Mesoporous zinc oxide-based drug delivery system offers an antifungal and immunoregulatory strategy for treating keratitis.

Fungal keratitis is a refractory eye disease that is prone to causing blindness. Fungal virulence and inflammatory responses are two major factors that accelerate the course of fungal keratitis. However, the current antifungal drugs used for treatment usually possess transient residence time on the ocular surface and low bioavailability deficiencies, which limit their therapeutic efficacy. In this work, natamycin (NATA)-loaded mesoporous zinc oxide (Meso-ZnO) was synthesized for treating Aspergillus fumigatus keratitis with excellent drug-loading and sustained drug release capacities. In addition to being a carrier for drug delivery, Meso-ZnO could restrict fungal growth in a concentration-dependent manner, and the transcriptome analysis of fungal hyphae indicated that it inhibited the mycotoxin biosynthesis, oxidoreductase activity and fungal cell wall formation. Meso-ZnO also promoted cell migration and exhibited anti-inflammatory role during fungal infection by promoting the activation of autophagy. In mouse models of fungal keratitis, Meso-ZnO/NATA greatly reduced corneal fungal survival, alleviated tissue inflammatory damage, and reduced neutrophils accumulation and cytokines expression. This study suggests that Meso-ZnO/NATA can be a novel and effective treatment strategy for fungal keratitis.

Extracellular vesicles from Candida albicans modulate immune cells function and play a protective role in fungal keratitis.

Fungal keratitis (FK) is a highly blinding infectious corneal disease caused by pathogenic fungi. Candida albicans (C. albicans) is one of the main pathogens of fungal keratitis. Extracellular vesicles (EVs), lipid bilayer compartments released by almost all living cells, including fungi, have garnered attention for their role in pathogenic microbial infection and host immune responses in recent years. Studies have reported that pretreating the host with fungal EVs can reduce the inflammatory response of the host when attacked by fungi and reduce the lethality of fungal infection. However, there are no studies that have evaluated whether C. albicans EVs can modulate the inflammatory response associated with C. albicans keratitis. Our study revealed that C. albicans EVs could activate the polymorphonuclear cells (PMNs) and promote their secretion of proinflammatory cytokines and nitric oxide (NO), enhance their phagocytic and fungicidal abilities against C. albicans. C. albicans EVs also induced a proinflammatory response in RAW264.7 cells, which was characterized by increased production of inflammatory cytokines and elevated expression of the chemokine CCL2. Similarly, stimulation of C. albicans EVs to RAW264.7 cells also enhanced the phagocytosis and killing ability of cells against C. albicans. Besides, in our in vivo experiments, after receiving subconjunctival injection of C. albicans EVs, C57BL/6 mice were infected with C. albicans. The results demonstrated that pre-exposure to C. albicans EVs could effectively diminish the severity of keratitis, reduce fungal load and improve prognosis. Overall, we conclude that C. albicans EVs can modulate the function of immune cells and play a protective role in C. albicans keratitis.

Biomimetic mercury immobilization by selenium functionalized polyphenylene sulfide fabric.

Highly efficient decontamination of elemental mercury (Hg0) remains an enormous challenge for public health and ecosystem protection. The artificial conversion of Hg0 into mercury chalcogenides could achieve Hg0 detoxification and close the global mercury cycle. Herein, taking inspiration from the bio-detoxification of mercury, in which selenium preferentially converts mercury from sulfoproteins to HgSe, we propose a biomimetic approach to enhance the conversion of Hg0 into mercury chalcogenides. In this proof-of-concept design, we use sulfur-rich polyphenylene sulfide (PPS) as the Hg0 transporter. The relatively stable, sulfur-linked aromatic rings result in weak adsorption of Hg0 on the PPS rather than the formation of metastable HgS. The weakly adsorbed mercury subsequently migrates to the adjacent selenium sites for permanent immobilization. The sulfur-selenium pair affords an unprecedented Hg0 adsorption capacity and uptake rate of 1621.9 mg g-1 and 1005.6 µg g-1 min-1, respectively, which are the highest recorded values among various benchmark materials. This work presents an intriguing concept for preparing Hg0 adsorbents and could pave the way for the biomimetic remediation of diverse pollutants.

