Efficient electrochemical oxidation of antibiotic wastewater using a graphene-loaded PbO2 membrane anode: Mechanisms and applications.

This paper aims to develop a flow-through electrochemical system with a series of graphene nanoparticles loaded PbO2 reactive electrochemical membrane electrodes (GNPs-PbO2 REMs) on porous Ti substrates with pore sizes of 100, 150, 300 and 600 µm, and apply them to treat antibiotic wastewater. Among them, the GNPs-PbO2 with Ti substrate of 150 µm (Ti-150/GNPs-PbO2) had superior electrochemical degradation performance over the REMs with other pore sizes due to its smaller crystal size, larger electrochemical active specific area, lower charge-transfer impedance and larger oxygen evolution potential. Under the relatively optimized conditions of initial pH of 5, current density of 15 mA cm-2, and membrane flux of 4.20 m3 (m2·h)-1, the Ti-150/GNPs-PbO2 REM realized 99.34% of benzylpenicillin sodium (PNG) removal with an EE/O of 6.52 kWh m-3. Its excellent performance could be explained as the increased mass transfer. Then three plausible PNG degradation pathways in the flow-through electrochemical system were proposed, and great stability and safety of Ti-150/GNPs-PbO2 REM were demonstrated. Moreover, a single-pass Ti-150/GNPs-PbO2 REM system with five-modules in series was designed, which could consistently treat real antibiotic wastewater in compliance with disposal requirements of China. Thus, this study evidenced that the flow-through electrochemical system with the Ti-150/GNPs-PbO2 REM is an efficient alternative for treating antibiotic wastewater.

Towards rapid formation of electroactive biofilm: insights from thermodynamics and electric field manipulation.

Electroactive biofilm (EAB) has garnered significant attention due to its effectiveness in pollutant remediation, electricity generation, and chemical synthesis. However, achieving precise control over the rapid formation of EAB presents challenges for the practical implementation of bioelectrochemical technology. In this study, we investigated the regulation of EAB formation by manipulating applied electric potential. We developed a modified XDLVO model for the applied electric field and quantitatively assessed the feasibility of existing rapid formation strategies for EAB. Our results revealed that electrostatic (EL) force significantly influenced EAB formation in the presence of the applied electric field, with the potential difference between the electrode and the microbial solution being the primary determinant of EL force. Compared to -0.2 V and 0 V vs.Ag/AgCl, EAB exhibited the highest electrochemical performance at 0.2 V vs.Ag/AgCl, with a maximum current density of 6.044 ± 0.10 A/m2, surpassing that at -0.2 V vs.Ag/AgCl and 0 V vs.Ag/AgCl by 1.73 times and 1.31 times, respectively. Furthermore, EAB demonstrated the highest biomass accumulation, measuring a thickness of 25 ± 2 µm at 0.2 V vs. Ag/AgCl, representing increases of 1.67 and 1.25 times compared to -0.2 V vs.Ag/AgCl and 0 V vs.Ag/AgCl, respectively. The strong electrostatic attraction under the anodic potential promoted the formation of a monolayer of biofilm. Additionally, the hydrophilicity and hydrophobicity of the biofilm were altered following inversion culture. The Lewis acid-base (AB) attraction offset the electrostatic repulsion caused by negative charges, it is beneficial for the formation of biofilms. This study, for the first time, elucidated the difference in the formation of cathode and anode biofilm from a thermodynamic perspective in the context of electric field introduction, laying the theoretical foundation for the directional regulation of the rapid formation of typical electroactive biofilms.

Cell-free chitosan/silk fibroin/bioactive glass scaffolds with radial pore for in situ inductive regeneration of critical-size bone defects.

Tissue-engineered is an effective method for repairing critical-size bone defects. The application of bioactive scaffold provides artificial matrix and suitable microenvironment for cell recruitment and extracellular matrix deposition, which can effectively accelerate the process of tissue regeneration. Among various scaffold properties, appropriate pore structure and distribution have been proven to play a crucial role in inducing cell infiltration differentiation and in-situ tissue regeneration. In this study, a chitosan (CS) /silk fibroin (SF) /bioactive glass (BG) composite scaffold with distinctive radially oriented pore structure was constructed. The composite scaffolds had stable physical and chemical properties, a unique pore structure of radial arrangement from the center to the periphery and excellent mechanical properties. In vitro biological studies indicated that the CS/SF/BG scaffold could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the expression of related genes due to the wide range of connected pore structures and released active elements. Furthermore, in vivo study showed CS/SF/BG scaffold with radial pores was more conducive to the repair of skull defects in rats with accelerated healing speed during the bone tissue remodeling process. These results demonstrated the developed CS/SF/BG scaffold would be a promising therapeutic strategy for the repair of bone defects regeneration.

