OsOFP6 Overexpression Alters Plant Architecture, Grain Shape, and Seed Fertility.

OVATE family proteins (OFPs) play important roles in plant growth and development, hormone signaling, and stress response pathways. However, the functions of OsOFPs in rice are largely unknown. In this study, a novel gain-of-function rice mutant, Osofp6-D, was identified. This mutant exhibited decreased plant height, erect leaves, reduced panicle size, short and wide seeds, delayed seed germination time, and reduced fertility. These phenotypic changes were attributed to the increased expression of OsOFP6, which was caused by a T-DNA insertion. Complementation of the Osofp6-D phenotype by knockout of OsOFP6 using the CRISPR/Cas9 system confirmed that the Osofp6-D phenotype was caused by OsOFP6 overexpression. In addition, transgenic plants overexpressing OsOFP6 with the 35S promoter mimicked the Osofp6-D phenotype. Cytological observations of the glumes showed that OsOFP6 overexpression altered the grain shape, mainly by altering the cell shape. Hormone response experiments showed that OsOFP6 was involved in the gibberellin (GA) and brassinolide (BR) signaling responses. Further studies revealed that OsOFP6 interacts with E3BB, which is orthologous to the Arabidopsis central organ size-control protein BIG BROTHER (BB). This study further elucidates the regulation mechanism of the rice OFP family on plant architecture and grain shape.

cGAS-STING pathway mediates activation of dendritic cell sensing of immunogenic tumors.

Type I interferons (IFN-I) play pivotal roles in tumor therapy for three decades, underscoring the critical importance of maintaining the integrity of the IFN-1 signaling pathway in radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, the specific mechanism by which IFN-I contributes to these therapies, particularly in terms of activating dendritic cells (DCs), remains unclear. Based on recent studies, aberrant DNA in the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) signaling pathway, which in turn produces IFN-I, which is essential for antiviral and anticancer immunity. Notably, STING can also enhance anticancer immunity by promoting autophagy, inflammation, and glycolysis in an IFN-I-independent manner. These research advancements contribute to our comprehension of the distinctions between IFN-I drugs and STING agonists in the context of oncology therapy and shed light on the challenges involved in developing STING agonist drugs. Thus, we aimed to summarize the novel mechanisms underlying cGAS-STING-IFN-I signal activation in DC-mediated antigen presentation and its role in the cancer immune cycle in this review.

The Dilemma of HSV-1 Oncolytic Virus Delivery: The Method Choice and Hurdles.

Oncolytic viruses (OVs) have emerged as effective gene therapy and immunotherapy drugs. As an important gene delivery platform, the integration of exogenous genes into OVs has become a novel path for the advancement of OV therapy, while the herpes simplex virus type 1 (HSV-1) is the most commonly used. However, the current mode of administration of HSV-1 oncolytic virus is mainly based on the tumor in situ injection, which limits the application of such OV drugs to a certain extent. Intravenous administration offers a solution to the systemic distribution of OV drugs but is ambiguous in terms of efficacy and safety. The main reason is the synergistic role of innate and adaptive immunity of the immune system in the response against the HSV-1 oncolytic virus, which is rapidly cleared by the body's immune system before it reaches the tumor, a process that is accompanied by side effects. This article reviews different administration methods of HSV-1 oncolytic virus in the process of tumor treatment, especially the research progress in intravenous administration. It also discusses immune constraints and solutions of intravenous administration with the intent to provide new insights into HSV-1 delivery for OV therapy.

Spectral properties inspired image enhancement for crystalline polymer powder impurity detection.

