A Natural Allele of a Transcription Factor in Rice Confers Broad-Spectrum Blast Resistance.

Rice feeds half the world's population, and rice blast is often a destructive disease that results in significant crop loss. Non-race-specific resistance has been more effective in controlling crop diseases than race-specific resistance because of its broad spectrum and durability. Through a genome-wide association study, we report the identification of a natural allele of a C2H2-type transcription factor in rice that confers non-race-specific resistance to blast. A survey of 3,000 sequenced rice genomes reveals that this allele exists in 10% of rice, suggesting that this favorable trait has been selected through breeding. This allele causes a single nucleotide change in the promoter of the bsr-d1 gene, which results in reduced expression of the gene through the binding of the repressive MYB transcription factor and, consequently, an inhibition of H2O2 degradation and enhanced disease resistance. Our discovery highlights this novel allele as a strategy for breeding durable resistance in rice.

Identification of important gene signatures in schizophrenia through feature fusion and genetic algorithm.

Schizophrenia is a debilitating psychiatric disorder that can significantly affect a patient's quality of life and lead to permanent brain damage. Although medical research has identified certain genetic risk factors, the specific pathogenesis of the disorder remains unclear. Despite the prevalence of research employing magnetic resonance imaging, few studies have focused on the gene level and gene expression profile involving a large number of screened genes. However, the high dimensionality of genetic data presents a great challenge to accurately modeling the data. To tackle the current challenges, this study presents a novel feature selection strategy that utilizes heuristic feature fusion and a multi-objective optimization genetic algorithm. The goal is to improve classification performance and identify the key gene subset for schizophrenia diagnostics. Traditional gene screening techniques are inadequate for accurately determining the precise number of key genes associated with schizophrenia. Our innovative approach integrates a filter-based feature selection method to reduce data dimensionality and a multi-objective optimization genetic algorithm for improved classification tasks. By combining the filtering and wrapper methods, our strategy leverages their respective strengths in a deliberate manner, leading to superior classification accuracy and a more efficient selection of relevant genes. This approach has demonstrated significant improvements in classification results across 11 out of 14 relevant datasets. The performance on the remaining three datasets is comparable to the existing methods. Furthermore, visual and enrichment analyses have confirmed the practicality of our proposed method as a promising tool for the early detection of schizophrenia.

OsmiR5519 regulates grain size and weight and down-regulates sucrose synthase gene RSUS2 in rice (Oryza sativa L.).

MAIN CONCLUSION: The up-regulation of OsmiR5519 results in the decrease of grain size, weight and seed setting rate. OsmiR5519 plays important roles in the process of grain filling and down-regulates sucrose synthase gene RSUS2. MicroRNAs (miRNAs) are one class of small non-coding RNAs that act as crucial regulators of plant growth and development. In rice, the conserved miRNAs were revealed to regulate the yield components, but the function of rice-specific miRNAs has been rarely studied. The rice-specific OsmiR5519 was found to be abundantly expressed during reproductive development, but its biological roles remain unknown. In this study, the function of rice-specific OsmiR5519 was characterized with the miR5519-overexpressing line (miR5519-OE) and miR5519-silenced line (STTM5519). At seedling stage, the content of sucrose, glucose and fructose was obviously lower in the leaves of miR5519-OE lines than those of wild-type (WT) line. The grain size and weight were decreased significantly in miR5519-OE lines, compared to those of WT rice. The cell width of hull in miR5519-OE was smaller than that in WT. The seed setting rate was notably reduced in miR5519-OE lines, but not in STTM5519 lines. Cytological observation demonstrated that the inadequate grain filling was the main reason for the decline of seed setting rate in miR5519-OE lines. The percentage of the defects of grain amounted to 40% in miR5519-OE lines, which almost equaled to the decreased value of seed setting rate. Furthermore, the sucrose synthase gene RSUS2 was identified as a target of OsmiR5519 via RNA ligase-mediated 3'-amplification of cDNA ends (3'-RLM-RACE), dual luciferase assays and transient expression assays. In summary, our results suggest that OsmiR5519 regulates grain size and weight and down-regulates RSUS2 in rice.

Natural allelic variation in GRAIN SIZE AND WEIGHT 3 of wild rice regulates the grain size and weight.

