OsCOPT7 is a copper exporter at the tonoplast and endoplasmic reticulum and controls Cu translocation to the shoots and grain of rice.

Copper (Cu) is an essential micronutrient for all living organisms but is also highly toxic in excess. Cellular homoeostasis of Cu is maintained by various transporters and metallochaperones. Here, we investigated the biological function of OsCOPT7, a member of the copper transporters (COPT) family, in Cu homoeostasis in rice. OsCOPT7 was mainly expressed in the roots and the expression was upregulated by Cu deficiency. OsCOPT7 was localized at the tonoplast and the endoplasmic reticulum. Knockout of OsCOPT7 increased Cu accumulation in the roots but decreased Cu concentrations in the shoots and grain. The knockout mutants contained higher concentrations of Cu in the roots cell sap but markedly lower concentrations of Cu in the xylem sap than wild-type plants. Seed setting and grain yield were reduced significantly in the knockout mutants grown in a low Cu soil. Knockout mutants were more tolerant to Cu toxicity. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that OsCOPT7 interacts physically with the rice Cu chaperone antioxidant protein 1 (OsATX1). Taken together, our results indicate that OsCOPT7 is a specific Cu transporter functioning to export Cu from the vacuoles and the ER and plays an important role in controlling the root-to-shoot Cu translocation in rice.

The OsZIP2 transporter is involved in root-to-shoot translocation and intervascular transfer of cadmium in rice.

Cadmium (Cd) is a toxic metal that poses serious threats to human health. Rice is a major source of dietary Cd but how rice plants transport Cd to the grain is not fully understood. Here, we characterize the function of the ZIP (ZRT, IRT-like protein) family protein, OsZIP2, in the root-to-shoot translocation of Cd and intervascular transfer of Cd in nodes. OsZIP2 is localized at the plasma membrane and exhibited Cd2+ transport activity when heterologously expressed in yeast. OsZIP2 is strongly expressed in xylem parenchyma cells in roots and in enlarged vascular bundles in nodes. Knockout of OsZIP2 significantly enhanced root-to-shoot translocation of Cd and alleviated the inhibition of root elongation by excess Cd stress; whereas overexpression of OsZIP2 decreased Cd translocation to shoots and resulted in Cd sensitivity. Knockout of OsZIP2 increased Cd allocation to the flag leaf but decreased Cd allocation to the panicle and grain. We further reveal that the variation of OsZIP2 expression level contributes to grain Cd concentration among rice germplasms. Our results demonstrate that OsZIP2 functions in root-to-shoot translocation of Cd in roots and intervascular transfer of Cd in nodes, which can be used for breeding low Cd rice varieties.

High-throughput screening of 222 pesticides in road environments in a megacity of northern China: A new approach to urban population exposure.

A large number of pesticides have been widely manufactured and applied, and are released into the environment with negative impact on human health. Pesticides are largely used in densely populated urban environments, in green zones, along roads and on private properties. In order to characterize the potential exposure related health effects of pesticide and their occurrence in the urban environment, 222 pesticides were screened and quantified in 228 road dust and 156 green-belt soil samples in autumn and spring from Harbin, a megacity in China, using GC-MS/MS base quantitative trace analysis. The results showed that a total of 33 pesticides were detected in road dust and green-belt soil, with the total concentrations of 650 and 236 ng/g (dry weight = dw), respectively. The concentrations of pesticides in road dust were significantly higher than that in green-belt soil. Pesticides in the environment were influenced by the seasons, with the highest concentrations of insecticides in autumn and the highest levels of herbicides in spring. In road dust, the concentrations of highways in autumn and spring (with the mean values of 94.1 and 68.2 ng/g dw) were much lower than that of the other road classes (arterial roads, sub-arterial roads and branch ways). Whereas in the green-belt soil, there was no significant difference in the concentration of pesticides between the different road classes. A first risk assessment was conducted to evaluate the potential adverse health effects of the pesticides, the results showed that the highest hazard index (HI) for a single pesticide in dust and soil was 0.12, the hazard index for children was higher than that for adults, with an overall hazard index of less than 1. Our results indicated that pesticide levels do not have a significant health impact on people.