Aspergillus fumigatus-Derived Extracellular Vesicles Mitigate Fungal Keratitis by Modulating the Immune Cell Function.

Fungal keratitis (FK) is a refractory global disease characterized by a high incidence of blindness and a lack of effective therapeutic options, and Aspergillus fumigatus (A. fumigatus, AF) is one of the most common causative fungi. This study aimed to investigate the role of extracellular vesicles (EVs) from A. fumigatus in the immune cell function and their protective role in A. fumigatus keratitis in order to explore their therapeutic potential. First, we isolated and characterized the EVs (AF-derived EVs). In vitro, we stimulated RAW264.7 cells and polymorphonuclear cells with AF-derived EVs. The expression levels of inflammatory factors increased in both immune cells along with an M1 polarization variation of RAW264.7 cells. After being incubated with AF-derived EVs, both immune cells exhibited an increased conidia-phagocytic index and a decreased conidia survival rate. In vivo, we injected EVs subconjunctivally on mice resulting in a heightened production of secretory immunoglobulin A (sIgA) in tear fluid. By the injection of EVs on mice in advance, a significant reduction in severity of A. fumigatus FK was witnessed by lower clinical scores, inflammatory appearances, and mitigated fungal load. Collectively, these results positioned AF-derived EVs as a promising and innovative immune therapy for combating FK, while also providing a platform for further investigation into developing an optimal formulation for modulating inflammation in the context of FK.

Hydrogen-Bonded Organic Framework Derived 2D N, O Co-Doped Carbon Nanobelt with Tunable Pseudocapacitive Contribution for Efficient Capacitive Deionization.

Defect engineering is recognized as an attractive method for modulating the electronic structure and physicochemical characteristics of carbon materials. Exploiting heteroatom-doped porous carbon with copious active sites has attracted great attention for capacitive deionization (CDI). However, traditional methods often rely on the utilization of additional heteroatom sources and strong corrosive activators, suffering from low doping efficiency, insufficient doping level, and potential biotoxicity. Herein, hydrogen-bonded organic frameworks (HOFs) are employed as precursors to synthesize N, O co-doped porous carbon via a simple and green reverse defect engineering strategy, achieving controllable heavy doping of heteroatoms. The N, O co-doping triggers significant pseudocapacitive contribution and the surface pore structure supports the formation of the electric double layer. Therefore, when HOF-derived N, O co-doped carbon is used as CDI electrodes, a superior salt adsorption capacity of 32.29 ± 1.42 mg g-1 and an outstanding maximum salt adsorption rate of 10.58 ± 0.46 mg g-1  min-1 at 1.6 V in 500 mg L-1 NaCl solution are achieved, which are comparable to those of state-of-the-art carbonaceous electrodes. This work exemplifies the effectiveness of the reverse nitrogen-heavy doping strategy on improving the carbon structure, shedding light on the further development of rational designed electrode materials for CDI.

The preparation and therapeutic effects of ß-glucan-specific nanobodies and nanobody-natamycin conjugates in fungal keratitis.

