TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Central and peripheral analgesic active components of triterpenoid saponins from Stauntonia chinensis and their action mechanism.

Triterpenoid saponins from Stauntonia chinensis have been proven to be a potential candidate for inflammatory pain relief. Our pharmacological studies confirmed that the analgesic role of triterpenoid saponins from S. chinensis occurred via a particular increase in the inhibitory synaptic response in the cortex at resting state and the modulation of the capsaicin receptor. However, its analgesic active components and whether its analgesic mechanism are limited to this are not clear. In order to further determine its active components and analgesic mechanism, we used the patch clamp technique to screen the chemical components that can increase inhibitory synaptic response and antagonize transient receptor potential vanilloid 1, and then used in vivo animal experiments to evaluate the analgesic effect of the selected chemical components. Finally, we used the patch clamp technique and molecular biology technology to study the analgesic mechanism of the selected chemical components. The results showed that triterpenoid saponins from S. chinensis could enhance the inhibitory synaptic effect and antagonize the transient receptor potential vanilloid 1 through different chemical components, and produce central and peripheral analgesic effects. The above results fully reflect that "traditional Chinese medicine has multi-component, multi-target, and multi-channel synergistic regulation".

Antifouling and Chemical-Resistant Nanofiltration Membrane Modulated by a Functionalized MWCNT Interlayer for Efficient Dye/Salt Separation at High Salinity.

Dye/salt separation in textile wastewater is of great importance. Membrane filtration technology is an environmentally friendly and effective approach to solve this issue. In this study, a thin-film composite membrane with a tannic acid (TA)-modified carboxylic multiwalled carbon nanotube (MWCNT) interlayer (M-TA) was prepared by interfacial polymerization with amino-functionalized graphene quantum dots (NGQDs) acting as aqueous monomers. The addition of the M-TA interlayer favored the formation of a thinner, more hydrophilic, and smoother selective skin layer for the composite membrane. The pure water permeability of the M-TA-NGQDs membrane was ∼9.32 L m-2 h-1 bar-1, which was higher than that of the NGQDs membrane without the interlayer. Meanwhile, the M-TA-NGQDs membrane presented better methyl orange (MO) rejection (97.79%) than the NGQDs membrane (87.51%). The optimal M-TA-NGQDs membrane exhibited excellent dye rejection (Congo red (CR): 99.61%; brilliant green (BG): 96.04%) and low salt rejection (NaCl < 15%). Noticeably, the M-TA-NGQDs membrane displayed effective selective separation performance (CR and BG > 99%) for dye/NaCl mixed solutions even at a high NaCl concentration of 50,000 mg/L. Furthermore, the M-TA-NGQDs membrane presented high water permeability recovery ratio values (91.02-98.20%). Importantly, the M-TA-NGQDs membrane showed excellent chemical stability (acid/alkali resistance). Generally, the fabricated M-TA-NGQDs membrane exhibited a great prospect for applications in dye wastewater treatment and water recycling, especially for the effective selective separation of dye/salt mixtures for high-salinity textile dyeing wastewater.

Thin-Film Nanocomposite Membranes with Nature-Inspired MOFs Incorporated for Removing Fluoroquinolone Antibiotics.