Methylated derivatives of polycyclic aromatic hydrocarbons in road dust, green belt soil and parking lot dust: occurrence, spatial distribution and emission sources.

Convenient transportation facilities not only bring the higher standard of living to big cities, but also bring some environmental pollution problems. In order to understand the presence and sources of methylated polycyclic aromatic hydrocarbons (Me-PAHs) in environmental samples and their association with total organic carbon (TOC), 49 Me-PAHs were analyzed in road dust, green belt soil and parking lot dust samples in Harbin. The results showed that the ranges of the total Me-PAHs (ΣMe-PAHs) content in road dust were 221-5826 ng/g in autumn and 697-7302 ng/g in spring, and those in green belt soil were 170-2509 ng/g and 155-9215 ng/g in autumn and spring, respectively. And ΣMe-PAHs content in parking lot dust ranged from 269 to 2515 ng/g in surface parking lots and from 778 to 10,052 ng/g in underground parking lots. In these samples, the composition profile of Me-PAHs was dominated by 4-ring Me-PAHs. The results of diagnostic ratios and principal component analysis (PCA) indicated that petrogenic and pyrogenic sources were the main sources of Me-PAHs in the samples. Spearman correlation analysis showed that there was no correlation for Me-PAHs in road dust and green belt soil on the same road. Furthermore, there was a significant positive relationship (0.12 ≤ R2 ≤ 0.67, P < 0.05) between Me-PAHs concentrations and the TOC content. This study demonstrated the presence of Me-PAHs with high concentrations in the road environment samples of Harbin.

MS/MS molecular networking-guided in-depth profiling of triterpenoid saponins from the fruit of Eleutherococcus senticosus and their neuroprotectivity evaluation.

INTRODUCTION: Eleutherococcus senticosus fruit (ESF) is a natural health supplement resource that has been extensively applied as a tonic for the nervous system. The structures and neural bioactivities of triterpenoid saponins (TS), which are the major constituents of ESF, have not been comprehensively analyzed thus far. OBJECTIVE: We conducted a complete in-depth MS/MS molecular networking (MN)-based targeted analysis of TS from the crude extract of ESF and investigated its neuroprotective value. METHODS: An MS/MS MN-guided strategy was used to rapidly present a series of precursor ions (PIs) of TS in a compound cluster as TS-targeted information used in the discovery and characterization of TS. In addition, a prepared TS-rich fraction of ESF was assayed for its restraining effects on ß-amyloid-induced inhibition of neurite outgrowth. RESULTS: A total of 87 TS were discovered using a PI tracking strategy, 28 of which were characterized as potentially undescribed structures according to their high-resolution MS values. Furthermore, the TS-rich fraction can significantly reduce ß-amyloid-induced damage to neural networks by promoting the outgrowth of neurites and axons. CONCLUSION: Our findings reveal the richness of TS in ESF and will accelerate their application in the treatment of neurodegenerative diseases.

The foaming properties of sweet potato protein hydrolysates produced by Alcalase and Ficin.

BACKGROUND: The processing of sweet potatoes generates a waste by-product rich in sweet potato protein (SPP). OBJECTIVE: In this study, the effects of the concentrations of Alcalase and Ficin, hydrolysis time and pH value on the foaming properties of SPP hydrolysates (SPPHs) determined via gas sparging method were investigated. RESULTS: The results showed that SPPH prepared by Alcalase exhibited a significantly higher foaming expansion (the highest of 576%) than that of the SPP (462%) but displayed a weaker liquid volume stability compared with SPPH hydrolyzed by Ficin. The molecular weight of SPPH prepared by Alcalase was distributed in 10-30 kDa. A good microbiological quality of the SPPH prepared by Alcalase in pH 13 has been confirmed, and it is suitable for food application with respect to its microbiological safety profile. CONCLUSIONS: SPPH (pH 13) could be further safely applied in food, especially as a food additive at low concentrations to create a better organic plant-based foaming agent for the food industry. © 2023 Society of Chemical Industry.

