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Li-Ping Yin,1 Fan Wang,2 Qian Li,2 Xiao-Ning Feng,3 Yan-Ling Li,2 Ling-Ling Li2 1Department of Oncology, The First Hospital Xingtai, Xingtai, Hebei, 054001, People’s Republic of China; 2Department of Tuberculosis, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, People’s Republic of China; 3Dosing Center, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, People’s Republic of ChinaCorrespondence: Ling-Ling Li, Department of Tuberculosis, Affiliated Hospital of Hebei University, No. 648 of Dongfeng East Road, Lianchi District, Baoding, Hebei, 071000, People’s Republic of China, Email lin1697g@126.comBackground: Patient safety is an important aspect of healthcare delivery and is critical to healthcare quality. An assessment of the attitudes of nursing staff in infectious diseases wards towards patient safety may identify deficiencies and allow for the development of educational programmes to train nursing staff to participate in good patient safety practices.Objective: To explore the current situation and influencing factors on nurses’ attitudes towards patient safety in infectious diseases wards.Methods: This cross-sectional study enrolled 446 nurses from infectious diseases wards in eight hospitals in the Hebei Province to participate in an electronic questionnaire survey from October to December 2020. The Chinese version of the safety attitude questionnaire was used to gather the opinions of these participants, and SPSS 22.0 statistical software was used to analyse the data.Results: The average score of safety attitudes towards patients was 3.59 ± 0.30. The scores for each dimension, from high to low, were as follows: management perception: 3.77 ± 0.42 points, pressure perception: 3.77 ± 0.42 points, safety atmosphere: 3.57 ± 0.43 points, job satisfaction: 3.57 ± 0.43 points, teamwork: 3.55 ± 0.50 points and working conditions: 3.50 ± 0.45 points. The results of the multiple stepwise regression analysis showed that the influential factors on nurses’ attitudes towards patient safety in infectious diseases wards were as follows: night shift working (β = 11.885, P = 0.000), years of nursing experience (β = 2.862, P = 0.001), education level (β = 4.462, P = 0.001) and marital status (β = 3.871, P = 1.002), which together explained 33.5% of the total variance.Conclusion: Nurses’ attitudes towards patient safety in infectious diseases wards were moderately high. Night shift work, years of nursing experience, education level and marital status affected nurses’ attitudes towards patient safety. Managers should focus on these groups of nurses and improve their working conditions and job satisfaction to further enhance patient safety.Keywords: infectious diseases wards, the nurse, patient safety attitude, influencing factors

Background: The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus (T2DM) is currently controversial. It is unknown whether this association can be gene realized across different populations., Aim: To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM., Methods: We searched PubMed, Embase, Web of Science, Cochrane Library, Medline, Baidu Academic, China National Knowledge Infrastructure, China Biomedical Liter-ature Database, and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12, 2022. Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature., Results: Twelve case-control studies (including 11273 cases and 11654 controls) met our inclusion criteria. In the full population, allelic model [odds ratio (OR): 1.19; 95% confidence interval (95%CI): 1.09-1.29; P < 0.0001], recessive model (OR: 1.20; 95%CI: 1.11-1.29; P < 0.0001), dominant model (OR: 1.27. 95%CI: 1.14-1.42; P < 0.0001), and codominant model (OR: 1.36; 95%CI: 1.15-1.60; P = 0.0003) (OR: 1.22; 95%CI: 1.10-1.36; P = 0.0002) indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM. In stratified analysis, this association was confirmed in Asian populations: allelic model (OR: 1.25; 95%CI: 1.13-1.37; P < 0.0001), recessive model (OR: 1.29; 95%CI: 1.11-1.49; P = 0.0007), dominant model (OR: 1.35; 95%CI: 1.20-1.52; P < 0.0001), codominant model (OR: 1.49; 95%CI: 1.22-1.81; P < 0.0001) (OR: 1.26; 95%CI: 1.16-1.36; P < 0.0001). In non-Asian populations, this association was not significant: Allelic model (OR: 1.06, 95%CI: 0.98-1.14; P = 0.12), recessive model (OR: 1.04; 95%CI: 0.75-1.42; P = 0.83), dominant model (OR: 1.06; 95%CI: 0.98-1.15; P = 0.15), codominant model (OR: 1.08; 95%CI: 0.82-1.42; P = 0.60. OR: 1.15; 95%CI: 0.95-1.39; P = 0.14)., Conclusion: KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population. Carriers of the C allele had a higher risk of T2DM. This association was not significant in non-Asian populations., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Observational studies have suggested a possible association between hypothyroidism and increased risk of ischemic stroke. However, a causal relationship remains unclear., Methods: Data on single nucleotide polymorphisms (SNPs) associated with hypothyroidism and ischemic stroke were sourced from the FinnGens database and the UK Biobank of European descent. Both databases underwent separate two-sample Mendelian randomization (MR) analyses. A subsequent meta-analysis of MR results using a random-effects model was conducted to determine the causal relationship between hypothyroidism and ischemic stroke., Results: All five analyses indicated a positive causal relationship between hypothyroidism and ischemic stroke. MR analysis of the association between hypothyroidism and ischemic stroke yielded a result of the inverse variance weighted (IVW) method at 4.7411 (1.3598-16.5308), p  = 0.0146. The analysis of ischemic stroke (without excluding controls) yielded a result of the IVW method of 4.5713 (1.3570-15.3986), p  = 0.0142. MR analysis with cerebral infarction yielded a result of the IVW method at 1.0110 (1.0006-1.0215), p  = 0.0373. The MR analysis with cerebrovascular disease sequelae yielded an IVW method result of 2.4556 (1.0291-5.8595), p  = 0.0429. Analysis for the sequelae of cerebrovascular disease (without excluding controls) yielded an IVW method result of 2.4217 (1.0217-5.7402), p  = 0.0446. No evidence of heterogeneity or horizontal pleiotropy was found. The meta-analysis of the five MR results was 2.24 (1.18-4.26), p  = 0.025., Conclusion: Our two-sample Mendelian randomization study suggested a causal relationship between hypothyroidism and ischemic stroke, indicating that hypothyroidism could be a risk factor for ischemic stroke. However, further studies are required to elucidate the underlying biological mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Shi, Shui, Liu, Bu, Liu and Yin.)

