Competition of Cd(II) and Pb(II) on the bacterial cells: a new insight from bioaccumulation based on NanoSIMS imaging.

Polymetallic exposure causes complex toxicity to microorganisms. In this study, we investigated the responses of Escherichia coli under co-existence of cadmium (Cd) and lead (Pb), primarily based on biochemical analysis and RNA sequencing. Cd completely inhibited bacterial growth at a concentration of 2.41 mmol/L, with its removal rate as low as <10%. In contrast, the Pb removal rate was >95% under equimolar sole Pb stress. In addition, the Raman analysis confirmed the loss of proteins for the bacterial cells. Under the co-existence of Cd and Pb, the Cd toxicity to E. coli was alleviated. Meanwhile, the biosorption of Pb cations was more intense during the competitive sorption with Cd. Transmission electron microscopy images showed that a few cells were elongated during incubation, i.e., the average cellular length increased from 1.535 ± 0.407 to 1.845 ± 0.620 µm. Moreover, NanoSIMS imaging showed that the intracellular distribution of Cd and Pb was coupled with sulfur. Genes regulating sulfate transporter were also upregulated to promote sulfate assimilation. Then, the subsequent production of biogenic sulfide and sulfur-containing amino acids was enhanced. Although this strategy based on S enrichment could resist the polymetallic stress, not all related genes were induced to upregulate under sole Cd stress. Therefore, the S metabolism might remodel the microbial resistance to variable occurrence of heavy metals. Furthermore, the competitive sorption (in contrast to sole Cd stress) could prevent microbial cells from strong Cd toxicity.IMPORTANCEMicrobial tolerance and resistance to heavy metals have been widely studied under stress of single metals. However, the polymetallic exposure seems to prevail in the environment. Though microbial resistance can alleviate the effects of exogenous stress, the taxonomic or functional response to polymetallic exposure is still not fully understood. We determined the strong cytotoxicity of cadmium (Cd) on growth, and cell elongation would be driven by Cd stress. The addition of appropriate lead (Pb) showed a stimulating effect on microbial bioactivity. Meanwhile, the biosorption of Pb was more intense during co-existence of Pb and Cd. Our work also revealed the spatial coupling of intracellular S and Cd/Pb. In particular, the S assimilation was promoted by Pb stress. This work elucidated the microbial responses to polymetallic exposure and may provide new insights into the antagonistic function during metal stresses.

Heterogeneous Photocatalytic Recycling of FeX2 /FeX3 for Efficient Halogenation of C-H Bonds Using NaX.

Environmental-friendly halogenation of C-H bonds using abundant, non-toxic halogen salts is in high demand in various chemical industries, yet the efficiency and selectivity of laboratory available protocols are far behind the conventional photolytic halogenation process which uses hazardous halogen sources. Here we report an FeX2 (X=Br, Cl) coupled semiconductor system for efficient, selective, and continuous photocatalytic halogenation using NaX as halogen source under mild conditions. Herein, FeX2 catalyzes the reduction of molecular oxygen and the consumption of generated oxygen radicals, thus boosting the generation of halogen radicals and elemental halogen for direct halogenation and indirect halogenation via the formation of FeX3 . Recycling of FeX2 and FeX3 during the photocatalytic process enables the halogenation of a wide range of hydrocarbons in a continuous flow, rendering it a promising method for applications.

Creating and Stabilizing an Oxidized Pd Surface under Reductive Conditions for Photocatalytic Hydrogenation of Aromatic Carbonyls.

Photocatalysis provides an eco-friendly route for the hydrogenation of aromatic carbonyls to O-free aromatics, which is an important refining process in the chemical industry that is generally carried out under high pressure of hydrogen at elevated temperatures. However, aromatic carbonyls are often only partially hydrogenated to alcohols, which readily desorbs and are hardly further deoxygenated under ambient conditions. Here, we show that by constructing an oxide surface over the Pd cocatalyst supported on graphitic carbon nitride, an alternative hydrogenation path of aromatic carbonyls becomes available via a step-wise acetalization and hydrogenation, thus allowing efficient and selective production of O-free aromatics. The PdO surface allows for optimum adsorption of reactants and intermediates and rapid abstraction of hydrogen from the alcohol donor, favoring fast acetalization of the carbonyls and their consecutive hydrogenation to O-free hydrocarbons. The photocatalytic hydrogenation of benzaldehyde into toluene shows a high selectivity of >90% and a quantum efficiency of ∼10.2% under 410 nm irradiation. By adding trace amounts of HCl to the reaction solution, the PdO surface remains stable and active for long-term operation at high concentrations, offering perspective for practical applications.

Copper Cocatalyst Modulated Radical Generation for Selective Heterogeneous Photosynthesis of α-Haloketones.