Fungal keratitis (FK) is a severe infectious corneal disease. Since traditional eye drops exhibit poor dissolution and high corneal toxicity, the efficacy of current treatments for FK remains limited. It is needed to develop new approaches to control the cornea damage from FK. In this study, a nanobody (Nb) specific to ß-glucan in the fungal cell wall was prepared. The conjugate of the Nb with natamycin (NAT), a traditional antifungal drug, was synthesized. Firstly, we found the Nb specific to ß-glucan inhibited fungal growth by disrupting cell wall and biofilm formation.. In addition, the content of ß-glucan in the fungal cell wall decreased after Nb treatment. The Nb also reduced the adhesion ability of fungal conidia to human corneal epithelial cells (HCECs). Further, we examined the difference between NAT and Nb-NAT in antifungal growth. Nb-NAT showed better antifungal effects than NAT which was caused by the interaction between Nb and ß-glucan. Moreover, Nb concentration below 0.5 mg/mL did not affect the viability of HCECs. Nb-NAT had less cytotoxicity and ocular surface irritation than NAT. Nb specific to ß-glucan attenuated Aspergillus fumigatus (A. fumigatus) virulence and relieved inflammatory responses in FK. Nb-NAT treatment of the cornea improved therapeutic effects compared with NAT. It decreased clinical scores and expression level of inflammatory factors. To our knowledge, this study is the first to report a Nb specific to ß-glucan and Nb-NAT for the treatment of FK. These unique functions of the Nb specific to ß-glucan and Nb-NAT would render it as an alternative molecule to control fungal infections including FK. STATEMENT OF SIGNIFICANCE: Fungal keratitis is a corneal disease with a high rate of blindness. Due to the poor dissolution and high corneal toxicity exhibited by traditional eye drops, the efficacy of current therapeutic treatments for fungal keratitis (FK) remains limited. To enhance the therapeutic effect of natamycin in treating fungal keratitis, this study developed an innovative approach by preparing a ß-glucan-specific nanobody and loading it with the antifungal drug natamycin. The ß-glucan-specific nanobody has the ability to control both fungal pathogen invasion and inflammation, which can cause damage to the cornea in FK. The conjugation with the ß-glucan-specific nanobody significantly increased the antifungal capacity of natamycin and reduced its toxicity. The further application of natamycin conjugated with the ß-glucan-specific nanobody could be expanded to other diseases caused by fungal pathogen infections.

Synergistic enhancement of redox pairs and functional groups for the removal of phenolic organic pollutants by activated PMS using silica-composited biochar: Mechanism and environmental toxicity assessment.

In present work, a novel catalyst of cobalt supported on silica-composited biochar (Co@ACFA-BC) derived from fly ash and agricultural waste was synthesized. A series of characterizations confirmed that Co3O4 and Al/Si-O compounds were successfully embedded on the surface of biochar, which triggered superior catalytic activity for PMS activation towards phenol degradation. Particularly, the Co@ACFA-BC/PMS system could completely degrade phenol in the wide pH range, and was almost unaffected by environmental factors including humic acid (HA), H2PO4-, HCO3-, Cl-, and NO3-. Further quenching experiment and EPR analysis proved that both radical (SO4·-, ·OH, O2·-) and non-radical (1O2) pathways were involved in the catalytic reaction system, and the excellent PMS activation was attributed to the electron pair cycling of Co2+/Co3+ and the active sites provided by Si-O-O and Si/Al-O bonds on the catalyst surface. Meanwhile, the carbon shell effectively inhibited the leaching of metal ions, enabling the Co@ACFA-BC catalyst to maintain excellent catalytic activity after four cycles. Finally, biological acute toxicity assay demonstrated that the toxicity of phenol could be significantly reduced after being treated by Co@ACFA-BC/PMS. Overall, this work provides a promising strategy for solid waste valorization and a feasible methodology for green and efficient treatment of refractory organic pollutants in water environment.

Effect of fetal lung maturation on the efficacy of acetaminophen for premature infants with patent ductus arteriosus.