A nanofiltration membrane functionalized with metal-organic frameworks (MOFs) is promising to enhance micropollutant removal and realize wastewater reclamation. However, the current MOF-based nanofiltration membranes still suffer from severe fouling problems with an indefinable mechanism when used for antibiotic wastewater treatment. Hence, we report a nature-inspired MOF-based thin-film nanocomposite (TFN-CU) membrane to explore its rejection and antifouling behavior. Compared with unmodified membranes, the optimal TFN-CU5 membrane (with 5 mg·mL-1 C-UiO-66-NH2) had high water permeance (17.66 ± 1.19 L·m-2·h-1·bar-1), exceptional rejection for norfloxacin (97.92 ± 2.28%) and ofloxacin (95.36 ± 1.03%), and excellent long-term stability for treating synthetic secondary effluent with antibiotic rejection over 90%. Furthermore, it also showed superior antifouling capability (flux recovery up to 95.86 ± 1.28%) in bovine serum albumin (BSA) filtration after fouling cycles. Deriving from the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) approach, the antifouling mechanism between BSA and the TFN-CU5 membrane was mainly attributed to the inhibited adhesion forces because the growing short-ranged acid-base interaction caused repulsive interfacial interactions. It is further revealed that BSA fouling behavior is slightly retarded under an alkaline environment, while strengthened in the presence of calcium ions and humic acid, as well as high ionic strength. In short, the nature-inspired MOF-based TFN membranes possess exceptional rejection and organic fouling resistance, giving insights into the design of antifouling membranes during antibiotic wastewater reclamation.

Low-pressure thin-film composite nanofiltration membranes with enhanced selectivity and antifouling property for effective dye/salt separation.

For better sustainable resource recovery and elevating the separation efficiency of dye/salt mixture, it is essential to develop an appropriate nanofiltration membrane for the treatment of textile dyeing wastewater containing relatively smaller molecule dyes. In this work, a novel composite polyamide-polyester nanofiltration membrane was fabricated by tailoring amino functionalized quantum dots (NGQDs) and ß-cyclodextrin (CD). An in-situ interfacial polymerization occurred between the synthesized NGQDs-CD and trimesoyl chloride (TMC) on the modified multi-carbon nanotubes (MWCNTs) substrate. The incorporation of NGQDs significantly elevated the rejection (increased by âˆ¼ 45.08%) of the resultant membrane for small molecular dye (Methyl orange, MO) compared to the pristine CD membrane at low pressure (1.5 bar). The newly developed NGQDs-CD-MWCNTs membrane exhibited enhanced water permeability without compromising the dye rejection compared to the pure NGQDs membrane. The improved performance of the membrane was primarily attributed to the synergistic effect of functionalized NGQDs and the special hollow-bowl structure of CD. The optimal NGQDs-CD-MWCNTs-5 membrane expressed pure water permeability of 12.35 L m-2h-1 bar-1 at the pressure of 1.5 bar. Noteworthily, the NGQDs-CD-MWCNTs-5 membrane not only showed high rejection for the larger molecular dye of Congo Red (CR, 99.50%) but also for the smaller molecular dye of MO (96.01%) and Brilliant Green (BG, 95.60%) with the permeability of 8.81, 11.40, and 6.37 L m-2h-1 bar-1, respectively at low pressure (1.5 bar). The rejection of inorganic salts by the NGQDs-CD-MWCNTs-5 membrane was 17.20% for sodium chloride (NaCl), 14.30% for magnesium chloride (MgCl2), 24.63% for magnesium sulfate (MgSO4), and 54.58% for sodium sulfate (Na2SO4), respectively. The great rejection of dyes remained in the dye/salt binary mixed system (higher than 99% for BG and CR, <21% for NaCl). Importantly, the NGQDs-CD-MWCNTs-5 membrane exhibited favorable antifouling performance and potential good operation stability performance. Consequently, the fabricated NGQDs-CD-MWCNTs-5 membrane suggested a prospective application for the reuse of salts and water in textile wastewater treatment owing to the effective selective separation performance.

Dual-function DEFENSIN 8 mediates phloem cadmium unloading and accumulation in rice grains.

