Identifying disulfidptosis subtypes in hepatocellular carcinoma through machine learning and preliminary exploration of its connection with immunotherapy.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. METHODS: We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. RESULTS: Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. CONCLUSION: The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets.

CF1 reduces grain-cadmium levels in rice (Oryza sativa).

Rice (Oryza sativa) is a leading source of dietary cadmium (Cd), a non-essential heavy metal that poses a serious threat to human health. There are significant variations in grain-Cd levels in natural rice populations, which make the breeding of low-Cd rice a cost-effective way to mitigate grain-Cd accumulation. However, the genetic factors that regulate grain-Cd accumulation have yet to be fully established, thereby hindering the development of low-Cd varieties. Here, we reported a low-Cd quantitative trait locus, CF1, that has the potential to reduce Cd accumulation in rice grains. CF1 is allelic to the metal transporter OsYSL2, which transports Fe from the roots to the shoots. However, it is incapable of binding Cd, and thus, reduces grain-Cd levels indirectly rather than directly in the form of upward delivery. Further analysis showed that high expression levels of CF1 improve Fe nutrition in the shoots, subsequently inhibiting Cd uptake by systemically inhibiting expression of the main Cd uptake gene OsNramp5 in the roots. Compared with the CF1 allele from '02428' (CF102428 ), higher expression levels of CF1 from 'TQ' (CF1TQ ) increased the Fe contents and decreased Cd levels in rice grains. In natural rice populations, CF1TQ was found to be a minor allele, while CF102428 is present in most japonica rice, suggesting that CF1TQ could be widely integrated into the japonica rice genome to generate low-Cd varieties. Overall, these results broaden our mechanistic understanding of the natural variation in grain-Cd accumulation, supporting marker-assisted selection of low-Cd rice.

WGX50 mitigates doxorubicin-induced cardiotoxicity through inhibition of mitochondrial ROS and ferroptosis.

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. METHODS: We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. RESULTS: Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. CONCLUSION: Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection.

The Harbinger transposon-derived gene PANDA epigenetically coordinates panicle number and grain size in rice.

Transposons significantly contribute to genome fractions in many plants. Although numerous transposon-related mutations have been identified, the evidence regarding transposon-derived genes regulating crop yield and other agronomic traits is very limited. In this study, we characterized a rice Harbinger transposon-derived gene called PANICLE NUMBER AND GRAIN SIZE (PANDA), which epigenetically coordinates panicle number and grain size. Mutation of PANDA caused reduced panicle number but increased grain size in rice, while transgenic plants overexpressing this gene showed the opposite phenotypic change. The PANDA-encoding protein can bind to the core polycomb repressive complex 2 (PRC2) components OsMSI1 and OsFIE2, and regulates the deposition of H3K27me3 in the target genes, thereby epigenetically repressing their expression. Among the target genes, both OsMADS55 and OsEMF1 were negative regulators of panicle number but positive regulators of grain size, partly explaining the involvement of PANDA in balancing panicle number and grain size. Moreover, moderate overexpression of PANDA driven by its own promoter in the indica rice cultivar can increase grain yield. Thus, our findings present a novel insight into the epigenetic control of rice yield traits by a Harbinger transposon-derived gene and provide its potential application for rice yield improvement.

A feedback loop between GATA2-AS1 and GATA2 promotes colorectal cancer cell proliferation, invasion, epithelial-mesenchymal transition and stemness via recruiting DDX3X.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor with a high risk of metastasis. Long non-coding RNAs (lncRNAs) have been reported to be implicated in cancer progression via regulating its nearby gene. Herein, we investigated the function of GATA binding protein 2 (GATA2) and lncRNA GATA2 antisense RNA 1 (GATA2-AS1) in CRC and the mechanism underlying their interaction. METHODS: Colony formation assay, flow cytometry analysis and transwell assay were implemented to detect cell proliferation, apoptosis and invasion. Western blot analysis and sphere formation assay were conducted to assess epithelial-mesenchymal transition (EMT) and cancer stemness of CRC cells. RNA pull down, RNA-binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and luciferase reporter assays were implemented to investigate the regulatory mechanism between GATA2-AS1 and GATA2. RESULTS: GATA2-AS1 and GATA2 were highly expressed in CRC cells. Knockdown of GATA2-AS1 and GATA2 impeded CRC cell proliferation, invasion, EMT and cancer stemness, and induced cell apoptosis. GATA2-AS1 expression was positively correlated with GATA2. GATA2-AS1 recruited DEAD-box helicase 3 X-linked (DDX3X) to stabilize GATA2 mRNA. GATA2 combined with GATA2-AS1 promoter to enhance GATA2-AS1 expression. CONCLUSION: Our study confirmed that a feedback loop between GATA2-AS1 and GATA2 promotes CRC progression, which might offer novel targets for CRC treatment.

