Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Cajaninstilbene acid derivatives conjugated with siderophores of 3-hydroxypyridin-4(1H)-ones as novel antibacterial agents against Gram-negative bacteria based on the Trojan horse strategy.

The low permeability of the outer membrane of Gram-negative bacteria is a serious obstacle to the development of new antibiotics against them. Conjugation of antibiotic with siderophore based on the "Trojan horse strategy" is a promising strategy to overcome the outer membrane obstacle. In this study, series of antibacterial agents were designed and synthesized by conjugating the 3-hydroxypyridin-4(1H)-one based siderophores with cajaninstilbene acid (CSA) derivative 4 which shows good activity against Gram-positive bacteria by targeting their cell membranes but is ineffective against Gram-negative bacteria. Compared to the inactive parent compound 4, the conjugates 45c or 45d exhibits significant improvement in activity against Gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae and especially P. aeruginosa (minimum inhibitory concentrations, MICs = 7.8-31.25 µM). The antibacterial activity of the conjugates is attributed to the CSA derivative moiety, and the action mechanism is by disruption of bacterial cell membranes. Further studies on the uptake mechanisms showed that the bacterial siderophore-dependent iron transport system was involved in the uptake of the conjugates. In addition, the conjugates 45c and 45d showed a lower cytotoxic effects in vivo and in vitro and a positive therapeutic effect in the treatment of C. elegans infected by P. aeruginosa. Overall, our work describes a new class and a promising 3-hydroxypyridin-4(1H)-one-CSA derivative conjugates for further development as antibacterial agents against Gram-negative bacteria.

A TA/Cu2+ Nanoparticle Enhanced Carboxymethyl Chitosan-Based Hydrogel Dressing with Antioxidant Properties and Promoting Wound Healing.

Background: As the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, burns, collisions and other factors. Wound healing in the skin is a long and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public. Methods: Here, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu2+) reinforced by copper ion crosslinked tannic acid (TA/Cu2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu2+ nanoparticles and CMCS-TA/Cu2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings. Results: The introduction of TA/Cu2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days). Conclusion: Experiments have proved that CMCS-TA/Cu2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair.

3-Hydroxypyridin-4(1H)-one Derivatives as pqs Quorum Sensing Inhibitors Attenuate Virulence and Reduce Antibiotic Resistance in Pseudomonas aeruginosa.

The development of quorum sensing inhibitors capable of decreasing the production of virulence factors is an effective strategy to overcome resistance in Pseudomonas aeruginosa due to the less selective pressure exerted on bacteria. In this study, a series of 3-hydroxypyridin-4(1H)-one derivatives bearing a 4-aminomethyl-1,2,3-triazole linker were designed and synthesized as antivirulence agents against P. aeruginosa. The most potent derivative 16e was identified as a selective inhibitor of the pqs system (IC50 = 3.7 µM) and its related virulence factor pyocyanin (IC50 = 2.7 µM). In addition, 16e exhibited moderate biofilm inhibition and significant inhibition of P. aeruginosa motility phenotypes with low cytotoxicity. Compound 16e showed an obvious antibacterial synergistic effect in combination with antibiotics such as ciprofloxacin and tobramycin in in vitro and in vivo Caenorhabditis elegans infection models. Overall, the excellent antivirulence properties of compound 16e make it a potential antibiotic adjuvant for the treatment of P. aeruginosa infections that may be advanced into preclinical development in the future.

Calcineurin suppresses rat H9c2 cardiomyocyteprotective autophagy under chronic intermittent hypoxia by downregulating the AMPK pathway.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes. However, whether calcineurin can regulate cardiomyocyte autophagy under conditions of chronic intermittent hypoxia (CIH) remains unclear. Here, we showed that CIH induced calcineurin activity in H9c2 cells, which attenuated adenosine monophosphate-activated protein kinase (AMPK) signaling and inhibited autophagy. In H9c2 cells, autophagy levels, LC3 expression, and AMPK phosphorylation were significantly elevated under conditions of CIH within 3 days. However, after 5 days of CIH, these effects were reversed and calcineurin activity and apoptosis were significantly increased. The calcineurin inhibitor 17-Allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo- [22.3.1.04,9]octacos-18- ene-2,3,10,16-tetrone (FK506) restored AMPK activation and LC3 expression and attenuated CIH-induced H9c2 cell apoptosis. In contrast, calcineurin overexpression significantly attenuated the increase in LC3 expression and enhanced H9c2 cell apoptosis under conditions of CIH. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9c2 cells expressing a kinase-dead K45R AMPK mutant. Autophagy inhibition abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicate that calcineurin suppresses adaptive autophagy during CIH by downregulating AMPK activation. Our findings reveal the underlying mechanism of calcineurin and autophagy regulation during H9c2 cell survival under conditions of CIH and may provide a new strategy for preventing CIH-induced cardiomyocyte damage.

