Milestones in understanding transport, sensing, and signaling of the plant nutrient phosphorus.

As an essential nutrient element, phosphorus (P) is primarily acquired and translocated as inorganic phosphate (Pi) by plant roots. Pi is often sequestered in the soil and becomes limited for plant growth. Plants have developed a sophisticated array of adaptive responses, termed P starvation responses, to cope with P deficiency by improving its external acquisition and internal utilization. Over the past 2 to 3 decades, remarkable progress has been made toward understanding how plants sense and respond to changing environmental P. This review provides an overview of the molecular mechanisms that regulate or coordinate P starvation responses, emphasizing P transport, sensing, and signaling. We present the major players and regulators responsible for Pi uptake and translocation. We then introduce how P is perceived at the root tip, how systemic P signaling is operated, and the mechanisms by which the intracellular P status is sensed and conveyed. Additionally, the recent exciting findings about the influence of P on plant-microbe interactions are highlighted. Finally, the challenges and prospects concerning the interplay between P and other nutrients and strategies to enhance P utilization efficiency are discussed. Insights obtained from this knowledge may guide future research endeavors in sustainable agriculture.

Nuclear factors NF-YC3 and NF-YBs positively regulate arbuscular mycorrhizal symbiosis in tomato.

The involvement of nuclear factor Y (NF-Y) in transcriptional reprogramming during arbuscular mycorrhizal symbiosis has been demonstrated in several plant species. However, a comprehensive picture is lacking. We showed that the spatial expression of NF-YC3 was observed in cortical cells containing arbuscules via the cis-regulatory element GCC boxes. Moreover, the NF-YC3 promoter was transactivated by the combination of CYCLOPS and autoactive calcium and calmodulin-dependent kinase (CCaMK) via GCC boxes. Knockdown of NF-YC3 significantly reduced the abundance of all intraradical fungal structures and affected arbuscule size. BCP1, SbtM1, and WRI5a, whose expression associated with NF-YC3 levels, might be downstream of NF-YC3. NF-YC3 interacted with NF-YB3a, NF-YB5c, or NF-YB3b, in yeast (Saccharomyces cerevisiae) and in planta, and interacted with NF-YA3a in yeast. Spatial expression of three NF-YBs was observed in all cell layers of roots under both mock and mycorrhizal conditions. Simultaneous knockdown of three NF-YBs, but not individually, reduced the fungal colonization level, suggesting that there might be functional redundancy of NF-YBs to regulate AM symbiosis. Collectively, our data suggest that NF-YC3 and NF-YBs positively regulate AM symbiosis in tomato, and arbuscule-related NF-YC3 may be an important downstream gene of the common symbiosis signaling pathway.

The costs and benefits of symbiotic interactions: variable effects of rhizobia and arbuscular mycorrhizae on Vigna radiata accessions.

BACKGROUND: The symbiosis among plants, rhizobia, and arbuscular mycorrhizal fungi (AMF) is one of the most well-known symbiotic relationships in nature. However, it is still unclear how bilateral/tripartite symbiosis works under resource-limited conditions and the diverse genetic backgrounds of the host. RESULTS: Using a full factorial design, we manipulated mungbean accessions/subspecies, rhizobia, and AMF to test their effects on each other. Rhizobia functions as a typical facilitator by increasing plant nitrogen content, plant weight, chlorophyll content, and AMF colonization. In contrast, AMF resulted in a tradeoff in plants (reducing biomass for phosphorus acquisition) and behaved as a competitor in reducing rhizobia fitness (nodule weight). Plant genotype did not have a significant effect on AMF fitness, but different mungbean accessions had distinct rhizobia affinities. In contrast to previous studies, the positive relationship between plant and rhizobia fitness was attenuated in the presence of AMF, with wild mungbean being more responsive to the beneficial effect of rhizobia and attenuation by AMF. CONCLUSIONS: We showed that this complex tripartite relationship does not unconditionally benefit all parties. Moreover, rhizobia species and host genetic background affect the symbiotic relationship significantly. This study provides a new opportunity to re-evaluate the relationships between legume plants and their symbiotic partners.

Arbuscular mycorrhizal symbiosis enhances tomato lateral root formation by modulating CEP2 peptide expression.