Grain size is important for yield in rice (Oryza sativa L.). Although many genes involved in grain size have been isolated, few can be used in breeding due to their interactions and phenotypic effects. Here, we describe natural variation in the granule-type quantitative trait locus GRAIN SIZE AND WEIGHT 3 (GSW3) located on chromosome 3 in wild rice (Oryza rufipogon Griff.) that encodes a GTPase-regulated protein and negatively regulates grain length, grain width, and 1,000-grain weight. The insertion of a 232-bp fragment of the genomic sequence in the wild rice, a natural allelic variant gene (GSW3), increased the expression levels and reduced the grain length and width and 1,000-grain weight. Knockout of GSW3 in the wild rice inbred line Huaye 3 increased the grain length and width and 1,000-grain weight. Introducing GSW3Huaye3 into cultivated rice line KJ01 and overexpressing GSW3Huaye3 in Huaye 3 resulted in reduced grain length and width and 1,000-grain weight, and grain size and 1,000-grain weight changes were closely related to GSW3 expression levels. GSW3 regulated the grain length and width simultaneously by promoting grain glume cell division and longitudinal and transverse cell growth. GSW3 was also involved in regulating the gibberellic acid signaling pathway and negatively regulated plant growth. Furthermore, a critical SNP in the GSW3 coding region was obviously correlated with grain size variation in a core collection of cultivated rice. This SNP resulted in an amino acid substitution from Gln to Arg at position 161 in GSW3, which reduced the grain size. Our study shows that GSW3 negatively regulates the grain shape, which could explain different grain shapes in modern cultivars and wild rice. GSW3 may also be used for breeding rice varieties with improved grain shapes and higher yield.

Prognostic value of the advanced lung cancer inflammation index in patients with gastric cancer after radical gastrectomy: a propensity-score matching cohort study and meta-analysis.

BACKGROUND: Insufficient evidence existed about the prognostic role of the advanced lung cancer inflammation index (ALI) for gastric cancer patients who underwent curative resection. The aim of this study was to identify the predictive ability of ALI for survival after curative gastrectomy. METHODS: We retrospectively analyzed 328 gastric cancer patients who received curative gastrectomy from the database of Chongqing University Cancer Hospital, and investigated the prognostic role of the preoperative ALI compared with clinicopathological variables and other serum biomarkers, such as preoperative neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and Lymphocyte-monocyte ratio (LMR). To minimize intergroup differences, propensity score matching (PSM) analysis was employed. Additionally, we performed a meta-analysis of four cohort studies published up to October 2023 following the PRISMA guidelines. RESULTS: In the overall cohort, patients in the low ALI group had a significantly worse overall survival compared to those in the high ALI group (P < 0.0001). Subgroup analysis identified that ALI maintained its prognostic significance across different subgroups. In addition, ROC analysis showed that ALI had a higher AUC value for 3-year overall survival compared to NLR, PLR, and LMR (0.576 vs. 0.573 vs. 0.557 vs. 0.557). Multivariate analysis indicated that ALI, other than other serum biomarkers, was an independent risk factor for decreased overall survival in GC patients following curative surgery (HR = 1.449; 95%CI: 1.028-2.045; P = 0.034). Consistently, PSM analysis supported all of these findings. The meta-analysis including 4 studies evaluating 2542 patients, confirmed the association between the low ALI and poor survival outcomes. CONCLUSION: The preoperative ALI was an independent prognostic factor for survival in gastric cancer patients who underwent curative gastrectomy.

Plum blossom low molecular weight polypeptide protects HaCaT cells against UVB-induced oxidative damage in vitro and underlying mechanism.