Natural variation in the HAN1 gene confers chilling tolerance in rice and allowed adaptation to a temperate climate.

Rice (Oryza sativa L.) is a chilling-sensitive staple crop that originated in subtropical regions of Asia. Introduction of the chilling tolerance trait enables the expansion of rice cultivation to temperate regions. Here we report the cloning and characterization of HAN1, a quantitative trait locus (QTL) that confers chilling tolerance on temperate japonica rice. HAN1 encodes an oxidase that catalyzes the conversion of biologically active jasmonoyl-L-isoleucine (JA-Ile) to the inactive form 12-hydroxy-JA-Ile (12OH-JA-Ile) and fine-tunes the JA-mediated chilling response. Natural variants in HAN1 diverged between indica and japonica rice during domestication. A specific allele from temperate japonica rice, which gained a putative MYB cis-element in the promoter of HAN1 during the divergence of the two japonica ecotypes, enhances the chilling tolerance of temperate japonica rice and allows it to adapt to a temperate climate. The results of this study extend our understanding of the northward expansion of rice cultivation and provide a target gene for the improvement of chilling tolerance in rice.

SIRT1 Regulates N6 -Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2-Dependent FTO SUMOylation.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase silent information regulator 1 (SIRT1) was discovered in HCC, and its presence is positively correlated with malignancy and metastasis. N6 -methyladenosine (m6 A) is the most prominent modification, but the exact mechanisms on how SIRT1 regulates m6 A modification to induce hepatocarcinogenesis remain unclear. APPROACH AND RESULTS: Here we demonstrate that SIRT1 exerts an oncogenic role by down-regulating fat mass and obesity-associated protein (FTO), which is an m6 A demethylase. A crucial component of small ubiquitin-related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)-216 site that promotes FTO degradation. Moreover, Guanine nucleotide-binding protein G (o) subunit alpha (GNAO1) is identified as m6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m6 A+ GNAO1 and down-regulates its mRNA expression. CONCLUSIONS: We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m6 A+ of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a target of SIRT1 for therapeutic agents to treat HCC.

ZINC TRANSPORTER5 and ZINC TRANSPORTER9 Function Synergistically in Zinc/Cadmium Uptake.

The elements Zinc (Zn) and cadmium (Cd) have similar chemical and physical properties, but contrasting physiological effects in higher organisms. In plants, Zn/Cd transport is mediated by various transporter proteins belonging to different families. In this study, we functionally characterized two Zn transporter genes in rice (Oryza sativa), ZINC TRANSPORTER5 (OsZIP5) and ZINC TRANSPORTER9 (OsZIP9), which are tandem duplicates and act synergistically in Zn/Cd uptake. Both genes encode plasma membrane-localized proteins with influx transporter activity. The expression profiles of OsZIP5 and OsZIP9 overlap in the root epidermis and respond to the local Zn status in the root. However, OsZIP9 is also regulated by systemic signals of Zn status from the shoot. OsZIP5 functions redundantly to OsZIP9, but has a relatively weaker effect. Plants with the knockout mutations oszip5, oszip9, or oszip5oszip9 show impaired Zn/Cd uptake. The decreased Zn/Cd levels and growth retardation in the oszip5 mutant are less severe than in the oszip9 mutant. However, the double mutant oszip5oszip9 showed an enhanced Zn deficiency phenotype compared with the single mutants, and few double-knockout plants were able to survive the entire growth cycle without excessive Zn supply. Transgenic plants overexpressing OsZIP9 had markedly enhanced Zn/Cd levels in the aboveground tissues and brown rice. The results of our study fill a gap in current knowledge of Zn uptake and improve our understanding of Zn/Cd accumulation in rice.

Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation.

BACKGROUND: Lung cancer is the most common malignant tumor in the world. The Whole-proteome microarray showed that ubiquitin ligase chromatin assembly factor 1 subunit B (CHAF1B) expression in A549/DDP cells is higher than in A549 cells. Our study explored the molecular mechanism of CHAF1B affecting cisplatin resistance in lung adenocarcinoma (LUAD). METHODS: Proteome microarray quantify the differentially expressed proteins between LUAD cell line A549 and its cisplatin-resistant strain A549/DDP. Quantitative real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB) confirmed the CHAF1B expression. Public databases analyzed the prognosis of LUAD patients with varied LUAD expression followed by the substrates prediction of CHAF1B. Public databases showed that nuclear receptor corepressor 2 (NCOR2) may be substrates of CHAF1B. WB detected that CHAF1B expression affected the expression of NCOR2. Cell and animal experiments and clinical data detected function and integrating mechanism of CHAF1B compounds. RESULTS: Proteome chips results indicated that CHAF1B, PPP1R13L, and CDC20 was higher than A549 in A549/DDP. Public databases showed that high expression of CHAF1B, PPP1R13L, and CDC20 was negatively correlated with prognosis in LUAD patients. PCR and WB results indicated higher CHAF1B expression in A549/DDP cells than that in A549 cells. NCOR2 and PPP5C were confirmed to be substrates of CHAF1B. CHAF1B knockdown significantly increased the sensitivity of cisplatin in A549/DDP cells and the upregulated NCOR2 expression. CHAF1B and NCOR2 are interacting proteins and the position of interaction between CHAF1B and NCOR2 was mainly in the nucleus. CHAF1B promotes ubiquitination degradation of NCOR2. Cells and animal experiments showed that under the action of cisplatin, after knockdown of CHAF1B and NCOR2 in A549/DDP group compared with CHAF1B knockdown alone, the cell proliferation and migratory ability increased and apoptotic rate decreased, and the growth rate and size of transplanted tumor increased significantly. Immunohistochemistry suggested that Ki-67 increased, while apoptosis-related indicators caspase-3 decreased significantly. Clinical data showed that patients with high expression of CHAF1B are more susceptible to cisplatin resistance. CONCLUSION: Ubiquitin ligase CAHF1B can induce cisplatin resistance in LUAD by promoting the ubiquitination degradation of NCOR2.

MiR-130b promotes the progression of oesophageal squamous cell carcinoma by targeting SASH1.

MiR-130b and SAM and SH3 domain containing 1 (SASH1) play an important role in many types of human cancers. The aim of our research was to study their interactions in the process of the proliferation and aggressiveness of oesophageal squamous cell carcinoma (ESCC) cells. Microarray analysis was done to screen the differentially expressed genes in the ESCC tissues. miR-130b and SASH1 mRNA levels in the ESCC tissues and cells were detected by qRT-PCR. Dual luciferase reporter system was used to verify the target relationship between miR-130b and SASH1. The effects of miR-130b on SASH1 expression were explored by western blot in KYSE30 and TE1 cell lines. CCK-8 assay, flow cytometry, Transwell, and wound healing assays were conducted to explore the effects of miR-130b and SASH1 in vitro. In addition, in vivo experiments were conducted to study the roles of miR-130b and SASH1. miR-130b was highly expressed, while SASH1 was the opposite in both the ESCC tissues and cells. The expression of SASH1 was inhibited by the direct binding of miR-130b. The inhibition of miR-130b reduced the proliferation and aggressiveness of ESCC cells, while it also induced apoptosis and cell cycle arrest in the ESCC cells by suppressing SASH1. The in vivo assay suggested that the overexpression of miR-130b promoted the growth of ESCC tumours. MiR-130b was up-regulated in the ESCC tumour tissues and cells, acting as a tumour promoter. A stimulating effect was demonstrated on ESCC cell growth and aggressiveness by suppressing SASH1, which is an anti-oncogene.

OsZIP7 functions in xylem loading in roots and inter-vascular transfer in nodes to deliver Zn/Cd to grain in rice.

