Impact of soft tissue around the knee on the efficacy of extracorporeal shockwave therapy in knee osteoarthritis.

Knee osteoarthritis (KOA) is the leading cause of knee pain in middle-aged and older individuals. Extracorporeal shockwave therapy (ESWT) has been applied to treat patients with KOA to reduce pain and improve function. Patients (n = 123) diagnosed with KOA who received ESWT were selected to participate in this study, and were grouped according to their body mass index (BMI). The treatment parameters were as follows: 8000 pulses, 2.0 bar, 0.25 mJ/mm2, and 6 Hz/s once per week for 8 weeks. The visual analog scale (VAS), Lequesne index, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were measured to assess knee pain and functional recovery according to BMI groups. Radiographs were used to measure the richness of the soft tissue around the knee joint. The correlation between the distribution of tissue, pain, and functional improvement was analyzed using the receiver operator characteristic curve. All the patients showed a reduction in pain after treatment compared to that before treatment (P < .01). As measured by the VAS, the Lequesne and WOMAC indexes, after the intervention, the pain and functional index of the overweight and above BMI group improved to a greater extent than that of the normal or below normal BMI group (P < .01). The area under the curve showed, with VAS as the demarcation criterion, when the tibial plateau soft tissue ratio, femoral intercondylar apex soft tissue ratio, and medial tibial soft tissue ratio exceeded 1.538, 1.534, and 1.296, respectively, the patient's pain relief was more pronounced the ESWT treatment was better. With pain in WOMAC as the demarcation criterion, the tibial plateau soft tissue ratio, femoral intercondylar apex soft tissue ratio, and medial tibial soft tissue ratio also are positively correlated with pain relief in patients. When the Lequesne and WOMAC scores were the demarcation criteria, the patients' function improved significantly when the patella apical soft tissue ratio exceeded 2.401 and 2.635, respectively. ESWT can effectively alleviate pain and improve knee function in patients with KOA, and the soft tissue around the knee joint should also be an important reference factor in KOA treatment.

Selenium Uptake, Transport, Metabolism, Reutilization, and Biofortification in Rice.

Selenium (Se) is an essential trace element for humans and other animals. The human body mainly acquires Se from plant foods, especially cereal grains. Rice is the staple food for more than half of the world's population. Increasing the Se concentration of rice grains can increase the average human dietary Se intake. This review summarizes recent advances in the molecular mechanisms of Se uptake, transport, subcellular distribution, retranslocation, volatilization, and Se-containing protein degradation in plants, especially rice. The strategies for improving Se concentration in rice grains by increasing Se accumulation, reducing Se volatilization, and optimizing Se form were proposed, which provide new insight into Se biofortification in rice by improving the utilization efficiency of Se.

Author Correction: Nitrate-NRT1.1B-SPX4 cascade integrates nitrogen and phosphorus signalling networks in plants.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nitrate-NRT1.1B-SPX4 cascade integrates nitrogen and phosphorus signalling networks in plants.

To ensure high crop yields in a sustainable manner, a comprehensive understanding of the control of nutrient acquisition is required. In particular, the signalling networks controlling the coordinated utilization of the two most highly demanded mineral nutrients, nitrogen and phosphorus, are of utmost importance. Here, we reveal a mechanism by which nitrate activates both phosphate and nitrate utilization in rice (Oryza sativa L.). We show that the nitrate sensor NRT1.1B interacts with a phosphate signalling repressor SPX4. Nitrate perception strengthens the NRT1.1B-SPX4 interaction and promotes the ubiquitination and degradation of SPX4 by recruiting NRT1.1B interacting protein 1 (NBIP1), an E3 ubiquitin ligase. This in turn allows the key transcription factor of phosphate signalling, PHR2, to translocate to the nucleus and initiate the transcription of phosphorus utilization genes. Interestingly, the central transcription factor of nitrate signalling, NLP3, is also under the control of SPX4. Thus, nitrate-triggered degradation of SPX4 activates both phosphate- and nitrate-responsive genes, implementing the coordinated utilization of nitrogen and phosphorus.

NRT1.1B improves selenium concentrations in rice grains by facilitating selenomethinone translocation.