BACKGROUND: Increasing amounts of ultraviolet radiation occur as ozone depletion causes the earth's ozone layer to be destroyed, making antioxidant efficacy a research hotspot. Previous studies on plum blossom have mostly focused on Volatile Oils, Flavonoids, Phenylpropanoids, and other compounds, whereas few studies have focused on low molecular weight polypeptide (LMWP) of plum blossom. This research provides a reference for the deep processing and utilization of plum blossom. OBJECTIVES: (a) Plum blossom low molecular weight polypeptides protect HaCaT cells against UVB-induced oxidative damage in vitro and the underlying mechanism. (b) Improve the theoretical basis for the intense processing and utilization of plum blossom. METHODS: The safe concentration of LMWP and the survival rate of HaCaT cells were determined using the CCK-8 experiment. The fluorescence intensity of reactive oxygen species (ROS) was identified using the dichlorofluorescin diacetate (DCFH-DA) method; Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were measured in ruptured cells; Western blot analysis was used to examine the expression levels of three proteins: nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and benzoquinone oxidoreductase 1 (NQO-1). RESULTS: It was noted that a certain concentration of LMWP could promote cell proliferation. In oxidatively damaged HaCaT cells, SOD levels and survival rates were markedly reduced, but ROS and MDA levels were elevated. However, after treatment with LMWP, the survival rate of the cells and SOD levels were markedly increased, and the levels of ROS and MDA were markedly decreased. As shown by Western blotting, the model group exhibited lower levels of Nrf2, HO-1, and NQO-1 expression than the control group, whereas LMWP-treated cells had significantly higher levels of Nrf2, HO-1, and NQO-1 expression than their model-treated counterparts. CONCLUSIONS: LMMP can effectively protect HaCaT cells against oxidative damage in vitro induced by UVB, and the underlying mechanism is linked to the activation of the transcription factor Nrf2.

Laparoscopic versus open gastrectomy for nonmetastatic T4a gastric cancer: a meta-analysis of reconstructed individual participant data from propensity score-matched studies.

BACKGROUND: ​The applicability of laparoscopy to nonmetastatic T4a patients with gastric cancer remains unclear due to the lack of high-quality evidence. The purpose of this study was to compare the survival rates of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for these patients through a meta-analysis of reconstructed individual participant data from propensity score-matched studies. METHODS: PubMed, Embase, Web of Science, Cochrane library and CNKI were examined for relevant studies without language restrictions through July 25, 2023. Individual participant data on overall survival (OS) and disease-free survival (DFS) were extracted from the published Kaplan-Meier survival curves. One-stage and two-stage meta-analyses were performed. In addition, data regarding surgical outcomes and recurrence patterns were also collected, which were meta-analyzed using traditional aggregated data. RESULTS: Six studies comprising 1860 patients were included for analysis. In the one-stage meta-analyses, the results demonstrated that LG was associated with a significantly better DFS (Random-effects model: P = 0.027; Restricted mean survival time [RMST] up to 5 years: P = 0.033) and a comparable OS (Random-effects model: P = 0.135; RMST up to 5 years: P = 0.053) than OG for T4a gastric cancer patients. Two-stage meta-analyses resulted in similar results, with a 13% reduced hazard of cancer-related death (P = 0.04) and 10% reduced hazard of overall mortality (P = 0.11) in the LG group. For secondary outcomes, the pooled results showed an association of LG with less estimated blood loss, faster postoperative recovery and more retrieved lymph nodes. CONCLUSION: Laparoscopic surgery for patients with nonmetastatic T4a disease is associated with a potential survival benefit and improved surgical outcomes.

Prophylactic drainage versus non-drainage following gastric cancer surgery: a meta-analysis of randomized controlled trials and observational studies.

BACKGROUND: The role of prophylactic drainage (PD) in gastrectomy for gastric cancer (GC) is not well-established. The purpose of this study is to compare the perioperative outcomes between the PD and non-drainage (ND) in GC patients undergoing gastrectomy. METHODS: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed up to December 2022. All eligible randomized controlled trials (RCTs) and observational studies were included and meta-analyzed separately. The registration number of this protocol is PROSPERO CRD42022371102. RESULTS: Overall, 7 RCTs (783 patients) and 14 observational studies (4359 patients) were ultimately included. Data from RCTs indicated that patients in the ND group had a lower total complications rate (OR = 0.68; 95%CI:0.47-0.98; P = 0.04; I2 = 0%), earlier time to soft diet (MD = - 0.27; 95%CI: - 0.55 to 0.00; P = 0.05; I2 = 0%) and shorter length of hospital stay (MD = - 0.98; 95%CI: - 1.71 to - 0.26; P = 0.007; I2 = 40%). While other outcomes including anastomotic leakage, duodenal stump leakage, pancreatic leakage, intra-abdominal abscess, surgical-site infection, pulmonary infection, need for additional drainage, reoperation rate, readmission rate, and mortality were not significantly different between the two groups. Meta-analyses on observational studies showed good agreement with the pooled results from RCTs, with higher statistical power. CONCLUSION: The present meta-analysis suggests that routine use of PD may not be necessary and even harmful in GC patients following gastrectomy. However, well-designed RCTs with risk-stratified randomization are still needed to validate the results of our study.