Molecular mechanisms underlying the toxicity and detoxification of trace metals and metalloids in plants.

Plants take up a wide range of trace metals/metalloids (hereinafter referred to as trace metals) from the soil, some of which are essential but become toxic at high concentrations (e.g., Cu, Zn, Ni, Co), while others are non-essential and toxic even at relatively low concentrations (e.g., As, Cd, Cr, Pb, and Hg). Soil contamination of trace metals is an increasing problem worldwide due to intensifying human activities. Trace metal contamination can cause toxicity and growth inhibition in plants, as well as accumulation in the edible parts to levels that threatens food safety and human health. Understanding the mechanisms of trace metal toxicity and how plants respond to trace metal stress is important for improving plant growth and food safety in contaminated soils. The accumulation of excess trace metals in plants can cause oxidative stress, genotoxicity, programmed cell death, and disturbance in multiple physiological processes. Plants have evolved various strategies to detoxify trace metals through cell-wall binding, complexation, vacuolar sequestration, efflux, and translocation. Multiple signal transduction pathways and regulatory responses are involved in plants challenged with trace metal stresses. In this review, we discuss the recent progress in understanding the molecular mechanisms involved in trace metal toxicity, detoxification, and regulation, as well as strategies to enhance plant resistance to trace metal stresses and reduce toxic metal accumulation in food crops.

A base-mediated aerobic oxidative synthesis of cyclopent-2-enol derivatives from doubly activated cyclopropanes and substituted acetonitriles.

We report here that polysubstituted cyclopent-2-enols can be constructed by the one-pot reaction of doubly activated cyclopropanes and α-EWG substituted acetonitriles under mild basic conditions via a domino-ring-opening-cyclization/deacylation/oxidation sequence. Moreover, the synthetic applications of these cyclopent-2-enols have been demonstrated in the late-stage derivatization into functionalized cyclopentapyrimidin-4-ones and 2-hydroxy cyclopentanones with good yields.

How to establishing an indicators framework for evaluating the performances in primary TB control institutions under the new TB control model? Based on a Delphi study conducted in Guangxi, China.

BACKGROUND: In China, the new TB control model of trinity form had been implemented in all parts, and the comprehensively evaluation to the performances in primary TB control institutions were closely related to the working capacity and quality of TB service, but there was still no an unified evaluation indicators framework in practice and few relevant studies. The purpose of this study was to establish an indicators framework for comprehensively evaluating the performances in primary TB control institutions under the new TB control model of trinity form in Guangxi, China. METHODS: The Delphi method was used to establish an indicators framework for comprehensively evaluating the performances in primary TB control institutions under the new TB control model of trinity form, and the analytic hierarchy process(AHP) was used to determine the weights of all levels of indicators, from September 2021 to December 2021 in Guangxi, China. RESULTS: A total of 14 experts who had at least 10 years working experience and engaged in TB prevention and control and public health management from health committee, CDC, TB designated hospitals and university of Guangxi were consulted in two rounds. The average age of the experts were (43.3 ± 7.549) years old, and the effective recovery rate of the questionnaire was 100.0%. The average value of authority coefficient of experts (Cr) in the two rounds of consultation was above 0.800. The Kendall's harmony coefficient (W) of experts' opinions on the first-level indicators, the second-level indicators and the third-level indicators were 0.786, 0.201 and 0.169, respectively, which were statistically significant (P < 0.05). Finally, an indicators framework was established, which included 2 first-level indicators, 10 second-level indicators and 37 third-level indicators. The results of analytic hierarchy process (AHP) showed that the consistency test of all levels of indicators were CI < 0.10, which indicating that the weight of each indicator was acceptable. CONCLUSION: The indicators framework established in this study was in line with the reality, had reasonable weights, and could provide a scientific evaluation tool for comprehensively evaluating the performances in primary TB control institutions under the new TB control model of trinity form in Guangxi, China.

Morphological and physiological correlates of among- individual variation in basal metabolic rate in two passerine birds.