Crystalline polymer powder inevitably incorporates certain impurities, including decomposed polymers or foreign particles. An essential criterion for assessing the quality of polymers is the quantity of contaminants in the powder. However, it is challenging to discern powder contaminants through machine vision due to the poor quality of images taken at production sites. Inspired by the spectral properties of crystalline polymers, this paper proposes an efficient image-based impurity detection method, which seeks to precisely and robustly detect contaminant content. Based on the changes in absorbance during polymer decomposition, a highly selective channel-weighted image enhancement approach is designed to emphasize the difference between impurities and normal particles. Then, using the prior information on the powder's attributes, an adaptive thresholding method is employed to categorize pixels belonging to impurities. Finally, a dataset of 119 12-megapixel photos from a chemical facility, where the average size of contaminants in images is 43 pixels, is used to evaluate the performance of the proposed algorithm. The results of the detection demonstrate that the proposed strategy for image enhancement has better selectivity to impurities than typical image enhancement methods.

CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway.

BACKGROUND: The upregulated expression of CXCL1 has been validated in colorectal cancer patients. As a potential biotherapeutic target for colorectal cancer, the mechanism by which CXCL1 affects the development of colorectal cancer is not clear. METHODS: Expression data of CXCL1 in colorectal cancer were obtained from the GEO database and verified using the GEPIA database and the TIMER 2.0 database. Knockout and overexpression of CXCL1 in colorectal cancer cells by CRISPR/Cas and "Sleeping Beauty" transposon-mediated gene editing techniques. Cell biological function was demonstrated by CCK-8, transwell chamber and Colony formation assay. RT-qPCR and Western Blot assays measured RNA and protein expression. Protein localization and expression were measured by immunohistochemistry and immunofluorescence. RESULTS: Bioinformatics analysis showed significant overexpression of CXCL1 in the colorectal cancer tissues compared to normal human tissues, and identified CXCL1 as a potential therapeutic target for colorectal cancer. We demonstrate that CXCL1 promotes the proliferation and migration of colon cancer cells and has a facilitative effect on tumor angiogenesis. Furthermore, CXCL1 elevation promoted the migration of M2-tumor associated macrophages (TAMs) while disrupting the aggregation of CD4+ and CD8+ T cells at tumor sites. Mechanistic studies suggested that CXCL1 activates the NF-κB pathway. In the in vivo colon cancer transplantation tumor model, treatment with the P300 inhibitor C646 significantly inhibited the growth of CXCL1-overexpressing colon cancer. CONCLUSION: CXCL1 promotes colon cancer development through activation of NF-κB/P300, and that CXCL1-based therapy is a potential novel strategy to prevent colon cancer development.

Effects of drought stress and elevated CO2 on starch fine structures and functional properties in indica rice.

The changes in rice starch fine structures and functional properties induced by drought, elevated CO2 (eCO2) and combined treatments remain to be elucidated comprehensively. In this study, starch molecular structures were characterized by size-exclusion chromatography and fluorophore-assisted carbohydrate electrophoresis, and the data from amylopectin chain-length distributions was fitted with a mathematical model to obtain parameters for statistical analysis. Starch crystalline structures, thermal and pasting properties of rice flour were also analyzed. All the treatments decreased the seed setting rate and increased chalky grains, reflecting the abnormal starch accumulation. However, eCO2 partially increased the seed setting rate and chalky grains under drought stress. The stress-treated starch samples had shorter amylopectin short and intermediate chains, the lower degree of ordered structures, but similar amylose content and relative crystallinity. This led to lower onset gelatinization temperature and paste viscosities, which may be responsible for the worse sensory quality of rice grains.

