Thin-wall hollow porous cystic-like graphitic carbon nitride with awakened n→π* electronic transitions and exceptional structural features for superior photocatalytic degradation of sulfamethoxazole.

Effective photoexcitation and carrier migration are the essential aspects to strengthen semiconductor-engaged redox reaction. Herein, a three-dimensional thin-wall hollow porous cystic-like g-C3N4 (HPCN) with curved layer edge was successfully fabricated via a non-template thermal-condensation strategy. The construction of unique distorted structure can evoke the hard-to-activate n→π* electronic transition to some extent, broadening the absorption spectrum to 800 nm. And benefiting from the multiple reflections of incident light, the effective photoactivation can be further achieved. Moreover, the thin-wall porous framework can shorten the diffusion distance and accelerate migration of photogenerated charge, favouring interfacial redox reactions. The optimized HPCN1.0 demonstrated an excellent photocatalytic degradation of SMX under blue-LED light irradiation, which was dramatically superior to that of pristine g-C3N4 (CN, 11.4 times). Ultimately, in consideration of reactions under several influencing factors with four different water samples, we demonstrated that the HPCN photocatalyst could be utilized far more productively for the elimination of SMX under real-world aqueous conditions. This work provides a straightforward approach for the removal of SMX and has immense potential to contribute to global scale environmental remediation.

Construction of double-functionalized g-C3N4 heterojunction structure via optimized charge transfer for the synergistically enhanced photocatalytic degradation of sulfonamides and H2O2 production.

Herein, supporting g-C3N4 embedded with benzene-ring (BCN) on P-modified g-C3N4 (PCN) successfully synthesized the homogeneous photocatalyst BCN/PCN (PBCN) via a simple thermal polymerization reaction. Under blue-light (LED) irradiation, the optimized PBCN (0.448 min-1) demonstrated excellent photocatalytic performance, attaining over 74 times the degradation rate for sulfisoxazole (SSZ) in contrast to non-functionalized g-C3N4 (CN, 0.006 min-1). Theoretical calculations revealed that the substitution of heterocyclic rings in the g-C3N4 triazine networks with benzene-rings enabled them to serve as electron donors, while promoting photoinduced spatial charge dissociation. Further, the carrier PCN tended to serve as electron acceptors to form electron-rich corner-phosphorous sites. Reactive species experiments demonstrate that the O2˙- and h+ constituted the primary photocatalytic mechanism of SSZ degradation. The potential SSZ degradation routes were predicted based on the transformation products via mass spectrometry. Finally, the composite materials also exhibited excellent photocatalytic activity in the conversion of solar energy to chemical energy (H2O2). This study guides the rational modification of g-C3N4-based semiconductors to achieve green energy production and beneficial ecological applications.

Efficient degradation of typical pharmaceuticals in water using a novel TiO2/ONLH nano-photocatalyst under natural sunlight.

Photocatalytic degradation of typical pharmaceuticals in natural sunlight and in actual water is of great significance. In this study, the oxygen or nitrogen linked heptazine-base polymer (ONLH) was successfully incorporated with TiO2 nanoparticles and formed a TiO2/ONLH nanocomposite which was responded to the natural sunlight. Under natural sunlight, the TiO2/ONLH can effectively degrade ten types of pharmaceuticals. In particular, fluoroquinolone containing N-piperazinyl, and cardiovascular drugs containing long aromatic side chains were easily degraded. The half-life of the best degradation performance of propranolol was less than 5 min. The rate constants of propranolol using the TiO2/ONLH were approximately six- and eight-fold higher than those of pristine TiO2 and ONLH, respectively. Two reactive species (OH and O2-) facilitated the rapid degradation of propranolol, which occurred primarily through the hydroxyl radical addition, ring-opening, and ipso substitution reactions. An acute toxicity test using luminescent bacteria indicated that the toxicity of the propranolol reaction solution gradually decreased with lower total organic carbon (TOC). According to the toxicity evaluation of monomer products, the TiO2/ONLH also reduced the generation of toxic transformation products. The effects of actual water/wastewater have further shown the TiO2/ONLH might be applied for the removal of pharmaceuticals in wastewater.

Selection of diverse strains to assess broad coverage of the bivalent FHbp meningococcal B vaccine.