Basal metabolic rate (BMR) has been shown to be a highly phenotypic flexibility trait within species. A significant proportion of an individual's energy budget is accounted for by BMR, hence among-individual variation in this trait may affect other energetic processes, as well as fitness. In this study, we measured BMR, organ mass, mitochondrial respiration capacities and cytochrome c oxidase (COX) activities in muscle and liver and circulating levels of plasma triiodothyronine (T3) in Chinese bulbuls (Pycnonotus sinensis) and Eurasian tree sparrows (Passer montanus). Our results showed that heart and kidney mass was positively correlated with BMR in Chinese bulbuls, whereas liver and kidney mass was positively correlated with BMR in Eurasian tree sparrows. Regarding metabolic biochemical markers of tissues, state 4 respiration and COX activity in the muscles of the Chinese bulbuls was correlated with BMR, while state 4 respiration in the muscle and liver was correlated with BMR in Eurasian tree sparrows. T3 was significantly and positively correlated with BMR in Chinese bulbuls and Eurasian tree sparrows. Consistent with the above results, our findings suggest that T3 levels play an important role in modulating BMR in Chinese bulbuls and Eurasian tree sparrows. Moreover, individual variation in BMR can be explained partly by morphological and physiological mechanisms.

Novel synthesis of fused spiro piperidone-cyclopropanes from cyclopropyl amides and electron-deficient alkenes.

We report here that a series of bridged O,O-ketal fused spiro piperidone-cyclopropane derivatives 3 can be constructed with excellent yields and good diastereoselectivity by the one-pot reaction of 1-acylcyclopropanecarboxamides 1 with electron-deficient alkene 2a (EWG = CHO) via the domino process involving [4 + 2] annulation/intermolecular electrophilic addition/intramolecular cyclization. Furthermore, reactions of 1 with 2b/2c (EWG = CN, COOMe), leading to spiro piperidone-cyclopropane derivatives 4 or 5 by base catalyst selection, were also presented.

Antioxidant defense response during hibernation and arousal in Chinese soft-shelled turtle Pelodiscus sinensis juveniles.

Antioxidant defense is essential for animals to cope with homeostasis disruption during hibernation. The present study aimed to investigate the antioxidant defense response of juvenile soft-shelled turtle Pelodiscus sinensis during hibernation and following arousal. Turtle brain, liver, and kidney samples were collected at pre-hibernation (17 °C mud temperature; MT), during hibernation (5.8 °C MT) and after arousal (20.1 °C MT) in the field. Transcript levels of NF-E2-related factor 2 (Nrf2) decreased significantly during hibernation and recovered after arousal in all tissues. Cerebral and nephric copper-zinc superoxide dismutase (Cu/Zn SOD), catalase (CAT), glutathione peroxidase 3 (GPx3) and nephric GPx4 mRNA showed similar changing patterns as Nrf2. Cerebral Mn SOD, GPx1 and nephric GPx1 up-regulated after arousal. Hepatic Cu/Zn SOD, GPx1 and GPx3 mRNA kept stable, except hepatic GPx4 increased during hibernation. Hepatic Mn SOD and CAT increased after arousal. In the GSH system, mRNA levels of glutathione synthetases (GSs) kept stable during hibernation and up-regulated after arousal in most tissues except nephric GS2 mRNA remained unchanged. Gene expressions of glutathione reductase (GR) exhibited a tissue specific changing pattern, while those of glutathione-S-Transferase (GST) shared a similar pattern among tissues: remained stable or down-regulated during hibernation then recovered in arousal. In contrast to these diverse responses in gene expressions, most of the antioxidant enzyme activities maintained high and stable. Overall, no preparation for oxidative stress (POS) strategy was found in enzymatic antioxidant system in P. sinensis juveniles during hibernation, the Chinese soft-shelled turtles were able to stay safe from potential oxidative stress during hibernation by maintaining high level activities/concentrations of the antioxidant enzymes/antioxidants.