Selenium (Se) is an essential trace element for humans and other animals, yet approximately one billion people worldwide suffer from Se deficiency. Rice is a staple food for over half of the world's population that is a major dietary source of Se. In paddy soils, rice roots mainly take up selenite. Se speciation analysis indicated that most of the selenite absorbed by rice is predominantly transformed into selenomethinone (SeMet) and retained in roots. However, the mechanism by which SeMet is transported in plants remains largely unknown. In this study, SeMet uptake was found to be an energy-dependent symport process involving H+ transport, with neutral amino acids strongly inhibiting SeMet uptake. We further revealed that NRT1.1B, a member of rice peptide transporter (PTR) family which plays an important role in nitrate uptake and transport in rice, displays SeMet transport activity in yeast and Xenopus oocyte. The uptake rate of SeMet in the roots and its accumulation rate in the shoots of nrt1.1b mutant were significantly repressed. Conversely, the overexpression of NRT1.1B in rice significantly promoted SeMet translocation from roots to shoots, resulting in increased Se concentrations in shoots and rice grains. With vascular-specific expression of NRT1.1B, the grain Se concentration was 1.83-fold higher than that of wild type. These results strongly demonstrate that NRT1.1B holds great potential for the improvement of Se concentrations in grains by facilitating SeMet translocation, and the findings provide novel insight into breeding of Se-enriched rice varieties.

Expression of the Nitrate Transporter Gene OsNRT1.1A/OsNPF6.3 Confers High Yield and Early Maturation in Rice.

Nitrogen (N) is a major driving force for crop yield improvement, but application of high levels of N delays flowering, prolonging maturation and thus increasing the risk of yield losses. Therefore, traits that enable utilization of high levels of N without delaying maturation will be highly desirable for crop breeding. Here, we show that OsNRT1.1A (OsNPF6.3), a member of the rice (Oryza sativa) nitrate transporter 1/peptide transporter family, is involved in regulating N utilization and flowering, providing a target to produce high yield and early maturation simultaneously. OsNRT.1A has functionally diverged from previously reported NRT1.1 genes in plants and functions in upregulating the expression of N utilization-related genes not only for nitrate but also for ammonium, as well as flowering-related genes. Relative to the wild type, osnrt1.1a mutants exhibited reduced N utilization and late flowering. By contrast, overexpression of OsNRT1.1A in rice greatly improved N utilization and grain yield, and maturation time was also significantly shortened. These effects were further confirmed in different rice backgrounds and also in Arabidopsis thaliana Our study paves a path for the use of a single gene to dramatically increase yield and shorten maturation time for crops, outcomes that promise to substantially increase world food security.

Identified molecular mechanism of interaction between environmental risk factors and differential expression genes in cartilage of Kashin-Beck disease.

As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs and differentially expression genes (DEGs) in KBD. The environmental response genes (ERGs) were analyzed in cartilage of KBD in comparison to normal controls.We searched 5 English and 3 Chinese databases from inception to September 2015, to identify case-control studies that examined ERFs for KBD using integrative meta-analysis and systematic review. Total RNA was isolated from articular cartilage of KBD patients and healthy controls. Human whole genome microarray chip (Agilent) was used to analyze the amplified, labeled, and hybridized total RNA, and the validated microarray data were partially verified using real-time quantitative polymerase chain reaction (qRT-PCR). The ERGs were derived from the Comparative Toxicogenomics Database. The identified ERGs were subjected to KEGG pathway enrichment, biological process (BP), and interaction network analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7, and STRING.The trace elements (selenium and iodine), vitamin E, and polluted grains (T-2 toxin/HT-2 toxin, deoxynivalenol, and nivalenol) were identified as the ERFs for KBD using meta-analysis and review. We identified 21 upregulated ERGs and 7 downregulated ERGs in cartilage with KBD compared with healthy controls, which involved in apoptosis, metabolism, and growth and development. KEGG pathway enrichment analysis found that 2 significant pathways were involved with PI3K-Akt signaling pathway and P53 signaling pathway, and gene ontology function analysis found 3 BPs involved with apoptosis, death, and cell death in KBD cartilage.According to previous results and our own research, we suggest that the trace element selenium and vitamin E induce PI3K-Akt signaling pathway and the mycotoxins (T-2 toxin/HT-2 toxin and DON) induce P53 signaling pathway, contributing to the development of KBD, and chondrocyte apoptosis and cell death.

Association of rs1137101 polymorphism in LEPR and susceptibility to knee osteoarthritis in a Northwest Chinese Han population.