OsmiRNA5488 Regulates the Development of Embryo Sacs and Targets OsARF25 in Rice (Oryza sativa L.).

Small RNAs are a class of non-coding RNAs that typically range from 20 to 24 nucleotides in length. Among them, microRNAs (miRNAs) are particularly important regulators for plant development. The biological function of the conserved miRNAs has been studied extensively in plants, while that of the species-specific miRNAs has been studied in-depth. In this study, the regulatory role of a rice-specific OsmiRNA5488 (OsmiR5488) was characterized with the miR5488-overexpressed line (miR5488-OE) and miR5488-silenced line (STTM-5488). The seed-setting rate was notably reduced in miR5488-OE lines, but not in STTM-5488 lines. Cytological observation demonstrated the different types of abnormal mature embryo sacs, including the degeneration of embryo sacs and other variant types, in miR5488-OE lines. The percentage of the abnormal mature embryo sacs accounted for the reduced value of the seed-setting rate. Furthermore, OsARF25 was identified as a target of OsmiR5488 via RNA ligase-mediated 3'-amplifification of cDNA ends, dual luciferase assays, and transient expression assays. The primary root length was decreased with the increases in auxin concentrations in miR5488-OE lines compared to wild-type rice. Summarily, our results suggested that OsmiR5488 regulates the seed-setting rate and down-regulates the targeted gene OsARF25.

An uncharacterized protein NY1 targets EAT1 to regulate anther tapetum development in polyploid rice.

BACKGROUND: Autotetraploid rice is a useful germplasm for the breeding of polyploid rice; however, low fertility is a major hindrance for its utilization. Neo-tetraploid rice with high fertility was developed from the crossing of different autotetraploid rice lines. Our previous research showed that the mutant (ny1) of LOC_Os07g32406 (NY1), which was generated by CRISPR/Cas9 knock-out in neo-tetraploid rice, showed low pollen fertility, low seed set, and defective chromosome behavior during meiosis. However, the molecular genetic mechanism underlying the fertility remains largely unknown. RESULTS: Here, cytological observations of the NY1 mutant (ny1) indicated that ny1 exhibited abnormal tapetum and middle layer development. RNA-seq analysis displayed a total of 5606 differentially expressed genes (DEGs) in ny1 compared to wild type (H1) during meiosis, of which 2977 were up-regulated and 2629 were down-regulated. Among the down-regulated genes, 16 important genes associated with tapetal development were detected, including EAT1, CYP703A3, CYP704B2, DPW, PTC1, OsABCG26, OsAGO2, SAW1, OsPKS1, OsPKS2, and OsTKPR1. The mutant of EAT1 was generated by CRISPR/Cas9 that showed abnormal tapetum and pollen wall formation, which was similar to ny1. Moreover, 478 meiosis-related genes displayed down-regulation at same stage, including 9 important meiosis-related genes, such as OsREC8, OsSHOC1, SMC1, SMC6a and DCM1, and their expression levels were validated by qRT-PCR. CONCLUSIONS: Taken together, these results will aid in identifying the key genes associated with pollen fertility, which offered insights into the molecular mechanism underlying pollen development in tetraploid rice.

Detection and analysis of long noncoding RNA expression profiles related to epithelial-mesenchymal transition in keloids.

BACKGROUND: The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of keloids is currently raising increasing attention. Long noncoding RNAs (lncRNAs) govern a variety of biological processes, such as EMT, and their dysregulation is involved in many diseases including keloid disease. The aim of this study was to identify differentially expressed EMT-related lncRNAs in keloid tissues versus normal tissues and to interpret their functions. RESULTS: Eleven lncRNAs and 16 mRNAs associated with EMT were identified to have differential expression between keloid and normal skin tissues (fold change > 1.5, P < 0.05). Gene Ontology (GO) analysis showed that these differentially expressed mRNAs functioned in the extracellular matrix, protein binding, the positive regulation of cellular processes, the Set1C/COMPASS complex and histone acetyltransferase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these mRNAs are involved in pathways in cancer. The lncRNA, XLOC_000587 may promote cell proliferation and migration by enhancing the expression of ENAH, while AF268386 may facilitate the invasive growth of keloids by upregulating DDR2. CONCLUSIONS: We characterized the differential expression profiles of EMT-related lncRNAs and mRNAs in keloids, which may contribute to preventing the occurrence and development of keloids by targeting the corresponding signaling pathways. These lncRNAs and mRNAs may provide biomarkers for keloid diagnosis and serve as potential targets for the treatment of this disease.