Accuracy of a clinical decision support system based on the 3-minute diagnostic interview for CAM-defined delirium: A validation study✰.

OBJECTIVE: To evaluate the accuracy of the 3D-DST for delirium assessment in older adults by the nurse researcher. METHODS: The 3D-DST was administered by a trained nurse researcher to assess delirium among eligible older adults (aged ≥70 years). The criteria for identifying delirium was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V). RESULTS: A total of 95 older adults were enrolled in the current study, and 23 patients were identified as positive for delirium by the psychiatrist. The sensitivity and specificity of the 3D-DST were 96% and 94%, respectively. High sensitivities of the 3D-DST were also observed among patients with hypoactive delirium (95%) and those with cognitive impairment (93%). CONCLUSION: The 3D-DST was demonstrated as an appropriate instrument with highly acceptable sensitivities and specificities for delirium detection in hospitalized older patients.

High-precision angular rate detection based on an optomechanical micro hemispherical shell resonator gyroscope.

Cavity optomechanics with picometer displacement measurement resolution has shown vital applications in high-precision sensing areas. In this paper, an optomechanical micro hemispherical shell resonator gyroscope (MHSRG) is proposed, for the first time. The MHSRG is driven by the strong opto-mechanical coupling effect based on the established whispering gallery mode (WGM). And the angular rate is characterized by measuring the transmission amplitude changing of laser coupled in and out from the optomechanical MHSRG based on the dispersive resonance wavelength shift and/or dissipative losses varying. The detailed operating principle of high-precision angular rate detection is theoretically explored and the fully characteristic parameters are numerically investigated. Simulation results show that the optomechanical MHSRG can achieve scale factor of 414.8 mV/ (°/ s) and angular random walk of 0.0555 °/ h1/2 when the input laser power is 3 mW and resonator mass is just 98 ng. Such proposed optomechanical MHSRG can be widely used for chip-scale inertial navigation, attitude measurement, and stabilization.

A tough and mechanically stable adhesive hydrogel for non-invasive wound repair.

Wound healing has been a great challenge throughout human history. Improper treatment for wounds is so easy to lead to infection and a series of serious symptoms, even death. Because of the ability of absorbing fluid and keeping a moist environment, the hydrogel with 3D networks is ideal candidate for wound dressing. More important, it has good biocompatibility. However, most of the hydrogel dressings reported have weak mechanical properties and adhesion properties, which greatly limit their clinical application. Herein, a tough adhesive hydrogel with good mechanical stability for non-invasive wound repair is reported. The hydrogel is composed of polyethylene glycol dimethacrylate (PEGDA), chitosan (CS) and chitin nano-whisker (CW). PEGDA and CS form interpenetrating network hydrogel through free radical polymerization reaction under the UV light. The introduction of CW further enhances the toughness of the hydrogel. The pH-sensitive CS can form adhesion to various materials through topological adhesion. As a wound closure repair material, PEGDA/CS/CW hydrogel not only has the characteristic of effectively closing the wound, defending against invading bacteria, and keeping the wound clean, but also has good tensile and mechanical stability, which is expected to realize the closure and repair of joints and other moving parts of the wound. This adhesive hydrogel is proven a promising material for wound closure repair.

3-Hydroxy-pyridin-4(1H)-ones as siderophores mediated delivery of isobavachalcone enhances antibacterial activity against pathogenic Pseudomonas aeruginosa.