Plant lateral root (LR) growth usually is stimulated by arbuscular mycorrhizal (AM) symbiosis. However, the molecular mechanism is still unclear. We used gene expression analysis, peptide treatment and virus-induced gene alteration assays to demonstrate that C-terminally encoded peptide (CEP2) expression in tomato was downregulated during AM symbiosis to mitigate its negative effect on LR formation through an auxin-related pathway. We showed that enhanced LR density and downregulated CEP2 expression were observed during mycorrhizal symbiosis. Synthetic CEP2 peptide treatment reduced LR density and impaired the expression of genes involved in indole-3-butyric acid (IBA, the precursor of IAA) to IAA conversion, auxin polar transport and the LR-related signaling pathway; however, application of IBA or synthetic auxin 1-naphthaleneacetic acid (NAA) to the roots may rescue both defective LR formation and reduced gene expression. CEP receptor 1 (CEPR1) might be the receptor of CEP2 because its knockdown plants did not respond to CEP2 treatment. Most importantly, the LR density of CEP2 overexpression or knockdown plants could not be further increased by AM inoculation, suggesting that CEP2 was critical for AM-induced LR formation. These results indicated that AM symbiosis may regulate root development by modulating CEP2, which affects the auxin-related pathway.

Upstream Open Reading Frame and Phosphate-Regulated Expression of Rice OsNLA1 Controls Phosphate Transport and Reproduction.

Rice (Oryza sativa) OsNLA1 has been proposed to play a crucial role in regulating phosphate (Pi) acquisition in roots, similar to that of Arabidopsis (Arabidopsis thaliana) AtNLA. However, unlike AtNLA, OsNLA1 is not a target of miR827, a Pi starvation-induced microRNA. It is, therefore, of interest to know whether the expression of OsNLA1 depends on Pi supply and how it is regulated. In this study, we provide evidence that OsNLA1 controls Pi acquisition by directing the degradation of several OsPHT1 Pi transporters (i.e. OsPT1/2/4/7/8/12). We further show that OsNLA1 has an additional function in reproduction and uncover the mechanism of its expression regulation. Analysis of mRNA levels, promoter-GUS activity, and protoplast transient expression showed that the expression of OsNLA1.1, the most abundant transcript variant, is up-regulated in response to increasing Pi supply. The OsNLA1 promoter region was found to contain an upstream open reading frame that is required for Pi-responsive expression regulation. OsNLA1 promoter activity was observed in roots, ligules, leaves, sheaths, pollen grains, and surrounding the vascular tissues of anthers, suggesting that OsNLA1 is important throughout the development of rice. Disruption of OsNLA1 resulted in increased Pi uptake from roots as well as impaired pollen development and reduced grain production. In summary, our study reveals that Pi-induced OsNLA1 expression regulated by a unique mechanism functions in Pi acquisition, Pi translocation, and reproductive success.

Transcriptome diversity among rice root types during asymbiosis and interaction with arbuscular mycorrhizal fungi.

Root systems consist of different root types (RTs) with distinct developmental and functional characteristics. RTs may be individually reprogrammed in response to their microenvironment to maximize adaptive plasticity. Molecular understanding of such specific remodeling--although crucial for crop improvement--is limited. Here, RT-specific transcriptomes of adult rice crown, large and fine lateral roots were assessed, revealing molecular evidence for functional diversity among individual RTs. Of the three rice RTs, crown roots displayed a significant enrichment of transcripts associated with phytohormones and secondary cell wall (SCW) metabolism, whereas lateral RTs showed a greater accumulation of transcripts related to mineral transport. In nature, arbuscular mycorrhizal (AM) symbiosis represents the default state of most root systems and is known to modify root system architecture. Rice RTs become heterogeneously colonized by AM fungi, with large laterals preferentially entering into the association. However, RT-specific transcriptional responses to AM symbiosis were quantitatively most pronounced for crown roots despite their modest physical engagement in the interaction. Furthermore, colonized crown roots adopted an expression profile more related to mycorrhizal large lateral than to noncolonized crown roots, suggesting a fundamental reprogramming of crown root character. Among these changes, a significant reduction in SCW transcripts was observed that was correlated with an alteration of SCW composition as determined by mass spectrometry. The combined change in SCW, hormone- and transport-related transcript profiles across the RTs indicates a previously overlooked switch of functional relationships among RTs during AM symbiosis, with a potential impact on root system architecture and functioning.

Role of vacuoles in phosphorus storage and remobilization.