Asymmetric Aza-Claisen Rearrangement between Enantioenriched α-Chiral Allylamines and Allenones.

An unprecedented asymmetric aza-Claisen rearrangement between enantioenriched α-chiral allylamines and allenones was found to proceed in the absence of catalysts and additives at room temperature. The rearrangement, followed by hydrolysis, provides convenient access to structurally diverse δ-chiral ß-diketones in good to excellent yields with excellent retention of enantiopurity. This protocol proved powerful for the construction of an all-carbon quaternary stereocenter with high enantiopurity.

NPRL2 promotes docetaxel chemoresistance in castration resistant prostate cancer cells by regulating autophagy through the mTOR pathway.

Docetaxel-based chemotherapy is recommended for metastatic castration-resistant prostate cancer (mCRPC). However, chemoresistance is inevitable and eventually progresses after several rounds of chemotherapy. Therefore, exploration of new therapeutic targets and molecular mechanisms that contribute to chemoresistance remains necessary. Our previous study accidentally demonstrated that expression of nitrogen permease regulator-like 2 (NPRL2), which is defined as a tumor suppressor, is upregulated in prostate cancer (PCa) and linked to poor prognosis, particularly in CRPC. The aim of this study was to investigate the role of NPRL2 in the chemoresistant CRPC cells. We found that NPRL2 was significantly overexpressed in docetaxel-resistant CRPC cells, while autophagy was enhanced and mTOR signaling was inhibited. Inhibiting NPRL2 increased the sensitivity to docetaxel in docetaxel-resistant CRPC cells, enhanced apoptosis and inhibited autophagy, and the opposite trends were observed when the mTOR inhibitor torin 1 was added to NPRL2-silenced cells. We further found that NPRL2 silenced docetaxel-resistant CRPC cells were sensitive to docetaxel in vivo. Briefly, our research reveals that overexpression of NPRL2 promotes chemoresistance by regulating autophagy via mTOR signaling and inhibits apoptosis in CRPC cells.

Loss of function of a rice TPR-domain RNA-binding protein confers broad-spectrum disease resistance.

Crops carrying broad-spectrum resistance loci provide an effective strategy for controlling infectious disease because these loci typically confer resistance to diverse races of a pathogen or even multiple species of pathogens. Despite their importance, only a few crop broad-spectrum resistance loci have been reported. Here, we report the identification and characterization of the rice bsr-k1 (broad-spectrum resistance Kitaake-1) mutant, which confers broad-spectrum resistance against Magnaporthe oryzae and Xanthomonas oryzae pv oryzae with no major penalty on key agronomic traits. Map-based cloning reveals that Bsr-k1 encodes a tetratricopeptide repeats (TPRs)-containing protein, which binds to mRNAs of multiple OsPAL (OsPAL1-7) genes and promotes their turnover. Loss of function of the Bsr-k1 gene leads to accumulation of OsPAL1-7 mRNAs in the bsr-k1 mutant. Furthermore, overexpression of OsPAL1 in wild-type rice TP309 confers resistance to M. oryzae, supporting the role of OsPAL1 Our discovery of the bsr-k1 allele constitutes a significant conceptual advancement and provides a valuable tool for breeding broad-spectrum resistant rice.

MircroRNA Profiles of Early Rice Inflorescence Revealed a Specific miRNA5506 Regulating Development of Floral Organs and Female Megagametophyte in Rice.

The developmental process of inflorescence and gametophytes is vital for sexual reproduction in rice. Multiple genes and conserved miRNAs have been characterized to regulate the process. The changes of miRNAs expression during the early development of rice inflorescence remain unknown. In this study, the analysis of miRNAs profiles in the early stage of rice inflorescence development identified 671 miRNAs, including 67 known and 44 novel differentially expressed miRNAs (DEMs). Six distinct clusters of miRNAs expression patterns were detected, and Cluster 5 comprised 110 DEMs, including unconserved, rice-specific osa-miR5506. Overexpression of osa-miR5506 caused pleiotropic abnormalities, including over- or under-developed palea, various numbers of floral organs and spikelet indeterminacy. In addition, the defects of ovaries development were frequently characterized by multiple megasporocytes, ovule-free ovary, megasporocyte degenerated and embryo sac degenerated in the transgenic lines. osa-miR5506 targeted REM transcription factor LOC_Os03g11370. Summarily, these results demonstrated that rice-specific osa-miR5506 plays an essential role in the regulation of floral organ number, spikelet determinacy and female gametophyte development in rice.

