New Barrier Role of Iron Plaque: Producing Interfacial Hydroxyl Radicals to Degrade Rhizosphere Pollutants.

Iron plaque, as a natural barrier between rice and soil, can reduce the accumulation of pollutants in rice by adsorption, contributing to the safe production of rice in contaminated soil. In this study, we unveiled a new role of iron plaque, i.e., producing hydroxyl radicals (·OH) by activating root-secreted oxygen to degrade pollutants. The ·OH was produced on the iron plaque surface and then diffused to the interfacial layer between the surface and the rhizosphere environment. The iron plaque activated oxygen via a successive three-electron transfer to produce ·OH, involving superoxide and hydrogen peroxide as the intermediates. The structural Fe(II) in iron plaque played a dominant role in activating oxygen rather than the adsorbed Fe(II), since the structural Fe(II) was thermodynamically more favorable for oxygen activation. The oxygen vacancies accompanied by the structural Fe(II) played an important role in oxygen activation to produce ·OH. The interfacial ·OH selectively degraded rhizosphere pollutants that could be adsorbed onto the iron plaque and was less affected by the rhizosphere environments than the free ·OH. This study uncovered the oxidative role of iron plaque mediated by its produced ·OH, reshaping our understanding of the role of iron plaque as a barrier for rice.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-C5a Antibody BDB-001 for Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial in Healthy Chinese Adults.

INTRODUCTION: Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the complement system to trigger a powerful "cytokine and chemokine storm" in viral infection. BDB-001, a recombinant human immunoglobulin G4 (IgG4) that specially binds to C5a, has the potential to inhibit the C5a-triggered cytokine storm in treating COVID-19 patients and other inflammation diseases. Here, we have explored its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adults. This trial is registered with http://www.chinadrugtrials.org.cn/(CTR20200429 ). METHODS: Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, and 8 mg/kg) and 1 multi-dose cohort (4 mg/kg), and received either BDB-001 or placebo (3:1) double-blindly. The safety and tolerability after administration were evaluated for 21 days for single-dose cohorts and 28 days for the multi-dose cohort. The pharmacokinetics of BDB-001 in plasma and pharmacodynamics as free C5a in plasma were analyzed. RESULTS: The incidence of drug-related adverse events (AEs) was low, and all AEs were mild or moderate: neither AEs ≥ 3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious adverse events (SAEs) were found. The area under the concentration-time curve from time zero to 480 h (AUC0-480h), that from time zero to infinity (AUCinf), and peak plasma concentration ©max) increased dose-dependently from 2 to 8 mg/kg in the single-dose cohorts and were characterized by a nonlinear pharmacokinetics of target-mediated drug disposal (TMDD). The accumulation index by AUC0-tau after five administrations (4 mg/kg) from the multi-dose cohort was 6.42, suggesting an accumulation effect. Furthermore, inhibition of C5a at the plasma level was observed. CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.

A hybrid metal-organic framework nanomedicine-mediated photodynamic therapy and hypoxia-activated cancer chemotherapy.

The hypoxic tumor microenvironment and photodynamic therapy (PDT)-aggravated hypoxia compromise the anticancer efficacy of chemotherapy, immunotherapy, and PDT. Thus, sophisticated nanomedicines that can activate their anticancer capability in situ in response to specific stimuli need to be developed. This study aimed to construct a hybrid nanomedicine that activated chemotherapy by inducing hypoxia, which synergized with PDT to promote antitumor outcomes, contrary to the strategies focusing on reversing tumor hypoxia. The hybridization of a porphyrin metal-organic framework (MOF) and gold nanoparticles (AuNPs) enhanced the stability of the hybrid nanomedicine against the phosphate in blood, thereby preventing the premature drug release during blood circulation. The surface modification with polyethylene glycol (PEG) markedly increased the tumor accumulation of the hybrid MOF nanomedicine, which encapsulated a hypoxia-activated prodrug (tirapazamine, TPZ), by enhancing its colloidal stability and pharmacokinetics. The loaded TPZ was rapidly released from the nanomedicine in response to the concentrated intracellular phosphate after cellular uptake, and was then converted into a potent anticancer drug in a hypoxic microenvironment exacerbated by continuous O2 consumption during PDT. In vitro and in vivo experiments demonstrated that the synergistic PDT and hypoxia-activated chemotherapy exhibited enhanced antitumor therapeutic efficiency and superior antimetastatic effect, and effectively ablated the tumor without recurrence. Therefore, the sophisticated nanomedicine reported here, which eliminated cancer cells by inducing a hypoxic tumor microenvironment, showed translational potential in future therapeutic development.