MenB-FHbp is a recombinant meningococcal serogroup B (MenB) vaccine composed of 2 factor H binding proteins (FHbps). Meningococcal vaccines targeting polysaccharide serogroup A, C, Y, and W capsules were licensed upon confirmation of bactericidal antibody induction after initial efficacy studies with serogroup A and C vaccines. Unlike meningococcal polysaccharide vaccines, wherein single strains demonstrated bactericidal antibodies per serogroup for each vaccine, MenB-FHbp required a more robust approach to demonstrate that bactericidal antibody induction could kill strains with diverse FHbp sequences. Serum bactericidal assays using human complement were developed for 14 MenB strains, representing breadth of meningococcal FHbp diversity of ~80% of circulating MenB strains. This work represents an innovative approach to license a non-toxin protein vaccine with 2 antigens representing a single virulence factor by an immune correlate, and uniquely demonstrates that such a vaccine provides coverage across bacterial strains by inducing broadly protective antibodies.

A novel synthetic carbon and oxygen doped stalactite-like g-C3N4 for broad-spectrum-driven indometacin degradation.

Achieving efficient solar utilization is a primary goal in the field of photocatalytic degradation of PPCPs. For this study, a broad-spectrum carbon and oxygen doped, porous g-C3N4 (COCN) was synthesized via a simple co-pyrolysis of dicyandiamide and methylamine hydroiodide (CH5N·HI). The 0.3COCN demonstrated an excellent photocatalytic degradation of indometacin (IDM), which was 5.9 times higher than bulk g-C3N4. The enhanced photocatalytic activity could be ascribed to the broad-spectrum utilization of solar light and improved charge separation efficiency. Reactive species (RSs) scavenging experiments have shown that O2·- and 1O2 were the dominant active species. Further, the 0.3COCN exhibits excellent yield of hydroxyl radicals which was confirmed by electron spin resonance (ESR) spectra. Meanwhile, the degradation pathways of IDM were proposed according the HRAM LC-MS/MS and total organic carbon (TOC). This research provided a new strategy for a broad-spectrum photocatalyst, and a promising strategy for environmental remediation.

Phosphate-modified m-Bi2O4 enhances the absorption and photocatalytic activities of sulfonamide: Mechanism, reactive species, and reactive sites.

Widespread usage of the sulfonamide class of antibiotics is causing increasing ecotoxicological concern, as they have the capacity to alter ambient ecosystems. Photocatalytic technology is an attractive yet challenging strategy for the degradation of antibiotics. For this work, the phosphate modification of m-Bi2O4 (Bi2O4-P) was prepared via a one-step hydrothermal process involving sodium bismuthate and sodium phosphate, which was employed for the degradation of sulfamethazine (SMZ) under visible light irradiation. The 0.5% Bi2O4-P exhibited excellent photocatalytic performance, which was 1.9 times that of pure m-Bi2O4. The photocatalytic degradation kinetics and mechanism of SMZ was investigated at different pH, whereupon it was revealed that m-Bi2O4-P exhibited improved SMZ adsorption and photocatalytic activities in contrast to pure m-Bi2O4. Compared with other four sulfonamide antibiotics, structures that contained additional methyl on the pyrimidine could be more easily attacked by phosphate modified m-Bi2O4. Reactive species (RS) scavenging experiments revealed that h+ was primarily responsible for the degradation of SMZ. Further studies of RS by ESR technology, and the results of photoelectrochemical properties showed phosphate-modified m-Bi2O4 could make greater use of photogenerated carriers, thereby producing additional RS. Based on the HRAM LC-MS/MS and the Frontier Molecular Orbital Theory, the degradation pathways of SMZ were proposed.

Insights into the synergetic mechanism of a combined vis-RGO/TiO2/peroxodisulfate system for the degradation of PPCPs: Kinetics, environmental factors and products.

In recent years, how to effectively remove emerging organic pollutants in water bodies has been studied extensively, especially in the actual complex water environment. In the present study, an effective wastewater treatment system that combined photocatalysis and an oxidizing agent was investigated. Specifically, visible-light driven reduced graphene oxide (RGO)/TiO2 composites were prepared, and peroxodisulfate (PDS) was used as electron acceptor to accelerate the photocatalytic activity of this material. The vis-RGO/TiO2/PDS system exhibited outstanding properties in the degradation of diclofenac (DCF), which was also facilitated by acidic conditions and Cl-. Lake water, tap water, river water and HCO3- decreased the DCF degradation rate, while NO3- affected the system only slightly. Low concentrations of fulvic acid (FA) promoted the degradation of DCF via the generation of excited states, whereas a high concentration of FA inhibited the degradation, which was likely due to the light screening effect. The photocatalytic mechanism revealed that PDS served as an electron acceptor for the promotion of electron-hole pair separation and the generation of additional reactive oxygen species, while the RGO served as an electric conductor. The active substances, h+, OH, 1O2, SO4- and O2- were generated in this system, O2- and h+ played significant roles in the degradation of DCF based electron spin resonance tests and radical quenching results. According to the mass spectrometry results, the amide bond cleavage, dechlorination reaction, hydroxyl addition reaction, and decarboxylation reaction were the primary transformative pathways.