The objective of this study was to evaluate the effect of maturing fetal lung on clinical efficacy of acetaminophen in the treatment of premature infants with patent ductus arteriosus (PDA). A total of 441 premature infants admitted to our hospital from May 2020 to May 2021 were recruited, including 152 premature infants receiving fetal lung maturation (13 cases of PDA closure with drug use and 2 cases failed) and 289 cases without maturing fetal lung (17 cases of PDA closure and 8 cases failed). Finally, a total of 30 cases were enrolled in this clinical trial. All infants were divided into groups A and B according to whether fetal lung maturation was adopted before delivery. In group A, 13 infants received fetal lung maturation, and 17 in group B did not undergo fetal lung maturation. Infants in both groups were orally given with acetaminophen. After 3-day treatment, the second course of treatment was given immediately if PDA was not closed. The PDA closure rate and patency rate of PDA at the end of 2 treatment courses were statistically compared between 2 groups. The feeding intolerance, upper gastrointestinal bleeding, renal failure, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, the age at total enteral nutrition and the length of hospital stay were also compared between 2 groups. After the 1st and 2nd treatment courses, the PDA closure rate in group A was 84.61%, significantly higher than 52.94% in group B (P < .05), whereas there was no significant difference in the PDA patency rate between 2 groups (P > .05). No significant differences were observed regarding the feeding intolerance, renal failure, necrotizing enterocolitis, periventricular-intraventricular hemorrhage, bronchopulmonary dysplasia, the length of hospital stay and the age at total enteral nutrition between 2 groups (all P > .05). In addition, the incidence of upper gastrointestinal bleeding in group A was 7.69%, slightly lower than 5.88% in group B (P > .05). Compared with premature infants untreated with fetal lung maturation interventions before delivery, premature infants who receive fetal lung maturation interventions combined with acetaminophen for PDA are likely to obtain a higher PDA closure rate and a lower incidence rate of the upper gastrointestinal bleeding.

Hinokitiol inhibits Aspergillus fumigatus by interfering with the cell membrane and cell wall.

Hinokitiol (ß-thujaplicin) is an important component of the essential oil extracted from Chamaecyparis obtuse, which prevents the decay and decomposition of temple and shrine buildings in Japan. Hinokiol has been shown to have a detrimental effect on various fungi such as Candida albicans and saprophytic fungi. However how hinokitiol works against Aspergillus fumigatus (A. fumigatus) has not been claimed. This study aims to investigate the adverse effects of hinokitiol on the disruption of the cell wall and cell membrane of A. fumigatus and to explore possible potential mechanisms or pathways. According to our results, hinokitiol negatively altered mycelium morphology, growth density, and cell plasma composition content. When incubated with human corneal epithelial cells (HCECs), hinokitiol saw a safe effect with concentrations below 12 µg/ml. Hinokitiol was shown to increase the cell membrane's permeability by decreasing the cell membrane's ergosterol content. The integrity of the cell wall was disrupted, as well as a significant increase in chitin degradation and chitinase activity. As determined by RNA-seq results, subsequent analysis, and qRT-PCR, altered transcript levels of cell walls and cell membranes-related genes (such as eglC) illustrated how hinokitiol affected the genetic profile of A. fumigatus. With this study, we recommend hinokitiol as an effective anti-A. fumigatus agent by reducing the amounts of key components in the cell wall and membrane by preventing production and accelerating breakdown.

Insights into the role of ·OH generated in Fe2+/CaO2/coal slime system for efficient extracellular polymeric substances degradation to improve dewaterability of sewage sludge.

The disposal of massive sewage sludge and coal slime is a problem facing municipalities in China. A hypothesis for the co-disposal of sludge and coal slime is proposed to improve dewaterability by utilizing the beneficial role of coal slime as a filter assist and CaO2 enhanced system in this research. Results showed that capillary suction time, specific resistance to filtration and water content decreased dramatically from 49.3 s, 13.2 × 1012 m/kg and 84.85% to 19.1 s, 1.0 × 1012 m/kg and 50.07%, respectively, under the optimal conditions with 0.3/0.1/0.3-Fe2+/CaO2/coal slime g/g DS. The hydroxyl radicals generated in the Fe2+/CaO2 process acted on extracellular polymeric substances (EPS), resulting in a drop in the ratio of α-helix/(ß-sheet + random coil) in the secondary structure of EPS proteins and a reduction in the concentration of aromatic proteins and tryptophan-like substances in TB-EPS, thereby enhancing the sludge dewaterability. Furthermore, coal slime as the skeleton building material induced a rise in sludge particle size and contact angle, lowering the hydrophilicity, compressibility of sludge and providing more channels to facilitate water flow. This work verified the promising application prospect of the Fe2+/CaO2/coal slime combined system in the enhancement of sludge dewaterability.