BACKGROUND: Osteoarthritis (OA) is a complex arthritic condition in which the genetic factor plays a crucial role. A single nucleotide polymorphism (SNP), rs1137101 (Gln223Arg) of leptin receptor (LEPR) gene has been demonstrated to be associated with susceptibility to knee OA. However, this association in Chinese Han population has never been examined. The present study aimed to investigate whether Gln223Arg was related to knee OA susceptibility in a Northwest Chinese population with Han ethnicity. METHODS: Gln223Arg polymorphisms were genotyped in 587 patients with confirmed knee OA and in 628 age- and sex-matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism analysis. Besides, LEPR genotypes were verified by direct DNA sequencing analysis on PCR products. RESULTS: The genotype and allele frequencies in LEPR SNP rs1137101 were significantly different between cases and control groups (chi-square = 6.52, P = 0.038 for genotype and chi-square = 5.06, P = 0.024 for allele frequencies; respectively). Rs1137101 was correlated with knee OA in the dominant genetic model (GG + GA versus AA) (P = 0.016) and a higher G allele frequency existed (P = 0.024) among all patients with knee OA and controls. On stratification analysis, the genotype GG and G allele were associated with susceptibility to knee OA in females, both young (≤65 years) and old groups (>65 years) and patients with mild knee OA. CONCLUSIONS: Our finding suggested that the genetic variant of LEPR gene rs1137101 is independently related to knee OA susceptibility in Northwest Chinese population with Han ethnicity and may serve as a potential biomarker to determine risk of knee OA.

Identification of microRNAs in rice root in response to nitrate and ammonium.

Nitrate and ammonium are two major nitrogen (N) sources for higher plants, but they differ in utilization and signaling. MicroRNAs (miRNAs) play an essential role in N signal transduction; however, knowledge remains limited about the regulatory role of miRNAs responsive to different N sources, especially in crop plants. To get global overview on miRNAs involved in N response in rice, we performed high-throughput small RNA-sequencing under different nitrate and ammonium treatments. The results demonstrated that only 16 and 11 miRNAs were significantly induced by nitrate and ammonium under short-term treatment, respectively. However, 60 differentially expressed miRNAs were found between nitrate and ammonium under long-term cultivation. These results suggested that miRNA response greatly differentiates between nitrate and ammonium treatments. Furthermore, 44 miRNAs were found to be differentially expressed between high- and low-N conditions. Our study reveals comprehensive expression profiling of miRNAs responsive to different N sources and different N treatments, which advances our understanding on the regulation of different N signaling and homeostasis mediated by miRNAs.

Is It the Appropriate Time to Stop Applying Selenium Enriched Salt in Kashin-Beck Disease Areas in China?

We aimed to identify significant factors of selenium (Se) nutrition of children in Kashin-Beck disease (KBD) endemic areas and non-KBD area in Shaanxi Province for providing evidence of whether it is the time to stop applying Se-enriched salt in KBD areas. A cross-sectional study contained 368 stratified randomly selected children aged 4-14 years was conducted with 24-h retrospective questionnaire based on a pre-investigation. Food and hair samples were collected and had Se contents determined with hydride generation atomic fluorescence spectrometry. Average hair Se content of 349.0 ± 60.2 ng/g in KBD-endemic counties was significantly lower than 374.1 ± 47.0 ng/g in non-KBD counties. It was significantly higher in the male children (365.2 ± 52.3 ng/g) than in the female (345.0 ± 62.2 ng/g, p = 0.002) and significantly higher in the 4.0-6.9 years group (375.2 ± 58.9 ng/g) than the 7.0-14.0 years group (347.0 ± 56.1 ng/g, p < 0.01). Gender, living area, Se intake without supplements, Se-enriched salt, oil source and protein intake were identified as significant factors of hair Se contents. Cereals, meat and milk were commonly included as significant food categories that mainly contributed to Se intake without supplement of the whole population. Balanced dietary structure without Se supplement could effectively enhance and maintain children's Se nutrition. It may be the time to stop applying Se-enriched salt in KBD areas in Shaanxi Province.

Variation in NRT1.1B contributes to nitrate-use divergence between rice subspecies.

Asian cultivated rice (Oryza sativa L.) consists of two main subspecies, indica and japonica. Indica has higher nitrate-absorption activity than japonica, but the molecular mechanisms underlying that activity remain elusive. Here we show that variation in a nitrate-transporter gene, NRT1.1B (OsNPF6.5), may contribute to this divergence in nitrate use. Phylogenetic analysis revealed that NRT1.1B diverges between indica and japonica. NRT1.1B-indica variation was associated with enhanced nitrate uptake and root-to-shoot transport and upregulated expression of nitrate-responsive genes. The selection signature of NRT1.1B-indica suggests that nitrate-use divergence occurred during rice domestication. Notably, field tests with near-isogenic and transgenic lines confirmed that the japonica variety carrying the NRT1.1B-indica allele had significantly improved grain yield and nitrogen-use efficiency (NUE) compared to the variety without that allele. Our results show that variation in NRT1.1B largely explains nitrate-use divergence between indica and japonica and that NRT1.1B-indica can potentially improve the NUE of japonica.

MicroRNA399 is involved in multiple nutrient starvation responses in rice.