Prognostic factors for patients with mass-forming intrahepatic cholangiocarcinoma: A case series of 68 patients.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer in humans after hepatocellular carcinoma and a rare epithelial malignancy that results in a poor prognosis. According to the Liver Cancer Study Group of Japan classification, ICC can be divided into three types: Mass-forming (MF) type, periductal-infiltrating (PI) type, and intraductal-growth type. The MF type is the most common, accounting for 57.1-83.6% of ICCs. Nevertheless, little is known about the epidemiology and treatment of MF ICC. AIM: To examine the prognostic factors for patients with MF ICC. METHODS: We carried out a retrospective analysis of consecutive patients with MF ICC treated at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital between January 2008 and December 2018. According to the treatment received, the patients were divided into either a resection group or an exploration group. RESULTS: The pooled 1-, 3-, and 5-year survival rates in the 68 patients with MF ICC were 66.5%, 36.3%, and 9.3%, respectively. Univariate analysis revealed that surgical resection (P < 0.001), nodal metastasis (P < 0.001), tumor location (P = 0.039), vascular invasion (P < 0.001), ascites (P < 0.001), and differentiation (P = 0.009) were significantly associated with the prognosis and survival of MF ICC. Multivariate analysis revealed that ascites (hazard ratio [HR] = 5.6, 95% confidence interval [CI]: 1.6-18.9, P = 0.006) and vascular invasion (HR = 2.5, 95%CI: 1.0-6.1, P = 0.045) were independent risk factors for MF ICC. The pooled 1-, 3-, and 5-year survival rates in the 19 patients of the exploration group were 5.3%, 5.3%, and 0, respectively. Among the 49 patients who underwent surgical resection, the pooled 1-, 3-, and 5-year survival rates were 93.5%, 49.7%, and 14.4%, respectively. Univariate and multivariate analyses revealed that vascular invasion (HR = 3.1, 95%CI: 1.2-8.5, P = 0.024) and nodal metastasis (HR = 3.2, 95%CI: 1.4-7.6, P = 0.008) were independent prognostic risk factors for surgical resection patients. CONCLUSION: The prognosis of MF ICC patients is dismal, especially those with ascites or vascular invasion. Surgical resection is a key factor in improving overall survival in patients with MF ICC, and vascular invasion and lymph node metastasis affect the efficacy of surgical resection.

The role of PPR proteins in posttranscriptional regulation of organelle components in plants.

Pentatricopeptide repeat (PPR) proteins constitute one of the largest protein families in land plants. They are sequence-specific RNA-binding proteins and play key roles in posttranscriptional processes within organelles. Their combined actions have profound effects on chloroplast photosynthetic electron transport chain and mitochondrial respiratory chain, affecting photosynthesis and respiration respectively, and ultimately on yield, fertility, and grain quality. Over the past decade, much has been learned about the molecular functions of these proteins on plant growth and development. However, due to the large size of this protein family, the functions of most members remain largely unknown. Here, we summarize the molecular mechanisms of PPR proteins functions on organelle genes, and effects on development of organelles and plants. Problems that need to be resolved are also identified. This article will provide a theoretical basis for understanding the functions of PPR protein family and genetic improvements of grain yield and quality.

Feasibility and safety of "bridging" pancreaticogastrostomy for pancreatic trauma in Landrace pigs.

BACKGROUND: In recent years, we created and employed a new anastomosis method, "bridging" pancreaticogastrostomy, to treat patients with extremely severe pancreatic injury. This surgery has advantages such as short length of surgery, low secondary trauma, rapid construction of shunts for pancreatic fluid, preventing second surgeries, and achieving good treatment outcomes in clinical practice. However, due to the limited number of clinical cases, there is a lack of strong evidence to support the feasibility and safety of this surgical procedure. Therefore, we carried out animal experiments to examine this procedure, which is reported here. AIM: To examine the feasibility and safety of a new rapid method of pancreaticogastrostomy, "bridging" pancreaticogastrostomy. METHODS: Ten Landrace pigs were randomized into the experimental and control groups, with five pigs in each group. "Bridging" pancreaticogastrostomy was performed in the experimental group, while routine mucosa-to-mucosa pancreaticogastrostomy was performed in the control group. After surgery, the general condition, amylase levels in drainage fluid on Days 1, 3, 5, and 7, fasting and 2-h postprandial blood glucose 6 mo after surgery, fasting, 2-h postprandial peripheral blood insulin, and portal vein blood insulin 6 mo after surgery were assessed. Resurgery was carried out at 1 and 6 mo after the former one to examine the condition of the abdominal cavity and firmness and tightness of the pancreaticogastric anastomosis and pancreas. RESULTS: After surgery, the general condition of the animals was good. One in the control group did not gain weight 6 mo after surgery, whereas significant weight gain was present in the others. There were significant differences on Days 1 and 3 after surgery between the two groups but no differences on Days 5 and 7. There were no differences in fasting and 2-h postprandial blood glucose and fasting and 2-h insulin values of postprandial peripheral blood and portal vein blood 6 mo after surgery between the two groups. One month after surgery, the sinus tract orifice/anastomosis was patent in the two groups. Six months after surgery, the sinus tract orifice/anastomosis was sealed, and pancreases in both groups presented with chronic pancreatitis. CONCLUSION: "Bridging" pancreaticogastrostomy is a feasible and safe a means of damage control surgery during the early stage of pancreatic injury.