In recent years, antibiotics have been continuously detected in waterbodies and thus has become an environmental problem, especially in China. However, current knowledge regarding the ecological hazards of antibiotics is mainly focusing on the induction of resistance in pathogenic microorganisms, treating antibiotic contamination as a public safety problem that seriously endangers human health, but relatively ignores its potential risk to aquatic organisms. As an important component of aquatic ecosystems, plankton play an important role in maintaining the stability of aquatic ecosystems. Meanwhile, plankton are very sensitive to environmental changes. Therefore, understanding the impact of antibiotics on plankton is the basis for assessing their ecological risk. To this end, we summarized current status of antibiotic contamination in China's aquatic environments, and analyzed the impacts of antibiotics on planktons. In addition to using metabolomics technology to reveal the negative impacts of antibiotics at the individual level, monitoring of antibiotics and plankton communities in the field needs to be strengthened in the future.

The IRON-REGULATED TRANSPORTER1 (IRT1) is critical for iron uptake in roots, and its exocytosis to the plasma membrane (PM) is regulated by detergent-resistant membranes. However, studies on IRT1 exocytosis and function in response to iron status are limited. Presently, we found that the histidine-rich motif (HRM) of MxIRT1 could bind to iron directly and HRM determined the delivery of MxIRT1 to the PM, after which the cholesterol recognition amino acid consensus (CRAC) motif-regulated MxIRT1 mediated metal transport. IMAC assay revealed that H192 was the vital site for HRM binding to Fe 2+ , and metal-binding activity was stopped after the deletion of HRM (MxIRT1∆HM) or in H192 site-directed mutants (H 192 A). MxIRT1∆HM or H 192 A in transgenic yeast and Arabidopsis failed to localize in the PM and displayed impaired iron absorption. In the PM, Y266 in CRAC was required for metal transport; Y266A transgenic Arabidopsis displayed the same root length, Cd 2+ flux, and Fe concentration as Arabidopsis mutant irt1 under iron-deficient conditions. Therefore, H192 in HRM may be an iron sensor to regulate delivery of MxIRT1 vesicles to the PM after binding with iron; Y266 in CRAC acts as an iron sensor for active metal transport under iron-deficient conditions.

IRON-REGULATED TRANSPORTER 1 (IRT1) is critical for iron uptake in roots, and its exocytosis to the plasma membrane (PM) is regulated by the iron status sensed by the histidine-rich domain (HRM). However, studies on the fate of IRT1 after fusion with PM in response to iron conditions are still limited. In this study, we found that K165 and K196 regulate the monoubiquitination of MxIRT1 (mUb-MxIRT1), which acts as a receptor delivering signals from HRM to downstream effectors such as clathrin to determine the fate of MxIRT1. Iron supply led MxIRT1 in the PM to monoubiquitin-dependent endocytosis which could be inhibited by endocytosis inhibitor TyrA23 or in the double site-directed mutant K165/K196R. Subsequently, the endocytosis pathway to the vacuole was inhibited by vacuolar protease inhibitor Leupeptin in excessive iron conditions and the inability of being able to respond to iron change, indicated by the protein accumulating in the PM, contributed to iron toxicity in K165/K196R transgenic Arabidopsis. With iron availability decreasing again, MxIRT1 could dock close to the PM waiting for to be recycled. Another monoubiquitination site, K26, was necessary for MxIRT1 Endoplasmic Reticulum (ER) export as site-directed mutant K26R lost the ability of PM targeting, and co-localized with the COPII subunit of the coat protein OsSec24. Therefore, after K26-directed ER export and iron-induced PM fusion, mUb-MxIRT1 determines subsequent vacuolar degradation or recycling to the PM via endocytosis for maintaining iron homeostasis.