The increasing evidences have revealed that microRNAs (miRNAs) play significant role in nutrient stress response. Previously, miR399 was documented to be induced by phosphorus (P) starvation and involved in regulating P starvation responses. To further investigate the function of miR399 in rice (Oryza sativa L.), we performed GeneChip analysis with OsmiR399 over-expressing plants. Interestingly, our results showed that, besides P starvation responsive genes, the expression of a number of genes involved in iron (Fe), potassium (K), sodium (Na), and calcium (Ca) absorption was dramatically up-regulated in OsmiR399 over-expressing plants. Consistently, the concentrations of Fe, K, Na, and Ca were also increased in OsmiR399 over-expressing plants. The expression of OsmiR399 was also up-regulated by these nutrient starvations, respectively. Moreover, the loss-of-function of LTN1, the down-stream target of OsmiR399, also resulted in the increase of multiple metal elements and the up-regulation of the absorption related genes. These results indicated that OsmiR399 participates in the regulation of multiple nutrient starvation responses, which also gives new view on understanding the interaction among different nutrients mediated by miR399.

Aged monkey brains reveal the role of ubiquitin-conjugating enzyme UBE2N in the synaptosomal accumulation of mutant huntingtin.

Although misfolded proteins are ubiquitinated and cleared by the proteasome, they can accumulate in synapses in aged neurons to promote synaptic dysfunction in a variety of neurodegenerative diseases, including Huntington's disease (HD), which is caused by polyglutamine expansion in huntingtin. The mechanism behind this aging-related phenomenon is unknown and has been difficult to investigate using animals with short life spans. With brain tissues from longer-lived rhesus monkeys of different ages, we found that aging reduces ubiquitin-proteasomal activity and also increases the level of ubiquitin-conjugating enzyme UBE2N (Ubc13) in synaptosomes. Synaptosomal fractions from aged monkey brain increase in vitro ubiquitinated huntingtin, whereas depletion of UBE2N markedly reduces this increase. Overexpressing UBE2N increases the aggregation of mutant huntingtin, and reducing UBE2N attenuates huntingtin aggregation in cellular and mouse models of HD. Our studies suggest that increased UBE2N plays a critical role in the synaptosomal accumulation of mutant huntingtin with age.

OsPT2, a phosphate transporter, is involved in the active uptake of selenite in rice.

• Selenite is a predominant form of selenium (Se) available to plants, especially in anaerobic soils, but the molecular mechanism of selenite uptake by plants is not well understood. • ltn1, a rice mutant previously shown to have increased phosphate (Pi) uptake, was found to exhibit higher selenite uptake than the wild-type in both concentration- and time-dependent selenite uptake assays. Respiratory inhibitors significantly inhibited selenite uptake in the wildtype and the ltn1 mutant, indicating that selenite uptake was coupled with H(+) and energy-dependent. Selenite uptake was greatly enhanced under Pi-starvation conditions, suggesting that Pi transporters are involved in selenite uptake. • OsPT2, the most abundantly expressed Pi transporter in the roots, is also significantly up-regulated in ltn1 and dramatically induced by Pi starvation. OsPT2-overexpressing and knockdown plants displayed significantly increased and decreased rates of selenite uptake, respectively, suggesting that OsPT2 plays a crucial role in selenite uptake. Se content in rice grains also increased significantly in OsPT2-overexpressing plants. • These data strongly demonstrate that selenite and Pi share similar uptake mechanisms and that OsPT2 is involved in selenite uptake, which provides a potential strategy for breeding Se-enriched rice varieties.

Multi-detector CT enterography with iso-osmotic mannitol as oral contrast for detecting small bowel disease.

AIM: To assess the feasibility and usefulness of multi-detector CT enterography with orally administered iso-osmotic mannitol as negative contrast in demonstrating small bowel disease. METHODS: Thirteen volunteers and 38 patients with various kinds of small bowel disease were examined. We administered about 1 500 mL iso-osmotic mannitol as negative contrast agent and then proceeded with helical CT scanning on a Siemens Sensation 16 scanner. All volunteers and patients were interviewed about their tolerance of the procedure. Two radiologists post-processed imaging data with MPR, thin MIP, VRT and INSPACE when necessary and then interpreted the scans, and adequacy of luminal distention was evaluated on a four-point scale. Demonstration of features of various kinds of small bowel disease was analyzed. RESULTS: The taste of iso-osmotic mannitol is good (slightly sweet) and acceptable by all. Small bowel distention was excellent and moderate in most volunteers and patients. CT features of many kinds of diseases such as tumors, Crohn's disease,and small bowel obstruction, etc. were clearly displayed. CONCLUSION: Multi-detector CT enterography with iso-osmotic mannitol as negative contrast to distend the small bowel is a simple, rapid, noninvasive and effective method of evaluating small bowel disease.