Generation of Marker-Free Transgenic Rice Resistant to Rice Blast Disease Using Ac/Ds Transposon-Mediated Transgene Reintegration System.

Rice blast is one of the most serious diseases of rice and a major threat to rice production. Breeding disease-resistant rice is one of the most economical, safe, and effective measures for the control of rice blast. As a complement to traditional crop breeding, the transgenic method can avoid the time-consuming process of crosses and multi-generation selection. In this study, maize (Zea mays) Activator (Ac)/Dissociation (Ds) transposon vectors carrying green fluorescent protein (GFP) and red fluorescent protein (mCherry) genetic markers were used for generating marker-free transgenic rice. Double fluorescent protein-aided counterselection against the presence of T-DNA was performed together with polymerase chain reaction (PCR)-based positive selection for the gene of interest (GOI) to screen marker-free progeny. We cloned an RNAi expression cassette of the rice Pi21 gene that negatively regulates resistance to rice blast as a GOI into the Ds element in the Ac/Ds vector and obtained marker-free T1 rice plants from 13 independent transgenic lines. Marker-free and Ds/GOI-homozygous rice lines were verified by PCR and Southern hybridization analysis to be completely free of transgenic markers and T-DNA sequences. qRT-PCR analysis and rice blast disease inoculation confirmed that the marker-free transgenic rice lines exhibited decreased Pi21 expression levels and increased resistance to rice blast. TAIL-PCR results showed that the Ds (Pi21-RNAi) transgenes in two rice lines were reintegrated in intergenic regions in the rice genome. The Ac/Ds vector with dual fluorescent protein markers offers more reliable screening of marker-free transgenic progeny and can be utilized in the transgenic breeding of rice disease resistance and other agronomic traits.

Construction and integration of genetic linkage maps from three multi-parent advanced generation inter-cross populations in rice.

BACKGROUND: The construction of genetic maps based on molecular markers is a crucial step in rice genetic and genomic studies. Pure lines derived from multiple parents provide more abundant genetic variation than those from bi-parent populations. Two four-parent pure-line populations (4PL1 and 4PL2) and one eight-parent pure-line population (8PL) were developed from eight homozygous indica varieties of rice by the International Rice Research Institute (IRRI). To the best of our knowledge, there have been no reports on linkage map construction and their integration in multi-parent populations of rice. RESULTS: We constructed linkage maps for the three multi-parent populations and conducted quantitative trait locus (QTL) mapping for heading date (HD) and plant height (PH) based on the three maps by inclusive composite interval mapping (ICIM). An integrated map was built from the three individual maps and used for QTL projection and meta-analysis. QTL mapping of the three populations was also conducted based on the integrated map, and the mapping results were compared with those from meta-analysis. The three linkage maps developed for 8PL, 4PL1 and 4PL2 had 5905, 4354 and 5464 bins and were 1290.16, 1720.01 and 1560.30 cM in length, respectively. The integrated map was 3022.08 cM in length and contained 10,033 bins. Based on the three linkage maps, 3, 7 and 9 QTLs were detected for HD while 6, 9 and 10 QTLs were detected for PH in 8PL, 4PL1 and 4PL2, respectively. In contrast, 19 and 25 QTLs were identified for HD and PH by meta-analysis using the integrated map, respectively. Based on the integrated map, 5, 9, and 10 QTLs were detected for HD while 3, 10, and 12 QTLs were detected for PH in 8PL, 4PL1 and 4PL2, respectively. Eleven of these 49 QTLs coincided with those from the meta-analysis. CONCLUSIONS: In this study, we reported the first rice linkage map constructed from one eight-parent recombinant inbred line (RIL) population and the first integrated map from three multi-parent populations, which provide essential information for QTL linkage mapping, meta-analysis, and map-based cloning in rice genetics and breeding.