A new racemic naphthyl-coumarin-based probe was found to bind covalently with amino acids in MeOH-KOH system and thereby generates distinct CD responses. The induced strong CD signals allowed quantitative enantiomeric excess analysis of amino acids and enantioselective sensing of amines and amino alcohols. The mechanism for the reaction of the coumarin-aldehyde probe with an amino acid was investigated by CD, UV-Vis, NMR, ESI-MS analyses and ECD calculation., (© 2022 The Authors. Published by Wiley-VCH GmbH.)

Background: Diabetes is one of the common chronic diseases in which susceptibility is determined by a combination of genetic and environmental factors, and more than 90% of diabetic patients are diabetes mellitus type 2 (T2DM). The existing studies on the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes are inconsistent across populations., Aim: We aim to explore the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes in different populations., Methods: We examined all studies before June 12, 2021, that associated CDKAL1 rs10946398 with T2DM. Heterogeneity was assessed by meta-analysis of allelic inheritance models (A vs. C), dominant inheritance models (AA vs. AC+CC), and recessive inheritance model (AA+AC vs. CC); I 2 was used to assess the heterogeneity (if I 2 < 50%, the fixed-effects model was used; if I 2 ≥ 50%, the random-effects model was used for data consolidation); correlation was judged by a forest map; potential publication bias was tested by the Egger test ( p > 0.05 indicates that there is no publication bias)., Results: Fourteen data totaling 30288 subjects, including 19272 controls and 11016 patients with T2DM, met our inclusion criteria. In the Asian population, the differences were statistically significant ( p < 0.01) for dominant genetic model (OR = 0.75, 95%CI = 0.64-0.88, p = 0.0003). But the allelic effect model (OR = 0.87, 95%CI = 0.75-1.02, p = 0.08) and the recessive genetic model (OR = 0.85, 95%CI = 0.66-1.10, p = 0.23) were not statistically significant ( p > 0.01). In the non-Asian population, the differences were statistically significant ( p < 0.01) for the allelic effect model (OR = 0.83, 95%CI = 0.77-0.88, p < 0.00001), the dominant model (OR = 0.79, 95%CI = 0.72-0.87, p < 0.00001), and the recessive model (OR = 0.78, 95%CI = 0.70-0.87, p < 0.0001)., Conclusion: In this study, CDKAL1 RS10946398 was positively associated with T2DM, but the association was different in Asian populations., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ning Xu et al.)

Background: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM., Objective: To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility., Methods: A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger's test were used to evaluate the publication bias of the selected included literature., Results: Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P < 0.00001), recessive (OR: 0.73; 95% CI: 0.45,1.18; P < 0.00001) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations., Conclusion: This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM., Competing Interests: The authors state that the study was conducted without any commercial or financial relationship., (Copyright © 2021 Wen-Jia Han et al.)

Diabetic peripheral neuropathic pain (DPNP) is defined as a pain directly caused by the abnormal somatosensory system in diabetics according to the International Association for the Study of Pain (IASP). The pain has a great impact on the quality of life of diabetic patients. It results in a decline of patients' personal ability to live, which may even cause depression. Over time, the decline in both physical and psychosocial function caused by neuropathic pain may lead to further aggravation of depressive symptoms. This article mainly reviews the prevalence rate, medical expenditure, clinical characteristics, neurobiological features and the treatment of DPNP comorbidity depression, hoping to find the research directions for further study in the future.

