The elite eating quality alleles Wxb and ALKb are regulated by OsDOF18 and coordinately improve head rice yield.

Head rice yield (HRY) measures rice milling quality and determines final grain yield and commercial value. Here, we report that two major quantitative trait loci for milling quality in rice, qMq-1 and qMq-2, represent allelic variants of Waxylv /Waxyb (hereafter Wx) encoding Granule-Bound Starch Synthase I (GBSSI) and Alkali Spreading Value ALKc /ALKb encoding Soluble Starch Synthase IIa (SSIIa), respectively. Complementation and overexpression transgenic lines in indica and japonica backgrounds confirmed that Wx and ALK coordinately regulate HRY by affecting amylose content, the number of amylopectin branches, amyloplast size, and thus grain filling and hardness. The transcription factor OsDOF18 acts upstream of Wx and ALK by activating their transcription. Furthermore, rice accessions with Wxb and ALKb alleles showed improved HRY over those with Wxlv and ALKc . Our study not only reveals the novel molecular mechanism underlying the formation of HRY but also provides a strategy for breeding rice cultivars with improved HRY.

RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma.

BACKGROUND: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. METHODS: Gene set enrichment analysis (GSEA) was conducted in the TCGA LIHC cohort to investigate the underlying biological mechanism of RIT1. Live cell imaging, immunofluorescence (IF) and flow cytometry assays were used to verify biological function of RIT1 in HCC mitosis. Subcutaneous xenografting of human HCC cells in BALB/c nude mice was utilized to assess tumor proliferation in vivo. RNA-seq, co-immunoprecipitation (Co-IP), mass spectrometry analyses, western blot and IF assays were employed to elucidate the mechanisms by which RIT1 regulates mitosis and promotes proliferation in HCC. RESULTS: Our findings demonstrate that RIT1 plays a crucial role in regulating mitosis in HCC. Knockdown of RIT1 disrupts cell division, leading to G2/M phase arrest, mitotic catastrophe, and apoptosis in HCC cells. SMC3 is found to interact with RIT1 and knockdown of SMC3 attenuates the proliferative effects mediated by RIT1 both in vitro and in vivo. Mechanistically, RIT1 protects and maintains SMC3 acetylation by binding to SMC3 and PDS5 during mitosis, thereby promoting rapid cell division and proliferation in HCC. Notably, we have observed an upregulation of SMC3 expression in HCC tissues, which is associated with poor patient survival and promotion of HCC cell proliferation. Furthermore, there is a significant positive correlation between the expression levels of RIT1, SMC3, and PDS5. Importantly, HCC patients with high expression of both RIT1 and SMC3 exhibit worse prognosis compared to those with high RIT1 but low SMC3 expression. CONCLUSIONS: Our findings underscore the crucial role of RIT1 in regulating mitosis in HCC and further demonstrate its potential as a promising therapeutic target for HCC treatment.

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers across the world. It has a poor prognosis and lacks effective therapies, especially for patients with advanced-stage cancer, indicating an urgent need for new therapies and novel therapeutic targets. Here, by screening the U.S. Food and Drug Administration drug library against HCC cell lines, we identified that flubendazole, a traditional anthelmintic drug, could prominently suppress HCC cells in vivo and in vitro. RNA sequence analysis and cellular thermal shift assays showed that flubendazole reduced the expression of PCSK9 protein by direct targeting. The increased expression of PCSK9 in HCC tissues was demonstrated to be correlated with poor prognosis, and the inhibitory ability of flubendazole was selectively dependent on PCSK9 expression. PCSK9 knockdown abolished the antitumor effects of flubendazole in HCC. Mechanistically, flubendazole inhibited the Hedgehog signaling pathway induced by PCSK9, resulting in the downregulation of smoothened (SMO) and GLI Family Zinc Finger 1 (Gli1). Moreover, combining flubendazole with lenvatinib was found more effective than administering lenvatinib only for HCC treatment in vivo and in vitro. These findings reveal the therapeutic potential of flubendazole against HCC and provide clues on new repurposed drugs and targets for cancer treatment.