A novel prognostic score model based on combining systemic and hepatic inflammation markers in the prognosis of HBV-associated hepatocellular carcinoma patients.

Objectives: The study aimed to evaluate the prognostic value of systemic inflammation markers [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Prognostic Nutritional Index (PNI)] and hepatic inflammation markers [aspartate aminotransferase-to-platelet ratio index (APRI), γ-glutamyl transferase (γ-GT)/alanine aminotransferase (ALT)] in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and further to develop a novel prognostic score model. Methods: A total of 401 cases with HBV-associated HCC who underwent hepatectomy as initial therapy were included in the analysis. Kaplan-Meier was performed to construct survival curves and receiver operating characteristic (ROC) analysis was used to detect the optimal cut-off value of markers. The prognostic score model was constructed using significant inflammation markers in the Cox model. Each factor was given a score of 1 and patients were stratified according to the scores. Results: In the Cox model, α-fetoprotein (AFP), ALT, tumour differentiation, maximum size of tumours, TNM stage, PNI and γ-GT/ALT were independently prognostic factors. We established a preoperative inflammation-based prognostic scoring model combining PNI and γ-GT/ALT. The novel preoperative inflammation-based prognostic score was superior (area under the curve [AUC], 0.659) to 7th tumour-node-metastasis (TNM) stage (AUC, 0.600) despite no statistical significance (p = .1036). Conclusion: PNI and γ-GT/ALT are independent predictors for prognosis. The novel prognostic score model based on systemic and hepatic inflammation markers is suitable for the prognosis evaluation in patients with HBV-associated HCC.

QTL Identification for Cooking and Eating Quality in indica Rice Using Multi-Parent Advanced Generation Intercross (MAGIC) Population.

Association mapping using a multi-parent advanced generation intercross (MAGIC) population provides a promising tool in genetic dissection of rice cooking and eating quality (CEQ). In this study, QTLs were identified for ten physicochemical properties related to CEQ using 508 F6 MAGIC lines. The whole population and eight founder lines were genotyped with 6K Illumina Infinium HD Assay. All traits had high heritability estimates and showed a large genetic variation in the MAGIC population. Highly significant phenotypic correlations were present between traits. AC was significantly positively correlated with PKT, TV, FV, SBV, PKT, and RT but significantly negatively correlated with GC and BDV. Seventeen QTLs were identified for all traits. GBSSI locus was hosted or closely to nine QTLs, qAC6, qGC6.1, qPKT6.1, qPKV6, qBDV6.1, qTV6.1, qFV6, qSBV6, and qRT6, suggesting that GBSSI impacts the overall CEQ. Another locus closed to SSIIa, located at 6.99 Mb, affects five traits, GC, PKT, BDV, SBV, and PT. The identified QTLs revealed small to modest effects where the highest percentage of phenotypic variance explained was 17.18%. These QTLs are directly relevant and useful in breeding for CEQ in indica rice. These results also confirmed that QTL mapping via association mapping using a MAGIC population is a powerful method in genetic analysis of complex traits.

Association Mapping of Ferrous, Zinc, and Aluminum Tolerance at the Seedling Stage in Indica Rice using MAGIC Populations.

