CaAl-Layered Double Hydroxides-Modified Biochar Composites Mitigate the Toxic Effects of Cu and Pb in Soil on Pea Seedlings.

Compound contamination of soil with heavy metals copper (Cu) and lead (Pb) triggered by mining development has become a serious problem. To solve this problem, in this paper, corncob kernel, which is widely available and inexpensive, was used as the raw material of biochar and modified by loading CaAl-layered double hydroxides to synthesize biochar-loaded CaAl-layered double hydroxide composites (CaAl-LDH/BC). After soil remediation experiments, either BC or CaAl-LDH/BC can increase soil pH, and the available phosphorus content and available potassium content in soil. Compared with BC, CaAl-LDH/BC significantly reduced the available content of Cu and Pb in the active state (diethylenetriaminepentaacetic acid extractable state) in the soil, and the passivation rate of Cu and Pb by a 2% dosage of CaAl-LDH/BC reached 47.85% and 37.9%, respectively. CaAl-LDH/BC can significantly enhance the relative abundance of beneficial microorganisms such as Actinobacteriota, Gemmatimonadota, and Luteimonas in the soil, which can help to enhance the tolerance and reduce the enrichment ability of plants to heavy metals. In addition, it was demonstrated by pea seedling (Pisum sativum L.) growing experiments that CaAl-LDH/BC increased plant fresh weight, root length, plant height, catalase (CAT) activity, and protein content, which promoted the growth of the plant. Compared with BC, CaAl-LDH/BC significantly reduced the Cu and Pb contents in pea seedlings, in which the Cu and Pb contents in pea seedlings were reduced from 31.97 mg/kg and 74.40 mg/kg to 2.92 mg/kg and 6.67 mg/kg, respectively, after a 2% dosage of CaAl-LDH/BC, which was a reduction of 90.84% and 91.03%, respectively. In conclusion, compared with BC, CaAl-LDH/BC improved soil fertility and thus the plant growth environment, and also more effectively reduced the mobility of heavy metals Cu and Pb in the soil to reduce the enrichment of Cu and Pb by plants.

Galacturonic acid-capsaicin prodrug for prolonged nociceptive-selective nerve blockade.

There is an urgent clinical need to develop nerve-blocking agents capable of inducing long duration sensory block without muscle weakness or paralysis to treat post-operative and chronic pain conditions. Here, we report a galacturonic acid-capsaicin (GalA-CAP) prodrug as an effective nociceptive-selective axon blocking agent. Capsaicin selectively acts on nociceptive signaling without motor nerve blockade or disruption of proprioception and touch sensation, and the galacturonic acid moiety enhance prodrug permeability across the restrictive peripheral nerve barriers (PNBs) via carrier-mediated transport by the facilitative glucose transporters (GLUTs). In addition, following prodrug transport across PNBs, the inactive prodrug is converted to active capsaicin through linker hydrolysis, leading to sustained drug release. A single injection of GalA-CAP prodrug at the sciatic nerves of rats led to nociceptive-selective nerve blockade lasting for 234 ± 37 h, which is a sufficient duration to address the most intense period of postsurgical pain. Furthermore, the prodrug markedly mitigated capsaicin-associated side effects, leading to a notable decrease in systemic toxicity, benign local tissue reactions, and diminished burning and irritant effects.

Discovery of Novel Potential Insecticide-Resistance Mutations in Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda, is a worldwide agricultural pest that invaded China in 2018, and has developed resistance to multiple insecticides. The evolution of insecticide resistance is facilitated by mutations of target genes responsible for conferring resistance. In this study, amplicon sequencing analyzed 21 sites in six resistance genes. In addition to known mutations, unknown variants were also found, including novel variants: F290C (ace-1 gene, 0.1% frequency), I1040T/V (CHSA gene, 0.1% frequency), A309T (GluCl gene, 0.1% frequency), and I4790T/V (RyR gene, 0.1% frequency). Additionally, molecular docking was employed to investigate the impact of the aforementioned new mutations on insecticide binding to proteins. The analyses indicated that the binding abilities were reduced, similar to the resistance mutations that were reported, implying these novel mutations may confer transitional resistance. This study may provide a foundation for understanding the functions of these novel mutations in the evolutionary processes that drive the emergence of insecticide resistance in this invasive species.