Neuroblastoma patient-derived cultures are enriched for a mesenchymal gene signature and reflect individual drug response.

Ex vivo evaluation of personalized models can facilitate individualized treatment selection for patients, and advance the discovery of novel therapeutic options. However, for embryonal malignancies, representative primary cultures have been difficult to establish. We developed patient-derived cell cultures (PDCs) from chemo-naïve and post-treatment neuroblastoma tumors in a consistent and efficient manner, and characterized their in vitro growth dynamics, histomorphology, gene expression, and functional chemo-response. From 34 neuroblastoma tumors, 22 engrafted in vitro to generate 31 individual PDC lines, with higher engraftment seen with metastatic tumors. PDCs displayed characteristic immunohistochemical staining patterns of PHOX2B, TH, and GD2 synthase. Concordance of MYCN amplification, 1p and 11q deletion between PDCs and patient tumors was 83.3%, 72.7%, and 80.0% respectively. PDCs displayed a predominantly mesenchymal-type gene expression signature and showed upregulation of pro-angiogenic factors that were similarly enriched in culture medium and paired patient serum samples. When tested with standard-of-care cytotoxics at human Cmax -equivalent concentrations, MYCN-amplified and non-MYCN-amplified PDCs showed a differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients' responses, and correlated with gene signatures of chemosensitivity. In this translational proof-of-concept study, early-phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated the individual molecular and phenotypic profile of patient tumors, and highlighted their potential as a platform for individualized ex vivo drug-response testing.

Comparative Cytological and Transcriptome Analysis Revealed the Normal Pollen Development Process and Up-Regulation of Fertility-Related Genes in Newly Developed Tetraploid Rice.

Autotetraploid rice is a useful germplasm for polyploid rice breeding; however, low seed setting is a major hindrance for its utilization. Here, we reported the development of a new tetraploid rice, Huoduo1 (H1), which has the characteristic of high fertility, from crossing generations of autotetraploid rice. Cytological observations displayed the high fertility of the pollen (95.62%) in H1, a lower percentage of pollen mother cell (PMC) abnormalities, and stable chromosome configurations during the pollen development process compared with its parents. Using RNA-seq analysis, we detected 440 differentially expressed genes (DEGs) in H1 compared with its parents. Of these DEGs, 193 were annotated as pollen fertility-related genes, and 129 (~66.8%) exhibited significant up-regulation in H1 compared with the parents, including three environmentally sensitive genic male sterility genes (TMS9-1, TMS5, and CSA), one meiosis gene (RAD51D), and three tapetal-related genes (MIL2, OsAP25, and OsAP37), which were validated by qRT-PCR in this study. Two genes, TMS9-1 and TMS5, were knocked out using CRISPR/Cas9 technology, and their mutants displayed low fertility and the abnormal development of pollen. Our findings provide evidence for the regulatory mechanisms of fertility in tetraploid rice and indicated that the up-regulation of pollen fertility-related genes may contribute to the high fertility in new tetraploid rice.

NPRL2 enhances autophagy and the resistance to Everolimus in castration-resistant prostate cancer.