Distribution characteristics and transformation mechanism of per- and polyfluoroalkyl substances in drinking water sources: A review.

Per- and polyfluoroalkyl substances (PFASs) have raised significant concerns within the realm of drinking water due to their widespread presence in various water sources. This prevalence poses potential risks to human health, ecosystems, and the safety of drinking water. However, there is currently a lack of comprehensive reviews that systematically categorize the distribution characteristics and transformation mechanisms of PFASs in drinking water sources. This review aims to address this gap by concentrating on the specific sources of PFASs contamination in Chinese drinking water supplies. It seeks to elucidate the migration and transformation processes of PFASs within each source, summarize the distribution patterns of PFASs in surface and subsurface drinking water sources, and analyze how PFASs molecular structure, solubility, and sediment physicochemical parameters influence their presence in both the water phase and sediment. Furthermore, this review assesses two natural pathways for PFASs degradation, namely photolysis and biodegradation. It places particular emphasis on understanding the degradation mechanisms and the factors that affect the breakdown of PFASs by microorganisms. The ultimate goal is to provide valuable insights for the prevention and control of PFAS contamination and the assurance of drinking water quality.

Source preventing mechanism of florfenicol resistance risk in water by VUV/UV/sulfite advanced reduction pretreatment.

To avoid the inhibition of microbial activity and the emergence of bacterial resistance, effective abiotic pretreatment methods to eliminate the antibacterial activity of target antibiotics before the biotreatment system for antibiotic-containing wastewater are necessary. In this study, the VUV/UV/sulfite system was developed as a pretreatment technique for the source elimination of florfenicol (FLO) resistance risk. Compared with the VUV/UV/persulfate and sole VUV photolysis, the VUV/UV/sulfite system had the highest decomposition rate (0.33 min‒1) and the highest defluorination (83.0%), resulting in the efficient elimination of FLO antibacterial activity with less than 2.0% mineralization, which would effectively retain the carbon sources for the sludge microorganisms in the subsequent biotreatment process. Furthermore, H• was confirmed to play a more important role in the elimination of FLO antibacterial activity by controlling the environmental conditions for the formation and transformation of reactive species and adding their scavengers. Based on the theoretical calculation and proposed photolytic intermediates, the elimination of FLO antibacterial activity was achieved by dechlorination, defluorination and removal of sulfomethyl groups. When the pretreated FLO-containing wastewater entered the biological treatment unit, the abundance of associated antibiotic resistance genes (ARGs) and the relative abundance of integrons were efficiently prevented by approximately 55.4% and 22.9%, respectively. These results demonstrated that the VUV/UV/sulfite system could be adopted as a promising pretreatment option for the source elimination of FLO resistance risk by target decomposition of its responsible structures before the subsequent biotreatment process.

Energy-efficient electrochemical degradation of ciprofloxacin by a Ti-foam/PbO2-GN composite electrode: Electrode characteristics, parameter optimization, and reaction mechanism.