Vacuoles play a fundamental role in storage and remobilization of various nutrients, including phosphorus (P), an essential element for cell growth and development. Cells acquire P primarily in the form of inorganic orthophosphate (Pi). However, the form of P stored in vacuoles varies by organism and tissue. Algae and yeast store polyphosphates (polyPs), whereas plants store Pi and inositol phosphates (InsPs) in vegetative tissues and seeds, respectively. In this review, we summarize how vacuolar P molecules are stored and reallocated and how these processes are regulated and co-ordinated. The roles of SYG1/PHO81/XPR1 (SPX)-domain-containing membrane proteins in allocating vacuolar P are outlined. We also highlight the importance of vacuolar P in buffering the cytoplasmic Pi concentration to maintain cellular homeostasis when the external P supply fluctuates, and present additional roles for vacuolar polyP and InsP besides being a P reserve. Furthermore, we discuss the possibility of alternative pathways to recycle Pi from other P metabolites in vacuoles. Finally, future perspectives for researching this topic and its potential application in agriculture are proposed.

Promoter-based identification of novel non-coding RNAs reveals the presence of dicistronic snoRNA-miRNA genes in Arabidopsis thaliana.

BACKGROUND: In the past few decades, non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression in eukaryotes. Most studies of ncRNAs in plants have focused on the identification of silencing microRNAs (miRNAs) and small interfering RNAs (siRNAs). Another important family of ncRNAs that has been well characterized in plants is the small nucleolar RNAs (snoRNAs) and the related small Cajal body-specific RNAs (scaRNAs). Both target chemical modifications of ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). In plants, the snoRNA genes are organized in clusters, transcribed by RNA Pol II from a common promoter and subsequently processed into mature molecules. The promoter regions of snoRNA polycistronic genes in plants are highly enriched in two conserved cis-regulatory elements (CREs), Telo-box and Site II, which coordinate the expression of snoRNAs and ribosomal protein coding genes throughout the cell cycle. RESULTS: In order to identify novel ncRNA genes, we have used the snoRNA Telo-box/Site II motifs combination as a functional promoter indicator to screen the Arabidopsis genome. The predictions generated by this process were tested by detailed exploration of available RNA-Seq and expression data sets and experimental validation. As a result, we have identified several snoRNAs, scaRNAs and 'orphan' snoRNAs. We also show evidence for 16 novel ncRNAs that lack similarity to any reported RNA family. Finally, we have identified two dicistronic genes encoding precursors that are processed to mature snoRNA and miRNA molecules. We discuss the evolutionary consequences of this result in the context of a tight link between snoRNAs and miRNAs in eukaryotes. CONCLUSIONS: We present an alternative computational approach for non-coding RNA detection. Instead of depending on sequence or structure similarity in the whole genome screenings, we have explored the properties of promoter regions of well-characterized ncRNAs. Interestingly, besides expected ncRNAs predictions we were also able to recover single precursor arrangement for snoRNA-miRNA. Accompanied by analyses performed on rice sequences, we conclude that such arrangement might have interesting functional and evolutionary consequences and discuss this result in the context of a tight link between snoRNAs and miRNAs in eukaryotes.

Nonredundant regulation of rice arbuscular mycorrhizal symbiosis by two members of the phosphate transporter1 gene family.

Pi acquisition of crops via arbuscular mycorrhizal (AM) symbiosis is becoming increasingly important due to limited high-grade rock Pi reserves and a demand for environmentally sustainable agriculture. Here, we show that 70% of the overall Pi acquired by rice (Oryza sativa) is delivered via the symbiotic route. To better understand this pathway, we combined genetic, molecular, and physiological approaches to determine the specific functions of two symbiosis-specific members of the PHOSPHATE TRANSPORTER1 (PHT1) gene family from rice, ORYsa;PHT1;11 (PT11) and ORYsa;PHT1;13 (PT13). The PT11 lineage of proteins from mono- and dicotyledons is most closely related to homologs from the ancient moss, indicating an early evolutionary origin. By contrast, PT13 arose in the Poaceae, suggesting that grasses acquired a particular strategy for the acquisition of symbiotic Pi. Surprisingly, mutations in either PT11 or PT13 affected the development of the symbiosis, demonstrating that both genes are important for AM symbiosis. For symbiotic Pi uptake, however, only PT11 is necessary and sufficient. Consequently, our results demonstrate that mycorrhizal rice depends on the AM symbiosis to satisfy its Pi demands, which is mediated by a single functional Pi transporter, PT11.