pH-responsive hybrid platelet membrane-coated nanobomb with deep tumor penetration ability and enhanced cancer thermal/chemodynamic therapy.

Background: Despite their outstanding properties in high surface-to-volume ratio and deep penetration, the application of ultrasmall nanoparticles for tumor theranostics remains limited because of their dissatisfied targeting performance and short blood circulation lifetime. Various synthetic materials with complex structures have been prepared as a multifunctional platform for loading ultrasmall nanoparticles. However, their use in nanomedicine is restricted because of unknown metabolic processes and potential physiological toxicity. Therefore, versatile and biocompatible nanoplatforms need to be designed through a simple yet effective method for realizing specific delivery and responsible release of ultrasmall nanoparticles. Methods: Iron-gallic acid coordination polymer nanodots (FeCNDs) exhibits outstanding photothermal ability and Fenton catalytic performance, which can be applied for tumor inhibition via hyperthermia and reactive oxygen species. A pH-responsive platelet-based hybrid membrane (pH-HCM) was prepared via co-extrusion and acted as a safe nanoplatform to load FeCNDs (pH-HCM@FeCNDs). Subsequently, their responsive performance and penetration ability were valued considering the multicellular sphere (MCS) model in an acidic or neutral environment. Thereafter, in vivo fluorescence image was performed to assess targeting capability of pH-HCM@FeCNDs. Finally, the corresponding antitumor and antimetastatic effects on orthotropic breast cancer were investigated. Results: In 4T1 MCS model, pH-HCM@FeCNDs group exhibited higher penetration efficiency (72.84%) than its non-responsive counterparts (17.77%) under an acidic environment. Moreover, the fluorescence intensity in pH-HCM@FeCNDs group was 3.18 times higher than that in group without targeting performance in the in vivo fluorescence image experiment. Finally, through in vivo experiments, pH-HCM@FeCNDs was confirmed to exhibit the best antitumor effect (90.33% tumor reduction) and antimetastatic effects (only 0.29% tumor coverage) on orthotropic breast cancer. Conclusions: Hybrid cell membrane was an ideal nanoplatform to deliver nanodots because of its good responsibility, satisfactory targeting ability, and excellent biocompatibility. Consequently, this study provides novel insights into the delivery and release of nanodots in a simple but effect method.

Mixture toxicity and uptake of 1-butyl-3-methylimidazolium bromide and cadmium co-contaminants in water by perennial ryegrass (Lolium perenne L.).

Ionic liquids, a kind of emerging and persistent organic contaminants, always coexist with heavy metals in aquatic and terrestrial environments. However, the feasibility of phytoremediation to remove ionic liquids and heavy metals co-contaminants is still unclear. Thus, in this study, the hydroponic experiment was conducted to investigate the combined effect of 1-butyl-3-methylimidazolium bromide ([C4mim]+Br-) and cadmium (Cd2+) on growth and physiological indictors of perennial ryegrass, together with their uptake and translocation by plants. Results show that the exposure of ryegrass to [C4mim]+ and Cd2+ mixture significantly inhibited the biomass growth and affected the photosynthetic pigments contents in leaves. The increases of lipid peroxidation and catalase, peroxidase activity were also observed under the co-exposure experiments. The mixture toxicity of [C4mim]+ and Cd2+ to ryegrass growth showed an additive effect predicted by concentration addition and independent action. [C4mim]+ uptake and acropetal translocation by ryegrass were significantly inhibited with dosing Cd2+. In contrast, [C4mim]+ had no obvious effect on Cd2+ uptake by ryegrass, while enhanced Cd2+ translocation from roots to shoots occurred with increasing [C4mim]+ dosages. These results indicate that the co-contamination of ionic liquids and heavy metals would affect their fates during phytoremediation.