Grain cadmium (Cd) is translocated from source to sink tissues exclusively via phloem, though the phloem Cd unloading transporter has not been identified yet. Here, we isolated and functionally characterized a defensin-like gene DEFENSIN 8 (DEF8) highly expressed in rice (Oryza sativa) grains and induced by Cd exposure in seedling roots. Histochemical analysis and subcellular localization detected DEF8 expression preferentially in pericycle cells and phloem of seedling roots, as well as in phloem of grain vasculatures. Further analysis demonstrated that DEF8 is secreted into extracellular spaces possibly by vesicle trafficking. DEF8 bound to Cd in vitro, and Cd efflux from protoplasts as well as loading into xylem vessels decreased in the def8 mutant seedlings compared with the wild type. At maturity, significantly less Cd accumulation was observed in the mutant grains. These results suggest that DEF8 is a dual function protein that facilitates Cd loading into xylem and unloading from phloem, thus mediating Cd translocation from roots to shoots and further allocation to grains, representing a phloem Cd unloading regulator. Moreover, essential mineral nutrient accumulation as well as important agronomic traits were not affected in the def8 mutants, suggesting DEF8 is an ideal target for breeding low grain Cd rice.

Long-term exposure to low levels of okadaic acid accelerates cell cycle progression in colonic epithelial cells via p53 and Jak/Stat3 signaling pathways.

As a major component of diarrheic shellfish poisoning (DSP) toxins, okadaic acid (OA) is widely distributed worldwide, and causes a series of serious public health problems. In colon tissue, previous studies have shown that high doses of OA can affect various intracellular processes, including destroy intercellular communication at gap junctions, induce cell apoptosis and trigger cell cycle arrest. However, there is a scarcity of studies on the effect and mechanism of action of low doses of OA in colonic tissues. In this study, we observed that exposure to low levels of OA altered cell cycle progression in vitro and in vivo. Investigation of the underlying mechanism revealed that OA induced alterations in the cell cycle by inhibiting the p53 signaling pathway or inducing the Jak/Stat3 signaling pathway. In conclusion, this study provides novel insights into the effect and mechanism underlying long-term exposure to low levels of OA.

Vacuolar nitrate efflux requires multiple functional redundant nitrate transporter in Arabidopsis thaliana.

Nitrate in plants is preferentially stored in vacuoles; however, how vacuolar nitrate is reallocated and to which biological process(es) it might contribute remain largely elusive. In this study, we functionally characterized three nitrate transporters NPF5.10, NPF5.14, and NPF8.5 that are tonoplast-localized. Ectopic expression in Xenopus laevis oocytes revealed that they mediate low-affinity nitrate transport. Histochemical analysis showed that these transporters were expressed preferentially in pericycle and xylem parenchyma cells. NPF5.10, NPF5.14, and NPF8.5 overexpression significantly decreased vacuolar nitrate contents and nitrate accumulation in Arabidopsis shoots. Further analysis showed that the sextuple mutant (npf5.10 npf5.14 npf8.5 npf5.11 npf5.12 npf5.16) had a higher 15NO3-uptake rate than the wild-type Col-0, but no significant difference was observed for nitrate accumulation between them. The septuple mutant (npf5.11 npf5.12 npf5.16 npf5.10 npf5.14 npf8.5 clca) generated by using CRISPR/Cas9 showed essentially decreased nitrate reallocation compared to wild type when exposed to nitrate starvation, though no further decrease was observed when compared to clca. Notably, NPF5.10, NPF5.14, and NPF8.5 as well as NPF5.11, NPF5.12, and NPF5.16 were consistently induced by mannitol, and more nitrate was detected in the sextuple mutant than in the wild type after mannitol treatment. These observations suggest that vacuolar nitrate efflux is regulated by several functional redundant nitrate transporters, and the reallocation might contribute to osmotic stress response other than mineral nutrition.

Loosely Sandwich-Structured Membranes Decorated with UiO-66-NH2 for Efficient Antibiotic Separation and Organic Solvent Resistance.