Excessive amounts of metal are toxic and severely affect plant growth and development. Understanding the genetic control of metal tolerance is crucial to improve rice resistance to Fe, Zn, and Al toxicity. The multi-parent advanced generation inter-cross (MAGIC) populations were genotyped using a 55 K rice SNP array and screened at the seedling stage for Fe, Zn, and Al toxicity using a hydroponics system. Association analysis was conducted by implementing a mixed linear model (MLM) for each of the five MAGIC populations double cross DC1 (founders were SAGC-08, HHZ5-SAL9-Y3-Y1, BP1976B-2-3-7-TB-1-1, PR33282-B-8-1-1-1-1-1), double cross DC2 (founders of double cross were FFZ1, CT 16658-5-2-2SR-2-3-6MP, IR 68, IR 02A127), eight parents population 8way (founders were SAGC-08, HHZ5-SAL9-Y3-Y1, BP1976B-2-3-7-TB-1-1, PR33282-B-8-1-1-1-1-1, FFZ1, CT 16658-5-2-2SR-2-3-6MP, IR 68, IR 02A127), DC12 (DC1+DC2) and rice multi-parent recombinant inbred line population RMPRIL (DC1+DC2+8way). A total of 21, 30, and 21 QTL were identified for Fe, Zn, and Al toxicity tolerance, respectively. For multi tolerance (MT) as Fe, Zn, and Al tolerance-related traits, three genomic regions, MT1.1 (chr.1: 35.4-36.3 Mb), MT1.2 (chr.1: 35.4-36.3 Mb), and MT3.2 (chr.3: 35.4-36.2 Mb) harbored QTL. The chromosomal regions MT2.1 (chr.2: 2.4-2.8 Mb), MT2.2 (chr.2: 24.5-25.8 Mb), MT4 (chr.4: 1.2 Mb Mb), MT8.1 (chr.8: 0.7-0.9 Mb), and MT8.2 (chr.8: 2.2-2.4 Mb) harbored QTL for Fe and Zn tolerance, while MT2.3 (chr.2: 30.5-31.6 Mb), MT3.1 (chr.3: 12.5-12.8 Mb), and MT6 (chr.6: 2.0-3.0 Mb) possessed QTL for Al and Zn tolerance. The chromosomal region MT9.1 (chr.9: 14.2-14.7 Mb) possessed QTL for Fe and Al tolerance. A total of 11 QTL were detected across different MAGIC populations and 12 clustered regions were detected under different metal conditions, suggesting that these genomic regions might constitute valuable regions for further marker-assisted selection (MAS) in breeding programs.

Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines.

Aldose reductase (AR) expression is elevated in the livers of patients with alcoholic liver diseases. However, the role of AR in the development of alcoholic liver diseases remains unclear. The aim of the present study was to determine the effect of AR inhibition on ethanol­induced hepatosteatosis in vivo and in vitro, and to identify possible underlying molecular mechanisms. Alcoholic fatty livers were induced in C57BL/6 mice by feeding the mice with Lieber­DeCarli liquid diets. The expression of AR protein was elevated in the liver tissue of C57BL/6 mice fed with an ethanol diet and in mouse AML12 liver cells exposed to ethanol. In addition to the elevation in AR, hepatic steatosis was observed in ethanol diet­fed mice, and this ethanol­induced steatosis was significantly attenuated by inhibiting AR activity with a specific inhibitor, zopolrestat. The suppressive effect of AR inhibition was associated with decreased levels of hepatic lipoperoxides, decreased protein expression of hepatic cytochrome P450 2E1 (CYP2E1), increased phosphorylation of 5'­AMP­activated protein kinase (AMPK) and decreased mRNA expression of tumor necrosis factor­α (TNF­α). Treatment with the AR inhibitor attenuated the level of lipid accumulation and oxidative stress, activated AMPK, and suppressed the mRNA expression of TNF­α, interleukin­6 and transforming growth factor­ß1 in ethanol­treated AML12 cells. The results of the present study demonstrated that inhibition of AR ameliorated alcoholic liver disease in vivo and in vitro, in part by activating AMPK, decreasing CYP2E1­mediated oxidative stress and ameliorating the expression of pro­inflammatory cytokines.