Rice has lower zinc (Zn) but higher cadmium (Cd) content in grains than other staple crops. Understanding the molecular mechanisms involved in Zn and Cd transportation could benefit homeostatic control, facilitating optimisation of Zn and Cd levels to provide maximum nutrition and safety. In this study, we functionally characterised in planta the rice (Oryza sativa) transporter OsZIP7, which encodes a plasma membrane-localised protein with influx transport activity for both Zn and Cd. OsZIP7 was expressed in parenchyma cells of vascular bundles in roots and nodes. OsZIP7 knockout resulted in retention of Zn and Cd in roots and basal nodes, which hindered their upward delivery to upper nodes and brown rice. And a short-term labelling experiment with the stable 67Zn isotope showed that Zn was distributed toward roots and basal regions and away from leaves in the mutant compared with wild-type rice. Thus, OsZIP7 plays an integral role in xylem loading in roots and inter-vascular transfer in nodes to preferentially deliver Zn and Cd to developing tissues and rice grains.

[Dosimetric verification of flattening filter free model based on TrueBeam accelerator using ArcCheck system].

OBJECTIVE: To study the feasibility of ArcCheck verification system in dosimetric verification for stereotactic radiotherapy (SRT) the stereotactic radiotherapy (SRT) with flattening filter free (FFF) model.
 Methods: A total of 76 cases under SRT treatment plans were introduced into ArcCheck phantom and recalculated. Threshold criteria was set as (3%, 3 mm, 10%) or (2%, 2 mm, 10%). The calculated dose distribution and the measured dose distribution of ArcCheck phantom were compared by means of distance to agree (DTA) and Gamma analysis method respectively.
 Results: Based on the threshold criteria (3%, 3 mm, 10%), the relative and absolute mean pass rates of SRT treatment plans by DTA and Gamma analysis were greater than 95%. Based on the threshold criteria (2%, 2 mm, 10%), the relative and absolute mean pass rates of SRT treatment plan by DTA and Gamma analysis were about 90%. The dose pass rate of Gamma analysis method was slightly higher than that of DTA analysis method (P<0.001).
 Conclusion: The ArcCheck verification system is a rapid and accurate method for SRT dose verification, and discrepancies are found in different analysis methods.

Multiple cold resistance loci confer the high cold tolerance adaptation of Dongxiang wild rice (Oryza rufipogon) to its high-latitude habitat.

KEY MESSAGE: Dongxiang wild rice is phylogenetically close to temperate japonica and contains multiple cold resistance loci conferring its adaptation to high-latitude habitat. Understanding the nature of adaptation in wild populations will benefit crop breeding in the development of climate-resilient crop varieties. Dongxiang wild rice (DXWR), the northernmost common wild rice known, possesses a high degree of cold tolerance and can survive overwintering in its native habitat. However, to date, it is still unclear how DXWR evolved to cope with low-temperature environment, resulting in limited application of DXWR in rice breeding programs. In this study, we carried out both QTL mapping and phylogenetic analysis to discern the genetic mechanism underlying the strong cold resistance. Through a combination of interval mapping and single locus analysis in two genetic populations, at least 13 QTLs for seedling cold tolerance were identified in DXWR. A phylogenetic study using both genome-wide InDel markers and markers associated with cold tolerance loci reveals that DXWR belongs to the Or-III group, which is most closely related to cold-tolerant Japonica rice rather than to the Indica cultivars that are predominant in the habitat where DXWR grows. Our study paves the way toward an understanding of the nature of adaptation to a northern habitat in O. rufipogon. The QTLs identified in DXWR in this study will be useful for molecular breeding of cold-tolerant rice.

Dietary ferulic acid improves growth performance of broilers via enhanced intestinal antioxidant capacity and barrier function.