EPAC inhibitor suppresses angiogenesis and tumor growth of triple-negative breast cancer.

AIMS: Exchange protein directly activated by cAMP 1 (EPAC1), a major isoform of guanine nucleotide exchange factors, is highly expressed in vascular endothelia cells and regulates angiogenesis in the retina. High intratumor microvascular densities (MVD) resulting from angiogenesis is responsible for breast cancer development. Downregulation of EPAC1 in tumor cell reduces triple-negative breast cancer (TNBC)-induced angiogenesis. However, whether Epac1 expressed in vascular endothelial cells contributes to angiogenesis and tumor development of TNBC remains elusive. MAIN METHODS: We employed NY0123, a previously identified potent EPAC inhibitor, to explore the anti-angiogenic biological role of EPAC1 in vitro and in vivo through vascular endothelial cells, rat aortic ring, Matrigel plug, and chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) assays, as well as the in vivo xenograft tumor models of TNBC in both chick embryo and mice. KEY FINDINGS: Inhibiting EPAC1 in vascular endothelial cells by NY0123 significantly suppresses angiogenesis and tumor growth of TNBC. In addition, NY0123 possesses a better inhibitory efficacy than ESI-09, a reported specific EPAC inhibitor tool compound. Importantly, inhibiting EPAC1 in vascular endothelia cells regulates the typical angiogenic signaling network, which is associated with not only vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR2) signaling, but also PI3K/AKT, MEK/ERK and Notch pathway. CONCLUSIONS: Our findings support that EPAC1 may serve as an effective anti-angiogenic therapeutic target of TNBC, and EPAC inhibitor NY0123 has the therapeutic potential to be developed for the treatment of TNBC.

Unravelling the removal mechanisms of trivalent arsenic by sulfidated nanoscale zero-valent iron: The crucial role of reactive oxygen species and the multiple effects of citric acid.

The remediation of arsenic-contaminated groundwater by sulfidated nanoscale zero-valent iron (S-nZVI) has raised considerable attention. However, the role of trivalent arsenic (As(III)) oxidation by S-nZVI in oxic conditions (S-nZVI/O2) remains controversial, and the comprehensive effect of citric acid (CA) prevalent in groundwater on As(III) removal by S-nZVI remains unclear. Herein, the mechanisms of reactive oxygen species (ROS) generation and multiple effects of CA on As(III) removal by S-nZVI/O2 were systematically explored. Results indicated that the removal efficiency of As(III) by S-nZVI/O2 (97.81 %) was prominently higher than that by S-nZVI (66.71 %), resulting from the significant production of ROS (mainly H2O2 and OH) under oxic conditions, which played a crucial role in promoting the As(III) oxidation. Additionally, CA had multiple effects on As(III) removal by S-nZVI/O2 system: (i) CA impeded the diffusion of As(III) towards S-nZVI and increased the secondary risk of immobilized As(III) re-releasing into the environment due to the Fe dissolution from S-nZVI; (ii) CA could significantly enhance the yields of OH from 25.29 to 133.00 µM via accelerating the redox cycle of Fe(II)/Fe(III) and increasing the oriented conversion rate of H2O2 to OH; (iii) CA could also enrich the types of ROS (such as O2- and 1O2) in favor of further As(III) oxidation. This study contributed novel findings regarding the control of As(III) contaminated groundwater using S-nZVI technologies.

Quercetin Alleviates Pulmonary Fibrosis in Silicotic Mice by Inhibiting Macrophage Transition and TGF-ß-Smad2/3 Pathway.