The α-haloketones are important precursors for synthetic chemistry and pharmaceutical applications; however, their production relies heavily on traditional synthetic methods via halogenation of ketones that are toxic and environmentally risky. Here, we report a heterogeneous photosynthetic strategy of α-haloketone production from aromatic olefins using copper-modified graphitic carbon nitride (Cu-C3N4) under mild reaction conditions. By employing NiX2 (X = Cl, Br) as the halogen source, a series of α-haloketones can be synthesized using atmospheric air as the oxidant under visible-light irradiation. In comparison with pristine carbon nitride, the addition of Cu as a cocatalyst provides a moderate generation rate of halogen radicals and selective reduction of molecular oxygen into •OOH radicals, thus leading to a high selectivity to α-haloketones. The Cu-C3N4 also exhibits high stability and versatility, rendering it a promising candidate for solar-driven synthetic applications.

Extracting extracellular polymeric substances from fungi in contrasts: from quantity to quality.

Many fungi are able to produce extracellular polymeric substances (EPS) for environmental, food, and industrial applications. This study evaluated the extraction (in vivo) of EPS from Rhodotorula mucilaginosa, a typical yeast with abundant EPS. Three extracting methods were set, i.e., heating, addition of NaCl during heating, and cation exchange resin (CER). The abundance of extracted proteins and polysaccharides showed evident contrasts (elevated to ~ 600 and 1700 mg/L, respectively) after heating at 70 °C in water. Although the higher temperature will increase the extracted abundance of EPS, the leakage of DNA would be enhanced due to cell rupture. The addition of NaCl further promoted the efficiency of extraction, either for proteins (from ~ 550 to ~ 650 mg/L) or polysaccharides (from ~ 1700 to ~ 2010 mg/L). Moreover, the biochemical results showed that the extracted abundance of EPS via heating was dramatically higher than that via CER. Additionally, DNA leakage in the CER treatment (2.0 g/g DW) was significantly higher (up to > 6 mg/L) than that under heating at 70 °C (< 2 mg/L). Furthermore, the three-dimensional excitation-emission matrix spectra showed two characteristic peaks of emission/excitation wavelength at 280/300 and 280/350, suggesting the relative high diversity of organic matters in EPS after heating treatments. Finally, a fluctuation of polysaccharide abundance in EPS at 500-1500 mg/L Pb2+ level was elucidated by the extraction based on heating treatment. This study hence confirmed that the heating method might be recommended for extraction of EPS from fungi in vivo KEY POINTS: • 3D-EEM results indicated that heating could extract more EPS compared with CER. • Heating treatments showed lower DNA leakage from fungi than CER treatments. • Addition of NaCl promoted the detachment of EPS from fungal cells in vivo.

Photocatalytic Abstraction of Hydrogen Atoms from Water Using Hydroxylated Graphitic Carbon Nitride for Hydrogenative Coupling Reactions.

Employing pure water, the ultimate green source of hydrogen donor to initiate chemical reactions that involve a hydrogen atom transfer (HAT) step is fascinating but challenging due to its large H-O bond dissociation energy (BDEH-O =5.1 eV). Many approaches have been explored to stimulate water for hydrogenative reactions, but the efficiency and productivity still require significant enhancement. Here, we show that the surface hydroxylated graphitic carbon nitride (gCN-OH) only requires 2.25 eV to activate H-O bonds in water, enabling abstraction of hydrogen atoms via dehydrogenation of pure water into hydrogen peroxide under visible light irradiation. The gCN-OH presents a stable catalytic performance for hydrogenative N-N coupling, pinacol-type coupling and dehalogenative C-C coupling, all with high yield and efficiency, even under solar radiation, featuring extensive impacts in using renewable energy for a cleaner process in dye, electronic, and pharmaceutical industries.

Tumor-Derived Extracellular Vesicles: Their Role in Immune Cells and Immunotherapy.

Nowadays, tumor has been the serious threat to human health and life. To further explore the mechanism of tumor genesis and development is necessarily for developing the effective treatment strategy. Extracellular vesicles are the vesicles secreted by almost all types of cells, and they play an important part in intercellular communication by transporting their cargoes. Immune cells are the vital components of the human defense system, which defense against infection and tumor through cytotoxicity, immune surveillance, and clearance. However, via release tumor-derived extracellular vesicles, tumor could induce immune cells dysfunction to facilitate its proliferation and metastasis. Studies have shown that tumor-derived extracellular vesicles play dual role on immune cells by their specific cargoes. Here, we reviewed the effects of tumor-derived extracellular vesicles on immune cells in recent years and also summarized their research progress in the tumor immunotherapy and diagnosis.

Clay-assisted protection of Enterobacter sp. from Pb (II) stress.

Clay minerals can adsorb both microorganisms and heavy metals. In this study, typical soil bacterium, Enterobacter sp. was applied to investigate the potential protection of the bacterial cells from Pb2+ stress by clay minerals. The sorption by two representative types of montmorillonite (Mt) were contrasted, i.e., Mts/Mtw with strong/weak CEC. There was no significant difference between the two clay minerals regarding their adsorption of Pb2+ cations in water (i.e., ~55 mg L-1). However, the sorption of bacterial cells on the two clay minerals showed evident contrasts, which resulted in the different capacity of Pb sorption. Mts with high CEC preferentially adsorbed abundant bacterial cells (rather than Pb2+) on its surface. The residual Pb2+ concentration in solution actually raised by 7.5% after the addition of Enterobacter sp. In addition, both the Pb-contaminated cells and "healthy" cells (with low Pb contamination) could be adsorbed onto Mt surface, whereas the latter dominated the adsorbents on Mts. This was due to that the Mts with high CEC could provide more exchangeable cations, building more cation bridging ligands between the microbial cells (whatever the types of cells) and clay surface. Furthermore, the adsorbed "healthy" bacterial cells might escape from clay surface via "self-liberating" mechanism, i.e., increasing electrostatic repulsion between the bacteria and clay during microbial decomposition of the medium. This study hence elucidated the protection of microorganisms from Pb2+ stress by Mt.