Encapsulation of indocyanine green into cell membrane capsules for photothermal cancer therapy.

UNLABELLED: Although indocyanine green (ICG) has promising applications in photothermal therapy (PPT) because of its low toxicity and high efficiency in inducing heat and singlet oxygen formation in response to near-infrared light with a wavelength of approximately 800nm, its clinical application has been restricted because of its rapid body clearance and poor water stability. Therefore, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged ICG by temporarily permeating the plasma membrane and resealing using positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape, with a diameter of approximately 800nm. The DOX and ICG encapsulation was confirmed by the UV-vis spectrum; a very small amount of DOX (0.8µg) and a very high amount of ICG (∼110µg) were encapsulated in 200µg CMCs. Encapsulation in the CMCs leads to sustained release of ICG, especially in the presence of positively charged DOX. The temperature enhancement and generation of ROS by ICG encapsulated in CMCs were confirmed upon laser irradiation in vitro, leading to cell death. CMCs@DOX/ICG also can significantly enhance the retention of ICG in a tumor after intratumoral injection in vivo. As a result, combination treatment with CMCs@DOX/ICG and laser irradiation demonstrated much better anticancer efficacy than that of free DOX/ICG and CMCs@ICG. The encapsulation of ICG into CMCs, especially with the assistance of DOX, significantly slows down the body clearance of ICG, with a retained PPT effect against tumors, an important step forward in the practical application of ICG in cancer therapy. STATEMENT OF SIGNIFICANCE: In this study, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged indocyanine green (ICG) by temporarily permeating the plasma membrane and resealing, in the presence of positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape, with a diameter of approximately 800nm. Encapsulation in the CMCs leads to sustained release of ICG and thus slower clearance inside body, especially in the presence of positively charged DOX. The system provides a better photothermal effect against tumors, an important step forward in the practical application of ICG in cancer therapy.

Quantitative evaluation of noncovalent interactions between polyphosphate and dissolved humic acids in aqueous conditions.

As one kind of phosphorus species, polyphosphate (poly-P) is ubiquitous in natural environments, and the potential interactions between poly-P and humic substances in the sediments or natural waters would influence the fate of poly-P in the environments. However, the mechanism of the interactions has not yet been understood clearly. In this work, the characteristics and mechanisms of the interactions between humic acids (HA) and two model poly-P compounds with various chain lengths have been investigated. Results show that a stable polyphosphate-HA complex would be formed through the noncovalent interactions, and hydrogen bond might be the main driving force for the binding process, which might be formed between the proton-accepting groups of poly-P (e.g., PO and P-O(-)) and the oxygen containing functional groups in HA. Our findings implied that the presence of humic substances in natural waters, soils and sediments would influence the potential transport and/or mobility of environmental poly-P.

Calcium effect on the metabolic pathway of phosphorus accumulating organisms in enhanced biological phosphorus removal systems.