Silicosis is a pulmonary disease caused by the inhalation of silica. There is a lack of early and effective prevention, diagnosis, and treatment methods, and addressing silicotic fibrosis is crucial. Quercetin, a flavonoid with anti-carcinogenic, anti-inflammatory, and antiviral properties, is known to have a suppressive effect on fibrosis. The present study aimed to determine the therapeutic effect of quercetin on silicotic mice and macrophage polarity. We found that quercetin suppressed silicosis in mice. It was observed that SiO2 activated macrophage polarity and the macrophage-to-myofibroblast transition (MMT) by transforming the growth factor-ß (TGF-ß)-Smad2/3 signaling pathway in silicotic mice and MH-S cells. Quercetin also attenuated the MMT and the TGF-ß-Smad2/3 signaling pathway in vivo and in vitro. The present study demonstrated that quercetin is a potential therapeutic agent for silicosis, which acts by regulating macrophage polarity and the MMT through the TGF-ß-Smad2/3 signaling pathway.

Resistance monitoring and mechanism in the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) for chlorantraniliprole from Sichuan Province, China.

The fall armyworm, Spodoptera frugiperda (Noctuidae: Lepidoptera), is a wide-reaching notorious insect pest of important cereal crops, which has developed resistance to multiple classes of insecticides. It invaded the Sichuan Province of China in 2019. In this study, we performed resistance monitoring of insecticides for 11 field-collected populations from Sichuan, and all the populations were susceptible to emamectin benzoate and chlorpyrifos. The variations in resistance level to indoxacarb (resistance ratio (RR), 9.23-45.53-fold), spinetoram (RR, 4.32-18.05-fold), and chlorantraniliprole (RR, 2.02-10.39-fold) were observed among these populations. To investigate the resistance mechanism of chlorantraniliprole, synergism tests were performed and showed that piperonyl butoxide had a slight synergistic effect on chlorantraniliprole for the QJ-20 population (1.43-fold) in moderate resistance (RR, 10.39-fold) compared with the treatment group without synergist. Furthermore, the expression scanning for resistance-related genes showed that five P450 genes (CYP6AE43, CYP321A8, CYP305A1, CYP49A1, and CYP306A1) and the ryanodine receptor gene (Ryr, chlorantraniliprole target) were overexpressed in the QJ-20 population. These results indicated that the fall armyworm in Sichuan has exhibited diverse susceptibilities to several classes of insecticides, and the overexpression of Ryr and several P450 genes may contribute to the development of resistance in S. frugiperda to chlorantraniliprole.

Selective removal of total Cr from a complex water matrix by chitosan and biochar modified-FeS: Kinetics and underlying mechanisms.

Cr(VI) is difficult to remove from wastewater via a one-step method because it is a type of oxyanion. Developing ARPs to selectively remove total Cr is critical for Cr(VI) remediation, including Cr(VI) adsorption-reduction and Cr(III) complexation. Hereon, chitosan and biochar modified-FeS (CTS-FeS@BC) was prepared to apply in the selective removal of total Cr from wastewaters. The results showed that the activity of amorphous FeS on CTS-FeS@BC for Cr(VI) removal (110.0 mg/g FeS) was significantly enhanced by CTS and BC, and efficiency was inhibited slightly by many anions and humic acid (HA). Meanwhile, the removal of total Cr by CTS-FeS@BC (99.1 mg/g FeS) via ARPs was improved by 1.2 and 40.3 times when compared with CTS-FeS and raw FeS, respectively. Besides, CTS-FeS@BC exhibited an outstanding selectivity for total Cr removal in metal cations-Cr binary solutions and in a complex water matrix. The mechanism of ARPs on CTS-FeS@BC demonstrated by the results of the 1,10-phenanthroline experiment and the distribution of Cr species was that Cr(VI) was first adsorbed by outer-sphere complexation for reduction, and then adsorbed Cr(III) combined with Fe(III) species to generate Fe(III)-Cr(III) complex for total Cr removal. Overall, this study provides an ARP to effectively solve Cr pollution in wastewaters.