A Machine Learning-Based Prediction of Diabetes Insipidus in Patients Undergoing Endoscopic Transsphenoidal Surgery for Pituitary Adenoma.

BACKGROUND: Diabetes insipidus (DI) is a common complication after endoscopic transsphenoidal surgery (TSS) for pituitary adenoma (PA), which affects the quality of life in patients. Therefore, there is a need to develop prediction models of postoperative DI specifically for patients who undergo endoscopic TSS. This study establishes and validates prediction models of DI after endoscopic TSS for patients with PA using machine learning algorithms. METHODS: We retrospectively collected information about patients with PA who underwent endoscopic TSS in otorhinolaryngology and neurosurgery departments between January 2018 and December 2020. The patients were randomly split into a training set (70%) and a test set (30%). The 4 machine learning algorithms (logistic regression, random forest, support vector machine, and decision tree) were used to establish the prediction models. Area under the receiver operating characteristic curves were calculated to compare the performance of the models. RESULTS: A total of 232 patients were included, and 78 patients (33.6%) developed transient DI after surgery. Data were randomly divided into a training set (n = 162) and a test set (n = 70) for development and validation of the model, respectively. The area under the receiver operating characteristic curve was highest in the random forest model (0.815) and lowest in the logistic regression model (0.601). Invasion of pituitary stalk was the most important feature for model performance, closely followed by macroadenomas, size classification of PA, tumor texture, and Hardy-Wilson suprasellar grade. CONCLUSIONS: Machine learning algorithms identify preoperative features of importance and reliably predict DI after endoscopic TSS for patients with PA. Such a prediction model may enable clinicians to develop individualized treatment strategy and follow-up management.

Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation.

Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.

The microbiota-gut-brain axis in pathogenesis of depression: A narrative review.

The microbiota-gut-brain axis is a bidirectional regulatory pathway between the brain and the gastrointestinal tract, which plays an important role in maintain homeostasis. Gut microbiota could influence the behavior, cognition, stress response and others via the axis. Depression is a complex psychiatric disease, giving rise to heavy social health and economic burden. In recent years, studies have shown that the gut microbiota are closely linked to the pathophysiological processes of depression. In this article, the interaction and its underlying mechanisms between depression and gut microbiota were summarized.

Escaping drought: The pectin methylesterase inhibitor gene Slpmei27 can significantly change drought resistance in tomato.

Drought stress will lead to a decrease in tomato yield and poor flavour, yield and quality, resulting in economic losses in agricultural production. Mining the key genes regulating tomato drought resistance is of great significance to improve the drought resistance of tomato plants. The cell wall can directly participate in the plant drought stress response as one of the main components of the cell wall, and the regulation of pectin content in plant drought resistance is still unclear. Here, the candidate gene Solyc08g006690 (Slpmei27) was obtained by fine mapping based on genome sequencing technology (BSA-seq) of late-maturing stress-resistant tomato mutants found in the field. Slpmei27 is expressed in the cell wall. The transient silencing of Slpmei27 by VIGS significantly improved the drought resistance of tomato. Meanwhile, Slpmei27 silencing could significantly change the cell wall structure of plants, change the stomatal pass rate, reduce the water loss rate of plants, improve the scavenging ability of reactive oxygen species, change the redox balance in plants, and thus improve the drought resistance of tomato. The promoter region of this gene contains a large number of hormone-response and stress-response binding sites. The promoter region of the Slpmei27 gene in the mutant could lower the expression of downstream genes. Through this study, the mechanism by which Slpmei27 improves tomato drought resistance was revealed, and the relationship between pectin methyl ester metabolism and plant drought resistance was established, providing a theoretical basis for the production of high-quality tomato materials with high drought resistance.

Slym1 control the color etiolation of leaves by facilitating the decomposition of chlorophyll in tomato.