Reducing energy comsuption is crucial to commercialize electrochemical oxidation technologies. In this study, a novel PbO2 composite electrode (Ti-foam/PbO2-GN) was successfully fabricated based on a porous titanium (Ti) foam substrate and a ß-PbO2 active layer embedded with multiple graphene (GN) interlayers, and applied as an anode for energy-efficient pulse electrochemical oxidation of ciprofloxacin (CIP). In contrast to PbO2 and Ti-foam/PbO2 electrodes, the Ti-foam/PbO2-GN electrode surface exhibited a more compact structure, smaller crystal grain size, and greater electrochemical active surface area. CIP removal of 89.7% was obtained with a low energy consumption (EE/O) of 6.17 kWh m-3 under pulse electrolysis conditions with a current density of 25.00 mA cm-2, pulse frequency of 5000 Hz, and pulse duty cycle of 50.0%. Up to 70.7% of the energy was saved in the pulse current mode compared to the direct current mode. Narrowing the electrode spacing to 2 cm facilitated the mass transfer process and enhanced oxidation efficiency. According to the intermediates identified, the pulse electrolysis of CIP primarily involved hydroxylation of the quinolone ring, breaking of the piperazine ring, defluorination, and decarboxylation processes, and a possible degradation mechanism of CIP was proposed. The continuous oxidation performance of CIP and the relatively low leaching of Pb2+ suggested that the Ti-foam/PbO2-GN electrode exhibited excellent stability, repeatability, and safety. The degradation results of CIP in real water also exhibits the great potential of environmental application. As a result, pulse electrochemical oxidation using a Ti-foam/PbO2-GN electrode has proven to be an energy-efficient and promising alternative for antibiotic wastewater treatment.

Biomimetic Hydroxyapatite Composite Coatings with a Variable Morphology Mediated by Silk Fibroin and Its Derived Peptides Enhance the Bioactivity on Titanium.

Various modifications performed on titanium alloy surfaces are shown to improve osteointegration and promote the long-term success of implants. In this work, a bioactive nanostructured hydroxyapatite (HA) composite coating with a variable morphology mediated by silk fibroin (SF) and its derived peptides (Cs) was prepared. Numerous experimental techniques were used to characterize the constructed coatings in terms of morphology, roughness, hydrophilicity, protein adsorption, in vitro biomineralization, and adhesion strength. The mixed protein layer with different contents of SF and Cs exhibited different secondary structures at different temperatures, effectively mediating the electrodeposited HA layer with different characteristics and finally forming proteins/HA composite coatings with versatile morphologies. The addition of Cs significantly improved the hydrophilicity and protein adsorption capacity of the composite coatings, while the electrodeposition of the HA layer effectively enhanced the adhesion between the composite coatings and Ti surface. In the in vitro mineralization experiments, all the composite coatings exhibited excellent apatite formation ability. Moreover, the composite coatings showed excellent cell growth and proliferation activity. Osteogenic induction experiments revealed that the coating could significantly increase the expression of specific osteogenic markers, including ALP, Col-I, Runx-2, and OCN. Overall, the proposed modification of the Ti implant surface by protein/HA coatings had good potential for clinical applications in enhancing bone induction and osteogenic activity of implants.

Mechanism of highly efficient electrochemical degradation of antibiotic sulfadiazine using a layer-by-layer GNPs/PbO2 electrode.

A PbO2 electrode integrating electrocatalytic and adsorptive functions was successfully fabricated by embedding layer-by-layer graphene nanoplatelets (GNPs) into ß-PbO2 active layer (GNPs/PbO2) and employed as anode for high-efficient removal of sulfadiazine (SDZ). In electrochemical degradation experiments, SDZ was quickly enriched on the surface of GNPs/PbO2 film via adsorption and then oxidized by ⋅OH in-site. In terms of the electrocatalytic performance and adsorption of electrode, the optimal electrodeposition time for each ß-PbO2 outer layer was 4 min (GNPs/PbO2-4). Compared with conventional PbO2 electrode, the layer-by-layer GNPs resulted in the smaller crystal size and denser surface of PbO2 electrode, thus facilitating the generation of active oxygen species. At the same time, the specific surface area, oxygen evolution potential (OEP) of the anode were enhanced and the charge-transfer resistance was reduced. For GNPs/PbO2-4 anode, the optimal conditions of electrochemical oxidation of SDZ were identified as initial pH 9, 50 mg/L of SDZ and 20 mA/cm2 of current density using response surface methodology (RSM), 98.15% of SDZ could be removed in this case. The contribution of radical oxidation and non-radical oxidation to SDZ removal was about 79% and 21%, respectively. Moreover, the reaction pathways of SDZ on the GNPs/PbO2-4 electrode involving hydroxylation, radical reaction and ring cleavage were speculated. Finally, the continuous SDZ degradation and accelerated service lifetime test suggested that the GNPs/PbO2-4 electrode was shown to be stable and repeatable, and the Pb2+ concentration was measured to ensure the safety of the treated solution. Consequently, the above findings provide an innovative way to design and prepare an effective and stable PbO2 electrode for electrochemical degradation of antibiotic wastewater.

