Genomic and phenotypic signatures provide insights into the wide adaptation of a global plant invader.

Invasive alien species are primary drivers of biodiversity loss and species extinction. Smooth cordgrass (Spartina alterniflora) is one of the most aggressive invasive plants in coastal ecosystems around the world. However, the genomic bases and evolutionary mechanisms underlying its invasion success have remained largely unknown. Here, we assembled a chromosome-level reference genome and performed phenotypic and population genomic analyses between native US and introduced Chinese populations. Our phenotypic comparisons showed that introduced Chinese populations have evolved competitive traits, such as early flowering time and greater plant biomass, during secondary introductions along China's coast. Population genomic and transcriptomic inferences revealed distinct evolutionary trajectories of low- and high-latitude Chinese populations. In particular, genetic mixture among different source populations, together with independent natural selection acting on distinct target genes, may have resulted in high genome dynamics of the introduced Chinese populations. Our study provides novel phenotypic and genomic evidence showing how smooth cordgrass rapidly adapts to variable environmental conditions in its introduced ranges. Moreover, candidate genes related to flowering time, fast growth, and stress tolerance (i.e., salinity and submergence) provide valuable genetic resources for future improvement of cereal crops.

[Effects of Balanced Fertilization and Straw Mulching on Soil Nutrients and Stoichiometry in Purple Soil Slope].

To explore the effects of long-term balanced fertilization and straw mulching on soil nutrients and stoichiometric ratios in purple soil sloping cropland, nine plots (length 7 m×width 3 m) were established in Dianjiang County as the research sample area of long-term farmland nitrogen and phosphorus loss monitoring. The following three treatments were set up:conventional mode (CK), balanced fertilization mode (M1), and balanced fertilization+straw mulching mode (M2), with three replications for each treatment to compare the contents of carbon (C), nitrogen (N), phosphorus (P), and potassium (K) and their stoichiometric changes under different treatments from 2018 to 2020. The results showed:K contents showed significant differences among the three treatments in 2018, in the order of CK>M2>M1. NO3--N and NH4+-N contents showed significant differences among the three treatments in 2019, both in the order of M1>M2>CK. Other nutrient contents showed no significant difference among different treatments each year. Soil C and N contents showed non-significant differences among different years. The total K contents of CK, M1, and M2 in 2018 were significantly higher than that in other years and were 78.26% and 98.79%, 19.13% and 35.4%, and 54.49% and 41.76% higher than that in 2019 and 2020, respectively. The total P content in the CK and M2 treatments decreased with years, and that of CK and M2 in 2018 was 20.29% and 10.67% and 39.68% and 17.33% higher than that in 2019 and 2020, respectively. The available potassium (AK) content of the three treatments showed non-significant differences among different years, whereas the contents of nitrate nitrogen (NO3--N), ammonium nitrogen (NH4+-N), and available phosphorus (AP) showed significant differences among the different treatments, with all being the highest in 2020. Soil C:P, C:K, N:P, N:K, and P:K ratios of each treatment showed significant differences among different years (P<0.05). Soil C:K, N:K, and AN:AP ratios all showed significant differences among different fertilization modes in 2018 and 2019, respectively (P<0.05). There was a significantly linearly positive relationship between soil C and N concentration and soil P and K concentration. There were very significant linear positive correlations between soil C:K and C:P, N:K, N:P, and P:K; N:K with C:P, P:K, and N:P; and N:P with C:P, N:P, and C:P. Soil P concentration was highly significantly linearly negatively correlated with C:K and N:K ratios. There were significant positive correlations between soil NO3--N, NH4+-N, AN:AP, and AN:AK; NH4+-N, AN:AP, and AN:AK; and AN:AP and AN:AK. The results suggested that balanced fertilization and straw mulching was a more suitable management mode for purple soil sloping cropland.

Vitamin A - modified Betulin polymer micelles with hepatic targeting capability for hepatic fibrosis protection.

Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility of homing devices with vitamin A(VA) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of VA modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ VAPPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/VAPPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/VAPPMs exhibited steady and continuous release for over 168 hours. Bt/VAPPMs had good biocompatibility at the cellular level, according to the safety evaluation, and elicited no inflammatory response in mice. More importantly, as uptake behavior studied in cells and bioimaging experiments in vivo, Bt/VAPPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/VAPPMs effectively inhibits collagen I expression in LX-2 cells in vitro, and this effect was also seen in a mouse model of liver fibrosis. Overall, results demonstrated that Bt/VAPPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.

