOX2 and CsLOX9 green fluorescent protein (GFP) fusion proteins localized to chloroplasts and the cytoplasm, respectively. RNA sequencing, quantitative reverse transcription-PCR and Northern blot analysis suggested that CsLOX5, 6 and 9 were predominantly expressed in seeds, flowers and roots, respectively. CsLOX2, 3, 4, 6 and 7 were up-regulated after attack by the insect Ectropis oblique, while CsLOX1 was induced after infection with the pathogen Glomerella cingulata. CsLOX3, 7 and 10 were up-regulated by JA but not ABA or salicylic acid. Long-term cold stress down-regulated CsLOX expression while a short duration of cold induced the expression of CsLOX1, 6 and 7. Alternatively spliced transcripts of six CsLOX genes were dynamically regulated through time and varied in relative abundances under the investigated stresses; we propose a mechanism of competing or compensating regulation between isoforms. This study improves our understanding of evolution of LOXs and regulation of their diverse functions in plants.

Global dissection of alternative splicing uncovers transcriptional diversity in tissues and associates with the flavonoid pathway in tea plant (Camellia sinensis).

BACKGROUND: Alternative splicing (AS) regulates mRNA at the post-transcriptional level to change gene function in organisms. However, little is known about the AS and its roles in tea plant (Camellia sinensis), widely cultivated for making a popular beverage tea. RESULTS: In our study, the AS landscape and dynamics were characterized in eight tissues (bud, young leaf, summer mature leaf, winter old leaf, stem, root, flower, fruit) of tea plant by Illumina RNA-Seq and confirmed by Iso-Seq. The most abundant AS (~ 20%) was intron retention and involved in RNA processes. The some alternative splicings were found to be tissue specific in stem and root etc. Thirteen co-expressed modules of AS transcripts were identified, which revealed a similar pattern between the bud and young leaves as well as a distinct pattern between seasons. AS events of structural genes including anthocyanidin reductase and MYB transcription factors were involved in biosynthesis of flavonoid, especially in vegetative tissues. The AS isoforms rather than the full-length ones were the major transcripts involved in flavonoid synthesis pathway, and is positively correlated with the catechins content conferring the tea taste. We propose that the AS is an important functional mechanism in regulating flavonoid metabolites. CONCLUSION: Our study provides the insight into the AS events underlying tea plant's uniquely different developmental process and highlights the important contribution and efficacy of alternative splicing regulatory function to biosynthesis of flavonoids.