Thin-film nanocomposite (TFN) membranes with efficient molecular separation and organic solvent resistance are active in demand in wastewater treatment and resource reclamation, meeting the goal of emission peaks and carbon neutrality. In this work, a simple and rational design strategy has been employed to construct a sandwich-structured membrane for removing fluoroquinolone antibiotics and recycling organic solvents. The sandwich-structured membrane is composed of a porous substrate, a hydrophilic tannic acid-polyethyleneimine (TA-PEI) interlayer, and a polyamide (PA) selective layer decorated with metal-organic framework (PA-MOF). Results manifest that the hydrophilic TA-PEI interlayer played a bridging and gutter effect to achieve effective control in amide storage, amine diffusion, and nanomaterial downward leakage at the immiscible interface. The PA-MOF selective layer has been changed to a loosely crumpled surface, endowing functionalities on the sandwich-structured membrane that included limited pores, strengthened electronegativity, and stronger hydrophilicity. Thus, an enhanced water flux of 87.23 ± 7.43 LMH was achieved by the TFN-2 membrane (0.04 mg·mL-1 UiO-66-NH2), which is more than five times that of the thin-film composite membrane (17.46 ± 3.88 LMH). The rejection against norfloxacin, ciprofloxacin, and levofloxacin is 92.94 ± 1.60%, 94.62 ± 1.29%, and 96.92 ± 1.05%, respectively, effectively breaking through the "trade-off" effect between membrane permeability and rejection efficiency. Further antifouling results showed that the sandwich-structured membrane had lower flux decay ratios (3.36∼7.07%) and higher flux recovery ratios (93.40∼98.40%), as well as superior long-term stability after 30 days of filtration. Moreover, organic solvent resistance testing confirms that the sandwich-structured membrane maintained stable solvent flux and better recovery rates in ethanol, acetone, isopropanol, and N,N-dimethylformamide. Detailed nanofiltration mechanism studies revealed that these outstanding performances are based on the joint effect of the TA-PEI interlayer and PA-MOF selective layer, proposing a new perspective to break through the bottleneck of nanofiltration application in a complex environment.

Overexpression of Karyopherin α2 in small cell carcinoma of the cervix correlates with poor prognosis.

BACKGROUND: Cervical small cell carcinoma (SCCC) is uncommon and little is known about its molecular markers. Karyopherin α2 (KPNA2) has been demonstrated in a variety of malignancies. Our objective was to determine whether the KPNA2 level is predictive of clinical outcome in patients with SCCC. METHODS: We detected KPNA2 expression by immunohistochemistry in SCCC tumors from 62 patients. The staining results were evaluated by H-score. The correlation among KPNA2 expression level, clinical characteristics, and prognosis was analyzed. RESULTS: KPNA2 expression was detected in tumor tissue from 55 patients with SCCC (55/62, 89%). High KPNA2 expression correlated significantly with International Federation of Gynecology and Obstetrics staging (P=0.035), tumor size (P=0.019), poorer overall survival (OS) (P=0.008), and poorer disease-free survival (P=0.004) compared to low KPNA2 expression. Multivariate analysis showed that KPNA2 expression level (P=0.037) and tumor size (P=0.046) were independent prognostic factors of OS. CONCLUSIONS: KPNA2 may be a molecular marker and indicator of prognosis in SCCC.

CJ14939, a Novel JAK Inhibitor, Increases Oxaliplatin-induced Cell Death Through JAK/STAT Pathway in Colorectal Cancer.

BACKGROUND/AIM: Colorectal cancer is reported to have the highest mortality rate among human malignancies. Although many research results for the treatment of colorectal cancer have been reported, there is no suitable treatment when resistance has developed. Therefore, it is necessary to develop new therapeutic agents. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling plays an essential role in cell differentiation, proliferation, and survival. Abnormal activation of the JAK/STAT signaling pathway, by gene mutation or amplification, may induce cancer development, and sustained JAK/STAT activation is involved in chemoresistance. While many therapeutic agents have been developed to treat colon cancer, there remains no drug to overcome resistance to chemotherapies. The purpose of this study was to determine the potential of CJ14939 as a novel JAK inhibitor for the treatment of colorectal cancer. MATERIALS AND METHODS: In this study, cell culture, cell death assay, 3- (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, colony formation assay, immunoblot analysis and tumor xenograft were applied. RESULTS: CJ14939 induced cell death, and inhibited phosphorylation of JAK1 and STAT3 in colorectal cancer cells. Furthermore, CJ14939 also promoted oxaliplatin-induced cell death, up-regulated expression of cleaved caspase-3, and down-regulated expression of phospho-JAK1 and phospho-STAT3. In vivo, co-treatment with CJ14939 and oxaliplatin notably reduced tumor growth when compared with CJ14939 or oxaliplatin treatment alone. CONCLUSION: This study identifies the important potential of CJ14939 in colorectal cancer treatment and suggests that combining CJ14939 with oxaliplatin might be a novel therapeutic strategy for patients with colorectal cancer.