Systematic form of pseudohypoaldosteronism Type I (PHA I) is a rare recessive homozygous inherited syndrome characterized by severe salt loss, hyperkalemia, hyponatremia, metabolic acidosis, hyperaldosteronism and hyperreninemia. It is caused by mutations in one of the genes encoding the α, β and γ subunits of epithelial sodium channels (ENaC). In this study, we performed whole exome sequencing on an infant patient with PHA I as well as nephropathy. The result presented a novel homozygous six-base deletion in the γ subunit encoding gene SCNN1G. Then we correlated the mutant to kidney damage, along with transcriptional alterations of genes involved in inflammation, oxidative stress and apoptosis, via in vitro and in vivo tests. In addition, it was demonstrated that the SCNN1G defects triggered programmed cell death via inhibiting miR-21 and upregulating PTEN, which then orchestrated the key downstream regulators, including Bcl2, Bax2, and cleaved Caspse-3 in a way that favors cell apoptosis. The study enhances our understanding of the pathophysiology of the disorder of PHA I and the mechanisms of renal damage induced by the novel defect., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: We aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images., Design: A prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2)., Results: AUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied., Conclusion: DLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients., Trial Registration Number: NCT02313649; Post-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose To investigate the diagnostic performance of two-dimensional (2D) shear-wave elastography (SWE) in chronic hepatitis B. Materials and Methods This prospective multicenter study from January 2015 to January 2016 was conducted at 12 hospitals and included 654 participants with chronic hepatitis B who had undergone liver biopsy and 2D SWE examination. Participants were divided into chronic infection and chronic hepatitis groups. The diagnostic performance of 2D SWE was compared with the aspartate amino transferase-to-platelet ratio index (APRI), the Fibrosis-4 index (FIB-4), and transient elastography (TE) by using a DeLong test and was also compared between two subgroups. Dual cutoff values for cirrhosis were determined with multilevel likelihood ratio analysis. Results Overall, 402 participants with chronic hepatitis B were enrolled (154 with chronic infection and 248 with chronic hepatitis). The areas under the receiver operating characteristic curve of 2D SWE (0.87; 95% confidence interval [CI]: 0.83, 0.90) were higher than those of TE (0.80; 95% CI: 0.68, 0.88), APRI (0.70; 95% CI: 0.65, 0.74), and FIB-4 (0.73; 95% CI: 0.69, 0.78) in cirrhosis. The high area under the receiver operating characteristic curve (0.92; 95% CI: 0.87, 0.96) was achieved in the chronic infection group and was significantly higher than that of the chronic hepatitis group (0.84; 95% CI: 0.78, 0.88; P = .017). Dual cutoff values with the likelihood ratios below 0.1 and above 10 (8.4 kPa and 11.0 kPa to rule out and rule in a diagnosis of cirrhosis, respectively) were effectively determined in chronic infection; a total of 81.2% (125 of 154) participants with cirrhosis were definitively diagnosed. Conclusion The performance of two-dimensional (2D) shear-wave elastography (SWE) was higher than that of other noninvasive methods. 2D SWE was most effective in ruling in and ruling out cirrhosis in participants with chronic infection, which may prompt antiviral treatment. © RSNA, 2018 Online supplemental material is available for this article.

Iron is essential for most living organisms. The iron-regulated transporter1 (IRT1) plays a major role in iron uptake in roots, and its trafficking from endoplasmic reticulum (ER) to plasma membrane (PM) is tightly coordinated with changes in iron environment. However, studies on the IRT1 response are limited. Here, we report that Malus xiaojinesis IRT1 (MxIRT1) associates with detergent-resistant membranes (DRMs, a biochemical counterpart of PM microdomains), whereas the PM microdomains are known platforms for signal transduction in the PM. Depending on the shift of MxIRT1 from microdomains to homogeneous regions in PM, MxIRT1-mediated iron absorption is activated by the cholesterol recognition/interaction amino acid consensus (CRAC) motif of MxIRT1. MxIRT1 initially associates with DRMs in ER via its transmembrane domain 1 (TMD1), and thus begins DRMs-dependent intracellular trafficking. Subsequently, MxIRT1 is sequestered in COPII vesicles via the ER export signal sequence in MxIRT1. These studies suggest that iron homeostasis is influenced by the CRAC motif and TMD1 domain due to their determination of MxIRT1-DRMs association., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mutations in the proline-rich transmembrane protein 2 (PRRT2) are associated with paroxysmal kinesigenic dyskinesia (PKD) and several other paroxysmal neurological diseases, but the PRRT2 function and pathogenic mechanisms remain largely obscure. Here we show that PRRT2 is a presynaptic protein that interacts with components of the SNARE complex and downregulates its formation. Loss-of-function mutant mice showed PKD-like phenotypes triggered by generalized seizures, hyperthermia, or optogenetic stimulation of the cerebellum. Mutant mice with specific PRRT2 deletion in cerebellar granule cells (GCs) recapitulate the behavioral phenotypes seen in Prrt2-null mice. Furthermore, recording made in cerebellar slices showed that optogenetic stimulation of GCs results in transient elevation followed by suppression of Purkinje cell firing. The anticonvulsant drug carbamazepine used in PKD treatment also relieved PKD-like behaviors in mutant mice. Together, our findings identify PRRT2 as a novel regulator of the SNARE complex and provide a circuit mechanism underlying the PRRT2-related behaviors.

Iron (Fe)-homeostasis in the plastids is closely associated with Fe transport proteins that prevent Fe from occurring in its toxic free ionic forms. However, the number of known protein families related to Fe transport in the plastids (about five) and the function of iron in non-green plastids is limited. In the present study, we report the functional characterization of Zea mays Fe deficiency-related 4 (ZmFDR4), which was isolated from a differentially expressed clone of a cDNA library of Fe deficiency-induced maize roots. ZmFDR4 is homologous to the bacterial FliP superfamily, coexisted in both algae and terrestrial plants, and capable of restoring the normal growth of the yeast mutant fet3fet4, which possesses defective Fe uptake systems. ZmFDR4 mRNA is ubiquitous in maize and is inducible by iron deficiency in wheat. Transient expression of the 35S:ZmFDR4-eGFP fusion protein in rice protoplasts indicated that ZmFDR4 maybe localizes to the plastids envelope and thylakoid. In 35S:c-Myc-ZmFDR4 transgenic tobacco, immunohistochemistry and immunoblotting confirmed that ZmFDR4 is targeted to both the chloroplast envelope and thylakoid. Meanwhile, ultrastructure analysis indicates that ZmFDR4 promotes the density of plastids and accumulation of starch grains. Moreover, Bathophenanthroline disulfonate (BPDS) colorimetry and inductively coupled plasma mass spectrometry (ICP-MS) indicate that ZmFDR4 is related to Fe uptake by plastids and increases seed Fe content. Finally, 35S:c-Myc-ZmFDR4 transgenic tobacco show enhanced photosynthetic efficiency. Therefore, the results of the present study demonstrate that ZmFDR4 functions as an iron transporter in monocot plastids and provide insight into the process of Fe uptake by plastids., (© 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.)