Energy-efficient electrochemical treatment of paracetamol using a PbO2 anode based on pulse electrodeposition strategy: Kinetics, energy consumption and mechanism.

The purpose of this research is to study the pulse electrochemical oxidation of paracetamol (PCT) using a novel PbO2 anode based on pulse electrodeposition strategy (PbO2-PE). The pulse electrodeposition strategy used to prepare a PbO2 anode resulted in rougher surface, higher directional specificity of ß(101) and more redox couples of Pb4+/Pb2+. Additionally, the oxygen evolution potential (OEP) and charge transfer resistance were also improved. When compared to direct current electrochemical oxidation process, pulse electrolysis in had a slightly higher PCT removal efficiency and active species (·OH and active chlorine) production, while 72.04% of energy consumption was saved. The effects of operating parameters on PCT degradation efficiency and specific energy consumption were studied. The findings suggested that the pulse electrochemical oxidation of PCT followed a pseudo-first-order kinetic model, with PCT removal reaching 98.63% after 60 min of electrolysis under optimal conditions. Possible mechanisms describing reaction pathways for PCT were also proposed. Finally, combinating with the economic feasibility and safety evaluation, we could conclude that pulse electrolysis with a PbO2-PE electrode was a promising option for improving the practicability of electrochemical treatment for refractory organic wastewater.

Electrochemical degradation of antibiotic enoxacin using a novel PbO2 electrode with a graphene nanoplatelets inter-layer: Characteristics, efficiency and mechanism.

A novel PbO2 electrode was fabricated by adding graphene nanoplatelets (GNP) inter-layer into ß-PbO2 active layer (called GNP-PbO2) and utilized to degradation of antibiotic enoxacin (ENO). The GNP-PbO2 electrode had a much rougher surface than the typical PbO2 electrode, with smaller crystal size and lower charge-transfer resistance at the electrode/electrolyte interface. Notably, the GNP inter-layer increased the oxygen evolution potential of PbO2 electrode (2.05 V vs. SCE), which was very beneficial to inhibit oxygen evolution and promote ·OH production. The relatively best operating parameters for ENO removal and energy efficiency were current density of 20 mA cm-2, initial pH of 7, initial ENO concentration of 100 mg L-1 and electrode distance of 4 cm. Furthermore, indirect radical oxidation was found to be the main way during electrolysis process. Based on the observed analysis of intermediate products, the main reaction pathways of ENO included hydroxylation, defluorination and piperazine ring-opening. Finally, combinating with the electro-oxidation capability, stability and safety evaluation, we can conclude that GNP-PbO2 is a promising anode for treatment of various organic pollutants in wastewater.

Photocross-linked silk fibroin/hyaluronic acid hydrogel loaded with hDPSC for pulp regeneration.

The construction of suitable biomaterials for pulp regeneration has always been a major challenge in the field of stomatology. Considering the complex and irregular anatomy of the root canal system, injectable hydrogels have received extensive attention as cell carriers in dental pulp regeneration. Here, we developed an injectable photocrosslinked methacrylylated silk fibroin (RSFMA)/methacrylylated hyaluronic acid (MeHA) composite hydrogel and characterized its physicochemical properties. The biocompatibility of encapsulated human dental pulp stem cells (hDPSCs) was subsequently investigated. With the addition of RSFMA, the pore size of the scaffolds became more regular with negligible change in porosity and exhibited excellent mechanical properties. Furthermore, the low concentration of RSFMA hydrogel in the composite hydrogel had higher cross-linking efficiency. In contrast to MeHA hydrogels, hDPSCs were encapsulated in hydrogels either in the absence or presence of high concentrations of RSFMA. The results indicated that cells in low-concentration RSFMA composite gel presented better growth ability, proliferation ability and osteogenic differentiation ability. This injectable photocrosslinked silk fibroin/hyaluronic acid hydrogel shows great potential in the field of dental pulp tissue engineering.

Learning from errors? The impact of erroneous example elaboration on learning outcomes of medical statistics in Chinese medical students.