The natural prenylated chalcone isobavachalcone (IBC) shows good antibacterial activity against Gram-positive bacteria but is ineffective against Gram-negative bacteria, most likely due to the outer membrane barrier of Gram-negative bacteria. The Trojan horse strategy has been shown to be an effective strategy to overcome the reduction in the permeability of the outer membrane of Gram-negative bacteria. In this study, eight different 3-hydroxy-pyridin-4(1H)-one-isobavachalcone conjugates were designed and synthesized based on the siderophore Trojan horse strategy. The conjugates exhibited 8- to 32-fold lower minimum inhibitory concentrations (MICs) and 32- to 177-fold lower half-inhibitory concentrations (IC50s) against Pseudomonas aeruginosa PAO1 as well as clinical multidrug-resistant (MDR) strains compared to the parent IBC under iron limitation. Further studies showed that the antibacterial activity of the conjugates was regulated by the bacterial iron uptake pathway under different iron concentration conditions. Studies on the antibacterial mechanism of conjugate 1b showed that it exerts antibacterial activity by disrupting cytoplasmic membrane integrity and inhibiting cell metabolism. Finally, conjugate 1b showed a lower cytotoxic effects on Vero cells than IBC and a positive therapeutic effect in the treatment of bacterial infections caused by Gram-negative bacteria PAO1. Overall, this work demonstrates that IBC can be delivered to Gram-negative bacteria when combined with 3-hydroxy-pyridin-4(1H)-ones as siderophores and provides a scientific basis for the development of effective antibacterial agents against Gram-negative bacteria.

Design and Synthesis of 3-Hydroxy-pyridin-4(1H)-ones-Ciprofloxacin Conjugates as Dual Antibacterial and Antibiofilm Agents against Pseudomonas aeruginosa.

Pseudomonas aeruginosa infections are often complicated by the fact that it can easily form a biofilm that increases its resistance to antibiotics. Consequently, the development of novel antibacterial agents against biofilm-associated drug-resistant P. aeruginosa is urgently needed. Herein, we report a series of 3-hydroxy-pyridin-4(1H)-ones-ciprofloxacin conjugates that were designed and synthesized as dual antibacterial and antibiofilm agents against P. aeruginosa. A potential 2-substituted 3-hydroxy-1,6-dimethylpyridin-4(1H)-one-ciprofloxacin conjugate (5e) was identified and had the best minimum inhibitory concentrations of 0.86 and 0.43 µM against P. aeruginosa 27853 and PAO1 and reduced 78.3% of biofilm formation. In addition, 5e eradicates mature biofilms and kills living bacterial cells that are incorporated into the biofilm. Studies on the antibiofilm mechanism of conjugates showed that 5e interferes with iron uptake by bacteria, inhibits their motility, and reduces the production of virulence. These results demonstrate that 3-hydroxy-pyridin-4(1H)-ones-ciprofloxacin conjugates are potent in the treatment of biofilm-associated drug-resistant P. aeruginosa infections.

Discovery of BRAF/HDAC Dual Inhibitors Suppressing Proliferation of Human Colorectal Cancer Cells.

The combination of histone deacetylase inhibitor and BRAF inhibitor (BRAFi) has been shown to enhance the antineoplastic effect and reduce the progress of BRAFi resistance. In this study, a series of (thiazol-5-yl)pyrimidin-2-yl)amino)-N-hydroxyalkanamide derivatives were designed and synthesized as novel dual inhibitors of BRAF and HDACs using a pharmacophore hybrid strategy. In particular, compound 14b possessed potent activities against BRAF, HDAC1, and HDAC6 enzymes. It potently suppressed the proliferation of HT-29 cells harboring BRAFV600E mutation as well as HCT116 cells with wild-type BRAF. The dual inhibition against BRAF and HDAC downstream proteins was validated in both cells. Collectively, the results support 14b as a promising lead molecule for further development and a useful tool for studying the effects of BRAF/HDAC dual inhibitors.

Nitrogen-doped carbon@TiO2 double-shelled hollow spheres as an electrochemical sensor for simultaneous determination of dopamine and paracetamol in human serum and saliva.

As the most commonly used antipyretic and analgesic drug, paracetamol (PA) coexists with neurotransmitter dopamine (DA) in real biological samples. Their simultaneous determination is extremely important for human health, but they also interfere with each other. In order to improve the conductivity, adsorption affinity, sensitivity, and selectivity of TiO2-based electrochemical sensor, N-doped carbon@TiO2 double-shelled hollow sphere (H-C/N@TiO2) is designed and synthesized by simple alcoholic and hydrothermal method, using polystyrene sphere (PS) as a template. Meanwhile, TiO2 hollow spheres (H-TiO2) or N-doped carbon hollow spheres (H-C/N) are also prepared by the same method. H-C/N@TiO2 has good conductivity, charge separation, and the highly enhanced and stable current responses for the detection of PA and DA. The detection limit and linear range are 50.0 nmol/L and 0.3-50 µmol/L for PA, 40.0 nmol/L and 0.3-50 µmol/L for DA, respectively, which are better than those of carbon-based sensors. Moreover, this electrochemical sensor, with high selectivity, strong anti-interference, high reliability, and long time durability, can be used for the simultaneous detection of PA and DA in human blood serum and saliva. The high electrochemical performance of H-C/N@TiO2 is attributed to the multi-functional combination of different layers, because of good conductivity, absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO2.

