To avoid zinc (Zn) toxicity, plants have developed a Zn homeostasis mechanism to cope with Zn excess in the surrounding soil. In this report, we uncovered the difference of a cross-homeostasis system between iron (Fe) and Zn in dealing with Zn excess in the Zn hyperaccumulator Arabidopsis halleri ssp. gemmifera and nonhyperaccumulator Arabidopsis thaliana. Arabidopsis halleri shows low expression of the Fe acquisition and deficiency response-related genes IRT1 and IRT2 compared with A. thaliana. In A. thaliana, lowering the expression of IRT1 and IRT2 through the addition of excess Fe to the medium increases Zn tolerance. Excess Zn induces significant Fe deficiency in A. thaliana and reduces Fe accumulation in shoots. By contrast, the accumulation of Fe in shoots of A. halleri was stable under various Zn treatments. Root ferric chelate reductase (FRO) activity and expression of FIT are low in A. halleri compared with A. thaliana. Overexpressing a ZIP family member IRT3 in irt1-1, rescues the Fe-deficient phenotype. A fine-tuned Fe homeostasis mechanism in A. halleri maintains optimum Fe level by Zn-regulated ZIP transporters and prevents high Zn uptake through Fe-regulated metal transporters, and in part be responsible for Zn tolerance

Spider silk is protein fibers with extraordinary mechanical properties. Up to now, it is still poorly understood how silk proteins are kept in a soluble form before spinning into fibers and how the protein molecules are aligned orderly to form fibers. Minor ampullate spidroin is one of the seven types of silk proteins, which consists of four types of domains: N-terminal domain, C-terminal domain (CTD), repetitive domain (RP) and linker domain (LK). Here we report the tertiary structure of CTD and secondary structures of RP and LK in aqueous solution, and their roles in protein stability, solubility and fiber formation. The stability and solubility of individual domains are dramatically different and can be explained by their distinct structures. For the tri-domain miniature fibroin, RP-LK-CTDMi, the three domains have no or weak interactions with one another at low protein concentrations (<1 mg/ml). The CTD in RP-LK-CTDMi is very stable and soluble, but it cannot stabilize the entire protein against chemical and thermal denaturation while it can keep the entire tri-domain in a highly water-soluble state. In the presence of shear force, protein aggregation is greatly accelerated and the aggregation rate is determined by the stability of folded domains and solubility of the disordered domains. Only the tri-domain RP-LK-CTDMi could form silk-like fibers, indicating that all three domains play distinct roles in fiber formation: LK as a nucleation site for assembly of protein molecules, RP for assistance of the assembly and CTD for regulating alignment of the assembled molecules.

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Prostate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression. Metastasis is the main factor leading to cancer progression and poor prognosis, and at the beginning of metastasis, epithelial‐to‐mesenchymal transition (EMT) is a crucial activation. However, the relationship between PMEPA1 and EMT in colorectal cancer metastasis is still poorly understood. In this study, we first testified that PMEPA1 expresses higher in tumour than normal tissue in Gene Expression Omnibus database, in the Cancer Genome Atlas (TCGA) as well as in the clinical data we collected. Moreover, the higher expression was associated with poor prognosis. We furthermore demonstrated PMEPA1 promotes colorectal cancer metastasis and EMT in vivo and in vitro. We found that PMEPA1 activates the bone morphogenetic proteins (BMP) signalling of TGF‐β signalling resulting in promoting EMT and accelerating the proliferation and metastasis of colorectal cancer.

Abstract:Objective: Three mainstream techniques-laparoscopic hepatectomy (LH), percutaneous radiofrequency ablation (pRFA), and open hepatectomy (OH)-were compared in this study, in terms of their efficacies in the treatment of small hepatocellular carcinoma (HCC). Methods: A comparative study was performed within a total of 94 patients diagnosed with small HCC in our hospital from 2005 to 2010, who underwent LH (28), RFA (33), or OH (33). They had either a single tumor lesion of less than 5 cm or up to three nodules with diameters of less than 3 cm each. Outcomes were carefully evaluated throughout a 3-year follow-up interval and statistically interpreted. Results: The pRFA group had a significantly lower disease-free survival rate compared with the two surgical groups (P=0.001) and significantly shorter overall survival (P=0.005), while the LH group and the OH group had no difference in survival results. For patients younger than 60 years old, surgical approaches offered a better long-term overall survival prognosis (P=0.008). There were no statistically significant differences among the three groups in overall survival for elderly patients (P=0.104). Conclusions: Among patients with small HCC, LH may provide better curative effects than pRFA without increasing complication rates. pRFA leads to faster recurrence than surgical resections. LH has similar therapeutic effects to OH and causes less trauma. For patients younger than 60 years old, LH may be the best curative treatment. Elderly patients may choose either surgery or pRFA.

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Spider silk is self-assembled from silk proteins or spidroins. C-terminal domains (CTDs) of various types of spidroins are relatively conserved in amino acid sequences and are suggested to adopt similar structures and perform similar functional roles in spidroin storage and silk formation. Here, we solved the structure of the CTD from a capture-spiral silk protein (CTDFl) and characterized its stability and fibril formation in the presence and absence of a reducing agent at different pH values. CTDFl adopts a dimeric structure with 8 helices, but the CTDs of other types of spidroins exist in a domain-swapped dimeric structure with 10 helices. Despite the structural differences, CTDFl is pH-responsive in stability and fibril formation, similar to the CTDs from minor and major ampullate spidroins. Thus, the functional role of CTDs in silk fiber formation seems conserved. Comparing wild-type CTDFl and its mutants, we found that the pH-responsive behavior results from the protonation of H76, which is conserved from different spider species. In addition, the fibril formation rate of CTDFl correlates with its instability, suggesting that structural changes are involved in fibril formation.

Background The relationship between birth weight and blood pressure has not been well explored in Chinese children and adolescents. The aim of this study was to investigate the relationship between birth weight and childhood blood pressure in China. Methods A total of 15324 children and adolescents (7919 boys and 7405 girls) aged 7–17 years were stratified into six birth weight groups. Analysis of covariance and binary logistic regression were used to analyse the relationship between birth weight and blood pressure while controlling for potential confounding factors, including age, gestational age, season of birth and area of residence. Results The group with birth weights from 2500 to 2999 g had the lowest prevalence of hypertension (8.9%). Lower birth weight children (< 2000 g) had significantly higher systolic blood pressure (SBP) (106.00 ± 0.72, P = 0.017), and children with heavier birth weights also had higher SBP (3500–3999 g, 105.13 ± 0.17, P < .001; ≥ 4000 g, 105.96 ± 0.27, P < .001). No significant relationship was found between birth weight and diastolic blood pressure (DBP). The overall rate of hypertension was 10.8% (12.1% in boys and 9.4% in girls). The median weight group (2500–2999 g) had the lowest rate of hypertension (8.9%). Compared with children in the median weight group, children with lower birth weight had a higher prevalence of hypertension (< 2000 g, OR = 1.85, 95% CI = 1.25–2.74; 2000–2499 g, OR = 1.57, 95% CI = 1.15–2.13), and groups with higher birth weights also had higher risks of hypertension (3500–3999 g, OR = 1.22, 95% CI = 1.02–1.45; ≥ 4000 g, OR = 1.42, 95% CI = 1.16–1.74). Conclusions Excluding the confounding effect of obesity, a U-shaped relationship between birth weight and risk of hypertension was found in children and adolescents in Chinese cities. Birth weight significantly influences SBP but has a minimal effect on DBP. Further basic research on foetal development and programming may shed light on this phenomenon.