BACKGROUND: Constructivism theory has suggested that constructing students' own meaning is essential to successful learning. The erroneous example can easily trigger learners' confusion and metacognition, which may "force" students to process the learning material and construct meaning deeply. However, some learners exhibit a low level of elaboration activity and spend little time on each example. Providing instructional scaffolding and elaboration training may be an efficient method for addressing this issue. The current study conducted a randomized controlled trial to examine the effectiveness of erroneous example elaboration training on learning outcomes and the mediating effects of metacognitive load for Chinese students in medical statistics during the COVID-19 pandemic. METHODS: Ninety-one third-year undergraduate medical students were randomly assigned to the training group (n = 47) and the control group (n = 44). Prerequisite course performance and learning motivation were collected as covariates. The mid-term exam and final exam were viewed as posttest and delayed-test to make sure the robustness of the training effect. The metacognitive load was measured as a mediating variable to explain the relationship between the training and academic performance. RESULTS: The training significantly improved both posttest and delayed-test performance compared with no training (Fposttest = 26.65, p < 0.001, Partial η2 = 0.23; Fdelayed test = 38.03, p < 0.001, Partial η2 = 0.30). The variation trend in metacognitive load in the two groups was significantly different (F = 2.24, p < 0.05, partial η2 = 0.20), but metacognitive load could not explain the positive association between the treatment and academic performance (ß = - 0.06, se = 0.24, 95% CI - 0.57 to 0.43). CONCLUSIONS: Erroneous example learning and metacognitive demonstrations are effective for academic performance in the domain of medical statistics, but their underlying mechanism merits further study.

Polydopamine-assisted immobilization of silk fibroin and its derived peptide on chemically oxidized titanium to enhance biological activity in vitro.

Biochemical modification can endow the surface of implants with superior biological activity. Herein, silk fibroin (SF) protein and its anionic derivative peptides (Cs) were covalently immobilized onto a titanium implant surface via a polydopamine layer. The successful conjugation of SF and Cs was revealed by X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), and contact angle measurements. The addition of Cs prevented the conformational transition of silk fibroin to silk II. The deposition of apatite on its surface was significantly accelerated, and the bioactive composite coating was observed to enhance protein adsorption and cell proliferation. More importantly, it also promoted the osteogenic differentiation of bone marrow stem cells (BMSCs) for the quantitative and qualitative detection of alkaline phosphatase (ALP) and alizarin red (ARS). Overall, the stable performance and enhanced osteogenic property of the composite coating promote an extensive application for clinical titanium-based implants.

Preparation and biological properties of silk fibroin/nano-hydroxyapatite/hyaluronic acid composite scaffold.

In this study, the silk fibroin/nano-hydroxyapatite/hyaluronic acid (SF/nHAp/HA) composite scaffolds with different HA contents were developed by blending, cross-linking and freeze-drying, and their physicochemical properties and cell biocompatibilityin vitrowere subsequently studied. It was observed that the molecular conformation of the composite scaffolds was mainly composed of silk I and a small amount of theß-sheets structure. On enhancing the HA content, the pore size of the scaffold decreased, while the porosity, water absorption, swelling ratio and mechanical properties were observed to increase. In particular, the SF/nHAp/HA scaffold with a 5.0 wt% ratio exhibited the highest water absorption and mechanical properties among the developed materials. In addition, thein vitrocytocompatibility analysis showed that the bone marrow mesenchymal stem cells exhibited excellent cell proliferation and osteogenic differentiation ability on the SF/nHAp/5.0 wt%HA scaffolds, as compared with the other scaffolds. It can be concluded that the developed composite scaffolds represent a promising class of materials for the bone tissue repair and regeneration.

Autonomous Robot for Removing Superficial Traumatic Blood.

Objective: To remove blood from an incision and find the incision spot is a key task during surgery, or else over discharge of blood will endanger a patient's life. However, the repetitive manual blood removal involves plenty of workload contributing fatigue of surgeons. Thus, it is valuable to design a robotic system which can automatically remove blood on the incision surface. Methods: In this paper, we design a robotic system to fulfill the surgical task of the blood removal. The system consists of a pair of dual cameras, a 6-DoF robotic arm, an aspirator whose handle is fixed to a robotic arm, and a pump connected to the aspirator. Further, a path-planning algorithm is designed to generate a path, which the aspirator tip should follow to remove blood. Results: In a group of simulating bleeding experiments on ex vivo porcine tissue, the contour of the blood region is detected, and the reconstructed spatial coordinates of the detected blood contour is obtained afterward. The BRR robot cleans thoroughly the blood running out the incision. Conclusions: This study contributes the first result on designing an autonomous blood removal medical robot. The skill of the surgical blood removal operation, which is manually operated by surgeons nowadays, is alternatively grasped by the proposed BRR medical robot.

