Structure-Based Rational and General Strategy for Stabilizing Single-Chain T-Cell Receptors to Enhance Affinity.

The T-cell receptor (TCR) is a crucial molecule in cellular immunity. The single-chain T-cell receptor (scTCR) is a potential format in TCR therapeutics because it eliminates the possibility of αß-TCR mispairing. However, its poor stability and solubility impede the in vitro study and manufacturing of therapeutic applications. In this study, some conserved structural motifs are identified in variable domains regardless of germlines and species. Theoretical analysis helps to identify those unfavored factors and leads to a general strategy for stabilizing scTCRs by substituting residues at exact IMGT positions with beneficial propensities on the consensus sequence of germlines. Several representative scTCRs are displayed to achieve stability optimization and retain comparable binding affinities with the corresponding αß-TCRs in the range of µM to pM. These results demonstrate that our strategies for scTCR engineering are capable of providing the affinity-enhanced and specificity-retained format, which are of great value in facilitating the development of TCR-related therapeutics.

[Effects of Different Water Managements and Soil Eh on Migration and Accumulation of Cd in Rice].

A pot experiment was conducted to study the effects of four modes of water managements on soil Eh values,bioavailability of soil Cd,migration and accumulation of Cd in rice.These four modes of water managements were moistening throughout the entire period of rice growth (M),moistening before filling stage and flooding after filling stage (M-F),flooding before filling stage and moistening after filling stage (F-M),and flooding throughout the entire period of rice growth (F).The results indicated that the exchangeable contents of Cd increased firstly and then declined with the soil Eh values changing from negative to positive.Compared with M,the other three modes (M-F,F-M,and F) significantly reduced the contents of Cd in all rice tissues,including roots,stems,husks and brown rice.Meanwhile,Cd contents in brown rice due to the treatments of M-F and F were 0.19 mg·kg-1 and 0.10 mg·kg-1,respectively.These Cd contents were lower than the limits of 0.2 mg·kg-1 in national food safety standard (GB 2762-2012).Compared with M,the other three modes significantly decreased Cd accumulation amounts in the aboveground parts of rice and also decreased Cd translocation factors in rice.There were significant positive exponential relations between soil Eh values and Cd accumulation amounts in the aboveground parts of rice,Cd translocation factors in rice,or Cd contents in brown rice.The rice biomass due to M-F treatment reached the maximum among the four modes.It was worthy to be mentioned that although Weiyou 46 was considered a variety rice with high Cd accumulation,Cd content in rice brown of Weiyou 46 could be lower than 0.2 mg·kg-1 in the 5 mg·kg-1 of Cd contaminated soil through proper water managements.In summary,M-F treatment ensured high rice yield with low Cd contents in brown rice and could be recommended as the irrigation mode in rice production.Simultaneously,maintaining soil Eh value between -160--130 mV was also important after the filling stage.

Impacts of rapeseed dregs on Cd availability in contaminated acid soil and Cd translocation and accumulation in rice plants.

The objective of the present study was to investigate the effects of rapeseed dregs (RSD, a commonly organic fertilizer in rural China) at application rates of 0, 0.75, 1.5, and 3.0 % on Cd availability in soil and its accumulation in rice plants (Oryza sativa L., Xiangwanxian 12#, and Weiyou 46#) by means of a pot experiment. The results showed that application of RSD resulted in a sharp decrease in the soil TCLP-extractable Cd content. However, the soil TCLP-extractable Cd content in amended soil gradually increased during the rice growing period. Application of RSD significantly increased Cd transport from root to shoot and the amount of Cd accumulated in the aerial part. RSD was an effective organic additive for increasing rice grain yield, but total Cd content in rice grain was also increased. At an application rate of 1.5-3.0 % RSD, the total Cd content in Weiyou 46# brown rice was 0.27-0.31 mg kg-1, which exceeded the standard safe limit (0.2 mg kg-1) and was also higher than that of Xiangwanxian 12# (0.04-0.14 mg kg-1). Therefore, Weiyou 46# had a higher dietary risk than Xiangwanxian 12# with RSD application. We do not recommend planting Weiyou 46# and applying more than 0.75 % RSD in Cd-contaminated paddy fields.

Accumulation of Heavy Metals in Vegetable Species Planted in Contaminated Soils and the Health Risk Assessment.

The objectives of the present study were to investigate heavy metal accumulation in 22 vegetable species and to assess the human health risks of vegetable consumption. Six vegetable types were cultivated on farmland contaminated with heavy metals (Pb, Cd, Cu, Zn, and As). The target hazard quotient (THQ) method was used to assess the human health risks posed by heavy metals through vegetable consumption. Clear differences were found in the concentrations of heavy metals in edible parts of the different vegetables. The concentrations of heavy metals decreased in the sequence as leafy vegetables > stalk vegetables/root vegetables/solanaceous vegetables > legume vegetables/melon vegetables. The ability of leafy vegetables to uptake and accumulate heavy metals was the highest, and that of melon vegetables was the lowest. This indicated that the low accumulators (melon vegetables) were suitable for being planted on contaminated soil, while the high accumulators (leafy vegetables) were unsuitable. In Shizhuyuan area, China, the total THQ values of adults and children through consumption of vegetables were 4.12 and 5.41, respectively, suggesting that the residents may be facing health risks due to vegetable consumption, and that children were vulnerable to the adverse effects of heavy metal ingestion.

[Synergetic Control of Bioavailability of Pb, Cd and As in the Rice Paddy System by Combined Amendments].

This paper studied the effects of applying two combined amendments LST (limestone+meerschaum+titanium dioxide) and LSF (limestone+meerschaum+ferric sulfate) at different ratios of 0, 1, 2, 4, 8 and 16 g·kg-1 on bioavailability Pb, Cd and As in paddy soil and bioaccumulation in rice plants through a pot experiment planting rice. The results indicated that: 1Compared with the control, applying LST and LSF could both significantly increase soil pH values (P<0.05), and LST increased the soil pH values more. 2Applying combined amendments LST and LSF with the amount of 1-16 g·kg-1 decreased exchangeable contents of soil Pb, Cd and As significantly by 16.8%-88.3%, 22.4%-73.7%, 2.25%-43.8%, and 20.2%-86.9%, 20.7%-51.2%, 18.0%-55.1%, respectively. LST and LSF significantly decreased contents of Pb, Cd and As of rice root, shoot, husk and brown rice. When the applying amount of LST and LSF was 16 g·kg-1, the contents of Pb, Cd and As in brown rice decreased by 50.7%, 64.7%, 34.1%, and 40.7%, 40.7%, 36.2%, respectively. 3The ability of rice organs transferring Pb and As was husk>rice straw>root, and that transferring Cd was husk >root >rice straw. The ability to transfer Pb, Cd and As from rice straw to brown rice was Cd >As >Pb. 4After applying LST and LSF, a significant positive relationship was observed between contents of Pb, Cd and As in brown rice and exchangeable contents of these elements in soil. Between contents of Pb, Cd and As in brown rice and soil pH values, there was a significant negative correlation.