Modeling facial perception in group context from a serial perception perspective.

By utilizing statistical properties and summary statistics, the visual system can efficiently integrate perception of spatially and temporally adjacent stimuli into perception of a given target. For instance, perception of a target face can either be biased positively toward previous faces (e.g. the serial dependence effect) or be biased negatively by surrounding faces in the same trial/space (e.g. spatial ensemble averaging). However, both aspects were investigated separately. As spatial and temporal processing share the same purpose to reduce redundancy in visual processing, if one statistical processing occurs, would the statistical processing in the other domain still exist or be discarded? We investigated this question by exploring whether serial dependence of face perception (of attractiveness and averageness) survives when the changed face perception in the group context occurs. The results of Markov Chain modeling and conventional methods suggested that serial dependence (the temporal aspect) co-occurs with changed face perception in the group context (the spatial aspect). We also utilized the Hidden Markov modeling, as a new mathematical method, to model statistical processing from both domains. The results confirmed the co-occurrence of temporal effect and changed face perception in the group context for both attractiveness and averageness, suggesting potentially different spatial and temporal compression mechanisms in high-level vision. Further modeling and cluster analysis further revealed that the detailed computation of spatially and temporally adjacent faces in the attractiveness and averageness processing were similar yet different among different individuals. This work builds a bridge to understanding mathematical principles underlying changed face perception in the group context from the serial perspective.

Compensation Mechanisms May Not Always Account for Enhanced Multisensory Illusion in Older Adults: Evidence from Sound-Induced Flash Illusion.

Sound-induced flash illusion (SiFI) is typical auditory dominance phenomenon in multisensory illusion. Although a number of studies have explored the SiFI in terms of age-related effects, the reasons for the enhanced SiFI in older adults are still controversial. In the present study, older and younger adults with equal visual discrimination were selected to explore age differences in SiFI effects, and to explore the neural indicators by resting-state functional magnetic resonance imaging (rs-fMRI) signals. A correlation analysis was calculated to examine the relationship between regional homogeneity (ReHo) and the SiFI. The results showed that both younger and older adults experienced significant fission and fusion illusions, and fission illusions of older adults were greater than that of younger adults. In addition, our results showed ReHo values of the left middle frontal gyrus (MFG), the right inferior frontal gyrus (IFG) and right superior frontal gyrus (SFG) were significantly positively correlated with the SiFI in older adults. More importantly, the comparison between older and younger adults showed that ReHo values of the right superior temporal gyrus (STG) decreased in older adults, and this was independent of the SiFI. The results indicated that when there was no difference in unisensory ability, the enhancement of multisensory illusion in older adults may not always be explained by compensation mechanisms.

Sperm associated antigen 4 promotes SREBP1-mediated de novo lipogenesis via interaction with lamin A/C and contributes to tumor progression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor and its progression is associated with altered lipid metabolism in precancerous lesions, such as non-alcoholic fatty liver disease. Here, we identified sperm associated antigen 4 (SPAG4), and explored its oncogenic role in HCC progression. Database analysis and immunohistochemistry indicated increased level of SPAG4 in HCC tissues which was of prognostic value. Gain/loss-of-function experiments showed that SPAG4 exerted oncogenic roles in HCC growth both in vitro and in vivo. RNA sequencing revealed activation of a lipogenic state and SREBP1-mediated pathway following SPAG4 overexpression. Mechanistically, the N-terminal region of SPAG4 bound to lamin A/C, which increased SREBP1 expression, nuclear translocation, and transcriptional activity. Treatment with orlistat, a lipid synthesis inhibitor, reversed SPAG4-mediated oncogenic effects, and its efficacy varied with SPAG4 level. The effect of orlistat was further amplified when combined with sorafenib in tumor xenograft mouse models. Our study provides evidence that SPAG4 mediates HCC progression by affecting lipid metabolism. Administration of orlistat combined with sorafenib reverses SPAG4-mediated oncogenesis in HCC cells and ectopic xenograft tumors in mice, suggesting that this pathway represents a potential target for HCC treatment.