To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784-0.923; AUC: 0.758-0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment.

The COP9 signalosome (CSN) plays an important role in proteasome-mediated degradation by regulating CUL1 rubylation of the SCF ligase and is involved in many crucial biological processes. Here, we demonstrate a link between IDEF1 accumulation and the decline in COP9 derubylation activity in response to iron deficiency (-Fe) in rice (Oryza sativa). CSN6 expression is rapidly down-regulated during Fe depletion, contributing to reduced CSN activity, as judged by CSN5 and CUL1 expression, indicating CSN6 is involved in the early stage response of -Fe. In contrast to CSN6, the IDEF1 protein and expression of several iron uptake/utilisation-related genes are increased in response to -Fe. Thus, we constructed CSN6 transgenic sense and antisense lines and found that experimental depletion of CSN6 results in accumulation of the IDEF1 protein and up-regulation of several iron uptake/utilisation-related genes. Furthermore, IDEF1 can be decorated with K48-linked polyubiquitin and degraded via the 26S proteasome. Accumulated IDEF1 in antisense lines led to increased chlorophyll and Fe content in seedlings during -Fe. Collectively, the cellular CSN6 level is decreased during early stages of -Fe to ensure the rapid accumulation of IDEF1, which in turn up-regulates several iron uptake/utilisation-related genes to help overcome -Fe stress in rice.

Background: The average incidence of preterm birth in the world is up to 11.1 %, and deaths of preterm children account for more than 50 % of neonatal deaths. Gastrointestinal function of preterm children with a gestational age less than 34 weeks is immaturely developed. For preterm children who can only be fed with formula due to their mothers' sickness, choosing a suitable formula can not only meet the high nutritional needs of preterm children, but also solve their low gastrointestinal tolerability, and is thus very important., Methods/design: The study is a prospective, randomized, single-blind and controlled clinical trial. Preterm children with a gestational age less than 34 weeks meeting the inclusion criteria who cannot be breastfed will be included. To demonstrate the application effect of extensively hydrolyzed milk protein formula on the target population, preterm children will be randomized into two groups, 185 subjects in each group. The observation group will be fed with extensively hydrolyzed milk protein (100 % whey protein) formula, while the control group will be fed with preterm children's formula until the children are discharged from the neonatal intensive care unit (NICU). All the formula involved in this study will be from Dumex. After discharge, both groups will be uniformly fed with formula for 0 to 6-month-old infants. For statistical analysis, a chi-square test and Student's t test will be applied using SAS 9.4., Discussion: This will be the first randomized controlled clinical study with long-term observation of the growth and development of preterm children during the NICU stay and at 3-month follow-up after discharge from the NICU. Results from this study will be used to determine whether the extensively hydrolyzed formula is more suitable for the low gastrointestinal tolerability of preterm children, and also whether feeding preterm children who are fed with such formula during the NICU stay with ordinary infant formula after discharge from the NICU would affect the normal growth and development of preterm children in the early stage of their lives., Trial Registration: This study was registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) with number ChiCTR-IOR-14005696 , on December 22, 2014.