A Sensitive and Flexible Capacitive Pressure Sensor Based on a Porous Hollow Hemisphere Dielectric Layer.

Capacitive pressure sensors based on porous structures have been widely researched and applied to a variety of practical applications. To date, it remains a big challenge to develop a capacitive pressure sensor with a high sensitivity and good linearity over a wide pressure range. In this paper, a sensitive, flexible, porous capacitive pressure sensor was designed and manufactured by means of the "salt template method" and man-made grooves. To this aim, the size of the salt particles used for forming pores/air voids, time taken for thorough dissolution of salt particles, and the depth of the man-made groove by a pin were taken into consideration to achieve a better effect. With pores and the groove, the sensor is more liable be compressed, which will result in a dramatic decrease in distance between the two electrodes and a conspicuous increase of the effective dielectric constant. The optimize-designed sensor represents a sensitivity 6-8 times more than the sensor without the groove in the pressure range of 0-10 kPa, not to mention the sensor without pores or the groove, and it can keep good linearity within the measurement range (0-50 kPa). Besides, the sensor shows a low detection limit of 3.5 Pa and a fast response speed (≈50 ms), which makes it possible to detect a tiny applied pressure immediately. The fabricated sensor can be applied to wearable devices to monitor finger and wrist bending, and it can be used in the object identification of mechanical claws and object cutting of mechanical arms, and so on.

MgxCu-biochar activated peroxydisulfate triggers reductive species for the reduction and enhanced electron-transfer degradation of electron-deficient aromatic pollutants.

In wastewater treatment by persulfate-based advanced oxidation processes (PS-AOPs), electron-deficient aromatic pollutants (EDAPs) are refractory to nonradical pathway. To explore an efficient degradation pathway for EDAPs, MgxCu-biochar (BC) (x = 0.5, 1, 1.5) activated peroxydisulfate (PDS) was developed, which could trigger reductive species (•H) to reduce EDAPs first, and subsequently facilitate electron-transfer degradation of reduced intermediates. The roles of Mg-doping in MgxCu-BC to promote PDS activation and 2,4-dibromophenol (DBP) degradation were investigated. The mechanisms were then explored via electron paramagnetic resonance (EPR), chemical probes and Density Functional Theory (DFT) calculations. The results showed that Mg-doping improved metal-support interactions (MSIs) of MgxCu-BC, inducing •H formation via electron transfer from Cu atoms during PDS activation, which was thermodynamically favorable. The degradation rate of DBP (kobs, 0.0494 min-1) and Br- release (5.35 mg L-1) in Mg1Cu-BC systems were more 31 and 33 times than that in Cu-BC/PDS system, respectively. The degradation mechanism of •H-enhanced electron transfer processes was that •H attacked one Br group of DBP, and then debrominated intermediates were mineralized by electron transfer processes in the Mg1Cu-BC/PDS system. Overall, this study reports a novel pathway in PS-AOPs for selective degradation of EDAPs in wastewaters.

Remediation of Cu and As contaminated water and soil utilizing biochar supported layered double hydroxide: Mechanisms and soil environment altering.

Preparing materials for simultaneous remediation of anionic and cationic heavy metals contamination has always been the focus of research. Herein a biochar supported FeMnMg layered double hydroxide (LDH) composites (LB) for simultaneous remediation of copper and arsenic contamination in water and soil has been assembled by a facile co-precipitation approach. Both adsorption isotherm and kinetics studies of heavy metals removal by LB were applied to look into the adsorption performance of adsorbents in water. Moreover, the adsorption mechanisms of Cu and As by LB were investigated, showing that Cu in aqueous solution was removed by the isomorphic substitution, precipitation and electrostatic adsorption while As was removed by complexation. In addition, the availability of Cu and As in the soil incubation experiments was reduced by 35.54%-63.00% and 8.39%-29.04%, respectively by using LB. Meanwhile, the addition of LB increased the activities of urease and sucrase by 93.78%-374.35% and 84.35%-520.04%, respectively, of which 1% of the dosage was the best. A phenomenon was found that the richness and structure of microbial community became vigorous within 1% dosage of LB, which indirectly enhanced the passivation and stabilization of heavy metals. These results indicated that the soil environment was significantly improved by LB. This research demonstrates that LB would be an imaginably forceful material for the remediation of anionic and cationic heavy metals in contaminated water and soil.