High-FOM Temperature Sensing Based on Hg-EIT-Like Liquid Metamaterial Unit.

High-performance temperature sensing is a key technique in modern Internet of Things. However, it is hard to attain a high precision while achieving a compact size for wireless sensing. Recently, metamaterials have been proposed to design a microwave, wireless temperature sensor, but precision is still an unsolved problem. By combining the high-quality factor (Q-factor) feature of a EIT-like metamaterial unit and the large temperature-sensing sensitivity performance of liquid metals, this paper designs and experimentally investigates an Hg-EIT-like metamaterial unit block for high figure-of-merit (FOM) temperature-sensing applications. A measured FOM of about 0.68 is realized, which is larger than most of the reported metamaterial-inspired temperature sensors.

Research on the reflection-type ELC-based optomechanical metamaterial.

In this paper, we propose a new kind of optomechanical metamaterial based on a planar ELC-type absorbing structure fabricated on the low-loss flexible substrate. The nonlinear coupling mechanism and nonlinear response phenomenon of the proposed optomechanical metamaterial driven by electromagnetic induced force are analyzed theoretically. The mechanical deformation/displacement and the mechanical resonance frequency shift of the metamaterial unit deposed on the flexible substrate are also numerically and experimentally demonstrated to reveal the coupling phenomenon of electromagnetic field and mechanical field. These results will help researchers to further understand the multi-physics interactions of optomechanical metamaterials and will promote the developments of new type of metasurface for high-efficiency dynamic electromagnetic wave controlling and formatting.

Discovery of the First Examples of Threonine Tyrosine Kinase PROTAC Degraders.

The first examples of threonine tyrosine kinase (TTK) PROTACs were designed and synthesized. Two of the most potent molecules, 8e and 8j, demonstrated strong TTK degradation in COLO-205 human colorectal cancer cells with DC50 values of 1.7 and 3.1 nM, respectively. Proteasome-mediated degradation by the compounds could last for approximately 8 h after washout. The degraders 8e and 8j demonstrated improved antiproliferative activities comparing with the structurally similar inhibitor counterparts 8q and 8r. Degraders 8e and 8j also demonstrated reasonable PK profiles and exhibited potent target degradation and in vivo anticancer efficacy in a xenograft mouse model of COLO-205 human colorectal cancer cells upon i.p. administration.

Long-term stable, high accuracy, and visual detection platform for In-field analysis of nitrite in food based on colorimetric test paper and deep convolutional neural networks.

Nitrite is one of the most common carcinogens in daily food. Its simple, rapid, inexpensive, and in-field measurement is important for food safety, based on the requirements of the standard from Codex Alimentarius Commission and China. Using polyacrylonitrile (PAN) and thin layer silica gel (SG), p-aminophenylcyclic acid (SA) and naphthalene ethylenediamine hydrochloride (NEH), as carriers and chromogenic agents, respectively, PAN-NSS as nitrite color sensor is proposed. After fixing and protecting of SA and NEH with layer-upon-layer PAN, the validity period of the test paper can be prolonged from 7 days to more than 30 days. The reproducibility of PAN-NSS preparation is ensured by electrospinning. Combined with PAN-NSS, deep convolutional neural network (DCNN) and APP as a visual monitoring platform, which has the functions of rapid sampling, data processing and transmission, intuitive feedback, etc., and provides a fully integrated detection system for field detection.

NDMA reduction mechanism of UDMH by O3/PMS technology.

Carcinogenic N, N-Dimethylnitrosamine (NDMA) has been reported to generate significantly during ozonation of fuel additive unsymmetrical dimethylhydrazine (UDMH), the combined ozone/Peroxy-Monosulfate (O3/PMS) technology was tried for reducing its formation in this study. The influence of PMS dosages, ozone concentrations, pH, Br- and humic acid (HA) on NDMA formation from UDMH were investigated. In addition, the reduction mechanisms were explored by intermediates identification and Gaussian calculation. The results demonstrated that O3/PMS technology was effective on NDMA reduction, reaching an efficiency of 81% with 80 µM PMS. Higher NDMA reduction rates were achieved by O3/PMS with increasing pH within the scope of research (from 5 to 9), achieving a maximum of 69.9% at pH 9. The presence of bromide ion facilitated NDMA generation during ozonation, but the reduction efficiency by O3/PMS slightly improved from 66.3% to 70.6%. The presence of HA reduced NDMA formation in O3/PMS system. The contribution of SO4•- on NDMA reduction accounted for ~64%, which was higher than that of •OH (41.4%); however, its promotion role on conversing UDMH to NDMA was lower than O3. Therefore, the technology could reduce NDMA formation effectively. In addition, the results of Gaussian calculation manifested that the N atom in -NH2 group of UDMH was easily attacked not only by •OH but also by O3, so it is the key path that determines final NDMA formation. This study would provide reference for reducing NDMA formation during ozonation of UDMH-containing water matrixes.