Phosphorus accumulating organisms (PAOs) have been found to act as glycogen-accumulating organisms (GAOs) under certain conditions, thus, the deterioration in the performance of enhanced biological phosphorus removal systems is not always attributed to the proliferation of GAOs. In this work, the effects of calcium on the metabolic pathway of PAOs were explored. It was found that when the influent Ca(2+) concentration was elevated, the tendency and extent of extracellular calcium phosphate precipitation increased, and the intracellular inert Ca-bound polyphosphate was synthesized, while the microbial population remained almost unchanged. The changes in the ratios of phosphorus released/acetate uptaken, the glycogen degraded/acetate uptaken and the poly-ß-hydroxyalkanoates synthesized/acetate uptaken during the anaerobic period confirm that, as the influent Ca(2+) concentration was increased, the polyphosphate-accumulating metabolism was partially shifted to the glycogen-accumulating metabolism. At an influent Ca(2+) around 50 mg/L, in addition to the extracellular calcium phosphate precipitation, the intracellular inert Ca-bound polyphosphate synthesis might also be involved in the metabolic change of PAOs. The results of the present work would be beneficial to better understand the biochemical metabolism of PAOs in enhanced biological phosphorus removal systems.

Phosphorus removal in an enhanced biological phosphorus removal process: roles of extracellular polymeric substances.

Phosphorus-accumulating organisms are considered to be the key microorganisms in the enhanced biological phosphorus removal (EBPR) process. A large amount of phosphorus is found in the extracellular polymeric substances (EPS) matrix of these microorganisms. However, the roles of EPS in phosphorus removal have not been fully understood. In this study, the phosphorus in the EBPR sludge was fractionated and further analyzed using quantitative (31)P nuclear magnetic resonance spectroscopy. The amounts and forms of phosphorus in EPS as well as their changes in an anaerobic-aerobic process were also investigated. EPS could act as a reservoir for phosphorus in the anaerobic-aerobic process. About 5-9% of phosphorus in sludge was reserved in the EPS at the end of the aerobic phase and might further contribute to the phosphorus removal. The chain length of the intracellular long-chain polyphosphate (polyP) decreased in the anaerobic phase and then recovered under aerobic conditions. However, the polyP in the EPS had a much shorter chain length than the intracellular polyP in the whole cycle. The migration and transformation of various forms of phosphorus among microbial cells, EPS, and bulk liquid were also explored. On the basis of these results, a model with a consideration of the roles of EPS was proposed, which is beneficial to elucidate the mechanism of phosphorus removal in the EBPR system.

Determination of chlorinated hydrocarbons in water using highly sensitive mid-infrared sensor technology.

Chlorinated aliphatic hydrocarbons and chlorinated aromatic hydrocarbons (CHCs) are toxic and carcinogenic contaminants commonly found in environmental samples, and efficient online detection of these contaminants is still challenging at the present stage. Here, we report an advanced Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) sensor for in-situ and simultaneous detection of multiple CHCs, including monochlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, trichloroethylene, perchloroethylene, and chloroform. The polycrystalline silver halide sensor fiber had a unique integrated planar-cylindric geometry, and was coated with an ethylene/propylene copolymer membrane to act as a solid phase extractor, which greatly amplified the analytical signal and contributed to a higher detection sensitivity compared to the previously reported sensors. This system exhibited a high detection sensitivity towards the CHCs mixture at a wide concentration range of 5~700 ppb. The FTIR-ATR sensor described in this study has a high potential to be utilized as a trace-sensitive on-line device for water contamination monitoring.

Species of phosphorus in the extracellular polymeric substances of EBPR sludge.

In this study, the species of extracellular phosphorus and their transformation during extracellular polymeric substances (EPS) extraction were explored by using (31)P nuclear magnetic resonance spectroscopy. Results show that the extraction methods had a substantial influence on the phosphorus species in the extracted EPS. Cation exchange resin method was more appropriate for extracting EPS from the enhanced biological phosphorus removal (EBPR) sludge. Orthophosphate, pyrophosphate and polyphosphate were the main species of phosphorus found to be present in the EPS, which together accounted for about 6.6-10.5% of the total phosphorus in the EBPR sludge. The high percentage of extracellular phosphorus and their diverse species might reveal a new insight into the characteristics of the phosphorus in EPS in EBPR system.

Elucidation of the thermal deterioration mechanism of bio-oil pyrolyzed from rice husk using Fourier transform infrared spectroscopy.