Regulating the exposed crystal facets of α-Fe2O3 to promote Fe2O3-modified biochar performance in heavy metals adsorption.

α-Fe2O3 modified biochar (Fe2O3/BC) was prepared to remove Cu(II), Pb(II) and As(V). By adjusting the calcination temperature, the morphology and exposed crystal facets of α-Fe2O3 on the biochar were changed which further affected the adsorption performance. The kinetics and isotherms were investigated systematically to reveal adsorption effect of the adsorbent on Cu(II), Pb(II) and As(V). The results indicated that chemisorption process was the dominant adsorption mechanism. Fe2O3/BC-350 exhibited superior adsorption capacity for Cu(II) (258.22 mg/g) and Pb(II) (390.60 mg/g), and Fe2O3/BC-250 showed relatively good adsorption capacity for As(V) (5.78 mg/g). By adsorption mechanism analysis, electrostatic adsorption, ion exchange, precipitation and complexation were coexisted in the process of removing metal ions by Fe2O3/BC. The repeatability test and the effect of ion strength exhibited the strong stability of Fe2O3/BC. Meanwhile, density functional theory (DFT) calculations manifested that the (202) facet of α-Fe2O3 on Fe2O3/BC-350 possessed the lowest adsorption energies of Cu(II) and Pb(II). While for As(V), it was the (104) facet of α-Fe2O3 on Fe2O3/BC-250 that exhibited the lowest adsorption energy. DFT results revealed that different Fe2O3/BC had different adsorption affinities to various heavy metals. In general, this work not only prepared a promising adsorbent via a simple procedure, but also served as a reference for researchers in designing absorbents with specific active facet for efficient heavy metals remediation.

Multicomponent adsorption of heavy metals onto biogenic hydroxyapatite: Surface functional groups and inorganic mineral facilitating stable adsorption of Pb(â ¡).

Due to the coexistence of various heavy metals in the contaminated environment, it is essential to comprehensively study the multicomponent adsorption of heavy metals in order to tackle these combined pollutants. Herein, the adsorption processes of Pb(Ⅱ), Cu(Ⅱ) and Cd(Ⅱ) by biogenic hydroxyapatite (BHAp) were investigated in single and multicomponent systems. The maximum adsorption capacity for Pb(Ⅱ), Cu(Ⅱ) and Cd(Ⅱ) by BHAp in single system reached 311.16, 82.05 and 92.54 mg g-1, respectively, while adsorption capacity for Cu(Ⅱ) and Cd(Ⅱ) in multicomponent system decreased more obviously than that of Pb(Ⅱ). Furthermore, the stability of Cu(Ⅱ) and Cd(Ⅱ) adsorbed on BHAp was indeed influenced in multicomponent system. By means of the characterization analysis, it was found that ion exchange was more instrumental in the adsorption processes of Cu(Ⅱ) and Cd(Ⅱ) in single system than in multicomponent system. Significantly, it was observed that the proportion of generally stable Pb(II) adsorbed on BHAp exceeded 95% in both single and multicomponent systems. This result might be due to the in-site growth of stable crystals of PbxCa10-x(PO4)6(OH)2, which was synergistically induced by surface functional groups and inorganic mineral of BHAp, and was unaffected by the coexistence of Cu(Ⅱ) and Cd(Ⅱ).

Corynebacterium sp. 2-TD Mediated Toxicity of 2-Tridecanone to Helicoverpa armigera.

