Enhanced reduction of Cd uptake by wheat plants using iron and manganese oxides combined with citrate in Cd-contaminated weakly alkaline arable soils.

Iron (Fe) and manganese (Mn) oxides can be used to remediate Cd-polluted soils due to their excellent performance in heavy metal adsorption. However, their remediation capability is rather limited, and a higher content of available Mn and Fe in soils can reduce Cd accumulation in wheat plants due to the competitive absorption effect. In this study, goethite and cryptomelane were first respectively used to immobilize Cd in Cd-polluted weakly alkaline soils, and sodium citrate was then added to increase the content of available Mn and Fe content for further reduction of wheat Cd absorption. In the first season, the content of soil-available Cd and Cd in wheat plants significantly decreased when cryptomelane, goethite and their mixture were used as the remediation agents. Cryptomelane showed a better remediation effect, which could be attributed to its higher adsorption performance. The grain Cd content could be decreased from 0.35 mg kg-1 to 0.25 mg kg-1 when the content of cryptomelane was controlled at 0.5%. In the second season, when sodium citrate at 20 mmol kg-1 was further added to the soils with 0.5% cryptomelane treatment in the first season, the content of soil available Cd was increased by 14.8%, and the available Mn content was increased by 19.5%, leading to a lower Cd content in wheat grains (0.16 mg kg-1) probably due to the competitive absorption. This work provides a new strategy for the remediation of slightly Cd-polluted arable soils with safe and high-quality production of wheat.

Mechanism for Fe(III) to decrease cadmium uptake of wheat plant: Rhizosphere passivation, competitive absorption and physiological regulation.

The presence of dissolved Fe(III) and Fe(III)-containing minerals has been found to alleviate cadmium (Cd) accumulation in wheat plants grown in Cd-contaminated soils, but the specific mechanism remains elusive. In this work, hydroponic experiments were conducted to dissect the mechanism for dissolved Fe(III) (0-2000 µmol L-1) to decrease Cd uptake of wheat plants and study the influence of Fe(III) concentration and Cd(II) pollution level (0-20 µmol L-1) on the Cd uptake process. The results indicated that dissolved Fe(III) significantly decreased Cd uptake through rhizosphere passivation, competitive absorption, and physiological regulation. The formation of poorly crystalline Fe(III) oxides facilitated the adsorption and immobilization of Cd(II) on the rhizoplane (over 80.4 %). In wheat rhizosphere, the content of CaCl2-extractable Cd decreased by 52.7 % when Fe(III) concentration was controlled at 2000 µmol L-1, and the presence of Fe(III) may reduce the formation of Cd(II)-organic acid complexes (including malic acid and succinic acid secreted by wheat roots), which could be attributed to competitive reactions. Down-regulation of Cd uptake genes (TaNramp5-a and TaNramp5-b) and transport genes (TaHMA3-a, TaHMA3-b and TaHMA2), along with up-regulation of the Cd efflux gene TaPDR8-4A7A, contributed much to the reduction of Cd accumulation in wheat plants in the presence of Fe(III). The inhibitory effect of Fe(III) on Cd uptake and transport in wheat plants declined with increasing Cd(II) concentration, particularly at 20 µmol L-1. This work provides important implications for remediating Cd-contaminated farmland soil and ensuring the safe production of wheat by using dissolved Fe(III) and Fe(III)-containing minerals.

Mechanisms for synergistically enhancing cadmium remediation performance of biochar: Silicon activation and functional group effects.

This work proposes an advanced biochar material (ß-CD@SiBC) for controllable transformation of specific silicon (Si) forms through endogenous Si activation and functional group introduction for efficient cadmium (Cd) immobilization and removal. The maximum adsorption capacity of ß-CD@SiBC for Cd(II) reached 137.6 mg g-1 with a remarkable removal efficiency of 99 % for 200 mg L-1Cd(II). Moreover, the developed ß-CD@SiBC flow column exhibited excellent performance at the environmental Cd concentration, with the final concentration meeting the environmental standard for surface water quality (0.05 mg L-1). The remediation mechanism of ß-CD@SiBC could be mainly attributed to mineral precipitation and ion exchange, which accounted for 42 % and 29 % of the remediation effect, respectively, while functional group introduction enhanced its binding stability with Cd. Overall, this work proposes the role and principle of transformation of Si forms within biochar, providing new strategies for better utilizing endogenous components in biomass.

Discovery of novel reversible inhibitor of DprE1 based on benzomorpholine for the treatment of tuberculosis.