Photosynthesis, as an important biological process of plants, produces organic substances for plant growth and development. Although the molecular mechanisms of photosynthesis had been well investigated, the relationship between chlorophyll synthesis and photosynthesis remains largely unknown. The leaf-color mutant was an ideal material for studying photosynthesis and chlorophyll synthesis, which had been seldom investigated in tomato. Here, we obtained a yellow leaf tomato mutant ym (The mutant plants from the line of zs4) in field. Transmission electron microscopy (TEM) and photosynthetic parameters results demonstrated that chloroplast's structure was obviously destroyed and photosynthetic capacity gets weak. The mutant was hybridized with the control to construct the F2 segregation population for sequencing. Slym1 gene, controlling yellow mutant trait, was identified using Bulked Segregation Analysis. Slym1 was up-regulated in the mutant and Slym1 was located in the nucleus. The genes associated with photosynthesis and chlorophyll synthesis were down-regulated in Slym1-OE transgenic tomato plants. The results suggested that Slym1 negatively regulate photosynthesis. Photosynthetic pigment synthesis related genes HEMA, HEMB1, CHLG and CAO were up-regulated in Slym1 silencing plants. The redundant Slym1 binding the intermediate proteins MP resulting in hindering the interaction between MP and HY5 due to the Slym1 with a high expression level in ym mutant, lead to lots of the HY5 with unbound state accumulates in cells, that could accelerate the decomposition of chlorophyll. Therefore, the yellow leaf-color mutant ym could be used as an ideal material for further exploring the relationship between leaf color mutant and photosynthesis and the specific mechanism.

Enhanced arsenic removal by reusable hexagonal CeO2/Fe2O3 nanosheets with exposed (0001) facet.

Arsenite in wastewater has caused increasing concern because of high toxicity and mobility. Iron oxides are widely available and regarded as effective adsorbents for arsenic. However, conventional iron oxides usually are only effective for arsenate (As(V)) adsorption by complexation, but not for As(III) adsorption because of their poor catalytic oxidation activities, which greatly limits arsenic removal efficiency. In this study, a uniform hexagonal FeCe bimetal oxide nanosheets (Fe0.21Ce0.29O) enclosed by high active (0001) planes was synthesized by a solvothermal method to improve the catalytic activity of Fe2O3. The experimental results showed that adsorption capacity of Fe0.21Ce0.29O reached 61.1 mg/g for arsenic and 70 % of that at equilibrium was achieved in <10 min. Based on characterization analyses and density functional theory simulation, the new insight in oxidation and complexation mechanism of arsenic was proposed. Firstly, As(III) was adsorbed to adsorbent surface by forming stable structure of Ce-O-As or Fe-O-As, and then converted into As(V) by dissolved oxygen under the catalysis of (0001) planes densely distributed on Fe2O3 and CeO2 surfaces. The formed As(V) species were bound on Fe0.21Ce0.29O surface by forming bidentate and monodentate surface complexes. Finally, the safety of As-containing solution treated with Fe0.21Ce0.29O was well proved by the zebrafish embryo developmental toxicity tests.

Clinical evaluation of the lot-to-lot consistency of an enterovirus 71 vaccine in a commercial-scale phase IV clinical trial.

OBJECTIVE: To evaluate the immunogenicity, safety and lot-to-lot consistency of an inactivated enterovirus 71 (EV71) vaccine cultured in bioreactors with different specifications after full immunization. METHODS: A randomized, double-blind trial was performed in 3,000 children aged 6 ~ 35 months with six vaccine batches, which were prepared in 40 L and 150 L bioreactors for three consecutive batches respectively. Children were immunized on day 0 and 28, serum samples were collected on day 0 and 56, and neutralizing antibody titers were determined by the microcytopathic method. Immediate reactions were recorded within 30 min, local and systemic symptoms were recorded within 0 ~ 28 days, and serious adverse events were recorded within 6 months. RESULTS: After immunization with two doses of the inactivated EV71 vaccine, the neutralizing antibody GMT was 825.52 ± 4.09, and the positive conversion rate was 96.18%, with no significant difference. The 95% CI of the serum neutralizing antibody GMT ratio between the two groups after immunization with the three vaccine batches produced in the 150 L and 40 L bioreactors ranged from .67 ~ 1.5. The overall incidence of adverse reactions, mainly grade 1 reactions, for all 6 batches from 0 to 28 days after vaccination was 49.62%, with no significant difference (p = .8736). The incidence of systemic adverse reactions, primarily fever and diarrhea, was 45.14%; the incidence of local adverse reactions, primarily erythema and tenderness, was 9.43%. CONCLUSION: The EV71 vaccine was highly immunogenic and safe in children aged 6-35 months, and 6 consecutive batches produced by the two bioreactors with different specifications were consistent.