[Characteristics of Runoff-related Total Nitrogen and Phosphorus Losses Under Long-term Fertilization and Cultivation on Purple Soil Sloping Croplands].

To elucidate the effects of long-term fertilization and cultivation on runoff rates and runoff-related nitrogen (N) and phosphorus (P) losses, the following five treatments were established on sloping purple soil cropland:① no fertilizer with downslope tillage (CK), ② combined application of manure and fertilizer with downslope tillage (T1), ③ chemical fertilizers with downslope tillage (T2), ④ chemical fertilizer with increasing fertilization with downslope tillage (T3), and ⑤ chemical fertilizer with contour tillage (T4). The runoff rate, runoff-related total N (TN), and total P (TP) concentrations and their loss rates from 104 erosive rainfall events were determined for the period 2008-2019. Results showed that although runoff rates were not significantly different among the fertilization treatments (P>0.05), runoff was markedly lower in fertilization treatments than in the CK treatment (P<0.05). Runoff-related TN concentrations were significantly higher in the CK compared to the fertilization treatments (P<0.05), while there were no significant differences among the T2, T3, and T4 treatments, which had higher concentrations than the T1 treatment. Runoff-related TP concentrations were significantly higher from the T1, T2, and T3 treatments than the CK treatment (P<0.05), and were significantly lower in the T4 than the CK treatment (P<0.05). TN loss rates were not significantly different among the fertilization treatments (P>0.05), but were all lower than the CK treatment (P<0.05). Furthermore, TP loss rates were not significantly different among the downslope treatments (P>0.05), but were all higher than the contour treatment (P<0.05). Runoff rates showed no significant relationships with TN and TP concentrations in the CK, T1, and T2 treatments but were significantly negatively linearly correlated in T3 (P<0.05) and significantly positively linearly correlated in T4 (P<0.05). These results potentially provide scientific guidance for the prevention and control of agricultural non-point source pollution on sloping croplands in the purple soil area.

[Seasonal Variations in Nitrogen and Phosphorus Concentration and Stoichiometry of Hanfeng Lake in the Three Gorges Reservoir Area].

Based on the seasonal changes in the nitrogen and phosphorus concentrations in Hanfeng Lake from March 2017 to February 2018, the nutrient limitation status was evaluated by the stoichiometric molar ratio of nitrogen and phosphorus. The results showed that the average concentrations of TN, DN, and NO3--N were 1.60, 1.25, and 0.91 mg·L-1 in Hanfeng Lake, respectively. The seasonal changes of those indicators were similar, showing the highest concentration in winter and lowest in summer. NO3--N accounted for TN significantly in the water body, and the concentrations of NH4+-N and NO2--N remained at low levels and changed steadily. The average concentrations of TP, DP, and PO43--P were 0.13, 0.09, and 0.06 mg·L-1, respectively. The changes in the concentrations of TP and DP were similar, showing a trend of increasing in spring and summer, and then decreasing in autumn and winter, while the PO43--P concentration showed the trend of fluctuated decrease. TN/TP varied from 11.07 to 56.02, with an average value of 29.23. TN/TP changed seasonally, with the highest value occurring in winter and the lowest value in summer. The conditions of the water body were conducive to growth and reproduction of algae for most of the time during sampling months. The water body was occasionally nitrogen limited and rarely phosphorus limited. The seasonal variation in TN/TP ratio was affected by several factors such as rainfall runoff, fertilizer use, sewage discharge, and aquatic biological activities. Further, protection strategies were proposed for the improvement of the water body in terms of present water quality characteristics in Hanfeng Lake.

[Spatial-temporal Distribution of Nutrients in Hanfeng Lake After Official Operation].