Krüppel-like factor 4 is involved in cell scattering induced by hepatocyte growth factor.

Hepatocyte growth factor/scatter factor (HGF) is unique by inducing epithelial cell scattering, a cellular event pivotal to HGF-mediated invasive-growth response essential for embryonic development and metastasis. Krüppel-like factor 4 (KLF4) is a multifunctional zinc-finger transcription factor involved in cell proliferation, differentiation and self-renewal. We herein present the first evidence for the functional connection between KLF4 and HGF-induced cell scattering. In particular, we found that KLF4 was upregulated by HGF in two independent epithelial cell types, HepG2 and MDCK, whereas KLF4 knockdown inhibited HGF-induced E-cadherin suppression and cell scattering. Moreover, enforced nuclear KLF4 expression alone was sufficient to upregulate KLF4, downregulate E-cadherin and trigger scattering. Chromatin immunoprecipitation (ChIP) analysis further revealed that KLF4 induced suppression of E-cadherin transcription by directly binding to the E-cadherin promoter. Additionally, we proved that HGF-induced upregulation of KLF4 transcription and cell scattering require activation of the MEK/ERK signaling pathway and the induction of early growth response 1 (EGR-1). At the mechanistic level, ChIP analysis validated a direct binding of EGR-1 to the KLF4 promoter to induce KLF4 transcription; in turn, EGR-1-induced KLF4 binds to its own promoter, thus creating a positive feedback mechanism to sustain KLF4 expression and the resultant cell scattering. We conclude that KLF4 upregulation by HGF represents a novel mechanism mediating HGF-induced cell scattering and perhaps other associated events such as cell migration and invasion.

Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines.

Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1-JNK and PERK-eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death.

Transcriptome analysis reveals the mechanisms for mycorrhiza-enhanced salt tolerance in rice.

More than half of the global population relies on rice as a staple food, but salinization of soil presents a great threat to rice cultivation. Although previous studies have addressed the possible benefits of arbuscular mycorrhizal (AM) symbiosis for rice under salinity stress, the underlying molecular mechanisms are still unclear. In this study, we found that mycorrhizal rice had better shoot and reproductive growth and a significantly higher K+/Na+ ratio in the shoot. The reactive oxygen species (ROS) scavenging capacity in rice shoots was also improved by AM symbiosis. To elucidate the molecular mechanisms required for AM-improved salt tolerance, transcriptome analysis revealing the differentially expressed genes (DEGs) based on the response to AM symbiosis, salinity or specific tissue was performed. Thirteen percent of DEGs showed tissue-preferred responses to both AM symbiosis and salt stress and might be the key genes contributing to AM-enhanced salt tolerance. Gene Ontology (GO) enrichment analysis identified GO terms specifically appearing in this category, including cell wall, oxidoreductase activity, reproduction and ester-related terms. Interestingly, GO terms related to phosphate (Pi) homeostasis were also found, suggesting the possible role of the Pi-related signaling pathway involved in AM-enhanced salt tolerance. Intriguingly, under nonsaline conditions, AM symbiosis influenced the expression of these genes in a similar way as salinity, especially in the shoots. Overall, our results indicate that AM symbiosis may possibly use a multipronged approach to influence gene expression in a way similar to salinity, and this modification could help plants be prepared for salt stress.

Association of Chinese herbal medicine use with the depression risk among the long-term breast cancer survivors: A longitudinal follow-up study.

Background: Breast cancer patients are at elevated risk of depression during treatment, thus provoking the chance of poor clinical outcomes. This retrospective cohort study aimed to investigate whether integrating Chinese herbal medicines citation(CHM) into conventional cancer therapy could decrease the risk of depression in the long-term breast cancer survivors. Methods: A cohort of patients aged 20-70 years and with newly diagnosed breast cancer during 2000-2008 was identified from a nationwide claims database. In this study, we focused solely on survivors of breast cancer at least1 year after diagnosis. After one-to-one matching for age, sex, and baseline comorbidities, breast cancer patients who received (n = 1,450) and did not receive (n = 1,450) CHM treatment were enrolled. The incidence rate and hazard ratio citation(HR) for depression between the two groups was estimated at the end of 2012. A Cox proportional hazard model was constructed to examine the impact of the CHM use on the risk of depression. Results: During the study period, the incidence rate of depression was significantly lower in the treated cohort than in the untreated cohort [8.57 compared with 11.01 per 1,000 person-years citation(PYs)], and the adjusted HR remained significant at 0.74 (95% CI 0.58-0.94) in a Cox proportional hazards regression model. The corresponding risk further decreasing to 43% among those using CHM for more than 1 year. Conclusion: Finding from this investigation indicated that the lower risk of depression observed in breast cancer patients treated with CHM, suggesting that CHM treatment should be considered for disease management toward breast cancer. Yet, the optimal administered dose should be determined in further clinical trials.