A combination of ssGSEA and mass cytometry identifies immune microenvironment in muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with varying clinical courses and responses to treatment. To improve the prognosis of patients, it is necessary to understand such heterogeneity. METHODS: We used single-sample gene set enrichment analysis to classify 35 MIBC cases into immunity-high and immunity-low groups. Bioinformatics analyses were conducted to compare the differences between these groups. Eventually, single-cell mass cytometry (CyTOF) was used to compare the characteristics of the immune microenvironment between the patients in the two groups. RESULTS: Compared with patients in the immunity-low group, patients in the immunity-high group had a higher number of tumor-infiltrating immune cells and greater enrichment of gene sets associated with antitumor immune activity. Furthermore, positive immune response-related pathways were more enriched in the immunity-high group. We identified 26 immune cell subsets, including cytotoxic T cells (Tcs), helper T cells (Ths), regulatory T cells (Tregs), B cells, macrophages, natural killer (NK) cells, and dendritic cells (DCs) using CyTOF. Furthermore, there was a higher proportion of CD45+ lymphocytes and enrichment of one Tc subset in the immunity-high group. Additionally, M2 macrophages were highly enriched in the immunity-low group. Finally, there was higher expression of PD-1 and Tim-3 on Tregs as well as a higher proportion of PD-1+ Tregs in the immunity-low group than in the immunity-high group. CONCLUSION: In summary, the immune microenvironments of the immunity-high and immunity-low groups of patients with MIBC are heterogeneous. Specifically, immune suppression was observed in the immune microenvironment of the patients in the immunity-low group.

Genetic mapping of ionomic quantitative trait loci in rice grain and straw reveals OsMOT1;1 as the putative causal gene for a molybdenum QTL qMo8.

Rice is a major dietary source of essential mineral nutrients and toxic elements (aka ionome) for humans. However, the genetic basis underlying the variation in ionome is still largely unknown. Here, we mapped 51 and 61 quantitative trait loci (QTLs) controlling the concentrations of 13 and 15 elements in rice (Oryza sativa L.) grain and straw, respectively, using a recombinant inbred lines (RILs) that were grown at three different field sites in 3 years. Several QTLs were repeatedly detected in both grain and straw or in multiple years; the resulting 87 unique QTLs with 17 of them (20%) were co-localized with previously reported corresponding QTLs and 70 were novel ionomic QTLs. At least, 14 genomic clusters that controlled the concentrations of multiple elements were identified. Furthermore, we identified a molybdate transporter gene OsMOT1;1 as the putative causal gene for a QTL controlling molybdenum concentration in both straw and grain. QTL analyses based on the concentrations of multiple elements in both grain and straw of RIL population grown in three field sites in 3 years allow us to identify tissue common QTLs and reproducible QTLs that were validated in multiple years. The identification of ionomic QTLs will be useful in revealing the molecular mechanisms underlying the accumulation of elements in rice and providing the opportunity to reduce the accumulation of toxic elements and enrich the accumulation of beneficial elements in rice grain.

OASTL-A1 functions as a cytosolic cysteine synthase and affects arsenic tolerance in rice.

Arsenic (As) contamination in paddy soil can cause phytotoxicity and elevated As accumulation in rice grains. Arsenic detoxification is closely linked to sulfur assimilation, but the genes involved have not been described in rice. In this study, we characterize the function of OASTL-A1, an O-acetylserine(thiol) lyase, in cysteine biosynthesis and detoxification of As in rice. Tissue expression analysis revealed that OsOASTL-A1 is mainly expressed in roots at the vegetative growth stage and in nodes at the reproductive stage. Furthermore, the expression of OsOASTL-A1 in roots was strongly induced by As exposure. Transgenic rice plants expressing pOsOASTL-A1::GUS (ß-glucuronidase) indicated that OsOASTL-A1 was strongly expressed in the outer cortex and the vascular cylinder in the root mature zone. Subcellular localization using OsOASTL-A1:eGFP (enhanced green fluorescent protein) fusion protein showed that OsOASTL-A1 was localized to the cytosol. In vivo and in vitro enzyme activity assays showed that OsOASTL-A1 possessed the O-acetylserine(thiol) lyase activity. Knockout of OsOASTL-A1 led to significantly lower levels of cysteine, glutathione, and phytochelatins in roots and increased sensitivity to arsenate stress. Furthermore, the osoastl-a1 knockout mutants reduced As accumulation in the roots, but increased As accumulation in shoots. We conclude that OsOASTL-A1 is the cytosolic O-acetylserine(thiol) lyase that plays an important role in non-protein thiol biosynthesis in roots for As detoxification.