In this study, the rationale for exploring the thermal deterioration mechanism of the bio-oil pyrolyzed from rice husk is established. This is based on identification of the unstable intermediates in the thermal deterioration process. Fourier transform infrared (FTIR) spectroscopy was used to monitor such a thermal deterioration process of bio-oil samples in thermal treatment and/or during long-term storage at ambient temperatures of 20-30 °C. Terminal olefins, as a key intermediate, so-called "signature", were identified qualitatively by using FTIR spectroscopy. A band shift observed at 880 cm(-1), which was assigned to the C-H out-of-plane deformation vibration of terminal olefins, indicates the start-up of the bio-oil thermal deterioration. A two-step pathway was proposed to describe the thermal deterioration process of bio-oil. This study suggests that the status of bio-oil could be rapidly monitored by the FTIR method.

Diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in patients with fever of unknown origin.

BACKGROUND: While fever of unknown origin (FUO) remains a challenging problem in clinical practice, fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) has been considered helpful in diagnosing its cause. The present study is set to evaluate the diagnostic value of PET/CT for patients with FUO. METHODS: We analyzed the records of 48 patients with FUO (34 men and 14 women; mean age of 57-year-old with a range between 24- and 82-year-old). The patients were examined by (18)F-FDG PET/CT and the results were compared to a final diagnosis that was established by additional procedures. RESULTS: A final diagnosis was established for 36 patients (75%). Among them, 15 patients had infectious diseases, 12 patients had malignancies, and 9 patients had non-infectious inflammatory diseases. Thirty-two abnormal PET/CT results correctly revealed the source of fever (true-positives). Abnormal PET/CT results were considered false-positives for 8 patients without diagnoses. Normal PET/CT results in 4 patients with no diagnoses were classified as true-negatives. Four patients with normal PET/CT results with diagnosed cause for FUO were considered false-negatives. Therefore, PET/CT had a positive predictive value of 80%, a negative predictive value of 50%, a sensitivity of 89%, and a specificity of 33% in patients with FUO. CONCLUSIONS: Our study demonstrated that FDG-PET/CT is a valuable imaging tool for the identification of the etiology in patients with FUO. The results suggest that this procedure may be considered as a second-line test, especially when conventional structural imaging was normal or unable to distinguish lesions from benign and malignant.

Multiresidue determination of thermolabile insecticides in cereal products by gas chromatography-mass spectrometry: evaluation with on-column injection and conventional hot splitless injection.

This communication presents a study on the simultaneous determination of thermolabile N-methylcarbamate and organophosphorus insecticides in cereal products by gas chromatography-mass spectrometry. The thermal stability of the multiple insecticides was evaluated with conventional hot splitless injection and on-column injection. The results obtained by GC-MS with these two injection techniques were compared in terms of the recovery, the limit of detection, the limit of qualification, and the reproducibility. With on-column injection, the pesticide recoveries in cereal samples were better than 82%, with relative standard deviations lower than 5.4%. The limits of qualification for most insecticides were in the range of 0.009-0.08 mg/kg, i. e. lower than the maximum residue limits established for insecticides in cereal products by the European Union. The long-term stability using on-column injection for analysis of insecticides in real samples was evaluated and normal chromatographic performance could be obtained within 50 analyses. The results revealed that it was possible for application of on-column injection in the analysis of thermolabile multiple insecticides in food sample after comprehensive sample clean-up, despite the highly contaminated nature of the column system.

An approach to the characterization of serum low-molecular weight proteins/peptides in liver injury using SELDI-TOF MS and factor analysis.

OBJECTIVES: The objective of this work was to investigate if the application of factor analysis to the SELDI-TOF MS data could contribute to the characterization of the serum low-molecular weight proteins/peptides in liver injury. DESIGN AND METHODS: Distinguished SELDI-TOF mass spectral peaks of the liver injury group were identified by comparing with those of the control group. Factor analysis was introduced to classify these peaks into different groups, assignable to the possible underlying factors. Based on original mass spectral plot, loading and current medical knowledge, the common characteristics of the peaks in same group were revealed and the underlying factors were tentatively defined. RESULTS: The SELDI profiles of liver injury group exhibit 43 discriminating peaks from the control group. Factor analysis extracted 4 common factors, which were the cholestasis, coagulation, attenuation and 9292 factors. And a plausible interpretation for some undetermined peaks was proposed. CONCLUSION: The application of factor analysis to SELDI-TOF MS data extracted valuable information out of complex and high-dimensional mass spectra data.