A rapid immunochromatographic strip for detecting capsid protein antigen p27 of avian leukosis virus was successfully developed based on two high-affinity monoclonal antibodies. The test strip could detect not only 600pg purified recombinant p27 protein but also quantified avian leukosis virus as low as 70 TCID50, which has comparative sensitivity to the commercial enzyme-linked immunosorbent assay (ELISA) kit. For the evaluation of this test strip, 1100 samples consisting of cloacal swabs, meconium collected from the earliest stool of one day old chicken and virus isolates were assessed both by the strip and by the commercial ELISA kit. The agreement between these two tests was 93.91%, 93.42% and 100%, respectively. The sensitivity and specificity of the strip were also calculated by using the ELISA kit as the standard. This immunochromatographic strip provides advantages of rapid and simple detection of capsid protein antigen p27 of avian leukosis virus, which could be applied as an on-site testing assay and used for control and eradication programs of avian leukosis disease., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Iron is essential for plants, but highly toxic when present in excess. Consequently, iron uptake by root transporters must be finely tuned to avoid excess uptake from soil under iron excess. The iron-regulated transporter of Malus xiaojinensis (MxIRT1), induced in roots under iron deficiency, is a highly effective iron(II) transporter. Here, we investigated how the presence of excessive iron leads to MxIRT1 degradation in yeast expressing this plant iron transporter protein. To determine the relationship between iron abundance and MxIRT1 degradation, relative levels of autophagy-related gene-8 (ATG8) mRNA and the active ATG8-phosphatidylethanolamine-conjugated (PE) protein were measured in wild-type yeast and the autophagic mutant strains atg1∆, atg5∆, atg7∆, ypt7∆ and tor1∆ under normal and excessive iron conditions. The data showed that the exposure of MxIRT1-eGFP-transformed wild-type and tor1∆ strains to excessive iron led to significantly increased levels of ATG8 transcript and ATG8-PE protein, which resulted in enhanced MxIRT1 degradation. Co-localization of mCherry-ATG8 and MxIRT1-eGFP provided evidence that these proteins interact during autophagy in yeast. While inhibition of autophagic initiation, autophagosome formation and vacuole fusion all decreased MxIRT1 degradation. PMSF inhibition of autophagy prevented degradation, leading to the accumulation of MxIRT1-containing vesicles in the vacuoles. MxIRT1-vesicles were sorted into autophagosomes for iron-induced degradation in yeast, whereas the endogenous iron(II) transporter Fet4 was degraded in an autophagy-independent manner. Moreover, immunoprecipitation showed that multimono-ubiquitins provided MxIRT1 with the ubiquitination signal. Together, three factors, iron excess, autophagy and mono-ubiquitination, affect the functional activity and stability of exogenous MxIRT1 in yeast, thereby preventing iron uptake via this root transporter., (Copyright © 2015 John Wiley & Sons, Ltd.)

Iron is abundant in the soil, but its low solubility in neutral or alkaline soils limits its uptake. Plants can rely on rhizosphere acidification to increase iron solubility. OsSEC27p was previously found to be a highly up-regulated gene in iron-deficient rice roots. Here, pH-dependent complementation assays using yeast mutants sec24Δ/SEC24 and sec27Δ/SEC27 showed that OsSEC27 could functionally complement SEC24 but not SEC27 in yeast; thus, it was renamed as OsSEC24. We found that OsSEC24-transgenic tobacco plants increased the length and number of roots under iron deficiency at pH 8.0. To explore how OsSEC24 confers tolerance to iron deficiency, we utilized transgenic tobacco, rice and rice protoplasts. H(+) flux measurements using Non-invasive Micro-test Technology (NMT) indicated that the transgenic OsSEC24 tobacco and rice enhanced H(+) efflux under iron deficiency. Conversely, the application of plasma membrane PM-H(+)-ATPase inhibitor vanadate elucidated that H(+) secretion increased by OsSEC24 was mediated by PM-H(+)-ATPase. OsPMA2 was used as a representative of iron deficiency-responsive PM-H(+)-ATPases in rice root via RT-PCR analysis. In transgenic rice protoplasts OsPMA2 was packaged into OsSEC24 vesicles after export from the ER through confocal-microscopy observation. Together, OsSEC24 vesicles, along with PM-H(+)-ATPases stimulate roots formation under iron deficiency by enhancing rhizosphere acidification., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Iron and zinc are essential in plant and human nutrition. Iron deficiency has been one of the causes of human mortality, especially in developing countries with high rice consumption. MxIRT1 is a ferrous transporter that has been screened from an iron-efficient genotype of the apple tree, Malus xiaojinensis Cheng et Jiang. In order to produce Fe-biofortified rice with MxIRT1 to solve the Fe-deficiency problem, plant expression vectors of pCAMBIA1302-MxIRT1:GFP and pCAMBIA1302-anti MxIRT1:GFP were constructed that led to successful production of transgenic rice. The transgenic plant phenotypes showed that the expression of endogenous OsIRT1 was suppressed by anti-MxIRT1 in antisense lines that acted as an opposing control, while sense lines had a higher tolerance under Zn- and Fe-deficient conditions. The iron and zinc concentration in T3 seeds increased by three times in sense lines when compared to the wild type. To understand the MxIRT1 cadmium uptake, the MxIRT1 cadmium absorption trait was compared with AtIRT1 and OsIRT1 in transgenic rice protoplasts, and it was found that MxIRT1 had the lowest Cd uptake capacity. MxIRT1 transgenic tobacco-cultured bright yellow-2 (BY-2) cells and rice lines were subjected to different Fe conditions and the results from the non-invasive micro-test technique showed that iron was actively transported compared to cadmium as long as iron was readily available in the environment. This suggests that MxIRT1 is a good candidate gene for plant Fe and Zn biofortification.