Dimethylarsinic acid is the causal agent inducing rice straighthead disease.

Straighthead disease is a physiological disorder in rice with symptoms of sterile spikelets, distorted husks, and erect panicles. Methylated arsenic species have been implicated as the causal agent of the disease, but direct evidence is lacking. Here, we investigated whether dimethylarsinic acid (DMA) causes straighthead disease and its effect on the transcriptome of young panicles. DMA addition caused typical straighthead symptoms in hydroponic culture, which were alleviated by silicon addition. DMA addition to soil at the tillering to flowering stages induced straighthead disease. Transgenic rice expressing a bacterial arsenite methyltransferase gene gained the ability to methylate arsenic to mainly DMA, with the consequence of inducing straighthead disease. Field surveys showed that seed setting rate decreased with increasing DMA concentration in the husk, with an EC50 of 0.18 mg kg-1. Transcriptomic analysis showed that 364 and 856 genes were significantly up- and down-regulated, respectively, in the young panicles of DMA-treated plants compared with control, whereas Si addition markedly reduced the number of genes affected. Among the differentially expressed genes, genes related to cell wall modification and oxidative stress responses were the most prominent, suggesting that cell wall metabolism is a sensitive target of DMA toxicity and silicon protects against this toxicity.

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.

BACKGROUND: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. METHODS: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. RESULTS: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. CONCLUSIONS: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

Bromodomains and Extra-Terminal (BET) Inhibitor JQ1 Suppresses Proliferation of Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolysis.

BACKGROUND Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro. MATERIAL AND METHODS Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot. RESULTS JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis. CONCLUSIONS The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL.

Progress on genome-wide CRISPR/Cas9 screening for functional genes and regulatory elements.

The CRISPR/Cas9 system is a powerful tool which has been extensively used for genome editing in the past few years. Nuclease-dead Cas9 (CRISPR/dCas9), a Cas9 protein mutant without splicing ability, along with loss-of- function (LOF), gain-of-function (GOF), or non-coding genes scanning approaches can reveal genome-scale functional determinants. CRISPR/Cas9 has been widely adopted to decipher disease mechanisms and pinpoint drug targets in the life science field, and also provide novel insights into animal genetics and breeding. In this review, we summarize the research progress in high-throughput CRISPR/Cas9 screening for revealing the functional genes and regulatory elements in the whole genome. We also highlight the applications of CRISPR/Cas9 system in the animal cells, providing a reference for gene editing and other related research in related fields.

The C-type ATP-Binding Cassette Transporter OsABCC7 Is Involved in the Root-to-Shoot Translocation of Arsenic in Rice.

Rice is a major dietary source of inorganic arsenic (As), a nonthreshold carcinogen. Reducing As accumulation in rice grain is of critical importance for food safety. In the present study, we investigated the role of a member of the rice C-type ATP-binding cassette (ABC) transporter (OsABCC) family, OsABCC7, in arsenite [As(III)] accumulation in rice. Quantitative real-time RT-PCR showed that OsABCC7 was expressed intensively in the roots and the expression was strongly suppressed by As(III) exposure. Transgenic rice plants expressing OsABCC7 Promoter-GUS (ß-glucuronidase) suggest that the gene was predominantly expressed in the xylem parenchyma cells in the stele region of the primary and lateral roots. Transient expression of OsABCC7: GFP fusion protein in Nicotiana benthamiana leaf cells showed that the protein was localized at the plasma membrane. When expressed in Xenopus laevis oocytes, OsABCC7 showed an efflux activity for As(III)-phytochelatin and As(III)-glutathione complexes, but not for As(III). Knockout of OsABCC7 in rice significantly decreased As concentration in the xylem sap and As concentration in the shoots, but had little effect on root As concentration. Taken together, our results indicate that OsABCC7 is involved in the root-to-shoot translocation of As(III).