Inhibition of aldose reductase ameliorates ethanol­induced steatosis in HepG2 cells.

Aldose reductase (AR) expression is increased in liver tissue of patients with ethanol­induced liver disease. However, the exact role of AR in the development of ethanol­induced liver disease has yet to be elucidated. The present study aimed to determine the effect of an AR inhibitor on ethanol­induced steatosis in HepG2 cells and to identify possible underlying molecular mechanisms. Steatosis was induced in HepG2 cells by stimulating cells with 100 mM absolute ethanol for 48 h. Oil Red O staining was used to detect the lipid droplet accumulation in cells. Western blot analyses were used to determine protein expression levels and reverse transcription­quantitative polymerase chain reaction was used to analyze mRNA expression levels. The results showed that AR protein expression was elevated in HepG2 cells stimulated with ethanol. HepG2 cells exhibited marked improvement of ethanol­induced lipid accumulation following treatment with the AR inhibitor zopolrestat. Phosphorylation levels of 5' adenosine monophosphate­activated protein kinase (AMPK) were markedly higher, whereas the mRNA expression levels of sterol­regulatory element­binding protein (SREBP)­1c and fatty acid synthase (FAS) were significantly lower in zopolrestat­treated and ethanol­stimulated HepG2 cells compared with in untreated ethanol­stimulated HepG2 cells. In addition, zopolrestat inhibited the ethanol­induced expression of tumor necrosis factor (TNF)­α. These results suggested that zopolrestat attenuated ethanol­induced steatosis by activating AMPK and subsequently inhibiting the expression of SREBP­1c and FAS, and by suppressing the expression of TNF­α in HepG2 cells.

Characterization of Three Rice Multiparent Advanced Generation Intercross (MAGIC) Populations for Quantitative Trait Loci Identification.

Three new rice ( L.) multiparent advanced generation intercross (MAGIC) populations were developed using eight elite rice varieties from different breeding programs. These three populations were two recombinant inbred line (RIL) populations derived from two 4-way crosses, DC1 and DC2, and one RIL population derived from an 8-way cross. These populations were genotyped using an Illumina Infinium rice 6K SNP chip. The potential of the three MAGIC populations in identifying marker-trait associations was demonstrated using the plant height (PH) and heading date (HD) measured in 2014. A population of 248 IRRI breeding lines and a population of 323 Chinese breeding lines were also included to compare genetic diversity and linkage disequilibrium (LD) pattern. Our study discovered that (i) the 8-way population had a higher gene diversity than the DC1, DC2, and IRRI populations; (ii) all three MAGIC populations showed no clear population structure; (iii) LD decayed to < 0.2 at about 2.5, 2.5, 1.25, 1.75, and 4.0 Mb for the DC1, DC2, 8-way, IRRI, and Chinese populations, respectively; and (iv) the 8-way population was more powerful than the DC1, DC2, and IRRI populations on QTL identification. The association analysis identified two and three QTL for PH and HD, respectively. Four of the five QTL had peak markers close to known genes. A novel QTL for PH was identified on chromosome 12 using the 8-way population. Therefore, our study suggests that the three new MAGIC populations are valuable resources for QTL identification.

Anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-κB/p53-apoptosis signaling pathway.