About a quarter of the world's population is infected with Mycobacterium tuberculosis, equivalent to about two billion people. With the emergence of multidrug-resistant tuberculosis, those existing anti-tuberculosis drugs no longer meet the demand for cure anymore; there is an urgent need for the development of new anti-tuberculosis drugs. Decaprenylphosphoryl-ß-D-ribose 2´-epimerase (DprE1) has been proven to be a potential antimycobacterial target, and several inhibitors have entered clinical trial. Herein, we designed and synthesized a series of compounds based on the indole and benzomorpholine by using the strategy of scaffold hopping. The preferred compound B18 showed strong antimycobacterial activity in H37Rv and drug-resistant clinical isolates. In addition, compound B18 did not exhibit antimycobacterial efficacy against other species of strains. Subsequently, the target of B18 was identified as DprE1 by analyzing spontaneous compound-resistant mutation data, and a docking study was performed to illustrate the binding mode between B18 and DprE1. In general, compound B18 is compatible to current DprE1 inhibitors, even higher phosphodiesterase 6C selectivity and plasma protein binding rate, which represent a new type of effective reversible DprE1 inhibitor. IMPORTANCE Drug therapy remains the cornerstone of tuberculosis (TB) treatment, yet first-line anti-tuberculosis drugs are associated with significant adverse effects that can compromise patient outcomes. Moreover, prolonged and widespread use has led to an alarming rise in drug-resistant strains of Mycobacterium tuberculosis, including multidrug-resistant [MDR-tuberculosis (TB)] and extensively drug-resistant (XDR-TB) forms. Urgent action is needed to develop novel anti-tuberculosis agents capable of overcoming these challenges. We report that compound B18, a decaprenylphosphoryl-ß-D-ribose 2´-epimerase inhibitor with a benzomorpholine backbone, exhibits potent activity against not only the non-pathogenic strain H37Ra, but also the pathogenic strain H37Rv and clinical MDR and XDR strains. Preliminary druggability studies indicate that B18 possesses high safety and acceptable pharmacokinetic properties, rendering it a promising candidate for further development as a novel anti-tuberculosis agent.

Value of Chemoradiotherapy based on the depth of invasion for the prognosis of oral squamous cell carcinoma / 口腔疾病防治

Objective @#To explore the prognostic value of chemoradiotherapy based on the depth of invasion (DOI) in patients with oral squamous cell carcinoma.@* Methods @#Patients with oral squamous cell carcinoma who received surgical treatment in a hospital from 2008 to 2016 were enrolled. The chi-square test was used to compare the effects of DOI on postoperative cervical lymph node metastasis and local recurrence. The effects of chemoradiotherapy on postoperative cervical lymph node metastasis, local recurrence, and survival were analyzed based on the DOI.@*Results@# A total of 111 patients with oral squamous cell carcinoma were included in this study. The postoperative local recurrence rate (P<0.05) and cervical lymph node metastasis rate (P<0.05) of patients with 5 mm < DOI ≤ 10 mm and DOI > 10 mm were significantly higher than those with DOI ≤ 5 mm. The time of postoperative recurrence was concentrated within two years after the operation. The greater the DOI was, the shorter the time to postoperative recurrence (P<0.05). The addition of postoperative chemoradiotherapy did not significantly improve the postoperative local recurrence rate, cervical lymph node metastasis or survival rate of patients with different DOIs (P > 0.05). @*Conclusion@#DOI has important predictive value for postoperative recurrence, cervical lymph node metastasis and survival rate. However, DOI cannot be used as an independent index to guide whether chemoradiotherapy is needed after oral cancer surgery.

Covalent inhibitors of EZH2: Design, synthesis and evaluation.

The histone lysine methyltransferase EZH2 has been implicated as a key component in cancer development. Up to date, there are only a few EZH2 covalent inhibitors. In this study, a new series of 3-acrylamido-2-methyl-N-((2-oxo-1,2-dihydropyridin-3-yl) methyl) benzamide derivatives were designed, synthesized, and demonstrated to act as EZH2 covalent inhibitors, among which SKLB-03176 was the most potent compound. SAM competition experiments, mass spectrometry, and washing-out assays proved that SKLB-03176 could covalently bind to the SAM pocket of EZH2. Remarkably, SKLB-03176 exhibited weak activity against other targets, such as 5 histone methyltransferases and more than 30 kinases. Besides, it could inhibit the activity of a variety of EZH2 mutants and significantly inhibit the expression of H3K27Me3 in cells. Furthermore, SKLB-03176 showed no cytotoxicity to normal cells. Our data suggested that SKLB-03176 could be used as a promising lead compound for the development of new EZH2 covalent inhibitors and a valuable chemical tool to study the biological functions of EZH2 or PRC2.

Genetic Dissection of Root Angle of Brassica napus in Response to Low Phosphorus.

Plant root angle determines the vertical and horizontal distribution of roots in the soil layer, which further influences the acquisition of phosphorus (P) in topsoil. Large genetic variability for the lateral root angle (root angle) was observed in a linkage mapping population (BnaTNDH population) and an association panel of Brassica napus whether at a low P (LP) or at an optimal P (OP). At LP, the average root angle of both populations became smaller. Nine quantitative trait loci (QTLs) at LP and three QTLs at OP for the root angle and five QTLs for the relative root angle (RRA) were identified by the linkage mapping analysis in the BnaTNDH population. Genome-wide association studies (GWASs) revealed 11 single-nucleotide polymorphisms (SNPs) significantly associated with the root angle at LP (LPRA). The interval of a QTL for LPRA on A06 (qLPRA-A06c) overlapped with the confidence region of the leading SNP (Bn-A06-p14439400) significantly associated with LPRA. In addition, a QTL cluster on chromosome C01 associated with the root angle and the primary root length (PRL) in the "pouch and wick" high-throughput phenotyping (HTP) system, the root P concentration in the agar system, and the seed yield in the field was identified in the BnaTNDH population at LP. A total of 87 genes on A06 and 192 genes on C01 were identified within the confidence interval, and 14 genes related to auxin asymmetric redistribution and root developmental process were predicted to be candidate genes. The identification and functional analyses of these genes affecting LPRA are of benefit to the cultivar selection with optimal root system architecture (RSA) under P deficiency in Brassica napus.