Cotton bollworm (Helicoverpa armigera) is a Lepidopteran noctuid pest with a global distribution. It has a wide range of host plants and can harm cotton, tomato, tobacco, and corn, as well as other crops. H. armigera larvae damage the flower buds, flowers, and fruits of tomato and cause serious losses to tomato production. Tomato uses the allelochemical 2-tridecanone to defend against this damage. So far, there have been no reports on whether the adaptation of H. armigera to 2-tridecanone is related to its symbiotic microorganisms. Our study found that Corynebacterium sp. 2-TD, symbiotic bacteria in H. armigera, mediates the toxicity of the 2-tridecanone to H. armigera. Corynebacterium sp. 2-TD, which was identified by 16S rDNA gene sequence analysis, was screened out using a basal salt medium containing a unique carbon source of 2-tridecanone. Then, Corynebacterium sp. 2-TD was confirmed to be distributed in the gut of H. armigera by quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). The survival rate of H. armigera increased by 38.3% under 2-tridecanone stress after inoculation with Corynebacterium sp. 2-TD. The degradation effect of Corynebacterium sp. 2-TD on 2-tridecanone was verified by ultra-high-performance liquid chromatography (UPLC). Our study is the first to report the isolation of gut bacteria that degrade 2-tridecanone from the important agricultural pest H. armigera and to confirm bacterial involvement in host adaptation to 2-tridecanone, which provides new insights into the adaptive mechanism of agricultural pests to host plants.

Mechanisms and influencing factors for electron transfer complex in metal-biochar nanocomposites activated peroxydisulfate.

The mechanisms and influencing factors for electron transfer complex need to be further studied by comparing radical and nonradical pathways. Herein, metal-biochar (BC) nanocomposites including CuO/BC, Fe3O4/BC and ZnO/BC were prepared to activate peroxydisulfate (PDS) for bisphenol A (BPA) degradation. The existence of electron transfer complex in CuO/BC-PDS system were directly demonstrated. Whereas radical pathway was dominant in Fe3O4/BC- and ZnO/BC-PDS systems for BPA degradation. There was a relationship between PDS adsorption and catalytic reaction. The rate-limiting step for BPA degradation in nonradical pathway was PDS adsorption, but in radical pathway was BPA degradation. Interestingly, among metal-BC, CuO/BC had the most effective performance in transformation of adsorbed PDS to electron transfer complex via out-sphere complexation. After pretreatment by PDS solutions, the separated CuO/BC achieved an efficiency of 60% in ensuing BPA degradation without re-addition of PDS. In addition, the activity of electron transfer complex in BPA degradation (kobs > 0.0480 min-1) was not affected by water matrix (e.g., Cl-, HCO3-, natural organic matter (NOM) and actual water bodies), but affected by solution property (i.e., dissolved oxygen and conductivity) and oxidant species. Moreover, in BPA degradation process, nonradical pathway exhibited lower ecotoxicity instead of radical pathway.

Bartonella type IV secretion effector BepC induces stress fiber formation through activation of GEF-H1.

Bartonella T4SS effector BepC was reported to mediate internalization of big Bartonella aggregates into host cells by modulating F-actin polymerization. After that, BepC was indicated to induce host cell fragmentation, an interesting cell phenotype that is characterized by failure of rear-end retraction during cell migration, and subsequent dragging and fragmentation of cells. Here, we found that expression of BepC resulted in significant stress fiber formation and contractile cell morphology, which depended on combination of the N-terminus FIC (filamentation induced by c-AMP) domain and C-terminus BID (Bartonella intracellular delivery) domain of BepC. The FIC domain played a key role in BepC-induced stress fiber formation and cell fragmentation because deletion of FIC signature motif or mutation of two conserved amino acid residues abolished BepC-induced cell fragmentation. Immunoprecipitation confirmed the interaction of BepC with GEF-H1 (a microtubule-associated RhoA guanosine exchange factor), and siRNA-mediated depletion of GEF-H1 prevented BepC-induced stress fiber formation. Interaction with BepC caused the dissociation of GEF-H1 from microtubules and activation of RhoA to induce formation of stress fibers. The ROCK (Rho-associated protein kinase) inhibitor Y27632 completely blocked BepC effects on stress fiber formation and cell contractility. Moreover, stress fiber formation by BepC increased the stability of focal adhesions, which consequently impeded rear-edge detachment. Overall, our study revealed that BepC-induced stress fiber formation was achieved through the GEF-H1/RhoA/ROCK pathway.