Preparation and biological properties of silk fibroin/nano-hydroxyapatite/graphene oxide scaffolds with an oriented channel-like structure.

Constructing an ideal bone tissue engineering scaffold has been one of the research hotspots in the biomedical field. Silk fibroin (SF), nano-hydroxyapatite (nHAp) and graphene oxide (GO) are excellent biomaterials, and have been studied and explored extensively. To better mimic natural bone, we fabricated a SF/nHAp/GO hybrid scaffold with an oriented channel-like structure by using directional temperature field freezing technology. A comparative analysis was carried out for the SF, SF/nHAp, unoriented SF/nHAp/GO and oriented SF/nHAp/GO scaffolds. The physical and chemical properties were studied by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and universal mechanical testing. The data showed that the oriented channel-like SF/nHAp/GO porous scaffold expressed high interconnectivity, suitable pore diameter and porosity and anisotropic mechanical properties. Cytocompatibility tests indicated that the oriented channel-like SF/nHAp/GO porous scaffold was more favorable for stimulating bone marrow mesenchymal stem cells (BMSCs) adhesion and proliferation. Additionally, human umbilical vein endothelial cells (HUVECs) grew unimpeded along the channel, indicating it had advantages for vascularization. For further testing in vitro, osteogenic induction was carried out on BMSCs inoculated on the above scaffolds, and then alkaline phosphatase (ALP) activity was tested and cell mineralization was observed. The results indicated that the oriented channel-like SF/nHAp/GO porous scaffold was more conducive to osteogenic differentiation of BMSCs. Hence, the material may prove to be a promising scaffold for bone tissue engineering.

Electrochemical oxidation of Acid Orange 7 azo dye using a PbO2 electrode: Parameter optimization, reaction mechanism and toxicity evaluation.

In this study, electrochemical oxidation of Acid Orange 7 (AO 7) azo dye has been investigated using a Fe-doped PbO2 electrode. The degradation of AO 7 followed pseudo-first-order reaction kinetics. The removals of AO 7, chemical oxygen demand (COD) and total organic carbon (TOC) were 87.15%, 49.88% and 44.94% after 60 min of electrolysis at the optimal conditions (Na2SO4 concentration 0.1 M, initial pH 5, initial AO 7 concentration 100 mg L-1 and applied current density 20 mA cm-2), respectively. And the corresponding degradation rate constant was 0.035 min-1. The intermediates formed during electrochemical process were identified, and a possible degradation pathway was proposed, which was initiated by the oxidation of azo bond (-NN-), hydroxylation and substitution reaction of -NH2 and -SO3H under the attack of OH, and ended with the formation of mineralization products such as NH4+, NO3-, SO42-, CO2 and H2O. The toxicity of treated AO 7 solution towards Vibrio fischeri increased slightly at first and then rapidly reduced to non-toxicity with prolonging time. The results indicate that electrochemical oxidation of AO 7 using Fe-doped PbO2 electrode is a promising way.

Electrochemical degradation of antibiotic levofloxacin by PbO2 electrode: Kinetics, energy demands and reaction pathways.

In this work, the electrochemical degradation of antibiotic levofloxacin (LFX) has been studied using a novel rare earth La, Y co-doped PbO2 electrode. The effect of applied current density, pH value and initial LFX concentration on the degradation performance were systematically evaluated. The results demonstrated that electrochemical oxidation of LFX over the La-Y-PbO2 electrode was highly effective and the reaction followed an apparent first-order kinetic model. Considering the degradation efficiency and energy efficiency, the relative optimal conditions are identified as current density 30 mA cm-2, pH 3 and initial LFX concentration 800 mg L-1. According to the identified products, a reaction mechanism has been proposed and the products were further oxidized to CO2, H2O, NH4+, NO3- and F-. A total of four aromatic intermediate products of LFX degradation were identified and the different structural changes to the LFX molecule included pepiperazinyl hydroxylation, decarboxylation and defluorination.