Malus xiaojinensis iron-regulated transporter 1 (Mx IRT1) is a highly effective inducible iron transporter in the iron efficient plant Malus xiaojinensis. As a multi-pass integral plasma membrane (PM) protein, Mx IRT1 is predicted to consist of eight transmembrane domains, with a putative N-terminal signal peptide (SP) of 1-29 amino acids. To explore the role of the putative SP, constructs expressing Mx IRT1 (with an intact SP) and Mx DsIRT1 (with a deleted SP) were prepared for expression in Arabidopsis and in yeast. Mx IRT1 could rescue the iron-deficiency phenotype of an Arabidopsis irt1 mutant, and complement the iron-limited growth defect of the yeast mutant DEY 1453 (fet3fet4). Furthermore, fluorescence analysis indicated that a chimeric Mx IRT1-eGFP (enhanced Green Fluorescent Protein) construct was translocated into the ER (Endoplasmic reticulum) for the PM sorting pathway. In contrast, the SP-deleted Mx DsIRT1 could not rescue either of the mutant phenotypes, nor direct transport of the GFP signal into the ER. Interestingly, immunoblot analysis indicated that the SP was not cleaved from the mature protein following transport into the ER. Taken together, data presented here provides strong evidence that an uncleaved SP determines ER-targeting of Mx IRT1 during the initial sorting stage, thereby enabling the subsequent transport and integration of this protein into the PM for its crucial role in iron uptake.

Aim: In this study, we investigated the therapeutic efficacy and potential mechanisms of rhein to mitigate chronic allograft nephropathy (CAN) in rats., Materials and Methods: Fisher rat donors and Lewis rat recipients were used to establish the CAN model. Thirty rats with transplanted kidneys were randomly divided into two groups: 16 untreated and 14 rhein = treated rats. Five Lewis rat controls underwent removal of their right kidneys. The Intervention group was administered rhein oral solution (100 mg kg(-1) d(-1)) by gavage after transplantation. The untreated and control groups were given 0.5% sodium carboxymethyl cellulose. Blood and urine samples were collected at 4, 8, and 16 weeks to examine renal function and total urine protein. Half of the rats in each group were sacrifice at 8 or 16 weeks to examine renal pathology. Immunohistochemical examination and real-time polymerase chain reaction of renal tissues were performed to detect expressions of transforming growth-β1(TGF-β1), hepatic growth factor (HGF), bone morphogenetic protein 7 (BMP7), frobronectin, and collgen IV., Results: Rhein improved renal function and significantly reduced renal fibrosis and interstitial inflammation. The levels of BMP7 and HGF were significantly elevated in the renal tissues of the rhein intervention group. In the meantime, fibronectin and collagen IV were decreased in the extracellular matrix. The expression of TGF-β1 was similar between these two groups., Conclusion: Rhein improved renal function and reduced renal fibrosis and interstitial inflammation by inducing production of HGF and BMP7., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Leaves of Lycium chinense L. are widely used in traditional Chinese medicine and as functional food in China and south-east Asia. Polyphenols are important active compounds in leaves of L. chinense L, but their compositions are still not very clear. Selenium has been reported to increase some components of plants. In this study, the composition of polyphenols of L. chinense leaves were analysed, and the effects of selenium on the polyphenols and other components were studied., Results: The main polyphenols were identified as rutin, chlorogenic acid, quercetin, kaempferol and apigenin-7-O-(6'-O-acetyl) glucose-rhamnose. Chlorogenic acid showed the highest average content of 78.36 g kg⁻¹. Rutin, quercetin and kaempferol were determined at low contents from 3.85 g kg⁻¹ to 7.08 g kg⁻¹. Correlation coefficients between selenium and chlorogenic acid, chlorophyll a, chlorophyll b and carotenoids were: R² = 0.963 (P = 0.002), 0.943 (P = 0.005), 0.957 (P = 0.003) and 0.943 (P = 0.005), respectively. Selenium (0.01-0.05 g kg⁻¹) significantly increased chlorogenic acid, chlorophyll and carotenoids by 200-400% and reduced rutin by 400-900%., Conclusion: L. chinense can be an alternative source of chlorogenic acid. Selenium significantly increased chlorogenic acid, chlorophyll a, chlorophyll b and carotenoids, hence increasing the medicinal value of L. chinense leaves. Rutin, quercetin, kaempferol and apigenin-7-O-(6'-O-acetyl) glucose-rhamnose proved to be not significantly influenced by selenium., (Copyright © 2012 Society of Chemical Industry.)

Objective: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) as an adjunctive method to standard therapy for patients with diabetic foot ulcers (DFU)., Methods: Randomized controlled trials (RCTs) of CHM to treat DFU were searched in the following electronic databases: MEDLINE; EMBASE; Chinese Biomedical Database (CBM); Cochrane Central Register of Controlled Trials (CENTRAL); Allied & Complementary Medicine Resources (AMED); and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two (2) researchers independently assessed the quality and validity of included trials and extracted outcome data for synthesis., Results: Six (6) trials were included for analysis. Compared to using standard therapy alone, CHM combined with standard therapy significantly increased the number of patients whose ulcers healed (risk ratio [RR], 0.62, [95% confidence interval (CI), 0.39-0.97]) and number of patients with at least a 30% reduction in the ulcer area (RR, 0.81 [95%CI, 0.71-0.92]). In addition, the two therapies combined significantly decreased the number of patients without any improvement (RR, 0.34 [95%CI, 0.21-0.53]). However, with respect to blood flow volume in the dorsal artery of the foot, no significant difference between the two therapies was observed (standardized mean difference, 1.71 [95% CI -1.25-4.67]), but the result favored the CHM combined with standard therapy group. Only 2 of 6 trials reported adverse events, which included nausea, epigastric pain, and dry mouth., Conclusions: CHM may be effective and safe as an adjunctive therapy for treating DFU. However, a firm conclusion could not be reached because of the poor quality of the included trials. Further trials with higher quality are justified.