Objective: In this study, the effects of dietary ferulic acid (FA) on the growth traits, antioxidant capacity, and intestinal barrier function of broilers were investigated. Methods: In total, 192 male Arbor Acres broilers were randomly allocated to one of three dietary groups (8 replicates of 8 birds each): control (CON) group (basal diet), FA100 group (basal diet + 100 mg/kg FA), or FA200 group (basal diet + 200 mg/kg FA). The duration of the feeding trial was 42 days. Results: higher average daily gain (ADG) and lower feed to gain (F/G) ratio during day 0 to day 21 were found in the FA100 and FA200 groups, while higher ADG and lower F/G during day 21 to day 42 were only found in FA200 group, compared to the CON group (p < 0.05). Serum levels of MDA and DAO on day 21 were lower in the FA100 and FA200 groups and those on day 42 were lower in the FA200 group, while GSH-Px level in the FA100 and FA200 groups on day 21 and that in the FA200 group on day 42 were increased (p < 0.05). On day 21, jejunal GSS expression was upregulated in the FA200 group (p < 0.05), while jejunal and ileal expression of NRF2 and Occludin as well as ileal expression of GPX1 and ZO1 were increased in the FA100 and FA200 groups compared to the CON group (p < 0.05). On day 42, mRNA expression of GSS, NRF2, SOD1, and GPX1 in the jejunum and ileum as well as Claudin2 in the jejunum and Occludin in the ileum were increased in the FA200 group (p < 0.05). Conclusion: Dietary FA addition could improve the growth performance, antioxidant capacity, and gut integrity of broilers. The current findings provided evidences that the adoption of FA can be as nutrition intervention measure to achieve high-efficient broiler production for poultry farmers.

Correction: Liu et al. RANBP2 Activates O-GlcNAcylation through Inducing CEBPα-Dependent OGA Downregulation to Promote Hepatocellular Carcinoma Malignant Phenotypes. Cancers 2021, 13, 3475.

In the original publication [...].

Association of four metalloids in the serum and urine of individuals with major depressive disorders: a case-control study.

Background: Major depressive disorder (MDD) pathogenesis may involve metalloids in a significant way. The aim of our study was to identify potential links between MDD and metalloid elements [boron (B), germanium (Ge), arsenic (As), antimony (Sb)]. Methods: A total of 72 MDD cases and 75 healthy controls (HCs) were recruited from Zhumadian Second People's Hospital in Henan Province, China. The levels of four metallic elements (B, Ge, As, and Sb) in the serum and urine were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results: In comparison to the HCs, the B, As, and Sb levels were considerably lower in the MDD group (p < 0.05) in the serum; the MDD group had significantly higher (p < 0.05) and significantly lower (p < 0.001) B and Sb levels in the urine. After adjusting for potential confounders, serum B (OR = 0.120; 95% CI, 0.048, 0.300; p < 0.001) and Sb (OR = 0.133; 95% CI, 0.055, 0.322; p < 0.001) showed a negative correlation with MDD. Urine B had a negative correlation (OR = 0.393; 95% CI, 0.193, 0.801; p = 0.01) with MDD, while urine Sb had a positive correlation (OR = 3.335; 95% CI, 1.654, 6.726; p = 0.001) with MDD. Conclusion: Our current research offers insightful hints for future investigation into the function of metalloids in connection to MDD processes.

THIS1 is a putative lipase that regulates tillering, plant height, and spikelet fertility in rice.

Proper branching and successful reproductive growth is of great importance for rice productivity. Substantial progress has been made in uncovering the molecular mechanisms underlying tillering control and spikelet sterility. However, rice tillering is developmentally controlled, and how it is regulated coordinately with reproductive growth remains unclear. This study characterized a rice mutant, the most obvious phenotypes of which are high tillering, reduced height, and infertile spikelets (named this1). Similarly to the high tiller number and dwarf mutants in rice, the increased tiller number of this1 plants is ascribed to the release of tiller bud outgrowth rather than to increased tiller bud formation. In the this1 mutant, however, the accelerated rate of branching was delayed until the stem elongation stage, while other mutants lost the ability to control branching at all developmental stages. The seed-setting rate of this1 was less than half that of the wild type, owing to defects in pollen maturation, anther dehiscence, and flower opening. Histological analyses showed that the mutation in this1 resulted in anisotropic cell expansion and cell division. Using a map-based cloning approach, This1 was found to encode a class III lipase. Homology searches revealed that THIS1 is conserved in both monocots and eudicots, suggesting that it plays fundamental role in regulating branch and spikelet fertility, as well as other aspects of developmental control. The relative change in expression of marker genes highlighted the possibility that This1 is involved in phytohormone signalling pathways, such as those for strigolactone and auxin. Thus, This1 provides joint control between shoot branching and reproductive development.