Xanthohumol may prevent and cure diabetes and atherosis, have oxidation resistance and antiviral function as well as anticancer effect preventing cancer cell metastasis. We investigate whether the anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-κB/p53-apoptosis signaling pathway. Human liver cancer HepG2 cell were treated with 10, 20, 30 and 40 µM xanthohumol for 48 h. The present study showed that the anticancer effect of xanthohumol was effective in inhibiting proliferation and inducing apoptosis of human liver cancer HepG2 cells. Furthermore, the caspase-3 activity of human liver cancer HepG2 cells was increased by xanthohumol. In addition, 48-h treatment with xanthohumol suppressed NF-κB expression and promoted p53, cleaved PARP, AIF and cytochrome c expression and downregulated XIAP and Bcl-2/Bax expression in human liver cancer HepG2 cells. Therefore, the anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through the NF-κB/p53-apoptosis signaling pathway.

Identification of stable QTLs causing chalk in rice grains in nine environments.

KEY MESSAGE: A novel QTL cluster for chalkiness on Chr04 was identified using single environment analysis and joint mapping across 9 environments in Asia and South American. QTL NILs showed that each had a significant effect on chalk. Chalk in rice grains leads to a significant loss in the proportion of marketable grains in a harvested crop, leading to a significant financial loss to rice farmers and traders. To identify the genetic basis of chalkiness, two sets of recombinant inbred lines (RILs) derived from reciprocal crosses between Lemont and Teqing were used to find stable QTLs for chalkiness. The RILs were grown in seven locations in Asia and Latin American and in two controlled environments in phytotrons. A total of 32 (21) and 46 (22) QTLs for DEC and PGWC, most of them explaining more than 10% of phenotypic variation, were detected based on single environment analysis in T/L (L/T) population, respectively. Seven (2) and 7 (3) QTLs for DEC and PGWC were identified in the T/L (L/T) population using joined analysis across all environments, respectively. Six major QTLs clusters were found on five chromosomes: 1, 2, 4, 5 and 11. The biggest cluster at id4007289-RM252 on Chr04 was a novelty, including 16 and 4 QTLs detected by single environment analysis and joint mapping across all environments, respectively. The detected digenic epistatic QTLs explained up to 13% of phenotypic variation, suggesting that epistasis play an important role in the genetic control of chalkiness in rice. QTL NILs showed that each QTL cluster had a significant effect on chalk. These chromosomal regions could be targets for MAS, fine mapping and map-based cloning for low chalkiness breeding.

The Usefulness of Known Genes/Qtls for Grain Quality Traits in an Indica Population of Diverse Breeding Lines Tested using Association Analysis.

BACKGROUND: A number of studies reported major genes/QTLs for rice grain shapes, chalkiness and starch physicochemical properties. For these finely mapped QTLs or cloned genes to make an impact in practical breeding, it is necessary to test their effects in different genetic backgrounds. In this study, two hundred nineteen markers for 20 starch synthesis genes, 41 fine mapped grain shape and related traits QTLs/genes, and 54 chalkiness QTLs/genes plus 15 additional markers and a large indica population of 375 advanced lines were used to identify marker-trait associations under 6 environments that can be used directly in breeding for grain quality traits. RESULTS: The significant associations detected by the QK model were used to declare the usefulness of the targeted genes/QTLs. A total of 65 markers were detected associations with grain quality trait at least in one environment. More phenotypic variations could be explained by haplotype than single marker, as exemplified by the starch biosynthesising genes. GBSSI was the major gene for AC and explained up to 55 % of the phenotypic variation, which also affected GC and accounted up to 11.31 % of the phenotypic variation. SSIIa was the major gene for chalkiness and explained up to 17 and 21 % of variation of DEC and PGWC, respectively. In addition, RMw513 and RM18068 were associated with DEC in 6 environments as well. Four markers (RGS1, RM15206, RMw513 and Indel1) tightly linked to GS3, gw5, and qGL7-2 were the most important ones for grain shapes. Allelic combinations between SSIIa and RMw513 revealed more variations in DEC. CONCLUSIONS: The validated markers for genes/QTLs with major effects could be directly used in breeding for grain quality via marker-assisted selection. Creating desirable allelic combinations by gene pyramiding might be an effective approach for the development of high quality breeding lines in rice.