TMD1 domain and CRAC motif determine the association and disassociation of MxIRT1 with detergent-resistant membranes.

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.

Deep learning Radiomics of shear wave elastography significantly improved diagnostic performance for assessing liver fibrosis in chronic hepatitis B: a prospective multicentre study.

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.

A novel SCNN1G mutation in a PHA I infant patient correlates with nephropathy.

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, ß 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.

Zea mays Fe deficiency-related 4 (ZmFDR4) functions as an iron transporter in the plastids of monocots.

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.

Liver Fibrosis with Two-dimensional US Shear-Wave Elastography in Participants with Chronic Hepatitis B: A Prospective Multicenter Study.

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.

Expression of Malus xiaojinensis IRT1 (MxIRT1) protein in transgenic yeast cells leads to degradation through autophagy in the presence of excessive iron.

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.

Over-expression of the MxIRT1 gene increases iron and zinc content in rice seeds.

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.

An uncleaved signal peptide directs the Malus xiaojinensis iron transporter protein Mx IRT1 into the ER for the PM secretory pathway.

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.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations.

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.

Exploring the causal factor effects of hypothyroidism on ischemic stroke: a two-sample Mendelian randomization study.

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.

Current situation of antibiotic contamination in China and the effect on plankton.

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.

A Cross-Sectional Descriptive Study on the Attitudes Towards Patient Safety and Influencing Factors of Nurses in Infectious Diseases Wards.

Background: 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 (ß = 11.885, P = 0.000), years of nursing experience (ß = 2.862, P = 0.001), education level (ß = 4.462, P = 0.001) and marital status (ß = 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.

Short stature associated with a novel mutation in the aggrecan gene: A case report and literature review.

BACKGROUND: Mutations in the aggrecan (ACAN) gene are identified in patients with: spondyloepiphyseal dysplasia, Kimberley type; short stature with advanced bone age (BA); in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans; and spondyloepimetaphyseal dysplasia, ACAN type. Heterozygous mutations contribute to spondyloepiphyseal dysplasia, Kimberley type (MIM#608361), which is a milder skeletal dysplasia. In contrast, homozygous mutations cause a critical skeletal dysplasia, which is called spondyloepimetaphyseal dysplasia, ACAN type (MIM#612813). Lately, investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA, in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans (MIM#165800). We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature, BA acceleration, and premature growth cessation. CASE SUMMARY: A 2-year-old male patient visited us due to growth retardation. The patient presented symmetrical short stature (height 79 cm, < -2 SD) without facial features and other congenital abnormalities. Whole-exome sequencing revealed a heterozygous pathogenic variant c. 871C>T (p. Gln291*) of ACAN, which was not yet reported in cases of short stature. This mutation was also detected in his father and paternal grandmother. According to the Human Gene Mutation Database, 67 ACAN mutations are registered. Most of these mutations are genetically inheritable, and very few children with short stature are associated with ACAN mutations. To date, heterozygous ACAN mutations have been reported in approximately 40 families worldwide, including a few individuals with a decelerated BA. CONCLUSION: Heterozygous c. 871C>T (p. Gln291*) variation of the ACAN gene was the disease-causing variant in this family. Collectively, our newly discovered mutation expanded the spectrum of ACAN gene mutations.

Monoubiquitinated MxIRT1 acts as an iron receptor to determine MxIRT1 vacuole degradation or plasma membrane recycling via endocytosis.

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.

HRM and CRAC in MxIRT1 act as iron sensors to determine MxIRT1 vesicle-PM fusion and metal transport.

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 Fe2+, and metal-binding activity was stopped after the deletion of HRM (MxIRT1∆HM) or in H192 site-directed mutants (H192A). MxIRT1∆HM or H192A 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, Cd2+ 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.

A Racemic Naphthyl-Coumarin-Based Probe for Quantitative Enantiomeric Excess Analysis of Amino Acids and Enantioselective Sensing of Amines and Amino Alcohols.

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.

Association of KCNQ1rs2237892C⟶T Gene with Type 2 Diabetes Mellitus: A Meta-Analysis.

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.

Association of CDKAL1 RS10946398 Gene Polymorphism with Susceptibility to Diabetes Mellitus Type 2: A Meta-Analysis.

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.

A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis.

Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-clinical animal data to assess the current evidence for rhein effects and mechanisms in treating diabetic nephropathy. Methods: The databases of PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP information database, Wanfang Data Information Site, and Chinese Biomedical Literature were searched for this review. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality of studies. A meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.3 and STATA/SE 12.0 software. This study was registered with PROSPERO, number CRD42018105220. Results: Twenty-five studies involving 537 animals were included. There was significant association of rhein with levels of blood glucose (P < 0.05), serum creatinine (Scr) (P < 0.05), urine protein (P < 0.05), kidney tubules injury index (P < 0.05), relative area of kidney collagen (P < 0.05), transforming growth factor-ß1 (P < 0.05), malondialdehyde (P < 0.05), and superoxide dismutase (P < 0.05) compared with that in the control group. No significant association between rhein and endothelin (P > 0.05) was found. Subgroup analysis showed that the hypoglycemic effect of rhein on type 2 diabetic nephropathy was better than on type 1 diabetic nephropathy (P < 0.05). Conclusions: These findings suggested that rhein has beneficial effects on animal models of diabetic nephropathy, and that the mechanisms are mostly involved with ameliorating levels of TGF-ß1, renal fibrosis, metabolism, and oxidative stress status. However, some factors such as possible publication bias, methodological quality, and sample size may affect the accuracy of positive findings. These limitations suggested that a cautious interpretation of the positive results of this systematic review and meta-analysis is necessary. Therefore, high methodological quality and well-reported animal experiments are needed in future research.

Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves.

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.