[Bioaccessibility and Health Risks of the Heavy Metals in Soil-Rice System of Southwest Fujian Province].

The bioaccessibility and health risks of heavy metals in soil-rice system of southwestern Fujian province were studied by combining a simple bioavailability extraction method (SBET) with a health risk assessment model. The results showed that some heavy metals in the agricultural soils and rice of southwestern Fujian province were enriched. The contents of Cd, Zn, Pb, and Cu were greater than the screening value of soil pollution risk for agricultural land (GB 15618-2018) by 32.4%, 15.5%, 14.1%, and 12.7% in the study areas, respectively. The accumulation ability of heavy metals was different and followed the approximately decreasing order of Cd > Zn > Cu > Ni > Hg > As > Cr > Pb. The bioaccessibility of heavy metals in soils and rice were quite different. The bioaccessibility of each heavy metal in rice was greater than the bioaccessibility of the heavy metals in soil, which indicated that the heavy metals in rice were more easily absorbed by the human body. The comprehensive non-carcinogenic risk index (HI) of heavy metals to adults and children was 2.71 and 4.06, respectively, indicating that there were non-carcinogenic risks. The comprehensive carcinogenic risk index (TCR) of heavy metals to adults and children was 1.42×10-3 and 5.28×10-4, respectively, indicating that there was a carcinogenic risk present. The non-carcinogenic risks were mainly due to As, while the carcinogenic risks were mainly contributed by Cd. The non-carcinogenic risk of children was higher than that of adults, while the carcinogenic risk of children was lower than that of adults. This result may be related to physiological characteristics, exposure period, and dietary intake. The dietary intake route may be the main pathway for heavy metals in the soil-rice system of southwest Fujian province to cause health risks. Therefore, more attention should be paid to the risks of dietary exposure in the risk management of heavy metals.

Bartonella quintana type IV secretion effector BepE-induced selective autophagy by conjugation with K63 polyubiquitin chain.

Bartonella effector proteins (named Beps) are substrates of VirB type IV secretion system for translocation into host cells evolved in Bartonella spp. Among these, BepE has been shown to protect cells from fragmentation effects triggered by other Beps and to promote in vivo dissemination of bacteria from the dermal site of inoculation to the bloodstream. Bacterial pathogens secreted effectors to modulate the interplay with host autophagy, either to combat autophagy to escape its bactericidal effect or to exploit autophagy to benefit intracellular replication. Here, we reported a distinct phenotype that selective autophagy in host cells is activated as a countermeasure, to attack BepE via conjugation with K63 polyubiquitin chain on BepE. We found that ectopic expression of Bartonella quintana BepE specifically induced punctate structures that colocalised with an autophagy marker (LC3-II) in host cells, in addition to filopodia and membrane ruffle formation. Two tandemly arranged Bartonella Intracellular Delivery (BID) domains in the BepE C-terminus, where ubiquitination of sister pairs of lysine residues was confirmed, were essential to activate host cell autophagy. Multiple polyubiquitin chain linkages of K27, K29, K33, and K63 were found to be conjugated at sites of K222 and K365 on BepE, of which K63 polyubiquitination on BepE K365 determined the selective autophagy (p62/SQSTM1 positive autophagy) independent of the PI3K pathway. Colocalisation of BepE with LAMP1 confirmed the maturation of BepE-induced autophagosomes in which BepE were targeted for degradation. Moreover, host cells employed selective autophagy to counter-attack BepE to rescue cells from BepE-induced endocytosis deficiency.