PCDHB15 as a potential tumor suppressor and epigenetic biomarker for breast cancer.

Breast cancer is among the most frequently diagnosed cancer types and the leading cause of cancer-related death in women. The mortality rate of patients with breast cancer is currently increasing, perhaps due to a lack of early screening tools. In the present study, using The Cancer Genome Atlas (TCGA) breast cancer dataset (n=883), it was determined that methylation of the protocadherin ß15 (PCDHB15) promoter was higher in breast cancer samples than that in normal tissues. A negative association between promoter methylation and expression of PCDHB15 was observed in the TCGA dataset and breast cancer cell lines. In TCGA cohort, lower PCDHB15 expression was associated with shorter relapse-free survival times. Treatment with the DNA methyltransferase inhibitor restored PCDHB15 expression in a breast cancer cell line; however, overexpression of PCDHB15 was shown to suppress colony formation. PCDHB15 methylation detected in circulating cell-free DNA (cfDNA) isolated from serum samples was higher in patients with breast cancer (40.8%) compared with that in patients with benign tumors (22.4%). PCDHB15 methylation was not correlated with any clinical parameters. Taken together, PCDHB15 is a potential tumor suppressor in cases of breast cancer, which can be epigenetically silenced via promoter methylation. PCDHB15 methylation using cfDNA is a novel minimally invasive epigenetic biomarker for the diagnosis and prognosis of breast cancer.

Phosphate import at the arbuscule: just a nutrient?

Central to the mutualistic arbuscular mycorrhizal symbiosis is the arbuscule, the site where symbiotic phosphate is delivered. Initial investigations in legumes have led to the exciting observation that symbiotic phosphate uptake not only enhances plant growth but also regulates arbuscule dynamics and is, furthermore, required for maintenance of the symbiosis. This review evaluates the possible role of the phosphate ion, not only as a nutrient but also as a signal that is necessary for reprogramming the host cortex cell for symbiosis.

A terahertz time-domain super-resolution imaging method using a local-pixel graph neural network for biological products.

The low image acquisition speed of terahertz (THz) time-domain imaging systems limits their application in biological products analysis. In the current study, a local pixel graph neural network was built for THz time-domain imaging super-resolution. The method could be applied to the analysis of any heterogeneous biological products as it only required a small number of sample images for training and particularly it focused on THz feature frequencies. The graph network applied the Fourier transform to graphs extracted from low-resolution (LR) images bringing an invariance of rotation and flip for local pixels, and the network then learnt the relationship between the state of graphs and the corresponding pixels to be reconstructed. With wood cores and seeds as examples, the images of these samples were captured by a THz time-domain imaging system for training and analysed by the method, achieving the root mean square error (RMSE) of pixels of 0.0957 and 0.1061 for the wood core and seed images, respectively. In addition, the reconstructed high-resolution (HR) images, LR images and true HR images at several feature frequencies were also compared in the current study. Results indicated that the method could not only reconstruct the spatial details and the useful signals from high noise signals at high feature frequencies but could also operate super-resolution in both spatial and spectral aspects.

Influence of three different anesthesia protocols on aged rat brain: a resting-state functional magnetic resonance imaging study.

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups. METHODS: Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests. RESULTS: Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed. CONCLUSION: ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.

High birth weight and its interaction with physical activity influence the risk of obesity in early school-aged children.