Aim: To establish a novel method for antibody analysis based on visual protein microarray., Methods: The antibodies spotted on the aldehyde-modified slides were incubated with corresponding antigens labeled by biotin, followed by silver enhancement detection method, and the chromogenic images were scanned by CCD camera., Results: The affinity and specificity of each antibody was assayed by this method and six antibodies were found to have higher specificity than the others. A detection limit of 0.4 microg/L was obtained for anti-globulinIIIC013, anti-albumin HPSIIB007, and anti-albumin HPSIIIB007., Conclusion: This method is simple, fast and visual. In addition, it needs less sample amount than traditional immunoassay and has potential to achieve high throughput.

Objective: To investigate the induction and culture of adventitious root of Panax notoginseng., Method: Three ways, induction from the explants of three-year-old P. notoginseng. The explants of regenerated shoots and calluses, were used to induce adventitious roots. The effects of 2, 4-dichlorophenoxyacetic acid, indole-3-butyric acid and naphthylacetic acid on adventitious root induction were investigated respectively. The effects of four modes of separating adventitious roots from the parent tissues on culture in vitro were compared., Result: Adventitious roots were successfully induced by three methods, of which the young flower bud callus was the best material for the induction of adventitious root. Indole-3-butyric acid possessed the strongest potency for induction. The liquid culture system was established by continuous culture of adventitious roots together with their parent tissues before separated., Conclusion: The acquisition and culture in vitro in liquid culture system of adventitious roots of P. notoginseng lay a foundation for the next investigation.

Many aspects of photosynthetic gene expression are posttranscriptionally regulated in C4 plants. To determine if RbcS mRNA untranslated regions (UTRs) in themselves could confer any characteristic C4 expression patterns, 5'- and 3'-UTRs of AhRbcS1 mRNA from the C4 dicot amaranth were linked to a gusA reporter gene. These were constitutively transcribed from a cauliflower mosaic virus promoter and assayed for posttranscriptional expression patterns in transgenic lines of the C4 dicot Flaveria bidentis. Three characteristic C4 expression patterns were conferred by heterologous AhRbcS1 UTRs in transgenic F. bidentis. First, the AhRbcS1 UTRs conferred strong translational enhancement of gusA expression, relative to control constructs lacking these UTRs. Second, while the UTRs did not appear to confer tissue-specific expression when analyzed by beta-glucuronidase activity assays, differences in gusA mRNA accumulation were observed in leaves, stems, and roots. Third, the AhRbcS1 UTRs conferred preferential gusA expression (enzyme activity and gusA mRNA accumulation) in leaf bundle sheath cells. AhRbcS1 UTR-mediated translational enhancement was also observed in transgenic C3 plants (tobacco [Nicotiana tabacum]) and in in vitro translation extracts. These mRNAs appear to be translated with different efficiencies in C4 versus C3 plants, indicating that processes determining overall translational efficiency may vary between these two categories of higher plants. Our findings suggest that the AhRbcS1 5'-UTR functions as a strong translational enhancer in leaves and other tissues, and may work synergistically with the 3'-UTR to modulate overall levels of Rubisco gene expression in different tissues and cell types of C4 plants.

Objective: To study the effectiveness of substitute valve at the popliteal vein in treatment of deep venous valve insufficiency of lower extremities., Methods: From January 1996 to August 2002, 27 patients were diagnosed having deep venous valve insufficiency of lower extremities by color Doppler and radiography with an average disease course of 17.4 years. All 27 patients had varicose vein, 25 pain, 22 swelling, 25 pigmentation in ankle area and 19 chronic ulcerations. Two cases had been treated with great saphenous vein ligation and striping. Average vein pressure in resting position was (11.00 +/- 0.73) kPa, and the ambulatory venous pressure was (9.14 +/- 0.68) kPa. All patients were treated with substitute valve at the popliteal vein, and great saphenous vein ligation and stripping, some were treated with subfascial endoscopic perforating veins ablation., Results: The average ambulatory venous pressure after operation was (5.94 +/- 0.82) kPa, were significantly different from that before operation(P < 0.01). The curative results were satisfactory, and all symptom and physical sign disappeared. After a mean follow-up period of 2-6 years, 21 cases had satisfactory results., Conclusion: Substitute valve at the popliteal vein have the value of widespread application.