BACKGROUND: Nitrogen permease regulator-like 2 (NPRL2) is reported to be a tumor suppressor candidate gene and involved in the mTOR signaling and drug resistance in several cancers. However, the role of NPRL2 in regulating the resistance to Everolimus (EVS), an inhibitor of the mTOR, in castration-resistant prostate cancer (CRPC) is still unclear. Therefore, in present study, we evaluated the role of NPRL2 and its potential resistance to EVS in CRPC. METHODS: NPRL2 expression levels in prostate tissues, including benign prostate hyperplasia (BPH) tissues, primary prostate cancer (PCa) tissues, CRPC tissues, and several PCa cell lines (LNCaP, PC3, and enzalutamide-resistant LNCaP, named LNPER) were be evaluated by immunohistochemistry, RT-PCR, and Western blot. Furthermore, we employed the loss or gain function of NPRL2 to determine the role of NPRL2 in regulating the proliferation, sensitivity to EVS, the mTOR signaling, autophagy in CRPC. Lastly, relationship between NPRL2 expression level and the efficacy of EVS were evaluated in mice tumor xenograft models. RESULTS: NPRL2 expression level is upregulated in PCa, particularly in the CRPC. NPRL2 over-expression promoted the proliferation, resistance to EVS, and NPRL2 silencing inhibited proliferation, enhanced sensitivity to EVS in PC3 and LNPER cells. Moreover, NPRL2-silencing increased the activity of mTOR signaling, and the autophagy attenuation induced by NPRL2-silencing in EVS-treated CRPC cells was associated with the increase of apoptosis. In addition, the growth prevention of NPRL2-silencing LNPER tumors in mice induced by EVS-treatment was associated with the autophagy attenuation and apoptosis increase. CONCLUSIONS: NPRL2 may act as a pro-growth factor in PCa. The high levels of NPRL2 expression in CRPC promote resistance to EVS by enhancing autophagy. NPRL2 may be a new therapeutic target for intervention of CRPC and a biomarker for predicting resistance to EVS in CRPC.

Targeting NPRL2 to enhance the efficacy of Olaparib in castration-resistant prostate cancer.

Castration-resistant prostate cancer (CRPC) lacks effective treatment, and studies have shown that PARPi inhibitors, such as Olaparib, are somewhat effective; however, the efficacy of Olaparib in CRPC still needs to be further improved. Nitrogen permease regulator-like 2 (NPRL2) is reported to be a tumor suppressor candidate gene and is closely related to the DNA repair pathway, which can affect the sensitivity of many chemotherapeutic drugs. However, there is no research on whether NPRL2 is associated with sensitivity to Olaparib. Hence, in the present study, we examined the NPRL2 expression levels in several PCa cell lines (LNCaP, PC3, and enzalutamide-resistant LNCaP, named LNPER) by Western blot. In addition, we investigated the role of NPRL2 expression and silencing in cell proliferation and in the regulation of ataxia telangiectasia mutated (ATM), which can mediate DNA repair and sensitivity to Olaparib. Furthermore, we performed in vitro and in vivo experiments to determine the mechanism of action of NPRL2 in adjusting Olaparib sensitivity. Our findings demonstrated that the NPRL2 expression level was upregulated in PCa cells, especially CRPC cells. NPRL2 overexpression promoted growth and resistance to Olaparib, and NPRL2 silencing inhibited proliferation, enhanced sensitivity to Olaparib, and increased CRRL2 expression in PCa cells. In addition, the Olaparib-induced growth delay in NPRL2-silenced PC3 tumors in mice correlated with ATM signaling downregulation, an apoptosis increase and migration/invasion suppression. Our results indicate that NPRL2 silencing enhances sensitivity to Olaparib treatment in CRPC and that NPRL2 may serve as a potential therapeutic target and predict resistance to Olaparib in CRPC.

Editing of the OsACS locus alters phosphate deficiency-induced adaptive responses in rice seedlings.

Phosphate (Pi) deficiency severely influences the growth and reproduction of plants. To cope with Pi deficiency, plants initiate morphological and biochemical adaptive responses upon sensing low Pi in the soil, and the plant hormone ethylene plays a crucial role during this process. However, how regulation of ethylene biosynthesis influences the Pi-induced adaptive responses remains unclear. Here, we determine the roles of rice 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS), the rate-limiting enzymes in ethylene biosynthesis, in response to Pi deficiency. Through analysis of tissue-specific expression of OsACS in response to Pi deficiency and OsACS mutants generated by CRISPR/Cas9 [clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9] genome editing, we found that two members of the OsACS family, i.e. OsACS1 and OsACS2, are involved but differed in their importance in controlling the remodeling of root system architecture, transcriptional regulation of Pi starvation-induced genes, and cellular phosphorus homeostasis. Interestingly, in contrast to the known inhibitory role of ethylene on root elongation, both OsACS mutants, especially OsACS1, almost fail to promote lateral root growth in response to Pi deficiency, demonstrating a stimulatory role for ethylene in lateral root development under Pi-deficient conditions. Together, this study provides new insights into the roles of ethylene in Pi deficiency response in rice seedlings and the isoform-specific function of OsACS genes in this process.