A general serial dependence among various facial traits: Evidence from Markov Chain and derivative of Gaussian.

The human vision system can extract a stable representation of the always-changing visual world. However, the mechanism underlying such perceptual continuity remains unclear. A possible candidate is the serial dependence: visual perception of an object is positively biased toward the visual input from the recent past. Does the visual system use one pattern of serial dependence for general purposes? Or different patterns of serial dependence for different visual tasks? Because different social facial traits (e.g., trustworthiness and dominance) are dissociable, it is reasonable to assume that the perception of different facial characteristics would require different patterns of serial dependences. In this study, we examine the existence and the similarities of the serial dependence(s) in the evaluation of seven facial characteristics (i.e., attractiveness, trustworthiness, confidence, dominance, intelligence, age, and aggressiveness). The convergent evidence from conventional Derivative of Gaussian fitting and Markov Chain modeling demonstrated that (1) serial dependence exists in judgments of all seven social facial characteristic, (2) the serial dependences of them are highly similar, and (3) the serial dependence follows the efficient coding. Thus it is highly possible that there exists a general serial dependence mechanism for (at least high-level) vision processing. Moreover, we used the Markov Chain modeling to better describe the transitional pattern of serial dependence, which is a kind of Markov process. These findings may shed light on future works regarding serial dependence, as well as face perception.

B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/ß-Catenin/Snail Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide, characterized with high heterogeneity and inclination to metastasize. Emerging evidence suggests that BAP31 gets involved in cancer progression with different kinds. It still remains unknown whether and how BAP31 plays a role in HCC metastasis. Epithelial-mesenchymal transition (EMT) has been a common feature in tumor micro-environment, whose inducer TGF-ß increased BAP31 expression in this research. Elevated expression of BAP31 was positively correlated with tumor size, vascular invasion and poor prognosis in human HCC. Ectopic expression of BAP31 promoted cell migration and invasion while BAP31 knockdown markedly attenuated metastatic potential in HCC cells and mice orthotopic xenografts. BAP31 induced EMT process, and enhanced the expression level of EMT-related factor Snail and decreased contents and membrane distribution of E-cadherin. BAP31 also activated AKT/ß-catenin pathway, which mediated its promotional effects on HCC metastasis. AKT inhibitor further counteracted the activated AKT/ß-catenin/Snail upon BAP31 over-expression. Moreover, silencing Snail in BAP31-overexpressed cells impaired enhanced migratory and invasive abilities of HCC cells. In HCC tissues, BAP31 expression was positively associated with Snail. In conclusion, BAP31 promotes HCC metastasis by activating AKT/ß-catenin/Snail pathway. Thus, our study implicates BAP31 as potential prognostic biomarker, and provides valuable information for HCC prognosis and treatment.

Dickkopf-1 autoantibody is a novel serological biomarker for non-small cell lung cancer.

OBJECTIVE: We investigated whether or not there are autoantibodies for DKK1 (Dickkopf-1) in patients with non-small cell lung cancer (NSCLC) and whether this autoantibody can be used for cancer detection. METHODS: The levels of DKK1 autoantibodies were determined in 93 NSCLC patients and 87 healthy controls. RESULTS: We found that, in the sera, the presence of autoantibody against DKK1 was highly correlated with NSCLC. High anti-DKK1 autoantibody titres were found in the sera of NSCLC patients, whereas low or negative titres were found in the control group. The ROC curve results showed that autoantibody immunoassay exhibited 62% sensitivity and 84% specificity. The sensitivity for the detection of NSCLC in stage I also reach 64.3%. Furthermore, a combined ELISA assays for both DKK1 and autoantibody DKK1 increased sensitivity and classified 81.7% (76/93) of the NSCLC patients as positive, whereas only 13.8 % (12/87) of healthy volunteers were falsely diagnosed as positive. CONCLUSIONS: Our results suggest that the detection of circulating DKK1 autoantibody could potentially serve as a useful non-invasive marker for determining lung cancer status.