The hydrograph of Hanfeng Lake, which is the largest pre-dam of theThree Gorges Reservoir, varied between the fluvial stage and lake stage after the lake was officially operated, resulting in large shifts in the aquatic biogeochemical processes. To explore the spatial-temporal distribution of nitrogen and phosphorus concentrations and identify their influencing factors in Hanfeng Lake, seven sampling sites were set up to monitor the changes of nutrients and other water indicators at different water depths monthly from January to December 2018. The results showed that completely vertical mixing across water profiles was observed. The nutrient concentrations were not significantly different between the top, middle, and bottom water depths (P>0.05). Total nitrogen concentration decreased from January to September but gradually increased from October to December, with a monthly average concentration of 1.52 mg·L-1. NO2--N concentration decreased in the first four months, increased sharply from May to June, and decreased from July to December with a monthly average concentration of 0.05 mg·L-1. NO3--N concentration gradually decreased from January to June, and gradually increased from July to December. NH4+-N concentration was the highest in July, with a concentration of 0.44 mg·L-1, and the change in other months was not notable, with a monthly average concentration of 0.09 mg·L-1. The concentrations of total phosphorus (TP), dissolved phosphorus, and soluble reactive phosphorus showed insignificant changes in trends throughout the year, with monthly average concentrations of 0.17 mg·L-1, 0.11 mg·L-1, and 0.05 mg·L-1, respectively. The phosphate concentration was mainly sourced from the upstream Nan River and Taoxi River, and gradually decreased from upper Zhendong to the downstream regulating dam. Of these nutrients, TP was the key factor in the growth of algae in Hanfeng Lake.

[Stoichiometric Characteristics of Purple Sloping Cropland Under Long-term Fertilization and Cultivation].

Clarification of the effects of long-term fertilization and cultivation on soil organic carbon (C), nitrogen (N), phosphorus (P), and potassium (K) contents and their stoichiometric ratios can contribute to existing research on the C and nutrient biogeochemical cycles and their interacting mechanisms. Such information is also of great significance to fertilization management and for the control of non-point pollution. Fifteen plots (8 m long, 4 m wide) were set up on a representative purple hillslope (15°). Five treatments (three replications) were used on the plots:i) no fertilizer with downslope cultivation (CK), ii) combined application of manure and fertilizer with downslope cultivation (T1), iii) chemical fertilizers with downslope cultivation (T2), iv) chemical fertilizer with increasing fertilization with downslope cultivation (T3), and v) chemical fertilizer with contour cultivation (T4). The C, N, P and K contents and their ratios in the five treatments corresponding to 0-10 cm and 10-20 cm soil depths were compared. The results showed that C, N and P contents for the different treatments were differed significant and could be ranked:T1 > T3 > T4 > T2 > CK (P<0.05). K content was not significantly different among the four fertilizations (P>0.05) but was significantly higher than the CK treatment (P<0.05), and could be ranked:T4 > T3 > T2 > T1 > CK. The C:N ratios in the five treatments were significantly different (P<0.05) at a soil depth of 10-20 cm (T4 > T3 > T1 > CK > T2). The C:P ratios in the five treatments were significantly different (P<0.05) at a soil depth of 0-10 cm (T1 > T3 > CK > T4 > T2). The C:K, N:P, N:K, and P:K ratios for the five treatments at both of the soil depths showed significant differences (P<0.05), and the C:K, N:K, and P:K were ranked as T1 > T3 > T4 > T2 > CK, whereas the N:P ratio was ranked as T1 > CK > T4 > T3 > T2. The C, N, P, and K contents and their stoichiometric ratios decreased with increasing soil depth. Soil C, N and P in the study site showed moderate variations based on their coefficient of variation (CV):37.50%, 38.91%, and 25.35%, respectively. Soil K on the other hand showed a weak variation (CV 5.03%). Soil C:N and C:P also showed a weak variation with a CV of 7.52% and 14.38%, respectively. Soil C:K, N:P, N:K, and P:K showed moderate variations, with a CV of 35.62%, 17.01%, 37.24% and 44.78%, respectively. There were significant positive interrelations among soil C, N, P, and K contents and their stoichiometric ratios (P<0.05). The average N:P ratio was 2.09, which was much lower than the average value for various soil types in China. Our results indicate that soil N is the key limiting nutrient in purple hillslope land, and that the combination of organic and inorganic fertilizers can effectively alleviate the N deficiency in the study area.

Immune suppression in chronic hepatitis B infection associated liver disease: A review.

Hepatitis B virus (HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer (HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer (NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC), NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBV-induced immune dysfunction and HBV-related liver diseases are not understood. In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC.

Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-ß pathways.