The nitrate transporter OsNPF7.9 mediates nitrate allocation and the divergent nitrate use efficiency between indica and japonica rice.

Nitrate allocation in Arabidopsis (Arabidopsis thaliana) represents an important mechanism for mediating plant environmental adaptation. However, whether this mechanism occurs or has any physiological/agronomic importance in the ammoniphilic plant rice (Oriza sativa L.) remains unknown. Here, we address this question through functional characterization of the Nitrate transporter 1/Peptide transporter Family (NPF) transporter gene OsNPF7.9. Ectopic expression of OsNPF7.9 in Xenopus oocytes revealed that the gene encodes a low-affinity nitrate transporter. Histochemical and in-situ hybridization assays showed that OsNPF7.9 expresses preferentially in xylem parenchyma cells of vasculature tissues. Transient expression assays indicated that OsNPF7.9 localizes to the plasma membrane. Nitrate allocation from roots to shoots was essentially decreased in osnpf7.9 mutants. Biomass, grain yield, and nitrogen use efficiency (NUE) decreased in the mutant dependent on nitrate availability. Further analysis demonstrated that nitrate allocation mediated by OsNPF7.9 is essential for balancing rice growth and stress tolerance. Moreover, our research identified an indica-japonica divergent single-nucleotide polymorphism occurring in the coding region of OsNPF7.9, which correlates with enhanced nitrate allocation to shoots of indica rice, revealing that divergent nitrate allocation might represent an important component contributing to the divergent NUE between indica and japonica subspecies and was likely selected as a favorable trait during rice breeding.

An automated COVID-19 triage pipeline using artificial intelligence based on chest radiographs and clinical data.

While COVID-19 diagnosis and prognosis artificial intelligence models exist, very few can be implemented for practical use given their high risk of bias. We aimed to develop a diagnosis model that addresses notable shortcomings of prior studies, integrating it into a fully automated triage pipeline that examines chest radiographs for the presence, severity, and progression of COVID-19 pneumonia. Scans were collected using the DICOM Image Analysis and Archive, a system that communicates with a hospital's image repository. The authors collected over 6,500 non-public chest X-rays comprising diverse COVID-19 severities, along with radiology reports and RT-PCR data. The authors provisioned one internally held-out and two external test sets to assess model generalizability and compare performance to traditional radiologist interpretation. The pipeline was evaluated on a prospective cohort of 80 radiographs, reporting a 95% diagnostic accuracy. The study mitigates bias in AI model development and demonstrates the value of an end-to-end COVID-19 triage platform.

The combined toxicity and mechanism of multi-walled carbon nanotubes and nano zinc oxide toward the cabbage.