Selective Degradation of Electron-Rich Organic Pollutants Induced by CuO@Biochar: The Key Role of Outer-Sphere Interaction and Singlet Oxygen.

Efficient degradation of organic pollutants by oxidative radicals is challenging in the complex soil environment because of the invalid consumption of radicals by nontarget background substances and the generation of secondary halogenated organic pollutants. Nonradical-based oxidation is a promising pollutant removal method due to its high selectivity and environmental adaptability. Herein, a biochar-supported sheetlike CuO (e-CuO@BC) was developed, which exhibited efficient activation of peroxydisulfate (PDS) via nonradical pathways. The activation mechanisms were identified as (i) formation of surface-bonding active complexes via an outer-sphere interaction between e-CuO@BC and PDS and (ii) the continuous generation of 1O2 by the cycling of the Cu(I)/Cu(II) redox couple. In addition, the activation of PDS primarily occurred at the crystal facet (001) of e-CuO occupied by Cu atoms and was well facilitated by the Cu-O-C bond, which induced electron-rich centers around CuO. Two oxidative species from PDS activation, including surface-bonding active complexes and 1O2, showed a highly selective degradation toward electron-rich pollutants. Moreover, a highly efficient mineralization of organic pollutants and an effective inhibition on the generation of toxic byproducts (i.e., halogenated organics) was indicated by the intermediate and final degradation products. This study provides a comprehensive understanding of the heterogeneous activation process of PS by the e-CuO@BC catalyst for electron-rich organic pollutant removal.

Evaluation of a recombinant five-antigen Staphylococcus aureus vaccine: The randomized, single-centre phase 1a/1b clinical trials.

BACKGROUND: Staphylococcus aureus is an important pathogen that causes hospital and community infections. To control Staphylococcus aureus infection and reduce the usage of antibiotics, we evaluated the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in healthy adults. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 1a study and a randomized, open-label phase 1b study. In phase 1a, we randomly allocated 144 healthy participants in a ratio of 1:1:1:1 to receive the low-(60 µg), middle-(120 µg), and high-dose (240 µg) vaccine or placebo at day 0, 3, 7 and 14. In phase 1b, 144 healthy participants were randomly allocated at a ratio of 1:1:1:1 to receive 0-3-7, 0/0-7, 0/0-3-7, 0/0-7-14 regimens to estimate the optimal strategy. The primary study endpoint was the incidence of solicited adverse events post-vaccination. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as the cellular immune responses and functional antibodies. RESULTS: There were 31 (86%), 30 (83%), and 32 (89%) of 36 participants in the low-, middle-, and high-dose group reported solicited adverse events, respectively, most of the adverse events were mild or moderate. In phase 1b, the dose-adjusted rFSAV (90 µg) showed a better safety profile in the four immune procedures, and no vaccine-related serious adverse events were reported. The antigen-specific binding antibodies started to increase at day 7 and reached the peak around day 14 to 21. The cellular immune responses and functional antibodies also were substantially above background levels. CONCLUSIONS: rFSAV is safe, well tolerated in healthy adults, elicits rapid and robust specific humoral and cellular immune responses with unconventional immunization procedure in phase 1a and 1b. It deserves to be noted and further explored. CLINICAL TRIALS REGISTRATION: NCT02804711 and NCT03966040.