BACKGROUND: High birth weight (HBW) is associated with childhood obesity, but with inconsistent results. This study investigated the relationship between HBW and childhood obesity, and further explored the interaction of HBW with behavioral and socio-economic determinants of obesity. METHODS: This cross-sectional study enrolled 1906 grade-two children of Guangzhou, China, from June to November, 2016. Overweight/obesity corresponded to a body mass index higher than the sex-age-specific criteria. Abdominal obesity was assessed using the sex-specific waist-height ratio cutoffs. The association of HBW with obesity was evaluated in multivariable logistic regression model. The relative excess risk due to interaction (RERI) and the attributable proportion of interaction (AP) indices were used to measure additive interaction, while applying the interaction of OR index for multiplicative interaction assessment. RESULTS: Children with HBW had an increased risk of overweight/obesity [odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.56-3.76] compared with those without HBW. Significant additive interaction of HBW with physical activity was found for overweight/obesity [relative excess risk due to interaction (RERI) = 2.69, 95% CI = 0.62-4.75; attributable proportion of interaction (AP) = 0.72, 95% CI = 0.42-1.02]. The HBW children with insufficient activity had higher odds of overweight/obesity compared to the non-HBW children with sufficient activity (OR = 3.75, 95% CI = 2.06-6.83). In addition, we identified a significant interaction of HBW with household income for abdominal obesity (RERI = 1.20, 95% CI = 0.02-2.37; AP = 0.76, 95% CI = 0.16-1.36). CONCLUSIONS: HBW confers an increased risk for childhood overweight/obesity. Physical activity attenuates the effect of HBW on overweight/obesity, and HBW possibly synergistically interacts with high household income to promote abdominal obesity in childhood.

Decreased risk of colorectal cancer among patients with type 2 diabetes receiving Chinese herbal medicine: a population-based cohort study.

OBJECTIVES: Patients with type 2 diabetes have a higher risk of colorectal cancer (CRC), but whether Chinese herbal medicines (CHMs) can reduce this risk is unknown. This study investigated the effect that CHMs have on CRC risk in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This cohort study used the Taiwanese National Health Insurance Research Database to identify 54 744 patients, newly diagnosed with type 2 diabetes, aged 20-70 years, who were receiving treatment between 1998 and 2007. From this sample, we randomly selected 14 940 CHMs users and 14 940 non-CHMs users, using propensity scores matching. All were followed through 2012 to record CRC incidence. Cox proportional hazards regression was used to compute the hazard ratio (HR) of CRC by CHMs use. RESULTS: During follow-up, 235 CHMs users and 375 non-CHMs users developed CRC, incidence rates of 1.73% and 2.47% per 1000 person-years, respectively. CHM users had a significantly reduced risk of CRC compared with non-CHM users (adjusted HR=0.71; 95% CI 0.60 to 0.84). The greatest effect was in those receiving CHMs for more than 1 year. Huang-Qin, Xue-Fu-Zhu-Yu-Tang, Shu-Jing-Huo-Xue-Tang, Liu-Wei-Di-Huang-Wan, Ji-Sheng-Shen-Qi-Wan, Gan-Lu-Yin, Shao-Yao-Gan-Cao-Tang and Ban-Xia-Xie-Xin-Tang were significantly associated with lower risk of CRC. CONCLUSION: Integrating CHMs into the clinical management of patients with type 2 diabetes may be beneficial in reducing the risk of CRC.

Arabidopsis IRT3 is a zinc-regulated and plasma membrane localized zinc/iron transporter.

ZIP transporters (ZRT, IRT-like proteins) are involved in the transport of iron (Fe), zinc (Zn) and other divalent metal cations. The expression of IRT3, a ZIP transporter, is higher in the Zn/cadmium (Cd) hyperaccumulator Arabidopsis halleri than is that of its ortholog in Arabidopsis thaliana, which implies a positive association of its expression with Zn accumulation in A. halleri. IRT3 genes from both A. halleri and A. thaliana functionally complemented the Zn uptake mutant Spzrt1 in Schizosaccharomyces pombe; and Zn uptake double mutant zrt1zrt2, Fe-uptake mutant fet3fet4 and conferred Zn and Fe uptake activity in Saccharomyces cerevisiae. By contrast, the manganese (Mn) uptake mutant smf1 phenotypes were not rescued. Insufficient Cd uptake for toxicity was found. Expression of IRT3-green fluorescent protein (GFP) fusion proteins in Arabidopsis root protoplasts indicated localization of both IRT3 proteins in the plasma membrane. Overexpressing AtIRT3 in A. thaliana led to increased accumulation of Zn in the shoot and Fe in the root of transgenic lines. Therefore, IRT3 functions as a Zn and Fe-uptake transporter in Arabidopsis.