The natural environment is a complex system, and there is never only one kind of nanomaterial entering the environment. However, many studies only considered the plant toxicity of one kind of nanomaterial and do not consider the influence of two or more kinds of nanomaterials on plant toxicity. Multi-walled carbon nanotubes (MWCNTs) and zinc oxide nanoparticles (ZnO NPs) are two common and widely used nanomaterials in water environment, so these two kinds of nanomaterials were chosen to explore the effects of their combined toxicity on cabbage. This study investigated the toxicity of MWCNTs combined with ZnO NPs on cabbage by measuring the length of roots and stems, chlorophyll content, oxidative stress, antioxidant enzyme activity, metal element content, and root scanning electron microscopy. The toxicity of single MWCNTs toward cabbage was attributed to direct oxidative damage, while the toxicity of single ZnO NPs toward cabbage was due to the high level of zinc concentration. Moreover, ZnO NPs (10 mg/L) ameliorated MWCNTs toxicity toward cabbage by improving the activity of antioxidant enzymes. ZnO NPs (50 and 100 mg/L) because of the high content of zinc disrupted the balance of other metals in the plant and increased the toxicity of MWCNTs. In conclusion, the combined toxicity of different concentrations and types of nanomaterials should be considered for a more accurate assessment of environmental risks.

An Enhanced Tree Routing Based on Reinforcement Learning in Wireless Sensor Networks.

In wireless sensor networks, tree-based routing can achieve a low control overhead and high responsiveness by eliminating the path search and avoiding the use of extensive broadcast messages. However, existing approaches face difficulty in finding an optimal parent node, owing to conflicting performance metrics such as reliability, latency, and energy efficiency. To strike a balance between these multiple objectives, in this paper, we revisit a classic problem of finding an optimal parent node in a tree topology. Our key idea is to find the best parent node by utilizing empirical data about the network obtained through Q-learning. Specifically, we define a state space, action set, and reward function using multiple cognitive metrics, and then find the best parent node through trial and error. Simulation results demonstrate that the proposed solution can achieve better performance regarding end-to-end delay, packet delivery ratio, and energy consumption compared with existing approaches.

Mitochondrial gene expression in different organs of Hoplobatrachus rugulosus from China and Thailand under low-temperature stress.

BACKGROUND: Hoplobatrachus rugulosus (Anura: Dicroglossidae) is distributed in China and Thailand and the former can survive substantially lower temperatures than the latter. The mitochondrial genomes of the two subspecies also differ: Chinese tiger frogs (CT frogs) display two identical ND5 genes whereas Thai tiger frogs (TT frogs) have two different ND5 genes. Metabolism of ectotherms is very sensitive to temperature change and different organs have different demands on energy metabolism at low temperatures. Therefore, we conducted studies to understand: (1) the differences in mitochondrial gene expression of tiger frogs from China (CT frogs) versus Thailand (TT frogs); (2) the differences in mitochondrial gene expression of tiger frogs (CT and TT frogs) under short term 24 h hypothermia exposure at 25 °C and 8 °C; (3) the differences in mitochondrial gene expression in three organs (brain, liver and kidney) of CT and TT frogs. RESULTS: Utilizing RT-qPCR and comparing control groups at 25 °C with low temperature groups at 8 °C, we came to the following results. (1) At the same temperature, mitochondrial gene expression was significantly different in two subspecies. The transcript levels of two identical ND5 of CT frogs were observed to decrease significantly at low temperatures (P < 0.05) whereas the two different copies of ND5 in TT frogs were not. (2) Under low temperature stress, most of the genes in the brain, liver and kidney were down-regulated (except for COI and ATP6 measured in brain and COI measured in liver of CT frogs). (3) For both CT and TT frogs, the changes in overall pattern of mitochondrial gene expression in different organs under low temperature and normal temperature was brain > liver > kidney. CONCLUSIONS: We mainly drew the following conclusions: (1) The differences in the structure and expression of the ND5 gene between CT and TT frogs could result in the different tolerances to low temperature stress. (2) At low temperatures, the transcript levels of most of mitochondrial protein-encoding genes were down-regulated, which could have a significant effect in reducing metabolic rate and supporting long term survival at low temperatures. (3) The expression pattern of mitochondrial genes in different organs was related to mitochondrial activity and mtDNA replication in different organs.

Two NPF transporters mediate iron long-distance transport and homeostasis in Arabidopsis.

