Context The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. Objective This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. Design A prospective, observational, posttrial study (NCT03290235). Setting, participants and intervention Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. Main outcomes measures Height SD score (Ht SDS) at 12, 24, and 36 months. Results A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. Conclusions PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.

Heavy metal pollution possesses potential hazards to plant, animal and human health, which has become the focus of recent attention. Hence, phytoremediation has been regarded as one of the most important remediation technologies for heavy-metal-contaminated soils. In this research, a dominant mine tailing plant, Macleaya cordata, was used as the experimental material to compare the metal transport and oxidative stress response in its roots under lead (Pb) and zinc (Zn) treatments. The result showed that Pb was mainly accumulated in the roots of M. cordata under the Pb treatment; less than 1% Pb was transported to the parts above. An analysis of the Zn content demonstrated a 39% accumulation in the shoots. The production of reactive oxygen species was detected using the in situ histological staining of roots, which showed that hydrogen peroxide in the root tips was observed to increase with the increase in both Pb and Zn concentrations. No significant superoxide anion changes were noted in the root tips under the Pb treatment. An analysis of the root enzyme activity showed that increase in NADPH oxidase activity can be responsible for the production of superoxide anions, subsequent the inhibition of root growth and decrease in antioxidant enzyme activities in the roots of M. cordata exposed to excess Zn. In total, this research provides evidence that the root of M. cordata has a high antioxidant capacity for Pb stress, so it can accumulate more Pb without oxidative damage. On the other hand, the Zn accumulated in the roots of M. cordata causes oxidative damage to the root tips, which can stimulate more Zn transport to the shoots to reduce the damage to the roots. This result will provide a basis for the application of M. cordata in the phytoremediation of soil polluted by Pb-Zn compounds.

Solanum nigrum is a cadmium (Cd) and zinc (Zn) accumulator with potential for phytoextraction of soil contaminated with heavy metals. However, how Zn affects Cd accumulation in S. nigrum remains unclear. In this study, S. nigrum seedlings were treated with 100 μmol·L⁻¹ Zn (Zn100), 100 μmol·L⁻¹ Cd (Cd100), and the Zn and Cd combination (Zn100+Cd100) for 10 days under hydroponic culture. Compared with Cd100, the Cd content in stems, leaves, and xylem saps was 1.8, 1.6, and 1.3 times more than that in Zn100+Cd100, respectively. In addition, the production of reactive oxygen species in leaves was significantly upregulated in Cd100 compared with the control, and it was downregulated in Zn100. Comparative analyses of transcriptomes and proteomes were conducted with S. nigrum leaves. Differentially expressed genes (DEGs) were involved in Cd uptake, transport, and sequestration, and the upregulation of some transporter genes of Zn transporters (ZIPs), a natural resistance associated macrophage protein (Nramp1), a metal–nicotianamine transporter (YSL2), ATP-binding cassette transporters (ABCs), oligopeptide transporters (OPTs), and metallothionein (MTs) and glutathione S-transferase (GSTs) genes was higher in Zn100+Cd100 than in Cd100. In addition, differentially expressed proteins (DEPs) involved in electron transport chain, ATP, and chlorophyll biosynthesis, such as malate dehydrogenases (MDHs), ATPases, and chlorophyll a/b binding proteins, were mostly upregulated in Zn100. The results indicate that Zn supplement increases Cd accumulation and tolerance in S. nigrum by upregulating ATP-dependent Cd transport and sequestration pathways.

Heavy metal pollution has potential hazards to plant, animal, and human health, and phytoremediation is recognized as a safe and efficient technique for the revegetation of heavy-metal-polluted soil. Macleaya cordata was found in heavily tailing areas with fast growth rates, large biomass, and huge taproots. In our study, the seedlings of M. cordata were exposed to cadmium (Cd), lead (Pb), copper (Cu), and zinc (Zn) in a Hoagland solution. After 20 days, the tolerance index as well as the content and distribution of Cd, Pb, Cu, and Zn in roots, stems, and leaves were determined. The results showed M. cordata had higher tolerance to Pb and Zn than to Cd and Cu under hydroponic culture conditions. Pb and Cu mainly accumulated in the roots, and the translocation efficiency to the shoots was very low, while about three-quarters of Zn concentrations in the plants were accumulated in the shoots; even the Cd content per shoot of M. cordata exceeded some Cd hyperaccumulators. In the present study, the metal ions in the roots or leaves of M. cordata were firstly determined in situ using dithizone staining, and the degree of root-tip staining was consistent with the amountof the total metal content in the roots. The addition of Zn or Cu in the Pb treatment solution increased the Pb content in the stems and leaves of M. cordata, while the addition of Zn or Cu in the Cd treatment solution had the opposite effect. Pb or Cd in the compound treatment decreased the Zn content in all parts of M. cordata. Our results suggest that Pb can be transported above ground via some special pathways in M. cordata. The different absorption and transport mechanisms of M. cordata in relation to Cd, Zn, Cu, and Pb can be important for the plant to be applied for the remediation of compound-polluted soil or water.

Background: Macleaya cordata is a traditional medicinal herb, and it has high tolerance and accumulation ability to heavy metals, which make it a good candidate species for studying phytoremediation. The objectives of this study were to investigate response and tolerance of M. cordata to lead (Pb) toxicity based on comparative analysis of transcriptome and proteome. Results: In this study, the seedlings of M. cordata cultured in Hoagland solution were treated with 100 µmol·L^− 1 Pb for 1 day (Pb 1d) or 7 days (Pb 7d), subsequently leaves of M. cordata were taken for the determination of Pb accumulation and hydrogen peroxide production (H₂O₂), meanwhile a total number of 223 significantly differentially expressed genes (DEGs) and 296 differentially expressed proteins (DEPs) were screened between control and Pb treatments. The results showed leaves of M. cordata had a special mechanism to maintain Pb at an appropriate level. Firstly, some DEGs were iron (Fe) deficiency-induced transporters, for example, genes of vacuolar iron transporter and three ABC transporter I family numbers were upregulated by Pb, which can maintain Fe homeostasis in cytoplasm or chloroplast. In addition, five genes of calcium (Ca²⁺) binding proteins were downregulated in Pb 1d, which may regulate cytoplasmic Ca²⁺ concentration and H₂O₂ signaling pathway. On the other hand, the cysteine synthase upregulated, glutathione S-transferase downregulated and glutathione reductase downregulated in Pb 7d can cause reduced glutathione accumulation and decrease Pb detoxification in leaves. Furthermore, DEPs of eight chlorophyll a/b binding proteins, five ATPases and eight ribosomal proteins can play a pivotal role on chloroplast turnover and ATP metabolism. Conclusions: Our results suggest that the proteins involved in Fe homeostasis and chloroplast turnover in mesophyll cells may play key roles in tolerance of M. cordata to Pb. This study offers some novel insights into Pb tolerance mechanism of plants, and the potential valuable for environmental remediation of this important medicinal plant.