Nitrogen-doped carbon@TiO2 double-shelled hollow spheres as an electrochemical sensor for simultaneous determination of dopamine and paracetamol in human serum and saliva / 药物分析学报

As the most commonly used antipyretic and analgesic drug,paracetamol(PA)coexists with neuro-transmitter dopamine(DA)in real biological samples.Their simultaneous determination is extremely important for human health,but they also interfere with each other.In order to improve the conductivity,adsorption affinity,sensitivity,and selectivity of TiO2-based electrochemical sensor,N-doped carbon@-TiO2 double-shelled hollow sphere(H-C/N@TiO2)is designed and synthesized by simple alcoholic and hydrothermal method,using polystyrene sphere(PS)as a template.Meanwhile,TiO2 hollow spheres(H-TiO2)or N-doped carbon hollow spheres(H-C/N)are also prepared by the same method.H-C/N@TiO2 has good conductivity,charge separation,and the highly enhanced and stable current responses for the detection of PA and DA.The detection limit and linear range are 50.0 nmol/L and 0.3-50 μmol/L for PA,40.0 nmol/L and 0.3-50 μmol/L for DA,respectively,which are better than those of carbon-based sen-sors.Moreover,this electrochemical sensor,with high selectivity,strong anti-interference,high reli-ability,and long time durability,can be used for the simultaneous detection of PA and DA in human blood serum and saliva.The high electrochemical performance of H-C/N@TiO2 is attributed to the multi-functional combination of different layers,because of good conductivity,absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO2.

Microstructure and Soil Wear Resistance of D517 Coating Deposited by Electric Spark Deposition.

The abrasion failure is the key factor for prolonging the service life and energy saving of furrow openers. The hardness enhancement was reported to be an effective strategy to increase the wear resistance against the soil abrasion. D517 coatings were deposited on Q235 steel by electric spark to improve the wear-resistant property with an affordable cost for farmers. The wear behavior of the coatings was characterized in a pin on disk friction equipment and a homemade soil abrasion simulation system. The soil adhesion, which is highly related to energy consumption, was also evaluated. Results showed that D517 coatings revealed dendrite structure with some randomly distributed carbides. The electric current exerted a great influence on the microstructure, hardness, friction coefficient, and soil wear rate. The wear rate of samples deposited with 80 A and 90 A reduced to 79% and 84%, respectively, as compared with the normalized heat-treated 65 Mn steel after 6 h in soil. This work provides a promising solution to increase the wear resistance of furrow openers. It needs to be noted that the coating would increase the soil adhesion of the opener, which needs to be further explored to decrease the energy consumption.

Benefit-risk assessment of metal bioavailability in edible fungi by biomimetic whole digestive tracts with digestion, metabolism, and absorption functions.

As worldwide edible fungi, Lentinula edodes and Agaricus bisporus accumulate both essential and harmful metals. Metal bioavailability is important for metal benefit-risk assessment. A full functional model of digestive tracts (including digestion, metabolism, and absorption) is established. Under the digestive tract functions, the bioaccessible and bioavailable metals are released from edible fungi and absorbed by intestinal tract, respectively. Based on bioavailable metal contents in the intestine, safe dosage and maximum consumption are 43.52 g/d and 248.7 g/d for Agaricus bisporu, 20.59/328.9 g/d (for males/ female) and 132.9 g/d for Lentinus edodes; V, Co, Ni, Cu, Zn, Se, Cr, Cd and Pb in Agaricus bisporus and Lentinula edodes are absorbed mainly in the large intestine; Fe is mainly absorbed in small intestine; edible fungi species-specificity in metal bioavailability is observed for As and Mn, which are mainly absorbed by small and large intestine for Agaricus bisporus and Lentinus edodes, respectively; and then metal toxicity on small and large intestine is disclosed. Metal benefit-risk is assessed by the content of monolayer liposome-extracted metal in the chyme from small and large intestine, which is controlled by the gastrointestinal functions, metal and edible fungi species.