Iron (Fe) transport and reallocation are essential to Fe homeostasis in plants, but it is unclear how Fe homeostasis is regulated, especially under stress. Here we report that NPF5.9 and its close homolog NPF5.8 redundantly regulate Fe transport and reallocation in Arabidopsis. NPF5.9 is highly upregulated in response to Fe deficiency. NPF5.9 expresses preferentially in vasculature tissues and localizes to the trans-Golgi network, and NPF5.8 showed a similar expression pattern. Long-distance Fe transport and allocation into aerial parts was significantly increased in NPF5.9-overexpressing lines. In the double mutant npf5.8 npf5.9, Fe loading in aerial parts and plant growth were decreased, which were partially rescued by Fe supplementation. Further analysis showed that expression of PYE, the negative regulator for Fe homeostasis, and its downstream target NAS4 were significantly altered in the double mutant. NPF5.9 and NPF5.8 were shown to also mediate nitrate uptake and transport, although nitrate and Fe application did not reciprocally affect each other. Our findings uncovered the novel function of NPF5.9 and NPF5.8 in long-distance Fe transport and homeostasis, and further indicated that they possibly mediate nitrate transport and Fe homeostasis independently in Arabidopsis.

Metagenomic Analysis Identifies Sex-Related Cecal Microbial Gene Functions and Bacterial Taxa in the Quail.

Background: Japanese quail (Coturnix japonica) are important and widely distributed poultry in China. Researchers continue to pursue genetic selection for heavier quail. The intestinal microbiota plays a substantial role in growth promotion; however, the mechanisms involved in growth promotion remain unclear. Results: We generated 107.3 Gb of cecal microbiome data from ten Japanese quail, providing a series of quail gut microbial gene catalogs (1.25 million genes). We identified a total of 606 main microbial species from 1,033,311 annotated genes distributed among the ten quail. Seventeen microbial species from the genera Anaerobiospirillum, Alistipes, Barnesiella, and Butyricimonas differed significantly in their abundances between the female and male gut microbiotas. Most of the functional gut microbial genes were involved in metabolism, primarily in carbohydrate transport and metabolism, as well as some active carbohydrate-degrading enzymes. We also identified 308 antibiotic-resistance genes (ARGs) from the phyla Bacteroidetes, Firmicutes and Euryarchaeota. Studies of the differential gene functions between sexes indicated that abundances of the gut microbes that produce carbohydrate-active enzymes varied between female and male quail. Bacteroidetes was the predominant ARG-containing phylum in female quail; Euryarchaeota was the predominant ARG-containing phylum in male quail. Conclusion: This article provides the first description of the gene catalog of the cecal bacteria in Japanese quail as well as insights into the bacterial taxa and predictive metagenomic functions between male and female quail to provide a better understanding of the microbial genes in the quail ceca.

Medical expenditure for lung cancer in China: a multicenter, hospital-based retrospective survey.

BACKGROUND: Lung cancer is the most prevalent cancer, and the leading cause of cancer-related deaths in China. The aim of this study was to estimate the direct medical expenditure incurred for lung cancer care and analyze the trend therein for the period 2002-2011 using nationally representative data in China METHODS: This study was based on 10-year, multicenter retrospective expenditure data collected from hospital records, covering 15,437 lung cancer patients from 13 provinces diagnosed during the period 2002-2011. All expenditure data were adjusted to 2011 to eliminate the effects of inflation using China's annual consumer price index. RESULTS: The direct medical expenditure for lung cancer care (in 2011) was 39,015 CNY (US$6,041) per case, with an annual growth rate of 7.55% from 2002 to 2011. Drug costs were the highest proportionally in the total medical expenditure (54.27%), followed by treatment expenditure (14.32%) and surgical expenditure (8.10%). Medical expenditures for the disease varied based on region, hospital level, type, and stage. CONCLUSION: The medical expenditure for lung cancer care is substantial in China. Drug costs and laboratory test are the main factors increasing medical costs.