Thrombospondin-4 1186G>C (A387P) is a sex-dependent risk factor for myocardial infarction: a large replication study with increased sample size from the same population.

BACKGROUND: Case-control studies have successfully identified many genetic associations for complex diseases but suffer from lack of reproducibility in the same population. Demonstrating weak genetic effect requires large sample sizes to minimize statistical bias. Based on a study examining 500 myocardial infarction (MI) patients and 500 controls from the genetically isolated Newfoundland population, we previously reported that thrombospondin-4 (THBS-4) 1186G>C variant associates with MI in women. To validate this sex-dependent association with the THBS-4 variant, we analyzed an additional 532 patients and 514 controls from the same population and the combined cohort consisting of 1032 patients and 1014 controls. METHODS: Genotyping of THBS-4 1186G>C was conducted using Taq Man 1186G>C (A3879P) (rs 1866389) genotyping technology on real-time polymerase chain reaction. RESULTS: The genotype distributions of THBS-4 1186G>C in the validation and combined cohorts were similar with those in our initial study, which supports genetic homogeneity in the studied population. The association of the CC genotype with MI in women (odds ratio [OR], 2.96; P = .008) reported in our initial cohort failed to achieve statistical significance in our validation cohort (OR, 1.53; P = .307) but was confirmed in the combined cohort (OR, 2.14; P = .009). In contrast to the results from the initial cohort was a significant association of the CC genotype with later onset MI in the validation (OR, 2.37; P = .029) and combined cohorts (OR, 2.22; P = .011). Moreover, the larger studied population gave statistical power to associate the CC genotype with risk of MI in the total patient population (OR, 1.58; P = .023). CONCLUSION: Homozygosity for the THBS-4 1186C variant is a weak risk factor for MI especially in older women.

Xrcc3 induces cisplatin resistance by stimulation of Rad51-related recombinational repair, S-phase checkpoint activation, and reduced apoptosis.

Eukaryotic cells respond to DNA damage by activation of DNA repair, cell cycle arrest, and apoptosis. Several reports suggest that such responses may be coordinated by communication between damage repair proteins and proteins signaling other cellular responses. The Rad51-guided homologous recombination repair system plays an important role in the recognition and repair of DNA interstrand crosslinks (ICLs), and cells deficient in this repair pathway become hypersensitive to ICL-inducing agents such as cisplatin and melphalan. We investigated the possible role of the Rad51-paralog protein Xrcc3 in drug resistance. Xrcc3 overexpression in MCF-7 cells resulted in 1) a 2- to 6-fold resistance to cisplatin/melphalan, 2) a 2-fold increase in drug-induced Rad51 foci, 3) an increased cisplatin-induced S-phase arrest, 4) decreased cisplatin-induced apoptosis, and 5) increased cisplatin-induced DNA synthesis arrest. Interestingly, Xrcc3 overexpression did not alter the doubling time or cell cycle progression in the absence of DNA damage. Furthermore, Xrcc3 overexpression is associated with increased Rad51C protein levels consistent with the known interaction of these two proteins. Our results demonstrate that Xrcc3 is an important factor in DNA cross-linking drug resistance in human tumor cells and suggest that the response of the homologous recombinational repair machinery and cell cycle checkpoints to DNA cross-linking agents is intertwined.

Regulation of cisplatin resistance and homologous recombinational repair by the TFIIH subunit XPD.

We have recently completed screening of the National Cancer Institute human tumor cell line panel and demonstrated that among four nucleotide excision repair proteins (XPA, XPB, XPD, and ERCC1), only the TFIIH subunit XPD endogenous protein levels correlate with alkylating agent drug resistance. In the present study, we extended this work by investigating the biological consequences of XPD overexpression in the human glioma cell line SK-MG-4. Our results indicate that XPD overexpression in SK-MG-4 cells leads to cisplatin resistance without affecting the nucleotide excision repair activity or UV light sensitivity of the cell. In contrast, in SK-MG-4 cells treated with cisplatin, XPD overexpression leads to increased Rad51-related homologous recombinational repair, increased sister chromatid exchanges, and accelerated interstrand cross-link removal. Moreover, we present biochemical evidence of an XPD-Rad51 protein interaction, which is modulated by DNA damage. To our knowledge, this is the first description of functional cross-talk between XPD and Rad51, which leads to bifunctional alkylating agent drug resistance and accelerated removal of interstrand cross-links.