Response surface optimization for determination of pesticide multiresidues by matrix solid-phase dispersion and gas chromatography.

An optimized multiresidue analysis method based on matrix solid-phase dispersion (MSPD) and gas chromatography (GC) is proposed for the determination of organochlorines and pyrethroids in the tea samples. Response surface methodology (RSM) was used to optimize the extraction conditions of MSPD, such as the sorbent type, eluent composition, dichloromethane concentration and eluting volume. Desirability function approach was employed to optimize the pesticide recoveries and matrix cleanup. Compromising the recoveries and cleanup degree, MSPD was carried out with Florisil as the sorbent and n-hexane-dichloromethane (1:1, v/v) as the eluent. The pesticide recoveries in tea samples were better than 80% spiked in the concentration range of 0.01-0.05mg/kg and the relative standard deviations were lower than 7%. The quantification limits of the pesticides were in the range of 0.002-0.06mg/kg, which were lower than the maximum residue limits of the pesticides in tea samples established by the European Union.

Establishment of highly differentiated immortalized human hepatocyte line with simian virus 40 large tumor antigen for liver based cell therapy.

Acute liver failure and metabolic liver disorder animal models have demonstrated that hepatocytes transplanted into the liver or spleen survive and participate in the liver repopulation process, and recent studies have documented the usefulness of hepatocyte transplantation in humans. However, despite the promising cell therapy, there are still many restrictions, such as the shortage of donor human livers and the limited lifespan and the functional insufficiency of primary cultured hepatocytes. The immortalized and highly differentiated human hepatocyte could provide an unlimited supply of transplantable cells. In this study, we established an efficient and highly differentiated immortalized human hepatocyte line for bioartificial liver and hepatocyte transplantation research. Hepatocytes isolated from the liver of a 25 year old, brain dead male were transfected with pcDNA3.1 (-) recombinant plasmid containing the genes encoding simian virus 40 (SV40) large tumor antigen. One of the hepatocyte clones, HepLL, displayed highly differentiated liver functions with immortalized characteristics and was selected with a 700-300 microg/ml of G418 technique in 42 days. To characterize this immortalized cell line for cell therapy in the near future, HepLL cells were studied with immunohistochemistry, reverse transcription-polymerase chain reactions, immunoblotting, and tumorigenicity tests. The results revealed that HepLL cells displayed morphologic characteristics of liver parenchymal cells, secreted albumin, synthesized urea and glycogen, and expressed liver enriched functional markers, but there were no tumorigenic qualities after transplantation into severe combined immunodeficiency mice. Thus this immortalized human hepatocyte line is expected to be a useful tool for studying the functions of differentiated human hepatocyte and a promising strategy to resolve the shortages of donor organs and the limits of primary human hepatocyte for transplantation and bioartificial liver support systems.

Reductive degradation of nitrobenzene in aqueous solution by zero-valent iron.

The reductive degradation of nitrobenzene (NB) by zero-valent iron was investigated. Experimental results showed that the degradation of NB was influenced by pH and NB concentration. The optimum pH value was found to be 3.0 for the reductive degradation of NB in the tested pH ranges of 3.0-12.0. The formation rate of aniline, a major reductive product of NB, followed zero-order kinetics at various pH levels. Furthermore, GC/MS analysis showed that aniline, azobenzene and azoxybenzene were the reductive products of NB by zero-valent iron. With the analysis of the products with GC/MS and FTIR, possible reductive pathways of NB by zero-valent iron were suggested.