The bivalent factor H binding protein meningococcal serogroup B vaccine elicits bactericidal antibodies against representative non-serogroup B meningococci.

MenB-FHbp (Trumenba®; bivalent rLP2086) is a meningococcal serogroup B vaccine containing 2 variants of the recombinant lipidated factor H binding protein (FHbp) antigen. The expression of FHbp, an outer membrane protein, is not restricted to serogroup B strains of Neisseria meningitidis (MenB). This study investigated whether antibodies elicited by MenB-FHbp vaccination also protect against non-MenB strains. Immunological responses were assessed in serum bactericidal assays using human complement (hSBAs) with non-MenB disease-causing test strains from Europe, Africa, and the United States. Importantly, FHbp variant distribution varies among meningococcal serogroups; therefore, strains that code for serogroup-specific prevalent variants (ie, representative of the 2 antigenically distinct FHbp subfamilies, designated subfamily A and subfamily B) and with moderate levels of FHbp surface expression were selected for testing by hSBA. After 2 or 3 doses of MenB-FHbp, 53% to 100% of individuals had bactericidal responses (hSBA titers ≥ 1:8) against meningococcal serogroup C, W, Y, and X strains, and 20% to 28% had bactericidal responses against serogroup A strains; in fact, these bactericidal responses elicited by MenB-FHbp antibodies against non-MenB strains, including strains associated with emerging disease, were greater than the serological correlate of protection for meningococcal disease (ie, hSBA titers ≥ 1:4). This is in comparison to a quadrivalent polysaccharide conjugate vaccine, MCV4 (Menactra®, targeting meningococcal serogroups A, C, W, and Y), which elicited bactericidal responses of 90% to 97% against the serogroup A, C, W, and Y strains and had no activity against serogroup X. Together, these results provide clinical evidence that MenB-FHbp may protect against meningococcal disease regardless of serogroup.

[Targeted imaging ability of a biotinylated imaging probe Biotin-S-S-Rhodol for breast cancer cells in vitro].

OBJECTIVE: To investigate performance of a biotinylated imaging probe 3a for targeted imaging of breast cancer cells. METHODS: Ultraviolet absorption spectrum and fluorescence spectrum were employed to analyze the spectral characteristics of 3a. The fluorescence spectrums of 3a treated with different concentrations of glutathione (GSH) were obtained to determine the sensibility of 3a to GSH. Flow cytometry was used to determine the cellular uptake of 3a by MCF-7 cells, MDA-MB-231 cells and Hs 578Bst cells in the presence or absence of biotin, and the imaging performance of 3a in the 3 cell lines was assessed under an inverted fluorescent microscope. The toxicity of 3a to the cells was evaluated using MTT method. RESULTS: 3a showed the strongest absorption peak at 510 nm, and its fluorescence emission signal was the strongest at 544 nm. As the concentration of GSH increased (0-6 mmol/L), 3a exhibited an increasing fluorescence signal at 544 nm. The cellular uptake of 3a was markedly higher in MDA-MB-231 cells and MCF-7 cells than in Hs 578Bst cells. The imaging studies showed that 3a had a good breast cancer cell-targeting property and produced clear images under fluorescent microscope. MTT assay demonstrated no obvious toxicity of 3a in Hs 578Bst cells even at the concentration of 20 µmol/L, but MCF-7 cells and MDA-MB-231 cells exposed to 2-20 µmol/L 3a showed a lowered cell viability. CONCLUSION: 3a is capable of targeted imaging of breast cancer cells mediated by biotin. 3a at the concentration of 2-20 µmol/L has minimal cytotoxicity to normal breast cells but can lower the viability of breast cancer cells.

Neisseria meningitidis Serogroup B Vaccine, Bivalent rLP2086, Induces Broad Serum Bactericidal Activity Against Diverse Invasive Disease Strains Including Outbreak Strains.

BACKGROUND: Bivalent rLP2086 (Trumenba), 1 of 2 meningococcal serogroup B (MnB) vaccines recently approved in the United States for the prevention of MnB disease in individuals 10-25 years of age, is composed of 2 lipidated factor H binding proteins from subfamilies A and B. This study evaluated the breadth of MnB strain coverage elicited by bivalent rLP2086 measured with serum bactericidal assays using human complement (hSBAs). METHODS: hSBA responses to diverse MnB clinical strains circulating in the United States and Europe (n = 23), as well as recent US university outbreak strains (n = 4), were evaluated. Individual prevaccination and postvaccination sera from adolescents and young adults previously enrolled in phase 2 clinical studies of bivalent rLP2086 were assessed. Responders were defined by an hSBA titer ≥1:8, which is more stringent than the accepted correlate of protection (hSBA titer ≥1:4). RESULTS: Baseline hSBA response rates were generally low; robust increases were observed after 2 and 3 doses of bivalent rLP2086, with hSBA responses to all test strains ranging from 31.8% to 100% and 55.6% to 100%, respectively. hSBA responses to strains expressing prevalent subfamily A and B factor H binding protein variants in the United States and Europe, A22 and B24, ranged from 88.0% to 95.0% and 81.0% to 100.0%, respectively, after dose 3. Substantial responses were also observed for recent US outbreak strains. CONCLUSIONS: Bivalent rLP2086 elicits robust hSBA responses to MnB strains expressing 14 factor H binding protein variants representing approximately 80% of MnB invasive isolates and different from vaccine antigens, suggesting that bivalent rLP2086 confers broad protection against diverse MnB disease-causing strains.

Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease.

Factor H binding proteins (fHBP), are bacterial surface proteins currently undergoing human clinical trials as candidate serogroup B Neisseria meningitidis (MnB) vaccines. fHBP protein sequences segregate into two distinct subfamilies, designated A and B. Here, we report the specificity and vaccine potential of mono- or bivalent fHBP-containing vaccines. A bivalent fHBP vaccine composed of a member of each subfamily elicited substantially broader bactericidal activity against MnB strains expressing heterologous fHBP than did either of the monovalent vaccines. Bivalent rabbit immune sera tested in serum bactericidal antibody assays (SBAs) against a diverse panel of MnB clinical isolates killed 87 of the 100 isolates. Bivalent human immune sera killed 36 of 45 MnB isolates tested in SBAs. Factors such as fHBP protein variant, PorA subtype, or MLST were not predictive of whether the MnB strain could be killed by rabbit or human immune sera. Instead, the best predictor for killing in the SBA was the level of in vitro surface expression of fHBP. The bivalent fHBP vaccine candidate induced immune sera that killed MnB isolates representing the major MLST complexes, prevalent PorA subtypes, and fHBP variants that span the breadth of the fHBP phylogenetic tree. Importantly, epidemiologically prevalent fHBP variants from both subfamilies were killed.

Detection of LP2086 on the cell surface of Neisseria meningitidis and its accessibility in the presence of serogroup B capsular polysaccharide.

The outer membrane protein LP2086, a human factor H binding protein, is undergoing clinical trials as a vaccine against invasive serogroup B meningococcal (MnB) disease. As LP2086 is a surface protein, expression of capsular polysaccharide could potentially limit accessibility of anti-LP2086 antibodies to LP2086 expressed on the surface of bacteria. To determine whether variability in expression levels of the serogroup B capsule (Cap B) might interfere with accessibility of anti-LP2086 antibody binding to LP2086, we evaluated the ability of anti-Cap B and anti-LP2086 antibodies to bind to the surface of 1263 invasive clinical MnB strains by flow cytometry. One of the anti-LP2086 monoclonal antibodies used recognizes virtually all LP2086 sequence variants. Our results show no correlation between the amount of Cap B expressed and the binding of anti-LP2086 antibodies. Furthermore, the susceptibility of MnB bacteria to lysis by anti-LP2086 immune sera was independent of the level of Cap B expressed. The data presented in this paper demonstrates that Cap B does not interfere with the binding of antibodies to LP2086 expressed on the outer membrane of MnB clinical isolates.

Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele.

Cytomegalovirus (CMV) is a major threat in patients undergoing allogeneic bone marrow transplantation. The adoptive transfer of CMV-specific cytotoxic T lymphocytes (CTLs) expanded from the blood of CMV-seropositive donors has been shown to effectively control CMV infection. However, the requirement for safe and effective antigen-presenting cells (APCs) for each patient precludes broad applicability of this successful form of therapy. Here we analyze the ability of artificial APCs (AAPCs) to activate and expand CMV-specific CTLs from peripheral blood of seropositive HLA A2.1+ donors. We demonstrate that AAPCs expressing the CMV P495 peptide or the full-length pp65 protein stimulate P495-specific CTLs at least as effectively as autologous, peptide-pulsed, peripheral blood mononuclear cells or EBV-transformed B cells. Starting from 100 mL of blood, the AAPCs reliably yield clinically relevant CTL numbers after a single stimulation. CTLs activated on AAPCs effectively kill CMV-infected fibroblasts and have a Tc1 memory effector phenotype identical to that of CTLs generated with autologous APCs. AAPCs thus offer a rapid, controlled, convenient, and highly reproducible system for expanding CMV-specific CTLs. Furthermore, the CTL expansion obtained with AAPCs encoding full-length pp65 indicates that AAPCs may be used to present known as well as unknown CTL epitopes in the context of the AAPC's HLA.