Effects of Dried Blueberry Pomace and Pineapple Pomace on Growth Performance and Meat Quality of Broiler Chickens.

The purpose of this study was to investigate the effects of dried blueberry pomace (BP) and pineapple pomace (PP) on the growth performance and meat quality of broiler chickens. A total of 240 1-day-old Ross 308 broiler chickens were randomly divided into 3 groups, with 10 replicates per treatment group and 8 birds per replicate (4 males and 4 females). The three groups were the control (CON) group, the 3% BP group, and 3% PP group. The entire trial period lasted 42 days. The results show that the average daily feed intake, average daily gain, and feed-to-gain ratio of the BP group and the PP group were not significantly different from those in the CON group (p > 0.05). Adding BP to the diet significantly reduced the proportion of liver and giblets (p < 0.05). Adding PP to the diet significantly reduced the proportion of liver, while the proportion of gizzard significantly increased (p < 0.05). The pH24h and L* of breast muscles were significantly lower in the PP group than in the CON group (p < 0.05). The water-holding capacity of the leg muscles in the BP group and the PP group was significantly lower than that in the CON group (p < 0.05). The crude protein content of breast muscle and the ether extract content of leg muscle in the BP group were significantly lower than those in the CON group (p < 0.05). In conclusion, the addition of 3% BP and PP to broiler chickens' diets had no adverse effects on growth performance or meat quality.

circRNA_0067717 promotes paclitaxel resistance in nasopharyngeal carcinoma by acting as a scaffold for TRIM41 and p53.

PURPOSE: Circular RNAs (circRNAs) play important roles in tumour progression. This study aimed to explore the mechanism of hsa_circ_0067717 (termed circRNA_0067717) promoting paclitaxel resistance in nasopharyngeal carcinoma (NPC). METHODS: We assayed CNE-1 and HNE-2 parental cell lines and the corresponding paclitaxel-resistant NPC cell lines using circRNA microarrays. RNA pull-down assay, RNA immunoprecipitation, and RNA fluorescence in situ hybridization were used to identify the molecular mechanisms. RESULTS: Here, we confirm that circRNA_0067717 is significantly upregulated in NPC paclitaxel-resistant cells and is associated with paclitaxel resistance in NPC. Mechanistically, circRNA_0067717 functions as a scaffold for TRIM41 protein (a ubiquitin E3 ligase) and p53 protein. In nasopharyngeal carcinoma paclitaxel-resistant cells, the highly expressed circRNA_0067717 can bind to more TRIM41 and p53 protein, promoting TRIM41-induced p53 ubiquitination and degradation, resulting in a decrease in p53 protein level. Moreover, the 1-176 nt area of circRNA_0067717 and the 301-425 nt region of circRNA_0067717 are the binding sites for p53 and TRIM41, respectively. The resistance of NPC cells to paclitaxel can be reduced by blocking these binding regions of circRNA_0067717. CONCLUSION: We demonstrate that circRNA_0067717 acts as a scaffold for TRIM41 and p53, enhancing paclitaxel chemoresistance in NPC by promoting TRIM41-induced p53 degradation via ubiquitination.

Identification of subspecies-divergent genetic loci responsible for mineral accumulation in rice grains.

Rice (Oryza sativa L.) is a major staple food that provides not only dietary calories but also trace elements for the global inhabitants. The insufficiency of mineral nutrients and the potential accumulation of excessive toxic elements in grains pose risks to human health. The substantial natural variations in mineral accumulation in rice grains presents potentials for genetic improvements of rice via biofortifications of essential mineral nutrients and eliminations of toxic elements in grains. However, the genetic mechanisms underlying the natural variations in mineral accumulation have not been fully explored to date owing to unstable phenotypic variations, which are attributed to poor genetic performance and strong environmental effects. In this study, we first compared the genetic performance of different normalization approaches in determining the grain-Cd, grain-Mn, and grain-Zn variations in rice in different genetic populations. Then through quantitative trait loci (QTLs) identification in two rice inter-ectype populations, three QTLs, including qCd7, qMn3, and qZn7, were identified and the QTLs were found to exhibit allelic differentiation in the different ecotypes. Our results were expected to broaden our understanding for mineral accumulation in rice and propose the potential functional alleles that can be explored for further genetic improvement of rice.