Late-stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)-dependent anticancer properties in vitro and in vivo. The present work aims to explore the anti-metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both in vitro and in vivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti-metastatic activity of DSF, while Cu alone had no effect. Furthermore, DSF/Cu inhibited both NF-κB and TGF-ß signalling, including the nuclear translocation of NF-κB subunits and the expression of Smad4, leading to down-regulation of Snail and Slug, which contributed to phenotype epithelial-mesenchymal transition (EMT). Finally, DSF/Cu inhibited the lung metastasis of Hep3B cells not only in a subcutaneous tumour model but also in an orthotopic liver metastasis assay. These results indicated that DSF/Cu suppressed the metastasis and EMT of hepatic carcinoma through NF-κB and TGF-ß signalling. Our study indicates the potential of DSF/Cu for therapeutic use.

PAQR3 gene expression and its methylation level in colorectal cancer tissues.

The aim of the present study was to investigate the PAQR3 gene expression and its methylation level in colorectal cancer tissues, as well as the association with colorectal cancer clinical data. In total, 54 cases of colorectal cancer tissue samples and normal adjacent tissue samples were collected between June, 2013 and July, 2014. RT-PCR and western blot analysis were used to detect the mRNA and protein levels of PAQR3 in colorectal samples, respectively. MSP was used to detect the methylation level of PAQR3 gene in colorectal samples, which was compared with colorectal data. The results showed that a decreased expression level of PAQR3 mRNA in colorectal cancer tissues and the expression reduction rate was 57.4% (31/54). Similarly, the expression level of PAQR3 protein was reduced in cancer tissues, and the reduction rate was 46.3% (25/54), while the protein expression reduction rate in cancer adjacent tissue was 5.6% (3/54), and the difference was statistically significant (P<0.05). Furthermore, the methylation rates of PAQR3 in cancer tissues and cancer adjacent tissues were 33.3% (18/54) and 5.6% (3/54), respectively. In addition, PAQR3 mRNA and protein levels in colorectal cancer tissues were associated with the differentiation degree, lymphatic metastasis and tumor infiltration depth. The methylation level of PAQR3 was associated with age, differentiated degree, lymphatic metastasis and tumor infiltration depth. In conclusion, the expression of PAQR3 mRNA and protein in colorectal cancer was reduced and methylation of PAQR3 occurred. Although the PAQR3 mRNA and protein levels were not associated with gender, age or the location of tumor, there was an association with differentiation degree, lymphatic metastasis and tumor infiltration depth. In addition, the methylation level of PAQR3 was not correlated with gender or tumor location, but was correlated with age, differentiation degree, lymphatic metastasis and tumor infiltration depth.

Multiple differential expression networks identify key genes in rectal cancer.

BACKGROUND: Rectal cancer is an important contributor to cancer mortality. OBJECTIVE: The objective of this paper is to identify key genes across three phenotypes (fungating, polypoid and polypoid & small-ulcer) of rectal cancer based on multiple differential expression networks (DENs). METHODS: Differential interactions and non-differential interactions were evaluated according to Spearman correlation coefficient (SCC) algorithm, and were selected to construct DENs. Topological analysis was performed for exploring hub genes in largest components of DENs. Key genes were denoted as intersections between nodes of DENs and rectal cancer associated genes from Genecards. Finally, we utilized hub genes to classify phenotypes of rectal cancer on the basis of support vector machines (SVM) methodology. RESULTS: We obtained 19 hub genes and total 12 common key genes of three largest components of DENs, and EGFR was the common element. The SVM results revealed that hub genes could classify phenotypes, and validated feasibility of DEN methods. CONCLUSIONS: We have successfully identified significant genes (such as EGFR and UBC) across fungating, polypoid and polypoid & small-ulcer phenotype of rectal cancer. They might be potential biomarkers for classification, detection and therapy of this cancer.

The Role of Immune Cells in Chronic HBV Infection.

Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses are important factors that determine whether HBV infection is cleared or persists. After infection, viral replication occurs inside hepatocytes, and the secretion of infectious virions can take place at high rates for decades. Consequently, HBV DNA and viral proteins, like HBV early antigen (HBeAg) and HBV surface antigen (HBsAg), can be easily detected in serum. Chronic infection with HBV is the result of an ineffective antiviral immune response towards the virus. In this review, we discuss the role of immune cells in chronic HBV infection.